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Sample records for pre-erythrocytic stage infection

  1. Malaria parasite pre-erythrocytic stage infection: Gliding and Hiding

    PubMed Central

    Vaughan, Ashley M.; Aly, Ahmed S. I.; Kappe, Stefan H. I.

    2008-01-01

    Summary Malaria is caused by red blood cell-infectious forms of Plasmodium parasites resulting in illness and possible death of infected hosts. The mosquito-borne sporozoite stage of the parasite and the initial infection in the liver, however cause little pathology and no symptoms. Nevertheless, these pre-erythrocytic parasite stages are attracting passionate research efforts not least because they are the most promising targets for malaria vaccine development. Here, we review how the infectious sporozoite makes its way to the liver, subsequently develops in hepatocytes and the factors, both parasite and host, involved in the interactions that occur during this ‘silent’ phase of infection. PMID:18779047

  2. Dendritic cells and the malaria pre-erythrocytic stage.

    PubMed

    Mauduit, Marjorie; See, Peter; Peng, Kaitian; Rénia, Laurent; Ginhoux, Florent

    2012-09-01

    Malaria remains one of the main infectious diseases in intertropical regions. The malaria parasite has a complex life cycle in its mammalian host, switching between variable forms as it traverses through different tissues and anatomic locations, either intra- or intercellularly. During its journey, the parasite encounters and interacts with the host immune system, which functions to prevent infections and limit ensuing pathologies. One important component of the host immune system is the dendritic cells (DC) network. DC form a heterogeneous group of pathogen-sensing and antigen-presenting cells that play a crucial role in the initiation of adaptive immunity. Here, we review the known and unknown interactions between the malaria parasites and the DC system, starting from the inoculation of the parasite in the skin up to its exit from the liver, also known as the pre-erythrocytic stage of the infection, and discuss how deciphering these interactions may contribute to our understanding of the Plasmodium parasite biology as well as to the induction of immune protection via vaccination. PMID:22418726

  3. DNA from pre-erythrocytic stage malaria parasites is detectable by PCR in the faeces and blood of hosts.

    PubMed

    Abkallo, Hussein M; Liu, Weimin; Hokama, Sarina; Ferreira, Pedro E; Nakazawa, Shusuke; Maeno, Yoshimasa; Quang, Nguyen T; Kobayashi, Nobuyuki; Kaneko, Osamu; Huffman, Michael A; Kawai, Satoru; Marchand, Ron P; Carter, Richard; Hahn, Beatrice H; Culleton, Richard

    2014-06-01

    Following the bite of an infective mosquito, malaria parasites first invade the liver where they develop and replicate for a number of days before being released into the bloodstream where they invade red blood cells and cause disease. The biology of the liver stages of malaria parasites is relatively poorly understood due to the inaccessibility of the parasites to sampling during this phase of their life cycle. Here we report the detection in blood and faecal samples of malaria parasite DNA throughout their development in the livers of mice and before the parasites begin their growth in the blood circulation. It is shown that parasite DNA derived from pre-erythrocytic stage parasites reaches the faeces via the bile. We then show that different primate malaria species can be detected by PCR in blood and faecal samples from naturally infected captive macaque monkeys. These results demonstrate that pre-erythrocytic parasites can be detected and quantified in experimentally infected animals. Furthermore, these results have important implications for both molecular epidemiology and phylogenetics of malaria parasites. In the former case, individuals who are malaria parasite negative by microscopy, but PCR positive for parasite DNA in their blood, are considered to be "sub-microscopic" blood stage parasite carriers. We now propose that PCR positivity is not necessarily an indicator of the presence of blood stage parasites, as the DNA could derive from pre-erythrocytic parasites. Similarly, in the case of molecular phylogenetics based on DNA sequences alone, we argue that DNA amplified from blood or faeces does not necessarily come from a parasite species that infects the red blood cells of that particular host.

  4. Protective CD8+ T cell responses against the pre-erythrocytic stages of malaria parasites: an overview.

    PubMed

    Oliveira-Ferreira, J; Daniel-Ribeiro, C

    2001-02-01

    CD8+ T cells have been implicated as critical effector cells in protection against the pre-erythrocytic stage of malaria in mice and humans following irradiated sporozoite immunization. Immunization experiments in animal models by several investigators have suggested different strategies for vaccination against malaria and many of the targets from liver stage malaria antigens have been shown to be immunogenic and to protect mice from the sporozoite challenge. Several prime/boost protocols with replicating vectors, such as vaccinia/influenza, with non-replicating vectors, such as recombinant particles derived from yeast transposon (Ty-particles) and modified vaccinia virus Ankara, and DNA, significantly enhanced CD8+ T cell immunogenicity and also the protective efficacy against the circumsporosoite protein of Plasmodium berghei and P. yeti. Based on these experimental results the development of a CD8+ T cell inducing vaccine has moved forward from epitope identification to planning stages of safety and immunogenicity trials of candidate vaccines.

  5. Malaria vaccine candidate antigen targeting the pre-erythrocytic stage of Plasmodium falciparum produced at high level in plants.

    PubMed

    Voepel, Nadja; Boes, Alexander; Edgue, Güven; Beiss, Veronique; Kapelski, Stephanie; Reimann, Andreas; Schillberg, Stefan; Pradel, Gabriele; Fendel, Rolf; Scheuermayer, Matthias; Spiegel, Holger; Fischer, Rainer

    2014-11-01

    Plants have emerged as low-cost production platforms suitable for vaccines targeting poverty-related diseases. Besides functional efficacy, the stability, yield, and purification process determine the production costs of a vaccine and thereby the feasibility of plant-based production. We describe high-level plant production and functional characterization of a malaria vaccine candidate targeting the pre-erythrocytic stage of Plasmodium falciparum. CCT, a fusion protein composed of three sporozoite antigens (P. falciparum cell traversal protein for ookinetes and sporozoites [PfCelTOS], P. falciparum circumsporozoite protein [PfCSP], and P. falciparum thrombospondin-related adhesive protein [PfTRAP]), was transiently expressed by agroinfiltration in Nicotiana benthamiana leaves, accumulated to levels up to 2 mg/g fresh leaf weight (FLW), was thermostable up to 80°C and could be purified to >95% using a simple two-step procedure. Reactivity of sera from malaria semi-immune donors indicated the immunogenic conformation of the purified fusion protein consisting of PfCelTOS, PfCSP_TSR, PfTRAP_TSR domains (CCT) protein. Total IgG from the CCT-specific mouse immune sera specifically recognized P. falciparum sporozoites in immunofluorescence assays and induced up to 35% inhibition in hepatocyte invasion assays. Featuring domains from three promising sporozoite antigens with different roles (attachment and cell traversal) in the hepatocyte invasion process, CCT has the potential to elicit broader immune responses against the pre-erythrocytic stage of P. falciparum and represents an interesting new candidate, also as a component of multi-stage, multi-subunit malaria vaccine cocktails. PMID:25200253

  6. IFNγ Responses to Pre-erythrocytic and Blood-stage Malaria Antigens Exhibit Differential Associations With Past Exposure and Subsequent Protection

    PubMed Central

    Jagannathan, Prasanna; Nankya, Felistas; Stoyanov, Cristina; Eccles-James, Ijeoma; Sikyomu, Esther; Naluwu, Kate; Wamala, Samuel; Nalubega, Mayimuna; Briggs, Jessica; Bowen, Katherine; Bigira, Victor; Kapisi, James; Kamya, Moses R.; Dorsey, Grant; Feeney, Margaret E.

    2015-01-01

    Background. The malaria-specific T-cell response is believed to be important for protective immunity. Antimalarial chemoprevention may affect this response by altering exposure to malaria antigens. Methods. We performed interferon γ (IFNγ) ELISpot assays to assess the cellular immune response to blood-stage and pre-erythrocytic antigens longitudinally from 1 to 3 years of age in 196 children enrolled in a randomized trial of antimalarial chemoprevention in Tororo, Uganda, an area of high transmission intensity. Results. IFNγ responses to blood-stage antigens, particularly MSP1, were frequently detected, strongly associated with recent malaria exposure, and lower in those adherent to chemoprevention compared to nonadherent children and those randomized to no chemoprevention. IFNγ responses to pre-erythrocytic antigens were infrequent and similar between children randomized to chemoprevention or no chemoprevention. Responses to blood-stage antigens were not associated with subsequent protection from malaria (aHR 0.96, P = .83), but responses to pre-erythrocytic antigens were associated with protection after adjusting for prior malaria exposure (aHR 0.52, P = .009). Conclusions. In this high transmission setting, IFNγ responses to blood-stage antigens were common and associated with recent exposure to malaria but not protection from subsequent malaria. Responses to pre-erythrocytic antigens were uncommon, not associated with exposure but were associated with protection from subsequent malaria. PMID:25520427

  7. Identification of Novel Pre-Erythrocytic Malaria Antigen Candidates for Combination Vaccines with Circumsporozoite Protein

    PubMed Central

    Sahu, Tejram; Malkov, Vlad; Morrison, Robert; Pei, Ying; Juompan, Laure; Milman, Neta; Zarling, Stasya; Anderson, Charles; Wong-Madden, Sharon; Wendler, Jason; Ishizuka, Andrew; MacMillen, Zachary W.; Garcia, Valentino; Kappe, Stefan H. I.; Krzych, Urszula; Duffy, Patrick E.

    2016-01-01

    Malaria vaccine development has been hampered by the limited availability of antigens identified through conventional discovery approaches, and improvements are needed to enhance the efficacy of the leading vaccine candidate RTS,S that targets the circumsporozoite protein (CSP) of the infective sporozoite. Here we report a transcriptome-based approach to identify novel pre-erythrocytic vaccine antigens that could potentially be used in combination with CSP. We hypothesized that stage-specific upregulated genes would enrich for protective vaccine targets, and used tiling microarray to identify P. falciparum genes transcribed at higher levels during liver stage versus sporozoite or blood stages of development. We prepared DNA vaccines for 21 genes using the predicted orthologues in P. yoelii and P. berghei and tested their efficacy using different delivery methods against pre-erythrocytic malaria in rodent models. In our primary screen using P. yoelii in BALB/c mice, we found that 16 antigens significantly reduced liver stage parasite burden. In our confirmatory screen using P. berghei in C57Bl/6 mice, we confirmed 6 antigens that were protective in both models. Two antigens, when combined with CSP, provided significantly greater protection than CSP alone in both models. Based on the observations reported here, transcriptional patterns of Plasmodium genes can be useful in identifying novel pre-erythrocytic antigens that induce protective immunity alone or in combination with CSP. PMID:27434123

  8. Identification of Novel Pre-Erythrocytic Malaria Antigen Candidates for Combination Vaccines with Circumsporozoite Protein.

    PubMed

    Speake, Cate; Pichugin, Alexander; Sahu, Tejram; Malkov, Vlad; Morrison, Robert; Pei, Ying; Juompan, Laure; Milman, Neta; Zarling, Stasya; Anderson, Charles; Wong-Madden, Sharon; Wendler, Jason; Ishizuka, Andrew; MacMillen, Zachary W; Garcia, Valentino; Kappe, Stefan H I; Krzych, Urszula; Duffy, Patrick E

    2016-01-01

    Malaria vaccine development has been hampered by the limited availability of antigens identified through conventional discovery approaches, and improvements are needed to enhance the efficacy of the leading vaccine candidate RTS,S that targets the circumsporozoite protein (CSP) of the infective sporozoite. Here we report a transcriptome-based approach to identify novel pre-erythrocytic vaccine antigens that could potentially be used in combination with CSP. We hypothesized that stage-specific upregulated genes would enrich for protective vaccine targets, and used tiling microarray to identify P. falciparum genes transcribed at higher levels during liver stage versus sporozoite or blood stages of development. We prepared DNA vaccines for 21 genes using the predicted orthologues in P. yoelii and P. berghei and tested their efficacy using different delivery methods against pre-erythrocytic malaria in rodent models. In our primary screen using P. yoelii in BALB/c mice, we found that 16 antigens significantly reduced liver stage parasite burden. In our confirmatory screen using P. berghei in C57Bl/6 mice, we confirmed 6 antigens that were protective in both models. Two antigens, when combined with CSP, provided significantly greater protection than CSP alone in both models. Based on the observations reported here, transcriptional patterns of Plasmodium genes can be useful in identifying novel pre-erythrocytic antigens that induce protective immunity alone or in combination with CSP. PMID:27434123

  9. Measurement of the T cell response to pre-erythrocytic vaccination in mice

    PubMed Central

    Guthmiller, Jenna J.; Zander, Ryan A.; Butler, Noah S.

    2016-01-01

    Whole attenuated parasite vaccines designed to elicit immunity against the clinically silent pre-erythrocytic stage of Plasmodium infection represent the most efficacious experimental platforms currently in clinical trial. Studies in rodents and humans show that T cells mediate vaccine-induced protection. Thus, determining the quantitative and qualitative properties of these T cells remains a major research focus. Most rodent models of pre-erythrocytic anti-Plasmodium vaccination focus on circumsporozoite-specific CD8 T cell responses in BALB/c mice. However, CD4 T cells and non-circumsporozoite-specific CD8 T cells also significantly contribute to protection. Here we describe alternative approaches that enable detection and functional characterization of total CD8 and CD4 T cell responses induced by pre-erythrocytic vaccination in mice. These flow cytometry-based approaches rely on monitoring the modulation of expressed integrins and co-receptors on the surface of T cells in vaccinated mice. The approaches enable direct determination of the magnitude, kinetics, distribution, phenotype, and functional features of T cell responses induced by infection or whole-parasite vaccination using any mouse-parasite species combination. PMID:26450376

  10. Discovery of Novel Plasmodium falciparum Pre-Erythrocytic Antigens for Vaccine Development

    PubMed Central

    Aguiar, Joao C.; Bolton, Jessica; Wanga, Joyce; Sacci, John B.; Iriko, Hideyuki; Mazeika, Julie K.; Han, Eun-Taek; Limbach, Keith; Patterson, Noelle B.; Sedegah, Martha; Cruz, Ann-Marie; Tsuboi, Takafumi; Hoffman, Stephen L.; Carucci, Daniel; Hollingdale, Michael R.; Villasante, Eileen D.; Richie, Thomas L.

    2015-01-01

    Background Nearly 100% protection against malaria infection can be achieved in humans by immunization with P. falciparum radiation-attenuated sporozoites (RAS). Although it is thought that protection is mediated by T cell and antibody responses, only a few of the many pre-erythrocytic (sporozoite and liver stage) antigens that are targeted by these responses have been identified. Methodology Twenty seven P. falciparum pre-erythrocytic antigens were selected using bioinformatics analysis and expression databases and were expressed in a wheat germ cell-free protein expression system. Recombinant proteins were recognized by plasma from RAS-immunized subjects, and 21 induced detectable antibody responses in mice and rabbit and sera from these immunized animals were used to characterize these antigens. All 21 proteins localized to the sporozoite: five localized to the surface, seven localized to the micronemes, cytoplasm, endoplasmic reticulum or nucleus, two localized to the surface and cytoplasm, and seven remain undetermined. PBMC from RAS-immunized volunteers elicited positive ex vivo or cultured ELISpot responses against peptides from 20 of the 21 antigens. Conclusions These T cell and antibody responses support our approach of using reagents from RAS-immunized subjects to screen potential vaccine antigens, and have led to the identification of a panel of novel P. falciparum antigens. These results provide evidence to further evaluate these antigens as vaccine candidates. Trial Registration ClinicalTrials.gov NCT00870987 ClinicalTrials.gov NCT00392015 PMID:26292257

  11. Cross-stage immunity for malaria vaccine development.

    PubMed

    Nahrendorf, Wiebke; Scholzen, Anja; Sauerwein, Robert W; Langhorne, Jean

    2015-12-22

    A vaccine against malaria is urgently needed for control and eventual eradication. Different approaches are pursued to induce either sterile immunity directed against pre-erythrocytic parasites or to mimic naturally acquired immunity by controlling blood-stage parasite densities and disease severity. Pre-erythrocytic and blood-stage malaria vaccines are often seen as opposing tactics, but it is likely that they have to be combined into a multi-stage malaria vaccine to be optimally safe and effective. Since many antigenic targets are shared between liver- and blood-stage parasites, malaria vaccines have the potential to elicit cross-stage protection with immune mechanisms against both stages complementing and enhancing each other. Here we discuss evidence from pre-erythrocytic and blood-stage subunit and whole parasite vaccination approaches that show that protection against malaria is not necessarily stage-specific. Parasites arresting at late liver-stages especially, can induce powerful blood-stage immunity, and similarly exposure to blood-stage parasites can afford pre-erythrocytic immunity. The incorporation of a blood-stage component into a multi-stage malaria vaccine would hence not only combat breakthrough infections in the blood should the pre-erythrocytic component fail to induce sterile protection, but would also actively enhance the pre-erythrocytic potency of this vaccine. We therefore advocate that future studies should concentrate on the identification of cross-stage protective malaria antigens, which can empower multi-stage malaria vaccine development.

  12. Complex Minigene Library Vaccination for Discovery of Pre-Erythrocytic Plasmodium T Cell Antigens

    PubMed Central

    Stone, Brad C.; Kas, Arnold; Billman, Zachary P.; Fuller, Deborah H.; Fuller, James T.; Shendure, Jay; Murphy, Sean C.

    2016-01-01

    Development of a subunit vaccine targeting liver-stage Plasmodium parasites requires the identification of antigens capable of inducing protective T cell responses. However, traditional methods of antigen identification are incapable of evaluating T cell responses against large numbers of proteins expressed by these parasites. This bottleneck has limited development of subunit vaccines against Plasmodium and other complex intracellular pathogens. To address this bottleneck, we are developing a synthetic minigene technology for multi-antigen DNA vaccines. In an initial test of this approach, pools of long (150 bp) antigen-encoding oligonucleotides were synthesized and recombined into vectors by ligation-independent cloning to produce two DNA minigene library vaccines. Each vaccine encoded peptides derived from 36 (vaccine 1) and 53 (vaccine 2) secreted or transmembrane pre-erythrocytic P. yoelii proteins. BALB/cj mice were vaccinated three times with a single vaccine by biolistic particle delivery (gene gun) and screened for interferon-γ-producing T cell responses by ELISPOT. Library vaccination induced responses against four novel antigens. Naïve mice exposed to radiation-attenuated sporozoites mounted a response against only one of the four novel targets (PyMDH, malate dehydrogenase). The response to PyMDH could not be recalled by additional homologous sporozoite immunizations but could be partially recalled by heterologous cross-species sporozoite exposure. Vaccination against the dominant PyMDH epitope by DNA priming and recombinant Listeria boosting did not protect against sporozoite challenge. Improvements in library design and delivery, combined with methods promoting an increase in screening sensitivity, may enable complex minigene screening to serve as a high-throughput system for discovery of novel T cell antigens. PMID:27070430

  13. Plasmodium vivax Pre-Erythrocytic–Stage Antigen Discovery: Exploiting Naturally Acquired Humoral Responses

    PubMed Central

    Molina, Douglas M.; Finney, Olivia C.; Arevalo-Herrera, Myriam; Herrera, Socrates; Felgner, Philip L.; Gardner, Malcolm J.; Liang, Xiaowu; Wang, Ruobing

    2012-01-01

    The development of pre-erythrocytic Plasmodium vivax vaccines is hindered by the lack of in vitro culture systems or experimental rodent models. To help bypass these roadblocks, we exploited the fact that naturally exposed Fy− individuals who lack the Duffy blood antigen (Fy) receptor are less likely to develop blood-stage infections; therefore, they preferentially develop immune responses to pre-erythrocytic–stage parasites, whereas Fy+ individuals experience both liver- and blood-stage infections and develop immune responses to both pre-erythrocytic and erythrocytic parasites. We screened 60 endemic sera from P. vivax-exposed Fy+ or Fy− donors against a protein microarray containing 91 P. vivax proteins with P. falciparum orthologs that were up-regulated in sporozoites. Antibodies against 10 P. vivax antigens were identified in sera from P. vivax-exposed individuals but not unexposed controls. This technology has promising implications in the discovery of potential vaccine candidates against P. vivax malaria. PMID:22826492

  14. Blood-stage immunity to Plasmodium chabaudi malaria following chemoprophylaxis and sporozoite immunization

    PubMed Central

    Nahrendorf, Wiebke; Spence, Philip J; Tumwine, Irene; Lévy, Prisca; Jarra, William; Sauerwein, Robert W; Langhorne, Jean

    2015-01-01

    Protection against malaria in humans can be achieved by repeated exposure to infected mosquito bites during prophylactic chloroquine treatment (chemoprophylaxis and sporozoites (CPS)). We established a new mouse model of CPS immunization to investigate the stage and strain-specificity of malaria immunity. Immunization with Plasmodium chabaudi by mosquito bite under chloroquine cover does not generate pre-erythrocytic immunity, which is acquired only after immunization with high sporozoite doses. Instead, CPS immunization by bite elicits long-lived protection against blood-stage parasites. Blood-stage immunity is effective against a virulent, genetically distinct strain of P. chabaudi. Importantly, if exposure to blood-stage parasitemia is extended, blood-stage parasites induce cross-stage immunity targeting pre-erythrocytic stages. We therefore show that CPS immunization can induce robust, long-lived heterologous blood-stage immunity, in addition to protection against pre-erythrocytic parasites following high dose sporozoite immunization. Cross-stage immunity elicited by blood-stage parasites may further enhance efficacy of this immunization regimen. DOI: http://dx.doi.org/10.7554/eLife.05165.001 PMID:25714922

  15. Comparative efficacy of pre-erythrocytic whole organism vaccine strategies against the malaria parasite.

    PubMed

    Friesen, Johannes; Matuschewski, Kai

    2011-09-16

    Despite major efforts over the past 50 years to develop a malaria vaccine, no product has been licensed yet. Irradiated sporozoites are the benchmark for an experimental live-attenuated malaria vaccine that induces potent protection against re-infection in humans and animal models. Lasting protection can also be elicited by parasite attenuation via tailored genetic modification or drug cover leading to renewed interest in whole-organism vaccination strategies. In this study, we systematically compared the protective efficacy of different whole-organism vaccination approaches in the Plasmodium berghei/C57bl/6 rodent malaria model. We applied blood stage parasitemia and quantitative RT-PCR of liver parasite loads as two complementary primary endpoints of a malaria challenge infection. We were able to demonstrate similar potency of genetic attenuation, i.e., uis3(-) and p36p(-) parasites, and prophylactic drug cover, i.e., azithromycin, pyrimethamine, primaquine and chloroquine, during sporozoite exposure in comparison to irradiated sporozoites. Importantly, when animals were covered with the antibiotic azithromycin during sporozoite exposure we observed superior protection. On the other end, immunizations with heat-killed and over-irradiated sporozoites failed to confer any detectable protection. Together, we show that systematic pre-clinical evaluation and quantification of vaccine efficacy is vital for identification of the most potent whole organism anti-malaria vaccine strategy.

  16. Analysis of a Multi-component Multi-stage Malaria Vaccine Candidate—Tackling the Cocktail Challenge

    PubMed Central

    Voepel, Nadja; Edgue, Gueven; Beiss, Veronique; Kapelski, Stephanie; Fendel, Rolf; Scheuermayer, Matthias; Pradel, Gabriele; Bolscher, Judith M.; Behet, Marije C.; Dechering, Koen J.; Hermsen, Cornelus C.; Sauerwein, Robert W.; Schillberg, Stefan; Reimann, Andreas; Fischer, Rainer

    2015-01-01

    Combining key antigens from the different stages of the P. falciparum life cycle in the context of a multi-stage-specific cocktail offers a promising approach towards the development of a malaria vaccine ideally capable of preventing initial infection, the clinical manifestation as well as the transmission of the disease. To investigate the potential of such an approach we combined proteins and domains (11 in total) from the pre-erythrocytic, blood and sexual stages of P. falciparum into a cocktail of four different components recombinantly produced in plants. After immunization of rabbits we determined the domain-specific antibody titers as well as component-specific antibody concentrations and correlated them with stage specific in vitro efficacy. Using purified rabbit immune IgG we observed strong inhibition in functional in vitro assays addressing the pre-erythrocytic (up to 80%), blood (up to 90%) and sexual parasite stages (100%). Based on the component-specific antibody concentrations we calculated the IC50 values for the pre-erythrocytic stage (17–25 μg/ml), the blood stage (40–60 μg/ml) and the sexual stage (1.75 μg/ml). While the results underline the feasibility of a multi-stage vaccine cocktail, the analysis of component-specific efficacy indicates significant differences in IC50 requirements for stage-specific antibody concentrations providing valuable insights into this complex scenario and will thereby improve future approaches towards malaria vaccine cocktail development regarding the selection of suitable antigens and the ratios of components, to fine tune overall and stage-specific efficacy. PMID:26147206

  17. Progress and prospects for blood-stage malaria vaccines

    PubMed Central

    Miura, Kazutoyo

    2016-01-01

    ABSTRACT There have been significant decreases in malaria mortality and morbidity in the last 10-15 years, and the most advanced pre-erythrocytic malaria vaccine, RTS,S, received a positive opinion from European regulators in July 2015. However, no blood-stage vaccine has reached a phase III trial. The first part of this review summarizes the pros and cons of various assays and models that have been and will be used to predict the efficacy of blood-stage vaccines. In the second part, blood-stage vaccine candidates that showed some efficacy in human clinical trials or controlled human malaria infection models are discussed. Then, candidates under clinical investigation are described in the third part, and other novel candidates and strategies are reviewed in the last part. PMID:26760062

  18. Bioluminescence Imaging to Detect Late Stage Infection of African Trypanosomiasis.

    PubMed

    Burrell-Saward, Hollie; Ward, Theresa H

    2016-01-01

    Human African trypanosomiasis (HAT) is a multi-stage disease that manifests in two stages; an early blood stage and a late stage when the parasite invades the central nervous system (CNS). In vivo study of the late stage has been limited as traditional methodologies require the removal of the brain to determine the presence of the parasites. Bioluminescence imaging is a non-invasive, highly sensitive form of optical imaging that enables the visualization of a luciferase-transfected pathogen in real-time. By using a transfected trypanosome strain that has the ability to produce late stage disease in mice we are able to study the kinetics of a CNS infection in a single animal throughout the course of infection, as well as observe the movement and dissemination of a systemic infection. Here we describe a robust protocol to study CNS infections using a bioluminescence model of African trypanosomiasis, providing real time non-invasive observations which can be further analyzed with optional downstream approaches. PMID:27284970

  19. Selection and refinement: the malaria parasite's infection and exploitation of host hepatocytes.

    PubMed

    Kaushansky, Alexis; Kappe, Stefan Hi

    2015-08-01

    Plasmodium parasites belong to the Apicomplexan phylum, which consists mostly of obligate intracellular pathogens that vary dramatically in host cell tropism. Plasmodium sporozoites are highly hepatophilic. The specific molecular mechanisms, which facilitate sporozoite selection and successful infection of hepatocytes, remain poorly defined. Here, we discuss the parasite and host factors which are critical to hepatocyte infection. We derive a model where sporozoites initially select host cells that constitute a permissive environment and then further refine the chosen hepatocyte during liver stage development, ensuring life cycle progression. While many unknowns of pre-erythrocytic infection remain, advancing models and technologies that enable analysis of human malaria parasites and of single infected cells will catalyze a comprehensive understanding of the interaction between the malaria parasite and its hepatocyte host. PMID:26102161

  20. Blood-stage malaria infection in diabetic mice.

    PubMed Central

    Elased, K; De Souza, J B; Playfair, J H

    1995-01-01

    Infection of mice with blood-stage Plasmodium yoelii and P. chabaudi malaria induced hypoglycaemia in normal mice and normalized the hyperglycaemia of mice made moderately diabetic with streptozotocin (STZ). Injection of parasite supernatants induced hypoglycaemia accompanied by hyperinsulinaemia in normal mice, and in STZ-diabetic mice induced a profound drop in blood glucose and restored insulin secretion; however, severely diabetic mice (two injections of STZ) remained hyperglycaemic with no change in insulin levels. We conclude that malaria infection and parasite-derived molecules lower blood glucose concentration, but only in the presence of some residual pancreatic function. Diabetic mice were less anaemic, exerted a significant control of parasitaemia, and showed enhanced phagocytic activity compared with normal mice. PMID:7882567

  1. Proteomic profiling of the infective trophozoite stage of Acanthamoeba polyphaga.

    PubMed

    Caumo, Karin Silva; Monteiro, Karina Mariante; Ott, Thiely Rodrigues; Maschio, Vinicius José; Wagner, Glauber; Ferreira, Henrique Bunselmeyer; Rott, Marilise Brittes

    2014-12-01

    Acanthamoeba polyphaga is a free-living protozoan pathogen, whose infective trophozoite form is capable of causing a blinding keratitis and fatal granulomatous encephalitis in humans. The damage caused by A. polyphaga trophozoites in human corneal or brain infections is the result of several different pathogenic mechanisms that have not yet been elucidated at the molecular level. We performed a comprehensive analysis of the proteins expressed by A. polyphaga trophozoites, based on complementary 2-DE MS/MS and gel-free LC-MS/MS approaches. Overall, 202 non-redundant proteins were identified. An A. polyphaga proteomic map in the pH range 3-10 was produced, with protein identification for 184 of 370 resolved spots, corresponding to 142 proteins. Additionally, 94 proteins were identified by gel-free LC-MS/MS. Functional classification revealed several proteins with potential importance for pathogen survival and infection of mammalian hosts, including surface proteins and proteins related to defense mechanisms. Our study provided the first comprehensive proteomic survey of the trophozoite infective stage of an Acanthamoeba species, and established foundations for prospective, comparative and functional studies of proteins involved in mechanisms of survival, development, and pathogenicity in A. polyphaga and other pathogenic amoebae.

  2. Parasitic infection in various stages life of cultured Acipenser persicus

    PubMed Central

    Adel, Milad; Safari, Reza; Yaghoubzadeh, Zahra; Fazli, Hassan; Khalili, Elham

    2016-01-01

    The present study was conducted to evaluate the status of the parasite fauna in Acipenser persicus at different development stages, in order to find prevention protocols for parasitic diseases in this valuable species. For this purpose, sampling from each sex breeder, 10 egg samples, 5-day-old larvae (n = 20), 20-day-old larvae (n = 80) and fingerling of A. persicus (n = 60) released in earthen ponds were done. After the bioassay and preparing wet mount from the internal and external organs, identification was done according to the keys. According to the results, no fauna parasites were isolated from egg samples and 5-day-old larvae; but Trichodina spp. was isolated from 20-day-old larvae. Also, the same protozoan was isolated from fingerling released in earthen ponds, the mean intensity, prevalence and range of contamination by fingerling were higher with compared to 20-day-old larvae. Trichodina sp. and Diplostomum spathaceum were isolated from skin and eyes of females, respectively. However, Trichodina sp. and Ichthyophthirius multifiliis were isolated from skin of male breeders. In this study, no parasites were isolated from internal organs of larves and fingerling but four intestinal parasites included: Cucullanus sphaerocephlaus, Anisakis sp., Skyrjabinopsilus semiarmatus, and Lepto-rhynchoides plagicephalu were isolated from internal organs of breeder. Based on a wide range of parasitic infection observed in various life stages of A. persicus, it seems necessary to consider hygienic and management measures. PMID:27226891

  3. Innate immunity induced by Plasmodium liver infection inhibits malaria reinfections.

    PubMed

    Liehl, Peter; Meireles, Patrícia; Albuquerque, Inês S; Pinkevych, Mykola; Baptista, Fernanda; Mota, Maria M; Davenport, Miles P; Prudêncio, Miguel

    2015-03-01

    Following transmission through a mosquito bite to the mammalian host, Plasmodium parasites first invade and replicate inside hepatocytes before infecting erythrocytes and causing malaria. The mechanisms limiting Plasmodium reinfections in humans living in regions of malaria endemicity have mainly been explored by studying the resistance induced by the blood stage of infection. However, epidemiologic studies have suggested that in high-transmission areas, preerythrocytic stages also activate host resistance to reinfection. This, along with the recent discovery that liver infections trigger a specific and effective type I interferon (IFN) response, prompted us to hypothesize that this pre-erythrocyte-stage-induced resistance is linked to liver innate immunity. Here, we combined experimental approaches and mathematical modeling to recapitulate field studies and understand the molecular basis behind such resistance. We present a newly established mouse reinfection model and demonstrate that rodent malaria liver-stage infection inhibits reinfection. This protection relies on the activation of innate immunity and involves the type I IFN response and the antimicrobial cytokine gamma IFN (IFN-γ). Importantly, mathematical simulations indicate that the predictions based on our experimental murine reinfection model fit available epidemiological data. Overall, our study revealed that liver-stage-induced innate immunity may contribute to the preerythrocytic resistance observed in humans in regions of malaria hyperendemicity.

  4. Stage-dependent model for Hantavirus infection: The effect of the initial infection-free period

    NASA Astrophysics Data System (ADS)

    Reinoso, José A.; de la Rubia, F. Javier

    2013-04-01

    We propose a stage-dependent model with constant delay to study the effect of the initial infection-free period on the spread of Hantavirus infection in rodents. We analyze the model under various extreme weather conditions, in the context of the El Niño-La Niña Southern Oscillation phenomenon, and show how these variations determine the evolution of the system significantly. When the scenario corresponds to El Niño, the system presents a demographic explosion and a delayed outbreak of Hantavirus infection, whereas if the scenario is the opposite there is a rapid decline of the population, but with a possible persistence period that may imply a considerable risk for public health, a fact that is in agreement with available field data. We use the model to simulate a historical evolution that resembles the processes that occurred in the 1990s.

  5. Prevalence of psychiatric disorders in early stages of HIV infection.

    PubMed

    Brown, G R; Rundell, J R; McManis, S E; Kendall, S N; Zachary, R; Temoshok, L

    1992-01-01

    As part of a military universal HIV screening program, 442 men were assessed for the presence of DSM-III-R defined psychiatric disorders and symptoms of anxiety and depression after notification of HIV seroconversion. Of them, 84.4% were in the earliest, asymptomatic stages of disease at the time of interview (96% did not have AIDS). The Structured Clinical Interview for DSM-III-R and Structured Interview Guide for the Hamilton Anxiety and Depression Scales were used. Relevant comparisons were made to Epidemiologic Catchment Area prevalence data. HIV seropositive men were more likely than age-matched men in the community to have current diagnoses of major depression (ages 18-44) and anxiety disorders (ages 25-44). Higher lifetime rates of major depression and alcohol use disorder, and high current prevalence of sexual dysfunction (21.7%) were noted. We conclude that men who become HIV seropositive have high rates of mood and substance use disorders prior to knowledge of seroconversion, and that early in the course of HIV infection men are at risk for developing major depression, anxiety disorders, and disorders of sexual desire. PMID:1438661

  6. Infrared spectral changes identified during different stages of herpes viruses infection in vitro.

    PubMed

    Erukhimovitch, V; Bogomolny, E; Huleihil, M; Huleihel, M

    2011-07-01

    Microscopic Fourier transform infrared spectroscopy (FTIR) which is based on the characteristic molecular vibrational spectra of cells was previously applied for the identification of various biological samples. In the present study, FTIR spectroscopy was used for the characterization of different stages during the development of herpes viruses infection. Vero cells in culture were infected with high and low doses of different herpes viruses [herpes simplex virus types 1 and 2 (HSV-1, -2) or varicella-zoster virus (VZV)], and cellular changes were observed by optical and electron microscopy and analyzed by FTIR microscopy at different periods of time post-infection. Specific different spectral changes were observed at various stages of the viral infection development. The spectral intensity in the 1220-1260 cm(-1) region (mainly attributed to phosphate levels) was considerably increased in all infected cells compared to normal uninfected cells during the early stages of the viral infection development. However, at the late stages of the viral infection development (when all the cells in the infected culture lost their spindle shape and became circular) the spectral intensities in this region significantly decreased in the infected compared to the control cells. In addition, the peak at 1023 cm(-1), attributed to carbohydrates, almost fully disappeared at early stages of the viral infection development, whereas at late stages of the infection it raised to an equivalent or higher level than that of the uninfected control cells. These results support the potential of developing FTIR microspectroscopy as a simple, reagent free method for the early detection and accurate differentiation of different stages during the development of herpes virus infection.

  7. Nitroheterocyclic drugs cure experimental Trypanosoma cruzi infections more effectively in the chronic stage than in the acute stage

    PubMed Central

    Francisco, Amanda Fortes; Jayawardhana, Shiromani; Lewis, Michael D.; White, Karen L.; Shackleford, David M.; Chen, Gong; Saunders, Jessica; Osuna-Cabello, Maria; Read, Kevin D.; Charman, Susan A.; Chatelain, Eric; Kelly, John M.

    2016-01-01

    The insect-transmitted protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, and infects 5–8 million people in Latin America. Chagas disease is characterised by an acute phase, which is partially resolved by the immune system, but then develops as a chronic life-long infection. There is a consensus that the front-line drugs benznidazole and nifurtimox are more effective against the acute stage in both clinical and experimental settings. However, confirmative studies have been restricted by difficulties in demonstrating sterile parasitological cure. Here, we describe a systematic study of nitroheterocyclic drug efficacy using highly sensitive bioluminescence imaging of murine infections. Unexpectedly, we find both drugs are more effective at curing chronic infections, judged by treatment duration and therapeutic dose. This was not associated with factors that differentially influence plasma drug concentrations in the two disease stages. We also observed that fexinidazole and fexinidazole sulfone are more effective than benznidazole and nifurtimox as curative treatments, particularly for acute stage infections, most likely as a result of the higher and more prolonged exposure of the sulfone derivative. If these findings are translatable to human patients, they will have important implications for treatment strategies. PMID:27748443

  8. The stability analysis of a general viral infection model with distributed delays and multi-staged infected progression

    NASA Astrophysics Data System (ADS)

    Wang, Jinliang; Liu, Shengqiang

    2015-01-01

    We investigate an in-host model with general incidence and removal rate, as well as distributed delays in virus infections and in productions. By employing Lyapunov functionals and LaSalle's invariance principle, we define and prove the basic reproductive number R0 as a threshold quantity for stability of equilibria. It is shown that if R0 > 1 , then the infected equilibrium is globally asymptotically stable, while if R0 ⩽ 1 , then the infection free equilibrium is globally asymptotically stable under some reasonable assumptions. Moreover, n + 1 distributed delays describe (i) the time between viral entry and the transcription of viral RNA, (ii) the n - 1 -stage time needed for activated infected cells between viral RNA transcription and viral release, and (iii) the time necessary for the newly produced viruses to be infectious (maturation), respectively. The model can describe the viral infection dynamics of many viruses such as HIV-1, HCV and HBV.

  9. Cancer Stage at Diagnosis in HIV-infected People and Transplant Recipients

    PubMed Central

    Shiels, Meredith S.; Copeland, Glenn; Goodman, Marc T.; Harrell, Janna; Lynch, Charles F.; Pawlish, Karen; Pfeiffer, Ruth M.; Engels, Eric A.

    2015-01-01

    Background It is unknown whether immunosuppression results in more aggressive, advanced stage cancers. As cancer stage is influenced both by tumor biology and medical surveillance, we assessed cancer stage in HIV-infected individuals and solid organ transplant recipients, two immunosuppressed groups with differences in healthcare utilization. Methods We used data on all cases of 15 cancer types, diagnosed during 1996–2010 in two studies that linked U.S. cancer registries to HIV and transplant registries. Odds ratios (ORs) for advanced (vs. local) disease were estimated comparing HIV and transplant populations to immunocompetent people in polytomous logistic regression models, adjusted for age, sex, race, registry and year. Results A total of 8,411 of 4.5 million cancer cases occurred in HIV-infected people, and 7,322 of 6.4 million cancer cases occurred in transplant recipients. Compared to immunocompetent people with cancer, HIV-infected people were more likely to be diagnosed with distant stage lung (OR=1.13), female breast (OR=1.99), and prostate cancers (OR=1.57), while transplant recipients had fewer distant stage lung (OR=0.54), female breast (OR=0.75) and prostate cancers (OR=0.72). Both immunosuppressed populations had a shift toward advanced stage melanoma (ORs: HIV=1.97; transplant=1.82) and bladder cancer (ORs: HIV=1.42; transplant=1.54). Conclusions Bladder cancer and melanoma were more likely to be diagnosed at non-local stage in both HIV-infected people and transplant recipients, suggesting a role of immunosuppression in their progression. Additionally, we observed a shift for some common cancers toward later stages in HIV-infected individuals and toward earlier stages in transplant recipients, consistent with differential access to medical care or surveillance. PMID:25739496

  10. Tools for the diagnosis of hepatitis C virus infection and hepatic fibrosis staging

    PubMed Central

    Saludes, Verónica; González, Victoria; Planas, Ramon; Matas, Lurdes; Ausina, Vicente; Martró, Elisa

    2014-01-01

    Hepatitis C virus (HCV) infection represents a major public health issue. Hepatitis C can be cured by therapy, but many infected individuals are unaware of their status. Effective HCV screening, fast diagnosis and characterization, and hepatic fibrosis staging are highly relevant for controlling transmission, treating infected patients and, consequently, avoiding end-stage liver disease. Exposure to HCV can be determined with high sensitivity and specificity with currently available third generation serology assays. Additionally, the use of point-of-care tests can increase HCV screening opportunities. However, active HCV infection must be confirmed by direct diagnosis methods. Additionally, HCV genotyping is required prior to starting any treatment. Increasingly, high-volume clinical laboratories use different types of automated platforms, which have simplified sample processing, reduced hands-on-time, minimized contamination risks and human error and ensured full traceability of results. Significant advances have also been made in the field of fibrosis stage assessment with the development of non-invasive methods, such as imaging techniques and serum-based tests. However, no single test is currently available that is able to completely replace liver biopsy. This review focuses on approved commercial tools used to diagnose HCV infection and the recommended hepatic fibrosis staging tests. PMID:24707126

  11. Febrile temperatures induce cytoadherence of ring-stage Plasmodium falciparum-infected erythrocytes.

    PubMed

    Udomsangpetch, Rachanee; Pipitaporn, Busaba; Silamut, Kamolrat; Pinches, Robert; Kyes, Sue; Looareesuwan, Sornchai; Newbold, Christopher; White, Nicholas J

    2002-09-01

    In falciparum malaria, the malaria parasite induces changes at the infected red blood cell surface that lead to adherence to vascular endothelium and other red blood cells. As a result, the more mature stages of Plasmodium falciparum are sequestered in the microvasculature and cause vital organ dysfunction, whereas the ring stages circulate in the blood stream. Malaria is characterized by fever. We have studied the effect of febrile temperatures on the cytoadherence in vitro of P. falciparum-infected erythrocytes. Freshly obtained ring-stage-infected red blood cells from 10 patients with acute falciparum malaria did not adhere to the principle vascular adherence receptors CD36 or intercellular adhesion molecule-1 (ICAM-1). However, after a brief period of heating to 40 degrees C, all ring-infected red blood cells adhered to CD36, and some isolates adhered to ICAM-1, whereas controls incubated at 37 degrees C did not. Heating to 40 degrees C accelerated cytoadherence and doubled the maximum cytoadherence observed (P < 0.01). Erythrocytes infected by ring-stages of the ICAM-1 binding clone A4var also did not cytoadhere at 37 degrees C, but after heating to febrile temperatures bound to both CD36 and ICAM-1. Adherence of red blood cells infected with trophozoites was also increased considerably by brief heating. The factor responsible for heat induced adherence was shown to be the parasite derived variant surface protein PfEMP-1. RNA analysis showed that levels of var mRNA did not differ between heated and unheated ring-stage parasites. Thus fever-induced adherence appeared to involve increased trafficking of PfEMP-1 to the erythrocyte membrane. Fever induced cytoadherence is likely to have important pathological consequences and may explain both clinical deterioration with fever in severe malaria and the effects of antipyretics on parasite clearance. PMID:12177447

  12. Alzheimer's disease Braak Stage progressions: reexamined and redefined as Borrelia infection transmission through neural circuits.

    PubMed

    MacDonald, Alan B

    2007-01-01

    Brain structure in health is a dynamic energized equation incorporating chemistry, neuronal structure, and circuitry components. The chemistry "piece" is represented by multiple neurotransmitters such as Acetylcholine, Serotonin, and Dopamine. The neuronal structure "piece" incorporates synapses and their connections. And finally circuits of neurons establish "architectural blueprints" of anatomic wiring diagrams of the higher order of brain neuron organizations. In Alzheimer's disease, there are progressive losses in all of these components. Brain structure crumbles. The deterioration in Alzheimer's is ordered, reproducible, and stepwise. Drs. Braak and Braak have described stages in the Alzheimer disease continuum. "Progressions" through Braak Stages benchmark "Regressions" in Cognitive function. Under the microscope, the Stages of Braak commence in brain regions near to the hippocampus, and over time, like a tsunami wave of destruction, overturn healthy brain regions, with neurofibrillary tangle damaged neurons "marching" through the temporal lobe, neocortex and occipital cortex. In effect the destruction ascends from the limbic regions to progressively destroy the higher brain centers. Rabies infection also "begins low and finishes high" in its wave of destruction of brain tissue. Herpes Zoster infections offer the paradigm of clinical latency of infection inside of nerves before the "marching commences". Varicella Zoster virus enters neurons in the pediatric years. Dormant virus remains inside the neurons for 50-80 years, tissue damage late in life (shingles) demonstrates the "march of the infection" down neural pathways (dermatomes) as linear areas of painful blisters loaded with virus from a childhood infection. Amalgamation of Zoster with Rabies models produces a hybrid model to explain all of the Braak Stages of Alzheimer's disease under a new paradigm, namely "Alzheimer's neuroborreliosis" in which latent Borrelia infections ascend neural circuits through

  13. Pseudomonas aeruginosa In Vitro Phenotypes Distinguish Cystic Fibrosis Infection Stages and Outcomes

    PubMed Central

    Rosenfeld, Margaret; Gibson, Ronald L.; Ramsey, Bonnie W.; Kulasekara, Hemantha D.; Retsch-Bogart, George Z.; Morgan, Wayne; Wolter, Daniel J.; Pope, Christopher E.; Houston, Laura S.; Kulasekara, Bridget R.; Khan, Umer; Burns, Jane L.; Miller, Samuel I.; Hoffman, Lucas R.

    2014-01-01

    Rationale: Pseudomonas aeruginosa undergoes phenotypic changes during cystic fibrosis (CF) lung infection. Although mucoidy is traditionally associated with transition to chronic infection, we hypothesized that additional in vitro phenotypes correlate with this transition and contribute to disease. Objectives: To characterize the relationships between in vitro P. aeruginosa phenotypes, infection stage, and clinical outcomes. Methods: A total of 649 children with CF and newly identified P. aeruginosa were followed for a median 5.4 years during which a total of 2,594 P. aeruginosa isolates were collected. Twenty-six in vitro bacterial phenotypes were assessed among the isolates, including measures of motility, exoproduct production, colony morphology, growth, and metabolism. Measurements and Main Results: P. aeruginosa phenotypes present at the time of culture were associated with both stage of infection (new onset, intermittent, or chronic) and the primary clinical outcome, occurrence of a pulmonary exacerbation (PE) in the subsequent 2 years. Two in vitro P. aeruginosa phenotypes best distinguished infection stages: pyoverdine production (31% of new-onset cultures, 48% of intermittent, 69% of chronic) and reduced protease production (31%, 39%, and 65%, respectively). The best P. aeruginosa phenotypic predictors of subsequent occurrence of a PE were mucoidy (odds ratio, 1.75; 95% confidence interval, 1.19–2.57) and reduced twitching motility (odds ratio, 1.43; 95% confidence interval, 1.11–1.84). Conclusions: In this large epidemiologic study of CF P. aeruginosa adaptation, P. aeruginosa isolates exhibited two in vitro phenotypes that best distinguished early and later infection stages. Among the many phenotypes tested, mucoidy and reduced twitching best predicted subsequent PE. These phenotypes indicate potentially useful prognostic markers of transition to chronic infection and advancing lung disease. PMID:24937177

  14. Dynamics of a Class of HIV Infection Models with Cure of Infected Cells in Eclipse Stage.

    PubMed

    Maziane, Mehdi; Lotfi, El Mehdi; Hattaf, Khalid; Yousfi, Noura

    2015-12-01

    In this paper, we propose two HIV infection models with specific nonlinear incidence rate by including a class of infected cells in the eclipse phase. The first model is described by ordinary differential equations (ODEs) and generalizes a set of previously existing models and their results. The second model extends our ODE model by taking into account the diffusion of virus. Furthermore, the global stability of both models is investigated by constructing suitable Lyapunov functionals. Finally, we check our theoretical results with numerical simulations.

  15. Fasciola hepatica induces eosinophil apoptosis in the migratory and biliary stages of infection in sheep.

    PubMed

    Escamilla, A; Bautista, M J; Zafra, R; Pacheco, I L; Ruiz, M T; Martínez-Cruz, S; Méndez, A; Martínez-Moreno, A; Molina-Hernández, V; Pérez, J

    2016-01-30

    The aim of the present work was to evaluate the number of apoptotic eosinophils in the livers of sheep experimentally infected with Fasciola hepatica during the migratory and biliary stages of infection. Four groups (n=5) of sheep were used; groups 1-3 were orally infected with 200 metacercariae (mc) and sacrificed at 8 and 28 days post-infection (dpi), and 17 weeks post-infection (wpi), respectively. Group 4 was used as an uninfected control. Apoptosis was detected using immunohistochemistry with a polyclonal antibody against anti-active caspase-3, and transmission electron microscopy (TEM). Eosinophils were identified using the Hansel stain in serial sections for caspase-3, and by ultrastructural features using TEM. At 8 and 28 dpi, numerous caspase-3(+) eosinophils were mainly found at the periphery of acute hepatic necrotic foci. The percentage of caspase -3(+) apoptotic eosinophils in the periphery of necrotic foci was high (46.1-53.9) at 8 and 28 dpi, respectively, and decreased in granulomas found at 28 dpi (6%). Transmission electron microscopy confirmed the presence of apoptotic eosinophils in hepatic lesions at 8 and 28 dpi. At 17 wpi, apoptotic eosinophils were detected in the infiltrate surrounding some enlarged bile ducts containing adult flukes. This is the first report of apoptosis induced by F. hepatica in sheep and the first study reporting apoptosis in eosinophils in hepatic inflammatory infiltrates in vivo. The high number of apoptotic eosinophils in acute necrotic tracts during the migratory and biliary stages of infection suggests that eosinophil apoptosis may play a role in F. hepatica survival during different stages of infection.

  16. ZIPCO, a putative metal ion transporter, is crucial for Plasmodium liver-stage development

    PubMed Central

    Sahu, Tejram; Boisson, Bertrand; Lacroix, Céline; Bischoff, Emmanuel; Richier, Quentin; Formaglio, Pauline; Thiberge, Sabine; Dobrescu, Irina; Ménard, Robert; Baldacci, Patricia

    2014-01-01

    The malaria parasite, Plasmodium, requires iron for growth, but how it imports iron remains unknown. We characterize here a protein that belongs to the ZIP (Zrt-, Irt-like Protein) family of metal ion transport proteins and have named ZIP domain-containing protein (ZIPCO). Inactivation of the ZIPCO-encoding gene in Plasmodium berghei, while not affecting the parasite's ability to multiply in mouse blood and to infect mosquitoes, greatly impairs its capacity to develop inside hepatocytes. Iron/zinc supplementation and depletion experiments suggest that ZIPCO is required for parasite utilization of iron and possibly zinc, consistent with its predicted function as a metal transporter. This is the first report of a ZIP protein having a crucial role in Plasmodium liver-stage development, as well as the first metal ion transporter identified in Plasmodium pre-erythrocytic stages. Because of the drastic dependence on iron of Plasmodium growth, ZIPCO and related proteins might constitute attractive drug targets to fight against malaria. PMID:25257508

  17. ZIPCO, a putative metal ion transporter, is crucial for Plasmodium liver-stage development.

    PubMed

    Sahu, Tejram; Boisson, Bertrand; Lacroix, Céline; Bischoff, Emmanuel; Richier, Quentin; Formaglio, Pauline; Thiberge, Sabine; Dobrescu, Irina; Ménard, Robert; Baldacci, Patricia

    2014-11-01

    The malaria parasite, Plasmodium, requires iron for growth, but how it imports iron remains unknown. We characterize here a protein that belongs to the ZIP (Zrt-, Irt-like Protein) family of metal ion transport proteins and have named ZIP domain-containing protein (ZIPCO). Inactivation of the ZIPCO-encoding gene in Plasmodium berghei, while not affecting the parasite's ability to multiply in mouse blood and to infect mosquitoes, greatly impairs its capacity to develop inside hepatocytes. Iron/zinc supplementation and depletion experiments suggest that ZIPCO is required for parasite utilization of iron and possibly zinc, consistent with its predicted function as a metal transporter. This is the first report of a ZIP protein having a crucial role in Plasmodium liver-stage development, as well as the first metal ion transporter identified in Plasmodium pre-erythrocytic stages. Because of the drastic dependence on iron of Plasmodium growth, ZIPCO and related proteins might constitute attractive drug targets to fight against malaria. PMID:25257508

  18. Dynamics of an HIV Model with Multiple Infection Stages and Treatment with Different Drug Classes.

    PubMed

    Wang, Xia; Song, Xinyu; Tang, Sanyi; Rong, Libin

    2016-02-01

    Highly active antiretroviral therapy can effectively control HIV replication in infected individuals. Some clinical and modeling studies suggested that viral decay dynamics may depend on the inhibited stages of the viral replication cycle. In this paper, we develop a general mathematical model incorporating multiple infection stages and various drug classes that can interfere with specific stages of the viral life cycle. We derive the basic reproductive number and obtain the global stability results of steady states. Using several simple cases of the general model, we study the effect of various drug classes on the dynamics of HIV decay. When drugs are assumed to be 100% effective, drugs acting later in the viral life cycle lead to a faster or more rapid decay in viremia. This is consistent with some patient and experimental data, and also agrees with previous modeling results. When drugs are not 100% effective, the viral decay dynamics are more complicated. Without a second population of long-lived infected cells, the viral load decline can have two phases if drugs act at an intermediate stage of the viral replication cycle. The slopes of viral load decline depend on the drug effectiveness, the death rate of infected cells at different stages, and the transition rate of infected cells from one to the next stage. With a second population of long-lived infected cells, the viral load decline can have three distinct phases, consistent with the observation in patients receiving antiretroviral therapy containing the integrase inhibitor raltegravir. We also fit modeling prediction to patient data under efavirenz (a nonnucleoside reverse-transcriptase inhibitor) and raltegravir treatment. The first-phase viral load decline under raltegravir therapy is longer than that under efavirenz, resulting in a lower viral load at initiation of the second-phase decline in patients taking raltegravir. This explains why patients taking a raltegravir-based therapy were faster to achieve

  19. Dynamics of an HIV Model with Multiple Infection Stages and Treatment with Different Drug Classes.

    PubMed

    Wang, Xia; Song, Xinyu; Tang, Sanyi; Rong, Libin

    2016-02-01

    Highly active antiretroviral therapy can effectively control HIV replication in infected individuals. Some clinical and modeling studies suggested that viral decay dynamics may depend on the inhibited stages of the viral replication cycle. In this paper, we develop a general mathematical model incorporating multiple infection stages and various drug classes that can interfere with specific stages of the viral life cycle. We derive the basic reproductive number and obtain the global stability results of steady states. Using several simple cases of the general model, we study the effect of various drug classes on the dynamics of HIV decay. When drugs are assumed to be 100% effective, drugs acting later in the viral life cycle lead to a faster or more rapid decay in viremia. This is consistent with some patient and experimental data, and also agrees with previous modeling results. When drugs are not 100% effective, the viral decay dynamics are more complicated. Without a second population of long-lived infected cells, the viral load decline can have two phases if drugs act at an intermediate stage of the viral replication cycle. The slopes of viral load decline depend on the drug effectiveness, the death rate of infected cells at different stages, and the transition rate of infected cells from one to the next stage. With a second population of long-lived infected cells, the viral load decline can have three distinct phases, consistent with the observation in patients receiving antiretroviral therapy containing the integrase inhibitor raltegravir. We also fit modeling prediction to patient data under efavirenz (a nonnucleoside reverse-transcriptase inhibitor) and raltegravir treatment. The first-phase viral load decline under raltegravir therapy is longer than that under efavirenz, resulting in a lower viral load at initiation of the second-phase decline in patients taking raltegravir. This explains why patients taking a raltegravir-based therapy were faster to achieve

  20. Lactobacilli are prominent in the initial stages of polymicrobial infection of dental pulp.

    PubMed

    Nadkarni, Mangala A; Simonian, Mary R; Harty, Derek W S; Zoellner, Hans; Jacques, Nicholas A; Hunter, Neil

    2010-05-01

    In earlier studies we used molecular methods to identify the major bacterial consortia associated with advanced dentin caries. These consortia are dominated by bacteria from the families Lactobacillaceae, Streptococcaceae, Veillonellaceae (formerly Acidaminococcaceae), Eubacteriaceae, and Lachnospiraceae from the phylum Firmicutes; Coriobacteriaceae, Bifidobacteriaceae, and Propionibacteriaceae from the phylum Actinobacteria; and Prevotellaceae from the phylum Bacteroidetes, as well as fusobacteria. The phases of infection of vital pulp tissue by dentin microorganisms remain obscure. In the present study, fluorescence in situ hybridization was performed on sections of tissue embedded in resin. Probes for 16S rRNA corresponding to the major taxa of bacteria in carious dentin were used to provide information on the characteristics of pulp infection. Lactobacilli were prominent in 7 of 8 pulps determined to be at a limited stage of infection. Established infection (6 pulps) showed a more complex profile, with lactobacilli persisting in all of the lesions and with invasion of the necrotic regions of tissue by Bacteroidetes, fusobacteria, Lachnospiraceae, and Coriobacteriaceae in particular. Advanced infections (7 pulps) were characterized by mixed anaerobic species, with a strong representation by Coriobacteriaceae and Lachnospiraceae. Lactobacilli were not represented at this stage. Typically, groups of organisms were spatially isolated within the pulp tissue. Analysis indicated that lactobacilli could invade vital pulp tissue to achieve a very high biomass that was not associated with a detectable local inflammatory infiltrate. The findings establish that invasion of the dental pulp can be associated with a pronounced selection from the complex microbial populations within carious dentin, suggesting specific pathogenicity. PMID:20200294

  1. Evaluation of immuno diagnostic assay for the exposure of stage specific filarial infection.

    PubMed

    Ravishankaran, Rajendran; Shridharan, Radhika Nagamangalam; Vishal, Lawrence Ansel; Meenakshisundaram, Sankaranarayanan; Karande, Anjali Anoop; Kaliraj, Perumal

    2016-03-01

    Lymphatic filariasis is a debilitating diseases caused by filarial parasitic nematodes. The infection may be acquired in childhood but the symptoms become apparent only in later life. To evaluate the success of any intervention, sensitive diagnostics were used to identify infection among endemic normals that are likely to develop microfilaremia in due course of time. Capture assay was standardized using the recombinant protein Brugia malayi Abundant Larval Transcript-2 (ALT-2) specific monoclonal and poly-clonal antibodies and evaluated with serum samples of clinical groups from high and low filarial infection area individuals (HIA/LIA), Endemic Normal (EN, n = 478), microfilaeremics (MF, n = 77), chronic pathology (CP, n = 57) and non endemic normal (NEN, n = 20). In order to assess stage-specific infection, ALT-2 capture assay was compared with the early reported Venom allergen homologue (VAH) and microfilariae specific SXP-1 capture assays. Of the 632 serum samples tested, ALT-2 and VAH capture assays detected circulating filarial antigen (CFA) in 57% and 52% of HIA-EN individuals, respectively. As expected, the VAH and SXP-1 capture assays were positive for 100 % of MF individuals. The described capture assays can be useful for the detection of early and stage-specific filarial infections in endemic regions of developing countries. PMID:27078646

  2. The relationship between cognitive reserve and the clinical stage of HIV infection.

    PubMed

    Alvarez-Tostado, Pablo; Inozemtseva, Olga; Aguiñiga, Miguel A; López, Enrique; Matute, Esmeralda

    2016-01-01

    The objective of this study was to determine whether the effect of cognitive reserve (CR) on neuropsychological functioning differs according to the clinical stage of HIV infection. A sample of 34 HIV-positive individuals aged 23-49, with a minimum of 9 years of formal education, was assessed. Participants were grouped according to the Centers for Disease Control and Prevention's (CDC) clinical stages (A = 10, B = 16, C = 8). CR was calculated for each clinical stage group in accordance with estimates of premorbid IQ, years of education, and occupational attainment. The sum of these three variables was then transformed into z-scores. Individuals above the median were classified as having "High" CR (HCR), those below the median were classified as "Low" CR (LCR). Participants completed an evaluation of cognitive and executive functions based on selected, modified tasks from the HIV University of Miami Annotated Neuropsychological test in Spanish (HUMANS). Assessment included the following domains: attention, memory (visual, verbal, and working memory), executive functions (cognitive flexibility, switching), language (naming), and visual constructive skills (block design). HCR outperformed LCR in all cognitive domains. Comparison of HCR and LCR in each clinical stage revealed that the effect of CR was stronger in stage B than in stages A and C, suggesting that this effect does indeed vary among stages.

  3. Two-stage hierarchical group testing for multiple infections with application to the Infertility Prevention Project

    PubMed Central

    Tebbs, Joshua M.; McMahan, Christopher S.; Bilder, Christopher R.

    2015-01-01

    Summary Screening for sexually transmitted diseases has benefited greatly from the use of group testing (pooled testing) to lower costs. With the development of assays that detect multiple infections, screening practices now involve testing pools of individuals for multiple infections simultaneously. Building on the research for single infection group testing procedures, we examine the performance of group testing for multiple infections. Our work is motivated by chlamydia and gonorrhea testing for the Infertility Prevention Project (IPP), a national program in the United States. We consider a two-stage pooling algorithm currently used to perform testing for the IPP. We first derive the operating characteristics of this algorithm for classification purposes (e.g., expected number of tests, misclassification probabilities, etc.) and identify pool sizes that minimize the expected number of tests. We then develop an expectation-maximization algorithm to estimate probabilities of infection using both group and individual retest responses. Our research shows that group testing can offer large cost savings when classifying individuals for multiple infections and can provide prevalence estimates that are actually more efficient than those from individual testing. PMID:24117173

  4. Cucumber Necrosis Virus Recruits Cellular Heat Shock Protein 70 Homologs at Several Stages of Infection

    PubMed Central

    Alam, Syed Benazir

    2015-01-01

    ABSTRACT RNA viruses often depend on host factors for multiplication inside cells due to the constraints of their small genome size and limited coding capacity. One such factor that has been exploited by several plant and animal viruses is heat shock protein 70 (HSP70) family homologs which have been shown to play roles for different viruses in viral RNA replication, viral assembly, disassembly, and cell-to-cell movement. Using next generation sequence analysis, we reveal that several isoforms of Hsp70 and Hsc70 transcripts are induced to very high levels during cucumber necrosis virus (CNV) infection of Nicotiana benthamiana and that HSP70 proteins are also induced by at least 10-fold. We show that HSP70 family protein homologs are co-opted by CNV at several stages of infection. We have found that overexpression of Hsp70 or Hsc70 leads to enhanced CNV genomic RNA, coat protein (CP), and virion accumulation, whereas downregulation leads to a corresponding decrease. Hsc70-2 was found to increase solubility of CNV CP in vitro and to increase accumulation of CNV CP independently of viral RNA replication during coagroinfiltration in N. benthamiana. In addition, virus particle assembly into virus-like particles in CP agroinfiltrated plants was increased in the presence of Hsc70-2. HSP70 was found to increase the targeting of CNV CP to chloroplasts during infection, reinforcing the role of HSP70 in chloroplast targeting of host proteins. Hence, our findings have led to the discovery of a highly induced host factor that has been co-opted to play multiple roles during several stages of the CNV infection cycle. IMPORTANCE Because of the small size of its RNA genome, CNV is dependent on interaction with host cellular components to successfully complete its multiplication cycle. We have found that CNV induces HSP70 family homologs to a high level during infection, possibly as a result of the host response to the high levels of CNV proteins that accumulate during infection

  5. Transcriptome Analysis of the Initial Stage of Acute WSSV Infection Caused by Temperature Change

    PubMed Central

    Sun, Yumiao; Li, Fuhua; Sun, Zheng; Zhang, Xiaojun; Li, Shihao; Zhang, Chengsong; Xiang, Jianhai

    2014-01-01

    White spot syndrome virus (WSSV) is the most devastating virosis threatening the shrimp culture industry worldwide. Variations of environmental factors in shrimp culture ponds usually lead to the outbreak of white spot syndrome (WSS). In order to know the molecular mechanisms of WSS outbreak induced by temperature variation and the biological changes of the host at the initial stage of WSSV acute infection, RNA-Seq technology was used to analyze the differentially expressed genes (DEGs) in shrimp with a certain amount of WSSV cultured at 18°C and shrimp whose culture temperature were raised to 25°C. To analyze whether the expression changes of the DEGs were due to temperature rising or WSSV proliferation, the expression of selected DEGs was analyzed by real-time PCR with another shrimp group, namely Group T, as control. Group T didn’t suffer WSSV infection but was subjected to temperature rising in parallel. At the initial stage of WSSV acute infection, DEGs related to energy production were up-regulated, whereas most DEGs related to cell cycle and positive regulation of cell death and were down-regulated. Triose phosphate isomerase, enolase and alcohol dehydrogenase involved in glycosis were up-regulated, while pyruvate dehydrogenase, citrate synthase and isocitrate dehydrogenase with NAD as the coenzyme involved in TCA pathway were down-regulated. Also genes involved in host DNA replication, including DNA primase, DNA topoisomerase and DNA polymerase showed down-regulated expression. Several interesting genes including crustin genes, acting binding or inhibiting protein genes, a disintegrin and metalloproteinase domain-containing protein 9 (ADAM9) gene and a GRP 78 gene were also analyzed. Understanding the interactions between hosts and WSSV at the initial stage of acute infection will not only help to get a deep insight into the pathogenesis of WSSV but also provide clues for therapies. PMID:24595043

  6. Separation of Plasmodium falciparum Late Stage-infected Erythrocytes by Magnetic Means

    PubMed Central

    Coronado, Lorena Michelle; Tayler, Nicole Michelle; Correa, Ricardo; Giovani, Rita Marissa; Spadafora, Carmenza

    2013-01-01

    Unlike other Plasmodium species, P. falciparum can be cultured in the lab, which facilitates its study 1. While the parasitemia achieved can reach the ≈40% limit, the investigator usually keeps the percentage at around 10%. In many cases it is necessary to isolate the parasite-containing red blood cells (RBCs) from the uninfected ones, to enrich the culture and proceed with a given experiment. When P. falciparum infects the erythrocyte, the parasite degrades and feeds from haemoglobin 2, 3. However, the parasite must deal with a very toxic iron-containing haem moiety 4, 5. The parasite eludes its toxicity by transforming the haem into an inert crystal polymer called haemozoin 6, 7. This iron-containing molecule is stored in its food vacuole and the metal in it has an oxidative state which differs from the one in haem 8. The ferric state of iron in the haemozoin confers on it a paramagnetic property absent in uninfected erythrocytes. As the invading parasite reaches maturity, the content of haemozoin also increases 9, which bestows even more paramagnetism on the latest stages of P. falciparum inside the erythrocyte. Based on this paramagnetic property, the latest stages of P. falciparum infected-red blood cells can be separated by passing the culture through a column containing magnetic beads. These beads become magnetic when the columns containing them are placed on a magnet holder. Infected RBCs, due to their paramagnetism, will then be trapped inside the column, while the flow-through will contain, for the most part, uninfected erythrocytes and those containing early stages of the parasite. Here, we describe the methodology to enrich the population of late stage parasites with magnetic columns, which maintains good parasite viability 10. After performing this procedure, the unattached culture can be returned to an incubator to allow the remaining parasites to continue growing. PMID:23486405

  7. Host and parasite thermal acclimation responses depend on the stage of infection.

    PubMed

    Altman, Karie A; Paull, Sara H; Johnson, Pieter T J; Golembieski, Michelle N; Stephens, Jeffrey P; LaFonte, Bryan E; Raffel, Thomas R

    2016-07-01

    Global climate change is expected to alter patterns of temperature variability, which could influence species interactions including parasitism. Species interactions can be difficult to predict in variable-temperature environments because of thermal acclimation responses, i.e. physiological changes that allow organisms to adjust to a new temperature following a temperature shift. The goal of this study was to determine how thermal acclimation influences host resistance to infection and to test for parasite acclimation responses, which might differ from host responses in important ways. We tested predictions of three, non-mutually exclusive hypotheses regarding thermal acclimation effects on infection of green frog tadpoles (Lithobates clamitans) by the trematode parasite Ribeiroia ondatrae with fully replicated controlled-temperature experiments. Trematodes or tadpoles were independently acclimated to a range of 'acclimation temperatures' prior to shifting them to new 'performance temperatures' for experimental infections. Trematodes that were acclimated to intermediate temperatures (19-22 °C) had greater encystment success across temperatures than either cold- or warm-acclimated trematodes. However, host acclimation responses varied depending on the stage of infection (encystment vs. clearance): warm- (22-28 °C) and cold-acclimated (13-19 °C) tadpoles had fewer parasites encyst at warm and cold performance temperatures, respectively, whereas intermediate-acclimated tadpoles (19-25 °C) cleared the greatest proportion of parasites in the week following exposure. These results suggest that tadpoles use different immune mechanisms to resist different stages of trematode infection, and that each set of mechanisms has unique responses to temperature variability. Our results highlight the importance of considering thermal responses of both parasites and hosts when predicting disease patterns in variable-temperature environments. PMID:27040618

  8. Host and parasite thermal acclimation responses depend on the stage of infection.

    PubMed

    Altman, Karie A; Paull, Sara H; Johnson, Pieter T J; Golembieski, Michelle N; Stephens, Jeffrey P; LaFonte, Bryan E; Raffel, Thomas R

    2016-07-01

    Global climate change is expected to alter patterns of temperature variability, which could influence species interactions including parasitism. Species interactions can be difficult to predict in variable-temperature environments because of thermal acclimation responses, i.e. physiological changes that allow organisms to adjust to a new temperature following a temperature shift. The goal of this study was to determine how thermal acclimation influences host resistance to infection and to test for parasite acclimation responses, which might differ from host responses in important ways. We tested predictions of three, non-mutually exclusive hypotheses regarding thermal acclimation effects on infection of green frog tadpoles (Lithobates clamitans) by the trematode parasite Ribeiroia ondatrae with fully replicated controlled-temperature experiments. Trematodes or tadpoles were independently acclimated to a range of 'acclimation temperatures' prior to shifting them to new 'performance temperatures' for experimental infections. Trematodes that were acclimated to intermediate temperatures (19-22 °C) had greater encystment success across temperatures than either cold- or warm-acclimated trematodes. However, host acclimation responses varied depending on the stage of infection (encystment vs. clearance): warm- (22-28 °C) and cold-acclimated (13-19 °C) tadpoles had fewer parasites encyst at warm and cold performance temperatures, respectively, whereas intermediate-acclimated tadpoles (19-25 °C) cleared the greatest proportion of parasites in the week following exposure. These results suggest that tadpoles use different immune mechanisms to resist different stages of trematode infection, and that each set of mechanisms has unique responses to temperature variability. Our results highlight the importance of considering thermal responses of both parasites and hosts when predicting disease patterns in variable-temperature environments.

  9. Whole transcriptome profiling of adult and infective stages of the trematode Opisthorchis felineus.

    PubMed

    Pomaznoy, Mikhail Yu; Logacheva, Maria D; Young, Neil D; Penin, Aleksey A; Ershov, Nikita I; Katokhin, Alexey V; Mordvinov, Viatcheslav A

    2016-02-01

    Opisthorchis felineus, the trematode belonging to the family Opisthorchiidae, is a causative agent of the infection called opisthorchiasis or liver fluke infection. Being a close relative of Opisthorchis viverrini and Clonorchis sinensis (oriental liver flukes) it is encountered in northern Eurasia, especially in Russia, Kazakhstan, Belarus, Ukraine, and Baltic countries. Whole genome data for oriental liver flukes revealed their adaptations for life in the bile duct but our knowledge of O. felineus is scarce. To address this knowledge gap and uncover evolutionary aspect of the adaptations on the transcriptomic level, we used RNA-sequencing approach to investigate two stages of the parasite residing in different hosts. Bioinformatic analysis revealed specific features affecting various biochemical pathways and gene networks. Namely, we observed the loss of genes involved in polyamine synthesis, methionine salvage and peroxisome biogenesis. Some of the gene families, like MD-2 lipid binding proteins, calmodulins and cathepsins on the contrary have expanded compared to free living eukaryotes. We identified significant differences between the stages in homeodomain-containing genes, G-protein coupled receptors, and neuroactive signaling systems. Granulin-like growth factors specific for O. felineus were also identified. In this work, we provide the first whole transcriptome investigation of this parasite. We also hope that these results will create a background for further molecular research of helminth infections and opisthorchiasis in particular. PMID:26363139

  10. End-Stage Renal Disease Among HIV-Infected Adults in North America

    PubMed Central

    Abraham, Alison G.; Althoff, Keri N.; Jing, Yuezhou; Estrella, Michelle M.; Kitahata, Mari M.; Wester, C. William; Bosch, Ronald J.; Crane, Heidi; Eron, Joseph; Gill, M. John; Horberg, Michael A.; Justice, Amy C.; Klein, Marina; Mayor, Angel M.; Moore, Richard D.; Palella, Frank J.; Parikh, Chirag R.; Silverberg, Michael J.; Golub, Elizabeth T.; Jacobson, Lisa P.; Napravnik, Sonia; Lucas, Gregory M.; Kirk, Gregory D.; Benson, Constance A.; Bosch, Ronald J.; Collier, Ann C.; Boswell, Stephen; Grasso, Chris; Mayer, Ken; Hogg, Robert S.; Harrigan, Richard; Montaner, Julio; Cescon, Angela; Brooks, John T.; Buchacz, Kate; Gebo, Kelly A.; Moore, Richard D.; Moore, Richard D.; Carey, John T.; Rodriguez, Benigno; Horberg, Michael A.; Silverberg, Michael J.; Thorne, Jennifer E.; Goedert, James J.; Jacobson, Lisa P.; Klein, Marina B.; Rourke, Sean B.; Burchell, Ann; Rachlis, Anita R.; Hunter-Mellado, Robert F.; Mayor, Angel M.; Gill, M. John; Deeks, Steven G.; Martin, Jeffrey N.; Saag, Michael S.; Mugavero, Michael J.; Willig, James; Eron, Joseph J.; Napravnik, Sonia; Kitahata, Mari M.; Crane, Heidi M.; Justice, Amy C.; Dubrow, Robert; Fiellin, David; Sterling, Timothy R.; Haas, David; Bebawy, Sally; Turner, Megan; Gange, Stephen J.; Anastos, Kathryn; Moore, Richard D.; Saag, Michael S.; Gange, Stephen J.; Althoff, Keri N.; Kitahata, Mari M.; McKaig, Rosemary G.; Justice, Amy C.; Freeman, Aimee M.; Moore, Richard D.; Freeman, Aimee M.; Lent, Carol; Kitahata, Mari M.; Van Rompaey, Stephen E.; Crane, Heidi M.; Webster, Eric; Morton, Liz; Simon, Brenda; Gange, Stephen J.; Althoff, Keri N.; Abraham, Alison G.; Lau, Bryan; Zhang, Jinbing; Jing, Jerry; Golub, Elizabeth; Modur, Shari; Hanna, David B.; Rebeiro, Peter; Wong, Cherise; Mendes, Adell

    2015-01-01

    Background. Human immunodeficiency virus (HIV)-infected adults, particularly those of black race, are at high-risk for end-stage renal disease (ESRD), but contributing factors are evolving. We hypothesized that improvements in HIV treatment have led to declines in risk of ESRD, particularly among HIV-infected blacks. Methods. Using data from the North American AIDS Cohort Collaboration for Research and Design from January 2000 to December 2009, we validated 286 incident ESRD cases using abstracted medical evidence of dialysis (lasting >6 months) or renal transplant. A total of 38 354 HIV-infected adults aged 18–80 years contributed 159 825 person-years (PYs). Age- and sex-standardized incidence ratios (SIRs) were estimated by race. Poisson regression was used to identify predictors of ESRD. Results. HIV-infected ESRD cases were more likely to be of black race, have diabetes mellitus or hypertension, inject drugs, and/or have a prior AIDS-defining illness. The overall SIR was 3.2 (95% confidence interval [CI], 2.8–3.6) but was significantly higher among black patients (4.5 [95% CI, 3.9–5.2]). ESRD incidence declined from 532 to 303 per 100 000 PYs and 138 to 34 per 100 000 PYs over the time period for blacks and nonblacks, respectively, coincident with notable increases in both the prevalence of viral suppression and the prevalence of ESRD risk factors including diabetes mellitus, hypertension, and hepatitis C virus coinfection. Conclusions. The risk of ESRD remains high among HIV-infected individuals in care but is declining with improvements in virologic suppression. HIV-infected black persons continue to comprise the majority of cases, as a result of higher viral loads, comorbidities, and genetic susceptibility. PMID:25409471

  11. Removal of Dolutegravir by Hemodialysis in HIV-Infected Patients with End-Stage Renal Disease

    PubMed Central

    Graterol, Fredzzia; Miranda, Cristina; Khoo, Saye; Bancu, Ioana; Amara, Alieu; Bonjoch, Anna; Clotet, Bonaventura

    2016-01-01

    Data on dolutegravir removal by hemodialysis are lacking. To study this, we measured dolutegravir plasma concentrations in samples of blood entering and leaving the dialyzer and of the resulting dialysate from 5 HIV-infected patients with end-stage renal disease. The median dolutegravir hemodialysis extraction ratio was 7%. The dolutegravir concentrations after the dialysis session remained far above the protein-binding-adjusted inhibitory concentration. Our results show minimal dolutegravir removal by hemodialysis, with no specific dolutegravir dosage adjustments required in this setting. (This study is registered at ClinicalTrials.gov under registration number NCT02487706.) PMID:26856824

  12. Removal of Dolutegravir by Hemodialysis in HIV-Infected Patients with End-Stage Renal Disease.

    PubMed

    Moltó, José; Graterol, Fredzzia; Miranda, Cristina; Khoo, Saye; Bancu, Ioana; Amara, Alieu; Bonjoch, Anna; Clotet, Bonaventura

    2016-04-01

    Data on dolutegravir removal by hemodialysis are lacking. To study this, we measured dolutegravir plasma concentrations in samples of blood entering and leaving the dialyzer and of the resulting dialysate from 5 HIV-infected patients with end-stage renal disease. The median dolutegravir hemodialysis extraction ratio was 7%. The dolutegravir concentrations after the dialysis session remained far above the protein-binding-adjusted inhibitory concentration. Our results show minimal dolutegravir removal by hemodialysis, with no specific dolutegravir dosage adjustments required in this setting. (This study is registered at ClinicalTrials.gov under registration number NCT02487706.).

  13. Titanium-copper-nitride coated spacers for two-stage revision of infected total hip endoprostheses

    PubMed Central

    Ellenrieder, Martin; Haenle, Maximilian; Lenz, Robert; Bader, Rainer; Mittelmeier, Wolfram

    2011-01-01

    Within the first two years after total hip arthroplasty implant-associated infection has become the second most common reason for a revision surgery. Two-stage implant exchange is frequently conducted using temporary spacers made of antibiotic-loaded cement in order to prevent a bacterial colonization on the spacer. Avoiding several disadvantages of cement spacers, a conventional hemi-endoprosthesis was equipped with a copper-containing implant coating for inhibition of bacterial biofilms. In the present paper details of this novel treatment concept are presented including a case report. PMID:22242097

  14. Transcriptome Analysis of the SL221 Cells at the Early Stage during Spodoptera litura Nucleopolyhedrovirus Infection

    PubMed Central

    Yu, Qian; Xiong, Youhua; Liu, Jianliang; Wen, Dongling; Wu, Xiaohui; Yin, Hanqi

    2016-01-01

    Spodoptera litura (S. litura) is one of the most destructive agricultural pests worldwide. There is urgent need for a nuclear polyhedrosis virus that is specific to S. litura. To date, there have been no reports regarding the responses of S. litura cells to early Spodoptera litura nucleopolyhedrovirus (SpltNPV) infection due to the lack of a reference genome and transcriptome for S. litura. In this study, a cell transcriptome from the host S. litura was assembled and used for Illumina strand-specific RNA sequencing (RNA-seq) to generate 99180 unigenes, representing the 18 hour infection cycle. More than 2000 S. litura genes were significant differentially regulated throughout the infection. The levels of viral mRNAs began to increase dramatically at 6 hpi, and this increase continued throughout the remainder of the infection. We focused on the expression of genes related to stress responses, apoptosis, metabolic enzymes and host cell innate immune system. A small subset of genes related to host stress response, especially for 62 ones being able to annotated as enzyme, ligand and receptor genes, were observed to be specifically differentially expressed at 6 hpi. At 18 hpi, 104 unigenes were continuously significantly changing from 0 hpi to 18 hpi, considered to be viral multiplication related genes, including 3 annotated SL221 unigenes and 81 viral genes, such as tetraspanin and iap gene. This information and further studies on the regulation of host gene expression by baculovirus infection at early stage will provide the tools needed to enhance the utility of this virus as an effective insecticide. PMID:26840182

  15. Differences in snail ecology lead to infection pattern variation of Echinostoma spp. larval stages.

    PubMed

    Zimmermann, Michael R; Luth, Kyle E; Esch, Gerald W

    2014-09-01

    The infection patterns of parasites are often tied to host behavior. Although most studies have investigated definitive hosts and their parasites, intermediate host behavior may play a role in shaping the distribution and accumulation of parasites, particularly the larval stages. In an attempt to answer this question, more than 4,500 pulmonate snails were collected from 11 states in the mid-Atlantic and Midwestern United States in the summer of 2012. These snails were necropsied and echinostome metecercariae were commonly observed infecting the snails as 2(nd) intermediate hosts (20.0%). The snails included species of 3 genera with distinct differences in the infection patterns of Echinostoma spp. metacercariae among them. Physa spp. (comprising of P. acuta and P. gyrina) snails exhibited a significantly higher prevalence of infection (23.5%) than both Lymnaea columella (11.6%) and Helisoma spp. (comprising of H. anceps and H. trivolvis) (14.2%; P < 0.05), with no difference in prevalence observed between the latter 2 genera (P > 0.05). The intensity of metacercariae within the snail hosts was significantly different between the 3 genera (P < 0.05), with L. columella having the highest intensity (24.3 ± 5.6), followed by Physa spp. (15.2 ± 1.5) and Helisoma spp. (5.0 ± 0.9). Differences in prevalence and intensity were also observed when the different snail families co-habited the same body of water. The disparities in infection patterns are likely due to distinct differences in the behavioral and feeding ecology of the snail hosts.

  16. Regular production of infective sporozoites of Plasmodium falciparum and P. vivax in laboratory-bred Anopheles albimanus.

    PubMed

    Hurtado, S; Salas, M L; Romero, J F; Zapata, J C; Ortiz, H; Arevalo-Herrera, M; Herrera, S

    1997-01-01

    One of the major constraints for studies on the sporogonic cycle of the parasites causing human malaria, and on the protective efficacy of pre-erythrocytic vaccines, is the scarcity of laboratory-reared Anopheles mosquitoes as a source of infective sporozoites. The aim of the present study was to reproduce the life-cycles of Plasmodium falciparum and P. vivax in the laboratory and so develop the ability to produce infective sporozoites of these two species regularly under laboratory conditions. Colonized Anopheles albimanus, of Buenaventura and Tecojate strains, were infected by feeding either on Plasmodium-infected blood, from human patients or experimentally inoculated Aotus monkeys, or on gametocytes of the P. falciparum NF-54 isolate grown in vitro. The monkeys were infected with the blood stages of a Colombian P. vivax isolate and then, after recovery, with the Santa Lucia strain of P. falciparum from El Salvador. Although both of the mosquito strains used were successfully infected with both parasite species, the Buenaventura strain of mosquito was generally more susceptible to infection than the Tecojate strain, and particularly to infection with the parasites from the patients, who lived where this strain of mosquitoes was originally isolated. Monkeys injected intravenously with the P. vivax sporozoites produced in the mosquitoes developed patent sexual and asexual parasitaemias; the gametocytes that developed could then be used to infect mosquitoes, allowing the development of more sporozoites. However, experimental infections failed to establish after the P. falciparum sporozoites were used to inoculate monkeys. The ability to reproduce the complete life cycle of P. vivax in the laboratory, from human to mosquito and then to monkey, should greatly facilitate many studies on vivax malaria and on the efficacy of candidate malaria vaccines. The availability of the sporogonic cycles of P. falciparum from three different sources should also permit a variety of

  17. Cowpea-Meloidogyne incognita interaction: Root proteomic analysis during early stages of nematode infection.

    PubMed

    Villeth, Gabriela R C; Carmo, Lilian S T; Silva, Luciano P; Fontes, Wagner; Grynberg, Priscila; Saraiva, Mario; Brasileiro, Ana C M; Carneiro, Regina M D; Oliveira, José T A; Grossi-de-Sá, Maria F; Mehta, Angela

    2015-05-01

    Cowpea (Vigna unguiculata L. Walp) is an important legume species well adapted to low fertility soils and prolonged drought periods. One of the main problems that cause severe yield losses in cowpea is the root-knot nematode Meloidogyne incognita. The aim of this work was to analyze the differential expression of proteins in the contrasting cultivars of cowpea CE 31 (highly resistant) and CE 109 (slightly resistant) during early stages of M. incognita infection. Cowpea roots were collected at 3, 6, and 9 days after inoculation and used for protein extraction and 2-DE analysis. From a total of 59 differential spots, 37 proteins were identified, mostly involved in plant defense, such as spermidine synthase, patatin, proteasome component, and nitrile-specifier protein. A follow-up study was performed by quantitative RT-PCR analysis of nine selected proteins and the results revealed a very similar upregulation trend between the protein expression profiles and the corresponding transcripts. This study also identified ACT and GAPDH as a good combination of reference genes for quantitative RT-PCR analysis of the pathosystem cowpea/nematode. Additionally, an interactome analysis showed three major pathways affected by nematode infection: proteasome endopeptidase complex, oxidative phosphorylation, and flavonoid biosynthesis. Taken together, the results obtained by proteome, transcriptome, and interactome approaches suggest that oxidative stress, ubiquitination, and glucosinolate degradation may be part of cowpea CE 31 resistance mechanisms in response to nematode infection. PMID:25736976

  18. Cowpea-Meloidogyne incognita interaction: Root proteomic analysis during early stages of nematode infection.

    PubMed

    Villeth, Gabriela R C; Carmo, Lilian S T; Silva, Luciano P; Fontes, Wagner; Grynberg, Priscila; Saraiva, Mario; Brasileiro, Ana C M; Carneiro, Regina M D; Oliveira, José T A; Grossi-de-Sá, Maria F; Mehta, Angela

    2015-05-01

    Cowpea (Vigna unguiculata L. Walp) is an important legume species well adapted to low fertility soils and prolonged drought periods. One of the main problems that cause severe yield losses in cowpea is the root-knot nematode Meloidogyne incognita. The aim of this work was to analyze the differential expression of proteins in the contrasting cultivars of cowpea CE 31 (highly resistant) and CE 109 (slightly resistant) during early stages of M. incognita infection. Cowpea roots were collected at 3, 6, and 9 days after inoculation and used for protein extraction and 2-DE analysis. From a total of 59 differential spots, 37 proteins were identified, mostly involved in plant defense, such as spermidine synthase, patatin, proteasome component, and nitrile-specifier protein. A follow-up study was performed by quantitative RT-PCR analysis of nine selected proteins and the results revealed a very similar upregulation trend between the protein expression profiles and the corresponding transcripts. This study also identified ACT and GAPDH as a good combination of reference genes for quantitative RT-PCR analysis of the pathosystem cowpea/nematode. Additionally, an interactome analysis showed three major pathways affected by nematode infection: proteasome endopeptidase complex, oxidative phosphorylation, and flavonoid biosynthesis. Taken together, the results obtained by proteome, transcriptome, and interactome approaches suggest that oxidative stress, ubiquitination, and glucosinolate degradation may be part of cowpea CE 31 resistance mechanisms in response to nematode infection.

  19. Is two-stage reimplantation effective for virulent pathogenic infection in a periprosthetic hip? A retrospective analysis

    PubMed Central

    Yoon, Yong-Cheol; Lakhotia, Devendra; Oh, Jong-Keon; Moon, Jun Gyu; Prashant, Kumar; Shon, Won Yong

    2015-01-01

    AIM: To investigate the effectiveness of two-stage reimplantation using antibiotic-loaded bone cement (ALBC) and the risk factors associated with failure to control periprosthetic joint infection (PJI). METHODS: We retrospectively reviewed 38 consecutive hips managed using two-stage reimplantation with ALBC. The mean follow-up period was 5.4 years (range: 2.5-9 years). RESULTS: The causative pathogens were isolated from 29 patients (76%), 26 of whom were infected with highly virulent organisms. Sixteen patients (42%) underwent at least two first-stage debridements. An increased debridement frequency correlated significantly with high comorbidity (P < 0.001), a lower preoperative Harris hip score (HHS; P < 0.001), antimicrobial resistance, and gram-negative and polymicrobial infection (P = 0.002). Of the 35 patients who underwent two-stage reimplantation, 34 showed no signs of recurrence of infection. The mean HHS improved from 46 ± 12.64 to 78 ± 10.55 points, with 7 (20%), 12 (34%), 11 (32%) and 5 (14%) patients receiving excellent, good, fair and poor ratings, respectively. CONCLUSION: The current study demonstrated that two-stage reimplantation could successfully treat PJI after hip arthroplasty. However, the ability of ALBC to eradicate infection was limited because frequent debridement was required in high-risk patients (i.e., patients who are either in poor general health due to associated comorbidities or harbor infections due to highly virulent, difficult-to-treat organisms). Level of evidence: Level IV. PMID:26495248

  20. Tantalum acetabular augments in one-stage exchange of infected total hip arthroplasty: a case-control study.

    PubMed

    Klatte, Till Orla; Kendoff, Daniel; Sabihi, Reza; Kamath, Atul F; Rueger, Johannes M; Gehrke, Thorsten

    2014-07-01

    During the one-stage exchange procedure for periprosthetic joint infection (PJI) after total hip arthroplasty (THA), acetabular defects challenge reconstructive options. Porous tantalum augments are an established tool for addressing acetabular destruction in aseptic cases, but their utility in septic exchange is unknown. This retrospective case-control study presents the initial results of tantalum augmentation during one-stage exchange for PJI. Primary endpoints were rates of re-infection and short-term complications associated with this technique. Study patients had no higher risk of re-infection with equivalent durability at early follow-up with a re-infection rate in both groups of 4%. In conclusion, tantalum augments are a viable option for addressing acetabular defects in one-stage exchange for septic THA. Further study is necessary to assess long-term durability when compared to traditional techniques for acetabular reconstruction.

  1. Dissecting host factors that regulate the early stages of tuberculosis infection.

    PubMed

    Agrawal, Neha; Bhattacharyya, Chandrika; Mukherjee, Ankur; Ullah, Ubaid; Pandit, Bhaswati; Rao, Kanury V S; Majumder, Partha P

    2016-09-01

    Incomplete understanding of mechanisms involved in the host-pathogen interactions constrains our efforts to eliminate tuberculosis. In many individuals, resulting from immune response to mycobacterial infection organised structures called granulomas are formed. To identify host responses that may control at least the early stages of infection, we employed an in vitro granuloma model. Here, human PBMCs were infected with live Mycobacterium tuberculosis in culture, and the appearance of granuloma-like structures was monitored over the next several days. Production of cytokines and chemokines in culture supernatants was monitored at various times, and the resulting temporal profiles were examined for possible correlations with either granuloma formation, or bacterial growth. While a positive association of TNF-α and IFN-γ secretion levels with extent of granuloma formation could clearly be identified, we were, however, unable to detect any statistically significant relationship between any cytokine/chemokine and bacterial growth. Examination of specific host cellular biochemical pathways revealed that either modulation of neutral lipid homeostasis through inhibition of the Gi-protein coupled receptor GPR109A, or regulation of host metabolic pathways through addition of vitamin D, provided a more effective means of controlling infection. A subsequent genotypic analysis for a select subset of genes belonging to pathways known to be significant for TB pathology revealed associations of polymorphisms with cytokine secretions and bacterial growth independently. Collectively therefore, the present study supports that key metabolic pathways of the host cell, rather than levels of relevant cytokines/chemokines might be more critical for regulating the intracellular mycobacterial load, in the context of granuloma formation. PMID:27553417

  2. Diagnosis of dengue infection using various diagnostic tests in the early stage of illness.

    PubMed

    Lolekha, Rangsima; Chokephaibulkit, Kulkanya; Yoksan, Sutee; Vanprapar, Nirun; Phongsamart, Wanatpreeya; Chearskul, Sanay

    2004-06-01

    In order to elucidate the usefulness of various tests in the early course of dengue infection, in terms of diagnosis and correlation with clinical severity, blood specimens were collected every 48 hours on 3 occasions from patients with clinical suspicion of dengue infection with fever for less than 4 days. Viral isolation was attempted by mosquito inoculation (MI), tissue culture inoculation (TC), and reverse transcriptase polymerase chain reaction (RT-PCR). Antibodies were detected by hemagglutination inhibition test (HI), an in-house-ELISA (IH-ELISA), and an ELISA by MRL diagnostics Clinical data were collected from the time of enrollment to complete recovery. Of the 40 patients enrolled, 31 were diagnosed as dengue infection and confirmed by either serology or viral isolation. Of these, 12 had primary infection and 19 had secondary infection. Dengue fever occurred in 9 cases. Dengue viruses were isolated from 28 out of 31 patients, and dengue hemorrhagic fever was diagnosed in 22 patients. Viral serotypes identified by viral isolation, and RT-PCR were concordant: DEN1 was isolated in 8, DEN2 in 13, DEN3 in 5, and DEN4 in 2 patients. Viral isolation yielded positive results on blood collected before the 5th day of fever. MI was more sensitive than TC. RT-PCR was less sensitive than viral isolation during the early days of fever, but became more sensitive after the 5th day of fever. RT-PCR was able to detect virus up to day 7-8 of fever, even after defervescence, and in the presence of antibody. During the febrile stage, serological diagnosis on blood samples taken 48 hours apart was carried out by HI, IH-ELISA, and MRL-ELISA, facilitating diagnosis in 3 (10%), 21 (67%), and 27 (87%) of patients, respectively. All of the patients with secondary infection were diagnosed by MRL-ELISA before defervescence. By the 8th day of fever, a serological diagnosis aided to diagnose in 9 (29%), 29 (93%), and 31 (100%) of patients by HI, IH-ELISA, and MRL-ELISA, respectively

  3. Transcriptional dynamics of Phytophthora infestans during sequential stages of hemibiotrophic infection of tomato.

    PubMed

    Zuluaga, Andrea P; Vega-Arreguín, Julio C; Fei, Zhangjun; Ponnala, Lalit; Lee, Sang Jik; Matas, Antonio J; Patev, Sean; Fry, William E; Rose, Jocelyn K C

    2016-01-01

    Hemibiotrophic plant pathogens, such as the oomycete Phytophthora infestans, employ a biphasic infection strategy, initially behaving as biotrophs, where minimal symptoms are exhibited by the plant, and subsequently as necrotrophs, feeding on dead plant tissue. The regulation of this transition and the breadth of molecular mechanisms that modulate plant defences are not well understood, although effector proteins secreted by the pathogen are thought to play a key role. We examined the transcriptional dynamics of P. infestans in a compatible interaction with its host tomato (Solanum lycopersicum) at three infection stages: biotrophy; the transition from biotrophy to necrotrophy; and necrotrophy. The expression data suggest a tight temporal regulation of many pathways associated with the suppression of plant defence mechanisms and pathogenicity, including the induction of putative cytoplasmic and apoplastic effectors. Twelve of these were experimentally evaluated to determine their ability to suppress necrosis caused by the P. infestans necrosis-inducing protein PiNPP1.1 in Nicotiana benthamiana. Four effectors suppressed necrosis, suggesting that they might prolong the biotrophic phase. This study suggests that a complex regulation of effector expression modulates the outcome of the interaction.

  4. Type I Interferons Regulate Immune Responses in Humans with Blood-Stage Plasmodium falciparum Infection

    PubMed Central

    Montes de Oca, Marcela; Kumar, Rajiv; de Labastida Rivera, Fabian; Amante, Fiona H.; Sheel, Meru; Faleiro, Rebecca J.; Bunn, Patrick T.; Best, Shannon E.; Beattie, Lynette; Ng, Susanna S.; Edwards, Chelsea L.; Boyle, Glen M.; Price, Ric N.; Anstey, Nicholas M.; Loughland, Jessica R.; Burel, Julie; Doolan, Denise L.; Haque, Ashraful; McCarthy, James S.; Engwerda, Christian R.

    2016-01-01

    Summary The development of immunoregulatory networks is important to prevent disease. However, these same networks allow pathogens to persist and reduce vaccine efficacy. Here, we identify type I interferons (IFNs) as important regulators in developing anti-parasitic immunity in healthy volunteers infected for the first time with Plasmodium falciparum. Type I IFNs suppressed innate immune cell function and parasitic-specific CD4+ T cell IFNγ production, and they promoted the development of parasitic-specific IL-10-producing Th1 (Tr1) cells. Type I IFN-dependent, parasite-specific IL-10 production was also observed in P. falciparum malaria patients in the field following chemoprophylaxis. Parasite-induced IL-10 suppressed inflammatory cytokine production, and IL-10 levels after drug treatment were positively associated with parasite burdens before anti-parasitic drug administration. These findings have important implications for understanding the development of host immune responses following blood-stage P. falciparum infection, and they identify type I IFNs and related signaling pathways as potential targets for therapies or vaccine efficacy improvement. PMID:27705789

  5. Use of a New Knee Prosthesis as an Articulating Spacer in Two-Stage Revision of Infected Total Knee Arthroplasty

    PubMed Central

    Fabrin, Jesper; Poulsen, Klaus; Schroder, Henrik Morville

    2016-01-01

    Purpose To report our experience with two-stage revision using a new femoral component (NFC) spacer (Depuy Synthes) as an articulating spacer. Materials and Methods In this retrospective study, we reviewed 22 two-stage revisions that were performed using an NFC spacer in 22 patients suspected of having an infected total knee arthroplasty (TKA) from December 2010 to March 2013. The result was considered successful when eradication of infection was achieved using only one NFC spacer. Results The average time from primary TKA to the first stage procedure was 29.1 months and the average time from the first stage procedure until the final second stage procedure was 12.7 weeks. The average range of motion increased from 82° preoperatively to 104° postoperatively. The American Knee Society Knee score increased from 29.3 points to 66 points. The Function score increased from 29.5 points to 64 points. Four cases were reinfected after two-stage revision. The mean follow-up was 37.6 months. Conclusions The new articulating spacer showed promising short-term results both with regard to eradication of infection and functional improvement. PMID:27595079

  6. Prevalence and intensity of infection with third stage larvae of Angiostrongylus cantonensis in mollusks from Northeast Thailand.

    PubMed

    Tesana, Smarn; Srisawangwong, Tuanchai; Sithithaworn, Paiboon; Laha, Thewarach; Andrews, Ross

    2009-06-01

    Prevalences and intensity of infection with Angiostrongylus cantonensis third stage larvae were examined in mollusks to determine whether they are potential intermediate hosts in eight provinces, northeast Thailand. Mollusk samples were collected from 24 reservoirs (3 reservoirs/province) in close to human cases during the previous year. Six out of 24 localities and 9 (3 new record species) out of 27 species were found with the infection. The highest intensity in infected species was found to be only one or two snails, whereas the majority had very low or no infection. The highest density was found in Pila pesmei and the lowest in Pila polita. The edible snails, P. polita, P. pesmei, and Hemiplecta distincta have the potential to transmit A. cantonensis to man. The varying density levels of larvae in infected snails may reflect observed variation in symptoms of people who traditionally eat a raw snail dish. PMID:19478262

  7. Genome expression and mRNA maturation at late stages of productive adenovirus type 2 infection.

    PubMed

    Wold, W S; Green, M; Brackmann, K H; Cartas, M A; Devine, C

    1976-11-01

    RNA from adenovirus 2-infected KB cells was annealed in liquid with RNA in vast excess to viral heavy (l) and light (r) 32P-labeled DNA strands. Hybridization kinetics were analyzed by computer to estimate the number of viral RNA abundance classes, their relative concentrations, and the fraction of each DNA strand from which they originated. Early whole cell RNA extracted 5 h postinfection annealed rapidly to 10 to 15% of l and r strands and then slowly to final values of 60 and 40% of l and r strands. By 9 h postinfection the expression of late genes was apparent and whole cell RNA annealed to 20 and 75% of l and r strands. Whole cell RNA extracted between 12 and 36 h postinfection annealed to 7 to 15% and 75 to 90% of l and r strands. Late nuclear RNA hybridized to 10 and 90% of l and r strands, and late polyribosomal RNA hybridized to 20 and 75% of l and r strands. Based upon kinetic analyses, we estimate that mRNA synthesized exclusively during late stages arises from about 6 to 8% and 45 to 49% of l and r strands. This assumes that the early class I mRNA (in low concentration late) originates from 8 to 10% and 6 to 10% of l and r strands and that early class II mRNA (in high concentration late) is derived from 2% and 8 to 13% of l and r strands. Mixing experiments indicated that early mRNA is a subset of RNA extracted from polyribosomes late after infection and that late nuclear RNA contains sequences complementary to early l strand class I nRNA. RNA-RNA hybrids were isolated from late mRNA containing sequences from 60% of l and r strands, but it is not known when these were synthesized, and therefore whether complementary RNA transcripts are synthesized late after infection, as they are known to be synthesized early. These results demonstrate that portions of the genome are transcribed into RNA sequences that remain confined to the nucleus and are not exported to polyribosomes as mRNA.

  8. Variation in infection prevention practices in dialysis facilities: results from the national opportunity to improve infection control in ESRD (End-Stage Renal Disease) project.

    PubMed

    Chenoweth, Carol E; Hines, Stephen C; Hall, Kendall K; Saran, Rajiv; Kalbfleisch, John D; Spencer, Teri; Frank, Kelly M; Carlson, Diane; Deane, Jan; Roys, Erik; Scholz, Natalie; Parrotte, Casey; Messana, Joseph M

    2015-07-01

    OBJECTIVE To observe patient care across hemodialysis facilities enrolled in the National Opportunity to Improve Infection Control in ESRD (end-stage renal disease) (NOTICE) project in order to evaluate adherence to evidence-based practices aimed at prevention of infection. SETTING AND PARTICIPANTS Thirty-four hemodialysis facilities were randomly selected from among 772 facilities in 4 end-stage renal disease participating networks. Facility selection was stratified on dialysis organization affiliation, size, socioeconomic status, and urban/rural status. MEASUREMENTS Trained infection control evaluators used an infection control worksheet to observe 73 distinct infection control practices at the hemodialysis facilities, from October 1, 2011, through January 31, 2012. RESULTS There was considerable variation in infection control practices across enrolled facilities. Overall adherence to recommended practices was 68% (range, 45%-92%) across all facilities. Overall adherence to expected hand hygiene practice was 72% (range, 10%-100%). Compliance to hand hygiene before and after procedures was high; however, during procedures hand hygiene compliance averaged 58%. Use of chlorhexidine as the specific agent for exit site care was 19% overall but varied from 0% to 35% by facility type. The 8 checklists varied in the frequency of perfect performance from 0% for meeting every item on the checklist for disinfection practices to 22% on the arteriovenous access practices at initiation. CONCLUSIONS Our findings suggest that there are many areas for improvement in hand hygiene and other infection prevention practices in end-stage renal disease. These NOTICE project findings will help inform the development of a larger quality improvement initiative at dialysis facilities.

  9. Gamma-delta T cell responses in subclinical and clinical stages of Bovine Mycobacterium Avium Paratuberculosis infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The early immune response to Mycobacterium avium subsp. paratuberculosis (MAP) in cattle is characterized by a Th1-like immune response effective in controlling bacterial proliferation during the subclinical stage of infection. In young calves nearly 60% of circulating lymphocytes are gamma delta T ...

  10. Improving Medical Residents' Attitudes toward HIV-Infected Persons through Training in an HIV Staging and Triage Clinic.

    ERIC Educational Resources Information Center

    Orlander, Jay D.; And Others

    1994-01-01

    A study assessed the effectiveness of a weekly outpatient clinic for staging and triage of newly identified human-immunodeficiency-virus (HIV)-infected patients on 21 medical residents' attitudes and knowledge regarding HIV patient care, as compared with 20 control students. Results indicated that the experience positively affected student…

  11. Generating a detailed protein profile of Fasciola hepatica during the chronic stage of infection in cattle.

    PubMed

    Haçarız, Orçun; Baykal, Ahmet Tarık; Akgün, Mete; Kavak, Pınar; Sağıroğlu, Mahmut Şamil; Sayers, Gearóid Patrick

    2014-06-01

    Fasciola hepatica is a trematode helminth causing a damaging disease, fasciolosis, in ruminants and humans. Comprehensive proteomic studies broaden our knowledge of the parasite's protein profile, and provide new insights into the development of more effective strategies to deal with fasciolosis. The objective of this study was to generate a comprehensive profile of F. hepatica proteins expressed during the chronic stage of infection in cattle by building on previous efforts in this area. The approach included an improved sample preparation procedure for surface and internal layers of the parasite, the application of nano-UPLC-ESI-qTOF-MS (nano-ultra-performance LC and ESI quadrupole TOF MS) integrated with different acquisition methods and in silico database search against various protein databases and a transcript database including a new assembly of publically available EST. Of a total of 776 identified proteins, 206 and 332 were specific to the surface and internal layers of the parasite, respectively. Furthermore, 238 proteins were common to both layers, with comparative differences of 172 proteins detected. Specific proteins not previously identified in F. hepatica, but shown to be immunomodulatory or potential drug targets for other parasites, are discussed.

  12. Generating a detailed protein profile of Fasciola hepatica during the chronic stage of infection in cattle.

    PubMed

    Haçarız, Orçun; Baykal, Ahmet Tarık; Akgün, Mete; Kavak, Pınar; Sağıroğlu, Mahmut Şamil; Sayers, Gearóid Patrick

    2014-06-01

    Fasciola hepatica is a trematode helminth causing a damaging disease, fasciolosis, in ruminants and humans. Comprehensive proteomic studies broaden our knowledge of the parasite's protein profile, and provide new insights into the development of more effective strategies to deal with fasciolosis. The objective of this study was to generate a comprehensive profile of F. hepatica proteins expressed during the chronic stage of infection in cattle by building on previous efforts in this area. The approach included an improved sample preparation procedure for surface and internal layers of the parasite, the application of nano-UPLC-ESI-qTOF-MS (nano-ultra-performance LC and ESI quadrupole TOF MS) integrated with different acquisition methods and in silico database search against various protein databases and a transcript database including a new assembly of publically available EST. Of a total of 776 identified proteins, 206 and 332 were specific to the surface and internal layers of the parasite, respectively. Furthermore, 238 proteins were common to both layers, with comparative differences of 172 proteins detected. Specific proteins not previously identified in F. hepatica, but shown to be immunomodulatory or potential drug targets for other parasites, are discussed. PMID:24733753

  13. Radiolabeling of infective third-stage larvae of Strongyloides stercoralis by feeding ( sup 75 Se)selenomethionine-labeled Escherichia coli to first- and second-stage larvae

    SciTech Connect

    Aikens, L.M.; Schad, G.A. )

    1989-10-01

    A technique is described for radiolabeling Strongyloides stercoralis larvae with ({sup 75}Se)selenomethionine. Cultures of an auxotrophic methionine-dependent stain of Escherichia coli were grown in a medium containing Dulbecco's modified Eagle's medium supplemented with 5% nutrient broth, amino acids, and ({sup 75}Se)selenomethionine. When the {sup 75}Se-labeled bacterial populations were in the stationary phase of growth, cultures were harvested and the bacteria dispersed on agar plates to serve as food for S. stercoralis larvae. Use of nondividing bacteria is important for successful labeling because the isotope is not diluted by cell division and death of larvae attributable to overgrowth by bacteria is prevented. First-stage S. stercoralis larvae were recovered from feces of infected dogs and reared in humid air at 30 C on agar plates seeded with bacteria. After 7 days, infective third-stage larvae were harvested. The mean specific activity of 6 different batches of larvae ranged from 75 to 330 counts per min/larva with 91.8 +/- 9.5% of the population labeled sufficiently to produce an autoradiographic focus during a practicable, 6-wk period of exposure. Labeled infective larvae penetrated the skin of 10-day-old puppies and migrated to the small intestine, where the developed to adulthood.

  14. Associations Between Helminth Infections, Plasmodium falciparum Parasite Carriage and Antibody Responses to Sexual and Asexual Stage Malarial Antigens.

    PubMed

    Ateba-Ngoa, Ulysse; Jones, Sophie; Zinsou, Jeannot Fréjus; Honkpehedji, Josiane; Adegnika, Ayola Akim; Agobe, Jean-Claude Dejon; Massinga-Loembe, Marguerite; Mordmüller, Benjamin; Bousema, Teun; Yazdanbakhsh, Maria

    2016-08-01

    Infections with helminths and Plasmodium spp. overlap in their geographical distribution. It has been postulated that helminth infections may influence malarial transmission by altering Plasmodium falciparum gametocytogenesis. This cross-sectional study assessed the effect of helminth infections on P. falciparum gametocyte carriage and on humoral immune responses to sexual stage antigens in Gabon. Schistosoma haematobium and filarial infections as well as P. falciparum asexual forms and gametocyte carriage were determined. The antibody responses measured were to sexual (Pfs230, Pfs48/45) and asexual P. falciparum antigens (AMA1, MSP1, and GLURP). A total of 287 subjects were included. The prevalence of microscopically detectable P. falciparum asexual parasites was higher in S. haematobium-infected subjects in comparison to their uninfected counterparts (47% versus 26%, P = 0.003), but this was not different when filarial infections were considered. Plasmodium falciparum gametocyte carriage was similar between Schistosoma- or filaria-infected and uninfected subjects. We observed a significant decrease of Pfs48/45 immunoglobulin G titer in S. haematobium-infected subjects (P = 0.037), whereas no difference was seen for Pfs230 antibody titer, nor for antibodies to AMA1, MSP1, or GLURP. Our findings suggest an effect of S. haematobium on antibody responses to some P. falciparum gametocyte antigens that may have consequences for transmission-blocking immunity. PMID:27273645

  15. Correlation of Humoral Immune Response in Southern Bluefin Tuna, T. maccoyii, with Infection Stage of the Blood Fluke, Cardicola forsteri

    PubMed Central

    Kirchhoff, Nicole T.; Leef, Melanie J.; Valdenegro, Victoria; Hayward, Craig J.; Nowak, Barbara F.

    2012-01-01

    The blood fluke, Cardicola forsteri, is a prevalent infection in ranched southern bluefin tuna. This project aimed to define the timing and intensity of the various developmental stages of C. forsteri within southern bluefin tuna as well as to relate infection to host pathology and immune response. Archival samples from several cohorts of T. maccoyii sampled from 2008 to 2010 were used in this study. The prevalence and intensity of C. forsteri infection was described using heart flushes and histological examination. Humoral immune response, i.e. C. forsteri specific antibody, lysozyme activity, and alternative complement activity, was also described. Based on the validated and detailed C. forsteri infection timeline, relationships between infection events, physiological response, and diagnosis were proposed. Immune response developed concurrently with C. forsteri infection, with the majority of physiological response coinciding with commencing egg production. Further research is needed to confirm the origin of C. forsteri antigen which is responsible for immune response development and how T. maccoyii immune response works against infection. To aide this research, further diagnostic methods for confirmation of infection need to be developed. PMID:23029217

  16. Response of Penaeus indicus females at two different stages of ovarian development to a lethal infection with Vibrio penaeicida.

    PubMed

    Avarre, J-C; Saulnier, D; Labreuche, Y; Ansquer, D; Tietz, A; Lubzens, Esther

    2003-01-01

    An association between vitellogenesis and the immune system was suggested in crustaceans from studies on plasma lipoproteins. The present research studies the effect of an experimentally induced bacterial infection on vitellogenesis in females of the shrimp Penaeus indicus, as a model for penaeid species. Pre-vitellogenic and vitellogenic P. indicus females were experimentally infected with an extremely pathogenic bacterium, Vibrio penaeicida. The peak in mortality occurred earlier in pre-vitellogenic animals than in vitellogenic ones, although the final mortality level ( approximately 64-74%) 52h post-infection was nearly the same for the two groups. Twenty hours after infection, the total number of haemocytes was significantly reduced in vitellogenic females while there was no change in the pre-vitellogenic group. Protein synthesis in ovaries was not significantly affected by infection, at the two stages of ovarian development. No differences were found in mRNA levels of shrimp ovarian peritrophin protein (SOP), but preliminary results showed that mRNA expression of vitellin (VT) was reduced in a heavily infected vitellogenic female. The total amount of lipids in the haemolymph of vitellogenic females was almost twice higher than that of pre-vitellogenic ones. However, there was no change in the total content of lipids, lipid classes and fatty acid distribution in haemolymph or hepatopancreas following infection. Although vitellogenic and pre-vitellogenic females probably respond differently to a lethal bacterial infection, physiological differences may be concealed by the rapid onset of mortality.

  17. Influence of Ribeiroia ondatrae (Trematoda: Digenea) infection on limb development and survival of northern leopard frogs (Rana pipiens): effects of host stage and parasite-exposure level

    USGS Publications Warehouse

    Schotthoefer, Anna M.; Koehler, Anson V.; Meteyer, Carol U.; Cole, Rebecca A.

    2003-01-01

    Recent evidence suggests that infection by larvae of the trematode Ribeiroia ondatrae accounts for a significant proportion of limb malformations currently observed in amphibian populations of North America. However, the effects of R. ondatrae infection on northern leopard frogs (Rana pipiens), one of the species most frequently reported with malformations, have not been adequately explored. Moreover, the risk factors associated with R. ondatrae-induced malformations have not been clearly identified. We examined the effects of timing of infection on tadpole survival and limb development. Rana pipiens tadpoles were individually exposed to R. ondatrae cercariae at the pre-limb-bud (Gosner stages 24 and 25), limb-bud (Gosner stages 27 and 28), or paddle (Gosner stages 31–33) stages of development and monitored through metamorphosis. The effects of infection were stage-specific. Infections acquired at the pre-limb-bud stage resulted in a high mortality rate (47.5–97.5%), whereas tadpoles infected at the limb-bud stage displayed a high malformation rate (16% overall), and the magnitude of effects increased with the level of exposure to cercariae. In contrast, infections acquired at the paddle stage had no effect on limb development or tadpole survival, which suggests that the timing of R. ondatrae infection in relation to the stage structure of tadpole populations in the wild is an important determinant of the degree to which populations are affected by R. ondatrae.

  18. Aggregation of Infective Stages of Parasites as an Adaptation and Its Implications for the Study of Parasite-Host Interactions.

    PubMed

    Morrill, André; Forbes, Mark R

    2016-02-01

    The causes and consequences of aggregation among conspecifics have received much attention. For infecting macroparasites, causes include variation among hosts in susceptibility and whether infective stages are aggregated in the environment. Here, we link these two phenomena and explore whether aggregation of infective stages in the environment is adaptive to parasites encountering host condition-linked defenses and what effect such aggregations have for parasite-host interactions. Using simulation models, we show that parasite fitness is increased by aggregates attacking a host, particularly when investment into defenses is high. The fitness benefit of aggregation remains despite inclusion of factors that should curb the benefits of aggregation, namely, mortality of low-condition hosts (those hosts expected to be most susceptible to parasitism) and costs of high coinfection. For sample sizes common in studies, aggregation of infective stages reduces the likelihood of detecting host condition-parasitism relations, even when host condition is the only other factor in models affecting parasitism. Thus, it is not surprising that the expected inverse relations between host condition and parasitism, commonly a premise in studies of parasite-host interactions, are inconsistently found. An understanding of how parasites encounter hosts is thus needed for developing theory for parasite-host ecological and evolutionary interactions.

  19. Primary stage of feline immunodeficiency virus infection: viral dissemination and cellular targets.

    PubMed Central

    Beebe, A M; Dua, N; Faith, T G; Moore, P F; Pedersen, N C; Dandekar, S

    1994-01-01

    The objective of this study was to identify cellular and organ targets of acute feline immunodeficiency virus (FIV) infection in vivo. Tissues of FIV-infected cats were studied at eight time points during the first 3 months after experimental infection. FIV nucleic acids were first detected by in situ hybridization 21 days after infection, approximately 1.5 weeks after lymph node enlargement was first observed and 3 weeks before the primary acute flu-like illness. The majority of FIV-infected cells were present in lymphoid organs, though low numbers of infected cells were noted in nonlymphoid organs as well. Germinal centers harbored many of the FIV-infected cells within lymphoid tissues. The thymic cortex was also a major site of early infection. Combined in situ hybridization and immunohistochemistry revealed that T lymphocytes were the primary target of early FIV infection in tissues of cats before the onset of clinical signs of acute illness. An unidentified population of mononuclear cells and a few macrophages were also infected. During the ensuing acute flu-like illness, the proportion of FIV-infected macrophages in tissues increased dramatically. This early shift in the predominant cellular localization of FIV from T lymphocytes to macrophages may be important for establishing viral persistence. Images PMID:8151773

  20. White spot syndrome virus induces metabolic changes resembling the warburg effect in shrimp hemocytes in the early stage of infection.

    PubMed

    Chen, I-Tung; Aoki, Takashi; Huang, Yun-Tzu; Hirono, Ikuo; Chen, Tsan-Chi; Huang, Jiun-Yan; Chang, Geen-Dong; Lo, Chu-Fang; Wang, Han-Ching

    2011-12-01

    The Warburg effect is an abnormal glycolysis response that is associated with cancer cells. Here we present evidence that metabolic changes resembling the Warburg effect are induced by a nonmammalian virus. When shrimp were infected with white spot syndrome virus (WSSV), changes were induced in several metabolic pathways related to the mitochondria. At the viral genome replication stage (12 h postinfection [hpi]), glucose consumption and plasma lactate concentration were both increased in WSSV-infected shrimp, and the key enzyme of the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PDH), showed increased activity. We also found that at 12 hpi there was no alteration in the ADP/ATP ratio and that oxidative stress was lower than that in uninfected controls. All of these results are characteristic of the Warburg effect as it is present in mammals. There was also a significant decrease in triglyceride concentration starting at 12 hpi. At the late stage of the infection cycle (24 hpi), hemocytes of WSSV-infected shrimp showed several changes associated with cell death. These included the induction of mitochondrial membrane permeabilization (MMP), increased oxidative stress, decreased glucose consumption, and disrupted energy production. A previous study showed that WSSV infection led to upregulation of the voltage-dependent anion channel (VDAC), which is known to be involved in both the Warburg effect and MMP. Here we show that double-stranded RNA (dsRNA) silencing of the VDAC reduces WSSV-induced mortality and virion copy number. For these results, we hypothesize a model depicting the metabolic changes in host cells at the early and late stages of WSSV infection.

  1. Single-virus tracking approach to reveal the interaction of Dengue virus with autophagy during the early stage of infection

    NASA Astrophysics Data System (ADS)

    Chu, Li-Wei; Huang, Yi-Lung; Lee, Jin-Hui; Huang, Long-Ying; Chen, Wei-Jun; Lin, Ya-Hsuan; Chen, Jyun-Yu; Xiang, Rui; Lee, Chau-Hwang; Ping, Yueh-Hsin

    2014-01-01

    Dengue virus (DENV) is one of the major infectious pathogens worldwide. DENV infection is a highly dynamic process. Currently, no antiviral drug is available for treating DENV-induced diseases since little is known regarding how the virus interacts with host cells during infection. Advanced molecular imaging technologies are powerful tools to understand the dynamics of intracellular interactions and molecular trafficking. This study exploited a single-virus particle tracking technology to address whether DENV interacts with autophagy machinery during the early stage of infection. Using confocal microscopy and three-dimensional image analysis, we showed that DENV triggered the formation of green fluorescence protein-fused microtubule-associated protein 1A/1B-light chain 3 (GFP-LC3) puncta, and DENV-induced autophagosomes engulfed DENV particles within 15-min postinfection. Moreover, single-virus particle tracking revealed that both DENV particles and autophagosomes traveled together during the viral infection. Finally, in the presence of autophagy suppressor 3-methyladenine, the replication of DENV was inhibited and the location of DENV particles spread in cytoplasma. In contrast, the numbers of newly synthesized DENV were elevated and the co-localization of DENV particles and autophagosomes was detected while the cells were treated with autophagy inducer rapamycin. Taken together, we propose that DENV particles interact with autophagosomes at the early stage of viral infection, which promotes the replication of DENV.

  2. Role of Suppressive Oral Antibiotics in Orthopedic Hardware Infections for Those Not Undergoing Two-Stage Replacement Surgery

    PubMed Central

    Keller, Sara C.; Cosgrove, Sara E.; Higgins, Yvonne; Piggott, Damani A.; Osgood, Greg; Auwaerter, Paul G.

    2016-01-01

    Background. The use of suppressive antibiotics in treatment of orthopedic hardware infections (OHIs), including spinal hardware infections, prosthetic joint infections, and infections of internal fixation devices, is controversial. Methods. Over a 4-year period at 2 academic medical centers, patients with OHI who were treated with debridement and retention of hardware components, with single-stage exchange, or without surgery were studied to determine whether use of oral antibiotics for at least 6 months after diagnosis impacts successful treatment of the infection at 1 year after diagnosis. Results. Of 89 patients in the study, 42 (47.2%) were free of clinical infection 1 year after initial diagnosis. Suppressive antibiotics used for at least 6 months after diagnosis was not associated with being free of clinical infection (adjusted odds ratio [aOR], 5.29; 95% confidence interval [CI], .74–37.80), but being on suppressive antibiotics at least 3 months after diagnosis was associated with being free of clinical infection (OR, 3.50; 95% CI, 1.30–9.43). Causative organisms impacted the likelihood of success; patients with methicillin-resistant Staphylococcus aureus as well as with Gram-negative rods were both less likely to have achieved clinical success at 1 year after surgery (aOR = 0.018, 95% CI = .0017–.19 and aOR = 0.20, 95% CI = .039–.99, respectively). Conclusions. Oral suppressive antibiotic therapy in treatment of OHI with retention of hardware for 3 months, but not 6 months, postdiagnosis increases the likelihood of treatment success. The organisms implicated in the infection directly impact the likelihood of treatment success. PMID:27747252

  3. Two-Stage Revision Total Knee Arthroplasty in Cases of Periprosthetic Joint Infection: An Analysis of 50 Cases

    PubMed Central

    Claassen, Leif; Plaass, Christian; Daniilidis, Kiriakos; Calliess, Tilman; von Lewinski, Gabriela

    2015-01-01

    Objectives: A periprosthetic joint infection (PJI) is a significant complication after total knee arthroplasty (TKA). Still there is no agreement on a perfect diagnosis and treatment algorithm. The aim of this study was to evaluate the success and revision rates after two-stage revision total knee arthroplasty (TKA) and factors that affect the success rate. Material and Methods: 50 consecutive two-stage revision TKAs were performed between January 2011 and December 2012. We retrospectively reviewed study patient's charts including demographics, prior surgeries, comorbidities, incidence of persistent infection and revisions. At the final follow-up examination the patient's satisfaction, pain level and disorders were evaluated. A successful clinical outcome was defined as a functioning prosthesis without wound healing disorders, no sinuses tracts or other clinical evidence of a persistent infection. Results : Re-implantation of prosthesis was performed in 47 cases; three patients received a septic arthrodesis. Twelve patients had a persistent infection despite two-stage re-implantation resulting in a success rate of 76.0%. In eight of these twelve patients an infecting germ was isolated during second-stage procedure. Three patients received another two-stage revision arthroplasty and one patient an above knee amputation. A revision was performed in 23 of 50 patients (46.0%). Factors that diminish the success rate were further operations after primary TKA (p = 0.048), prior revision arthroplasties after TKA (p = 0.045), nicotine abuse (p = 0.048), Charlson comorbidity index above a score of 2 (p = 0.031) and a mixed flora during first-stage procedure (p < 0.001). Age, sex, immune status, chronic anticoagulant use, rheumatoid arthritis, body mass index and the presence of multidrug resistant germs showed no significant effect on success rate (p > 0.05). Conclusion : We found that patients who required surgery after the primary TKA, had a higher Charlson comorbidity

  4. Peanut gene expression profiling in developing seeds at different reproduction stages during Aspergillus parasiticus infection

    PubMed Central

    Guo, Baozhu; Chen, Xiaoping; Dang, Phat; Scully, Brian T; Liang, Xuanqiang; Holbrook, C Corley; Yu, Jiujiang; Culbreath, Albert K

    2008-01-01

    Background Peanut (Arachis hypogaea L.) is an important crop economically and nutritionally, and is one of the most susceptible host crops to colonization of Aspergillus parasiticus and subsequent aflatoxin contamination. Knowledge from molecular genetic studies could help to devise strategies in alleviating this problem; however, few peanut DNA sequences are available in the public database. In order to understand the molecular basis of host resistance to aflatoxin contamination, a large-scale project was conducted to generate expressed sequence tags (ESTs) from developing seeds to identify resistance-related genes involved in defense response against Aspergillus infection and subsequent aflatoxin contamination. Results We constructed six different cDNA libraries derived from developing peanut seeds at three reproduction stages (R5, R6 and R7) from a resistant and a susceptible cultivated peanut genotypes, 'Tifrunner' (susceptible to Aspergillus infection with higher aflatoxin contamination and resistant to TSWV) and 'GT-C20' (resistant to Aspergillus with reduced aflatoxin contamination and susceptible to TSWV). The developing peanut seed tissues were challenged by A. parasiticus and drought stress in the field. A total of 24,192 randomly selected cDNA clones from six libraries were sequenced. After removing vector sequences and quality trimming, 21,777 high-quality EST sequences were generated. Sequence clustering and assembling resulted in 8,689 unique EST sequences with 1,741 tentative consensus EST sequences (TCs) and 6,948 singleton ESTs. Functional classification was performed according to MIPS functional catalogue criteria. The unique EST sequences were divided into twenty-two categories. A similarity search against the non-redundant protein database available from NCBI indicated that 84.78% of total ESTs showed significant similarity to known proteins, of which 165 genes had been previously reported in peanuts. There were differences in overall expression

  5. A preliminary study on in vitro transmission of Dirofilaria immitis infective stage larvae by Aedes aegypti (L.) (Diptera: Culicidae).

    PubMed

    Tiawsirisup, Sonthaya; Khlaikhayai, Thodsatham; Nithiuthai, Suwannee

    2005-01-01

    This study was performed to study an in vitro transmission of infective stage larvae from the mosquito proboscis. There were five experiments with 949 mosquitoes. Liverpool strain of Aedes aegypti (L.) were used in this study. They were allowed to feed on D. immitis infected dogs with different microfilarial levels which were 1,650, 1,950, 9,000, 9,250, and 11,550 microfilariae per one ml of blood. Mosquitoes were forced to feed on solution (5% sucrose in 5% dog serum) in capillary tubes for 20 minutes at 7-34 days post-blood feeding. Solutions in capillary tubes then were examined and mosquitoes were dissected and examined for D. immitis larvae under a light microscope. Second stage larvae could be found in the abdomen and malpighian tubules of mosquitoes and third stage larvae can be found in the abdomen, malpighian tubules, thorax, and proboscis of mosquitoes with different levels of infection. No larvae were detected in the solution in capillary tubes of all experiments. PMID:16438186

  6. Parasite-induced ER stress response in hepatocytes facilitates Plasmodium liver stage infection.

    PubMed

    Inácio, Patricia; Zuzarte-Luís, Vanessa; Ruivo, Margarida T G; Falkard, Brie; Nagaraj, Nagarjuna; Rooijers, Koos; Mann, Matthias; Mair, Gunnar; Fidock, David A; Mota, Maria M

    2015-08-01

    Upon infection of a mammalian host, Plasmodium parasites first replicate inside hepatocytes, generating thousands of new parasites. Although Plasmodium intra-hepatic development represents a substantial metabolic challenge to the host hepatocyte, how infected cells respond to and integrate this stress remains poorly understood. Here, we present proteomic and transcriptomic analyses, revealing that the endoplasmic reticulum (ER)-resident unfolded protein response (UPR) is activated in host hepatocytes upon Plasmodium berghei infection. The expression of XBP1s--the active form of the UPR mediator XBP1--and the liver-specific UPR mediator CREBH is induced by P. berghei infection in vivo. Furthermore, this UPR induction increases parasite liver burden. Altogether, our data suggest that ER stress is a central feature of P. berghei intra-hepatic development, contributing to the success of infection. PMID:26113366

  7. Parasite-induced ER stress response in hepatocytes facilitates Plasmodium liver stage infection

    PubMed Central

    Inácio, Patricia; Zuzarte-Luís, Vanessa; Ruivo, Margarida TG; Falkard, Brie; Nagaraj, Nagarjuna; Rooijers, Koos; Mann, Matthias; Mair, Gunnar; Fidock, David A; Mota, Maria M

    2015-01-01

    Upon infection of a mammalian host, Plasmodium parasites first replicate inside hepatocytes, generating thousands of new parasites. Although Plasmodium intra-hepatic development represents a substantial metabolic challenge to the host hepatocyte, how infected cells respond to and integrate this stress remains poorly understood. Here, we present proteomic and transcriptomic analyses, revealing that the endoplasmic reticulum (ER)-resident unfolded protein response (UPR) is activated in host hepatocytes upon Plasmodium berghei infection. The expression of XBP1s—the active form of the UPR mediator XBP1—and the liver-specific UPR mediator CREBH is induced by P. berghei infection in vivo. Furthermore, this UPR induction increases parasite liver burden. Altogether, our data suggest that ER stress is a central feature of P. berghei intra-hepatic development, contributing to the success of infection. PMID:26113366

  8. Parasite-induced ER stress response in hepatocytes facilitates Plasmodium liver stage infection.

    PubMed

    Inácio, Patricia; Zuzarte-Luís, Vanessa; Ruivo, Margarida T G; Falkard, Brie; Nagaraj, Nagarjuna; Rooijers, Koos; Mann, Matthias; Mair, Gunnar; Fidock, David A; Mota, Maria M

    2015-08-01

    Upon infection of a mammalian host, Plasmodium parasites first replicate inside hepatocytes, generating thousands of new parasites. Although Plasmodium intra-hepatic development represents a substantial metabolic challenge to the host hepatocyte, how infected cells respond to and integrate this stress remains poorly understood. Here, we present proteomic and transcriptomic analyses, revealing that the endoplasmic reticulum (ER)-resident unfolded protein response (UPR) is activated in host hepatocytes upon Plasmodium berghei infection. The expression of XBP1s--the active form of the UPR mediator XBP1--and the liver-specific UPR mediator CREBH is induced by P. berghei infection in vivo. Furthermore, this UPR induction increases parasite liver burden. Altogether, our data suggest that ER stress is a central feature of P. berghei intra-hepatic development, contributing to the success of infection.

  9. Rationale for one stage exchange of infected hip replacement using uncemented implants and antibiotic impregnated bone graft

    PubMed Central

    Winkler, Heinz

    2009-01-01

    Infection of a total hip replacement (THR) is considered a devastating complication, necessitating its complete removal and thorough debridement of the site. It is undoubted that one stage exchange, if successful, would provide the best benefit both for the patient and the society. Still the fear of re-infection dominates the surgeons´ decisions and in the majority of cases directs them to multiple stage protocols. However, there is no scientifically based argument for that practice. Successful eradication of infection with two stage procedures is reported to average 80% to 98%. On the other hand a literature review of Jackson and Schmalzried (CORR 2000) summarizing the results of 1,299 infected hip replacements treated with direct exchange (almost exclusively using antibiotic loaded cement), reports of 1,077 (83%) having been successful. The comparable results suggest, that the major factor for a successful outcome with traditional approaches may be found in the quality of surgical debridement and dead space management. Failures in all protocols seem to be caused by small fragments of bacterial colonies remaining after debridement, whereas neither systemic antibiotics nor antibiotic loaded bone cement (PMMA) have been able to improve the situation significantly. Reasons for failure may be found in the limited sensitivity of traditional bacterial culturing and reduced antibiotic susceptibility of involved pathogens, especially considering biofilm formation. Whenever a new prosthesis is implanted into a previously infected site the surgeon must be aware of increased risk of failure, both in single or two stage revisions. Eventual removal therefore should be easy with low risk of additional damage to the bony substance. On the other hand it should also have potential of a good long term result in case of success. Cemented revisions generally show inferior long term results compared to uncemented techniques; the addition of antibiotics to cement reduces its

  10. Induction of immune response in macaque monkeys infected with simian-human immunodeficiency virus having the TNF-{alpha} gene at an early stage of infection

    SciTech Connect

    Shimizu, Yuya; Miyazaki, Yasuyuki; Ibuki, Kentaro; Suzuki, Hajime; Kaneyasu, Kentaro; Goto, Yoshitaka; Hayami, Masanori; Miura, Tomoyuki; Haga, Takeshi . E-mail: a0d518u@cc.miyazaki-u.ac.jp

    2005-12-20

    TNF-{alpha} has been implicated in the pathogenesis of, and the immune response against, HIV-1 infection. To clarify the roles of TNF-{alpha} against HIV-1-related virus infection in an SHIV-macaque model, we genetically engineered an SHIV to express the TNF-{alpha} gene (SHIV-TNF) and characterized the virus's properties in vivo. After the acute viremic stage, the plasma viral loads declined earlier in the SHIV-TNF-inoculated monkeys than in the parental SHIV (SHIV-NI)-inoculated monkeys. SHIV-TNF induced cell death in the lymph nodes without depletion of circulating CD4{sup +} T cells. SHIV-TNF provided some immunity in monkeys by increasing the production of the chemokine RANTES and by inducing an antigen-specific proliferation of lymphocytes. The monkeys immunized with SHIV-TNF were partly protected against a pathogenic SHIV (SHIV-C2/1) challenge. These findings suggest that TNF-{alpha} contributes to the induction of an effective immune response against HIV-1 rather than to the progression of disease at the early stage of infection.

  11. Contribution of mammary epithelial cells to the immune response during early stages of a bacterial infection to Staphylococcus aureus

    PubMed Central

    2014-01-01

    To differentiate between the contribution of mammary epithelial cells (MEC) and infiltrating immune cells to gene expression profiles of mammary tissue during early stage mastitis, we investigated in goats the in vivo transcriptional response of MEC to an experimental intra mammary infection (IMI) with Staphylococcus aureus, using a non-invasive RNA sampling method from milk fat globules (MFG). Microarrays were used to record gene expression patterns during the first 24 hours post-infection (hpi). This approach was combined with laser capture microdissection of MEC from frozen slides of mammary tissue to analyze some relevant genes at 30 hpi. During the early stages post-inoculation, MEC play an important role in the recruitment and activation of inflammatory cells through the IL-8 signalling pathway and initiate a sharp induction of innate immune genes predominantly associated with the pro-inflammatory response. At 30 hpi, MEC express genes encoding different acute phase proteins, including SAA3, SERPINA1 and PTX3 and factors, such as S100A12, that contribute directly to fighting the infection. No significant change in the expression of genes encoding caseins was observed until 24 hpi, thus validating our experimental model to study early stages of infection before the occurrence of tissue damage, since the milk synthesis function is still operative. This is to our knowledge the first report showing in vivo, in goats, how MEC orchestrate the innate immune response to an IMI challenge with S. aureus. Moreover, the non-invasive sampling method of mammary representative RNA from MFG provides a valuable tool to easily follow the dynamics of gene expression in MEC to search for sensitive biomarkers in milk for early detection of mastitis and therefore, to successfully improve the treatment and thus animal welfare. PMID:24521038

  12. Brugia malayi: vaccination of jirds with /sup 60/cobalt-attenuated infective stage larvae protects against homologous challenge

    SciTech Connect

    Yates, J.A.; Higashi, G.I.

    1985-11-01

    Vaccination of inbred jirds (Meriones unguiculatus) with /sup 60/cobalt radiation-attenuated Brugia malayi infective stage larvae (L3) protected against homologous challenge given either subcutaneously (sc) or by the intraperitoneal (ip) route. Groups of jirds vaccinated once sc with 75, 15 Krad L3 showed from 69% to 91% reduction in recovered worms after ip challenge infection compared to infection in non-vaccinated control jirds, while 75% reduction in mean worm burden was seen in jirds receiving sc challenge infection. A single sc vaccination with 75, 10 or 20 Krad L3 produced no protection (10 Krad) and 64% reduction in recovered worms (20 Krad). Therefore the 15 Krad dose appeared to be best. A marked increase in anti-B. malayi antibody in vaccinated jirds was seen (by ELISA) immediately after challenge infection and an immunofluorescence assay showed that L3 incubated in serum from vaccinated jirds were completely and uniformly covered with specific antibody. Eosinophil-rich granulomas containing dead and moribund L3 were recovered from vaccinated jirds. This model of protective immunity in a Brugia-susceptible small rodent may provide a useful system for identification of molecularly defined filarial-protective immunogens.

  13. Management of chronic hepatitis C virus infection in patients with end-stage renal disease: a review

    PubMed Central

    Aguirre Valadez, Jonathan; García Juárez, Ignacio; Rincón Pedrero, Rodolfo; Torre, Aldo

    2015-01-01

    Infection with hepatitis C virus (HCV) is highly prevalent in chronic kidney disease (CKD) patients, mainly in those on hemodialysis (HD). The seroprevalence of HCV in developing countries ranges between 7% and 40%. Risk factors for this infection in the CKD population include the number of blood transfusions, duration of end-stage renal disease (ESRD), and prevalence of HCV in HD. Chronic HCV infection in patients with ESRD is associated with an increase in morbidity and mortality in the pre and post kidney transplant periods. The increase in mortality is directly associated with liver complications and an elevated cardiovascular risk in HCV-infected patients on hemodialysis. Antiviral treatment may improve the prognosis of patients with HCV, and standard interferon remains the cornerstone of treatment. Treatment of HCV in patients with CKD is complex, but achieving a sustained viral response may decrease the frequency of complications after transplantation. It appears that HCV-infected patients who remain on maintenance dialysis are at increased risk of death compared with HCV patients undergoing renal transplantation. PMID:25767389

  14. The Biting Midge Culicoides sonorensis (Diptera: Ceratopogonidae) Is Capable of Developing Late Stage Infections of Leishmania enriettii

    PubMed Central

    Seblova, Veronika; Sadlova, Jovana; Vojtkova, Barbora; Votypka, Jan; Carpenter, Simon; Bates, Paul Andrew; Volf, Petr

    2015-01-01

    Background Despite their importance in animal and human health, the epidemiology of species of the Leishmania enriettii complex remains poorly understood, including the identity of their biological vectors. Biting midges of the genus Forcipomyia (Lasiohelea) have been implicated in the transmission of a member of the L. enriettii complex in Australia, but the far larger and more widespread genus Culicoides has not been investigated for the potential to include vectors to date. Methodology/Principal Findings Females from colonies of the midges Culicoides nubeculosus Meigen and C. sonorensis Wirth & Jones and the sand fly Lutzomyia longipalpis Lutz & Nevia (Diptera: Psychodidae) were experimentally infected with two different species of Leishmania, originating from Australia (Leishmania sp. AM-2004) and Brazil (Leishmania enriettii). In addition, the infectivity of L. enriettii infections generated in guinea pigs and golden hamsters for Lu. longipalpis and C. sonorensis was tested by xenodiagnosis. Development of L. enriettii in Lu. longipalpis was relatively poor compared to other Leishmania species in this permissive vector. Culicoides nubeculosus was not susceptible to infection by parasites from the L. enriettii complex. In contrast, C. sonorensis developed late stage infections with colonization of the thoracic midgut and the stomodeal valve. In hamsters, experimental infection with L. enriettii led only to mild symptoms, while in guinea pigs L. enriettii grew aggressively, producing large, ulcerated, tumour-like lesions. A high proportion of C. sonorensis (up to 80%) feeding on the ears and nose of these guinea pigs became infected. Conclusions/Significance We demonstrate that L. enriettii can develop late stage infections in the biting midge Culicoides sonorensis. This midge was found to be susceptible to L. enriettii to a similar degree as Lutzomyia longipalpis, the vector of Leishmania infantum in South America. Our results support the hypothesis that some

  15. Transcriptional changes of cytokines in rooster testis and epididymis during sexual maturation stages and Salmonella infection.

    PubMed

    Anastasiadou, M; Michailidis, G

    2016-08-01

    Infection of rooster testis and epididymis by pathogens can lead to impaired fertility, resulting in economic losses in the poultry industry. Antimicrobial protection of rooster reproductive organs is, therefore, an important aspect of reproductive physiology. Salmonellosis is one of the most important zoonotic diseases, caused by Salmonella bacteria including Salmonella Enteritidis (SE) and is usually the result of infection of the reproductive organs. Thus, knowledge of the endogenous innate immune mechanisms of the rooster testis and epididymis is an emerging aspect of reproductive physiology. Cytokines are key factors for stimulating the immune response and inflammation in chickens to Salmonella infection. In the present study the expression profile of 11 pro-inflammatory cytokine genes in the rooster testis and epididymis in vivo and transcriptional changes in these organs during sexual maturation and SE infection were investigated. Gene expression analysis data revealed that in both testis and epididymis nine cytokines namely the IL-1β, IL-6, IL-8, IL-10, IL-12, IL-15, IL-16, IL-17 and IL-18 genes were expressed, while no mRNA transcripts were detected in both organs for IL-2 and IL-4. Furthermore, the expression of various cytokine genes during sexual maturation appeared to be developmentally regulated, while SE infection resulted in a significant up-regulation of IL-1β, -6, -12 and -18 genes in the testis and an increase in the mRNA relative abundance of IL-1β, -6, -12, -16 and -18 in the epididymis of SE-infected sexually mature 28-week-old roosters. These results suggest a cytokine-mediated immune response mechanism against Salmonella infection in the rooster reproductive tract. PMID:27289435

  16. Transcriptional changes of cytokines in rooster testis and epididymis during sexual maturation stages and Salmonella infection.

    PubMed

    Anastasiadou, M; Michailidis, G

    2016-08-01

    Infection of rooster testis and epididymis by pathogens can lead to impaired fertility, resulting in economic losses in the poultry industry. Antimicrobial protection of rooster reproductive organs is, therefore, an important aspect of reproductive physiology. Salmonellosis is one of the most important zoonotic diseases, caused by Salmonella bacteria including Salmonella Enteritidis (SE) and is usually the result of infection of the reproductive organs. Thus, knowledge of the endogenous innate immune mechanisms of the rooster testis and epididymis is an emerging aspect of reproductive physiology. Cytokines are key factors for stimulating the immune response and inflammation in chickens to Salmonella infection. In the present study the expression profile of 11 pro-inflammatory cytokine genes in the rooster testis and epididymis in vivo and transcriptional changes in these organs during sexual maturation and SE infection were investigated. Gene expression analysis data revealed that in both testis and epididymis nine cytokines namely the IL-1β, IL-6, IL-8, IL-10, IL-12, IL-15, IL-16, IL-17 and IL-18 genes were expressed, while no mRNA transcripts were detected in both organs for IL-2 and IL-4. Furthermore, the expression of various cytokine genes during sexual maturation appeared to be developmentally regulated, while SE infection resulted in a significant up-regulation of IL-1β, -6, -12 and -18 genes in the testis and an increase in the mRNA relative abundance of IL-1β, -6, -12, -16 and -18 in the epididymis of SE-infected sexually mature 28-week-old roosters. These results suggest a cytokine-mediated immune response mechanism against Salmonella infection in the rooster reproductive tract.

  17. A switch in infected erythrocyte deformability at the maturation and blood circulation of Plasmodium falciparum transmission stages.

    PubMed

    Tibúrcio, Marta; Niang, Makhtar; Deplaine, Guillaume; Perrot, Sylvie; Bischoff, Emmanuel; Ndour, Papa Alioune; Silvestrini, Francesco; Khattab, Ayman; Milon, Geneviève; David, Peter H; Hardeman, Max; Vernick, Kenneth D; Sauerwein, Robert W; Preiser, Peter R; Mercereau-Puijalon, Odile; Buffet, Pierre; Alano, Pietro; Lavazec, Catherine

    2012-06-14

    Achievement of malaria elimination requires development of novel strategies interfering with parasite transmission, including targeting the parasite sexual stages (gametocytes). The formation of Plasmodium falciparum gametocytes in the human host takes several days during which immature gametocyte-infected erythrocytes (GIEs) sequester in host tissues. Only mature stage GIEs circulate in the peripheral blood, available to uptake by the Anopheles vector. Mechanisms underlying GIE sequestration and release in circulation are virtually unknown. We show here that mature GIEs are more deformable than immature stages using ektacytometry and microsphiltration methods, and that a switch in cellular deformability in the transition from immature to mature gametocytes is accompanied by the deassociation of parasite-derived STEVOR proteins from the infected erythrocyte membrane. We hypothesize that mechanical retention contributes to sequestration of immature GIEs and that regained deformability of mature gametocytes is associated with their release in the bloodstream and ability to circulate. These processes are proposed to play a key role in P falciparum gametocyte development in the host and to represent novel and unconventional targets for interfering with parasite transmission.

  18. Houttuynia cordata targets the beginning stage of herpes simplex virus infection.

    PubMed

    Hung, Pei-Yun; Ho, Bing-Ching; Lee, Szu-Yuan; Chang, Sui-Yuan; Kao, Chuan-Liang; Lee, Shoei-Sheng; Lee, Chun-Nan

    2015-01-01

    Herpes simplex virus (HSV), a common latent virus in humans, causes certain severe diseases. Extensive use of acyclovir (ACV) results in the development of drug-resistant HSV strains, hence, there is an urgent need to develop new drugs to treat HSV infection. Houttuynia cordata (H. cordata), a natural herbal medicine, has been reported to exhibit anti-HSV effects which is partly NF-κB-dependent. However, the molecular mechanisms by which H. cordata inhibits HSV infection are not elucidated thoroughly. Here, we report that H. cordata water extracts (HCWEs) inhibit the infection of HSV-1, HSV-2, and acyclovir-resistant HSV-1 mainly via blocking viral binding and penetration in the beginning of infection. HCWEs also suppress HSV replication. Furthermore, HCWEs attenuate the first-wave of NF-κB activation, which is essential for viral gene expressions. Further analysis of six compounds in HCWEs revealed that quercetin and isoquercitrin inhibit NF-κB activation and additionally, quercetin also has an inhibitory effect on viral entry. These results indicate that HCWEs can inhibit HSV infection through multiple mechanisms and could be a potential lead for development of new drugs for treating HSV.

  19. Houttuynia cordata Targets the Beginning Stage of Herpes Simplex Virus Infection

    PubMed Central

    Hung, Pei-Yun; Ho, Bing-Ching; Lee, Szu-Yuan; Chang, Sui-Yuan; Kao, Chuan-Liang; Lee, Shoei-Sheng; Lee, Chun-Nan

    2015-01-01

    Herpes simplex virus (HSV), a common latent virus in humans, causes certain severe diseases. Extensive use of acyclovir (ACV) results in the development of drug-resistant HSV strains, hence, there is an urgent need to develop new drugs to treat HSV infection. Houttuynia cordata (H. cordata), a natural herbal medicine, has been reported to exhibit anti-HSV effects which is partly NF-κB-dependent. However, the molecular mechanisms by which H. cordata inhibits HSV infection are not elucidated thoroughly. Here, we report that H. cordata water extracts (HCWEs) inhibit the infection of HSV-1, HSV-2, and acyclovir-resistant HSV-1 mainly via blocking viral binding and penetration in the beginning of infection. HCWEs also suppress HSV replication. Furthermore, HCWEs attenuate the first-wave of NF-κB activation, which is essential for viral gene expressions. Further analysis of six compounds in HCWEs revealed that quercetin and isoquercitrin inhibit NF-κB activation and additionally, quercetin also has an inhibitory effect on viral entry. These results indicate that HCWEs can inhibit HSV infection through multiple mechanisms and could be a potential lead for development of new drugs for treating HSV. PMID:25643242

  20. Houttuynia cordata targets the beginning stage of herpes simplex virus infection.

    PubMed

    Hung, Pei-Yun; Ho, Bing-Ching; Lee, Szu-Yuan; Chang, Sui-Yuan; Kao, Chuan-Liang; Lee, Shoei-Sheng; Lee, Chun-Nan

    2015-01-01

    Herpes simplex virus (HSV), a common latent virus in humans, causes certain severe diseases. Extensive use of acyclovir (ACV) results in the development of drug-resistant HSV strains, hence, there is an urgent need to develop new drugs to treat HSV infection. Houttuynia cordata (H. cordata), a natural herbal medicine, has been reported to exhibit anti-HSV effects which is partly NF-κB-dependent. However, the molecular mechanisms by which H. cordata inhibits HSV infection are not elucidated thoroughly. Here, we report that H. cordata water extracts (HCWEs) inhibit the infection of HSV-1, HSV-2, and acyclovir-resistant HSV-1 mainly via blocking viral binding and penetration in the beginning of infection. HCWEs also suppress HSV replication. Furthermore, HCWEs attenuate the first-wave of NF-κB activation, which is essential for viral gene expressions. Further analysis of six compounds in HCWEs revealed that quercetin and isoquercitrin inhibit NF-κB activation and additionally, quercetin also has an inhibitory effect on viral entry. These results indicate that HCWEs can inhibit HSV infection through multiple mechanisms and could be a potential lead for development of new drugs for treating HSV. PMID:25643242

  1. Multi-Agent Simulations of the Immune Response to Hiv during the Acute Stage of Infection

    NASA Astrophysics Data System (ADS)

    Walshe, R.; Ruskin, H. J.; Callaghan, A.

    Results of multi-agent based simulations of the immune response to HIV during the acute phase of infection are presented here. The model successfully recreates the viral dynamics associated with the acute phase of infection, i.e., a rapid rise in viral load followed by a sharp decline to what is often referred to as a "set point", a result of T-cell response and emergence of HIV neutralizing antibodies. The results indicate that sufficient T Killer cell response is the key factor in controlling viral growth during this phase with antibody levels of critical importance only in the absence of a sufficient T Killer response.

  2. Detecting Presymptomatic Infection Is Necessary to Forecast Major Epidemics in the Earliest Stages of Infectious Disease Outbreaks

    PubMed Central

    Thompson, Robin N.; Gilligan, Christopher A.; Cunniffe, Nik J.

    2016-01-01

    We assess how presymptomatic infection affects predictability of infectious disease epidemics. We focus on whether or not a major outbreak (i.e. an epidemic that will go on to infect a large number of individuals) can be predicted reliably soon after initial cases of disease have appeared within a population. For emerging epidemics, significant time and effort is spent recording symptomatic cases. Scientific attention has often focused on improving statistical methodologies to estimate disease transmission parameters from these data. Here we show that, even if symptomatic cases are recorded perfectly, and disease spread parameters are estimated exactly, it is impossible to estimate the probability of a major outbreak without ambiguity. Our results therefore provide an upper bound on the accuracy of forecasts of major outbreaks that are constructed using data on symptomatic cases alone. Accurate prediction of whether or not an epidemic will occur requires records of symptomatic individuals to be supplemented with data concerning the true infection status of apparently uninfected individuals. To forecast likely future behavior in the earliest stages of an emerging outbreak, it is therefore vital to develop and deploy accurate diagnostic tests that can determine whether asymptomatic individuals are actually uninfected, or instead are infected but just do not yet show detectable symptoms. PMID:27046030

  3. Immunopathologic changes in the thymus during the acute stage of experimentally induced feline immunodeficiency virus infection in juvenile cats.

    PubMed Central

    Woo, J C; Dean, G A; Pedersen, N C; Moore, P F

    1997-01-01

    The feline thymus is a target organ and site of viral replication during the acute stage of feline immunodeficiency virus (FIV) infection. This was demonstrated by histologic, immunohistologic, flow cytometric, and virologic tests. Thymic lesions developed after 28 days postinoculation (p.i.) and included thymitis, premature cortical involution, and medullary B-cell hyperplasia with germinal center formation and epithelial distortion. Alterations in thymocyte subsets also developed. Fewer CD4+ CD8- cells were detected at 28 days p.i., while an increase in CD4- CD8+ cells resulted in an inversion of the thymic CD4/CD8 ratio of single-positive cells, similar to events in peripheral blood. Provirus was present in all thymocyte subpopulations including cortical CD1(hi), CD1(lo), and B cells. The CD1(hi) thymocyte proviral burden increased markedly after 56 days p.i., coincident with the presence of infiltrating inflammatory cells. Increased levels of provirus in the CD1(lo) thymocyte subpopulation were detected prior to 56 days p.i. This was likely due to inclusion of infected infiltrating inflammatory cells which could not be differentiated from mature, medullary thymocytes. Proviral levels in B cells also increased from 70 days p.i. Morphologic alterations, productive viral infection, and altered thymocyte subpopulations suggest that thymic function is compromised, thus contributing to the inability of FIV-infected cats to replenish the peripheral T-cell pool. PMID:9343221

  4. Metabolic profiles of soybean roots during early stages of Fusarium tucumaniae infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soybean germplasm exhibits various levels of resistance to Fusarium tucumaniae, the main causal agent of sudden death syndrome (SDS) of soybean in Argentina. In this study, two soybean genotypes, one susceptible (NA 4613) and one partially resistant (DM 4670) to SDS infection, were inoculated with F...

  5. RNAi screening reveals proteasome- and Cullin3-dependent stages in vaccinia virus infection.

    PubMed

    Mercer, Jason; Snijder, Berend; Sacher, Raphael; Burkard, Christine; Bleck, Christopher Karl Ernst; Stahlberg, Henning; Pelkmans, Lucas; Helenius, Ari

    2012-10-25

    A two-step, automated, high-throughput RNAi silencing screen was used to identify host cell factors required during vaccinia virus infection. Validation and analysis of clustered hits revealed previously unknown processes during virus entry, including a mechanism for genome uncoating. Viral core proteins were found to be already ubiquitinated during virus assembly. After entering the cytosol of an uninfected cell, the viral DNA was released from the core through the activity of the cell's proteasomes. Next, a Cullin3-based ubiquitin ligase mediated a further round of ubiquitination and proteasome action. This was needed in order to initiate viral DNA replication. The results accentuate the value of large-scale RNAi screens in providing directions for detailed cell biological investigation of complex pathways. The list of cell functions required during poxvirus infection will, moreover, provide a resource for future virus-host cell interaction studies and for the discovery of antivirals. PMID:23084750

  6. Batrachochytrium dendrobatidis infection patterns among Panamanian amphibian species, habitats and elevations during epizootic and enzootic stages.

    PubMed

    Brem, Forrest M R; Lips, Karen R

    2008-09-24

    The pathogenic fungus Batrachochytrium dendrobatidis (Bd) has caused declines of many amphibian populations, yet the full course of the epizootic has rarely been observed in wild populations. We determined effects of elevation, habitat, and aquatic index (AI) on prevalence of infection among Panamanian amphibians sampled along 2 elevational transects. Amphibian populations on the Santa Fé transect (SFT) had declined in 2002, while those on the El Copé transect (ECT) were healthy until September 2004. In 2004 we sampled Bd along both transects, surveying the SFT 2 yr after decline, and surveying the ECT 4 mo prior to the arrival of Bd, during the epizootic, and 2 mo later. Overall prevalence of Bd along the ECT increased from 0.0 (95% CI 0.00-0.0003) to 0.51 (95% CI 0.48-0.55) over a 3 mo period, accompanied by significant decreases in amphibian abundance and species richness in all habitats. Prevalence of infection on the ECT was highest along riparian transects and at higher elevations, but not among levels of AI. Prevalence of infection on the SFT was highest in pool transects, and at higher elevations, but not among levels of AI. Riparian amphibian abundance and species richness also declined at SFT following detection of Bd in 2002. Variation among species, microenvironmental conditions, and the length of coexistence with Bd may contribute to observed differences in prevalence of Bd and in population response.

  7. Circulating gastrin and ghrelin levels in patients with colorectal cancer: correlation with tumour stage, Helicobacter pylori infection and BMI.

    PubMed

    D'Onghia, V; Leoncini, R; Carli, R; Santoro, A; Giglioni, S; Sorbellini, F; Marzocca, G; Bernini, A; Campagna, S; Marinello, E; Vannoni, D

    2007-01-01

    Many studies have pointed out a possible role of gut peptides, including gastrin and ghrelin, in the pathogenesis and natural history of gastrointestinal malignancies, one of the most common death cause in the Western world. The objective of this work is to check gastrin and ghrelin serum levels in patients with colorectal cancer according to tumour's location, stage, Helicobacter pylori infection and BMI, in order to understand the two peptides' behaviour through the tumour's natural history and evaluate their assay's use in research and clinical practice. Twenty-nine subjects affected by colorectal cancer and 50 healthy controls were studied. Circulating gastrin and ghrelin levels and H. pylori serum antibodies were assessed by radioimmunologic assay and ELISA method. Gastrin and ghrelin serum levels were respectively slightly higher and significantly lower in colon cancer patients than in controls. Gastrin levels were higher in patients carrying left colon cancer and H. pylori infection while ghrelin levels were lower in both these groups. Both hormones' serum levels decreased from tumour earlier to later stages. Significant differences persisted in the correlation between BMI and ghrelin levels in controls but not in patients. Additional studies are necessary to ascertain the significance of gastrin and ghrelin opposite behaviour in colon cancer probably linked with interferences in endocrine pathways involving other gut peptides in this compromised condition. PMID:17258885

  8. Parasite distribution and early-stage encephalitis in Sarcocystis calchasi infections in domestic pigeons (Columba livia f. domestica).

    PubMed

    Maier, Kristina; Olias, Philipp; Enderlein, Dirk; Klopfleisch, Robert; Mayr, Sylvia L; Gruber, Achim D; Lierz, Michael

    2015-01-01

    Pigeon protozoal encephalitis is a biphasic, neurologic disease of domestic pigeons (Columba livia f. domestica) caused by the apicomplexan parasite Sarcocystis calchasi. Despite severe inflammatory lesions of the brain, associated parasitic stages have only rarely been identified and the cause of the lesions is still unclear. The aim of this study was therefore to characterize the tissue distribution of S. calchasi within pigeons between the two clinical phases and during the occurrence of neurological signs. For this purpose, a semi-quantitative real-time polymerase chain reaction (PCR) was developed. Forty-five domestic pigeons were infected orally (via a cannula into the crop) with 200 S. calchasi sporocysts and euthanized in groups of three pigeons at intervals of 2 to 10 days over a period of 61 days. Tissue samples including brain and skeletal muscle were examined by histology, immunohistochemistry, and PCR. Schizonts were detected in the liver of one pigeon at day 10 post infection. A mild encephalitis was detected at day 20 post infection, around 4 weeks before the onset of neurological signs. At the same time, immature sarcocysts were present in the skeletal muscle. In seven pigeons a few sarcocysts were identified in the brain, but not associated with any lesion. These results suggest that the encephalitis is induced at a very early stage of the S. calchasi lifecycle rather than in the chronic phase of pigeon protozoal encephalitis. Despite the increasing severity of lesions in the central nervous system, the amount of sarcocysts did not increase. This supports the hypothesis of a delayed-type hypersensitivity response as the cause of the encephalitis. The study also demonstrated that S. calchasi DNA is detectable in tissues negative by histological methods, indicating a higher sensitivity of the real-time PCR.

  9. Fighting while parasitized: can nematode infections affect the outcome of staged combat in beetles?

    PubMed

    Vasquez, David; Willoughby, Anna; Davis, Andrew K

    2015-01-01

    The effects of non-lethal parasites may be felt most strongly when hosts engage in intense, energy-demanding behaviors. One such behavior is fighting with conspecifics, which is common among territorial animals, including many beetle species. We examined the effects of parasites on the fighting ability of a saproxylic beetle, the horned passalus (Odontotaenius disjunctus, Family: Passalidae), which is host to a non-lethal nematode, Chondronema passali. We pitted pairs of randomly-chosen (but equally-weighted) beetles against each other in a small arena and determined the winner and aggression level of fights. Then we examined beetles for the presence, and severity of nematode infections. There was a non-significant tendency (p = 0.065) for the frequency of wins, losses and draws to differ between beetles with and without C. passali; non-parasitized individuals (n = 104) won 47% of their fights while those with the parasite (n = 88) won 34%, a 13% difference in wins. The number of nematodes in a beetle affected the outcome of fights between infected and uninfected individuals in an unexpected fashion: fighting ability was lowest in beetles with the lowest (p = 0.033), not highest (p = 0.266), nematode burdens. Within-fight aggression was highest when both beetles were uninfected and lowest when both were infected (p = 0.034). Collectively, these results suggest the nematode parasite, C. passali, is associated with a modest reduction in fighting ability in horned passalus beetles, consistent with the idea that parasitized beetles have lower energy available for fighting. This study adds to a small but growing body of evidence showing how parasites negatively influence fighting behavior in animals.

  10. Fighting while Parasitized: Can Nematode Infections Affect the Outcome of Staged Combat in Beetles?

    PubMed Central

    Vasquez, David; Willoughby, Anna; Davis, Andrew K.

    2015-01-01

    The effects of non-lethal parasites may be felt most strongly when hosts engage in intense, energy-demanding behaviors. One such behavior is fighting with conspecifics, which is common among territorial animals, including many beetle species. We examined the effects of parasites on the fighting ability of a saproxylic beetle, the horned passalus (Odontotaenius disjunctus, Family: Passalidae), which is host to a non-lethal nematode, Chondronema passali. We pitted pairs of randomly-chosen (but equally-weighted) beetles against each other in a small arena and determined the winner and aggression level of fights. Then we examined beetles for the presence, and severity of nematode infections. There was a non-significant tendency (p = 0.065) for the frequency of wins, losses and draws to differ between beetles with and without C. passali; non-parasitized individuals (n = 104) won 47% of their fights while those with the parasite (n = 88) won 34%, a 13% difference in wins. The number of nematodes in a beetle affected the outcome of fights between infected and uninfected individuals in an unexpected fashion: fighting ability was lowest in beetles with the lowest (p = 0.033), not highest (p = 0.266), nematode burdens. Within-fight aggression was highest when both beetles were uninfected and lowest when both were infected (p = 0.034). Collectively, these results suggest the nematode parasite, C. passali, is associated with a modest reduction in fighting ability in horned passalus beetles, consistent with the idea that parasitized beetles have lower energy available for fighting. This study adds to a small but growing body of evidence showing how parasites negatively influence fighting behavior in animals. PMID:25830367

  11. Experimental caprine neosporosis: the influence of gestational stage on the outcome of infection.

    PubMed

    Porto, Wagnner José Nascimento; Regidor-Cerrillo, Javier; Kim, Pomy de Cássia Peixoto; Benavides, Julio; Silva, Ana Clécia dos Santos; Horcajo, Pilar; Oliveira, Andrea Alice da Fonseca; Ferre, Ignacio; Mota, Rinaldo Aparecido; Ortega-Mora, Luis Miguel

    2016-02-11

    Here, we assessed outcome of experimental infection by Neospora caninum in goats intravenously inoculated with 10(6) tachyzoites of the Nc-Spain7 isolate at 40 (G1), 90 (G2) and 120 (G3) days of gestation. Infected goats had fever between 5 and 9 days post inoculation (dpi); all were seropositive at the time of abortion/birth. Foetal death occurred in G1 from 10 to 21 dpi (n = 7) and in G2 from 27 to 35 dpi (n = 4). Goats in G2 also had seropositive stillbirth (n = 1) and healthy kids (n = 2). G3 goats (n = 7) had 3 seropositive and 3 seronegative weak kids, and 2 seronegative healthy kids. Parasite DNA detection in placentomes was 100% in G2, 85.7% in G3 and in G1 was detected only in placentomes from the goats with foetal losses from 17 dpi (100%). Parasites were detected in foetal/kid brain (>85.7%) and liver (≥ 50%) of G2 and G3, and in G1 after 17 dpi (100%). The highest parasite loads were detected in the placentomes of G1 from 17 dpi and G2, and in foetal tissues of G1 from 17 dpi and G3. Multifocal necrotic lesions were observed in the placentas of the three groups, but they were larger and more frequent in G1 and G2. Similar lesions were observed in foetal tissues, but they were more frequent in G3. These findings suggest that, as observed in cattle and sheep, the clinical consequences of N. caninum in pregnant goats are dependent in part on the time of gestation when animals were infected.

  12. Depressed Hypoxic and Hypercapnic Ventilatory Responses at Early Stage of Lethal Avian Influenza A Virus Infection in Mice

    PubMed Central

    Pollock, Zemmie; Harrod, Kevin S.; Xu, Fadi

    2016-01-01

    H5N1 virus infection results in ~60% mortality in patients primarily due to respiratory failure, but the underlying causes of mortality are unclear. The goal of this study is to reveal respiratory disorders occurring at the early stage of infection that may be responsible for subsequent respiratory failure and death. BALB/c mice were intranasally infected with one of two H5N1 virus strains: HK483 (lethal) or HK486 (non-lethal) virus. Pulmonary ventilation and the responses to hypoxia (HVR; 7% O2 for 3 min) and hypercapnia (HCVR; 7% CO2 for 5 min) were measured daily at 2 days prior and 1, 2, and 3 days postinfection (dpi) and compared to mortality typically by 8 dpi. At 1, 2, and 3 dpi, immunoreactivities (IR) of substance P (SP-IR) in the nodose ganglion or tyrosine hydroxylase (TH-IR) in the carotid body coupled with the nucleoprotein of influenza A (NP-IR) was examined in some mice, while arterial blood was collected in others. Our results showed that at 2 and 3 dpi: 1) both viral infections failed to alter body temperature and weight, V˙CO2, or induce viremia while producing similarly high lung viral titers; 2) HK483, but not HK486, virus induced tachypnea and depressed HVR and HCVR without changes in arterial blood pH and gases; and 3) only HK483 virus led to NP-IR in vagal SP-IR neurons, but not in the carotid body, and increased density of vagal SP-IR neurons. In addition, all HK483, rather than HK486, mice died at 6 to 8 dpi and the earlier death was correlated with more severe depression of HVR and HCVR. Our data suggest that tachypnea and depressed HVR/HCVR occur at the early stage of lethal H5N1 viral infection associated with viral replication and increased SP-IR density in vagal neurons, which may contribute to the respiratory failure and death. PMID:26808681

  13. Serological and molecular evidence of enterovirus infection in patients with end-stage dilated cardiomyopathy.

    PubMed Central

    Muir, P.; Nicholson, F.; Illavia, S. J.; McNeil, T. S.; Ajetunmobi, J. F.; Dunn, H.; Starkey, W. G.; Reetoo, K. N.; Cary, N. R.; Parameshwar, J.; Banatvala, J. E.

    1996-01-01

    OBJECTIVE: To study the relative diagnostic value of enterovirus-specific molecular biological and serological assays in patients with end-stage dilated cardiomyopathy, and to investigate the possible role of other cardiotropic viruses in dilated cardiomyopathy. DESIGN: Analysis of recipient myocardial tissue and serum from patients with dilated cardiomyopathy and controls undergoing cardiac transplantation for end-stage cardiac disease. SETTING: University virology department and transplantation unit. METHODS: Reverse transcriptase-polymerase chain reaction and nucleotide sequence analysis of myocardial RNA and DNA; enterovirus-specific in situ hybridization; enterovirus-specific immunoglobulin M detection. RESULTS: Enterovirus RNA was detected in myocardial tissue from only a small proportion of (five of 75) hearts. However, although enterovirus-specific immunoglobulin M responses were detected in 22 (28%) of 39 controls patients, a significantly higher prevalence was observed among patients with dilated cardiomyopathy (22 (56%) of 39 patients; P < 0.005). All enteroviruses detected in myocardium showed greatest nucleotide sequence homology with coxsackievirus type B3. Detection of enterovirus RNA in myocardium by the polymerase chain reaction and by in situ hybridisation gave comparable results. Other potentially cardiotropic virus genomes, including human cytomegalovirus, influenzaviruses, and coronaviruses were not detected in myocardium. CONCLUSION: This study found that enterovirus-specific immunoglobulin M responses provided the strongest evidence of enterovirus involvement in patients with end-stage dilated cardiomyopathy. However, the high background prevalence of these responses limits their diagnostic value. The finding that enteroviruses detected in myocardium were coxsackievirus type B3 accords with recent findings in patients with acute myocarditis, and indicates that this serotype is the major cardiotropic human enterovirus. Images PMID:8868984

  14. Pf155/RESA protein influences the dynamic microcirculatory behavior of ring-stage Plasmodium falciparum infected red blood cells

    NASA Astrophysics Data System (ADS)

    Diez-Silva, Monica; Park, Yongkeun; Huang, Sha; Bow, Hansen; Mercereau-Puijalon, Odile; Deplaine, Guillaume; Lavazec, Catherine; Perrot, Sylvie; Bonnefoy, Serge; Feld, Michael S.; Han, Jongyoon; Dao, Ming; Suresh, Subra

    2012-08-01

    Proteins exported by Plasmodium falciparum to the red blood cell (RBC) membrane modify the structural properties of the parasitized RBC (Pf-RBC). Although quasi-static single cell assays show reduced ring-stage Pf-RBCs deformability, the parameters influencing their microcirculatory behavior remain unexplored. Here, we study the dynamic properties of ring-stage Pf-RBCs and the role of the parasite protein Pf155/Ring-Infected Erythrocyte Surface Antigen (RESA). Diffraction phase microscopy revealed RESA-driven decreased Pf-RBCs membrane fluctuations. Microfluidic experiments showed a RESA-dependent reduction in the Pf-RBCs transit velocity, which was potentiated at febrile temperature. In a microspheres filtration system, incubation at febrile temperature impaired traversal of RESA-expressing Pf-RBCs. These results show that RESA influences ring-stage Pf-RBCs microcirculation, an effect that is fever-enhanced. This is the first identification of a parasite factor influencing the dynamic circulation of young asexual Pf-RBCs in physiologically relevant conditions, offering novel possibilities for interventions to reduce parasite survival and pathogenesis in its human host.

  15. Infections of Larval Stages of Dicrocoelium dendriticum and Brachylaima sp. in Brown Garden Snail, Helix aspersa, in Turkey.

    PubMed

    Köse, Mustafa; Eser, Mustafa; Kartal, Kürşat; Bozkurt, Mehmet Fatih

    2015-10-01

    The aim of this study was to determine the presence and prevalence of larval stages of Dicrocoelium dendriticum and Brachylaima sp. in the first intermediate host, a species of land snail, Helix aspersa, in Turkey. A total of 211 snails were collected in April-May 2014 from pastures in Mersin District. Larval stages of D. dendriticum were identified under a light microscope. Hepatopancreas from naturally infected H. aspersa snails were examined histologically. The prevalence of larval stages of D. dendriticum and Brachylaima sp. in H. aspersa snails was found to be 2.4% and 1.9%, respectively, in Mersin, Turkey. Cercariae were not matured in sporocysts at the beginning of April; however, it was observed that cercariae matured and started to leave sporocysts by early-May. Thus, it was concluded that H. aspersa acts as an intermediate host to D. dendriticumin and Brachylaima sp. in Mersin, Turkey. A digenean trematode Brachylaima sp. was seen for the first time in Turkey.

  16. Metabolic profiles of soybean roots during early stages of Fusarium tucumaniae infection.

    PubMed

    Scandiani, María M; Luque, Alicia G; Razori, María V; Ciancio Casalini, Lucila; Aoki, Takayuki; O'Donnell, Kerry; Cervigni, Gerardo D L; Spampinato, Claudia P

    2015-01-01

    Soybean germplasm exhibits various levels of resistance to Fusarium tucumaniae, the main causal agent of sudden death syndrome (SDS) of soybean in Argentina. In this study, two soybean genotypes, one susceptible (NA 4613) and one partially resistant (DM 4670) to SDS infection, were inoculated with F. tucumaniae. Disease symptoms were scored at 7, 10, 14, and 25 days post-inoculation (dpi). The greatest difference in the area under the disease progress curve (AUDPC) values among genotypes was observed at 25 dpi. In order to detect early metabolic markers that could potentially discriminate between susceptible and resistant genotypes, gas chromatography-mass spectrometry (GC-MS) analyses of root samples were performed. These analyses show higher levels of several amino acids and the polyamine cadaverine in the inoculated than in the uninoculated susceptible cultivar at 7 dpi. Principal component analysis (PCA) revealed that the metabolic profile of roots harvested at the earliest time points from the inoculated susceptible genotype was clearly differentiated from the rest of the samples. Furthermore, variables associated with the first principal component were mainly amino acids. Taken together, the results indicate that the pathogen induced the susceptible plant to accumulate amino acids in roots at early time points after infection, suggesting that GC-MS-based metabolomics could be used for the rapid characterization of cultivar response to SDS. PMID:25336687

  17. A multi-stage compartmental model for HIV-infected individuals: I--waiting time approach.

    PubMed

    Billard, L; Dayananda, P W A

    2014-03-01

    Traditionally, epidemic processes have focused on establishing systems of differential-difference equations governing the number of individuals at each stage of the epidemic. Except for simple situations such as when transition rates are linear, these equations are notoriously intractable mathematically. In this work, the process is described as a compartmental model. The model also allows for individuals to go directly from any prior compartment directly to a final stage corresponding to death. This allows for the possibility that individuals can die earlier due to some non-disease related cause. Then, the model is based on waiting times in each compartment. Survival probabilities of moving from a given compartment to another compartment are established. While our approach can be used for general epidemic processes, our framework is for the HIV/AIDS process. It is then possible to establish the impact of the HIV/AIDS epidemic process on, e.g., insurance premiums and payouts and health-care costs. The effect of changing model parameter values on these entities is investigated.

  18. Evidence for the expression of actomyosin in the infective stage of the sporozoan protist Eimeria.

    PubMed

    Preston, T M; King, C A

    1992-04-01

    A high-speed supernatant extract was obtained from infective oocysts of Eimeria tenella homogenised in a sucrose-low ionic strength buffer. Immunoblotting showed this soluble, micropore-filtered preparation (designated E1) to be rich in actin. E1 underwent superprecipitation on addition of ATP but not its non-hydrolysable analogue AMP.PMP--behaviour typical of an actomyosin solution. The superprecipitate fluoresced strongly in the presence of rhodamine-phalloidin (indicative of the presence of F-actin) and electron microscopy of negatively-stained preparations of this flocculent matter confirmed the abundance of filamentous material within it. This is the first demonstration of a functional actomyosin isolated from a member of the economically important phylum Apicomplexa. PMID:1525837

  19. Experimental infections of rabbits with proliferative and latent stages of Besnoitia besnoiti.

    PubMed

    Liénard, Emmanuel; Pop, Loredana; Prevot, Françoise; Grisez, Christelle; Mallet, Virginie; Raymond-Letron, Isabelle; Bouhsira, Émilie; Franc, Michel; Jacquiet, Philippe

    2015-10-01

    Cattle besnoitiosis due to Besnoitia besnoiti is spreading across Europe and is responsible for severe economic losses in newly infected herds. Experimentally speaking, rabbits have been found to be susceptible to this parasite. The adaptation of B. besnoiti to rabbits may offer a new, easier and cheaper model of investigation for this disease. This study compared the virulence between tachyzoites and bradyzoites of B. besnoiti in rabbits. Eighteen New Zealand rabbits were allocated into three groups of six animals each. The rabbits from the control (group C), "tachyzoite" (group T) and "bradyzoite" (group B) groups were subcutaneously injected in the right flank with 66 μg of ovalbumin, 6.10(6) tachyzoites (125th passage on Vero cells) and 6.10(6) bradyzoites (collected from a natural infected cow) of B. besnoiti, respectively. Clinical follow-up and blood sampling for serological survey and qPCR were performed during 10 weeks until euthanasia. Molecular and immunohistochemistry examination was achieved on 25 samples of tissue per rabbit. Seroconversion occurred in group T without any clinical signs. Rabbits of group B exhibited a febrile condition (temperature above 40 °C from day 8 to day 11 following injection) with positive qPCR in blood. Cysts of B. besnoiti were found on skin samples and organs of rabbits from group B in tissue explored with threshold cycle (Ct) values below 30. These results suggest a higher virulence of bradyzoites in rabbits than Vero cell-cultivated tachyzoites. The proposed model could be used to assess the in vivo effectiveness of vaccine or drugs against cattle besnoitiosis.

  20. Analysis of the Transcriptome of the Infective Stage of the Beet Cyst Nematode, H. schachtii

    PubMed Central

    Fosu-Nyarko, John; Nicol, Paul; Naz, Fareeha; Gill, Reetinder; Jones, Michael G. K.

    2016-01-01

    The beet cyst nematode, Heterodera schachtii, is a major root pest that significantly impacts the yield of sugar beet, brassicas and related species. There has been limited molecular characterisation of this important plant pathogen: to identify target genes for its control the transcriptome of the pre-parasitic J2 stage of H. schachtii was sequenced using Roche GS FLX. Ninety seven percent of reads (i.e., 387,668) with an average PHRED score > 22 were assembled with CAP3 and CLC Genomics Workbench into 37,345 and 47,263 contigs, respectively. The transcripts were annotated by comparing with gene and genomic sequences of other nematodes and annotated proteins on public databases. The annotated transcripts were much more similar to sequences of Heterodera glycines than to those of Globodera pallida and root knot nematodes (Meloidogyne spp.). Analysis of these transcripts showed that a subset of 2,918 transcripts was common to free-living and plant parasitic nematodes suggesting that this subset is involved in general nematode metabolism and development. A set of 148 contigs and 183 singletons encoding putative homologues of effectors previously characterised for plant parasitic nematodes were also identified: these are known to be important for parasitism of host plants during migration through tissues or feeding from cells or are thought to be involved in evasion or modulation of host defences. In addition, the presence of sequences from a nematode virus is suggested. The sequencing and annotation of this transcriptome significantly adds to the genetic data available for H. schachtii, and identifies genes primed to undertake required roles in the critical pre-parasitic and early post-parasitic J2 stages. These data provide new information for identifying potential gene targets for future protection of susceptible crops against H. schachtii. PMID:26824923

  1. Analysis of the Transcriptome of the Infective Stage of the Beet Cyst Nematode, H. schachtii.

    PubMed

    Fosu-Nyarko, John; Nicol, Paul; Naz, Fareeha; Gill, Reetinder; Jones, Michael G K

    2016-01-01

    The beet cyst nematode, Heterodera schachtii, is a major root pest that significantly impacts the yield of sugar beet, brassicas and related species. There has been limited molecular characterisation of this important plant pathogen: to identify target genes for its control the transcriptome of the pre-parasitic J2 stage of H. schachtii was sequenced using Roche GS FLX. Ninety seven percent of reads (i.e., 387,668) with an average PHRED score > 22 were assembled with CAP3 and CLC Genomics Workbench into 37,345 and 47,263 contigs, respectively. The transcripts were annotated by comparing with gene and genomic sequences of other nematodes and annotated proteins on public databases. The annotated transcripts were much more similar to sequences of Heterodera glycines than to those of Globodera pallida and root knot nematodes (Meloidogyne spp.). Analysis of these transcripts showed that a subset of 2,918 transcripts was common to free-living and plant parasitic nematodes suggesting that this subset is involved in general nematode metabolism and development. A set of 148 contigs and 183 singletons encoding putative homologues of effectors previously characterised for plant parasitic nematodes were also identified: these are known to be important for parasitism of host plants during migration through tissues or feeding from cells or are thought to be involved in evasion or modulation of host defences. In addition, the presence of sequences from a nematode virus is suggested. The sequencing and annotation of this transcriptome significantly adds to the genetic data available for H. schachtii, and identifies genes primed to undertake required roles in the critical pre-parasitic and early post-parasitic J2 stages. These data provide new information for identifying potential gene targets for future protection of susceptible crops against H. schachtii. PMID:26824923

  2. Variation in microfilariae and infective stages of two types of Wuchereria bancrofti from the Thai-Myanmar border.

    PubMed

    Jitpakdi, A; Choochote, W; Panart, P; Insun, P; Panart, K; Pitasawat, B; Prajakwong, S

    1999-12-01

    Comparative morphometric and morphological studies of microfilariae and infective stages were undertaken in nocturnally periodic and subperiodic Wuchereria bancrofti. For microfilariae, the body dimensions of nocturnally periodic (NP) were significantly smaller than nocturnally subperiodic (NSP), i.e., body length 268.03+/-14.75 microm (NP), 307.61+/-11.52 microm (NSP); cephalic space length 4.21+/-0.62 microm (NP), 5.32+/-0.79 microm (NSP); head to nerve ring 49.39+/-5.43 microm (NP), 57.40+/-4.46 microm (NSP); innenkörper length 33.05+/-5.89 microm (NP), 44.02+/-8.71 microm (NSP); cephalic space width 4.28+/-0.59 microm (NP), 6.04+/-0.68 microm (NSP); body width at nerve ring 5.01+/-0.57 microm (NP), 7.45+/-0.75 microm (NSP). The number of nuclei between the cephalic space and nerve ring of NP (66.67+/-5.19) was also significantly less than in NSP (94.74+/-6.95). For infective stages, the body dimensions of NP were significantly smaller than NSP, i.e., body length 1632.50+/-131.48 microm (NP), 2002.63+/-222.60 microm (NSP); head to nerve ring 103.09+/-7.47 microm (NP), 122.44+/-9.62 microm (NSP); head to oesophago-intestinal junction 567.69+/-94.84 microm (NP), 666.75+/-110.08 microm (NSP); body width at oesophago-intestinal junction 23.15+/-1.55 microm (NP), 26.78+/-1.62 microm (NSP). It is too early to infer the NP type as an additional sibling species of W. bancrofti but it is reasonable to treat it as a new variety and additional work is needed to clarify its status.

  3. Towards a vaccine against asexual blood stage infection by Plasmodium falciparum.

    PubMed

    Dubois, P; Pereira da Silva, L

    1995-01-01

    In this paper, we will summarize the progress obtained in the malaria vaccine project developed by the Institut Pasteur groups interacting through the International Network of Pasteur Institutes over the last fifteen years. While trying to follow the progress in scientific and technological concepts and methodologies, the basic approach was still essentially the same as that followed by Pasteur and his acolytes to try to artificially reproduce the natural processes that lead to the development of immunity to infection and disease. A longitudinal study of two villages from the Sine Saloum area of Senegal, Dielmo and N'Diop, conducted in recent years by teams of the Institut Pasteur of Dakar, Senegal, in collaboration with the local ORSTOM malaria unit has led to the detailed analysis of the natural acquisition of premunition against Plasmodium falciparum malaria in endemic areas. The Saimiri model developed at the Pasteur Institute in Cayenne, was an important step forward in terms of studies on the mechanisms of action of protective antibodies and on vaccinations assays. If we accept the conclusions of the Pasteur groups' research on the experimental primate model and on the development of natural immunity (premunition) in highly endemic areas, the main inhibitor of progress in vaccine development is our poor understanding of the regulation of the immune response. Therefore, the general approaches that were followed for vaccine development must now be further explored using the continually developing tools of immunology and molecular biology, to elucidate regulations of the immune responses to the parasite, and identify the molecular mechanisms used by the parasite to generate and change antigen specificities.

  4. Disentangling the influence of parasite genotype, host genotype and maternal environment on different stages of bacterial infection in Daphnia magna.

    PubMed

    Hall, Matthew D; Ebert, Dieter

    2012-08-22

    Individuals naturally vary in the severity of infectious disease when exposed to a parasite. Dissecting this variation into genetic and environmental components can reveal whether or not this variation depends on the host genotype, parasite genotype or a range of environmental conditions. Complicating this task, however, is that the symptoms of disease result from the combined effect of a series of events, from the initial encounter between a host and parasite, through to the activation of the host immune system and the exploitation of host resources. Here, we use the crustacean Daphnia magna and its parasite Pasteuria ramosa to show how disentangling genetic and environmental factors at different stages of infection improves our understanding of the processes shaping infectious disease. Using compatible host-parasite combinations, we experimentally exclude variation in the ability of a parasite to penetrate the host, from measures of parasite clearance, the reduction in host fecundity and the proliferation of the parasite. We show how parasite resistance consists of two components that vary in environmental sensitivity, how the maternal environment influences all measured aspects of the within-host infection process and how host-parasite interactions following the penetration of the parasite into the host have a distinct temporal component.

  5. Neospora caninum: the First Demonstration of the Enteroepithelial Stages in the Intestines of a Naturally Infected Dog.

    PubMed

    Kul, O; Atmaca, H T; Anteplioglu, T; Ocal, N; Canpolat, S

    2015-07-01

    A 1.5-month-old Kangal breed puppy from a dairy cattle farm died after showing severe diarrhoea and incoordination. Necropsy examination revealed multifocal pulmonary consolidation and necrosis and fibrinohaemorrhagic enteritis. Microscopically, there was necrotic and purulent bronchopneumonia, myocarditis and non-purulent encephalitis. In the jejunum and ileum there was villous atrophy and crypt hyperplasia with oocyst-like and schizont-like structures in the epithelia. Immunohistochemically, Neospora caninum antigen was detected in association with the intestinal protozoal structures, degenerative neurons and areas of necrosis in the lungs and heart. Polymerase chain reaction confirmed that the organism was N. caninum and not Toxoplasma gondii. The seroprevalence for N. caninum was 74.2% (49/66 animals) for the cattle and 57.1% (4/7 animals) for dogs on this farm. This report documents fatal systemic neosporosis and enteroepithelial stages of N. caninum in a naturally infected puppy. To the authors' knowledge, this is the first definition of intestinal neosporosis in a naturally infected dog as well as the first evidence of fatal canine neosporosis in Turkey. PMID:25981437

  6. Effect of Thai 'koi-hoi' food flavoring on the viability and infectivity of the third-stage larvae of Angiostrongylus cantonensis (Nematoda: Angiostrongylidae).

    PubMed

    Eamsobhana, Praphathip; Yoolek, Adisak; Yong, Hoi-Sen

    2010-03-01

    The effect of the food flavoring of 'koi-hoi', a popular Thai snail dish, on the viability and infectivity of Angiostrongylus (=Parastrongylus) cantonensis third-stage larvae was assessed in a mouse model. Groups of 50 each of actively moving, non-motile coiled, and extended larvae were obtained from experimentally infected snail meat, after one-hour exposure to standard 'koi-hoi' flavoring. These larvae and groups of 50 unexposed moving larvae (control) were individually fed to each group of three experimental BALB/c mice. The effect on Angiostrongylus worm burden was measured after 3 weeks of infection. Infectivity of the motile larvae after exposure to 'koi-hoi' food flavoring was 38 + or - 5.29%. This was highly significantly lower than the infectivity (62 + or - 7.21%) of the control (unexposed) third-stage larvae (chi(2) = 17.28, P < 0.001). In the non-motile larvae resulting from exposure to the food flavoring, no adult worm was recovered from the extended larvae, indicating that they were no longer alive and unable to cause infection. A small proportion (3.33 + or - 2.31%) of the coiled larvae developed into young adult worms, indicating that mobility alone is not a definitive indicator of viability. The present study confirms that the food flavoring components of 'koi-hoi' dish adversely affect the viability and infectivity of A. cantonensis larvae. Exposure of the third-stage larvae to 'koi-hoi' food flavoring resulted in decreased viability and eventually death. Prolonged treatment with food flavoring to inactivate/immobilize and then kill the infective, third-stage larvae of A. cantonensis in snail meat prior to consumption may be one of the possible economical means of reducing human infection. PMID:19931504

  7. Infection of Goose with Genotype VIId Newcastle Disease Virus of Goose Origin Elicits Strong Immune Responses at Early Stage

    PubMed Central

    Xu, Qianqian; Chen, Yuqiu; Zhao, Wenjun; Zhang, Tingting; Liu, Chenggang; Qi, Tianming; Han, Zongxi; Shao, Yuhao; Ma, Deying; Liu, Shengwang

    2016-01-01

    Newcastle disease (ND), caused by virulent strains of Newcastle disease virus (NDV), is a highly contagious disease of birds that is responsible for heavy economic losses for the poultry industry worldwide. However, little is known about host-virus interactions in waterfowl, goose. In this study, we aim to characterize the host immune response in goose, based on the previous reports on the host response to NDV in chickens. Here, we evaluated viral replication and mRNA expression of 27 immune-related genes in 10 tissues of geese challenged with a genotype VIId NDV strain of goose origin (go/CH/LHLJ/1/06). The virus showed early replication, especially in digestive and immune tissues. The expression profiles showed up-regulation of Toll-like receptor (TLR)1–3, 5, 7, and 15, avian β-defensin (AvBD) 5–7, 10, 12, and 16, cytokines [interleukin (IL)-8, IL-18, IL-1β, and interferon-γ], inducible NO synthase (iNOS), and MHC class I in some tissues of geese in response to NDV. In contrast, NDV infection suppressed expression of AvBD1 in cecal tonsil of geese. Moreover, we observed a highly positive correlation between viral replication and host mRNA expressions of TLR1-5 and 7, AvBD4-6, 10, and 12, all the cytokines measured, MHC class I, FAS ligand, and iNOS, mainly at 72 h post-infection. Taken together, these results demonstrated that NDV infection induces strong innate immune responses and intense inflammatory responses at early stage in goose which may associate with the viral pathogenesis. PMID:27757109

  8. Association of caveolin with Chlamydia trachomatis inclusions at early and late stages of infection.

    PubMed

    Norkin, L C; Wolfrom, S A; Stuart, E S

    2001-06-10

    The mechanism by which the intracellular bacterial pathogen Chlamydia trachomatis enters eukaryotic cells is poorly understood. There are conflicting reports of entry occurring by clathrin-dependent and clathrin-independent processes. We report here that C. trachomatis serovar K enters HEp-2 and HeLa 229 epithelial cells and J-774A.1 mouse macrophage/monocyte cells via caveolin-containing sphingolipid and cholesterol-enriched raft microdomains in the host cell plasma membranes. First, filipin and nystatin, drugs that specifically disrupt raft function by cholesterol chelation, each impaired entry of C. trachomatis serovar K. In control experiments, filipin did not impair entry of the same organism by an antibody-mediated opsonic process, nor did it impair entry of BSA-coated microspheres. Second, the chlamydia-containing endocytic vesicles specifically reacted with antisera against the caveolae marker protein caveolin. These vesicles are known to become the inclusions in which parasite replication occurs. They avoid fusion with lysosomes and instead traffic to the Golgi region, where they intercept Golgi-derived vesicles that recycle sphingolipids and cholesterol to the plasma membrane. We also report that late-stage C. trachomatis inclusions continue to display high levels of caveolin, which they likely acquire from the exocytic Golgi vesicles. We suggest that the atypical raft-mediated entry process may have important consequences for the host-pathogen interaction well after entry has occurred. These consequences include enabling the chlamydial vesicle to avoid acidification and fusion with lysosomes, to traffic to the Golgi region, and to intercept sphingolipid-containing vesicles from the Golgi.

  9. Preadult Stage Parasites and Multiple Timed Exposure to Infective Larvae Are Involved in Development of Limb Edema in Brugia malayi-Infected Indian Leaf Monkeys (Presbytis entellus)†

    PubMed Central

    Murthy, P. K.; Khan, M. A.; Rajani, H. B.; Srivastava, V. M. L.

    2002-01-01

    The pathogenesis of filarial limb edema is not known. The role of parasitological variables and parasite-mediated phenomena in the development of limb edema was investigated in the Presbytis entellus-Brugia malayi model. Infection was initiated with subcutaneous inoculation of infective third-stage larvae (L3), and the animals were reexposed to different doses of L3 at the prepatent, patent, and diminishing microfilaremia (0 to 5% of peak microfilaremia count) stages of infection. A large L3 inoculum size and repeated inoculation in the ankle region during the prepatent, patent, and diminishing microfilaremia stages of infection were found to be necessary for reproducible induction of limb edema. The preadult stage of the parasite was found to be the most potent inducer of limb edema, followed by L5 and L4. The presence of the proinflammatory cytokines tumor necrosis factor alpha, interleukin-1β, and interleukin-6 in edema fluid in the leg receiving the parasite challenge indicated that the limb edema development was due to parasite-mediated cytokine responses. The absence of bacterial infection or anti-streptolysin O titer in the edema fluid and blood indicated that bacterial infection is not necessary for the development of limb edema. PMID:12093695

  10. Isoform patterns of chitinase and beta-1,3-glucanase in maturing corn kernels (Zea mays L.) associated with Aspergillus flavus milk stage infection.

    PubMed

    Ji, C; Norton, R A; Wicklow, D T; Dowd, P F

    2000-02-01

    Isoform patterns of chitinase and beta-1,3-glucanase of maturing kernels of yellow dent corn (Pioneer 3394) infected with Aspergillus flavus at the milk stage were investigated through polyacrylamide gel electrophoresis (PAGE). Proteins on the sodium dodecyl sulfate (SDS) gel with an apparent molecular mass range of 23-46 kDa were differentially present in the kernels infected with both aflatoxin-producing and non-aflatoxin-producing strains of A. flavus. From in-gel (native PAGE) enzyme activity assays, three bands corresponding to chitinase isoforms and two bands corresponding to beta-1,3-glucanase isoforms were detected in the infected kernels. One chitinase isoform of 29 kDa was present only in the infected kernels, and another one of 28 kDa was present in both infected and noninfected kernels. They were judged to be acidic on the basis of their migration on an acrylamide isoelectric focusing (IEF) gel. For the beta-1,3-glucanase, one isoform of 35 kDa was present in both infected and noninfected kernels, but another one, a 33 kDa isoform, was present only in the infected kernels. Both acidic and basic beta-1,3-glucanase isoforms were detected in the IEF gel. The results of this study are the first to demonstrate patterns of enhanced or inducible proteins in maturing corn kernels in response to A. flavus infection at the milk stage. The results also indicate that only particular isoforms of the two hydrolytic enzymes are involved in the maturing corn kernels infected at the milk stage with A. flavus.

  11. EVALUATION OF THE THERAPEUTIC EFFICACY OF LEVAMISOLE HYDROCHLORIDE ON THIRD-STAGE LARVAE OF Lagochilascaris minor IN EXPERIMENTALLY INFECTED MICE

    PubMed Central

    CAMPOS, Dulcinéa Maria Barbosa; BARBOSA, Alverne Passos; OLIVEIRA, Jayrson Araújo; BARBOSA, Carlos Augusto Lopes; LOBO, Tamara Flavia Correa; SILVA, Luana Gabriella; THOMAZ, Douglas Vieira; PEIXOTO, Josana de Castro

    2016-01-01

    Lagochilascariosis, a disease caused by Lagochilascaris minor, affects the neck, sinuses, tonsils, lungs, the sacral region, dental alveoli, eyeballs and the central nervous system of humans. A cycle of autoinfection may occur in human host tissues characterized by the presence of eggs, larvae and adult worms. This peculiarity of the cycle hinders therapy, since there are no drugs that exhibit ovicidal, larvicidal and vermicidal activity. Given these facts, we studied the action of levamisole hydrochloride on third-stage larvae in the migration phase (G1) and on encysted larvae (G3) of L. minor. To this end, 87 inbred mice of the C57BL/6 strain were divided into test groups comprising 67 animals (G1-37; G3-30) and a control group (G2-10; G4-10) with 20 animals. Each animal was inoculated orally with 2,000 infective eggs of the parasite. The animals of the test groups were treated individually with a single oral dose of levamisole hydrochloride at a concentration of 0.075 mg. The drug was administered either 30 minutes prior to the parasite inoculation (G1 animals) or 120 days after the inoculation (G3 animals). The mice in the control groups were not treated with the drug. After the time required for the migration and the encysting of L. minor larvae, all the animals were euthanized and their tissues examined. The data were analyzed using the Student's unpaired t-test and the Levene test. The groups showed no statistically significant difference. Levamisole hydrochloride was ineffective on third-stage larvae of L. minor. These findings explain the massive expulsion of live adult worms, as well as the use of long treatment schemes, owing to the persistence of larvae and eggs in human parasitic lesions. PMID:27253745

  12. EVALUATION OF THE THERAPEUTIC EFFICACY OF LEVAMISOLE HYDROCHLORIDE ON THIRD-STAGE LARVAE OF Lagochilascaris minor IN EXPERIMENTALLY INFECTED MICE.

    PubMed

    Campos, Dulcinéa Maria Barbosa; Barbosa, Alverne Passos; Oliveira, Jayrson Araújo; Barbosa, Carlos Augusto Lopes; Lobo, Tamara Flavia Correa; Silva, Luana Gabriella; Thomaz, Douglas Vieira; Peixoto, Josana de Castro

    2016-01-01

    Lagochilascariosis, a disease caused by Lagochilascaris minor, affects the neck, sinuses, tonsils, lungs, the sacral region, dental alveoli, eyeballs and the central nervous system of humans. A cycle of autoinfection may occur in human host tissues characterized by the presence of eggs, larvae and adult worms. This peculiarity of the cycle hinders therapy, since there are no drugs that exhibit ovicidal, larvicidal and vermicidal activity. Given these facts, we studied the action of levamisole hydrochloride on third-stage larvae in the migration phase (G1) and on encysted larvae (G3) of L. minor. To this end, 87 inbred mice of the C57BL/6 strain were divided into test groups comprising 67 animals (G1-37; G3-30) and a control group (G2-10; G4-10) with 20 animals. Each animal was inoculated orally with 2,000 infective eggs of the parasite. The animals of the test groups were treated individually with a single oral dose of levamisole hydrochloride at a concentration of 0.075 mg. The drug was administered either 30 minutes prior to the parasite inoculation (G1 animals) or 120 days after the inoculation (G3 animals). The mice in the control groups were not treated with the drug. After the time required for the migration and the encysting of L. minor larvae, all the animals were euthanized and their tissues examined. The data were analyzed using the Student's unpaired t-test and the Levene test. The groups showed no statistically significant difference. Levamisole hydrochloride was ineffective on third-stage larvae of L. minor. These findings explain the massive expulsion of live adult worms, as well as the use of long treatment schemes, owing to the persistence of larvae and eggs in human parasitic lesions. PMID:27253745

  13. Dose confirmation studies for monepantel, an amino-acetonitrile derivative, against fourth stage gastro-intestinal nematode larvae infecting sheep.

    PubMed

    Hosking, B C; Dobson, D P; Stein, P A; Kaminsky, R; Bapst, B; Mosimann, D; Mason, P C; Seewald, W; Strehlau, G; Sager, H

    2009-03-23

    Monepantel is the first compound from the recently discovered amino-acetonitrile derivative (AAD) class of anthelmintics to be developed for use in sheep. Nine dose confirmation studies were conducted in Australia, New Zealand and Switzerland to confirm the minimum therapeutic oral dose of monepantel to control fourth stage (L4) gastro-intestinal nematode larvae in sheep (target species were Haemonchus contortus, Teladorsagia (Ostertagia) circumcincta, Teladorsagia trifurcata, Trichostrongylus axei, Trichostrongylus colubriformis, Trichostrongylus vitrinus, Cooperia curticei, Cooperia oncophora, Nematodirusbattus, Nematodirusfilicollis, Nematodirus spathiger, Chabertia ovina and Oesophagostomum venulosum). In each study, sheep infected with a defined selection of the target nematodes were treated with 2.5mg monepantel/kg liveweight. Following euthanasia and worm counting, efficacy was calculated against worm counts from untreated control groups. The results demonstrate high (95<100%) efficacy of monepantel when administered orally to sheep at 2.5mg/kg for most species tested. Efficacy levels against N. spathiger and O. venulosum were variable and failed to meet the required regulatory standard (> or =90%) in some studies. Efficacy was demonstrated against L4 stages of nematodes known to be resistant to either benzimidazole and/or levamisole anthelmintics (macrocyclic lactone resistant isolates were not available for testing). The broad-spectrum activity of monepantel against L4 larvae of common gastro-intestinal nematodes in sheep and its favorable safety profile represents a significant advance in the treatment of parasitic gastro-enteritis in this animal species. No adverse effects related to treatment with monepantel were observed. PMID:19135310

  14. Cathepsin Gene Family Reveals Transcriptome Patterns Related to the Infective Stages of the Salmon Louse Caligus rogercresseyi

    PubMed Central

    Maldonado-Aguayo, Waleska; Chávez-Mardones, Jacqueline; Gonçalves, Ana Teresa; Gallardo-Escárate, Cristian

    2015-01-01

    Cathepsins are proteases involved in the ability of parasites to overcome and/or modulate host defenses so as to complete their own lifecycle. However, the mechanisms underlying this ability of cathepsins are still poorly understood. One excellent model for identifying and exploring the molecular functions of cathepsins is the marine ectoparasitic copepod Caligus rogercresseyi that currently affects the Chilean salmon industry. Using high-throughput transcriptome sequencing, 56 cathepsin-like sequences were found distributed in five cysteine protease groups (B, F, L, Z, and S) as well as in an aspartic protease group (D). Ontogenic transcriptome analysis evidenced that L cathepsins were the most abundant during the lifecycle, while cathepsins B and K were mostly expressed in the larval stages and adult females, thus suggesting participation in the molting processes and embryonic development, respectively. Interestingly, a variety of cathepsins from groups Z, L, D, B, K, and S were upregulated in the infective stage of copepodid, corroborating the complexity of the processes involved in the parasitic success of this copepod. Putative functional roles of cathepsins were conjectured based on the differential expressions found and on roles previously described in other phylogenetically related species. Moreover, 140 single nucleotide polymorphisms (SNP) were identified in transcripts annotated for cysteine and aspartic proteases located into untranslated regions, or the coding region. This study reports for the first time the presence of cathepsin-like genes and differential expressions throughout a copepod lifecycle. The identification of cathepsins together with functional validations represents a valuable strategy for pinpointing target molecules that could be used in the development of new delousing drugs or vaccines against C. rogercresseyi. PMID:25923525

  15. Development of life stages of Leptotrombidium imphalum and Leptotrombidium chiangraiensis (Acari: Trombiculidae) uninfected and infected with the scrub typhus rickettsia, Orientia tsustugamushi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Leptotrombidium chiangraiensis Tanskul and Linthicum and Leptotrombidium imphalum Vercammen-Grandjean are important vectors of scrub typhus in ricefield habitats in northern Thailand. The developmental biology of all stages of the life cycle of two generations of mites infected with Orientia tsutsug...

  16. Morphological and morphometric differentiation of dorsal-spined first stage larvae of lungworms, (Nematoda: Protostrongylidae) infecting muskoxen (Ovibos moschatus) in the Central Canadian Arctic

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Umingmakstrongylus pallikuukensis and Varestrongylus eleguneniensis are the two most common protostrongylid nematodes infecting muskoxen in the North American Arctic and Subarctic. First stage larvae (L1) of both these lungworms have a characteristic dorsal spine originating at the level of proxima...

  17. Colletotrichum orbiculare WHI2, a Yeast Stress-Response Regulator Homolog, Controls the Biotrophic Stage of Hemibiotrophic Infection Through TOR Signaling.

    PubMed

    Harata, Ken; Nishiuchi, Takumi; Kubo, Yasuyuki

    2016-06-01

    The hemibiotrophic fungus Colletotrichum orbiculare first establishes a biotrophic infection stage in cucumber (Cucumber sativus) epidermal cells and subsequently transitions to a necrotrophic stage. Here, we found that C. orbiculare established hemibiotrophic infection via C. orbiculare WHI2, a yeast stress regulator homolog, and TOR (target of rapamycin) signaling. Plant defense responses such as callose deposition, H2O2, and antimicrobial proteins were strongly induced by the C. orbiculare whi2Δ mutant, resulting in defective pathogenesis. Expression analysis of biotrophy-specific genes evaluated by the promoter VENUS fusion gene indicated weaker VENUS signal intensity in the whi2Δ mutant, thereby suggesting that C. orbiculare WHI2 plays a key role in regulating biotrophic infection of C. orbiculare. The involvement of CoWHI2 in biotrophic infection was further explored with a DNA microarray. In the Cowhi2Δ mutant, TOR-dependent ribosomal protein-related genes were strikingly upregulated compared with the wild type. Moreover, callose deposition in the host plant after inoculation with the Cowhi2Δ mutant treated with rapamycin, which inhibits TOR activity, was reduced, and the mutant remained biotrophic in contrast to the untreated mutant. Thus, regulation of TOR by Whi2 is apparently crucial to the biotrophic stage of hemibiotrophic infection in C. orbiculare.

  18. Colletotrichum orbiculare WHI2, a Yeast Stress-Response Regulator Homolog, Controls the Biotrophic Stage of Hemibiotrophic Infection Through TOR Signaling.

    PubMed

    Harata, Ken; Nishiuchi, Takumi; Kubo, Yasuyuki

    2016-06-01

    The hemibiotrophic fungus Colletotrichum orbiculare first establishes a biotrophic infection stage in cucumber (Cucumber sativus) epidermal cells and subsequently transitions to a necrotrophic stage. Here, we found that C. orbiculare established hemibiotrophic infection via C. orbiculare WHI2, a yeast stress regulator homolog, and TOR (target of rapamycin) signaling. Plant defense responses such as callose deposition, H2O2, and antimicrobial proteins were strongly induced by the C. orbiculare whi2Δ mutant, resulting in defective pathogenesis. Expression analysis of biotrophy-specific genes evaluated by the promoter VENUS fusion gene indicated weaker VENUS signal intensity in the whi2Δ mutant, thereby suggesting that C. orbiculare WHI2 plays a key role in regulating biotrophic infection of C. orbiculare. The involvement of CoWHI2 in biotrophic infection was further explored with a DNA microarray. In the Cowhi2Δ mutant, TOR-dependent ribosomal protein-related genes were strikingly upregulated compared with the wild type. Moreover, callose deposition in the host plant after inoculation with the Cowhi2Δ mutant treated with rapamycin, which inhibits TOR activity, was reduced, and the mutant remained biotrophic in contrast to the untreated mutant. Thus, regulation of TOR by Whi2 is apparently crucial to the biotrophic stage of hemibiotrophic infection in C. orbiculare. PMID:27018615

  19. Multi-Stage Tuberculosis Subunit Vaccine Candidate LT69 Provides High Protection against Mycobacterium tuberculosis Infection in Mice

    PubMed Central

    Niu, Hongxia; Peng, Jinxiu; Bai, Chunxiang; Liu, Xun; Hu, Lina; Luo, Yanping; Wang, Bingxiang; Zhang, Ying; Chen, Jianzhu; Yu, Hongjuan; Xian, Qiaoyang; Zhu, Bingdong

    2015-01-01

    Effective tuberculosis (TB) vaccine should target tubercle bacilli with various metabolic states and confer long-term protective immunity. In this study, we constructed a novel multi-stage TB subunit vaccine based on fusion protein ESAT6-Ag85B-MPT64(190-198)-Mtb8.4-HspX (LT69 for short) which combined early expressed antigens and latency-associated antigen. The fusion protein was mixed with an adjuvant being composed of N, N’-dimethyl-N, N’-dioctadecylammonium bromide (DDA) and polyriboinosinic polyribocytidylic acid (PolyI:C) to construct subunit vaccine, whose immunogenicity and protective ability were evaluated in C57BL/6 mice. The results showed that LT69 had strong immunogenicity and high protective effect against Mycobacterium tuberculosis (M. tuberculosis) H37Rv aerosol challenge. Low-dose (2 μg) of LT69 generated long-term immune memory responses and provided effective protection, which was even higher than traditional vaccine BCG did at 30 weeks post the last vaccination. In conclusion, multistage subunit vaccine LT69 showed high and long-term protection against M. tuberculosis infection in mice, whose effect could be enhanced by using a relative low dosage of antigen. PMID:26098302

  20. Stages of HIV Infection

    MedlinePlus

    ... Disease Dementia Hospitalization and Palliative Care Friends & Family Dating and Marriage Family Planning Mixed-Status Couples Discrimination ... New Media Tools Blogs Mashups Mobile Office Hours Online Collaboration Tools Photo Sharing Sites Podcasts QR Codes ...

  1. Comparison of the Galleria baiting technique and a direct extraction method for recovering Steinernema (Nematoda: Rhabditida) infective-stage juveniles from soil.

    PubMed

    Sturhan, D; Mrácek, Z

    2000-01-01

    Forty soil samples from forests and other biotopes in Germany and the Czech Republic were studied for the presence of entomopathogenic nematodes using the Galleria bait method at the same time as a sieving-decanting method for direct extraction of infective-stage juveniles. Five Steinernema species were recovered from the samples from Germany and four species from the samples from Czechia. All five species were recovered with both methods, but the baiting technique was generally less effective and mixtures of species were frequently undetected. The direct extraction method provided quantitative estimates of infective-stage juvenile density but no information on their infectivity or on morphological characters of adults, and nematode cultures could not be established.

  2. Rapid and Slow Progressors Show Increased IL-6 and IL-10 Levels in the Pre-AIDS Stage of HIV Infection

    PubMed Central

    de Medeiros, Rúbia M.; Valverde-Villegas, Jacqueline M.; Junqueira, Dennis M.; Gräf, Tiago; Lindenau, Juliana D.; de Mello, Marineide G.; Vianna, Priscila; Almeida, Sabrina E. M.; Chies, Jose Artur B.

    2016-01-01

    Cytokines are intrinsically related to disease progression in HIV infection. We evaluated the plasma levels of Th1/Th2/Th17 cytokines in extreme progressors, including slow (SPs) and rapid (RPs) progressors, who were thus classified based on clinical and laboratory follow-up covering a period of time before the initiation of HAART, ranging from 93–136.5 months for SPs and 7.5–16.5 months for RPs. Analyses were also performed based on the different stages of HIV infection (chronic, pre-HAART individuals—subjects sampled before initiating HAART but who initiated therapy from 12 to 24 months—and those receiving HAART). The plasma cytokine levels of 16 HIV-infected rapid progressors and 25 slow progressors were measured using a Human Th1/Th2/Th17 CBA kit. The IL-6 and IL-10 plasma levels differed significantly between the stages of HIV infection. The IL-6 levels were higher in slow progressors pre-HAART than in chronically infected SPs and HIV-seronegative individuals. The IL-10 levels were higher in slow progressors pre-HAART than in slow progressors receiving HAART and HIV-seronegative controls, and in rapid progressors, the IL-10 levels were higher in pre-HAART subjects than in HIV-seronegative controls. The results reflect the changes in the cytokine profile occurring during different clinical stages in HIV+ subjects. Our results suggest an association between increased IL-6 and IL-10 levels and pre-HAART stages independent of the slow or rapid progression status of the subjects. Thus, increased IL-6 and IL-10 levels could indicate a global inflammatory status and could be used as markers of the disease course in HIV-infected individuals. PMID:27214135

  3. Toxoplasma gondii Antigens Recognized by IgG Antibodies Differ between Mice with and without Active Proliferation of Tachyzoites in the Brain during the Chronic Stage of Infection

    PubMed Central

    Hester, James; Mullins, Jeremi; Sa, Qila; Payne, Laura; Mercier, Corinne; Cesbron-Delauw, Marie-France

    2012-01-01

    We examined whether tachyzoite proliferation in the brains of immunocompetent hosts during the chronic stage of infection with Toxoplasma gondii induces production of IgG antibodies that recognize parasite antigens different from those recognized by the antibodies of infected hosts that do not have tachyzoite growth. For this purpose, two groups of CBA/J mice, which display continuous tachyzoite growth in their brains during the later stage of infection, were infected, and one group received treatment with sulfadiazine to prevent tachyzoite proliferation during the chronic stage of infection. T. gondii antigens recognized by the IgG antibodies from these two groups of mice were compared using immunoblotting following separation of tachyzoite antigens by two-dimensional gel electrophoresis. Several antigens, including the microneme protein MIC2, the cyst matrix protein MAG1, and the dense granule proteins GRA4 and GRA7, were commonly recognized by IgG antibodies from both groups of mice. There were multiple antigens recognized mostly by IgG antibodies of only one group of mice, either with or without cerebral tachyzoite growth. The antigens recognized only by or mostly by the antibodies of mice with cerebral tachyzoite growth include MIC6, the rhoptry protein ROP1, GRA2, one heat shock protein HSP90, one (putative) HSP70, and the myosin heavy chain. These results indicate that levels of IgG antibody to only selected T. gondii antigens increase in association with cerebral tachyzoite proliferation (reactivation of infection) in immunocompetent hosts with chronic infection. PMID:22851753

  4. Early stages of simian immunodeficiency virus infection in lymph nodes. Evidence for high viral load and successive populations of target cells.

    PubMed Central

    Chakrabarti, L.; Isola, P.; Cumont, M. C.; Claessens-Maire, M. A.; Hurtrel, M.; Montagnier, L.; Hurtrel, B.

    1994-01-01

    Lymph nodes obtained from 14 macaques sacrificed at early time points following experimental inoculation with simian immunodeficiency virus were analyzed by in situ hybridization for virus load and virus cellular tropism. The lymph nodes presented a remarkably high viral load during the early phase of infection, as viral RNA was detected in as many as 2% of lymph node cells 1 week after inoculation. At this stage, macrophages and T4 lymphocytes were identified by combined immunohistochemistry and in situ hybridization as the target cells of the virus. Simian immunodeficiency virus-positive macrophages concentrated in the subcapsular sinuses, suggesting an entry of infected cells via the afferent lymphatics. A shift in the pattern of viral infection was observed at 2 weeks after inoculation, with a concentration of viral RNA in the germinal centers of the developing lymphoid follicles. Follicular dendritic cells were found to be the major target of the virus at this stage. Follicular dendritic cells were associated with high levels of viral RNA but little or no detectable viral DNA, suggesting that the virus was present mostly in the form of viral particles trapped at the cell surface. Follicular dendritic cell-associated virus persisted at high levels for 2 months before subsiding, indicating that follicular dendritic cells constituted a major reservoir of the virus during the early stages of simian immunodeficiency virus infection. Images Figure 2 Figure 4 Figure 5 Figure 6 PMID:8203463

  5. Efficacy of OZ439 (artefenomel) against early Plasmodium falciparum blood-stage malaria infection in healthy volunteers

    PubMed Central

    McCarthy, James S.; Baker, Mark; O'Rourke, Peter; Marquart, Louise; Griffin, Paul; Hooft van Huijsduijnen, Rob; Möhrle, Jörg J.

    2016-01-01

    Objectives OZ439, or artefenomel, is an investigational synthetic ozonide antimalarial with similar potency, but a significantly improved pharmacokinetic profile, compared with artemisinins. We wished to measure key pharmacokinetic and pharmacodynamic parameters and the pharmacokinetic/pharmacodynamic relationship of artefenomel in humans to guide the drug's further development as combination therapy in patients. Patients and methods We tested artefenomel in the human induced blood-stage malaria (IBSM) model. Plasmodium infection was monitored by quantitative PCR (qPCR) and upon reaching 1000 parasites/mL single doses of 100, 200 and 500 mg of artefenomel were administered orally with evaluation of drug exposure and parasitaemia until rescue treatment after 16 days or earlier, if required. Results A single 100 mg dose had only a transient effect, while the 200 mg dose resulted in a significant reduction in parasitaemia before early recrudescence. At the highest (500 mg) dose, initial clearance of parasites below the limit of detection of qPCR was observed, with a 48 h parasite reduction ratio (PRR48) >10 000 and a parasite clearance half-life of 3.6 h (95% CI 3.4–3.8 h). However, at this dose, recrudescence was seen in four of eight subjects 6–10 days after treatment. Pharmacokinetic/pharmacodynamic modelling predicted an MIC of 4.1 ng/mL. Conclusions These results confirm the antimalarial potential of artefenomel for use in a single-exposure combination therapy. The observations from this study support and will assist further clinical development of artefenomel. PMID:27272721

  6. Infection.

    PubMed

    Miclau, Theodore; Schmidt, Andrew H; Wenke, Joseph C; Webb, Lawrence X; Harro, Janette M; Prabhakara, Ranjani; Shirtliff, Mark E

    2010-09-01

    Musculoskeletal infection is a clinical problem with significant direct healthcare costs. The prevalence of infection after closed, elective surgery is frequently estimated to be less than 2%, but in severe injuries, posttraumatic infection rates have been reported as 10% or greater. Although clinical infections are found outside the realm of medical devices, it is clear that the enormous increase of infections associated with the use of implants presents a major challenge worldwide. This review summarizes recent advances in the understanding, diagnosis, and treatment of musculoskeletal infections.

  7. One-stage débridement and knee fusion for infected total knee arthroplasty using the hybrid frame.

    PubMed

    VanRyn, Jacques S; Verebelyi, David M

    2002-01-01

    In 1997 and 1998, a hybrid fixator was used for a one-step arthrodesis in 2 cases of infected total knee arthroplasty. One patient had rheumatoid arthritis, and the other had an infected reimplant arthroplasty. Neither patient was a candidate for reimplantation. Fusions were achieved with the hybrid frame in an average of 10 weeks. All signs of local and systemic infections were eliminated. After 24 months for patient 1 and 37 months for patient 2, both are infection-free and ambulatory without the aid of a wheelchair. PMID:11805940

  8. The 11,600-MW protein encoded by region E3 of adenovirus is expressed early but is greatly amplified at late stages of infection.

    PubMed Central

    Tollefson, A E; Scaria, A; Saha, S K; Wold, W S

    1992-01-01

    We have reported that an 11,600-MW (11.6K) protein is coded by region E3 of adenovirus. We have now prepared two new antipeptide antisera that have allowed us to characterize this protein further. The 11.6K protein migrates as multiple diffuse bands having apparent Mws of about 14,000, 21,000, and 31,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunoblotting as well as virus mutants with deletions in the 11.6K gene were used to show that the various gel bands represent forms of 11.6K. The 11.6K protein was synthesized in very low amounts during early stages of infection, from the scarce E3 mRNAs d and e which initiate from the E3 promoter. However, 11.6K was synthesized very abundantly at late stages of infection, approximately 400 times the rate at early stages, from new mRNAs termed d' and e'. Reverse transcriptase-polymerase chain reaction and RNA blot experiments indicated that mRNAs d' and e' had the same body (the coding portion) and the same middle exon (the y leader) as early E3 mRNAs d and e, but mRNAs d' and e' were spliced at their 5' termini to the major late tripartite leader which is found in all mRNAs in the major late transcription unit. mRNAs d' and e' and the 11.6K protein were the only E3 mRNAs and protein that were scarce early and were greatly amplified at late stages of infection. This suggests that specific cis- or trans-acting sequences may function to enhance the splicing of mRNAs d' and e' at late stages of infection and perhaps to suppress the splicing of mRNAs d and e at early stages of infection. We propose that the 11.6K gene be considered not only a member of region E3 but also a member of the major late transcription unit. Images PMID:1316473

  9. Infection in advanced chronic kidney disease leads to increased risk of cardiovascular events, end-stage kidney disease and mortality.

    PubMed

    Cheikh Hassan, Hicham I; Tang, Mila; Djurdjev, Ognjenka; Langsford, David; Sood, Manish M; Levin, Adeera

    2016-10-01

    The risk of infection in advanced chronic kidney disease (CKD) and its subsequent impact on adverse outcomes are not well established. Therefore, we determined the association of an infectious episode with the subsequent risk of cardiovascular ischemia, congestive heart failure, end-stage kidney disease or mortality in a Canadian prospective cohort (CanPREDDICT) of patients with advanced CKD (eGFR: 15-45 ml/min/1.73m(2)) followed by nephrologists for up to 5 years. Infectious episodes were classified by anatomic location and identified by positive culture, hospital admission, or use of antibiotics. Competing risk models were used to examine the time-varying risk of infection and the risk of cardiovascular ischemia, congestive heart failure, or end-stage kidney disease accounting for the competing risk of mortality. All outcomes were independently adjudicated. Of 2370 patients (mean age, 68 years; mean baseline eGFR, 28.2 mL/min/1.73m(2)), 575 patients (24.3%) had recorded infections; 378 had 1 infection episode, whereas 197 had 2 or more episodes, the most common being urinary and respiratory. An infectious episode was independently associated with an increased risk of cardiovascular ischemia (hazard ratio 1.80, 95% confidence interval 1.24-2.60), congestive heart failure (hazard ratio, 3.2; confidence interval, 2.25-4.61), end-stage kidney disease (hazard ratio, 1.58; confidence interval, 1.22-2.05) or mortality (hazard ratio, 3.39; confidence interval, 2.65-4.33). Thus, there is a high risk of infection in advanced CKD being associated with subsequent adverse outcomes. PMID:27591084

  10. Infection in advanced chronic kidney disease leads to increased risk of cardiovascular events, end-stage kidney disease and mortality.

    PubMed

    Cheikh Hassan, Hicham I; Tang, Mila; Djurdjev, Ognjenka; Langsford, David; Sood, Manish M; Levin, Adeera

    2016-10-01

    The risk of infection in advanced chronic kidney disease (CKD) and its subsequent impact on adverse outcomes are not well established. Therefore, we determined the association of an infectious episode with the subsequent risk of cardiovascular ischemia, congestive heart failure, end-stage kidney disease or mortality in a Canadian prospective cohort (CanPREDDICT) of patients with advanced CKD (eGFR: 15-45 ml/min/1.73m(2)) followed by nephrologists for up to 5 years. Infectious episodes were classified by anatomic location and identified by positive culture, hospital admission, or use of antibiotics. Competing risk models were used to examine the time-varying risk of infection and the risk of cardiovascular ischemia, congestive heart failure, or end-stage kidney disease accounting for the competing risk of mortality. All outcomes were independently adjudicated. Of 2370 patients (mean age, 68 years; mean baseline eGFR, 28.2 mL/min/1.73m(2)), 575 patients (24.3%) had recorded infections; 378 had 1 infection episode, whereas 197 had 2 or more episodes, the most common being urinary and respiratory. An infectious episode was independently associated with an increased risk of cardiovascular ischemia (hazard ratio 1.80, 95% confidence interval 1.24-2.60), congestive heart failure (hazard ratio, 3.2; confidence interval, 2.25-4.61), end-stage kidney disease (hazard ratio, 1.58; confidence interval, 1.22-2.05) or mortality (hazard ratio, 3.39; confidence interval, 2.65-4.33). Thus, there is a high risk of infection in advanced CKD being associated with subsequent adverse outcomes.

  11. Two-Stage Revision Total Hip Arthroplasty for Periprosthetic Infections Using Antibiotic-Impregnated Cement Spacers of Various Types and Materials

    PubMed Central

    Takahira, Naonobu; Moriya, Mitsutoshi; Yamamoto, Takeaki; Minegishi, Yojiro; Sakai, Rina; Itoman, Moritoshi; Takaso, Masashi

    2013-01-01

    Antibiotic-impregnated hip cement spacers of various types and materials have been used in the treatment of periprosthetic hip infections. We developed a handmade spacer by using polymethylmethacrylate (PMMA) and/or α-tricalcium phosphate (α-TCP). In this study, we retrospectively reviewed the surgical outcomes in 36 consecutive patients treated with 2-stage revision total hip arthroplasty by using our antibiotic-impregnated hip cement spacers. We aimed to analyze the infection control and reinfection rates after revision surgery. Moreover, we analyzed the possible predictors of postoperative reinfection. After exclusion of 1 patient who died immediately after the first-stage surgery, infection was controlled in 33 of the 36 hips (success rate, 91.7%). Two of these 33 hips underwent resection arthroplasty. Of the 36 hips that had been treated with the antibiotic-cement spacer, 31 hips (86.1%) were eligible for the second-stage prosthesis re-implantation. The 31 protocol hip joints of patients followed up for >6 months (mean, 48.6 months). Ten of these 31 hips (32.3%) became reinfected. No possible predictor examined differed significantly between the reinfection-positive and reinfection-negative groups. However, spacers consisting of PMMA cement alone were associated with the highest risk of reinfection. Therefore, α-TCP-containing antibiotic-impregnated hip cement spacers might decrease the reinfection rate in patients undergoing re-implantation. PMID:24381509

  12. Two-Stage Revision for Infected Total Knee Arthroplasty: Based on Autoclaving the Recycled Femoral Component and Intraoperative Molding Using Antibiotic-Impregnated Cement on the Tibial Side

    PubMed Central

    Lee, Byoung-Joo; Yoon, Seong-Dae

    2015-01-01

    Background The purpose of this study was to determine the degree of infection control and postoperative function for new articulating metal-on-cement spacer. Methods A retrospective study of 19 patients (20 cases), who underwent a two-stage revision arthroplasty using mobile cement prosthesis, were followed for a minimum of 2 years. This series consisted of 16 women and 3 men, having an overall mean age of 71 years. During the first stage of revision, the femoral implant and all the adherent cement was removed, after which it was autoclaved before replacement. The tibial component was removed and a doughy state, antibiotic-impregnated cement was inserted on the tibial side. To achieve joint congruency, intraoperative molding was performed by flexing and extending the knee joint. Each patient was evaluated clinically and radiologically. The clinical assessments included range of motion, and the patients were scored as per the Hospital for Special Surgery (HSS) and Knee Society (KS) criteria. Results The mean range of knee joint motion was 70° prior to the first stage operation and 72° prior to the second stage revision arthroplasty; following revision arthroplasty, it was 113° at the final follow-up. The mean HSS score and KS knee and function scores were 86, 82, and 54, respectively, at the final follow-up. The success rate in terms of infection eradication was 95% (19/20 knees). No patient experienced soft tissue contracture requiring a quadriceps snip. Conclusions This novel technique provides excellent radiological and clinical outcomes. It offers a high surface area of antibiotic-impregnated cement, a good range of motion between first and second stage revision surgery for the treatment of chronic infection after total knee arthroplasty, and is of a reasonable cost. PMID:26330952

  13. In Vivo Antiprotozoal Activity of the Chloroform Extract from Carica papaya Seeds against Amastigote Stage of Trypanosoma cruzi during Indeterminate and Chronic Phase of Infection

    PubMed Central

    Ortega-Pacheco, Antonio; Perez-Gutierrez, Salud; Guzman-Marin, Eugenia

    2014-01-01

    In order to evaluate the antiprotozoal activity of the chloroform extract of Carica papaya seeds during the subacute and chronic phase of infection of Trypanosoma cruzi, doses of 50 and 75 mg/kg were evaluated during the subacute phase, including a mixture of their main components (oleic, palmitic, and stearic acids). Subsequently, doses of 50 and 75 mg/kg in mice during the chronic phase of infection (100 dpi) were also evaluated. It was found that chloroform extract was able to reduce the amastigote nests numbers during the subacute phase in 55.5 and 69.7% (P > 0.05) as well as in 56.45% in animals treated with the mixture of fatty acids. Moreover, the experimental groups treated with 50 and 75 mg/kg during the chronic phase of the infection showed a significant reduction of 46.8 and 53.13% respectively (P < 0.05). It is recommended to carry out more studies to determine if higher doses of chloroformic extract or its administration in combination with other antichagasic drugs allows a better response over the intracellular stage of T. cruzi in infected animal models and determine if the chloroform extract of C. papaya could be considered as an alternative for treatment during the indeterminate and chronic phase of the infection. PMID:25276216

  14. In Vivo Antiprotozoal Activity of the Chloroform Extract from Carica papaya Seeds against Amastigote Stage of Trypanosoma cruzi during Indeterminate and Chronic Phase of Infection.

    PubMed

    Jimenez-Coello, Matilde; Acosta-Viana, Karla Y; Ortega-Pacheco, Antonio; Perez-Gutierrez, Salud; Guzman-Marin, Eugenia

    2014-01-01

    In order to evaluate the antiprotozoal activity of the chloroform extract of Carica papaya seeds during the subacute and chronic phase of infection of Trypanosoma cruzi, doses of 50 and 75 mg/kg were evaluated during the subacute phase, including a mixture of their main components (oleic, palmitic, and stearic acids). Subsequently, doses of 50 and 75 mg/kg in mice during the chronic phase of infection (100 dpi) were also evaluated. It was found that chloroform extract was able to reduce the amastigote nests numbers during the subacute phase in 55.5 and 69.7% (P > 0.05) as well as in 56.45% in animals treated with the mixture of fatty acids. Moreover, the experimental groups treated with 50 and 75 mg/kg during the chronic phase of the infection showed a significant reduction of 46.8 and 53.13% respectively (P < 0.05). It is recommended to carry out more studies to determine if higher doses of chloroformic extract or its administration in combination with other antichagasic drugs allows a better response over the intracellular stage of T. cruzi in infected animal models and determine if the chloroform extract of C. papaya could be considered as an alternative for treatment during the indeterminate and chronic phase of the infection. PMID:25276216

  15. Pineapple juice for digestion of swamp eel viscera for harvesting infective-stage larva of Gnathostoma spp.

    PubMed

    Soogarun, Suphan; Suwansaksri, Jamsai; Wiwanitkit, Viroj

    2004-06-01

    Third-stage larvae were used as antigen in the diagnosis of gnathostomiasis in Western blot analysis. Normally, the larvae were obtained from digestion of eel's liver (Fluta alba) by the enzyme pepsin. We used pineapple juice (Ananus comosus) instead of enzyme pepsin in harvesting Gnathostoma spinigerum third-stage larvae. The difference in recovered larvae numbers, between pineapple juice and pepsin, were not statistically significantly different (p>0.05). The larvae from pepsin and pineapple juice digestion were cultivated on BME for 7 days; the survival rates were not significantly different (p>0.05). Thus, pineapple juice is another enzyme of choice for recovering Gnathostoma spinigerum third-stage larvae.

  16. Altered microRNA expression and pre-mRNA splicing events reveal new mechanisms associated with early stage Mycobacterium avium subspecies paratuberculosis infection

    PubMed Central

    Liang, Guanxiang; Malmuthuge, Nilusha; Guan, Yongjuan; Ren, Yuwei; Griebel, Philip J.; Guan, Le Luo

    2016-01-01

    The molecular regulatory mechanisms of host responses to Mycobacterium avium subsp. paratuberculosis (MAP) infection during the early subclinical stage are still not clear. In this study, surgically isolated ileal segments in newborn calves (n = 5) were used to establish in vivo MAP infection adjacent to an uninfected control intestinal compartment. RNA-Seq was used to profile the whole transcriptome (mRNAs) and the microRNAome (miRNAs) of ileal tissues collected at one-month post-infection. The most related function of the differentially expressed mRNAs between infected and uninfected tissues was “proliferation of endothelial cells”, indicating that MAP infection may lead to the over-proliferation of endothelial cells. In addition, 46.2% of detected mRNAs displayed alternative splicing events. The pre-mRNA of two genes related to macrophage maturation (monocyte to macrophage differentiation-associated) and lysosome function (adenosine deaminase) showed differential alternative splicing events, suggesting that specific changes in the pre-mRNA splicing sites may be a mechanism by which MAP escapes host immune responses. Moreover, 9 miRNAs were differentially expressed after MAP infection. The integrated analysis of microRNAome and transcriptome revealed that these miRNAs might regulate host responses to MAP infection, such as “proliferation of endothelial cells” (bta-miR-196 b), “bacteria recognition” (bta-miR-146 b), and “regulation of the inflammatory response” (bta-miR-146 b). PMID:27102525

  17. High specificity of line-immunoassay based algorithms for recent HIV-1 infection independent of viral subtype and stage of disease

    PubMed Central

    2011-01-01

    Background Serologic testing algorithms for recent HIV seroconversion (STARHS) provide important information for HIV surveillance. We have shown that a patient's antibody reaction in a confirmatory line immunoassay (INNO-LIATM HIV I/II Score, Innogenetics) provides information on the duration of infection. Here, we sought to further investigate the diagnostic specificity of various Inno-Lia algorithms and to identify factors affecting it. Methods Plasma samples of 714 selected patients of the Swiss HIV Cohort Study infected for longer than 12 months and representing all viral clades and stages of chronic HIV-1 infection were tested blindly by Inno-Lia and classified as either incident (up to 12 m) or older infection by 24 different algorithms. Of the total, 524 patients received HAART, 308 had HIV-1 RNA below 50 copies/mL, and 620 were infected by a HIV-1 non-B clade. Using logistic regression analysis we evaluated factors that might affect the specificity of these algorithms. Results HIV-1 RNA <50 copies/mL was associated with significantly lower reactivity to all five HIV-1 antigens of the Inno-Lia and impaired specificity of most algorithms. Among 412 patients either untreated or with HIV-1 RNA ≥50 copies/mL despite HAART, the median specificity of the algorithms was 96.5% (range 92.0-100%). The only factor that significantly promoted false-incident results in this group was age, with false-incident results increasing by a few percent per additional year. HIV-1 clade, HIV-1 RNA, CD4 percentage, sex, disease stage, and testing modalities exhibited no significance. Results were similar among 190 untreated patients. Conclusions The specificity of most Inno-Lia algorithms was high and not affected by HIV-1 variability, advanced disease and other factors promoting false-recent results in other STARHS. Specificity should be good in any group of untreated HIV-1 patients. PMID:21943091

  18. Mandarin Fish Caveolin 1 Interaction with Major Capsid Protein of Infectious Spleen and Kidney Necrosis Virus and Its Role in Early Stages of Infection

    PubMed Central

    Jia, Kun-Tong; Wu, Yan-Yan; Liu, Zhao-Yu; Mi, Shu; Zheng, Yi-Wen; He, Jian; Weng, Shao-Ping; Li, Shengwen Calvin

    2013-01-01

    Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus from the family Iridoviridae. ISKNV is one of the major agents that cause mortality and economic losses to the freshwater fish culture industry in Asian countries, particularly for mandarin fish (Siniperca chuatsi). In the present study, we report that the interaction of mandarin fish caveolin 1 (mCav-1) with the ISKNV major capsid protein (MCP) was detected by using a virus overlay assay and confirmed by pulldown assay and coimmunoprecipitation. This interaction was independent of the classic caveolin 1 scaffolding domain (CSD), which is responsible for interacting with several signaling proteins and receptors. Confocal immunofluorescence microscopy showed that ISKNV MCP colocalized with mCav-1 in the perinuclear region of virus-infected mandarin fish fry (MFF-1) cells, which appeared as soon as 4 h postinfection. Subcellular fractionation analysis showed that ISKNV MCP was associated with caveolae in the early stages of viral infection. RNA interference silencing of mCav-1 did not change virus-cell binding but efficiently inhibited the entry of virions into the cell. Taken together, these results suggested that mCav-1 plays an important role in the early stages of ISKNV infection. PMID:23283951

  19. A Mechanistic Model of Botrytis cinerea on Grapevines That Includes Weather, Vine Growth Stage, and the Main Infection Pathways

    PubMed Central

    González-Domínguez, Elisa; Caffi, Tito; Ciliberti, Nicola; Rossi, Vittorio

    2015-01-01

    A mechanistic model for Botrytis cinerea on grapevine was developed. The model, which accounts for conidia production on various inoculum sources and for multiple infection pathways, considers two infection periods. During the first period (“inflorescences clearly visible” to “berries groat-sized”), the model calculates: i) infection severity on inflorescences and young clusters caused by conidia (SEV1). During the second period (“majority of berries touching” to “berries ripe for harvest”), the model calculates: ii) infection severity of ripening berries by conidia (SEV2); and iii) severity of berry-to-berry infection caused by mycelium (SEV3). The model was validated in 21 epidemics (vineyard × year combinations) between 2009 and 2014 in Italy and France. A discriminant function analysis (DFA) was used to: i) evaluate the ability of the model to predict mild, intermediate, and severe epidemics; and ii) assess how SEV1, SEV2, and SEV3 contribute to epidemics. The model correctly classified the severity of 17 of 21 epidemics. Results from DFA were also used to calculate the daily probabilities that an ongoing epidemic would be mild, intermediate, or severe. SEV1 was the most influential variable in discriminating between mild and intermediate epidemics, whereas SEV2 and SEV3 were relevant for discriminating between intermediate and severe epidemics. The model represents an improvement of previous B. cinerea models in viticulture and could be useful for making decisions about Botrytis bunch rot control. PMID:26457808

  20. Monocyte- and Neutrophil-Derived CXCL10 Impairs Efficient Control of Blood-Stage Malaria Infection and Promotes Severe Disease.

    PubMed

    Ioannidis, Lisa J; Nie, Catherine Q; Ly, Ann; Ryg-Cornejo, Victoria; Chiu, Chris Y; Hansen, Diana S

    2016-02-01

    CXCL10, or IFN-γ-inducible protein 10, is a biomarker associated with increased risk for Plasmodium falciparum-mediated cerebral malaria (CM). Consistent with this, we have previously shown that CXCL10 neutralization or genetic deletion alleviates brain intravascular inflammation and protects Plasmodium berghei ANKA-infected mice from CM. In addition to organ-specific effects, the absence of CXCL10 during infection was also found to reduce parasite biomass. To identify the cellular sources of CXCL10 responsible for these processes, we irradiated and reconstituted wild-type (WT) and CXCL10(-/-) mice with bone marrow from either WT or CXCL10(-/-) mice. Similar to CXCL10(-/-) mice, chimeras unable to express CXCL10 in hematopoietic-derived cells controlled infection more efficiently than WT controls. In contrast, expression of CXCL10 in knockout mice reconstituted with WT bone marrow resulted in high parasite biomass levels, higher brain parasite and leukocyte sequestration rates, and increased susceptibility to CM. Neutrophils and inflammatory monocytes were identified as the main cellular sources of CXCL10 responsible for the induction of these processes. The improved control of parasitemia observed in the absence of CXCL10-mediated trafficking was associated with a preferential accumulation of CXCR3(+)CD4(+) T follicular helper cells in the spleen and enhanced Ab responses to infection. These results are consistent with the notion that some inflammatory responses elicited in response to malaria infection contribute to the development of high parasite densities involved in the induction of severe disease in target organs.

  1. Infection.

    PubMed

    Saigal, Gaurav; Nagornaya, Natalya; Post, M Judith D

    2016-01-01

    Imaging is useful in the diagnosis and management of infections of the central nervous system. Typically, imaging findings at the outset of the disease are subtle and nonspecific, but they often evolve to more definite imaging patterns in a few days, with less rapidity than for stroke but faster than for neoplastic lesions. This timing is similar to that of noninfectious inflammatory brain disease, such as multiple sclerosis. Fortunately, imaging patterns help to distinguish the two kinds of processes. Other than for sarcoidosis, the meninges are seldom involved in noninfectious inflammation; in contrast, many infectious processes involve the meninges, which then enhance with contrast on computed tomography (CT) or magnetic resonance imaging (MRI). However, brain infection causes a vast array of imaging patterns. Although CT is useful when hemorrhage or calcification is suspected or bony detail needs to be determined, MRI is the imaging modality of choice in the investigation of intracranial infections. Imaging sequences such as diffusion-weighted imaging help in accurately depicting the location and characterizing pyogenic infections and are particularly useful in differentiating bacterial infections from other etiologies. Susceptibility-weighted imaging is extremely useful for the detection of hemorrhage. Although MR spectroscopy findings can frequently be nonspecific, certain conditions such as bacterial abscesses show a relatively specific spectral pattern and are useful in diagnosing and constituting immediate therapy. In this chapter we review first the imaging patterns associated with involvement of various brain structures, such as the epidural and subdural spaces, the meninges, the brain parenchyma, and the ventricles. Involvement of these regions is illustrated with bacterial infections. Next we illustrate the patterns associated with viral and prion diseases, followed by mycobacterial and fungal infections, to conclude with a review of imaging findings

  2. Clinical trial in healthy malaria-naïve adults to evaluate the safety, tolerability, immunogenicity and efficacy of MuStDO5, a five-gene, sporozoite/hepatic stage Plasmodium falciparum DNA vaccine combined with escalating dose human GM-CSF DNA

    PubMed Central

    Richie, Thomas L.; Charoenvit, Yupin; Wang, Ruobing; Epstein, Judith E.; Hedstrom, Richard C.; Kumar, Sanjai; Luke, Thomas C.; Freilich, Daniel A.; Aguiar, Joao C.; Sacci, Jr., John B.; Sedegah, Martha; Nosek, Jr., Ronald A.; De La Vega, Patricia; Berzins, Mara P.; Majam, Victoria F.; Abot, Esteban N.; Ganeshan, Harini; Richie, Nancy O.; Banania, Jo Glenna; Baraceros, Maria Fe B.; Geter, Tanya G.; Mere, Robin; Bebris, Lolita; Limbach, Keith; Hickey, Bradley W.; Lanar, David E.; Ng, Jennifer; Shi, Meng; Hobart, Peter M.; Norman, Jon A.; Soisson, Lorraine A.; Hollingdale, Michael R.; Rogers, William O.; Doolan, Denise L.; Hoffman, Stephen L.

    2012-01-01

    When introduced in the 1990s, immunization with DNA plasmids was considered potentially revolutionary for vaccine development, particularly for vaccines intended to induce protective CD8 T cell responses against multiple antigens. We conducted, in 1997−1998, the first clinical trial in healthy humans of a DNA vaccine, a single plasmid encoding Plasmodium falciparum circumsporozoite protein (PfCSP), as an initial step toward developing a multi-antigen malaria vaccine targeting the liver stages of the parasite. As the next step, we conducted in 2000–2001 a clinical trial of a five-plasmid mixture called MuStDO5 encoding pre-erythrocytic antigens PfCSP, PfSSP2/TRAP, PfEXP1, PfLSA1 and PfLSA3. Thirty-two, malaria-naïve, adult volunteers were enrolled sequentially into four cohorts receiving a mixture of 500 μg of each plasmid plus escalating doses (0, 20, 100 or 500 μg) of a sixth plasmid encoding human granulocyte macrophage-colony stimulating factor (hGM-CSF). Three doses of each formulation were administered intramuscularly by needle-less jet injection at 0, 4 and 8 weeks, and each cohort had controlled human malaria infection administered by five mosquito bites 18 d later. The vaccine was safe and well-tolerated, inducing moderate antigen-specific, MHC-restricted T cell interferon-γ responses but no antibodies. Although no volunteers were protected, T cell responses were boosted post malaria challenge. This trial demonstrated the MuStDO5 DNA and hGM-CSF plasmids to be safe and modestly immunogenic for T cell responses. It also laid the foundation for priming with DNA plasmids and boosting with recombinant viruses, an approach known for nearly 15 y to enhance the immunogenicity and protective efficacy of DNA vaccines. PMID:23151451

  3. Pasteurella multocida non-native joint infection after a dog lick: A case report describing a complicated two-stage revision and a comprehensive review of the literature

    PubMed Central

    Philip W, Lam; Page, Andrea V

    2015-01-01

    Prosthetic joint infections (PJIs) are commonly caused by pathogens such as Staphylococcus aureus and coagulase-negative staphylococci; however, other microbial etiologies and specific risk factors are increasingly recognized. Pasteurella multocida is a Gram-negative coccobacillus that is part of the normal oral flora in many animals, and is particularly common in dogs and cats. PJIs caused by P multocida have been reported only rarely in the literature and typically occur in the context of an animal bite or scratch. The present article describes a P multocida joint infection that occurred after a dog lick and complicated a two-stage revision arthroplasty. A comprehensive review of the literature regarding P multocida PJIs follows. PMID:26361490

  4. NOS2 Variants Reveal a Dual Genetic Control of Nitric Oxide Levels, Susceptibility to Plasmodium Infection, and Cerebral Malaria

    PubMed Central

    Trovoada, Maria de Jesus; Martins, Madalena; Ben Mansour, Riadh; Sambo, Maria do Rosário; Fernandes, Ana B.; Antunes Gonçalves, Lígia; Borja, Artur; Moya, Roni; Almeida, Paulo; Costa, João; Marques, Isabel; Macedo, M. Paula; Coutinho, António; Narum, David L.

    2014-01-01

    Nitric oxide (NO) is a proposed component of malaria pathogenesis, and the inducible nitric oxide synthase gene (NOS2) has been associated to malaria susceptibility. We analyzed the role of NOS2 polymorphisms on NO bioavailability and on susceptibility to infection, Plasmodium carrier status and clinical malaria. Two distinct West African sample collections were studied: a population-based collection of 1,168 apparently healthy individuals from the Príncipe Island and a hospital-based cohort of 269 Angolan children. We found that two NOS2 promoter single-nucleotide polymorphism (SNP) alleles associated to low NO plasma levels in noninfected individuals were also associated to reduced risk of pre-erythrocytic infection as measured anti-CSP antibody levels (6.25E–04 < P < 7.57E–04). In contrast, three SNP alleles within the NOS2 cistronic region conferring increased NO plasma levels in asymptomatic carriers were strongly associated to risk of parasite carriage (8.00E–05 < P < 7.90E–04). Notwithstanding, three SNP alleles in this region protected from cerebral malaria (7.90E–4 < P < 4.33E–02). Cohesively, the results revealed a dual regimen in the genetic control of NO bioavailability afforded by NOS2 depending on the infection status. NOS2 promoter variants operate in noninfected individuals to decrease both NO bioavailability and susceptibility to pre-erythrocytic infection. Conversely, NOS2 cistronic variants (namely, rs6505469) operate in infected individuals to increase NO bioavailability and confer increased susceptibility to unapparent infection but protect from cerebral malaria. These findings corroborate the hypothesis that NO anti-inflammatory properties impact on different steps of malaria pathogenesis, explicitly by favoring infection susceptibility and deterring severe malaria syndromes. PMID:24379293

  5. NOS2 variants reveal a dual genetic control of nitric oxide levels, susceptibility to Plasmodium infection, and cerebral malaria.

    PubMed

    Trovoada, Maria de Jesus; Martins, Madalena; Ben Mansour, Riadh; Sambo, Maria do Rosário; Fernandes, Ana B; Antunes Gonçalves, Lígia; Borja, Artur; Moya, Roni; Almeida, Paulo; Costa, João; Marques, Isabel; Macedo, M Paula; Coutinho, António; Narum, David L; Penha-Gonçalves, Carlos

    2014-03-01

    Nitric oxide (NO) is a proposed component of malaria pathogenesis, and the inducible nitric oxide synthase gene (NOS2) has been associated to malaria susceptibility. We analyzed the role of NOS2 polymorphisms on NO bioavailability and on susceptibility to infection, Plasmodium carrier status and clinical malaria. Two distinct West African sample collections were studied: a population-based collection of 1,168 apparently healthy individuals from the Príncipe Island and a hospital-based cohort of 269 Angolan children. We found that two NOS2 promoter single-nucleotide polymorphism (SNP) alleles associated to low NO plasma levels in noninfected individuals were also associated to reduced risk of pre-erythrocytic infection as measured anti-CSP antibody levels (6.25E-04 < P < 7.57E-04). In contrast, three SNP alleles within the NOS2 cistronic region conferring increased NO plasma levels in asymptomatic carriers were strongly associated to risk of parasite carriage (8.00E-05 < P < 7.90E-04). Notwithstanding, three SNP alleles in this region protected from cerebral malaria (7.90E-4 < P < 4.33E-02). Cohesively, the results revealed a dual regimen in the genetic control of NO bioavailability afforded by NOS2 depending on the infection status. NOS2 promoter variants operate in noninfected individuals to decrease both NO bioavailability and susceptibility to pre-erythrocytic infection. Conversely, NOS2 cistronic variants (namely, rs6505469) operate in infected individuals to increase NO bioavailability and confer increased susceptibility to unapparent infection but protect from cerebral malaria. These findings corroborate the hypothesis that NO anti-inflammatory properties impact on different steps of malaria pathogenesis, explicitly by favoring infection susceptibility and deterring severe malaria syndromes.

  6. The early stages of the immune response of the European abalone Haliotis tuberculata to a Vibrio harveyi infection.

    PubMed

    Cardinaud, Marion; Dheilly, Nolwenn M; Huchette, Sylvain; Moraga, Dario; Paillard, Christine

    2015-08-01

    Vibrio harveyi is a marine bacterial pathogen responsible for episodic abalone mortalities in France, Japan and Australia. In the European abalone, V. harveyi invades the circulatory system in a few hours after exposure and is lethal after 2 days of infection. In this study, we investigated the responses of European abalone immune cells over the first 24 h of infection. Results revealed an initial induction of immune gene expression including Rel/NF-kB, Mpeg and Clathrin. It is rapidly followed by a significant immuno-suppression characterized by reduced cellular hemocyte parameters, immune response gene expressions and enzymatic activities. Interestingly, Ferritin was overexpressed after 24 h of infection suggesting that abalone attempt to counter V. harveyi infection using soluble effectors. Immune function alteration was positively correlated with V. harveyi concentration. This study provides the evidence that V. harveyi has a hemolytic activity and an immuno-suppressive effect in the European abalone. PMID:25766281

  7. Serum, liver, and lung levels of the major extracellular matrix components at the early stage of BCG-induced granulomatosis depending on the infection route.

    PubMed

    Kim, L B; Shkurupy, V A; Putyatina, A N

    2015-01-01

    Experiments on the model of mouse BCG-induced granulomatous showed that the content of glycosaminoglycans and proteoglycans in the extracellular matrix of the liver and lungs are changed at the early stages of inflammation (days 3 and 30 postinfection) before cell destruction in the organs begins. This is related to degradation of extracellular matrix structures. Their high content in the blood and interstitium probably contributes to the formation of granulomas, fibroblast proliferation and organ fibrosis. These processes depend on the infection route that determines different conditions for generalization of the inflammation process. Intravenous method of vaccine injection is preferable to use when designing the experiments simulating tuberculosis granulomatosis, especially for the analysis of its early stages. PMID:25573360

  8. Serum, liver, and lung levels of the major extracellular matrix components at the early stage of BCG-induced granulomatosis depending on the infection route.

    PubMed

    Kim, L B; Shkurupy, V A; Putyatina, A N

    2015-01-01

    Experiments on the model of mouse BCG-induced granulomatous showed that the content of glycosaminoglycans and proteoglycans in the extracellular matrix of the liver and lungs are changed at the early stages of inflammation (days 3 and 30 postinfection) before cell destruction in the organs begins. This is related to degradation of extracellular matrix structures. Their high content in the blood and interstitium probably contributes to the formation of granulomas, fibroblast proliferation and organ fibrosis. These processes depend on the infection route that determines different conditions for generalization of the inflammation process. Intravenous method of vaccine injection is preferable to use when designing the experiments simulating tuberculosis granulomatosis, especially for the analysis of its early stages.

  9. PRO-C3-Levels in Patients with HIV/HCV-Co-Infection Reflect Fibrosis Stage and Degree of Portal Hypertension

    PubMed Central

    Mandorfer, Mattias; Byrjalsen, Inger; Schierwagen, Robert; Schwabl, Philipp; Karsdal, Morten A.; Anadol, Evrim; Strassburg, Christian P.; Rockstroh, Jürgen; Peck-Radosavljevic, Markus; Møller, Søren; Bendtsen, Flemming; Krag, Aleksander; Reiberger, Thomas; Trebicka, Jonel

    2014-01-01

    Background Liver-related deaths represent the leading cause of mortality among patients with HIV/HCV-co-infection, and are mainly related to complications of fibrosis and portal hypertension. In this study, we aimed to evaluate the structural changes by the assessment of extracellular matrix (ECM) derived degradation fragments in peripheral blood as biomarkers for fibrosis and portal hypertension in patients with HIV/HCV co-infection. Methods Fifty-eight patients (67% male, mean age: 36.5 years) with HIV/HCV-co-infection were included in the study. Hepatic venous pressure gradient (HVPG) was measured in forty-three patients. The fibrosis stage was determined using FIB4 -Score. ECM degraded products in peripheral blood were measured using specific ELISAs (C4M, MMP-2/9 degraded type IV collagen; C5M, MMP-2/9 degraded type V collagen; PRO-C3, MMP degraded n-terminal propeptide of type III collagen). Results As expected, HVPG showed strong and significant correlations with FIB4-index (rs = 0.628; p = 7*10−7). Interestingly, PRO-C3 significantly correlated with HVPG (rs = 0.354; p = 0.02), alanine aminotransferase (rs = 0.30; p = 0.038), as well as with FIB4-index (rs = 0.3230; p = 0.035). C4M and C5M levels were higher in patients with portal hypertension (HVPG>5 mmHg). Conclusion PRO-C3 levels reflect liver injury, stage of liver fibrosis and degree of portal hypertension in HIV/HCV-co-infected patients. Furthermore, C4M and C5M were associated with increased portal pressure. Circulating markers of hepatic ECM remodeling might be helpful in the diagnosis and management of liver disease and portal hypertension in patients with HIV/HCV coinfection. PMID:25265505

  10. Monocyte- and Neutrophil-Derived CXCL10 Impairs Efficient Control of Blood-Stage Malaria Infection and Promotes Severe Disease.

    PubMed

    Ioannidis, Lisa J; Nie, Catherine Q; Ly, Ann; Ryg-Cornejo, Victoria; Chiu, Chris Y; Hansen, Diana S

    2016-02-01

    CXCL10, or IFN-γ-inducible protein 10, is a biomarker associated with increased risk for Plasmodium falciparum-mediated cerebral malaria (CM). Consistent with this, we have previously shown that CXCL10 neutralization or genetic deletion alleviates brain intravascular inflammation and protects Plasmodium berghei ANKA-infected mice from CM. In addition to organ-specific effects, the absence of CXCL10 during infection was also found to reduce parasite biomass. To identify the cellular sources of CXCL10 responsible for these processes, we irradiated and reconstituted wild-type (WT) and CXCL10(-/-) mice with bone marrow from either WT or CXCL10(-/-) mice. Similar to CXCL10(-/-) mice, chimeras unable to express CXCL10 in hematopoietic-derived cells controlled infection more efficiently than WT controls. In contrast, expression of CXCL10 in knockout mice reconstituted with WT bone marrow resulted in high parasite biomass levels, higher brain parasite and leukocyte sequestration rates, and increased susceptibility to CM. Neutrophils and inflammatory monocytes were identified as the main cellular sources of CXCL10 responsible for the induction of these processes. The improved control of parasitemia observed in the absence of CXCL10-mediated trafficking was associated with a preferential accumulation of CXCR3(+)CD4(+) T follicular helper cells in the spleen and enhanced Ab responses to infection. These results are consistent with the notion that some inflammatory responses elicited in response to malaria infection contribute to the development of high parasite densities involved in the induction of severe disease in target organs. PMID:26718341

  11. Characterization of hemocyanin from the mud crab Scylla paramamosain and its expression analysis in different tissues, at various stages, and under Vibrio parahaemolyticus infection.

    PubMed

    Wang, J; Zhang, F Y; Song, W; Fang, Y B; Hu, J H; Zhao, M; Jiang, K J; Ma, L B

    2015-12-11

    Hemocyanin is an important respiratory protein in many arthropod and mollusk species. Here, four cDNAs (SpHc1, SpHc2, SpHc3, and SpHc4), encoding distinct hemocyanin subunits from Scylla paramamosain were cloned using EST analyses and the rapid amplification of cDNA ends. The four full-length cDNA fragments (SpHc1-4) were 2281, 2002, 2184, and 2069 bp, respectively, and they encoded four putative proteins (570-676 amino acids) with a molecular mass of ~65.0-76.8 kDa. Quantitative real-time PCR analyses revealed that the four genes were mainly expressed in the hepatopancreas, testis, and hemocytes. SpHc mRNA expression during continuous developmental stages in zoeal phases (Z1, Z2, Z3, Z4, and Z5), megalopa, and juvenile crab I stages were also detected. The expression levels of SpHc3 and SpHc4 were higher than that of SpHc1 and SpHc2 during the first six stages, and they sharply declined during the juvenile stage. After infection with Vibrio parahaemolyticus, the temporal expression of both the four SpHc mRNAs in the megalopa stage rapidly declined during the first 3 h, followed by upregulation and peak expression at 12 h after the challenge. The expression levels of the four SpHc subunits were upregulated at 48 h after the challenge, and were then gradually downregulated. These findings suggest that hemocyanin may potentially be involved in the crab immune response, and that the role of the four subunits may differ in different tissues and during various developmental stages.

  12. Characterization of hemocyanin from the mud crab Scylla paramamosain and its expression analysis in different tissues, at various stages, and under Vibrio parahaemolyticus infection.

    PubMed

    Wang, J; Zhang, F Y; Song, W; Fang, Y B; Hu, J H; Zhao, M; Jiang, K J; Ma, L B

    2015-01-01

    Hemocyanin is an important respiratory protein in many arthropod and mollusk species. Here, four cDNAs (SpHc1, SpHc2, SpHc3, and SpHc4), encoding distinct hemocyanin subunits from Scylla paramamosain were cloned using EST analyses and the rapid amplification of cDNA ends. The four full-length cDNA fragments (SpHc1-4) were 2281, 2002, 2184, and 2069 bp, respectively, and they encoded four putative proteins (570-676 amino acids) with a molecular mass of ~65.0-76.8 kDa. Quantitative real-time PCR analyses revealed that the four genes were mainly expressed in the hepatopancreas, testis, and hemocytes. SpHc mRNA expression during continuous developmental stages in zoeal phases (Z1, Z2, Z3, Z4, and Z5), megalopa, and juvenile crab I stages were also detected. The expression levels of SpHc3 and SpHc4 were higher than that of SpHc1 and SpHc2 during the first six stages, and they sharply declined during the juvenile stage. After infection with Vibrio parahaemolyticus, the temporal expression of both the four SpHc mRNAs in the megalopa stage rapidly declined during the first 3 h, followed by upregulation and peak expression at 12 h after the challenge. The expression levels of the four SpHc subunits were upregulated at 48 h after the challenge, and were then gradually downregulated. These findings suggest that hemocyanin may potentially be involved in the crab immune response, and that the role of the four subunits may differ in different tissues and during various developmental stages. PMID:26681010

  13. Acceptability of a stage-matched expert system intervention to increase condom use among women at high risk of HIV infection in New York City.

    PubMed

    Brown-Peterside, P; Redding, C A; Ren, L; Koblin, B A

    2000-04-01

    There is an urgent need to develop and implement effective methods for sexual behavior change to curb the spread of HIV. Condoms remain one of the most effective strategies for achieving this, yet consistent condom use is generally low, especially among those at highest risk. This article describes the acceptability of an interactive computer-based expert system designed to increase condom use in women at high risk of HIV infection. The expert system is based on the transtheoretical stages of change model. Using a computer, participants respond to questions about their attitudes and behavior toward using condoms and receive immediate feedback which is matched to their readiness to use condoms. The women were found to be at all stages of change for condom use, although a large proportion of the women (42%) were at early stages of behavior change because they were considering but not using condoms every time during sex with men. The expert system was found to be acceptable to this high-risk group of women. They almost unanimously agreed that they found the feedback useful, would return to use the system again, and would recommend it to a friend. These findings indicate that traditional intervention strategies which assume individuals are ready to use condoms consistently would be appropriate for only about one third of these women, underscoring the importance and potential utility of stage-matched interventions. PMID:10833041

  14. Nervous necrosis virus replicates following the embryo development and dual infection with iridovirus at juvenile stage in grouper.

    PubMed

    Kuo, Hsiao-Che; Wang, Ting-Yu; Hsu, Hao-Hsuan; Chen, Peng-Peng; Lee, Szu-Hsien; Chen, Young-Mao; Tsai, Tieh-Jung; Wang, Chien-Kai; Ku, Hsiao-Tung; Lee, Gwo-Bin; Chen, Tzong-Yueh

    2012-01-01

    Infection of virus (such as nodavirus and iridovirus) and bacteria (such as Vibrio anguillarum) in farmed grouper has been widely reported and caused large economic losses to Taiwanese fish aquaculture industry since 1979. The multiplex assay was used to detect dual viral infection and showed that only nervous necrosis virus (NNV) can be detected till the end of experiments (100% mortality) once it appeared. In addition, iridovirus can be detected in a certain period of rearing. The results of real-time PCR and in situ PCR indicated that NNV, in fact, was not on the surface of the eggs but present in the embryo, which can continue to replicate during the embryo development. The virus may be vertically transmitted by packing into eggs during egg development (formation) or delivering into eggs by sperm during fertilization. The ozone treatment of eggs may fail to remove the virus, so a new strategy to prevent NNV is needed. PMID:22563447

  15. Morphology of the infective larval stage of the equid parasite Habronema muscae (Spirurida: Habronematidae), from houseflies (Musca domestica).

    PubMed

    Buzzell, Gerald R; Tariq, Saeed; Traversa, Donato; Schuster, Rolf

    2011-03-01

    The infective larva of the spirurid nematode Habronema muscae, a parasite of houseflies, was measured and specimens fixed in Karnovsky's fluid were examined by scanning electron microscopy. The oral opening contains six teeth and is surrounded by large bilobed dorsal and ventral lips and smaller lateral lips. A pair of amphids lie behind the lateral lips. There are two rows of four cephalic papillae. The body is deeply ridged, both transversely and longitudinally. The caudal end of the worm is studded by small papillae. The position of the anal opening is somewhat ambiguous. These larval morphological features are discussed, as well as the changes which must have occurred in the metamorphosis of the infective larva to the adult in the stomach of horses. PMID:20949282

  16. Growth of HIV-Infected Children in the Early Stage of Antiretroviral Treatment: A Retrospective Cohort Study in China.

    PubMed

    Hu, Ran; Mu, Weiwei; Sun, Xin; Wu, Hao; Pang, Lin; Wang, Liming; Zhao, Qingxia; Wu, Yasong; Zhao, Decai; Chen, Meiling; Ma, Ye; Zhang, Fujie

    2016-08-01

    Malnutrition and human immunodeficiency virus (HIV)-related complications are commonly seen in HIV-infected children, and these have been shown in high-prevalent areas such as Africa. Antiviral therapy (ART) has notably controlled disease progression, whereas it effectively reverses underweight and growth retardation in HIV-infected children. This study was conducted to evaluate the growth status after initiation of ART in HIV-infected children in China. A retrospective cohort study was conducted based on the National Science and Technology Major Project. HIV-infected children who initiated antiretroviral treatment between January 1st, 2012 and December 31st, 2012 were followed up to December 31st, 2014. Z-scores of height and weight were calculated by WHO Anthro (plus). Linear mixed-effects models were used to model trajectories of weight- and height-for-age Z-scores. Seven hundred forty-four participants enrolled in the study, with 585 participants and 712 participants who had WAZ (weight-for-age Z-score) and HAZ (height-for-age Z-score), respectively, before initiation of ART. Among them, 125 (21.4%) were underweight and 301 (42.3%) were stunted. After treatment, among the 125 underweight children, WAZ improved in 69 patients, regained more than -2 on average. Among the 301 stunted children, HAZ improved in 123 patients, regained more than -2 on average. WAZ improved for the first 6 months by 0.052 units each month and then stabilized, whereas HAZ consistently improved by 0.014 units each month over time. Antiretroviral treatment reversed the adverse effects of HIV to some degree. Early diagnosis and treatment, with an effective nutrition program, is necessary to improve malnutrition further. PMID:27509236

  17. Single stage and multistage classification models for the prediction of liver fibrosis degree in patients with chronic hepatitis C infection.

    PubMed

    Hashem, Ahmed M; Rasmy, M Emad M; Wahba, Khaled M; Shaker, Olfat G

    2012-03-01

    Predicting significant fibrosis or cirrhosis in patients with hepatitis C virus has persistently preoccupied the research agenda of many specialized research centers. Many studies have been conducted to evaluate the use of readily available laboratory tests to predict significant fibrosis or cirrhosis with the purpose to substantially reduce the number of biopsies performed. Although many of them reported significant predictive values of several serum markers for the diagnosis of cirrhosis, none of these diagnostic techniques was successful in accurately predicting early stages of liver fibrosis. Therefore, in this study a single stage classification model and a multistage stepwise classification model based on Neural Network, Decision Tree, Logistic Regression, and Nearest Neighborhood clustering, have been developed to predict individual's liver fibrosis degree. Results showed that the area under the receiver operator curve (AUROC) values of the multistage model ranged from 0.874 to 0.974 which is a higher range than what is reported in current researches with similar conditions.

  18. [The effect of betain on biology and morphology of developmental stages of Eimeria acervulina in broiler chicks experimentally infected].

    PubMed

    Teixeira, Marcel; Niang, Tania Marcia S; Gomes, Augusto V da C; Lopes, Carlos Wilson G

    2006-01-01

    Purposing to investigate the betaine effect on biology and morphology of developmental stages of Eimeria acervulina, 420 broiler chicks Cobb were experimentally inoculated with 2 x 10(5) sporulated oocysts and housed in battery cages in a block design with five treatments and six replicates each, including a positive control, a group treated with salinomycin and growth promoter plus three levels of betaine as additive in the feed at 0.05, 0.10 and 0.15%. Measurements of oocysts, sporocysts and endogenous stages were performed as morphological parameters, while pre patent and patent periods and sporulation time were taken as biological parameters. Morphology was also associated with the mathematical constant Phi (1.618) to evaluate possible relationship. Betaine was able to cause modifications in both biology and morphology of oocysts and sporocysts, whereas it was weakly able to affect developmental stages based on trophozoites and macrogamonts measurements. According to the measures of sporocysts E. acervulina development was closely related to Phi. PMID:17196124

  19. Value of the oral swab for the molecular diagnosis of dogs in different stages of infection with Leishmania infantum.

    PubMed

    Aschar, Mariana; de Oliveira, Eveline Tozzi Braga; Laurenti, Marcia Dalastra; Marcondes, Mary; Tolezano, Jose Eduardo; Hiramoto, Roberto Mitsuyoshi; Corbett, Carlos Eduardo P; da Matta, Vania Lucia Ribeiro

    2016-07-30

    This study was based on the need to employ a sensitive and specific method with samples that could be easily collected for diagnosing dogs infected with Leishmania infantum. To this end, we used real time-PCR (qPCR) to assess the value of the oral swab (OS) in detecting infected sick dogs (SD; n=62), including, for the first time, the analysis of apparently healthy infected dogs (AD; n=30), both from endemic areas for visceral leishmaniasis (VL). For comparison, we also evaluated the performance of the conjunctival swab (CS), blood (BL), lymph node (LN) and serology. We detected the presence of Leishmania DNA in the oral cavity in 62 out of the 92 dogs studied. The OS positivity (67.4%) was equivalent to the CS (68.5%) (p>0.05), higher than BL (52.2%) (p≤0.05), and lower than LN (84.8%) (p≤0.05). OS and CS performed well in SD dogs (82.3% and 83.9%, respectively) but not in AD dogs (36.7% for both samples). BL showed the lowest positivity (52.2%) and provided equivalent results between AD (60.0%) and SD (48.4%) dogs (p>0.05). LN yielded the highest positivity (84.8%), and it was also higher in the SD population (93.5%) compared to the AD population (66.7%) (p≤0.05). Parasite load was high in LN, moderate in OS and CS, and low in BL, showing the relationship between the levels of parasitism and the positivity rates found in these samples. Serology was positive in 82.2% of the SD group and in 70% of the AD dogs (p>0.05). Among the 20 seronegative dogs, seven (35%) were positive in either OS or CS, and 12 (60%) were positive when both noninvasive samples were jointly considered. The OS/CS combination resulted in a significant increase of positivity (p≤0.05) for the AD dogs (from 36.7% to 63.4%), as well as OS/serology (80%) and OS/CS/serology (83.4%). For the SD population, positivity reached up to 95.2% with the same combinations, showing that combination of samples and/or tests is required for the identification of dogs infected with L. infantum and that the

  20. Efficacy of a milbemycin oxime-praziquantel combination product against adult and immature stages of Toxocara cati in cats and kittens after induced infection.

    PubMed

    Schenker, R; Bowman, D; Epe, C; Cody, R; Seewald, W; Strehlau, G; Junquera, P

    2007-04-10

    Two studies were performed to examine the efficacy of milbemycin oxime against fourth-stage larvae or adults of Toxocara cati. In the study to determine efficacy against fourth-stage larvae, 20 domestic shorthair cats were inoculated with 500 embryonated eggs. Four weeks after inoculation, the animals were allocated to two groups, and cats in one group were treated with medicated tablets containing 4 mg milbemycin oxime and 10mg praziquantel (MILBEMAX) and cats in the other group with placebo tablets. Seven days after treatment the animals were euthanatized and necropsied for worm counting. The number of worms found was significantly (p=0.0002) lower in cats treated with medicated tablets than in cats treated with placebo tablets. The reduction in the number of worms was 96.53%. In the study to determine efficacy against mature adult worms, 13 kittens were inoculated with T. cati embryonated eggs. On day 45 after inoculation and after the infection had been confirmed through faecal examinations for 11 out of the 13 animals, the 11 infected animals were allocated to two groups and treated as in the first study. Seven days after treatment, all animals were euthanatized and necropsied for worm counting. The number of worms found was significantly (p=0.0043) lower in kittens treated with medicated tablets than in kittens treated with placebo tablets. The reduction in the number of worms was 95.90%. No adverse effects were recorded during either study. It is concluded that the milbemycin oxime-praziquantel tablets that were used are efficacious for the control of T. cati infections in cats. PMID:17140736

  1. Susceptibility of Brassica species to cauliflower mosaic virus infection is related to a specific stage in the virus multiplication cycle.

    PubMed

    Saunders, K; Lucy, A P; Covey, S N

    1990-08-01

    The relative susceptibilities and symptom responses of different Brassica species to infection by cauliflower mosaic virus (CaMV) have been compared and related to molecular events of the virus multiplication cycle. Variants of B. rapa (genome descriptor aa) were highly susceptible to infection by CaMV strain Cabb B-JI and contained relatively large amounts of virus; B. oleracea (cc) variants showed low susceptibility and contained small amounts of virus. B. nigra (bb) and allotetraploid species. B. juncea (aabb), B. napus (aacc) and B. carinata (bbcc), showed moderate responses to CaMV. CaMV unencapsidated DNA forms were isolated from different Brassica plants and examined by two-dimensional gel electrophoresis and blot hybridization. Viral RNA was estimated by dot blot analysis. These analyses showed differences in accumulation of key viral replication cycle intermediates within the broad range of host plants studied. The most susceptible species contained relatively small amounts of supercoiled (SC) DNA, a component of the CaMV mini-chromosome, but abundant viral transcripts and reverse transcription replication products. Tolerant plant hosts contained high levels of SC DNA but low levels of viral transcripts and reverse transcription DNA products. Allotetraploids contained SC DNA, RNA transcripts and replication product levels which were generally intermediate between those of their respective progenitor species. Evidence is presented that accumulation of CaMV SC DNA in the less susceptible host species is probably not due to autonomous DNA replication or tissue-specific expression. We conclude that a major component of the susceptibility of Brassica plants (and probably all CaMV host species) to CaMV infection is the level of viral minichromosome expression, influenced directly by the host genotype.

  2. Influence of stripe rust infection on the photosynthetic characteristics and antioxidant system of susceptible and resistant wheat cultivars at the adult plant stage.

    PubMed

    Chen, Yang-Er; Cui, Jun-Mei; Su, Yan-Qiu; Yuan, Shu; Yuan, Ming; Zhang, Huai-Yu

    2015-01-01

    Wheat stripe rust (Puccinia striiformis f. sp. tritici, Pst), is one of the most serious diseases of wheat (Triticum aestivum L.) worldwide. To gain a better understanding of the protective mechanism against stripe rust at the adult plant stage, the differences in photosystem II and antioxidant enzymatic systems between susceptible and resistant wheat in response to stripe rust disease (P. striiformis) were investigated. We found that chlorophyll fluorescence and the activities of the antioxidant enzymes were higher in resistant wheat than in susceptible wheat after stripe rust infection. Compared with the susceptible wheat, the resistant wheat accumulated a higher level of D1 protein and a lower level of reactive oxygen species after infection. Furthermore, our results demonstrate that D1 and light-harvesting complex II (LHCII) phosphorylation are involved in the resistance to stripe rust in wheat. The CP29 protein was phosphorylated under stripe rust infection, like its phosphorylation in other monocots under environmental stresses. More extensive damages occur on the thylakoid membranes in the susceptible wheat compared with the resistant wheat. The findings provide evidence that thylakoid protein phosphorylation and antioxidant enzyme systems play important roles in plant responses and defense to biotic stress.

  3. Immunological signature of the different clinical stages of the HTLV-1 infection: establishing serum biomarkers for HTLV-1-associated disease morbidity.

    PubMed

    Starling, Ana Lúcia Borges; Coelho-Dos-Reis, Jordana Grazziela Alves; Peruhype-Magalhães, Vanessa; Pascoal-Xavier, Marcelo Antônio; Gonçalves, Denise Utsch; Béla, Samantha Ribeiro; Lambertucci, José Roberto; Labanca, Ludimila; Souza Pereira, Silvio Roberto; Teixeira-Carvalho, Andréa; Ribas, João Gabriel; Trindade, Bruno Caetano; Faccioli, Lucia Helena; Carneiro-Proietti, Anna Bárbara Freitas; Martins-Filho, Olindo Assis

    2015-01-01

    This study aimed at establishing the immunological signature and an algorithm for clinical management of the different clinical stages of the HTLV-1-infection based on serum biomarkers. A panel of serum biomarkers was evaluated by four sets of innovative/non-conventional data analysis approaches in samples from 87 HTLV-1 patients: asymptomatic carriers (AC), putative HTLV-1 associated myelopathy/tropical spastic paraparesis (pHAM/TSP) and HAM/TSP. The analysis of cumulative curves and molecular signatures pointed out that HAM/TSP presented a pro-inflammatory profile mediated by CXCL10/LTB-4/IL-6/TNF-α/IFN-γ, counterbalanced by IL-4/IL-10. The analysis of biomarker networks showed that AC presented a strongly intertwined pro-inflammatory/regulatory net with IL-4/IL-10 playing a central role, while HAM/TSP exhibited overall immune response toward a predominant pro-inflammatory profile. At last, the classification and regression trees proposed for clinical practice allowed for the construction of an algorithm to discriminate AC, pHAM and HAM/TSP patients with the elected biomarkers: IFN-γ, TNF-α, IL-10, IL-6, IL-4 and CysLT. These findings reveal a complex interaction among chemokine/leukotriene/cytokine in HTLV-1 infection and suggest the use of the selected but combined biomarkers for the follow-up/diagnosis of disease morbidity of HTLV-1-infected individuals.

  4. Efficient monitoring of the blood-stage infection in a malaria rodent model by the rotating-crystal magneto-optical method

    NASA Astrophysics Data System (ADS)

    Orbán, Ágnes; Rebelo, Maria; Molnár, Petra; Albuquerque, Inês S.; Butykai, Adam; Kézsmárki, István

    2016-03-01

    Intense research efforts have been focused on the improvement of the efficiency and sensitivity of malaria diagnostics, especially in resource-limited settings for the detection of asymptomatic infections. Our recently developed magneto-optical (MO) method allows the accurate quantification of malaria pigment crystals (hemozoin) in blood by their magnetically induced rotation. First evaluations of the method using β-hematin crystals and in vitro P. falciparum cultures implied its potential for high-sensitivity malaria diagnosis. To further investigate this potential, here we study the performance of the method in monitoring the in vivo onset and progression of the blood-stage infection in a rodent malaria model. Our results show that the MO method can detect the first generation of intraerythrocytic P. berghei parasites 66–76 hours after sporozoite injection, demonstrating similar sensitivity to Giesma-stained light microscopy and exceeding that of flow cytometric techniques. Magneto-optical measurements performed during and after the treatment of P. berghei infections revealed that both the follow up under treatment and the detection of later reinfections are feasible with this new technique. The present study demonstrates that the MO method – besides being label and reagent-free, automated and rapid – has a high in vivo sensitivity and is ready for in-field evaluation.

  5. Influence of stripe rust infection on the photosynthetic characteristics and antioxidant system of susceptible and resistant wheat cultivars at the adult plant stage

    PubMed Central

    Chen, Yang-Er; Cui, Jun-Mei; Su, Yan-Qiu; Yuan, Shu; Yuan, Ming; Zhang, Huai-Yu

    2015-01-01

    Wheat stripe rust (Puccinia striiformis f. sp. tritici, Pst), is one of the most serious diseases of wheat (Triticum aestivum L.) worldwide. To gain a better understanding of the protective mechanism against stripe rust at the adult plant stage, the differences in photosystem II and antioxidant enzymatic systems between susceptible and resistant wheat in response to stripe rust disease (P. striiformis) were investigated. We found that chlorophyll fluorescence and the activities of the antioxidant enzymes were higher in resistant wheat than in susceptible wheat after stripe rust infection. Compared with the susceptible wheat, the resistant wheat accumulated a higher level of D1 protein and a lower level of reactive oxygen species after infection. Furthermore, our results demonstrate that D1 and light-harvesting complex II (LHCII) phosphorylation are involved in the resistance to stripe rust in wheat. The CP29 protein was phosphorylated under stripe rust infection, like its phosphorylation in other monocots under environmental stresses. More extensive damages occur on the thylakoid membranes in the susceptible wheat compared with the resistant wheat. The findings provide evidence that thylakoid protein phosphorylation and antioxidant enzyme systems play important roles in plant responses and defense to biotic stress. PMID:26442087

  6. Efficient monitoring of the blood-stage infection in a malaria rodent model by the rotating-crystal magneto-optical method

    PubMed Central

    Orbán, Ágnes; Rebelo, Maria; Molnár, Petra; Albuquerque, Inês S.; Butykai, Adam; Kézsmárki, István

    2016-01-01

    Intense research efforts have been focused on the improvement of the efficiency and sensitivity of malaria diagnostics, especially in resource-limited settings for the detection of asymptomatic infections. Our recently developed magneto-optical (MO) method allows the accurate quantification of malaria pigment crystals (hemozoin) in blood by their magnetically induced rotation. First evaluations of the method using β-hematin crystals and in vitro P. falciparum cultures implied its potential for high-sensitivity malaria diagnosis. To further investigate this potential, here we study the performance of the method in monitoring the in vivo onset and progression of the blood-stage infection in a rodent malaria model. Our results show that the MO method can detect the first generation of intraerythrocytic P. berghei parasites 66–76 hours after sporozoite injection, demonstrating similar sensitivity to Giesma-stained light microscopy and exceeding that of flow cytometric techniques. Magneto-optical measurements performed during and after the treatment of P. berghei infections revealed that both the follow up under treatment and the detection of later reinfections are feasible with this new technique. The present study demonstrates that the MO method – besides being label and reagent-free, automated and rapid – has a high in vivo sensitivity and is ready for in-field evaluation. PMID:26983695

  7. Efficient monitoring of the blood-stage infection in a malaria rodent model by the rotating-crystal magneto-optical method.

    PubMed

    Orbán, Ágnes; Rebelo, Maria; Molnár, Petra; Albuquerque, Inês S; Butykai, Adam; Kézsmárki, István

    2016-01-01

    Intense research efforts have been focused on the improvement of the efficiency and sensitivity of malaria diagnostics, especially in resource-limited settings for the detection of asymptomatic infections. Our recently developed magneto-optical (MO) method allows the accurate quantification of malaria pigment crystals (hemozoin) in blood by their magnetically induced rotation. First evaluations of the method using β-hematin crystals and in vitro P. falciparum cultures implied its potential for high-sensitivity malaria diagnosis. To further investigate this potential, here we study the performance of the method in monitoring the in vivo onset and progression of the blood-stage infection in a rodent malaria model. Our results show that the MO method can detect the first generation of intraerythrocytic P. berghei parasites 66-76 hours after sporozoite injection, demonstrating similar sensitivity to Giesma-stained light microscopy and exceeding that of flow cytometric techniques. Magneto-optical measurements performed during and after the treatment of P. berghei infections revealed that both the follow up under treatment and the detection of later reinfections are feasible with this new technique. The present study demonstrates that the MO method - besides being label and reagent-free, automated and rapid - has a high in vivo sensitivity and is ready for in-field evaluation. PMID:26983695

  8. Correlation of Deoxynivalenol Accumulation in Fusarium-Infected Winter and Spring Wheat Cultivars with Secondary Metabolites at Different Growth Stages.

    PubMed

    Etzerodt, Thomas; Gislum, Rene; Laursen, Bente B; Heinrichson, Kirsten; Gregersen, Per L; Jørgensen, Lise N; Fomsgaard, Inge S

    2016-06-01

    Fusarium infection in wheat causes Fusarium head blight, resulting in yield losses and contamination of grains with trichothecenes. Some plant secondary metabolites inhibit accumulation of trichothecenes. Eighteen Fusarium infected wheat cultivars were harvested at five time points and analyzed for the trichothecene deoxynivalenol (DON) and 38 wheat secondary metabolites (benzoxazinoids, phenolic acids, carotenoids, and flavonoids). Multivariate analysis showed that harvest time strongly impacted the content of secondary metabolites, more distinctly for winter wheat than spring wheat. The benzoxazinoid 2-β-glucopyranoside-2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA-glc), α-tocopherol, and the flavonoids homoorientin and orientin were identified as potential inhibitors of DON accumulation. Several phenolic acids, lutein and β-carotene also affected DON accumulation, but the effect varied for the two wheat types. The results could form a basis for choosing wheat cultivars using metabolite profiling as a marker for selecting wheat cultivars with improved resistance against Fusarium head blight and accumulation of trichothecene toxins in wheat heads. PMID:27195655

  9. Morphological and morphometric differentiation of dorsal-spined first stage larvae of lungworms (Nematoda: Protostrongylidae) infecting muskoxen (Ovibos moschatus) in the central Canadian Arctic.

    PubMed

    Kafle, Pratap; Lejeune, Manigandan; Verocai, Guilherme G; Hoberg, Eric P; Kutz, Susan J

    2015-12-01

    Umingmakstrongylus pallikuukensis and Varestrongylus eleguneniensis are the two most common protostrongylid nematodes infecting muskoxen in the North American Arctic and Subarctic. First stage larvae (L1) of these lungworms have considerable morphological similarity that makes their differential diagnosis very difficult. Using light microscopy, we studied in detail the L1 of these two species and identified the key differences in morphological and morphometric attributes. Thirty L1 of each species from naturally infected muskox were heat-killed and then assessed for morphological and morphometric features that could be used for species-level differentiation. Key differentiating features include: length and morphology of the tail extension, curvature of the body, ventral post-anal transverse cuticular striations, and total body length. A laboratory guide for differentiation of L1 based on these species-specific characters was prepared and used by an experienced observer to identify an additional 35 L1 extracted from a different set of fecal samples from free-ranging muskoxen with mixed infections. The identities of these L1 were confirmed by sequence analysis of the ITS-2 region of the nuclear ribosomal DNA. Accuracy of morphological identification was 100 percent, reflecting the reliability of the proposed guide for differentiation. Using the guide, three minimally trained lab assistants each fixed and accurately identified 10 of 10 randomly selected L1. Ability to morphologically differentiate these facilitates the monitoring of overlapping range expansion of both parasites in the Canadian Arctic. Studies enabling species-level parasite identification are also critical for defining biodiversity, detecting mixed infections, and understanding host-parasite interactions. Morphological identification is a simple, reliable and cost-effective alternative to labor and equipment intensive molecular methods and can easily be performed in low resource settings.

  10. Morphological and morphometric differentiation of dorsal-spined first stage larvae of lungworms (Nematoda: Protostrongylidae) infecting muskoxen (Ovibos moschatus) in the central Canadian Arctic

    PubMed Central

    Kafle, Pratap; Lejeune, Manigandan; Verocai, Guilherme G.; Hoberg, Eric P.; Kutz, Susan J.

    2015-01-01

    Umingmakstrongylus pallikuukensis and Varestrongylus eleguneniensis are the two most common protostrongylid nematodes infecting muskoxen in the North American Arctic and Subarctic. First stage larvae (L1) of these lungworms have considerable morphological similarity that makes their differential diagnosis very difficult. Using light microscopy, we studied in detail the L1 of these two species and identified the key differences in morphological and morphometric attributes. Thirty L1 of each species from naturally infected muskox were heat-killed and then assessed for morphological and morphometric features that could be used for species-level differentiation. Key differentiating features include: length and morphology of the tail extension, curvature of the body, ventral post-anal transverse cuticular striations, and total body length. A laboratory guide for differentiation of L1 based on these species-specific characters was prepared and used by an experienced observer to identify an additional 35 L1 extracted from a different set of fecal samples from free-ranging muskoxen with mixed infections. The identities of these L1 were confirmed by sequence analysis of the ITS-2 region of the nuclear ribosomal DNA. Accuracy of morphological identification was 100 percent, reflecting the reliability of the proposed guide for differentiation. Using the guide, three minimally trained lab assistants each fixed and accurately identified 10 of 10 randomly selected L1. Ability to morphologically differentiate these facilitates the monitoring of overlapping range expansion of both parasites in the Canadian Arctic. Studies enabling species-level parasite identification are also critical for defining biodiversity, detecting mixed infections, and understanding host–parasite interactions. Morphological identification is a simple, reliable and cost-effective alternative to labor and equipment intensive molecular methods and can easily be performed in low resource settings. PMID

  11. Phagosomal Acidification Prevents Macrophage Inflammatory Cytokine Production to Malaria, and Dendritic Cells Are the Major Source at the Early Stages of Infection: IMPLICATION FOR MALARIA PROTECTIVE IMMUNITY DEVELOPMENT.

    PubMed

    Wu, Xianzhu; Gowda, Nagaraj M; Gowda, D Channe

    2015-09-18

    Inflammatory cytokines produced at the early stages of malaria infection contribute to shaping protective immunity and pathophysiology. To gain mechanistic insight into these processes, it is important to understand the cellular origin of cytokines because both cytokine input and cytokine-producing cells play key roles. Here, we determined cytokine responses by monocytes, macrophages, and dendritic cells (DCs) to purified Plasmodium falciparum and Plasmodium berghei ANKA, and by spleen macrophages and DCs from Plasmodium yoelii 17NXL-infected and P. berghei ANKA-infected mice. The results demonstrate that monocytes and macrophages do not produce inflammatory cytokines to malaria parasites and that DCs are the primary source early in infection, and DC subsets differentially produce cytokines. Importantly, blocking of phagosomal acidification by inhibiting vacuolar-type H(+)-ATPase enabled macrophages to elicit cytokine responses. Because cytokine responses to malaria parasites are mediated primarily through endosomal Toll-like receptors, our data indicate that the inability of macrophages to produce cytokines is due to the phagosomal acidification that disrupts endosomal ligand-receptor engagement. Macrophages efficiently produced cytokines to LPS upon simultaneously internalizing parasites and to heat-killed Escherichia coli, demonstrating that phagosomal acidification affects endosomal receptor-mediated, but not cell surface receptor-mediated, recognition of Toll-like receptor agonists. Enabling monocytes/macrophages to elicit immune responses to parasites by blocking endosomal acidification can be a novel strategy for the effective development of protective immunity to malaria. The results have important implications for enhancing the efficacy of a whole parasite-based malaria vaccine and for designing strategies for the development of protective immunity to pathogens that induce immune responses primarily through endosomal receptors.

  12. Stress-Induced Glucocorticoids at the Earliest Stages of Herpes Simplex Virus-1 Infection Suppress Subsequent Antiviral Immunity, Implicating Impaired Dendritic Cell Function

    PubMed Central

    Elftman, Michael D.; Hunzeker, John T.; Mellinger, Jennifer C.; Bonneau, Robert H.; Norbury, Christopher C.; Truckenmiller, Mary E.

    2013-01-01

    The systemic elevation of psychological stress-induced glucocorticoids strongly suppresses CD8+ T cell immune responses resulting in diminished antiviral immunity. However, the specific cellular targets of stress/glucocorticoids, the timing of exposure, the chronology of immunological events, and the underlying mechanisms of this impairment are incompletely understood. In this study, we address each of these questions in the context of a murine cutaneous HSV infection. We show that exposure to stress or corticosterone in only the earliest stages of an HSV-1 infection is sufficient to suppress, in a glucocorticoid receptor-dependent manner, the subsequent antiviral immune response after stress/corticosterone has been terminated. This suppression resulted in early onset and delayed resolution of herpetic lesions, reduced viral clearance at the site of infection and draining popliteal lymph nodes (PLNs), and impaired functions of HSV-specific CD8+ T cells in PLNs, including granzyme B and IFN-γ production and the ability to degranulate. In knockout mice lacking glucocorticoid receptors only in T cells, we show that these impaired CD8+ T cell functions are not due to direct effects of stress/corticosterone on the T cells, but the ability of PLN-derivcd dendritic cells to prime HSV-1–specific CD8+ T cells is functionally impaired. These findings highlight the susceptibility of critical early events in the generation of an antiviral immune response to neuroendocrine modulation and implicate dendritic cells as targets of stress/glucocorticoids in vivo. These findings also provide insight into the mechanisms by which the clinical use of glucocorticoids contributes to altered immune responses in patients with viral infections or tumors. PMID:20089700

  13. Morphological and morphometric differentiation of dorsal-spined first stage larvae of lungworms (Nematoda: Protostrongylidae) infecting muskoxen (Ovibos moschatus) in the central Canadian Arctic.

    PubMed

    Kafle, Pratap; Lejeune, Manigandan; Verocai, Guilherme G; Hoberg, Eric P; Kutz, Susan J

    2015-12-01

    Umingmakstrongylus pallikuukensis and Varestrongylus eleguneniensis are the two most common protostrongylid nematodes infecting muskoxen in the North American Arctic and Subarctic. First stage larvae (L1) of these lungworms have considerable morphological similarity that makes their differential diagnosis very difficult. Using light microscopy, we studied in detail the L1 of these two species and identified the key differences in morphological and morphometric attributes. Thirty L1 of each species from naturally infected muskox were heat-killed and then assessed for morphological and morphometric features that could be used for species-level differentiation. Key differentiating features include: length and morphology of the tail extension, curvature of the body, ventral post-anal transverse cuticular striations, and total body length. A laboratory guide for differentiation of L1 based on these species-specific characters was prepared and used by an experienced observer to identify an additional 35 L1 extracted from a different set of fecal samples from free-ranging muskoxen with mixed infections. The identities of these L1 were confirmed by sequence analysis of the ITS-2 region of the nuclear ribosomal DNA. Accuracy of morphological identification was 100 percent, reflecting the reliability of the proposed guide for differentiation. Using the guide, three minimally trained lab assistants each fixed and accurately identified 10 of 10 randomly selected L1. Ability to morphologically differentiate these facilitates the monitoring of overlapping range expansion of both parasites in the Canadian Arctic. Studies enabling species-level parasite identification are also critical for defining biodiversity, detecting mixed infections, and understanding host-parasite interactions. Morphological identification is a simple, reliable and cost-effective alternative to labor and equipment intensive molecular methods and can easily be performed in low resource settings. PMID

  14. Interferon-Based Treatment of Hepatitis C Virus Infection Reduces All-Cause Mortality in Patients With End-Stage Renal Disease

    PubMed Central

    Hsu, Yueh-Han; Hung, Peir-Haur; Muo, Chih-Hsin; Tsai, Wen-Chen; Hsu, Chih-Cheng; Kao, Chia-Hung

    2015-01-01

    Abstract The long-term survival of end-stage renal disease (ESRD) patients with hepatitis C virus (HCV) infection who received interferon treatment has not been extensively evaluated. The HCV cohort was the ESRD patients with de novo HCV infection from 2004 to 2011; they were classified into treated and untreated groups according to interferon therapy records. Patients aged <20 years and those with a history of hepatitis B, kidney transplantation, or cancer were excluded. The control cohort included ESRD patients without HCV infection matched 4:1 to the HCV cohort by age, sex, and year of ESRD registration. We followed up all study participants until kidney transplantation, death, or the end of 2011, whichever came first. We assessed risk of all-cause mortality by using the multivariate Cox proportional hazard model with time-dependent covariate. In the HCV cohort, 134 patients (6.01%) received interferon treatment. Compared with the uninfected control cohort, the treated group had a lower risk of death (hazard ratio 0.47, 95% confidence interval [CI] 0.22–0.99). The untreated group had a 2.62-fold higher risk (95% CI 1.24–5.55) of death compared with the treated group. For the HCV cohort without cirrhosis or hepatoma, the risk of death in the treated group was further markedly reduced (hazard ratio 0.17, 95% CI 0.04–0.68) compared with that in the control cohort. For ESRD patients with HCV infection, receiving interferon treatment is associated with a survival advantage. Such an advantage is more prominent in HCV patients without cirrhosis or hepatoma. PMID:26632730

  15. End-stage renal disease and African American race are independent predictors of mild liver fibrosis in patients with chronic hepatitis C infection.

    PubMed

    Aslinia, F M; Wasan, S K; Mindikoglu, A L; Adeyemo, O A; Philosophe, B; Drachenberg, C; Howell, C D

    2012-05-01

    Recipients of haemodialysis for end-stage renal disease (ESRD) have a higher prevalence of hepatitis C virus (HCV) infection relative to the general US population. However, the natural course of HCV infection in patients with renal failure, including African Americans (AAs) and Caucasian Americans (CAs), is not well known. We compared the degree of liver inflammation and fibrosis in AA and CA patients with HCV infection, with and without ESRD. This was a cross-sectional study of 156 HCV patients with ESRD (130 AAs and 26 CAs) with a liver biopsy between 1992 and 2005. The control group consisted of 138 patients (50 AAs; 88 CAs) with HCV infections and a serum creatinine <1.5 mg/dL with a liver biopsy between 1995 and 1998. Specimens were graded for inflammation and fibrosis using Knodell histological activity index. Compared to patients without renal impairment, HCV patients with renal failure were older and more likely to be AA. Patients with renal impairment had lower mean serum transaminases, a higher mean serum alkaline phosphatase levels (all P < 0.0001) and less hepatic necro-inflammation (Knodell histological activity index -I, II and III; P < 0.05) and fibrosis (Knodell histological activity index -IV; P < 0.0001). There were no racial differences in serum liver chemistry and histology scores among patients with renal failure. In a multivariate analysis, younger age, ESRD, AA race and a lower serum alkaline phosphatase were associated with lower odds for advanced liver fibrosis. Thus, HCV patients with ESRD had a lower degree of hepatic inflammation and fibrosis compared to those without renal disease, independent of race.

  16. Genome-wide Prediction and Functional Validation of Promoter Motifs Regulating Gene Expression in Spore and Infection Stages of Phytophthora infestans

    PubMed Central

    Roy, Sourav; Kagda, Meenakshi; Judelson, Howard S.

    2013-01-01

    Most eukaryotic pathogens have complex life cycles in which gene expression networks orchestrate the formation of cells specialized for dissemination or host colonization. In the oomycete Phytophthora infestans, the potato late blight pathogen, major shifts in mRNA profiles during developmental transitions were identified using microarrays. We used those data with search algorithms to discover about 100 motifs that are over-represented in promoters of genes up-regulated in hyphae, sporangia, sporangia undergoing zoosporogenesis, swimming zoospores, or germinated cysts forming appressoria (infection structures). Most of the putative stage-specific transcription factor binding sites (TFBSs) thus identified had features typical of TFBSs such as position or orientation bias, palindromy, and conservation in related species. Each of six motifs tested in P. infestans transformants using the GUS reporter gene conferred the expected stage-specific expression pattern, and several were shown to bind nuclear proteins in gel-shift assays. Motifs linked to the appressoria-forming stage, including a functionally validated TFBS, were over-represented in promoters of genes encoding effectors and other pathogenesis-related proteins. To understand how promoter and genome architecture influence expression, we also mapped transcription patterns to the P. infestans genome assembly. Adjacent genes were not typically induced in the same stage, including genes transcribed in opposite directions from small intergenic regions, but co-regulated gene pairs occurred more than expected by random chance. These data help illuminate the processes regulating development and pathogenesis, and will enable future attempts to purify the cognate transcription factors. PMID:23516354

  17. Evidences of protection against blood-stage infection of Plasmodium falciparum by the novel protein vaccine SE36.

    PubMed

    Horii, Toshihiro; Shirai, Hiroki; Jie, Li; Ishii, Ken J; Palacpac, Nirianne Q; Tougan, Takahiro; Hato, Mariko; Ohta, Nobuo; Bobogare, Albino; Arakaki, Nana; Matsumoto, Yoshitsugu; Namazue, Junko; Ishikawa, Toyokazu; Ueda, Shigeharu; Takahashi, Michiaki

    2010-09-01

    An effective malaria vaccine is a public health priority. Proteins expressed during the blood-stage of the parasite life cycle have been proposed as good vaccine candidates. No such blood-stage vaccine, however, is available against Plasmodium falciparum, the deadliest Plasmodium species. We show here that P. falciparum serine repeat antigen 5 (SERA5) is a potential vaccine immunogen. We have constructed a new recombinant molecule of SERA5, namely SE36, based on previously reported SE47' molecule by removing the serine repeats. Epidemiological study in the holo-endemic population of Solomon Islands shows highly significant correlation of sero-conversion and malaria protective immunity against this antigen. Animal experiments using non-human primates, and a human phase 1a clinical trial assessed SE36 vaccine immunogenicity. Vaccination of squirrel monkeys with SE36 protein and aluminum hydroxyl gel (SE36/AHG) conferred protection against high parasitemia and boosted serum anti-SE36 IgG after P. falciparum parasite challenge. SE36/AHG was highly immunogenic in chimpanzees, where serum anti-SE36 IgG titers last more than one year. Phase 1a clinical trial (current controlled trials, ISRCTN78679862) demonstrated the safety and immunogenicity of SE36/AHG with 30 healthy adults and 10 placebo controls. Three subcutaneous administrations of 50 and 100microg dose of SE36/AHG were well-tolerated, with no severe adverse events; and resulted in 100% sero-conversion in both dose arms. The current research results for SE36/AHG provide initial clinical validation for future trials and suggest clues/strategies for further vaccine development. PMID:20493274

  18. CD4+ T-lymphocyte telomere length is related to fibrosis stage, clinical outcome and treatment response in chronic hepatitis C virus infection

    PubMed Central

    Hoare, Matthew; Gelson, William T.H.; Das, Abhi; Fletcher, Jean M.; Davies, Susan E.; Curran, Martin D.; Vowler, Sarah L.; Maini, Mala K.; Akbar, Arne N.; Alexander, Graeme J.M.

    2010-01-01

    Background & Aims Increasing age is associated with impaired immune function and in chronic HCV infection specifically, with progressive fibrosis, liver failure, HCC and impaired responses to antiviral therapy. T-lymphocyte telomere length declines with age. We hypothesised that shorter T-lymphocyte telomere length would be associated with poor clinical outcome in HCV infection. Methods Circulating T-lymphocyte telomere length, an objective measure of immune senescence, was measured by flow-FISH in 135 HCV-RNA-positive, treatment-naïve patients and 41 healthy controls in relation to clinical outcome. Results Shorter CD4+CD45RO+ T-lymphocyte telomeres were associated with severe fibrosis (p = 0.003), independent of male sex (p = 0.04), CMV positivity (p = 0.003), previous HBV infection (p = 0.007), and age (p = ns) in viraemic patients compared to controls. There were inverse correlations between CD4+CD45RO+ telomere length and fibrosis stage (p <0.001), portal tract inflammatory grade (p = 0.035), prothrombin time (p <0.001) and bilirubin (p = 0.001). One hundred and twenty-four viraemic individuals were followed prospectively to a composite endpoint of death, hepatic decompensation or HCC. Independent of age, those with shorter CD4+CD45RO+ telomeres were less likely to be complication free after 2-years than those with longer telomeres (86% versus 96%, p = 0.009) with an age-adjusted hazard ratio of 0.93 (0.90–0.96). In addition, CD4+CD45RO+ telomere length predicted successful antiviral therapy (p = 0.001) independent of other factors. Conclusions CD4+ T-lymphocyte telomere length, independent of age, was related to inflammatory grade, fibrosis stage, laboratory indices of severity, subsequent hepatic decompensation and treatment outcome in patients with chronic HCV infection. PMID:20462651

  19. Recruitment of Factor H as a Novel Complement Evasion Strategy for Blood-Stage Plasmodium falciparum Infection.

    PubMed

    Kennedy, Alexander T; Schmidt, Christoph Q; Thompson, Jennifer K; Weiss, Greta E; Taechalertpaisarn, Tana; Gilson, Paul R; Barlow, Paul N; Crabb, Brendan S; Cowman, Alan F; Tham, Wai-Hong

    2016-02-01

    The human complement system is the frontline defense mechanism against invading pathogens. The coexistence of humans and microbes throughout evolution has produced ingenious molecular mechanisms by which microorganisms escape complement attack. A common evasion strategy used by diverse pathogens is the hijacking of soluble human complement regulators to their surfaces to afford protection from complement activation. One such host regulator is factor H (FH), which acts as a negative regulator of complement to protect host tissues from aberrant complement activation. In this report, we show that Plasmodium falciparum merozoites, the invasive form of the malaria parasites, actively recruit FH and its alternative spliced form FH-like protein 1 when exposed to human serum. We have mapped the binding site in FH that recognizes merozoites and identified Pf92, a member of the six-cysteine family of Plasmodium surface proteins, as its direct interaction partner. When bound to merozoites, FH retains cofactor activity, a key function that allows it to downregulate the alternative pathway of complement. In P. falciparum parasites that lack Pf92, we observed changes in the pattern of C3b cleavage that are consistent with decreased regulation of complement activation. These results also show that recruitment of FH affords P. falciparum merozoites protection from complement-mediated lysis. Our study provides new insights on mechanisms of immune evasion of malaria parasites and highlights the important function of surface coat proteins in the interplay between complement regulation and successful infection of the host.

  20. Preliminary studies by ELISA on the antigen and antibody dynamics in the early stages of experimental infections with Trypanosoma evansi in cattle.

    PubMed

    Thammasart, S; Kanitpun, R; Saithasao, M; Kashiwazaki, Y

    2001-05-01

    Six 6-month-old bulls were experimentally infected with five different isolates of Trypanosoma evansi; two received the same isolate and the other four received different isolates. The parasitaemias and serum antigen levels were monitored regularly by the haematocrit centrifuge technique (HCT) and antigen-detection ELISA (Ag-ELISA), respectively. Trypanosomal antigen was demonstrated by the Ag-ELISA by 10-14 days post inoculation in four cattle, while parasitaemias were first found to be positive in individual cattle over a longer period of time post inoculation (6-28 days). In two cattle, the Ag-ELISA values were also positive when the animals were found to harbour trypanosomes by the HCT and only turned negative 3 days after treatment, while the ELISA values fluctuated during the experiment in another two bulls. The remaining two cattle never produced positive ELISA results despite positive parasitological results. The antibody titres in all six cattle started to rise around 10 days post inoculation and then stayed high throughout the experiment. It was concluded that the Ag-ELISA would produce some false negative results in the early stages of T. evansi infection owing to variations in the balance of parasitaemia and antibody levels in the circulation, and in the pathogenicity of parasite strains. PMID:11360798

  1. Human immunodeficiency virus type 1 long terminal repeat variants from 42 patients representing all stages of infection display a wide range of sequence polymorphism and transcription activity.

    PubMed Central

    Estable, M C; Bell, B; Merzouki, A; Montaner, J S; O'Shaughnessy, M V; Sadowski, I J

    1996-01-01

    Despite extensive in vitro studies identifying a myriad of cellular transcription factors that bind the human immunodeficiency virus type 1 5' long terminal repeat (LTR), the relative contribution of these factors to human immunodeficiency virus type 1 replication in infected individuals remains obscure. To address this question, we investigated 478 proviral quasispecies derived from uncultured peripheral blood mononuclear cells of 42 patients representing all stages of infection. In addition to highly conserved TATA box, SP-1, and NF-kappaB sites, the Ets core and an adjacent 5'-ACYGCTGA-3' motif were extremely conserved. Importantly, the most frequent naturally occurring length polymorphism (MFNLP) duplicated 5'-ACYGCTGA-3' motifs in LTRs in which this same motif was disrupted or in LTRs in which a single point mutation to the Ets core ablated binding of c-Ets 1 and another factor distinct from both c-Ets 1 and Elf 1. The MFNLP's location was precise (position -121) and surprisingly frequent (38% of patients) and demarcated LTR Nef-coding sequences from LTR noncoding sequences that appear to be evolving independently. Aside from these features, we found no definitive clinical or transcription phenotype common to all MFNLP LTRs. We also found previously described and novel point polymorphisms, including some conferring TAR-dependent and TAR- independent Tat unresponsiveness, and showed that differential binding of nuclear factor(s) to a TCTAA TATA box variant may be the mechanism for the latter. PMID:8648743

  2. trans-dominant interference with virus infection at two different stages by a mutant envelope protein of Friend murine leukemia virus.

    PubMed Central

    Matano, T; Odawara, T; Ohshima, M; Yoshikura, H; Iwamoto, A

    1993-01-01

    A dominant negative mutant Friend murine leukemia virus (FMLV) env gene was cloned from an immunoselected Friend erythroleukemia cell. The mutant env had a point mutation which resulted in a Cys-to-Arg substitution at the 361st amino acid in the FMLV envelope protein (Env). The mutant Env was retained in the endoplasmic reticulum (ER) and accumulated because of its slow degradation. The NIH 3T3 cells expressing the mutant env were resistant to ecotropic Moloney MLV (MoMLV) penetration, suggesting that the mutant Env traps the ecotropic MLV receptors in the ER. When the mutant env gene was transfected into and expressed in the cells persistently infected with MoMLV, the wild-type Env was trapped in the ER, and the MoMLV production was suppressed. Thus, the mutant Env accumulating in the ER trans-dominantly and efficiently interfered with the ecotropic MLV infection at both the early and the late stages. Images PMID:8445721

  3. Comparative proteomic analysis reveals that T3SS, Tfp, and xanthan gum are key factors in initial stages of Citrus sinensis infection by Xanthomonas citri subsp. citri.

    PubMed

    Facincani, Agda P; Moreira, Leandro M; Soares, Márcia R; Ferreira, Cristiano B; Ferreira, Rafael M; Ferro, Maria I T; Ferro, Jesus A; Gozzo, Fabio C; de Oliveira, Julio C F

    2014-03-01

    The bacteria Xanthomonas citri subsp. citri (Xac) is the causal agent of citrus canker. The disease symptoms are characterized by localized host cell hyperplasia followed by tissue necrosis at the infected area. An arsenal of bacterial pathogenicity- and virulence-related proteins is expressed to ensure a successful infection process. At the post-genomic stage of Xac, we used a proteomic approach to analyze the proteins that are displayed differentially over time when the pathogen attacks the host plant. Protein extracts were prepared from infectious Xac grown in inducing medium (XAM1) for 24 h or from host citrus plants for 3 or 5 days after infection, detached times to evaluate the adaptation and virulence of the pathogen. The protein extracts were proteolyzed, and the peptides derived from tryptic digestion were investigated using liquid chromatography and tandem mass spectrometry. Changes in the protein expression profile were compared with the Xac genome and the proteome recently described under non-infectious conditions. An analysis of the proteome of Xac under infectious conditions revealed proteins directly involved in virulence such as the type III secretion system (T3SS) and effector proteins (T3SS-e), the type IV pilus (Tfp), and xanthan gum biosynthesis. Moreover, four new mutants related to proteins detected in the proteome and with different functions exhibited reduced virulence relative to the wild-type proteins. The results of the proteome analysis of infectious Xac define the processes of adaptation to the host and demonstrate the induction of the virulence factors of Xac involved in plant-pathogen interactions.

  4. Soil moisture modulates the effects of the timing and amount of rainfall on faecal moisture and development of Haemonchus contortus and Trichostrongylus colubriformis to infective third stage larvae.

    PubMed

    Khadijah, S; Kahn, L P; Walkden-Brown, S W; Bailey, J N; Bowers, S F

    2013-09-23

    Recent experiments on the effects of rainfall and/or soil moisture (SM) on development of sheep gastro-intestinal nematodes to infective L3 stage have used soil of relatively low moisture content in small experimental samples that dry out faster than field soil. To determine whether higher and more sustained SM content modulates the effects of rainfall amount and timing on faecal moisture (FM) and development of H. contortus and T. colubriformis to infective third stage larvae (L3), a climate-controlled chamber experiment was conducted. It was designed to test the effects of rainfall amount (0, 12 and 24 mm), rainfall timing (days -1, 0 and 3 relative to faecal deposition) and soil moisture maintained at 10, 20 and 30% on these variables. Total recovery of L3 14 days after faecal deposition was significantly affected by SM, rainfall timing and their interaction (P<0.01), but not by rainfall amount or species or other two-way interactions. Recovery of L3 was maximal (28%) with a SM treatment of 30% and simulated rainfall on day 3. Faecal moisture was significantly affected by collection day, SM treatment, rainfall amount and rainfall timing with significant interaction between many of these effects (P<0.05). A positive linear association between FM and total L3 recovery was strongest on day 4 after faecal deposition (R(2)=0.64, P<0.001) for H. contortus and day 6 (R(2)=0.78, P<0.001) for T. colubriformis. Overall the results show that SM is able to modulate the effects of rainfall timing and amount with increased SM acting to broaden the window of opportunity for the free-living stages to respond to post deposition rainfall to complete development to L3. If SM is maintained in the range 10-30%, the reported benefits of early rainfall (days -1 and 0) of up to 24 mm appear to be negated with later rainfall (day 3) proving more beneficial. These results require field confirmation.

  5. Soil moisture modulates the effects of the timing and amount of rainfall on faecal moisture and development of Haemonchus contortus and Trichostrongylus colubriformis to infective third stage larvae.

    PubMed

    Khadijah, S; Kahn, L P; Walkden-Brown, S W; Bailey, J N; Bowers, S F

    2013-09-23

    Recent experiments on the effects of rainfall and/or soil moisture (SM) on development of sheep gastro-intestinal nematodes to infective L3 stage have used soil of relatively low moisture content in small experimental samples that dry out faster than field soil. To determine whether higher and more sustained SM content modulates the effects of rainfall amount and timing on faecal moisture (FM) and development of H. contortus and T. colubriformis to infective third stage larvae (L3), a climate-controlled chamber experiment was conducted. It was designed to test the effects of rainfall amount (0, 12 and 24 mm), rainfall timing (days -1, 0 and 3 relative to faecal deposition) and soil moisture maintained at 10, 20 and 30% on these variables. Total recovery of L3 14 days after faecal deposition was significantly affected by SM, rainfall timing and their interaction (P<0.01), but not by rainfall amount or species or other two-way interactions. Recovery of L3 was maximal (28%) with a SM treatment of 30% and simulated rainfall on day 3. Faecal moisture was significantly affected by collection day, SM treatment, rainfall amount and rainfall timing with significant interaction between many of these effects (P<0.05). A positive linear association between FM and total L3 recovery was strongest on day 4 after faecal deposition (R(2)=0.64, P<0.001) for H. contortus and day 6 (R(2)=0.78, P<0.001) for T. colubriformis. Overall the results show that SM is able to modulate the effects of rainfall timing and amount with increased SM acting to broaden the window of opportunity for the free-living stages to respond to post deposition rainfall to complete development to L3. If SM is maintained in the range 10-30%, the reported benefits of early rainfall (days -1 and 0) of up to 24 mm appear to be negated with later rainfall (day 3) proving more beneficial. These results require field confirmation. PMID:23632251

  6. Rates of cardiovascular events and deaths are associated with advanced stages of HIV-infection: results of the HIV HEART study 7, 5 year follow-up

    PubMed Central

    Esser, Stefan; Eisele, Lewin; Schwarz, Birte; Schulze, Christina; Holzendorf, Volker; Brockmeyer, Nobert H; Hower, Martin; Kwirant, Friedhelm; Rudolph, Roland; Neumann, Till; Reinsch, Nico

    2014-01-01

    Introduction Cardiovascular diseases are increasing in aging HIV-positive patients (HIV+). Impact of traditional cardiovascular risk factors, HIV-specific parameters and antiretroviral therapy (ART) on the incidence of cardiovascular events (CVE) and on the mortality rate are investigated in different HIV+ cohorts. Methods The HIV HEART (HIVH) study is an ongoing prospective observational cohort study in the German Ruhr area to assess the frequency and clinical course of cardiac disorders in 1481 HIV+ by standardized non-invasive cardiovascular screening. CVE were defined as diagnosed or documented myocardial infarction, coronary heart disease, arterial coronary intervention, stent implantation, bypass operation and stroke. Results 1481 HIV+ subjects (mean age: 49.3±10.7 years (y), female: 15.6%) were included. 130 CVE and 90 deaths were documented until the end of 7, 5 year follow-up of HIVH. Mean duration of the HIV-infection was 12.9±6.8 y. HIV+ were treated with ART on average for 8.6±6.8 y. According to the CDC classification of the HIV-infection, HIV+ were distributed over the clinical categories (A:34.6%; B:31.4% and C:33.9%) while more than the half had an advanced immunodeficiency (I:8.3%; II:41.1%; III:50.7%). Advanced clinical and immunological stages were significantly (p<0.001) associated with higher incidences of deaths (A:16.7%; B:26.7%; C:56.7% and I:6.7%; II:27.7%; III:65.6%) and CVE (A:17.7%; B:33.1%; C:49.2% and I:3.1%; II:32.3%; III:64.6%) but not with the duration of HIV-infection (per y: Hazard ratio (HR): 0.91 [0.88–0.94]) and ART (per y: HR: 0.81 [0.79–0.84]) adjusted for age. The proportion of deceased HIV+ with HIV-RNA ≥50 copies/mL and lower CD4-cell counts at their last visit is significantly higher compared with living HIV+ without CVE (HIV-RNA ≥50 copies/mL: 25.6% vs 14.7%). Median CD4-cells: 286.5 cells/µL (IQR: 168.8–482.8) versus 574 cells/µL (IQR: 406–786). 96.1% of the living HIV+ with CVE had HIV-RNA<50 copies

  7. A glass fiber-reinforced composite - bioactive glass cranioplasty implant: A case study of an early development stage implant removed due to a late infection.

    PubMed

    Posti, Jussi P; Piitulainen, Jaakko M; Hupa, Leena; Fagerlund, Susanne; Frantzén, Janek; Aitasalo, Kalle M J; Vuorinen, Ville; Serlo, Willy; Syrjänen, Stina; Vallittu, Pekka K

    2015-03-01

    This case study describes the properties of an early development stage bioactive glass containing fiber-reinforced composite calvarial implant with histology that has been in function for two years and three months. The patient is a 33-year old woman with a history of substance abuse, who sustained a severe traumatic brain injury later unsuccessfully treated with an autologous bone flap and a custom-made porous polyethylene implant. She was thereafter treated with developmental stage glass fiber-reinforced composite - bioactive glass implant. After two years and three months, the implant was removed due to an implant site infection. The implant was analyzed histologically, mechanically, and in terms of chemistry and dissolution of bioactive glass. Mechanical integrity of the load bearing fiber-reinforced composite part of the implant was not affected by the in vivo period. Bioactive glass particles demonstrated surface layers of hydroxyapatite like mineral and dissolution, and related increase of pH was considerably less after two and three months period than that for fresh bioactive glass. There was a difference in the histology of the tissues inside the implant areas near to the margin of the implant that absorbed blood during implant installation surgery, showed fibrous tissue with blood vessels, osteoblasts, collagenous fibers with osteoid formation, and tiny clusters of more mature hard tissue. In the center of the implant, where there was less absorbed blood, only fibrous tissue was observed. This finding is in line with the combined positron emission tomography - computed tomography examination with (18F)-fluoride marker, which demonstrated activity of the mineralizing bone by osteoblasts especially at the area near to the margin of the implant 10 months after implantation. Based on these promising reactions found in the bioactive glass containing fiber-reinforced composite implant that has been implanted for two years and three months, calvarial

  8. A glass fiber-reinforced composite - bioactive glass cranioplasty implant: A case study of an early development stage implant removed due to a late infection.

    PubMed

    Posti, Jussi P; Piitulainen, Jaakko M; Hupa, Leena; Fagerlund, Susanne; Frantzén, Janek; Aitasalo, Kalle M J; Vuorinen, Ville; Serlo, Willy; Syrjänen, Stina; Vallittu, Pekka K

    2015-03-01

    This case study describes the properties of an early development stage bioactive glass containing fiber-reinforced composite calvarial implant with histology that has been in function for two years and three months. The patient is a 33-year old woman with a history of substance abuse, who sustained a severe traumatic brain injury later unsuccessfully treated with an autologous bone flap and a custom-made porous polyethylene implant. She was thereafter treated with developmental stage glass fiber-reinforced composite - bioactive glass implant. After two years and three months, the implant was removed due to an implant site infection. The implant was analyzed histologically, mechanically, and in terms of chemistry and dissolution of bioactive glass. Mechanical integrity of the load bearing fiber-reinforced composite part of the implant was not affected by the in vivo period. Bioactive glass particles demonstrated surface layers of hydroxyapatite like mineral and dissolution, and related increase of pH was considerably less after two and three months period than that for fresh bioactive glass. There was a difference in the histology of the tissues inside the implant areas near to the margin of the implant that absorbed blood during implant installation surgery, showed fibrous tissue with blood vessels, osteoblasts, collagenous fibers with osteoid formation, and tiny clusters of more mature hard tissue. In the center of the implant, where there was less absorbed blood, only fibrous tissue was observed. This finding is in line with the combined positron emission tomography - computed tomography examination with (18F)-fluoride marker, which demonstrated activity of the mineralizing bone by osteoblasts especially at the area near to the margin of the implant 10 months after implantation. Based on these promising reactions found in the bioactive glass containing fiber-reinforced composite implant that has been implanted for two years and three months, calvarial

  9. Susceptibility of zona-intact and zona-free in vitro-produced bovine embryos at different stages of development to infection with bovine herpesvirus-1.

    PubMed

    Vanroose, G; Nauwynck, H; Van Soom, A; Vanopdenbosch, E; de Kruif, A

    1997-05-01

    The aim of the present study was to determine if BHV-1 is able to replicate within in vitro produced embryos and to investigate the degree to which the zona pellucida (ZP) is able to protect in vitro produced embryos against infection with BHV-1. Both ZP-intact and ZP-free matured oocytes, zygotes (1 d post insemination; 1dpi), 8-cell stage embryos (3 dpi), morulae (6 dpi) were incubated for 1 h in 1 ml of MEM containing 10(7.7) TCID(50)/ml BHV-1 (Cooper strain). Three titers (10(5.7), 10(6.7) and 10(7.7) TCID(50)/ml) of the Cooper strain were used for incubation of hatched blastocysts (9 dpi). Bovine embryonic lung cells (BEL) on microcarriers were inoculated following the same protocol as for the embryos. At 0, 12, 24, 36 and 48 h post inoculation (hpi), groups of embryos and BEL cells were collected for virus titration and for the determination of the percentage of viral antigen positive cells by immunofluorescence. For the 3 developmental stages in ZP-free embryos, similar maximal intracellular virus progeny titers were obtained at 24 to 48 hpi ranging from 10(1.32) to 10(1.43) TCID(50)/ 100 embryonic cells. The intracellular virus titer in the BEL cells peaked at 10(3.08) TCID(50)/ 100 BEL cells. The percentage of cells which expressed viral antigens was 13% in ZP-free hatched blastocysts, 17% in ZP-free morulae and 100% in BEL cells. In ZP-intact embryos, no replication of BHV-1 was detected. These results clearly show that only after removal of the zona pellucida, BHV-1 is able to replicate within the in vitro produced embryos, with only a subset of embryonic cells being fully susceptible.

  10. Single or dual experimental infections with Vibrio aestuarianus and OsHV-1 in diploid and triploid Crassostrea gigas at the spat, juvenile and adult stages.

    PubMed

    Azéma, Patrick; Travers, Marie-Agnès; Benabdelmouna, Abdellah; Dégremont, Lionel

    2016-09-01

    French production of the Pacific cupped oyster, Crassostrea gigas, is currently threatened by two pathogens, OsHV-1 and V. aestuarianus. While oysters selected for their higher resistance to OsHV-1 are now available for the industry, the impact of V. aestuarianus on such oysters is unknown, especially for triploids. In addition, experimental infection has used the virus or the bacteria alone, but there have been no investigations of dual exposure to these pathogens. This study is the first report of single or dual exposure in spat (Spat1 and Spat2), juvenile and adult naïve oysters. For each of the two stocks evaluated, unselected oysters and oysters selected for their higher resistance to OsHV-1 infection were tested, as well as their triploid siblings of the selected oysters produced using cytochalasin B. We confirmed that resistance to OsHV-1 infection and susceptibility to V. aestuarianus increased with age and size, although selected oysters were not significantly impacted by OsHV-1 whatever their ploidy, size or age. We found different mortality patterns depending on the pathogen tested. The mortality pattern was similar for oysters exposed to OsHV-1 or to both pathogens in the Spat1 trial (4months old and 1.9g). The mortality pattern was similar for oysters exposed to V. aestuarianus or to both pathogens in the Adult trial (25months old and 63.1g). Surprisingly, mortality was much higher (ranging from 75.9% to 100%), in particular for the selected oysters, for the Spat2 (8months old/3.9g) and Juvenile trials (16months old/18.4g) given a dual exposure, regardless of the level of selection for OsHV-1 and the ploidy state. Our findings highlight an important threat for oyster farmers: oysters exposed to both pathogens could experience dramatic mortality rates, even in oysters selected for their higher resistance to OsHV-1. Finally, our study demonstrated for the first time that triploid oysters were more susceptible to experimental challenges with V

  11. A PfRH5-based vaccine is efficacious against heterologous strain blood-stage Plasmodium falciparum infection in aotus monkeys.

    PubMed

    Douglas, Alexander D; Baldeviano, G Christian; Lucas, Carmen M; Lugo-Roman, Luis A; Crosnier, Cécile; Bartholdson, S Josefin; Diouf, Ababacar; Miura, Kazutoyo; Lambert, Lynn E; Ventocilla, Julio A; Leiva, Karina P; Milne, Kathryn H; Illingworth, Joseph J; Spencer, Alexandra J; Hjerrild, Kathryn A; Alanine, Daniel G W; Turner, Alison V; Moorhead, Jeromy T; Edgel, Kimberly A; Wu, Yimin; Long, Carole A; Wright, Gavin J; Lescano, Andrés G; Draper, Simon J

    2015-01-14

    Antigenic diversity has posed a critical barrier to vaccine development against the pathogenic blood-stage infection of the human malaria parasite Plasmodium falciparum. To date, only strain-specific protection has been reported by trials of such vaccines in nonhuman primates. We recently showed that P. falciparum reticulocyte binding protein homolog 5 (PfRH5), a merozoite adhesin required for erythrocyte invasion, is highly susceptible to vaccine-inducible strain-transcending parasite-neutralizing antibody. In vivo efficacy of PfRH5-based vaccines has not previously been evaluated. Here, we demonstrate that PfRH5-based vaccines can protect Aotus monkeys against a virulent vaccine-heterologous P. falciparum challenge and show that such protection can be achieved by a human-compatible vaccine formulation. Protection was associated with anti-PfRH5 antibody concentration and in vitro parasite-neutralizing activity, supporting the use of this in vitro assay to predict the in vivo efficacy of future vaccine candidates. These data suggest that PfRH5-based vaccines have potential to achieve strain-transcending efficacy in humans.

  12. Characterization and cloning of metallo-proteinase in the excretory/secretory products of the infective-stage larva of Trichinella spiralis.

    PubMed

    Lun, H M; Mak, C H; Ko, R C

    2003-05-01

    Inhibitor sensitivity assays using azocaesin and FTC-caesin as substrates showed that the excretory/secretory (E/S) products of the infective-stage larvae of Trichinella spiralis contained serine, metallo-, cysteine and aspartic proteinases. The activity of the metallo-proteinase was zinc ion dependent (within a range of ZnSO(4) concentrations). Gelatin-substrate gel electrophoresis revealed two bands of molecular mass 48 and 58 kDa which were sensitive to the metallo-proteinase inhibitor EDTA. The former peptide was probably a cleavage product of the latter. The authenticity of the 58 kDa metallo-proteinase as an E/S product was confirmed by immunoprecipitation. Using PCR and RACE reactions, a complete nucleotide sequence of the metallo-proteinase gene was obtained. It comprised 2,223 bp with an open reading frame encoding 604 amino acid residues. The 3' untranslated region consisted of 352 bp, including a polyadenylation signal AATAA. A consensus catalytic zinc-binding motif was present. The conserved domains suggest that the cloned metallo-proteinase belongs to the astacin family and occurs as a single copy gene with 11 introns and 10 exons. Cluster analysis showed that the sequence of the metallo-proteinase gene of T. spiralis resembles those of Caenorhabdites elegans and Strongyloides stercoralis. PMID:12743801

  13. Evaluation of viral load thresholds for predicting new WHO Stage 3 and 4 events in HIV-infected children receiving highly active antiretroviral therapy

    PubMed Central

    Siberry, George K; Harris, D. Robert; Oliveira, Ricardo Hugo; Krauss, Margot R.; Hofer, Cristina B.; Tiraboschi, Adriana Aparecida; Marques, Heloisa; Succi, Regina C.; Abreu, Thalita; Negra, Marinella Della; Mofenson, Lynne M.; Hazra, Rohan

    2012-01-01

    Background This study evaluated a wide range of viral load (VL) thresholds to identify a cut-point that best predicts new clinical events in children on stable highly-active antiretroviral therapy (HAART). Methods Cox proportional hazards modeling was used to assess the adjusted risk of World Health Organization stage 3 or 4 clinical events (WHO events) as a function of time-varying CD4, VL, and hemoglobin values in a cohort study of Latin American children on HAART ≥ 6 months. Models were fit using different VL cut-points between 400 and 50,000 copies/mL, with model fit evaluated on the basis of the minimum Akaike Information Criterion (AIC) value, a standard model fit statistic. Results Models were based on 67 subjects with WHO events out of 550 subjects on study. The VL cutpoints of > 2600 copies/mL and > 32,000 copies/mL corresponded to the lowest AIC values and were associated with the highest hazard ratios [2.0 (p = 0.015) and 2.1 (p = 0.0058), respectively] for WHO events. Conclusions In HIV-infected Latin American children on stable HAART, two distinct VL thresholds (> 2,600 copies/mL and > 32,000 copies/mL) were identified for predicting children at significantly increased risk of HIV-related clinical illness, after accounting for CD4 level, hemoglobin level, and other significant factors. PMID:22343177

  14. A PfRH5-Based Vaccine Is Efficacious against Heterologous Strain Blood-Stage Plasmodium falciparum Infection in Aotus Monkeys

    PubMed Central

    Douglas, Alexander D.; Baldeviano, G. Christian; Lucas, Carmen M.; Lugo-Roman, Luis A.; Crosnier, Cécile; Bartholdson, S. Josefin; Diouf, Ababacar; Miura, Kazutoyo; Lambert, Lynn E.; Ventocilla, Julio A.; Leiva, Karina P.; Milne, Kathryn H.; Illingworth, Joseph J.; Spencer, Alexandra J.; Hjerrild, Kathryn A.; Alanine, Daniel G.W.; Turner, Alison V.; Moorhead, Jeromy T.; Edgel, Kimberly A.; Wu, Yimin; Long, Carole A.; Wright, Gavin J.; Lescano, Andrés G.; Draper, Simon J.

    2015-01-01

    Summary Antigenic diversity has posed a critical barrier to vaccine development against the pathogenic blood-stage infection of the human malaria parasite Plasmodium falciparum. To date, only strain-specific protection has been reported by trials of such vaccines in nonhuman primates. We recently showed that P. falciparum reticulocyte binding protein homolog 5 (PfRH5), a merozoite adhesin required for erythrocyte invasion, is highly susceptible to vaccine-inducible strain-transcending parasite-neutralizing antibody. In vivo efficacy of PfRH5-based vaccines has not previously been evaluated. Here, we demonstrate that PfRH5-based vaccines can protect Aotus monkeys against a virulent vaccine-heterologous P. falciparum challenge and show that such protection can be achieved by a human-compatible vaccine formulation. Protection was associated with anti-PfRH5 antibody concentration and in vitro parasite-neutralizing activity, supporting the use of this in vitro assay to predict the in vivo efficacy of future vaccine candidates. These data suggest that PfRH5-based vaccines have potential to achieve strain-transcending efficacy in humans. PMID:25590760

  15. Hierarchical Cluster Analysis of Three-Dimensional Reconstructions of Unbiased Sampled Microglia Shows not Continuous Morphological Changes from Stage 1 to 2 after Multiple Dengue Infections in Callithrix penicillata

    PubMed Central

    Diniz, Daniel G.; Silva, Geane O.; Naves, Thaís B.; Fernandes, Taiany N.; Araújo, Sanderson C.; Diniz, José A. P.; de Farias, Luis H. S.; Sosthenes, Marcia C. K.; Diniz, Cristovam G.; Anthony, Daniel C.; da Costa Vasconcelos, Pedro F.; Picanço Diniz, Cristovam W.

    2016-01-01

    It is known that microglial morphology and function are related, but few studies have explored the subtleties of microglial morphological changes in response to specific pathogens. In the present report we quantitated microglia morphological changes in a monkey model of dengue disease with virus CNS invasion. To mimic multiple infections that usually occur in endemic areas, where higher dengue infection incidence and abundant mosquito vectors carrying different serotypes coexist, subjects received once a week subcutaneous injections of DENV3 (genotype III)-infected culture supernatant followed 24 h later by an injection of anti-DENV2 antibody. Control animals received either weekly anti-DENV2 antibodies, or no injections. Brain sections were immunolabeled for DENV3 antigens and IBA-1. Random and systematic microglial samples were taken from the polymorphic layer of dentate gyrus for 3-D reconstructions, where we found intense immunostaining for TNFα and DENV3 virus antigens. We submitted all bi- or multimodal morphological parameters of microglia to hierarchical cluster analysis and found two major morphological phenotypes designated types I and II. Compared to type I (stage 1), type II microglia were more complex; displaying higher number of nodes, processes and trees and larger surface area and volumes (stage 2). Type II microglia were found only in infected monkeys, whereas type I microglia was found in both control and infected subjects. Hierarchical cluster analysis of morphological parameters of 3-D reconstructions of random and systematic selected samples in control and ADE dengue infected monkeys suggests that microglia morphological changes from stage 1 to stage 2 may not be continuous. PMID:27047345

  16. Hierarchical Cluster Analysis of Three-Dimensional Reconstructions of Unbiased Sampled Microglia Shows not Continuous Morphological Changes from Stage 1 to 2 after Multiple Dengue Infections in Callithrix penicillata.

    PubMed

    Diniz, Daniel G; Silva, Geane O; Naves, Thaís B; Fernandes, Taiany N; Araújo, Sanderson C; Diniz, José A P; de Farias, Luis H S; Sosthenes, Marcia C K; Diniz, Cristovam G; Anthony, Daniel C; da Costa Vasconcelos, Pedro F; Picanço Diniz, Cristovam W

    2016-01-01

    It is known that microglial morphology and function are related, but few studies have explored the subtleties of microglial morphological changes in response to specific pathogens. In the present report we quantitated microglia morphological changes in a monkey model of dengue disease with virus CNS invasion. To mimic multiple infections that usually occur in endemic areas, where higher dengue infection incidence and abundant mosquito vectors carrying different serotypes coexist, subjects received once a week subcutaneous injections of DENV3 (genotype III)-infected culture supernatant followed 24 h later by an injection of anti-DENV2 antibody. Control animals received either weekly anti-DENV2 antibodies, or no injections. Brain sections were immunolabeled for DENV3 antigens and IBA-1. Random and systematic microglial samples were taken from the polymorphic layer of dentate gyrus for 3-D reconstructions, where we found intense immunostaining for TNFα and DENV3 virus antigens. We submitted all bi- or multimodal morphological parameters of microglia to hierarchical cluster analysis and found two major morphological phenotypes designated types I and II. Compared to type I (stage 1), type II microglia were more complex; displaying higher number of nodes, processes and trees and larger surface area and volumes (stage 2). Type II microglia were found only in infected monkeys, whereas type I microglia was found in both control and infected subjects. Hierarchical cluster analysis of morphological parameters of 3-D reconstructions of random and systematic selected samples in control and ADE dengue infected monkeys suggests that microglia morphological changes from stage 1 to stage 2 may not be continuous. PMID:27047345

  17. Assessment of humoral immune responses to blood-stage malaria antigens following ChAd63-MVA immunization, controlled human malaria infection and natural exposure.

    PubMed

    Biswas, Sumi; Choudhary, Prateek; Elias, Sean C; Miura, Kazutoyo; Milne, Kathryn H; de Cassan, Simone C; Collins, Katharine A; Halstead, Fenella D; Bliss, Carly M; Ewer, Katie J; Osier, Faith H; Hodgson, Susanne H; Duncan, Christopher J A; O'Hara, Geraldine A; Long, Carole A; Hill, Adrian V S; Draper, Simon J

    2014-01-01

    The development of protective vaccines against many difficult infectious pathogens will necessitate the induction of effective antibody responses. Here we assess humoral immune responses against two antigens from the blood-stage merozoite of the Plasmodium falciparum human malaria parasite--MSP1 and AMA1. These antigens were delivered to healthy malaria-naïve adult volunteers in Phase Ia clinical trials using recombinant replication-deficient viral vectors--ChAd63 to prime the immune response and MVA to boost. In subsequent Phase IIa clinical trials, immunized volunteers underwent controlled human malaria infection (CHMI) with P. falciparum to assess vaccine efficacy, whereby all but one volunteer developed low-density blood-stage parasitemia. Here we assess serum antibody responses against both the MSP1 and AMA1 antigens following i) ChAd63-MVA immunization, ii) immunization and CHMI, and iii) primary malaria exposure in the context of CHMI in unimmunized control volunteers. Responses were also assessed in a cohort of naturally-immune Kenyan adults to provide comparison with those induced by a lifetime of natural malaria exposure. Serum antibody responses against MSP1 and AMA1 were characterized in terms of i) total IgG responses before and after CHMI, ii) responses to allelic variants of MSP1 and AMA1, iii) functional growth inhibitory activity (GIA), iv) IgG avidity, and v) isotype responses (IgG1-4, IgA and IgM). These data provide the first in-depth assessment of the quality of adenovirus-MVA vaccine-induced antibody responses in humans, along with assessment of how these responses are modulated by subsequent low-density parasite exposure. Notable differences were observed in qualitative aspects of the human antibody responses against these malaria antigens depending on the means of their induction and/or exposure of the host to the malaria parasite. Given the continued clinical development of viral vectored vaccines for malaria and a range of other diseases

  18. Nitric Oxide is Involved in the Upregulation of IFN-γ and IL-10 mRNA Expression by CD8+ T Cells During the Blood Stages of P. chabaudi AS Infection in CBA/Ca Mice

    PubMed Central

    Legorreta-Herrera, M; Rivas-Contreras, S; Ventura-Gallegos, JL; Zentella-Dehesa, A

    2011-01-01

    Nitric oxide (NO) is involved in the clearance of several types of bacteria, viruses and parasites. Although the roles of NO and CD8+ T cells in the immune response to malaria have been extensively studied, their actual contributions during the blood stages of malaria infection remain unclear. In this work, we corroborate that serum NO levels are not associated with the in vivo elimination of the blood stages of Plasmodium chabaudi AS. In addition, we show that CD8+ T cells exhibit increased apoptosis and up regulate the expression of TNF-α mRNA on day 4 post-infection and IFN-γ and IL-10 mRNA on day 11 post-infection. Interestingly, only the levels of IFN-γ and IL-10 expression are affected when iNOS is inhibited with aminoguanidine (AG), suggesting that NO could be involved in the activation of CD8+ T cells during the blood stages of plasmodium infection. PMID:22110391

  19. Limited Interference at the Early Stage of Infection between Two Recombinant Novirhabdoviruses: Viral Hemorrhagic Septicemia Virus and Infectious Hematopoietic Necrosis Virus▿ †

    PubMed Central

    Biacchesi, Stéphane; Lamoureux, Annie; Mérour, Emilie; Bernard, Julie; Brémont, Michel

    2010-01-01

    The genome sequence of a hypervirulent novirhabdovirus, viral hemorrhagic septicemia virus (VHSV) French strain 23-75, was determined. Compared to the genome of the prototype Fil3 strain, a number of substitutions, deletions, and insertions were observed. Following the establishment of a plasmid-based minigenome replication assay, recombinant VHSV (rVHSV) was successfully recovered. rVHSV exhibits wild-type-like growth properties in vitro as well as in vivo in rainbow trout. The dispensable role of NV for the novirhabdovirus replication was confirmed by generating rVHSV-ΔNV, in which the NV gene was deleted. This deletion mutant was shown to be as debilitated as that previously described for infectious hematopoietic necrosis virus (IHNV), a distantly related novirhabdovirus (S. Biacchesi, M. I. Thoulouze, M. Bearzotti, Y. X. Yu, and M. Bremont, J. Virol. 74:11247-11253, 2000). Recombinant VHSV and IHNV expressing tdTomato and GFPmax reporter genes, respectively, were generated, demonstrating the potential of these rhabdoviruses to serve as viral vectors. Interestingly, rIHNV-GFPmax could be recovered using the replicative complex proteins of either virus, whereas rVHSV-Tomato could be recovered only by using its own replicative complex, reflecting that the genome signal sequences of VHSV are relatively distant from those of IHNV and do not allow their cross-recognition. Moreover, the use of heterologous protein combinations underlined the importance of strong protein-protein interactions for the formation of a functional ribonucleoprotein complex. The rIHNV-GFPmax and rVHSV-Tomato viruses were used to simultaneously coinfect cell monolayers. It was observed that up to 74% of the cell monolayer was coinfected by both viruses, demonstrating that a limited interference phenomenon exists during the early stage of primary infection, and it was not mediated by a cellular antiviral protein or by some of the viral proteins. PMID:20631140

  20. Parasite-Specific CD4+ IFN-γ+ IL-10+ T Cells Distribute within Both Lymphoid and Nonlymphoid Compartments and Are Controlled Systemically by Interleukin-27 and ICOS during Blood-Stage Malaria Infection.

    PubMed

    Villegas-Mendez, Ana; Shaw, Tovah N; Inkson, Colette A; Strangward, Patrick; de Souza, J Brian; Couper, Kevin N

    2016-01-01

    Immune-mediated pathology in interleukin-10 (IL-10)-deficient mice during blood-stage malaria infection typically manifests in nonlymphoid organs, such as the liver and lung. Thus, it is critical to define the cellular sources of IL-10 in these sensitive nonlymphoid compartments during infection. Moreover, it is important to determine if IL-10 production is controlled through conserved or disparate molecular programs in distinct anatomical locations during malaria infection, as this may enable spatiotemporal tuning of the regulatory immune response. In this study, using dual gamma interferon (IFN-γ)-yellow fluorescent protein (YFP) and IL-10-green fluorescent protein (GFP) reporter mice, we show that CD4(+) YFP(+) T cells are the major source of IL-10 in both lymphoid and nonlymphoid compartments throughout the course of blood-stage Plasmodium yoelii infection. Mature splenic CD4(+) YFP(+) GFP(+) T cells, which preferentially expressed high levels of CCR5, were capable of migrating to and seeding the nonlymphoid tissues, indicating that the systemically distributed host-protective cells have a common developmental history. Despite exhibiting comparable phenotypes, CD4(+) YFP(+) GFP(+) T cells from the liver and lung produced significantly larger quantities of IL-10 than their splenic counterparts, showing that the CD4(+) YFP(+) GFP(+) T cells exert graded functions in distinct tissue locations during infection. Unexpectedly, given the unique environmental conditions within discrete nonlymphoid and lymphoid organs, we show that IL-10 production by CD4(+) YFP(+) T cells is controlled systemically during malaria infection through IL-27 receptor signaling that is supported after CD4(+) T cell priming by ICOS signaling. The results in this study substantially improve our understanding of the systemic IL-10 response to malaria infection, particularly within sensitive nonlymphoid organs. PMID:26459508

  1. Parasite-Specific CD4+ IFN-γ+ IL-10+ T Cells Distribute within Both Lymphoid and Nonlymphoid Compartments and Are Controlled Systemically by Interleukin-27 and ICOS during Blood-Stage Malaria Infection

    PubMed Central

    Villegas-Mendez, Ana; Shaw, Tovah N.; Inkson, Colette A.; Strangward, Patrick; de Souza, J. Brian

    2015-01-01

    Immune-mediated pathology in interleukin-10 (IL-10)-deficient mice during blood-stage malaria infection typically manifests in nonlymphoid organs, such as the liver and lung. Thus, it is critical to define the cellular sources of IL-10 in these sensitive nonlymphoid compartments during infection. Moreover, it is important to determine if IL-10 production is controlled through conserved or disparate molecular programs in distinct anatomical locations during malaria infection, as this may enable spatiotemporal tuning of the regulatory immune response. In this study, using dual gamma interferon (IFN-γ)–yellow fluorescent protein (YFP) and IL-10–green fluorescent protein (GFP) reporter mice, we show that CD4+ YFP+ T cells are the major source of IL-10 in both lymphoid and nonlymphoid compartments throughout the course of blood-stage Plasmodium yoelii infection. Mature splenic CD4+ YFP+ GFP+ T cells, which preferentially expressed high levels of CCR5, were capable of migrating to and seeding the nonlymphoid tissues, indicating that the systemically distributed host-protective cells have a common developmental history. Despite exhibiting comparable phenotypes, CD4+ YFP+ GFP+ T cells from the liver and lung produced significantly larger quantities of IL-10 than their splenic counterparts, showing that the CD4+ YFP+ GFP+ T cells exert graded functions in distinct tissue locations during infection. Unexpectedly, given the unique environmental conditions within discrete nonlymphoid and lymphoid organs, we show that IL-10 production by CD4+ YFP+ T cells is controlled systemically during malaria infection through IL-27 receptor signaling that is supported after CD4+ T cell priming by ICOS signaling. The results in this study substantially improve our understanding of the systemic IL-10 response to malaria infection, particularly within sensitive nonlymphoid organs. PMID:26459508

  2. Dysregulated expression of IFN-γ and IL-10 and impaired IFN-γ-mediated responses at different disease stages in patients with genital herpes simplex virus-2 infection

    PubMed Central

    SINGH, R; KUMAR, A; CREERY, W D; RUBEN, M; GIULIVI, A; DIAZ-MITOMA, F

    2003-01-01

    Cell-mediated T-helper type-1 (Th1) responses play a vital role in the immunopathogenesis of genital infections caused by herpes simplex virus 2 (HSV-2). We investigated the role of Th responses in HSV-2 infection at different disease stages by analysing the production of Th cytokines in HSV-stimulated peripheral blood mononuclear cells (PBMCs). IFN-γ production decreased over time following a recurrence, whereas levels of IL-10, and to a lesser extent IL-2, remained elevated during this period. In addition, PBMCs from asymptomatic seropositive individuals produced high levels of IFN-γ and low levels of IL-10, in contrast to individuals with a history of genital ulcers. Following a recurrence, virus copy number in the genital lesions decreased progressively over time, in a manner similar to IFN-γ production by HSV-2-stimulated PBMCs. Enhanced production of IFN-γ may modulate HSV replication and B7 expression on monocytic cells of HSV-infected individuals. In contrast to seronegative controls, IFN-γ failed to enhance B7 expression on monocytic cells of HSV-infected individuals. In addition, monocytic cells from HSV-2-infected individuals with recurrent disease supported greater HSV replication than did those of HSV-infected asymptomatic individuals or seronegative controls. Furthermore, addition of IFN-γ resulted in enhanced HSV replication in monocytic cells of HSV-infected individuals with recurrent disease, in contrast to the inhibition observed in HSV-seropositive asymptomatic individuals and seronegative controls. Taken together, our results suggest that dysregulated production of IFN-γ at different disease stages and the impaired ability of monocytic cells to respond to IFN-γ may play a role in the pathogenesis of recurrent genital herpes disease. PMID:12823283

  3. Factors associated with initiation of antiretroviral therapy in the advanced stages of HIV infection in six Ethiopian HIV clinics, 2012 to 2013

    PubMed Central

    Nash, Denis; Tymejczyk, Olga; Gadisa, Tsigereda; Kulkarni, Sarah Gorrell; Hoffman, Susie; Yigzaw, Muluneh; Elul, Batya; Remien, Robert H; Lahuerta, Maria; Daba, Shalo; El Sadr, Wafaa; Melaku, Zenebe

    2016-01-01

    Introduction Most HIV-positive persons in sub-Saharan Africa initiate antiretroviral therapy (ART) with advanced infection (late ART initiation). Intervening on the drivers of late ART initiation is a critical step towards achieving the full potential of HIV treatment scale-up. This study aimed to identify modifiable factors associated with late ART initiation in Ethiopia. Methods From 2012 to 2013, Ethiopian adults (n=1180) were interviewed within two weeks of ART initiation. Interview data were merged with HIV care histories to assess correlates of late ART initiation (CD4+ count <150 cells/µL or World Health Organization Stage IV). Results The median CD4 count at enrolment in HIV care was 263 cells/µL (interquartile range (IQR): 140 to 390) and 212 cells/µL (IQR: 119 to 288) at ART initiation. Overall, 31.2% of participants initiated ART late, of whom 85.1% already had advanced HIV disease at enrolment. Factors associated with higher odds of late ART initiation included male sex (vs. non-pregnant females; adjusted odds ratio (aOR): 2.02; 95% CI: 1.50 to 2.73), high levels of psychological distress (vs. low/none, aOR: 1.96; 95% CI: 1.34 to 2.87), perceived communication barriers with providers (aOR: 2.42, 95% CI: 1.24 to 4.75), diagnosis via provider initiated testing (vs. voluntary counselling and testing, aOR: 1.47, 95% CI: 1.07 to 2.04), tuberculosis (TB) treatment prior to ART initiation (aOR: 2.16, 95% CI: 1.43 to 3.25) and a gap in care of six months or more prior to ART initiation (aOR: 2.02, 95% CI: 1.10 to 3.72). Testing because of partner illness/death (aOR: 0.64, 95% CI: 0.42 to 0.95) was associated with lower odds of late ART initiation. Conclusions Programmatic initiatives promoting earlier diagnosis, engagement in pre-ART care, and integration of TB and HIV treatments may facilitate earlier ART initiation. Men and those experiencing psychological distress may also benefit from targeted support prior to ART initiation. PMID:27113335

  4. Evidence of MRSE on a gentamicin and vancomycin impregnated polymethyl-methacrylate (PMMA) bone cement spacer after two-stage exchange arthroplasty due to periprosthetic joint infection of the knee

    PubMed Central

    2014-01-01

    Background Periprosthetic joint infections (PJI) are often treated by two stage exchange with the use of an antibiotic impregnated spacer. Most of the two-stage exchange algorithms recommend the implantation of an antibiotic-impregnated spacer during the first stage for a period of 2–24 weeks before reimplantation of the new prosthesis. For the spacer to have a therapeutic effect, the local antibiotic concentration must be greater than the minimal inhibition concentration (MIC) against the pathogens causing the PJI. It must remain so for the entire spacer period, otherwise recurrence of infection or resistances might occur. The question as to whether a sufficient concentration of antibiotics in vivo is reached for the entire spacer period has not been answered satisfactorily. Case presentation We here present a case of a histologically confirmed chronic PJI 20 month after primary arthroplasty. The primary knee arthroplasty was performed due to osteoarthritis of the joint. Initial assessment did not detect a causative pathogen, and two stage exchange with a vancomycin-gentamycin impregnated spacer was performed. At the time of reimplantation, sonication of the explanted spacer revealed a multi-resistant strain of staphylococcus epidermidis on the device and in the joint. Adaption of the therapy and prolonged treatment successfully eradicated the infection. Conclusion According to the authors’ knowledge, the case presented here confirms for the first time the surface contamination (proven through sonication) of a vancomycin-/gentamicin- impregnated Vancogenx®-spacer with a MRSE after ten weeks of implantation. This case study demonstrates the difficulties still associated with the diagnostics of PJI and the published different two stage treatment regimes with the use of antibiotic impregnated spacers. PMID:24641471

  5. A multi-stage compartmental model for HIV-infected individuals: II--application to insurance functions and health-care costs.

    PubMed

    Billard, L; Dayananda, P W A

    2014-03-01

    Stochastic population processes have received a lot of attention over the years. One approach focuses on compartmental modeling. Billard and Dayananda (2012) developed one such multi-stage model for epidemic processes in which the possibility that individuals can die at any stage from non-disease related causes was also included. This extra feature is of particular interest to the insurance and health-care industries among others especially when the epidemic is HIV/AIDS. Rather than working with numbers of individuals in each stage, they obtained distributional results dealing with the waiting time any one individual spent in each stage given the initial stage. In this work, the impact of the HIV/AIDS epidemic on several functions relevant to these industries (such as adjustments to premiums) is investigated. Theoretical results are derived, followed by a numerical study.

  6. Targeting of a Fixed Bacterial Immunogen to Fc Receptors Reverses the Anti-Inflammatory Properties of the Gram-Negative Bacterium, Francisella tularensis, during the Early Stages of Infection

    PubMed Central

    Babadjanova, Zulfia; Wiedinger, Kari; Gosselin, Edmund J.; Bitsaktsis, Constantine

    2015-01-01

    Production of pro-inflammatory cytokines by innate immune cells at the early stages of bacterial infection is important for host protection against the pathogen. Many intracellular bacteria, including Francisella tularensis, the agent of tularemia, utilize the anti-inflammatory cytokine IL-10, to evade the host immune response. It is well established that IL-10 has the ability to inhibit robust antigen presentation by dendritic cells and macrophages, thus suppressing the generation of protective immunity. The pathogenesis of F. tularensis is not fully understood, and research has failed to develop an effective vaccine to this date. In the current study, we hypothesized that F. tularensis polarizes antigen presenting cells during the early stages of infection towards an anti-inflammatory status characterized by increased synthesis of IL-10 and decreased production of IL-12p70 and TNF-α in an IFN-ɣ-dependent fashion. In addition, F. tularensis drives an alternative activation of alveolar macrophages within the first 48 hours post-infection, thus allowing the bacterium to avoid protective immunity. Furthermore, we demonstrate that targeting inactivated F. tularensis (iFt) to Fcγ receptors (FcɣRs) via intranasal immunization with mAb-iFt complexes, a proven vaccine strategy in our laboratories, reverses the anti-inflammatory effects of the bacterium on macrophages by down-regulating production of IL-10. More specifically, we observed that targeting of iFt to FcγRs enhances the classical activation of macrophages not only within the respiratory mucosa, but also systemically, at the early stages of infection. These results provide important insight for further understanding the protective immune mechanisms generated when targeting immunogens to Fc receptors. PMID:26114641

  7. Infection of Mouse Macrophages by Seasonal Influenza Viruses Can Be Restricted at the Level of Virus Entry and at a Late Stage in the Virus Life Cycle

    PubMed Central

    Londrigan, Sarah L.; Short, Kirsty R.; Ma, Joel; Gillespie, Leah; Rockman, Steven P.; Brooks, Andrew G.

    2015-01-01

    ABSTRACT Airway epithelial cells are susceptible to infection with seasonal influenza A viruses (IAV), resulting in productive virus replication and release. Macrophages (MΦ) are also permissive to IAV infection; however, virus replication is abortive. Currently, it is unclear how productive infection of MΦ is impaired or the extent to which seasonal IAV replicate in MΦ. Herein, we compared mouse MΦ and epithelial cells for their ability to support genomic replication and transcription, synthesis of viral proteins, assembly of virions, and release of infectious progeny following exposure to genetically defined IAV. We confirm that seasonal IAV differ in their ability to utilize cell surface receptors for infectious entry and that this represents one level of virus restriction. Following virus entry, we demonstrate synthesis of all eight segments of genomic viral RNA (vRNA) and mRNA, as well as seven distinct IAV proteins, in IAV-infected mouse MΦ. Although newly synthesized hemagglutinin (HA) and neuraminidase (NA) glycoproteins are incorporated into the plasma membrane and expressed at the cell surface, electron microscopy confirmed that virus assembly was defective in IAV-infected MΦ, defining a second level of restriction late in the virus life cycle. IMPORTANCE Seasonal influenza A viruses (IAV) and highly pathogenic avian influenza viruses (HPAI) infect macrophages, but only HPAI replicate productively in these cells. Herein, we demonstrate that impaired virus uptake into macrophages represents one level of restriction limiting infection by seasonal IAV. Following uptake, seasonal IAV do not complete productive replication in macrophages, representing a second level of restriction. Using murine macrophages, we demonstrate that productive infection is blocked late in the virus life cycle, such that virus assembly is defective and newly synthesized virions are not released. These studies represent an important step toward identifying host-encoded factors

  8. Gastrointestinal T Lymphocytes Retain High Potential for Cytokine Responses but Have Severe CD4+ T-Cell Depletion at All Stages of Simian Immunodeficiency Virus Infection Compared to Peripheral Lymphocytes

    PubMed Central

    Smit-McBride, Zeljka; Mattapallil, Joseph J.; McChesney, Michael; Ferrick, David; Dandekar, Satya

    1998-01-01

    Gastrointestinal complications in human immunodeficiency virus (HIV) infection are indicative of impaired intestinal mucosal immune system. We used simian immunodeficiency virus (SIV)-infected rhesus macaques as an animal model for HIV to determine pathogenic effects of SIV on intestinal T lymphocytes. Intestinal CD4+ T-cell depletion and the potential for cytokine responses were examined during SIV infection and compared with results for lymphocytes from lymph nodes and blood. Flow cytometric analysis demonstrated severe depletion of CD4+CD8− single-positive T cells and CD4+CD8+ double-positive T cells in intestinal lamina propria lymphocytes (LPL) and intraepithelial lymphocytes (IEL) during primary SIV infection which persisted through the entire course of SIV infection. In contrast, CD4+ T-cell depletion was gradual in peripheral lymph nodes and blood. Flow cytometric analysis of intracellular gamma interferon (IFN-γ) and interleukin-4 (IL-4) production following short-term mitogenic activation revealed that LPL retained same or higher capacity for IFN-γ production in all stages of SIV infection compared to uninfected controls, whereas peripheral blood mononuclear cells displayed a gradual decline. The CD8+ T cells were the major producers of IFN-γ. There was no detectable change in the frequency of IL-4-producing cells in both LPL and peripheral blood mononuclear cells. Thus, severe depletion of CD4+ LPL and IEL in primary SIV infection accompanied by altered cytokine responses may reflect altered T-cell homeostasis in intestinal mucosa. This could be a mechanism of SIV-associated enteropathy and viral pathogenesis. Dynamic changes in intestinal T lymphocytes were not adequately represented in peripheral lymph nodes or blood. PMID:9658111

  9. Effects of intra-mammary bacterial infection with coagulase negative staphylococci and stage of lactation on shedding of epithelial cells and infiltration of leukocytes into milk: comparison among cows, goats and sheep.

    PubMed

    Leitner, Gabriel; Merin, Uzi; Krifucks, Oleg; Blum, Shlomo; Rivas, Ariel L; Silanikove, Nissim

    2012-06-30

    The effects of mammary gland bacterial infection and stage of lactation on leukocyte infiltration into the mammary gland were compared among cows, goats and sheep. Animals were at two stages of lactation: mid or late. In mid-lactation animals, bacterial-free glands and coagulase negative Staphylococcus (CNS)-infected glands were compared. In late lactation only uninfected glands were studied. Of mid-lactation bacteria-free animals, goats had the highest number of leukocytes and % polymorphonuclears (PMNs), whereas sheep had the lowest and leukocytes number in cows were intermediate between sheep and goats. Based on %PMN, two cell clusters were found in sheep, which overlapped with the parallel cell clusters of cows and goats, but with a slightly higher number of leukocytes in each cell cluster. At late lactation, goats had higher values for %PMN and leukocyte numbers in comparison to cows, which had a similar cellular profile to sheep. The cellular immune response to CNS infection was similar for the three animal species, although the number of cells was different, while the basal cell level at mid-lactation and especially at the end of lactation was species specific.

  10. Monocytotropic human immunodeficiency virus type 1 (HIV-1) variants detectable in all stages of HIV-1 infection lack T-cell line tropism and syncytium-inducing ability in primary T-cell culture.

    PubMed Central

    Schuitemaker, H; Kootstra, N A; de Goede, R E; de Wolf, F; Miedema, F; Tersmette, M

    1991-01-01

    We previously demonstrated a correlation between the presence of syncytium-inducing (SI) human immunodeficiency virus type 1 (HIV-1) variants showing tropism for cell line H9 and the occurrence of rapid CD4 cell decline and progression to AIDS. In contrast, in stable asymptomatic individuals, we detected only isolates with low replication rates that were non-syncytium-inducing (NSI) and nontropic for the H9 cell line. Here, we investigated the monocytotropism of established HIV-1 isolates with a panel of isolates and with biological HIV-1 clones with distinct phenotypes. Moreover, the prevalence and biological phenotypes of monocytotropic HIV-1 variants in the course of HIV-1 infection were analyzed in comparative primary isolation studies on peripheral blood lymphocytes (PBL) and monocyte-derived macrophages (MDM). In cell-free infection studies with MDM from eight blood donors, 13 of 17 NSI isolates but only 4 of 14 SI isolates were able to infect MDM. NSI isolates also infected significantly more different donors than SI variants (median, 3 of 8 versus 0 of 8). This enhanced monocytotropism of NSI isolates was confirmed in experiments with biological HIV-1 clones with distinct phenotypes recovered from the same donor. To investigate the prevalence and biological phenotypes of monocytotropic variants in different stages of HIV-1 infection, sequential isolates from peripheral blood mononuclear cell samples from nine asymptomatic individuals, five of whom progressed to AIDS and seven of whom had a known time of seroconversion, were recovered by cocultivation with both PBL and MDM. Monocytotropic variants were obtained from 37 of 42 time points. All monocytotropic variants were NSI in PBL culture and non-T-cell-line tropic, even when SI, T-cell-line-tropic HIV-1 variants could be recovered from the same patient sample by cocultivation with PBL. We conclude that monocytotropic HIV-1 variants mostly have an NSI phenotype in PBL and, in contrast to SI variants, are

  11. Disseminated Mycobacterium abscessus Complex Infection Manifesting as Multiple Areas of Lymphadenitis and Skin Abscess in the Preclinical Stage of Acute Lymphocytic Leukemia.

    PubMed

    Tahara, Masahiro; Yatera, Kazuhiro; Yamasaki, Kei; Orihashi, Takeshi; Hirosawa, Makoto; Ogoshi, Takaaki; Noguchi, Shingo; Nishida, Chinatsu; Ishimoto, Hiroshi; Yonezawa, Akihito; Tsukada, Junichi; Mukae, Hiroshi

    2016-01-01

    A 37-year-old woman was admitted to a hospital due to a prolonged fever and a rash on her legs. She had systemic lymphadenitis and a skin abscess on her left leg. Pathological findings of a left leg skin biopsy revealed abscess formation with granulomatous dermatitis, Mycobacterium abscessus complex was cultured from the resected left supraclavicular lymph node, and disseminated M. abscessus complex infection was diagnosed. She was treated with combination treatment with antimicrobials and percutaneous drainage, and her clinical findings improved. Four months later, she developed acute lymphocytic leukemia. Leukemia is a risk factor for disseminated M. abscessus complex infection, even before developing leukemia.

  12. Disseminated Mycobacterium abscessus Complex Infection Manifesting as Multiple Areas of Lymphadenitis and Skin Abscess in the Preclinical Stage of Acute Lymphocytic Leukemia.

    PubMed

    Tahara, Masahiro; Yatera, Kazuhiro; Yamasaki, Kei; Orihashi, Takeshi; Hirosawa, Makoto; Ogoshi, Takaaki; Noguchi, Shingo; Nishida, Chinatsu; Ishimoto, Hiroshi; Yonezawa, Akihito; Tsukada, Junichi; Mukae, Hiroshi

    2016-01-01

    A 37-year-old woman was admitted to a hospital due to a prolonged fever and a rash on her legs. She had systemic lymphadenitis and a skin abscess on her left leg. Pathological findings of a left leg skin biopsy revealed abscess formation with granulomatous dermatitis, Mycobacterium abscessus complex was cultured from the resected left supraclavicular lymph node, and disseminated M. abscessus complex infection was diagnosed. She was treated with combination treatment with antimicrobials and percutaneous drainage, and her clinical findings improved. Four months later, she developed acute lymphocytic leukemia. Leukemia is a risk factor for disseminated M. abscessus complex infection, even before developing leukemia. PMID:27374685

  13. Thai koi-hoi snail dish and angiostrongyliasis due to Angiostrongylus cantonensis: Effects of food flavoring and alcoholic drink on the third-stage larvae in infected snail meat.

    PubMed

    Eamsobhana, Praphathip; Yoolek, Adisak; Punthuprapasa, Paibulaya; Yong, Hoi-Sen

    2009-04-01

    Human infection with the rat lungworm Angiostrongylus cantonensis (Parastrongylus cantonensis) in Thailand, especially in the northeastern region, is associated with the habit of eating koi-hoi, which contains raw snail meat. Infection results from the snails being carriers of the larval parasite. The present study was conducted to assess the effect of food flavorings in koi-hoi, alcohol, and exposure time of the two variable on the infective larvae of A. cantonensis. Infected Biomphalaria glabrata snails were used for koi-hoi preparation. Raw snail meat was mixed with koi-hoi flavoring and left at room temperature for various time periods ranging from 5 to 60 minutes. At a predetermined time, two pieces of snail meat were removed at random and examined for viability (as determined by motility) of the parasitic third-stage larvae. At the same time, two random pieces of snail meat were removed and treated with 10 mL of a local 40% alcoholic drink for 30 minutes before examination of larval viability. Exposure of infected snail meat for 10 minutes or more to koi-hoi food flavoring resulted in significantly more nonmotile (dying or dead) larvae. Addition of the local alcoholic drink after exposure to the flavoring exerted an additional killing effect on the larvae. Despite long exposure time, both the koi-hoi flavoring and addition of alcoholic drink were not completely effective in killing the infective larvae in the snail meat. Thorough cooking of the food intended for human consumption should still be practiced. PMID:19272010

  14. Stage design

    DOEpatents

    Shacter, J.

    1975-12-01

    A method is described of cycling gases through a plurality of diffusion stages comprising the steps of admitting the diffused gases from a first diffusion stage into an axial compressor, simultaneously admitting the undiffused gases from a second diffusion stage into an intermediate pressure zone of said compressor corresponding in pressure to the pressure of said undiffused gases, and then admitting the resulting compressed mixture of diffused and undiffused gases into a third diffusion stage.

  15. [The nature of changes of some immunophysiological characteristics in bream (Abramis brama) infected with plerocercoids (Ligula intestinalis) at various stages of parasite development].

    PubMed

    Silkina, N I; Mikriakov, V R; Mikriakov, D V

    2012-01-01

    The data from studies of the antimicrobial properties of blood serum, the content of total lipids, and antioxidant activity of immunocompetent tissues and organs of breams Abramis brama infected with plerocercoids Ligula intestinalis depending on the phase of development of the parasite are presented. The quantitative characteristics of the studied parameters are determined.

  16. Fatal Case of Brucellosis Misdiagnosed in Early Stages of Brucella suis Infection in a 46-Year-Old Patient with Marfan Syndrome

    PubMed Central

    Carrington, M.; Choe, U.; Ubillos, S.; Stanek, D.; Campbell, M.; Wansbrough, L.; Lee, P.; Churchwell, G.; Rosas, K.; Zaki, S. R.; Drew, C.; Paddock, C. D.; DeLeon-Carnes, M.; Guerra, M.; Hoffmaster, A. R.; Tiller, R. V.

    2012-01-01

    We report a fatal case of Brucella suis endocarditis initially misdiagnosed by automated identification systems as Ochrobactrum anthropi infection in a patient with a history of Marfan syndrome and recreational feral swine hunting. This report emphasizes the need to consider brucellosis as a part of the differential diagnosis of acute febrile illness, particularly in patients with known risk of exposure. PMID:22495564

  17. Life-history studies on two molecular strains of mesocestoides (Cestoda: Mesocestoididae): identification of sylvatic hosts and infectivity of immature life stages.

    PubMed

    Padgett, Kerry A; Boyce, Walter M

    2004-02-01

    Life-cycle studies were conducted on 2 molecular strains of Mesocestoides tapeworms that represent different evolutionary lineages (clades A and B). Wild carnivores, reptiles, and rodents were examined for tapeworm infections at 2 enzootic sites: (1) San Miguel Island (SMI), a small island off the coast of southern California and (2) Hopland Research and Extension Center (HREC), a field station in northern California. Results indicate that deer mice (Peromyscus maniculatus) and coyotes (Canis latrans) may play an important role in the life cycles of Mesocestoides (clades A and B) in California. Over half the coyotes at HREC and at least a third of the population of island fox (Urocyon littoralis) at SMI were found to harbor clade A adult Mesocestoides spp. One of every 4 Mesocestoides-infected coyotes had tapeworms representing both clades A and B. Experimental inoculations revealed that proglottids (clades A and B) were not directly infectious to rodents, reptiles, or dogs. On the other hand, mice, lizards, and hamsters fed tetrathyridia of Mesocestoides spp. (clades A or B) developed peritoneal tetrathyridial infections. A dog that was fed tetrathyridia (clade B) developed an adult tapeworm infection. Acephalic metacestodes given orally to western fence lizards, laboratory mice, or domestic dogs did not result in metacestode or adult tapeworm infections. Whereas most clade A acephalic metacestodes from dogs were asexually proliferative, clade A tetrathyridia isolated from wild deer mice did not show evidence of asexual replication. Our study supports the hypothesis that a second, as of yet unidentified, intermediate host is necessary to complete the life cycles of Mesocestoides spp., and that acephalic metacestodes represent an aberrant form, incapable of further development. PMID:15040675

  18. Estimation of bovine leukemia virus (BLV) proviral load harbored by lymphocyte subpopulations in BLV-infected cattle at the subclinical stage of enzootic bovine leucosis using BLV-CoCoMo-qPCR

    PubMed Central

    2013-01-01

    Background Bovine leukemia virus (BLV) is associated with enzootic bovine leukosis (EBL), which is the most common neoplastic disease of cattle. BLV infection may remain clinically silent at the aleukemic (AL) stage, cause persistent lymphocytosis (PL), or, more rarely, B cell lymphoma. BLV has been identified in B cells, CD2+ T cells, CD3+ T cells, CD4+ T cells, CD8+ T cells, γ/δ T cells, monocytes, and granulocytes in infected cattle that do not have tumors, although the most consistently infected cell is the CD5+ B cell. The mechanism by which BLV causes uncontrolled CD5+ B cell proliferation is unknown. Recently, we developed a new quantitative real-time polymerase chain reaction (PCR) method, BLV-CoCoMo-qPCR, which enabled us to demonstrate that the proviral load correlates not only with BLV infection, as assessed by syncytium formation, but also with BLV disease progression. The present study reports the distribution of BLV provirus in peripheral blood mononuclear cell subpopulations isolated from BLV-infected cows at the subclinical stage of EBL as examined by cell sorting and BLV-CoCoMo-qPCR. Results Phenotypic characterization of five BLV-infected but clinically normal cattle with a proviral load of > 100 copies per 1 × 105 cells identified a high percentage of CD5+ IgM+ cells (but not CD5- IgM+ B cells, CD4+ T cells, or CD8+T cells). These lymphocyte subpopulations were purified from three out of five cattle by cell sorting or using magnetic beads, and the BLV proviral load was estimated using BLV-CoCoMo-qPCR. The CD5+ IgM+ B cell population in all animals harbored a higher BLV proviral load than the other cell populations. The copy number of proviruses infecting CD5- IgM+ B cells, CD4+ cells, and CD8+ T cells (per 1 ml of blood) was 1/34 to 1/4, 1/22 to 1/3, and 1/31 to 1/3, respectively, compared with that in CD5+ IgM+ B cells. Moreover, the BLV provirus remained integrated into the genomic DNA of CD5+ IgM+ B cells, CD5- IgM+ B cells, CD4+ T

  19. The post-transcriptional regulator CsrA plays a central role in the adaptation of bacterial pathogens to different stages of infection in animal hosts.

    PubMed

    Lucchetti-Miganeh, Céline; Burrowes, Elizabeth; Baysse, Christine; Ermel, Gwennola

    2008-01-01

    The importance of Csr post-transcriptional systems is gradually emerging; these systems control a variety of virulence-linked physiological traits in many pathogenic bacteria. This review focuses on the central role that Csr systems play in the pathogenesis of certain bacteria and in the establishment of successful infections in animal hosts. Csr systems appear to control the 'switch' between different physiological states in the infection process; for example switching pathogens from a colonization state to a persistence state. Csr systems are controlled by two-component sensor/regulator systems and by non-coding RNAs. In addition, recent findings suggest that the RNA chaperone Hfq may play an integral role in Csr-mediated bacterial adaptation to the host environment.

  20. The post-transcriptional regulator CsrA plays a central role in the adaptation of bacterial pathogens to different stages of infection in animal hosts.

    PubMed

    Lucchetti-Miganeh, Céline; Burrowes, Elizabeth; Baysse, Christine; Ermel, Gwennola

    2008-01-01

    The importance of Csr post-transcriptional systems is gradually emerging; these systems control a variety of virulence-linked physiological traits in many pathogenic bacteria. This review focuses on the central role that Csr systems play in the pathogenesis of certain bacteria and in the establishment of successful infections in animal hosts. Csr systems appear to control the 'switch' between different physiological states in the infection process; for example switching pathogens from a colonization state to a persistence state. Csr systems are controlled by two-component sensor/regulator systems and by non-coding RNAs. In addition, recent findings suggest that the RNA chaperone Hfq may play an integral role in Csr-mediated bacterial adaptation to the host environment. PMID:18174122

  1. Cardamom Bushy Dwarf Virus Infection in Large Cardamom Alters Plant Selection Preference, Life Stages, and Fecundity of Aphid Vector, Micromyzus kalimpongensis (Hemiptera: Aphididae).

    PubMed

    Ghosh, Amalendu; Das, Amrita; Vijayanandraj, S; Mandal, Bikash

    2016-02-01

    Cardamom bushy dwarf virus (CBDV) causes foorkey disease of large cardamom (Ammomum subulatum Roxburgh) in the eastern sub-Himalayan mountains. Although the aphid Micromyzus kalimpongensis Basu (Hemiptera: Aphididae) is known as a vector of CBDV, its behavior in dissemination of CBDV has not been investigated. In the present study, M. kalimpongensis was observed to colonize in higher number on CBDV-infected large cardamom plants compared with the healthy plants in the several plantations in Sikkim and Darjeeling hills. The affinity of M. kalimpongensis to the diseased large cardamom plants was further confirmed in a contained field experiment with intact plant as well as in a laboratory bioassay with the plant extract, where significantly higher number of aphids settled on the diseased plants or extracts compared with the healthy counterparts. Aphids grown on CBDV-infected large cardamom plants had shortened nymphal period and increased longevity and fecundity compared with those grown on the healthy plants. In the contained field experiment, M. kalimpongensis migrated to the CBDV-infected plants, colonized there, acquired CBDV, and once the diseased plants withered, migrated to healthy plants, which eventually became diseased. Our results suggest a general pattern of spread of CBDV by M. kalimpongensis where CBDV-infected plants attract or arrest and stimulate emergence and migration of viruliferous aphids that otherwise are sedentary in the underground plant parts of large cardamom. To our knowledge, this is the first study that shows the influence of a plant virus from the family Nanoviridae in altering behavior of its insect vector that favors its dissemination. PMID:26518036

  2. Cardamom Bushy Dwarf Virus Infection in Large Cardamom Alters Plant Selection Preference, Life Stages, and Fecundity of Aphid Vector, Micromyzus kalimpongensis (Hemiptera: Aphididae).

    PubMed

    Ghosh, Amalendu; Das, Amrita; Vijayanandraj, S; Mandal, Bikash

    2016-02-01

    Cardamom bushy dwarf virus (CBDV) causes foorkey disease of large cardamom (Ammomum subulatum Roxburgh) in the eastern sub-Himalayan mountains. Although the aphid Micromyzus kalimpongensis Basu (Hemiptera: Aphididae) is known as a vector of CBDV, its behavior in dissemination of CBDV has not been investigated. In the present study, M. kalimpongensis was observed to colonize in higher number on CBDV-infected large cardamom plants compared with the healthy plants in the several plantations in Sikkim and Darjeeling hills. The affinity of M. kalimpongensis to the diseased large cardamom plants was further confirmed in a contained field experiment with intact plant as well as in a laboratory bioassay with the plant extract, where significantly higher number of aphids settled on the diseased plants or extracts compared with the healthy counterparts. Aphids grown on CBDV-infected large cardamom plants had shortened nymphal period and increased longevity and fecundity compared with those grown on the healthy plants. In the contained field experiment, M. kalimpongensis migrated to the CBDV-infected plants, colonized there, acquired CBDV, and once the diseased plants withered, migrated to healthy plants, which eventually became diseased. Our results suggest a general pattern of spread of CBDV by M. kalimpongensis where CBDV-infected plants attract or arrest and stimulate emergence and migration of viruliferous aphids that otherwise are sedentary in the underground plant parts of large cardamom. To our knowledge, this is the first study that shows the influence of a plant virus from the family Nanoviridae in altering behavior of its insect vector that favors its dissemination.

  3. Role of BK virus infection in end-stage renal disease patients waiting for kidney transplantation--viral replication dynamics from pre- to post-transplant.

    PubMed

    Mitterhofer, Anna Paola; Tinti, Francesca; Pietropaolo, Valeria; Umbro, Ilaria; Anzivino, Elena; Bellizzi, Anna; Zavatto, Assunta; Poli, Luca; Berloco, Pasquale Bartolomeo; Taliani, Gloria

    2014-03-01

    We report the prevalence of BK virus (BKV) infection before renal transplantation and the dynamics of BKV viremia from pre- to post-transplantation. We assessed 60 kidney transplanted patients from a single cohort in Italy, treated with identical immunosuppressive therapy, for BK viremia at pre-transplantation, 12 h, and three and six months post-transplantation. Polymerase chain reaction showed that the prevalence of plasma BKV replication--considered a marker of infection--was 20% in pre-transplant patients. All pre-transplant-positive patients remained positive post-transplant, whereas the majority of pre-transplant-negative patients remained negative. Viremia dynamics classification revealed three clusters of patients: Cluster A++, pre-transplant-positive patients (20%) who tested positive at least once post-transplant; Cluster B-+, pre-transplant-negative patients (28%) who tested positive at least once post-transplant; and Cluster C- -, pre-transplant-negative patients (52%) who remained negative throughout. These clusters presented significant differences related to the prevalence of substantially positive patients with high plasma viral load (>10(3) copies/mL) in cluster A, but not in donors' or grafts' characteristics. We suggest that pre-transplant viral status should be considered as an additional risk factor for post-transplant BKV replication. Therefore, pre-transplant BKV infection screening in kidney transplant patients should be performed for improving planning of personalized immunosuppressant schemes and specific post-transplant surveillance.

  4. Characterization of tuberculous granulomas in different stages of progression and associated tertiary lymphoid tissue in goats experimentally infected with Mycobacterium avium subsp. hominissuis.

    PubMed

    Schinköthe, Jan; Köhler, Heike; Liebler-Tenorio, Elisabeth M

    2016-08-01

    Oral infection of goats with Mycobacterium avium subsp. hominissuis (MAH) resulted in a large variety of granulomas in organized gut-associated lymphatic tissues and intestinal lymph nodes. To characterize the cellular composition of granulomas, CD4(+), CD8(+), γδ, B lymphocytes and plasma, CD25(+), CD68(+), MHC-II(+), Ki67(+) and endothelial cells were labeled in consecutive frozen sections by immunohistochemistry and acid fast bacilli (AFB) by Kinyoun stain. Granulomas with extensive necrosis, little mineralization and variable numbers of AFB surrounded by many CD4(+) T cells, but only few epitheloid macrophages were observed in severely sick goats at 2-3mpi. They were interpreted as exuberant immune reaction. Organized granulomas with very few AFB were seen in clinically healthy goats at 13mpi. The necrotic cores were surrounded by a zone of granulomatous infiltrate with many epitheloid macrophages and few lymphocytes. This zone was initially wide and highly vascularized and became progressively smaller. It was enclosed by an increasing layer of connective tissue. All organized granulomas were surrounded by compartimentalized tertiary lymphoid tissue. The granulomas in experimental infection of goats with MAH reflect the heterogeneity of lesions seen in mycobacterial infections of humans and ruminants and are therefore valuable for comparative research. PMID:27477506

  5. Altered cellular infiltration and cytokine levels during early Mycobacterium tuberculosis sigC mutant infection are associated with late-stage disease attenuation and milder immunopathology in mice

    PubMed Central

    Abdul-Majid, Khairul-Bariah; Ly, Lan H; Converse, Paul J; Geiman, Deborah E; McMurray, David N; Bishai, William R

    2008-01-01

    Background Mouse virulence assessments of certain Mycobacterium tuberculosis mutants have revealed an immunopathology defect in which high tissue CFU counts are observed but the tissue pathology and lethality are reduced. M. tuberculosis mutants which grow and persist in the mouse lungs, but have attenuated disease progression, have the immunopathology (imp) phenotype. The antigenic properties of these strains may alter the progression of disease due to a reduction in host immune cell recruitment to the lungs resulting in disease attenuation and prolonged host survival. Results In this study we focused on the mouse immune response to one such mutant; the M. tuberculosis ΔsigC mutant. Aerosol infection of DBA/2 and SCID mice with the M. tuberculosis ΔsigC mutant, complemented mutant and wild type strain showed proliferation of mutant bacilli in mouse lungs, but with decreased inflammation and mortality in DBA/2 mice. SCID mice shared the same phenotype as the DBA/2 mice in response to the ΔsigC mutant, however, they succumbed to the infection faster. Bronchoalveolar lavage (BAL) fluid analysis revealed elevated numbers of infiltrating neutrophils in the lungs of mice infected with wild type and complemented ΔsigC mutant strains but not in mice infected with the ΔsigC mutant. In addition, DBA/2 mice infected with the ΔsigC mutant had reduced levels of TNF-α, IL-1β, IL-6 and IFN-γ in the lungs. Similarly, there was a reduction in proinflammatory cytokines in the lungs of SCID mice. In contrast to the mouse model, the ΔsigC mutant had reduced initial growth in guinea pig lungs. A possible mechanism of attenuation in the ΔsigC mutant may be a reduction in neutrophilic-influx in the alveolar spaces of the lungs, and decreased proinflammatory cytokine secretion. In contrast to mouse data, the M. tuberculosis ΔsigC mutant proliferates slowly in guinea pig lungs, a setting characterized by caseating necrosis. Conclusion Our observations suggest that the

  6. Stearylamine Liposomal Delivery of Monensin in Combination with Free Artemisinin Eliminates Blood Stages of Plasmodium falciparum in Culture and P. berghei Infection in Murine Malaria

    PubMed Central

    Rohra, Shilpa; Raza, Mohsin; Hasan, Gulam Mustafa; Dutt, Suparna

    2015-01-01

    The global emergence of drug resistance in malaria is impeding the therapeutic efficacy of existing antimalarial drugs. Therefore, there is a critical need to develop an efficient drug delivery system to circumvent drug resistance. The anticoccidial drug monensin, a carboxylic ionophore, has been shown to have antimalarial properties. Here, we developed a liposome-based drug delivery of monensin and evaluated its antimalarial activity in lipid formulations of soya phosphatidylcholine (SPC) cholesterol (Chol) containing either stearylamine (SA) or phosphatidic acid (PA) and different densities of distearoyl phosphatidylethanolamine-methoxy-polyethylene glycol 2000 (DSPE-mPEG-2000). These formulations were found to be more effective than a comparable dose of free monensin in Plasmodium falciparum (3D7) cultures and established mice models of Plasmodium berghei strains NK65 and ANKA. Parasite killing was determined by a radiolabeled [3H]hypoxanthine incorporation assay (in vitro) and microscopic counting of Giemsa-stained infected erythrocytes (in vivo). The enhancement of antimalarial activity was dependent on the liposomal lipid composition and preferential uptake by infected red blood cells (RBCs). The antiplasmodial activity of monensin in SA liposome (50% inhibitory concentration [IC50], 0.74 nM) and SPC:Chol-liposome with 5 mol% DSPE-mPEG 2000 (IC50, 0.39 nM) was superior to that of free monensin (IC50, 3.17 nM), without causing hemolysis of erythrocytes. Liposomes exhibited a spherical shape, with sizes ranging from 90 to 120 nm, as measured by dynamic light scattering and high-resolution electron microscopy. Monensin in long-circulating liposomes of stearylamine with 5 mol% DSPE-mPEG 2000 in combination with free artemisinin resulted in enhanced killing of parasites, prevented parasite recrudescence, and improved survival. This is the first report to demonstrate that monensin in PEGylated stearylamine (SA) liposome has therapeutic potential against malaria

  7. Ethical issues in a stage 1 cognitive-behavioral therapy feasibility study and trial to reduce alcohol use among HIV-infected outpatients in western Kenya.

    PubMed

    Papas, Rebecca K; Gakinya, Benson N; Baliddawa, Joyce B; Martino, Steve; Bryant, Kendall J; Meslin, Eric M; Sidle, John E

    2012-07-01

    Epidemics of both HIV/AIDS and alcohol abuse in sub-Saharan Africa have spurred the conduct of local behavioral therapy trials for these problems, but the ethical issues involved in these trials have not been fully examined. In this paper, we discuss ethical issues that emerged during the conduct of a behavioral intervention adaptation and trial using cognitive-behavioral therapy to reduce alcohol use among HIV-infected outpatients in Eldoret, Kenya. The study was performed within our multinational collaboration, the USAID-Academic Model Providing Access to Healthcare Partnership. We discuss relevant ethical considerations and how we addressed them. PMID:22850141

  8. Telbivudine treatment of hepatitis B virus-infected pregnant women at different gestational stages for the prevention of mother-to-child transmission

    PubMed Central

    Tan, Zhangmin; Yin, Yuzhu; Zhou, Jin; Wu, Lingling; Xu, Chengfang; Hou, Hongying

    2016-01-01

    Abstract This prospective study evaluated the viability of telbivudine for blocking mother-to-child transmission (MTCT) of hepatitis B virus (HBV) infection. Pregnant women positive for the hepatitis B surface antigen began telbivudine treatment before 14 weeks of gestation (i.e., early), between 14 and 28 weeks of gestation (late), or not at all (control). In the late-treatment group, 55 women terminated telbivudine therapy within puerperium. All neonates underwent routine hepatitis B immunoglobulin plus vaccination. Mothers and infants were followed for 7 months after birth. Pregnancy outcomes were similar among the 3 groups. HBV MTCT rates in the early and late treatment and control groups were 0, 0, and 4.69%, respectively. The rates of infant vaccination success among the 3 groups were similar, as were neonatal outcomes including birth weights, asphyxia, hyperbilirubinemia, Apgar score, birth defects, and weight and height at 7 months. Puerperal discontinuation of telbivudine did not increase the alanine transaminase value at 7 months after birth, but increased serum HBV DNA levels, and rates of positive hepatitis Be-antigen. Telbivudine treatment in HBV-infected pregnant women was associated with lower serum HBV DNA levels and reduced rates of HBV MTCT; there were no associated changes in pregnancy or neonatal outcomes at birth or 7 months after birth, or in the rate of infant vaccination success. Puerperal drug withdrawal after short-term antiviral therapy will not influence hepatic function, but may increase virus replication. PMID:27749537

  9. Interferon-Based Treatment of Hepatitis C Virus Infection Reduces All-Cause Mortality in Patients With End-Stage Renal Disease: An 8-Year Nationwide Cohort Study in Taiwan.

    PubMed

    Hsu, Yueh-Han; Hung, Peir-Haur; Muo, Chih-Hsin; Tsai, Wen-Chen; Hsu, Chih-Cheng; Kao, Chia-Hung

    2015-11-01

    The long-term survival of end-stage renal disease (ESRD) patients with hepatitis C virus (HCV) infection who received interferon treatment has not been extensively evaluated.The HCV cohort was the ESRD patients with de novo HCV infection from 2004 to 2011; they were classified into treated and untreated groups according to interferon therapy records. Patients aged <20 years and those with a history of hepatitis B, kidney transplantation, or cancer were excluded. The control cohort included ESRD patients without HCV infection matched 4:1 to the HCV cohort by age, sex, and year of ESRD registration. We followed up all study participants until kidney transplantation, death, or the end of 2011, whichever came first. We assessed risk of all-cause mortality by using the multivariate Cox proportional hazard model with time-dependent covariate.In the HCV cohort, 134 patients (6.01%) received interferon treatment. Compared with the uninfected control cohort, the treated group had a lower risk of death (hazard ratio 0.47, 95% confidence interval [CI] 0.22-0.99). The untreated group had a 2.62-fold higher risk (95% CI 1.24-5.55) of death compared with the treated group. For the HCV cohort without cirrhosis or hepatoma, the risk of death in the treated group was further markedly reduced (hazard ratio 0.17, 95% CI 0.04-0.68) compared with that in the control cohort.For ESRD patients with HCV infection, receiving interferon treatment is associated with a survival advantage. Such an advantage is more prominent in HCV patients without cirrhosis or hepatoma.

  10. A New Nonpolar N-Hydroxy Imidazoline Lead Compound with Improved Activity in a Murine Model of Late-Stage Trypanosoma brucei brucei Infection Is Not Cross-Resistant with Diamidines

    PubMed Central

    Ríos Martínez, Carlos H.; Miller, Florence; Ganeshamoorthy, Kayathiri; Glacial, Fabienne; Kaiser, Marcel; de Koning, Harry P.; Eze, Anthonius A.; Lagartera, Laura; Herraiz, Tomás

    2014-01-01

    Treatment of late-stage sleeping sickness requires drugs that can cross the blood-brain barrier (BBB) to reach the parasites located in the brain. We report here the synthesis and evaluation of four new N-hydroxy and 12 new N-alkoxy derivatives of bisimidazoline leads as potential agents for the treatment of late-stage sleeping sickness. These compounds, which have reduced basicity compared to the parent leads (i.e., are less ionized at physiological pH), were evaluated in vitro against Trypanosoma brucei rhodesiense and in vivo in murine models of first- and second-stage sleeping sickness. Resistance profile, physicochemical parameters, in vitro BBB permeability, and microsomal stability also were determined. The N-hydroxy imidazoline analogues were the most effective in vivo, with 4-((1-hydroxy-4,5-dihydro-1H-imidazol-2-yl)amino)-N-(4-((1-hydroxy-4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)benzamide (14d) showing 100% cures in the first-stage disease, while 15d, 16d, and 17d appeared to slightly improve survival. In addition, 14d showed weak activity in the chronic model of central nervous system infection in mice. No evidence of reduction of this compound with hepatic microsomes and mitochondria was found in vitro, suggesting that N-hydroxy imidazolines are metabolically stable and have intrinsic activity against T. brucei. In contrast to its unsubstituted parent compound, the uptake of 14d in T. brucei was independent of known drug transporters (i.e., T. brucei AT1/P2 and HAPT), indicating a lower predisposition to cross-resistance with other diamidines and arsenical drugs. Hence, the N-hydroxy bisimidazolines (14d in particular) represent a new class of promising antitrypanosomal agents. PMID:25421467

  11. Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With Stage II-IV HIV-Associated Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-09-19

    AIDS-Related Hodgkin Lymphoma; Classical Hodgkin Lymphoma; HIV Infection; Stage IIA Hodgkin Lymphoma; Stage IIB Hodgkin Lymphoma; Stage IIIA Hodgkin Lymphoma; Stage IIIB Hodgkin Lymphoma; Stage IVA Hodgkin Lymphoma; Stage IVB Hodgkin Lymphoma

  12. Third Stage

    NASA Video Gallery

    Once the third stage finishes its work, Kepler will have sufficient energy to leave the gravitational pull of Earth and go into orbit around the Sun, trailing behind Earth and slowly drifting away ...

  13. Transcription of the Epstein-Barr virus nuclear antigen 1 (EBNA1) gene occurs before induction of the BCR2 (Cp) EBNA gene promoter during the initial stages of infection in B cells.

    PubMed

    Schlager, S; Speck, S H; Woisetschläger, M

    1996-06-01

    The purpose of this study was to gain insights into the regulation of Epstein-Barr virus (EBV) gene transcription during the establishment of viral latency in B cells. During the early stages of EBV infection in B lymphocytes, transcription of six viral nuclear antigens (EBNAs) is initiated from an early promoter (Wp). This is followed by a switch of promoter usage to an upstream promoter, Cp, whose activity is autoregulated by both EBNA1 and EBNA2. Previously it was demonstrated that infection of primary B cells with EBNA2-negative (EBNA2-) EBNA4-mutant (EBNA4mut) virus resulted only in the expression of mutant EBNA4 protein and failure to express the other EBNA gene products (C. Rooney H. G. Howe, S. H. Speck, and G. Miller, J. Virol. 63:1531-1539, 1989). We extended this research to demonstrate that Wp-to-Cp switching did not occur upon infection of primary B cells with an EBNA2- EBNA4mut virus (M. Woisetschlaeger, X. W. Jin, C. N. Yandara, L. A. Furmanski, J. L. Strominger, and S. H. Speck, Proc. Natl. Acad. Sci. USA 88:3942-3946, 1991). Further characterization of this phenomenon led to the identification of an EBNA2-dependent enhancer upstream of Cp. On the basis of these data, a model was proposed in which initial transcription from Wp gives rise to the expression of EBNA2 and EBNA4, and then transcription is upregulated from Cp via the EBNA2- dependent enhancer (Woisetschlaeger et al., as noted above). Implicit in this model is that transcription of the EBNA1 and EBNA3a to -3c genes is dependent on the switch from Wp to Cp, since primary cells infected with EBNA2- EBNA4mut virus fail to switch and also fail to express these viral antigens. Here we critically evaluate this model and demonstrate, in contrast to the predictions of the model, that transcription of both the EBNA1 and EBNA2 genes precedes activation of Cp. Furthermore, the level of EBNA1 gene transcription was strongly reduced in primary B cells infected with EBNA2- EBNA4mut virus compared with

  14. Specific Antibody Production by Blood B Cells is Retained in Late Stage Drug-naïve HIV-infected Africans

    PubMed Central

    Béniguel, Lydie; Bégaud, Evelyne; Cognasse, Fabrice; Gabrié, Philippe; Mbolidi, Christophe D.; Marovich, Mary A.; Cazorla, Céline; Lucht, Frédéric; Genin, Christian; Garraud, Olivier

    2004-01-01

    Unseparated peripheral blood mononuclear cells (PBMCs) obtained from drug-naïve African individuals living in a context of multi-infections and presenting with high viral load (VL), were cultured in vitro and tested for their ability to produce antibodies (Abs) reacting with HIV-1 antigens. Within these PBMCs, circulating B cells were differentiated in vitro and produced IgG Abs against not only ENV, but also GAG and POL proteins. Under similar experimental conditions, HAART treated patients produced Abs to ENV proteins only. The in vitro antibody production by drug-naïve individuals' PBMCs depended on exogenous cytokines (IL-2 and IL-10) but neither on the re-stimulation of reactive cells in cultures by purified HIV-1-gp 160 antigen nor on the re-engagement of CD40 surface molecules. Further, it was not abrogated by the addition of various monoclonal Abs (mAbs) to co-stimulatory molecules. This suggests that the in vitro antibody production by drug-naïve individuals' PBMCs resulted from the maturation of already envelope and core antigen-primed, differentiated B cells, presumably pre-plasma cells, which are not known to circulate at homeostasy. As in vitro produced Abs retained the capacity of binding antigen and forming complexes, this study provides pre-clinical support for functional humoral responses despite major HIV- and other tropical pathogen-induced B cell perturbations. PMID:15330447

  15. Multiple Circulating Infections Can Mimic the Early Stages of Viral Hemorrhagic Fevers and Possible Human Exposure to Filoviruses in Sierra Leone Prior to the 2014 Outbreak

    PubMed Central

    Boisen, Matthew L.; Schieffelin, John S.; Goba, Augustine; Oottamasathien, Darin; Jones, Abigail B.; Shaffer, Jeffrey G.; Hastie, Kathryn M.; Hartnett, Jessica N.; Momoh, Mambu; Fullah, Mohammed; Gabiki, Michael; Safa, Sidiki; Zandonatti, Michelle; Fusco, Marnie; Bornholdt, Zach; Abelson, Dafna; Gire, Stephen K.; Andersen, Kristian G.; Tariyal, Ridhi; Stremlau, Mathew; Cross, Robert W.; Geisbert, Joan B.; Pitts, Kelly R.; Geisbert, Thomas W.; Kulakoski, Peter; Wilson, Russell B.; Henderson, Lee; Sabeti, Pardis C.; Grant, Donald S.; Garry, Robert F.; Saphire, Erica O.; Khan, Sheik Humarr

    2015-01-01

    Abstract Lassa fever (LF) is a severe viral hemorrhagic fever caused by Lassa virus (LASV). The LF program at the Kenema Government Hospital (KGH) in Eastern Sierra Leone currently provides diagnostic services and clinical care for more than 500 suspected LF cases per year. Nearly two-thirds of suspected LF patients presenting to the LF Ward test negative for either LASV antigen or anti-LASV immunoglobulin M (IgM), and therefore are considered to have a non-Lassa febrile illness (NLFI). The NLFI patients in this study were generally severely ill, which accounts for their high case fatality rate of 36%. The current studies were aimed at determining possible causes of severe febrile illnesses in non-LF cases presenting to the KGH, including possible involvement of filoviruses. A seroprevalence survey employing commercial enzyme-linked immunosorbent assay tests revealed significant IgM and IgG reactivity against dengue virus, chikungunya virus, West Nile virus (WNV), Leptospira, and typhus. A polymerase chain reaction–based survey using sera from subjects with acute LF, evidence of prior LASV exposure, or NLFI revealed widespread infection with Plasmodium falciparum malaria in febrile patients. WNV RNA was detected in a subset of patients, and a 419 nt amplicon specific to filoviral L segment RNA was detected at low levels in a single patient. However, 22% of the patients presenting at the KGH between 2011 and 2014 who were included in this survey registered anti-Ebola virus (EBOV) IgG or IgM, suggesting prior exposure to this agent. The 2014 Ebola virus disease (EVD) outbreak is already the deadliest and most widely dispersed outbreak of its kind on record. Serological evidence reported here for possible human exposure to filoviruses in Sierra Leone prior to the current EVD outbreak supports genetic analysis that EBOV may have been present in West Africa for some time prior to the 2014 outbreak. PMID:25531344

  16. Multiple circulating infections can mimic the early stages of viral hemorrhagic fevers and possible human exposure to filoviruses in Sierra Leone prior to the 2014 outbreak.

    PubMed

    Boisen, Matthew L; Schieffelin, John S; Goba, Augustine; Oottamasathien, Darin; Jones, Abigail B; Shaffer, Jeffrey G; Hastie, Kathryn M; Hartnett, Jessica N; Momoh, Mambu; Fullah, Mohammed; Gabiki, Michael; Safa, Sidiki; Zandonatti, Michelle; Fusco, Marnie; Bornholdt, Zach; Abelson, Dafna; Gire, Stephen K; Andersen, Kristian G; Tariyal, Ridhi; Stremlau, Mathew; Cross, Robert W; Geisbert, Joan B; Pitts, Kelly R; Geisbert, Thomas W; Kulakoski, Peter; Wilson, Russell B; Henderson, Lee; Sabeti, Pardis C; Grant, Donald S; Garry, Robert F; Saphire, Erica O; Branco, Luis M; Khan, Sheik Humarr

    2015-02-01

    Lassa fever (LF) is a severe viral hemorrhagic fever caused by Lassa virus (LASV). The LF program at the Kenema Government Hospital (KGH) in Eastern Sierra Leone currently provides diagnostic services and clinical care for more than 500 suspected LF cases per year. Nearly two-thirds of suspected LF patients presenting to the LF Ward test negative for either LASV antigen or anti-LASV immunoglobulin M (IgM), and therefore are considered to have a non-Lassa febrile illness (NLFI). The NLFI patients in this study were generally severely ill, which accounts for their high case fatality rate of 36%. The current studies were aimed at determining possible causes of severe febrile illnesses in non-LF cases presenting to the KGH, including possible involvement of filoviruses. A seroprevalence survey employing commercial enzyme-linked immunosorbent assay tests revealed significant IgM and IgG reactivity against dengue virus, chikungunya virus, West Nile virus (WNV), Leptospira, and typhus. A polymerase chain reaction-based survey using sera from subjects with acute LF, evidence of prior LASV exposure, or NLFI revealed widespread infection with Plasmodium falciparum malaria in febrile patients. WNV RNA was detected in a subset of patients, and a 419 nt amplicon specific to filoviral L segment RNA was detected at low levels in a single patient. However, 22% of the patients presenting at the KGH between 2011 and 2014 who were included in this survey registered anti-Ebola virus (EBOV) IgG or IgM, suggesting prior exposure to this agent. The 2014 Ebola virus disease (EVD) outbreak is already the deadliest and most widely dispersed outbreak of its kind on record. Serological evidence reported here for possible human exposure to filoviruses in Sierra Leone prior to the current EVD outbreak supports genetic analysis that EBOV may have been present in West Africa for some time prior to the 2014 outbreak.

  17. Honeybee (Apis mellifera) Venom Reinforces Viral Clearance during the Early Stage of Infection with Porcine Reproductive and Respiratory Syndrome Virus through the Up-Regulation of Th1-Specific Immune Responses

    PubMed Central

    Lee, Jin-A; Kim, Yun-Mi; Hyun, Pung-Mi; Jeon, Jong-Woon; Park, Jin-Kyu; Suh, Guk-Hyun; Jung, Bock-Gie; Lee, Bong-Joo

    2015-01-01

    Porcine reproductive and respiratory syndrome (PRRS) is a chronic and immunosuppressive viral disease that is responsible for substantial economic losses for the swine industry. Honeybee venom (HBV) is known to possess several beneficial biological properties, particularly, immunomodulatory effects. Therefore, this study aimed at evaluating the effects of HBV on the immune response and viral clearance during the early stage of infection with porcine reproductive and respiratory syndrome virus (PRRSV) in pigs. HBV was administered via three routes of nasal, neck, and rectal and then the pigs were inoculated with PRRSV intranasally. The CD4+/CD8+ cell ratio and levels of interferon (IFN)-γ and interleukin (IL)-12 were significantly increased in the HBV-administered healthy pigs via nasal and rectal administration. In experimentally PRRSV-challenged pigs with virus, the viral genome load in the serum, lung, bronchial lymph nodes and tonsil was significantly decreased, as was the severity of interstitial pneumonia, in the nasal and rectal administration group. Furthermore, the levels of Th1 cytokines (IFN-γ and IL-12) were significantly increased, along with up-regulation of pro-inflammatory cytokines (TNF-α and IL-1β) with HBV administration. Thus, HBV administration—especially via the nasal or rectal route—could be a suitable strategy for immune enhancement and prevention of PRRSV infection in pigs. PMID:26008237

  18. Changes in immune gene expression and resistance to bacterial infection in lobster (Homarus gammarus) post-larval stage VI following acute or chronic exposure to immune stimulating compounds.

    PubMed

    Hauton, C; Brockton, V; Smith, V J

    2007-01-01

    Real-time PCR was used to measure changes in transcript abundance of genes encoding important immune proteins, namely prophenoloxidase (proPO gene), beta-1,3-glucan binding protein (betaGBP gene) and a 12.2 kDa antimicrobial peptide (amp gene) in post-larval stage VI (PLVI) juveniles of the European lobster, Homarus gammarus. Gene expression was studied in both healthy PLVI and following single or repeat exposure to a range of compounds claimed to induce immune reactivity. A single acute (3-h) exposure to any of the tested stimulants did not produce a significant increase in expression of either the proPO or betaGBP genes, measured 6h after stimulation. However, there were a small sub-group of positive responders, identified mainly from betaGBP expression, within the experimental groups stimulated with either a beta-1,3-glucan or an alginate. There was also no significant increase in the expression of any of the three genes tested 24 h after repeated weekly (3-h) exposures to a either the beta-1,3-glucan or the alginate over the longer (36-day) period. The results do show that amp is expressed at an extremely high level compared to proPO or betaGBP in healthy animals and a significant correlation was found between the expression of proPO and both betaGBP and amp, irrespective of whether or not the larvae were stimulated. None of the immune stimulated compounds improved survival of PLVI challenged with the opportunistic pathogen, Listonella anguillarum, or the lobster pathogen, Aerococcus viridans var. homari. Thus, we found no evidence to support recent claims that immunity and disease resistance can be primed or promoted within a given population of crustaceans or that these animals exhibit functional immune memory to some soluble immune elicitors. PMID:16569431

  19. Incidence of WHO Stage 3 and 4 Events, Tuberculosis, and Mortality in Untreated, HIV-Infected Children Enrolling in Care Before 1 Year of Age: An Iedea (International Epidemiologic Databases To Evaluate AIDS) East Africa Regional Analysis

    PubMed Central

    Ciaranello, Andrea; Lu, Zhigang; Ayaya, Samuel; Losina, Elena; Musick, Beverly; Vreeman, Rachel; Freedberg, Kenneth A.; Abrams, Elaine J.; Dillabaugh, Lisa; Doherty, Katie; Ssali, John; Yiannoutsos, Constantin T.; Wools-Kaloustian, Kara

    2014-01-01

    Background Few studies have reported CD4%- and age-stratified rates of WHO Stage 3 (WHO3) events, WHO Stage 4 (WHO4) events, tuberculosis (TB), and mortality in HIV-infected infants before initiation of antiretroviral therapy (ART). Methods HIV-infected children enrolled before 1 year of age in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) East Africa region (10/01/2002-11/30/2008) were included. We estimated incidence rates of earliest clinical event (WHO3, WHO4, and TB), prior to ART initiation per local guidelines, stratified by current age (< or ≥6 months) and current CD4% (<15%, 15–24%, ≥25%). CD4%-stratified mortality rates were estimated separately for children who did not experience a clinical event (“background” mortality) and for children who experienced an event, including “acute” mortality (≤30 days post-event) and “later” mortality (>30 days post-event). Results Among 847 children (median enrollment age: 4.8 months; median pre-ART follow-up: 10.8 months; 603 (71%) with ≥1 CD4% recorded), event rates were comparable for those aged <6 and ≥6 months. Current CD4% was associated with risk of WHO4 events for children <6 months old, and with all evaluated events for children ≥6 months old (p<0.05). “Background” mortality was 3.7–8.4/100py. “Acute” mortality (≤30 days post-event) was 33.8/100py (after TB) and 41.1/100py (after WHO3 or WHO4). “Later” mortality (>30 days post-event) ranged by CD4% from 4.7–29.1/100py. Conclusions In treatment-naïve, HIV-infected infants, WHO3, WHO4, and TB events were common before and after 6 months of age and led to substantial increases in mortality. Early infant HIV diagnosis and treatment are critically important, regardless of CD4%. PMID:24378935

  20. Baculovirus-Vectored Multistage Plasmodium vivax Vaccine Induces Both Protective and Transmission-Blocking Immunities against Transgenic Rodent Malaria Parasites

    PubMed Central

    Mizutani, Masanori; Iyori, Mitsuhiro; Blagborough, Andrew M.; Fukumoto, Shinya; Funatsu, Tomohiro; Sinden, Robert E.

    2014-01-01

    A multistage malaria vaccine targeting the pre-erythrocytic and sexual stages of Plasmodium could effectively protect individuals against infection from mosquito bites and provide transmission-blocking (TB) activity against the sexual stages of the parasite, respectively. This strategy could help prevent malaria infections in individuals and, on a larger scale, prevent malaria transmission in communities of endemicity. Here, we describe the development of a multistage Plasmodium vivax vaccine which simultaneously expresses P. vivax circumsporozoite protein (PvCSP) and P25 (Pvs25) protein of this species as a fusion protein, thereby acting as a pre-erythrocytic vaccine and a TB vaccine, respectively. A new-concept vaccine platform based on the baculovirus dual-expression system (BDES) was evaluated. The BDES-Pvs25-PvCSP vaccine displayed correct folding of the Pvs25-PvCSP fusion protein on the viral envelope and was highly expressed upon transduction of mammalian cells in vitro. This vaccine induced high levels of antibodies to Pvs25 and PvCSP and elicited protective (43%) and TB (82%) efficacies against transgenic P. berghei parasites expressing the corresponding P. vivax antigens in mice. Our data indicate that our BDES, which functions as both a subunit and DNA vaccine, can offer a promising multistage vaccine capable of delivering a potent antimalarial pre-erythrocytic and TB response via a single immunization regimen. PMID:25092912

  1. Infection and Other Complications

    MedlinePlus

    ... Stage 3 Infection and Other Complications NLN Position Papers Lymphedema Awareness Campaign Education Kits Educational Videos What ... Patients (8) LymphLink Articles (175) FAQ's (6) Position Papers (9) LSAP Perspective (9) Become a member now » ...

  2. A toolbox to study liver stage malaria.

    PubMed

    Prudêncio, Miguel; Mota, Maria M; Mendes, António M

    2011-12-01

    The first obligatory phase of mammalian infection by Plasmodium parasites, the causative agents of malaria, occurs in the liver of the host. This stage of Plasmodium infection bears enormous potential for anti-malarial intervention. Recent technological progress has strongly contributed to overcoming some of the long-standing difficulties in experimentally assessing hepatic infection by Plasmodium. Here, we review appropriate infection models and infection assessment tools, and provide a comprehensive description of recent advances in experimental strategies to investigate the liver stage of malaria. These issues are discussed in the context of current challenges in the field to provide researchers with the technical tools that enable effective experimental approaches to study liver stage malaria.

  3. Long-Term Monitoring of Microsporidia, Cryptosporidium and Giardia Infections in Western Lowland Gorillas (Gorilla gorilla gorilla) at Different Stages of Habituation in Dzanga Sangha Protected Areas, Central African Republic

    PubMed Central

    Kvetonova, Dana; Mynarova, Anna; Shutt, Kathryn A.; Pomajbikova, Katerina; Kalousova, Barbora; Modry, David; Benavides, Julio; Todd, Angelique; Kvac, Martin

    2013-01-01

    Background Infectious diseases pose one of the greatest threats to endangered species, and a risk of gastrointestinal parasite transmission from humans to wildlife has always been considered as a major concern of tourism. Increased anthropogenic impact on primate populations may result in general changes in communities of their parasites, and also in a direct exchange of parasites between humans and primates. Aims To evaluate the impact of close contact with humans on the occurrence of potentially zoonotic protists in great apes, we conducted a long-term monitoring of microsporidia, Cryptosporidium and Giardia infections in western lowland gorillas at different stages of the habituation process, humans, and other wildlife in Dzanga-Sangha Protected Areas in the Central African Republic. Results We detected Encephalitozoon cuniculi genotypes I and II (7.5%), Enterocytozoon bieneusi genotype D and three novel genotypes (gorilla 1–3) (4.0%), Giardia intestinalis subgroup A II (2.0%) and Cryptosporidium bovis (0.5%) in gorillas, whereas in humans we found only G. intestinalis subgroup A II (2.1%). In other wild and domestic animals we recorded E. cuniculi genotypes I and II (2.1%), G. intestinalis assemblage E (0.5%) and C. muris TS03 (0.5%). Conclusion Due to the non-specificity of E. cuniculi genotypes we conclude that detection of the exact source of E. cuniculi infection is problematic. As Giardia intestinalis was recorded primarily in gorilla groups with closer human contact, we suggest that human-gorilla transmission has occurred. We call attention to a potentially negative impact of habituation on selected pathogens which might occur as a result of the more frequent presence of humans in the vicinity of both gorillas under habituation and habituated gorillas, rather than as a consequence of the close contact with humans, which might be a more traditional assumption. We encourage to observe the sections concerning hygiene from the IUCN best practice guidelines

  4. Malaria Blood Stage Suppression of Liver Stage Immunity by Dendritic Cells

    PubMed Central

    Ocaña-Morgner, Carlos; Mota, Maria M.; Rodriguez, Ana

    2003-01-01

    Malaria starts with Plasmodium sporozoites infection of the host's liver, where development into blood stage parasites occurs. It is not clear why natural infections do not induce protection against the initial liver stage and generate low CD8+ T cell responses. Using a rodent malaria model, we show that Plasmodium blood stage infection suppresses CD8+ T cell immune responses that were induced against the initial liver stage. Blood stage Plasmodium affects dendritic cell (DC) functions, inhibiting maturation and the capacity to initiate immune responses and inverting the interleukin (IL)-12/IL-10 secretion pattern. The interaction of blood stage parasites with DCs induces the secretion of soluble factors that inhibit the activation of CD8+ T cells in vitro and the suppression of protective CD8+ T cell responses against the liver stage in vivo. We propose that blood stage infection induces DCs to suppress CD8+ T cell responses in natural malaria infections. This evasion mechanism leaves the host unprotected against reinfection by inhibiting the immune response against the initial liver stage of the disease. PMID:12538654

  5. Central line infections - hospitals

    MedlinePlus

    ... infection; CVC - infection; Central venous device - infection; Infection control - central line infection; Nosocomial infection - central line infection; Hospital acquired infection - central line infection; Patient safety - central ...

  6. Second Stage Separation

    NASA Video Gallery

    When the second stage burn is complete, the spacecraft and third stage are spun up to 55 rpm to stabilize the third stage during its short firing. The second stage is then jettisoned and the third ...

  7. Gene expression analyses of immune responses in Atlantic salmon during early stages of infection by salmon louse (Lepeophtheirus salmonis) revealed bi-phasic responses coinciding with the copepod-chalimus transition

    PubMed Central

    2011-01-01

    Background The salmon louse (Lepeophtheirus salmonis Krøyer), an ectoparasitic copepod with a complex life cycle causes significant losses in salmon aquaculture. Pesticide treatments against the parasite raise environmental concerns and their efficacy is gradually decreasing. Improvement of fish resistance to lice, through biological control methods, needs better understanding of the protective mechanisms. We used a 21 k oligonucleotide microarray and RT-qPCR to examine the time-course of immune gene expression changes in salmon skin, spleen, and head kidney during the first 15 days after challenge, which encompassed the copepod and chalimus stages of lice development. Results Large scale and highly complex transcriptome responses were found already one day after infection (dpi). Many genes showed bi-phasic expression profiles with abrupt changes between 5 and 10 dpi (the copepod-chalimus transitions); the greatest fluctuations (up- and down-regulation) were seen in a large group of secretory splenic proteases with unknown roles. Rapid sensing was witnessed with induction of genes involved in innate immunity including lectins and enzymes of eicosanoid metabolism in skin and acute phase proteins in spleen. Transient (1-5 dpi) increase of T-cell receptor alpha, CD4-1, and possible regulators of lymphocyte differentiation suggested recruitment of T-cells of unidentified lineage to the skin. After 5 dpi the magnitude of transcriptomic responses decreased markedly in skin. Up-regulation of matrix metalloproteinases in all studied organs suggested establishment of a chronic inflammatory status. Up-regulation of putative lymphocyte G0/G1 switch proteins in spleen at 5 dpi, immunoglobulins at 15 dpi; and increase of IgM and IgT transcripts in skin indicated an onset of adaptive humoral immune responses, whereas MHCI appeared to be down-regulated. Conclusions Atlantic salmon develops rapid local and systemic reactions to L. salmonis, which, however, do not result in

  8. [ZIKA--VIRUS INFECTION].

    PubMed

    Velev, V

    2016-01-01

    This review summarizes the knowledge of the scientific community for Zika-virus infection. It became popular because of severe congenital damage causes of CNS in newborns whose mothers are infected during pregnancy, as well as the risk of pandemic distribution. Discusses the peculiarities of the biology and ecology of vectors--blood-sucking mosquitoes Aedes; stages in the spread of infection and practical problems which caused during pregnancy. Attention is paid to the recommendations that allow leading national and international medical organizations to deal with the threat Zika-virus infection. PMID:27509655

  9. [ZIKA--VIRUS INFECTION].

    PubMed

    Velev, V

    2016-01-01

    This review summarizes the knowledge of the scientific community for Zika-virus infection. It became popular because of severe congenital damage causes of CNS in newborns whose mothers are infected during pregnancy, as well as the risk of pandemic distribution. Discusses the peculiarities of the biology and ecology of vectors--blood-sucking mosquitoes Aedes; stages in the spread of infection and practical problems which caused during pregnancy. Attention is paid to the recommendations that allow leading national and international medical organizations to deal with the threat Zika-virus infection.

  10. T-cell immunity to peptide epitopes of liver-stage antigen 1 in an area of Papua New Guinea in which malaria is holoendemic.

    PubMed Central

    Connelly, M; King, C L; Bucci, K; Walters, S; Genton, B; Alpers, M P; Hollingdale, M; Kazura, J W

    1997-01-01

    Liver-stage antigen 1 (LSA1) is one of several pre-erythrocytic antigens considered for inclusion in a multiantigen, multistage subunit vaccine against falciparum malaria. We examined T-cell proliferation and cytokine responses to peptides corresponding to amino acids 84 to 107, 1813 to 1835, and 1888 to 1909 of LSA1 in asymptomatic adults living in an area of Papua New Guinea where malaria is holoendemic. Whereas T cells from North Americans never exposed to malaria did not respond to any of the peptides, those from 52 of 55 adults from the area where malaria is endemic had vigorous proliferation responses to one or more of the LSA1 peptides (mean stimulation indices of 6.8 to 7.2). Gamma interferon (IFN-gamma) production driven by LSA1 peptides ranged from 34 to more than 3,500 pg/2 x 10(6) cells, was derived primarily from CD8+ cells, and was dissociated from T-cell proliferation. The frequencies of IFN-gamma response to the amino acid 1819 to 1835 and 1888 to 1909 peptides were significantly greater than that to the amino acid 84 to 107 peptide (87 and 88% versus 33% of subjects; P < 0.0001). In contrast to proliferation and IFN-gamma, interleukin 4 (IL-4) and/or IL-5 responses to LSA1 peptides were detected in only 18% of the subjects. These data show that T-cell immunity to epitopes in the N- and C-terminal regions of LSA1 are common in persons living in this area of Papua New Guinea where malaria is endemic. The dominance of type 1 CD8 cell IFN-gamma responses is consistent with a role for this T-cell population in immunity to liver-stage Plasmodium falciparum in humans. PMID:9393799

  11. DENGUE INFECTION IN PREGNANCY.

    PubMed

    Khamim, Kriangsak; Khamim, Boonluck; Pengsaa, Krisana

    2015-01-01

    While dengue infection is still on the increase in adults in Thailand, it also affects pregnant women, especially pregnant teenagers. This study was designed to investigate dengue infection during pregnancy. Seven cases of dengue infection in pregnant women were admitted to Ban Pong Hospital, Ratchaburi, Thailand, between 2008 and 2012. Dengue infection presented in all pregnancy trimesters. There were two severe cases: one was dengue hemorrhagic fever in the first trimester, and the second was at a critical stage of the infection during labor. There were three cases of abortion. These three cases included one complete, one incomplete, and one threatened abortion, with rising hematocrits of 22.8%, 17.1%, and 14.7%, respectively. Two out of the three teenage pregnancies experienced complete and threatened abortions, while the third abortion case was a threatened abortion pregnancy at the critical stage of infection during intrapartum. Leukopenia was identified in six out of seven women. Low baseline hematocrit and low maximum hematocrit were laboratory findings. Clinical management involved administration of intravenous fluids and antipyretics. Favorable outcomes can be obtained through early diagnosis and supportive treatment. The morbidity profile can be more serious in teenage pregnancies. Additional studies should be conducted to establish whether low baseline hematocrit, low percentages of rising hematocrit in pregnant women with dengue infection, and abortions (with a high degree of increasing hematocrit during the critical stage of the disease) are typical clinical signs.

  12. DENGUE INFECTION IN PREGNANCY.

    PubMed

    Khamim, Kriangsak; Khamim, Boonluck; Pengsaa, Krisana

    2015-01-01

    While dengue infection is still on the increase in adults in Thailand, it also affects pregnant women, especially pregnant teenagers. This study was designed to investigate dengue infection during pregnancy. Seven cases of dengue infection in pregnant women were admitted to Ban Pong Hospital, Ratchaburi, Thailand, between 2008 and 2012. Dengue infection presented in all pregnancy trimesters. There were two severe cases: one was dengue hemorrhagic fever in the first trimester, and the second was at a critical stage of the infection during labor. There were three cases of abortion. These three cases included one complete, one incomplete, and one threatened abortion, with rising hematocrits of 22.8%, 17.1%, and 14.7%, respectively. Two out of the three teenage pregnancies experienced complete and threatened abortions, while the third abortion case was a threatened abortion pregnancy at the critical stage of infection during intrapartum. Leukopenia was identified in six out of seven women. Low baseline hematocrit and low maximum hematocrit were laboratory findings. Clinical management involved administration of intravenous fluids and antipyretics. Favorable outcomes can be obtained through early diagnosis and supportive treatment. The morbidity profile can be more serious in teenage pregnancies. Additional studies should be conducted to establish whether low baseline hematocrit, low percentages of rising hematocrit in pregnant women with dengue infection, and abortions (with a high degree of increasing hematocrit during the critical stage of the disease) are typical clinical signs. PMID:26506742

  13. Interleukin-1 (IL-1) signaling in intestinal stromal cells controls KC/ CXCL1 secretion, which correlates with recruitment of IL-22- secreting neutrophils at early stages of Citrobacter rodentium infection.

    PubMed

    Lee, Yong-Soo; Yang, Hyungjun; Yang, Jin-Young; Kim, Yeji; Lee, Su-Hyun; Kim, Ji Heui; Jang, Yong Ju; Vallance, Bruce A; Kweon, Mi-Na

    2015-08-01

    Attaching and effacing pathogens, including enterohemorrhagic Escherichia coli in humans and Citrobacter rodentium in mice, raise serious public health concerns. Here we demonstrate that interleukin-1 receptor (IL-1R) signaling is indispensable for protection against C. rodentium infection in mice. Four days after infection with C. rodentium, there were significantly fewer neutrophils (CD11b+ Ly6C+ Ly6G+) in the colons of IL-1R−/− mice than in wild-type mice. Levels of mRNA and protein of KC/CXCL1 were also significantly reduced in colon homogenates of infected IL-1R−/− mice relative to wild-type mice. Of note, infiltrated CD11b+ Ly6C+ Ly6G+ neutrophils were the main source of IL-22 secretion after C. rodentium infection. Interestingly, intestinal stromal cells isolated from IL-1R−/− mice secreted lower levels of KC/CXCL1 than stromal cells from wild-type mice during C. rodentium infection. Similar effects were found when mouse intestinal stromal cells and human nasal polyp stromal cells were treated with IL-1R antagonists (i.e., anakinra) in vitro. These results suggest that IL-1 signaling plays a pivotal role in activating mucosal stromal cells to secrete KC/CXCL1, which is essential for infiltration of IL-22-secreting neutrophils upon bacterial infection.

  14. Meningococcal Infections

    MedlinePlus

    ... are a type of bacteria that cause serious infections. The most common infection is meningitis, which is an inflammation of the ... also cause other problems, including a serious bloodstream infection called sepsis. Meningococcal infections can spread from person ...

  15. Pancreatic Cancer Stage 3

    MedlinePlus

    ... historical Searches are case-insensitive Pancreatic Cancer Stage 3 Add to My Pictures View /Download : Small: 720x576 ... Large: 3000x2400 View Download Title: Pancreatic Cancer Stage 3 Description: Stage III pancreatic cancer; drawing shows cancer ...

  16. Congenital Cytomegalovirus Infection.

    PubMed

    Bale, James F.; Miner, Lonnie; Petheram, Susan J.

    2002-05-01

    Intrauterine infection with cytomegalovirus (CMV), a betaherpesvirus, remains the most frequent congenital virus infection in many regions of the world. Although most CMV-infected newborns lack signs of CMV infection, approximately 10% have signs that can consist of low birth weight, jaundice, hepatosplenomegaly, skin rash, microcephaly, and chorioretinitis. Neonates with signs of CMV infection at birth have high rates of audiologic and neurodevelopmental sequelae. Although postnatal therapy with ganciclovir transiently reduces virus shedding and may lessen the audiologic consequences of CMV in some infected infants, additional strategies are needed to prevent congenital CMV disease and to improve the neurodevelopmental prognosis of infants infected with CMV in utero. Some cases of intrauterine infections can be prevented in susceptible women by avoiding contact with the urine or saliva of young children who may be shedding CMV. Vaccines against CMV remain in the experimental stages of development. Termination of pregnancy can be offered to women whose infants have evidence of intrauterine CMV infection and sonographic signs of central nervous system damage. Infants who survive symptomatic intrauterine infections have high rates of neurodevelopmental sequelae and require comprehensive evaluation and therapy through center and home-based early intervention programs. PMID:11931729

  17. Plasmodium vivax liver stage development and hypnozoite persistence in human liver-chimeric mice.

    PubMed

    Mikolajczak, Sebastian A; Vaughan, Ashley M; Kangwanrangsan, Niwat; Roobsoong, Wanlapa; Fishbaugher, Matthew; Yimamnuaychok, Narathatai; Rezakhani, Nastaran; Lakshmanan, Viswanathan; Singh, Naresh; Kaushansky, Alexis; Camargo, Nelly; Baldwin, Michael; Lindner, Scott E; Adams, John H; Sattabongkot, Jetsumon; Prachumsri, Jetsumon; Kappe, Stefan H I

    2015-04-01

    Plasmodium vivax malaria is characterized by periodic relapses of symptomatic blood stage parasite infections likely initiated by activation of dormant liver stage parasites-hypnozoites. The lack of tractable P. vivax animal models constitutes an obstacle in examining P. vivax liver stage infection and drug efficacy. To overcome this obstacle, we have used human liver-chimeric (huHep) FRG KO mice as a model for P. vivax infection. FRG KO huHep mice support P. vivax sporozoite infection, liver stage development, and hypnozoite formation. We show complete P. vivax liver stage development, including maturation into infectious exo-erythrocytic merozoites as well as the formation and persistence of hypnozoites. Prophylaxis or treatment with the antimalarial primaquine can prevent and eliminate liver stage infection, respectively. Thus, P. vivax-infected FRG KO huHep mice are a model to investigate liver stage development and dormancy and may facilitate the discovery of drugs targeting relapsing malaria.

  18. Profoundly Reduced CD1c+ Myeloid Dendritic Cell HLA-DR and CD86 Expression and Increased Tumor Necrosis Factor Production in Experimental Human Blood-Stage Malaria Infection

    PubMed Central

    Minigo, Gabriela; Burel, Julie; Tipping, Peta E.; Piera, Kim A.; Amante, Fiona H.; Engwerda, Christian R.; Good, Michael F.; Doolan, Denise L.; Anstey, Nicholas M.; McCarthy, James S.; Woodberry, Tonia

    2016-01-01

    Dendritic cells (DCs) are sentinels of the immune system that uniquely prime naive cells and initiate adaptive immune responses. CD1c (BDCA-1) myeloid DCs (CD1c+ mDCs) highly express HLA-DR, have a broad Toll-like receptor (TLR) repertoire, and secrete immune modulatory cytokines. To better understand immune responses to malaria, CD1c+ mDC maturation and cytokine production were examined in healthy volunteers before and after experimental intravenous Plasmodium falciparum infection with 150- or 1,800-parasite-infected red blood cells (pRBCs). After either dose, CD1c+ mDCs significantly reduced HLA-DR expression in prepatent infections. Circulating CD1c+ mDCs did not upregulate HLA-DR after pRBC or TLR ligand stimulation and exhibited reduced CD86 expression. At peak parasitemia, CD1c+ mDCs produced significantly more tumor necrosis factor (TNF), whereas interleukin-12 (IL-12) production was unchanged. Interestingly, only the 1,800-pRBC dose caused a reduction in the circulating CD1c+ mDC count with evidence of apoptosis. The 1,800-pRBC dose produced no change in T cell IFN-γ or IL-2 production at peak parasitemia or at 3 weeks posttreatment. Overall, CD1c+ mDCs are compromised by P. falciparum exposure, with impaired HLA-DR and CD86 expression, and have an increased capacity for TNF but not IL-12 production. A first prepatent P. falciparum infection is sufficient to modulate CD1c+ mDC responsiveness, likely contributing to hampered effector T cell cytokine responses and assisting parasite immune evasion. PMID:26902728

  19. Profoundly Reduced CD1c+ Myeloid Dendritic Cell HLA-DR and CD86 Expression and Increased Tumor Necrosis Factor Production in Experimental Human Blood-Stage Malaria Infection.

    PubMed

    Loughland, Jessica R; Minigo, Gabriela; Burel, Julie; Tipping, Peta E; Piera, Kim A; Amante, Fiona H; Engwerda, Christian R; Good, Michael F; Doolan, Denise L; Anstey, Nicholas M; McCarthy, James S; Woodberry, Tonia

    2016-05-01

    Dendritic cells (DCs) are sentinels of the immune system that uniquely prime naive cells and initiate adaptive immune responses. CD1c (BDCA-1) myeloid DCs (CD1c(+) mDCs) highly express HLA-DR, have a broad Toll-like receptor (TLR) repertoire, and secrete immune modulatory cytokines. To better understand immune responses to malaria, CD1c(+) mDC maturation and cytokine production were examined in healthy volunteers before and after experimental intravenous Plasmodium falciparum infection with 150- or 1,800-parasite-infected red blood cells (pRBCs). After either dose, CD1c(+) mDCs significantly reduced HLA-DR expression in prepatent infections. Circulating CD1c(+) mDCs did not upregulate HLA-DR after pRBC or TLR ligand stimulation and exhibited reduced CD86 expression. At peak parasitemia, CD1c(+) mDCs produced significantly more tumor necrosis factor (TNF), whereas interleukin-12 (IL-12) production was unchanged. Interestingly, only the 1,800-pRBC dose caused a reduction in the circulating CD1c(+) mDC count with evidence of apoptosis. The 1,800-pRBC dose produced no change in T cell IFN-γ or IL-2 production at peak parasitemia or at 3 weeks posttreatment. Overall, CD1c(+) mDCs are compromised by P. falciparum exposure, with impaired HLA-DR and CD86 expression, and have an increased capacity for TNF but not IL-12 production. A first prepatent P. falciparum infection is sufficient to modulate CD1c(+) mDC responsiveness, likely contributing to hampered effector T cell cytokine responses and assisting parasite immune evasion.

  20. Presence of Rheumatoid Factor during Chronic HCV Infection Is Associated with Expansion of Mature Activated Memory B-Cells that Are Hypo-Responsive to B-Cell Receptor Stimulation and Persist during the Early Stage of IFN Free Therapy

    PubMed Central

    Reyes-Avilés, Elane; Kostadinova, Lenche; Rusterholtz, Anne; Cruz-Lebrón, Angelica; Falck-Ytter, Yngve; Anthony, Donald D.

    2015-01-01

    Approximately half of those with chronic hepatitis C virus (HCV) infection have circulating rheumatoid factor (RF), and a portion of these individuals develop cryoglobulinemic vasculitis. B cell phenotype/function in relation to RF in serum has been unclear. We examined B cell subset distribution, activation state (CD86), cell cycle state (Ki67), and ex-vivo response to BCR, TLR9 and TLR7/8 stimulation, in chronic HCV-infected donors with or without RF, and uninfected donors. Mature-activated B-cells of HCV-infected donors had lower CD86 expression compared to uninfected donors, and in the presence of RF they also showed reduced CD86 expression in response to BCR and TLR9 stimulation. Additionally, mature activated memory B cells of HCV RF+ donors less commonly expressed Ki67+ than HCV RF- donors, and did not proliferate as well in response to BCR stimulation. Proportions of mature-activated B cells were enhanced, while naïve B-cells were lower in the peripheral blood of HCV-RF+ compared to RF- and uninfected donors. None of these parameters normalize by week 8 of IFN free direct acting antiviral (DAA) therapy in HCV RF+ donors, while in RF- donors, mature activated B cell proportions did normalize. These data indicate that while chronic HCV infection alone results in a lower state of activation in mature activated memory B cells, the presence of RF in serum is associated with a more pronounced state of unresponsiveness and an overrepresentation of these B cells in the blood. This phenotype persists at least during the early time window after removal of HCV from the host. PMID:26649443

  1. Hookworm infection

    MedlinePlus

    Hookworm disease; Ground itch; Ancylostoma duodenale infection; Necator americanus infection; Parasitic infection - hookworm ... The last 2 types also occur in animals. Hookworm disease is common in the moist tropics and ...

  2. Vaginal Infections

    MedlinePlus

    ... Two common vaginal infections are bacterial vaginosis and yeast infections . Bacterial vaginosis (BV) happens when a certain ... increases the chances that you’ll get BV. Yeast infections happen when a fungus (a type of ...

  3. Staphylococcal Infections

    MedlinePlus

    ... of bacteria. There are over 30 types, but Staphylococcus aureus causes most staph infections (pronounced "staff infections"), including ... Some staph bacteria such as MRSA (methicillin-resistant Staphylococcus aureus) are resistant to certain antibiotics, making infections harder ...

  4. Whipworm infection

    MedlinePlus

    ... of the large intestine with a type of roundworm. ... Whipworm infection is caused by the roundworm Trichuris trichiura. It is a common infection that mainly affects children. Children may become infected if they swallow soil contaminated with whipworm ...

  5. Eye Infections

    MedlinePlus

    Your eyes can get infections from bacteria, fungi, or viruses. Eye infections can occur in different parts of the eye and can affect just one eye or both. Two common eye infections are Conjunctivitis - also known as pinkeye. Conjunctivitis is ...

  6. Bone Infections

    MedlinePlus

    ... of the body, bones can get infected. The infections are usually bacterial, but can also be fungal. ... bloodstream. People who are at risk for bone infections include those with diabetes, poor circulation, or recent ...

  7. Immunity to erythrocytic stages of malarial parasites.

    PubMed

    Long, C A; Daly, T M; Kima, P; Srivastava, I

    1994-01-01

    In those individuals who live in endemic areas, immunity to malaria is slow to develop and stage-specific. The nature and antigenic specificity of this response, which may involve components of both cell-mediated and humoral immunity, is not well understood. Rodent models provide useful systems to explore the spectrum of host responses that may contribute to resolution of erythrocytic-stage infection or possibly to pathogenesis. Moreover, these models allow identification of plasmodial molecules that can induce different types of host responses. Two different mouse model systems, Plasmodium yoelii yoelii and P. chabaudi adami are presented. These have been selected because resolution of infection by P. yoelii yoelii has been shown to require B cell-dependent mechanisms, while control of acute P. chabaudi adami infection can be achieved by T cell-dependent mechanisms. A monoclonal antibody that provides passive protection to P. yoelii challenge infection has been shown to recognize the cysteine-rich, carboxyl-terminal region of the merozoite surface protein-1. This region, obtained in an appropriate configuration from recombinant Escherichia coli, can induce significant protective immune responses in naive mice. In contrast, cell-mediated immune mechanisms make a major contribution to resolution of asexual-stage P. chabaudi adami infection. An empirical approach using continuous flow electrophoresis has identified several low molecular weight plasmodial proteins that can induce partial protective responses in susceptible hosts. These observations are briefly discussed with respect to human malaria.

  8. Lunar Module Ascent Stage

    NASA Technical Reports Server (NTRS)

    1969-01-01

    The Lunar Module 'Spider' ascent stage is photographed from the Command/Service Module on the fifth day of the Apollo 9 earth-orbital mission. The Lunar Module's descent stage had already been jettisoned.

  9. Stages of Adolescence

    MedlinePlus

    ... Español Text Size Email Print Share Stages of Adolescence Page Content Article Body Adolescence, these years from puberty to adulthood, may be roughly divided into three stages: early adolescence, generally ages eleven to fourteen; middle adolescence, ages ...

  10. Breast cancer staging

    MedlinePlus

    Doctors use 7 main stages to describe breast cancer. Stage 0, also called carcinoma in situ. This is cancer that is confined to the lobules or ducts in the breast. It has not spread to surrounding tissue. ...

  11. Ovarian Cancer Stage IV

    MedlinePlus

    ... hyphen, e.g. -historical Searches are case-insensitive Ovarian Cancer Stage IV Add to My Pictures View /Download : ... 1200x1335 View Download Large: 2400x2670 View Download Title: Ovarian Cancer Stage IV Description: Drawing of stage IV shows ...

  12. Ovarian Cancer Stage IIIC

    MedlinePlus

    ... hyphen, e.g. -historical Searches are case-insensitive Ovarian Cancer Stage IIIC Add to My Pictures View /Download : ... 1530x1350 View Download Large: 3060x2700 View Download Title: Ovarian Cancer Stage IIIC Description: Drawing of stage IIIC shows ...

  13. Ovarian Cancer Stage II

    MedlinePlus

    ... hyphen, e.g. -historical Searches are case-insensitive Ovarian Cancer Stage II Add to My Pictures View /Download : ... 1650x675 View Download Large: 3300x1350 View Download Title: Ovarian Cancer Stage II Description: Three-panel drawing of stage ...

  14. Ovarian Cancer Stage I

    MedlinePlus

    ... hyphen, e.g. -historical Searches are case-insensitive Ovarian Cancer Stage I Add to My Pictures View /Download : ... 1650x675 View Download Large: 3300x1350 View Download Title: Ovarian Cancer Stage I Description: Three-panel drawing of stage ...

  15. Beyond Erikson's Eight Stages.

    ERIC Educational Resources Information Center

    Whitney, Ruth

    1979-01-01

    Erik Erikson has described eight stages of the healthy personality. This essay offers a revised version of the eight stages. Although most individuals develop through the eight stages, each is personally unique because patterns of fluctuation between safety and growth differ from one individual to another. (Author)

  16. [Neonatal herpes simplex infection].

    PubMed

    van Ham-Borawitz, Veronique E J; Stam, Edo D; Welborn, Kathleen M; Sas, Theo C J

    2016-01-01

    Neonatal encephalitis caused by herpes simplex virus (HSV) is a familiar disease with a high mortality and morbidity rate. Isolated skin-eye-mouth infection is less familiar among professionals. In this article we present two neonates with an isolated skin lesion caused by an HSV infection. Of the neonates infected with HSV, 40-45% show isolated skin-eye-mouth disease. With correct treatment, the risk of spread to the central nervous system will decrease from 50-60% to 5-10%. Typical HSV skin lesions may present at a late stage of the disease or may be masked by a secondary bacterial infection. When a neonate presents with atypical skin lesions starting 7-12 days after the birth, immediate testing for HSV and immediate treatment are required, to decrease the risk of further progression of the disease.

  17. Second stage of labor.

    PubMed

    Cheng, Yvonne W; Caughey, Aaron B

    2015-06-01

    Current American College of Obstetricians and Gynecologists' definition of prolonged second stage diagnoses 10% to 14% of nulliparous and 3% to 3.5% of multiparous women as having a prolonged second stage. The progression of labor in modern obstetrics may have deviated from the current labor norms established in the 1950s, likely due to differences in obstetric population characteristics and variation in clinical practice. Optimal management of the second stage in women with and without epidural remains debatable. Although prolonged second stage is associated with increased risk of maternal morbidity, conflicting data exist regarding the duration of second stage and associated neonatal morbidity and mortality.

  18. Susceptibility of different developmental stages of large pine weevil Hylobius abietis (Coleoptera: Curculionidae) to entomopathogenic fungi and effect of fungal infection to adult weevils by formulation and application methods.

    PubMed

    Ansari, Minshad A; Butt, Tariq M

    2012-09-15

    The large pine weevil, Hylobius abietis, is a major pest in European conifer forests causing millions of Euros of damage annually. Larvae develop in the stumps of recently felled trees; the emerging adults feed on the bark of seedlings and may kill them. This study investigated the susceptibility of different developmental stages of H. abietis to commercial and commercially viable isolates of entomopathogenic fungi, Metarhizium and Beauveria. All the developmental stages of H. abietis can be killed by Metarhizium robertsii, Metarhizium brunneum, and Beauveria bassiana. The most virulent isolate of M. robertsii ARSEF4556 caused 100% mortality of pupae, larvae and adults on day 4, 6 and 12, respectively. This strain was further tested against adult weevils in different concentrations (10(5)-10(8) conidia cm(-2) or ml(-1)) using two types of fungal formulation: 'dry' conidia and 'wet' conidia (suspended in 0.03% aq. Tween 80) applied on different substrates (tissue paper, peat and Sitka spruce seedlings). 'Dry' conidia were more effective than 'wet' conidia on tissue paper and on spruce or 'dry' conidia premixed in peat. The LC(50) value for 'dry' conidia of isolate ARSEF4556 was three folds lower than 'wet' conidia on tissue paper. This study showed that 'dry' conidia are more effective than 'wet' conidia, causing 100% adult mortality within 12 days. Possible strategies for fungal applications are discussed in light of the high susceptibility of larvae and pupae to fungal pathogen.

  19. Cetuximab, Cisplatin, and Radiation Therapy in Treating Patients With Stage IB, Stage II, Stage III, or Stage IVA Cervical Cancer

    ClinicalTrials.gov

    2014-12-29

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  20. HIV-Resistant Gene Modified Stem Cells and Chemotherapy in Treating Patients With Lymphoma With HIV Infection

    ClinicalTrials.gov

    2016-09-06

    HIV Infection; Stage I Adult Hodgkin Lymphoma; Stage I Adult Non-Hodgkin Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage II Adult Non-Hodgkin Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Non-Hodgkin Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Non-Hodgkin Lymphoma

  1. Staged electrostatic precipitator

    DOEpatents

    Miller, Stanley J.; Almlie, Jay C.; Zhuang, Ye

    2016-03-01

    A device includes a chamber having an air inlet and an air outlet. The device includes a plurality of stages including at least a first stage adjacent a second stage. The plurality of stages are disposed in the chamber and each stage has a plurality of discharge electrodes disposed in an interior region and is bounded by an upstream baffle on an end proximate the air inlet and bounded by a downstream baffle on an end proximate the air outlet. Each stage has at least one sidewall between the upstream baffle and the downstream baffle. The sidewall is configured as a collection electrode and has a plurality of apertures disposed along a length between the upstream baffle and the downstream baffle. The upstream baffle of the first stage is positioned in staggered alignment relative to the upstream baffle of the second stage and the downstream baffle of the first stage are positioned in staggered alignment relative to the downstream baffle of the second stage.

  2. Two stage catalytic combustor

    NASA Technical Reports Server (NTRS)

    Alvin, Mary Anne (Inventor); Bachovchin, Dennis (Inventor); Smeltzer, Eugene E. (Inventor); Lippert, Thomas E. (Inventor); Bruck, Gerald J. (Inventor)

    2010-01-01

    A catalytic combustor (14) includes a first catalytic stage (30), a second catalytic stage (40), and an oxidation completion stage (49). The first catalytic stage receives an oxidizer (e.g., 20) and a fuel (26) and discharges a partially oxidized fuel/oxidizer mixture (36). The second catalytic stage receives the partially oxidized fuel/oxidizer mixture and further oxidizes the mixture. The second catalytic stage may include a passageway (47) for conducting a bypass portion (46) of the mixture past a catalyst (e.g., 41) disposed therein. The second catalytic stage may have an outlet temperature elevated sufficiently to complete oxidation of the mixture without using a separate ignition source. The oxidation completion stage is disposed downstream of the second catalytic stage and may recombine the bypass portion with a catalyst exposed portion (48) of the mixture and complete oxidation of the mixture. The second catalytic stage may also include a reticulated foam support (50), a honeycomb support, a tube support or a plate support.

  3. Infection and Cardiovascular Disease

    ClinicalTrials.gov

    2016-02-17

    Cardiovascular Diseases; Coronary Disease; Cerebrovascular Accident; Heart Diseases; Myocardial Infarction; Infection; Chlamydia Infections; Cytomegalovirus Infections; Helicobacter Infections; Atherosclerosis

  4. Liver-stage malaria parasites vulnerable to diverse chemical scaffolds

    PubMed Central

    Derbyshire, Emily R.; Prudêncio, Miguel; Mota, Maria M.; Clardy, Jon

    2012-01-01

    Human malaria infection begins with a one-time asymptomatic liver stage followed by a cyclic symptomatic blood stage. All high-throughput malaria drug discovery efforts have focused on the cyclic blood stage, which has limited potential for the prophylaxis, transmission blocking, and eradication efforts that will be needed in the future. To address these unmet needs, a high-throughput phenotypic liver-stage Plasmodium parasite screen was developed to systematically identify molecules with liver-stage efficacy. The screen recapitulates liver-stage infection by isolating luciferase-expressing Plasmodium berghei parasites directly from the salivary glands of infected mosquitoes, adding them to confluent human liver cells in 384-well plates, and measuring luciferase activity after a suitable incubation period. Screening 5,375 known bioactive compounds identified 37 liver-stage malaria inhibitors with diverse modes of action, as shown by inhibition time course experiments. Further analysis of the hits in the Food and Drug Administration-approved drug subset revealed compounds that seem to act specifically on the liver stage of infection, suggesting that this phase of the parasite’s life cycle presents a promising area for new drug discovery. Notably, many active compounds in this screen have molecular structures and putative targets distinctly different from those of known antimalarial agents. PMID:22586124

  5. Third molar infections.

    PubMed

    Gutiérrez-Pérez, José Luis

    2004-01-01

    Pericoronitis is an infectious disease often associated with the eruption of a third molar. It can be either acute (serous and suppurative) or chronic. Pain is usually the predominant symptom in acute stages, whereas chronic forms of the disease may display very few symptoms. Both present exudate. The infection is multimicrobial, predominantly caused strictly by betalactamase-producing anaerobeic microorganisms. Treatment measures are symptomatic, antimicrobial and surgical. Antimicrobial treatment is indicated for preoperative prophylaxis when there is a high risk of postoperative infection and, during the acute stages of suppurative pericoronitis when surgery must be postponed. First-line treatment in this case consists of amoxicillin with associated clavulanic acid. Although surgical treatment of pericoronitis presenting at the third molar is indicated as a Grade C recommendation for extraction, it is the most common indication for extraction of a retained third molar, owing to the improved quality of life it can offer the patient.

  6. Coronavirus Infections

    MedlinePlus

    ... may be able to reduce your risk of infection by washing your hands often with soap and ... sick. There is no vaccine to prevent coronavirus infection. There are no specific treatments. You can relieve ...

  7. Campylobacter infection

    MedlinePlus

    ... infection occurs in the small intestine from a bacteria called Campylobacter jejuni . It is a type of food poisoning. ... Campylobacter enteritis is a common cause of intestinal infection . ... of traveler's diarrhea or food poisoning . People most often ...

  8. Gastrointestinal Infections.

    PubMed

    Alby, Kevin; Nachamkin, Irving

    2016-06-01

    Gastrointestinal infections in the immunocompromised host are caused by the common bacterial, viral, fungal, and parasitic agents that also cause infections in the immunocompetent host. Of special consideration is that immunocompromised patients may be at increased risk for infection or disease severity and by pathogens not seen in the competent host. This chapter reviews the various agents, risk factors, and diagnostic approaches to detect gastrointestinal infections in this patient population. PMID:27337464

  9. Staging Early Esophageal Cancer.

    PubMed

    Old, O J; Isabelle, M; Barr, H

    2016-01-01

    Staging esophageal cancer provides a standardized measure of the extent of disease that can be used to inform decisions about therapy and guide prognosis. For esophageal cancer, the treatment pathways vary greatly depending on stage of disease, and accurate staging is therefore crucial in ensuring the optimal therapy for each patient. For early esophageal cancer (T1 lesions), endoscopic resection can be curative and simultaneously gives accurate staging of depth of invasion. For tumors invading the submucosa or more advanced disease, comprehensive investigation is required to accurately stage the tumor and assess suitability for curative resection. A combined imaging approach of computed tomography (CT), positron emission tomography (PET), and endoscopic ultrasound (EUS) offers complementary diagnostic information and gives the greatest chance of accurate staging. Staging laparoscopy can identify peritoneal disease and small superficial liver lesions that could be missed on CT or PET, and alters management in up to 20 % of patients. Optical diagnostic techniques offer the prospect of further extending the possibilities of endoscopic staging in real time. Optical coherence tomography can image superficial lesions and could provide information on depth of invasion for these lesions. Real-time lymph node analysis using optical diagnostics such as Raman spectroscopy could be used to support immediate endoscopic therapy without waiting for results of cytology or further investigations. PMID:27573772

  10. A Hypoderma diana (Diptera: Hypodermatidae) infection in a horse.

    PubMed

    Hendrikx, W M; Jansen, J; de Vries, T J

    1989-01-01

    An infection with second-stage larvae of the warble-fly H. diana in a horse is described. The second-stage larvae were incapable of developing into the third stage, because horses are unsuitable hosts and because the infected horse was treated with an insecticide. Since the horse was used for dragging trees in the forests, the infection was likely contracted via contact with H. diana, a normal parasite of roe deer in the Netherlands. PMID:2718349

  11. Staging for vulvar cancer.

    PubMed

    Hacker, Neville F; Barlow, Ellen L

    2015-08-01

    Vulvar cancer has been staged by the International Federation of Gynaecology and Obstetrics (FIGO) since 1969, and the original staging system was based on clinical findings only. This system provided a very good spread of prognostic groupings. Because vulvar cancer is virtually always treated surgically, the status of the lymph nodes is the most important prognostic factor and this can only be determined with certainty by histological examination of resected lymph nodes, FIGO introduced a surgical staging system in 1988. This was modified in 1994 to include a category of microinvasive vulvar cancer (stage IA), because such patients have virtually no risk of lymph node metastases. This system did not give a reasonably even spread of prognostic groupings. In addition, patients with stage III disease were shown to be a heterogeneous group prognostically, and the number of positive nodes and the morphology of those nodes were not taken into account. A new surgical staging system for vulvar cancer was introduced by FIGO in 2009. Initial retrospective analyses have suggested that this new staging system has overcome the major deficiencies in the 1994 system.

  12. Heterologous Infection During Chagas' Disease

    NASA Astrophysics Data System (ADS)

    Sibona, G. J.; Condat, C. A.; Cossi Isasi, S.

    2007-05-01

    Human populations are often infected with more than one parasite strain. This is frequently the case with ChagasŠ disease, which is endemic to large regions of Latin America. In the present work we study the dynamics of the heterologous infection for this disease, using a model for the interaction between the trypanosoma cruzi parasite and the immune system. We find the dependence of the nature of the post-acute stage on the parameters characterizing the inoculated infectious strains.

  13. Staging Airliner Service

    NASA Technical Reports Server (NTRS)

    Hahn, Andrew S.

    2007-01-01

    There is a general consensus building that historically high fuel prices and greater public awareness of the emissions that result from burning fuel are going to be long-term concerns for those who design, build, and operate airliners. The possibility of saving both fuel and reducing emissions has rekindled interest in breaking very long-range airline flights into multiple stages or even adopting in-flight refueling. It is likely that staging will result in lower fuel burn, and recent published reports have suggested that the savings are substantial, particularly if the airliner is designed from the outset for this kind of operation. Given that staging runs against the design and operation historical trend, this result begs for further attention. This paper will examine the staging question, examining both analytic and numeric performance estimation methodologies to quantify the likely amount of fuel savings that can be expected and the resulting design impacts on the airliner.

  14. Understanding cancer staging

    MedlinePlus

    ... the body. The spread of cancer is called metastasis . Cancer staging is used to help describe the ... cancer has spread to nearby lymph nodes (N) Metastasis (M) , or if and how much the cancer ...

  15. Stages of Pregnancy

    MedlinePlus

    ... your baby in these three stages. First trimester (week 1-week 12) First trimester See how your baby is ... is each pregnancy. Return to top Second trimester (week 13-week 28) Second trimester See how your ...

  16. Cryogenic Propulsion Stage

    NASA Technical Reports Server (NTRS)

    Jones, David

    2011-01-01

    The CPS is an in-space cryogenic propulsive stage based largely on state of the practice design for launch vehicle upper stages. However, unlike conventional propulsive stages, it also contains power generation and thermal control systems to limit the loss of liquid hydrogen and oxygen due to boil-off during extended in-space storage. The CPS provides the necessary (Delta)V for rapid transfer of in-space elements to their destinations or staging points (i.e., E-M L1). The CPS is designed around a block upgrade strategy to provide maximum mission/architecture flexibility. Block 1 CPS: Short duration flight times (hours), passive cryo fluid management. Block 2 CPS: Long duration flight times (days/weeks/months), active and passive cryo fluid management.

  17. Stages of Pancreatic Cancer

    MedlinePlus

    ... cancer) cells form in the tissues of the pancreas. The pancreas is a gland about 6 inches ... spleen , and bile ducts . Tests that examine the pancreas are used to detect (find), diagnose, and stage ...

  18. Radar stage uncertainty

    USGS Publications Warehouse

    Fulford, J.M.; Davies, W.J.

    2005-01-01

    The U.S. Geological Survey is investigating the performance of radars used for stage (or water-level) measurement. This paper presents a comparison of estimated uncertainties and data for radar water-level measurements with float, bubbler, and wire weight water-level measurements. The radar sensor was also temperature-tested in a laboratory. The uncertainty estimates indicate that radar measurements are more accurate than uncorrected pressure sensors at higher water stages, but are less accurate than pressure sensors at low stages. Field data at two sites indicate that radar sensors may have a small negative bias. Comparison of field radar measurements with wire weight measurements found that the radar tends to measure slightly lower values as stage increases. Copyright ASCE 2005.

  19. Precision adjustable stage

    DOEpatents

    Cutburth, Ronald W.; Silva, Leonard L.

    1988-01-01

    An improved mounting stage of the type used for the detection of laser beams is disclosed. A stage center block is mounted on each of two opposite sides by a pair of spaced ball bearing tracks which provide stability as well as simplicity. The use of the spaced ball bearing pairs in conjunction with an adjustment screw which also provides support eliminates extraneous stabilization components and permits maximization of the area of the center block laser transmission hole.

  20. Multiple stage railgun

    DOEpatents

    Hawke, Ronald S.; Scudder, Jonathan K.; Aaland, Kristian

    1982-01-01

    A multiple stage magnetic railgun accelerator (10) for accelerating a projectile (15) by movement of a plasma arc (13) along the rails (11,12). The railgun (10) is divided into a plurality of successive rail stages (10a-n) which are sequentially energized by separate energy sources (14a-n) as the projectile (15) moves through the bore (17) of the railgun (10). Propagation of energy from an energized rail stage back towards the breech end (29) of the railgun (10) can be prevented by connection of the energy sources (14a-n) to the rails (11,12) through isolation diodes (34a-n). Propagation of energy from an energized rail stage back towards the breech end of the railgun can also be prevented by dividing the rails (11,12) into electrically isolated rail sections (11a-n, 12a-n). In such case means (55a-n) are used to extinguish the arc at the end of each energized stage and a fuse (31) or laser device (61) is used to initiate a new plasma arc in the next energized rail stage.

  1. Bioimpedance Spectroscopy in Detecting Lower-Extremity Lymphedema in Patients With Stage I, Stage II, Stage III, or Stage IV Vulvar Cancer Undergoing Surgery and Lymphadenectomy

    ClinicalTrials.gov

    2016-02-09

    Lymphedema; Perioperative/Postoperative Complications; Stage IA Vulvar Cancer; Stage IB Vulvar Cancer; Stage II Vulvar Cancer; Stage IIIA Vulvar Cancer; Stage IIIB Vulvar Cancer; Stage IIIC Vulvar Cancer; Stage IVA Vulvar Cancer; Stage IVB Vulvar Cancer

  2. Chemotherapy Toxicity On Quality of Life in Older Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-02-09

    Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IB Fallopian Tube Cancer; Stage IC Fallopian Tube Cancer; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIB Fallopian Tube Cancer; Stage IIC Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIC Fallopian Tube Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  3. 2-Stage Classification Modeling

    1994-11-01

    CIRCUIT2.4 is used to design optimum two-stage classification configurations and operating conditions for energy conservation. It permits simulation of five basic grinding-classification circuits, including one single-stage and four two-stage classification arrangements. Hydrocyclones, spiral classifiers, and sieve band screens can be simulated, and the user may choose the combination of devices for the flowsheet simulation. In addition, the user may select from four classification modeling methods to achieve the goals of a simulation project using themore » most familiar concepts. Circuit performance is modeled based on classification parameters or equipment operating conditions. A modular approach was taken in designing the program, which allows future addition of other models with relatively minor changes.« less

  4. 2-Stage Classification Modeling

    SciTech Connect

    Baltich, L. K.

    1994-11-01

    CIRCUIT2.4 is used to design optimum two-stage classification configurations and operating conditions for energy conservation. It permits simulation of five basic grinding-classification circuits, including one single-stage and four two-stage classification arrangements. Hydrocyclones, spiral classifiers, and sieve band screens can be simulated, and the user may choose the combination of devices for the flowsheet simulation. In addition, the user may select from four classification modeling methods to achieve the goals of a simulation project using the most familiar concepts. Circuit performance is modeled based on classification parameters or equipment operating conditions. A modular approach was taken in designing the program, which allows future addition of other models with relatively minor changes.

  5. Staging of prostate cancer.

    PubMed

    Cheng, Liang; Montironi, Rodolfo; Bostwick, David G; Lopez-Beltran, Antonio; Berney, Daniel M

    2012-01-01

    Prostatic carcinoma (PCa) is a significant cause of cancer morbidity and mortality worldwide. Accurate staging is critical for prognosis assessment and treatment planning for PCa. Despite the large volume of clinical activity and research, the challenge to define the most appropriate and clinically relevant staging system remains. The pathologically complex and uncertain clinical course of prostate cancer further complicates the design of staging classification and a substaging system suitable for individualized care. This review will focus on recent progress and controversial issues related to prostate cancer staging. The 2010 revision of the American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumour, node and metastasis (TNM) system is the most widely used staging system at this time. Despite general acceptance of the system as a whole, there is controversy and uncertainty about its application, particularly for T2 subclassification. The three-tiered T2 classification system for organ-confined prostate cancer is superfluous, considering the biology and anatomy of PCa. A tumour size-based substaging system may be considered in the future TNM subclassification of pT2 cancer. Lymph node status is one of the most important prognostic factors for prostate cancer. Nevertheless, clinical outcomes in patients with positive lymph nodes are variable. Identification of patients at the greatest risk of systemic progression helps in the selection of appropriate therapy. The data suggest that the inherent aggressiveness of metastatic prostate cancer is closely linked to the tumour volume of lymph node metastasis. We recommend that a future TNM staging system should consider subclassification of node-positive cancer on the basis of nodal cancer volume, using the diameter of the largest nodal metastasis and/or the number of positive nodes.

  6. Staging of prostate cancer.

    PubMed

    Cheng, Liang; Montironi, Rodolfo; Bostwick, David G; Lopez-Beltran, Antonio; Berney, Daniel M

    2012-01-01

    Prostatic carcinoma (PCa) is a significant cause of cancer morbidity and mortality worldwide. Accurate staging is critical for prognosis assessment and treatment planning for PCa. Despite the large volume of clinical activity and research, the challenge to define the most appropriate and clinically relevant staging system remains. The pathologically complex and uncertain clinical course of prostate cancer further complicates the design of staging classification and a substaging system suitable for individualized care. This review will focus on recent progress and controversial issues related to prostate cancer staging. The 2010 revision of the American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumour, node and metastasis (TNM) system is the most widely used staging system at this time. Despite general acceptance of the system as a whole, there is controversy and uncertainty about its application, particularly for T2 subclassification. The three-tiered T2 classification system for organ-confined prostate cancer is superfluous, considering the biology and anatomy of PCa. A tumour size-based substaging system may be considered in the future TNM subclassification of pT2 cancer. Lymph node status is one of the most important prognostic factors for prostate cancer. Nevertheless, clinical outcomes in patients with positive lymph nodes are variable. Identification of patients at the greatest risk of systemic progression helps in the selection of appropriate therapy. The data suggest that the inherent aggressiveness of metastatic prostate cancer is closely linked to the tumour volume of lymph node metastasis. We recommend that a future TNM staging system should consider subclassification of node-positive cancer on the basis of nodal cancer volume, using the diameter of the largest nodal metastasis and/or the number of positive nodes. PMID:22212080

  7. Postpartum Infections

    MedlinePlus

    ... Drug Interactions Pill Identifier Commonly searched drugs Aspirin Metformin Warfarin Tramadol Lactulose Ranitidine News & Commentary Recent News ... Muscle Disorders Brain, Spinal Cord, and Nerve Disorders Cancer Children's Health Issues ... Bladder and Kidney Infections Breast Infection Postpartum Blood Clots Postpartum Thyroid Disorders Postpartum ...

  8. Infection Control

    MedlinePlus

    ... These steps are part of infection control. Proper hand washing is the most effective way to prevent the spread of infections in hospitals. If you are a patient, don't be afraid to remind friends, family and health care providers to wash their hands before getting close to you. Other ...

  9. Salmonella Infections

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infections with bacteria of the genus Salmonella are responsible for both acute and chronic poultry diseases. These diseases cause economically significant losses for poultry producers in many nations and absorb large investments of public and private resources in testing and control efforts. Infect...

  10. Stage cementing apparatus

    SciTech Connect

    Blamford, D.M.; Easter, J.H.

    1988-06-21

    A stage cementing apparatus for selectively passing cement from the interior passage of a casing to the annulus between the exterior of the casing and borehole, the casing having an upper portion and a lower portion, is described comprising: a barrel secured to the upper portion of the casing; a mandrel secured to the lower portion of the casing, and a stage cementing tool having a generally cylindrical configuration adapted for attachment to the lower end of the barrel about a portion of the mandrel.

  11. Staged fluidized bed

    DOEpatents

    Mallon, R.G.

    1983-05-13

    The invention relates to oil shale retorting and more particularly to staged fluidized bed oil shale retorting. Method and apparatus are disclosed for narrowing the distribution of residence times of any size particle and equalizing the residence times of large and small particles in fluidized beds. Particles are moved up one fluidized column and down a second fluidized column with the relative heights selected to equalize residence times of large and small particles. Additional pairs of columns are staged to narrow the distribution of residence times and provide complete processing of the material.

  12. Infection of Plasmodiophora brassicae in Chinese cabbage.

    PubMed

    Ji, R; Zhao, L; Xing, M; Shen, X; Bi, Q; Peng, S; Feng, H

    2014-12-19

    Brassica crops infected by Plasmodiophora brassicae can produce root galls (clubroots) and be prevented from growing normally. To understand the series of changes that occur in the host root during root gall production, the resistance character of 21 Chinese cabbage lines were identified and then resistant and susceptible lines were used for infection observation. Hydroponic technology system was used for plants growing, and the infection process of P. brassicae in the roots of resistant and susceptible Chinese cabbage was examined based on morphology and microscopic characteristics using micoscope. In susceptible Chinese cabbage, the root hair infection stage occurred over approximately 7 days after inoculation, the cortical infection happened over approximatly 14 days after inoculation, and clubroots formed in approximately 30 days after inoculation. However, in resistant Chinese cabbage, the pathogen could be prevented and maintained in the root hair infection stage. This research provides a foundation for the subsequent studies of cabbage resistance of P. brassicae.

  13. [Diagnosis and treatment of periprosthetic infections].

    PubMed

    Lenz, M; Hofmann, G O; Mückley, T

    2012-06-01

    The differentiation of periprosthetic infections into early onset and late onset infections is the determining factor fores the therapeutic strategy. The diagnosis of chronic unapparent infections is sometimes difficult. The therapeutic success, especially in early onset infections, is essentially influenced by a well-timed diagnosis and an immediate therapy. Surgical wound debridement with preservation of the prosthesis, one-stage replacement and two-stage replacement all with concomitant appropriate systemically administered double combined antibiotics are therapeutic options depending on factors, such as the duration of the infection. Prosthesis replacement is currently the only option to treat biofilm colonization of endoprosthetic surfaces. The bacterial adhesion on polyethylene can be extremely resistant. Due to the therapeutic consequences, periprosthetic infections remain one of the worst complications in endoprosthetic joint replacement.

  14. One-stage vs. three-stage repair in anorectal malformation with rectovestibular fistula

    PubMed Central

    Amanollahi, Omid; Ketabchian, Saman

    2016-01-01

    Background: Anorectal malformations (ARMs) disease is one of the congenital anomalies with an incidence of about 1 in 5000 neonate births, and treatment requires surgical intervention. Selecting the one- or three-step surgical procedure to treat the disease, especially in female neonates with rectovestibular fistula, is a subject of debate. This study aims to compare the advantages and disadvantages of these two methods. Materials and Methods: Forty female neonates with ARM and rectovestibular fistula between March 2011 and March 2013 were included in the study, and they were divided into two equal groups. Allocation of the first case was random, and all cases were then allocated alternatively (every other subject was assigned to a treatment group) until each group received 20 cases equally patients of study group underwent a one-stage posterior sagittal anorectoplasty (PSARP) and in control group patients underwent a three-stage operation (colostomy, PSARP, and closure of colostomy). The complications during and after the surgery were recorded in both groups, and the results were compared. Results: In the control group, only one case (5%) of wound infection and dehiscence was seen, whereas in the one-stage study group, six cases (30%) of wound infection and dehiscence were seen (P value = 0.046). However, regarding the incidence of other complications, such as iatrogenic vaginal injury as well as final recovery, no considerable differences were seen between the two groups. Conclusions: Despite more surgical site infections and dehiscence in the one-stage repair, but due to the numerous advantages compared to the three-stage method, which is more time-consuming, more costly, and causes more adverse effect on parents and children, performing the one-stage repair is recommended for this anomaly. PMID:27251519

  15. Public Opinion, Public Policy, and HIV Infection.

    ERIC Educational Resources Information Center

    West, Jane

    1989-01-01

    A four-stage framework for considering the development of public policy in regard to the issue of HIV (Human Immunodeficiency Virus) infection is offered. The phases are denial, irrationality, acceptance, and the development of a rational response. Federal antidiscrimination policies which include persons with HIV infections as disabled are…

  16. Antibody response to Plasmodium vivax antigens in Fy-negative individuals from the Colombian Pacific coast.

    PubMed

    Herrera, Sócrates; Gómez, Andrés; Vera, Omaira; Vergara, Juana; Valderrama-Aguirre, Augusto; Maestre, Amanda; Méndez, Fabián; Wang, Ruobing; Chitnis, Chetan E; Yazdani, Syed S; Arévalo-Herrera, Myriam

    2005-11-01

    The Duffy antigen (Fy) is necessary for Plasmodium vivax invasion of human erythrocytes. Some populations have a highly prevalent Fy-negative phenotype; such persons are naturally protected from P. vivax blood infection but are expected to completely support the P. vivax pre-erythrocytic cycle, representing a valuable model for studying the immune response during these parasitic stages. We typed 214 individuals, mostly Afro-Colombians, from a P. vivax-endemic area for Fy expression and determined the antibody response to P. vivax pre-erythrocytic (sporozoites and CS) and blood-stage antigens (blood forms, P. vivax merozoite surface protein 1, and P. vivax Duffy binding protein [PvDBP]). Antibody titers to P. vivax circumsporozoite protein, P11, and N-terminal peptides and the number of responders were similar in Fy-negative and Fy-positive individuals. The number of responders to sporozoites, blood forms, and PvDBP were different between these groups. Thus, Fy-negative individuals from malaria-endemic areas can be used to study the immune response to the P. vivax liver phase without interference of the erythrocytic cycle.

  17. Photoacoustic spectroscopy of man infecting protozoans

    NASA Astrophysics Data System (ADS)

    Acosta-Avalos, D.; Alvarado-Gil, J. J.; Vargas, H.

    1998-08-01

    In this paper the fundamentals of photothermal spectroscopy are presented, special emphasis is done in the obtention of the optical absorption spectra. It is shown that this spectroscopy can be used successfully for the monitoring of protozoans that could infect the human. The usefulness of the technique is illustrated in the special case of Leishmania, where it is possible to find that the stage when the protozoan infect vertebrate cells show important differences in relation to the protozoans infecting insects.

  18. Photoacoustic spectroscopy of man infecting protozoans

    SciTech Connect

    Acosta-Avalos, D.; Alvarado-Gil, J. J.; Vargas, H.

    1998-08-28

    In this paper the fundamentals of photothermal spectroscopy are presented, special emphasis is done in the obtention of the optical absorption spectra. It is shown that this spectroscopy can be used successfully for the monitoring of protozoans that could infect the human. The usefulness of the technique is illustrated in the special case of Leishmania, where it is possible to find that the stage when the protozoan infect vertebrate cells show important differences in relation to the protozoans infecting insects.

  19. Crescentic ramp turbine stage

    NASA Technical Reports Server (NTRS)

    Lee, Ching-Pang (Inventor); Tam, Anna (Inventor); Kirtley, Kevin Richard (Inventor); Lamson, Scott Henry (Inventor)

    2007-01-01

    A turbine stage includes a row of airfoils joined to corresponding platforms to define flow passages therebetween. Each airfoil includes opposite pressure and suction sides and extends in chord between opposite leading and trailing edges. Each platform includes a crescentic ramp increasing in height from the leading and trailing edges toward the midchord of the airfoil along the pressure side thereof.

  20. Pancreatic Cancer Stage 4

    MedlinePlus

    ... lung, liver, and peritoneal cavity. An inset shows cancer cells spreading from the pancreas, through the blood and lymph system, to another ... abdomen that contains the intestines, stomach, and liver). Cancer may also have spread to ... pancreas or to lymph nodes. Stage IV pancreatic cancer. ...

  1. Stage a Water Show

    ERIC Educational Resources Information Center

    Frasier, Debra

    2008-01-01

    In the author's book titled "The Incredible Water Show," the characters from "Miss Alaineus: A Vocabulary Disaster" used an ocean of information to stage an inventive performance about the water cycle. In this article, the author relates how she turned the story into hands-on science teaching for real-life fifth-grade students. The author also…

  2. STS upper stage operations

    NASA Technical Reports Server (NTRS)

    Kitchens, M. D.; Schnyer, A. D.

    1977-01-01

    Several design/development and operational approaches for STS upper stages are being pursued to realize maximum operational and economic benefits upon the introduction of the STS in the 1980s. The paper focuses special attention on safety operations, launch site operations and on-orbit operations.

  3. End-Stage.

    ERIC Educational Resources Information Center

    Moua, Mai Neng

    2001-01-01

    Through her reflections on dealing with dialysis for end-stage renal disease and awaiting a kidney transplant, the author presents insights into how her experience was shaped by the physical, emotional, and multicultural forces she faced. Among the issues discussed are her ambivalent feelings between pursuing a regular lifestyle and receiving…

  4. Nail infections.

    PubMed

    Jules, K T; Bonar, P L

    1989-04-01

    Nail infections are and will continue to be a diagnostic and therapeutic challenge to all foot physicians. Attention to basic concepts of accurate detailed history and physical examination will aid in the determination of the etiology of these infections. Following basic guidelines of incision and drainage, gram stain, soaks, and antibiotics will be the cornerstone of initial treatment of pyogenic infections. Upon resolution of the acute infection a permanent treatment plan can be constituted based on the etiology. Nail infections of mycotic nature require an understanding by both patient and doctor as to the difficulty and resistance to treatment of this problem. It is the authors' opinion that aggressive persistent treatment will provide the best long-term result when dealing with mycotic infections. This may require nail removal, local and systemic treatment as well as change in shoe environment. As we have seen and is stated throughout this text, the nail and its pathologic processes can be a mirror of systemic disease. Many times a dystrophic infected nail may be the initial clinical presentation of a much more involved disease process. It is the responsibility and duty of all foot physicians to have a total understanding of knowledge of normal and pathologic process that affect the nail plates, nail bed, and surrounding nail proper. I hope this article will stimulate the foot physician to approach the disease of the nail with a high index of suspicion and respect. PMID:2650850

  5. Relationship of tadpole stage to location of echinostome cercaria encystment and the consequences for tadpole survival

    USGS Publications Warehouse

    Schotthoefer, A.M.; Cole, R.A.; Beasley, V.R.

    2003-01-01

    The effect of echinostome infections on the survival of Rana pipiens tadpoles was examined in relation to developmental stage of tadpoles. Individual tadpoles of Gosner stages 25, 27, 32a??33, and 37a??39 were exposed to 1 of 4 levels of cercariae (0, 20, 50, or 100). Only tadpoles at stage 25, the earliest stage infected, died within a 5-day experimental period. This stage-specific mortality rate could be explained, in part, by the stage-specific location of encystment of cercariae, which was documented in a separate experiment. In accordance with kidney development, cercariae predominately encysted in the pronephroi during early stages of tadpole development (stages 25 through 31a??32) and only in the mesonephroi and associated ducts at later stages (stages 37 through 46). As the mesonephros develops, renal capacity presumably increases. Thus, tadpoles died only when metacercariae concentrated in the functional portion of the kidney with the most limited renal capacity. As tadpoles aged, they also became less susceptible to infections. On average, 69.5% of cercariae that were exposed to stage 25a??26 tadpoles successfully encysted, compared with only 8.4% of cercariae exposed to stage 37a??38 tadpoles. Exposures of metamorphic frogs (poststage 46) to cercariae revealed that these individuals can become infected with echinostomes. Collectively, our data highlight the host stagea??dependent dynamics of tadpolea??echinostome interactions.

  6. Human Influenza Virus Infections.

    PubMed

    Peteranderl, Christin; Herold, Susanne; Schmoldt, Carole

    2016-08-01

    Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact. Accordingly, particular efforts are made to advance our knowledge on the disease biology and pathology and recent studies have brought new insights into IAV adaptation mechanisms to the human host, as well as into the key players in disease pathogenesis on the host side. Current antiviral strategies are only efficient at the early stages of the disease and are challenged by the genomic instability of the virus, highlighting the need for novel antiviral therapies targeting the pulmonary host response to improve viral clearance, reduce the risk of bacterial coinfection, and prevent or attenuate acute lung injury. This review article summarizes our current knowledge on the molecular basis of influenza infection and disease progression, the key players in pathogenesis driving severe disease and progression to lung failure, as well as available and envisioned prevention and treatment strategies against influenza virus infection. PMID:27486731

  7. Human Influenza Virus Infections.

    PubMed

    Peteranderl, Christin; Herold, Susanne; Schmoldt, Carole

    2016-08-01

    Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact. Accordingly, particular efforts are made to advance our knowledge on the disease biology and pathology and recent studies have brought new insights into IAV adaptation mechanisms to the human host, as well as into the key players in disease pathogenesis on the host side. Current antiviral strategies are only efficient at the early stages of the disease and are challenged by the genomic instability of the virus, highlighting the need for novel antiviral therapies targeting the pulmonary host response to improve viral clearance, reduce the risk of bacterial coinfection, and prevent or attenuate acute lung injury. This review article summarizes our current knowledge on the molecular basis of influenza infection and disease progression, the key players in pathogenesis driving severe disease and progression to lung failure, as well as available and envisioned prevention and treatment strategies against influenza virus infection.

  8. Mycobacterial Infections

    MedlinePlus

    ... many different kinds. The most common one causes tuberculosis. Another one causes leprosy. Still others cause infections ... aren't "typical" because they don't cause tuberculosis. But they can still harm people, especially people ...

  9. Rotavirus Infections

    MedlinePlus

    Rotavirus is a virus that causes gastroenteritis. Symptoms include severe diarrhea, vomiting, fever, and dehydration. Almost all children in the U.S. are likely to be infected with rotavirus before ...

  10. Skin Infections

    MedlinePlus

    ... nearby What to Do Teach kids not to pop, pick at, or scratch pimples, pus-filled infections, ... Your Skin Abscess Impetigo Ringworm Cellulitis Should I Pop My Pimple? Tips for Taking Care of Your ...

  11. Bacterial Infections

    MedlinePlus

    ... body will learn to resist them causing antibiotic resistance. Later, you could get or spread an infection that those antibiotics cannot cure. NIH: National Institute of Allergy and Infectious Diseases

  12. Salmonella Infections

    MedlinePlus

    ... vegetables. You also can get infected after handling pets, especially reptiles like snakes, turtles, and lizards. Symptoms include Fever Diarrhea Abdominal cramps Headache Possible nausea, vomiting, and loss of appetite Symptoms usually last 4-7 days. ...

  13. Hantavirus Infections

    MedlinePlus

    ... can enter the air. People can get the disease if they breathe infected air or come into contact with rodents or their urine or droppings. You cannot catch it from people. Early symptoms of HPS include ...

  14. Pneumococcal Infections

    MedlinePlus

    ... doctor will do a physical exam and health history. Possible tests may include blood, imaging, or lab tests. Treatment is with antibiotics. Vaccines can prevent pneumococcal infections. There are two ...

  15. Hand Infections

    MedlinePlus

    ... spread to others. Necrotizing Fasciitis, or “Flesh-Eating Bacteria” Necrotizing fasciitis is a very rare but severe infection. Streptococcus pyogenes or other “flesh-eating bacteria” enter the body through a cut. Bacteria toxins ...

  16. Giardia Infections

    MedlinePlus

    ... a parasite called Giardia intestinalis. It lives in soil, food, and water. It may also be on ... Doctors use several drugs to treat it. The best way to prevent giardia infection is to practice ...

  17. Staphylococcal Infections

    MedlinePlus

    ... number of skin infections (eg, impetigo, pimples, boils). Staphylococcus aureus also causes toxin-related illnesses, including toxic shock syndrome, scalded skin syndrome, and staphylococcal-related food poisoning. In fact, ... Staphylococcus that you should be familiar with include the ...

  18. Norovirus Infections

    MedlinePlus

    Noroviruses are a group of related viruses. Infection with these viruses causes an illness called gastroenteritis, an inflammation of the stomach and intestines. It can spread from person to person, or ...

  19. Ear Infections

    MedlinePlus

    MENU Return to Web version Ear Infections Overview How does the ear work? A tube called the eustachian (say: "you-stay-shee-an") tube connects the middle ear with the back of the nose. Normally this ...

  20. Yeast Infections

    MedlinePlus

    Candida is the scientific name for yeast. It is a fungus that lives almost everywhere, including in ... infection that causes white patches in your mouth Candida esophagitis is thrush that spreads to your esophagus, ...

  1. MICE Staging and Status

    NASA Astrophysics Data System (ADS)

    Hanlet, Pierrick

    2010-03-01

    Ionization cooling will be a key technique for a high-intensity Neutrino Factory or Muon Collider. The Muon Ionization Cooling Experiment (MICE) is a high-precision, staged accelerator experiment being performed at Rutherford Appleton Laboratory in the UK. Its goal is the first demonstration, with 0.1% resolution, of the feasibility of reducing the transverse emittance of a beam of muons by ionization cooling in low-Z absorbers. MICE is being staged in the following steps: I. Creating and characterizing a beam of muons; II. Measuring their emittance; III. Systematic comparison of successive measurements; IV. Inserting absorber; V. Reaccelerating longitudinally; and VI. Complete "10%-cooling" test. Step I is currently in progress with Step II to commence next year; completion of Step VI is anticipated in ˜2012.

  2. Saturn IB Second Stage (S-IVB Stage)

    NASA Technical Reports Server (NTRS)

    1968-01-01

    This cutaway drawing shows the S-IVB stage in its Saturn IB configuration. As a part of the Marshall Space Flight Center's (MSFC) 'building block' approach to the Saturn development, the S-IVB stage was utilized in the Saturn IB launch vehicle as a second stage and, later, the Saturn V launch vehicle as a third stage. The stage was powered by a single J-2 engine, initially capable of 200,000 pounds of thrust.

  3. The Nef-Infectivity Enigma: Mechanisms of Enhanced Lentiviral Infection

    PubMed Central

    Vermeire, Jolien; Vanbillemont, Griet; Witkowski, Wojciech; Verhasselt, Bruno

    2011-01-01

    The Nef protein is an essential factor for lentiviral pathogenesis in humans and other simians. Despite a multitude of functions attributed to this protein, the exact role of Nef in disease progression remains unclear. One of its most intriguing functions is the ability of Nef to enhance the infectivity of viral particles. In this review we will discuss current insights in the mechanism of this well-known, yet poorly understood Nef effect. We will elaborate on effects of Nef, on both virion biogenesis and the early stage of the cellular infection, that might be involved in infectivity enhancement. In addition, we provide an overview of different HIV-1 Nef domains important for optimal infectivity and briefly discuss some possible sources of the frequent discrepancies in the field. Hereby we aim to contribute to a better understanding of this highly conserved and therapeutically attractive Nef function. PMID:22103831

  4. Staged Event Architecture

    SciTech Connect

    Hoschek, Wolfgang; Berket, Karlo

    2005-05-30

    Sea is a framework for a Staged Event Architecture, designed around non-blocking asynchronous communication facilities that are decoupled from the threading model chosen by any given application, Components for P networking and in-memory communication are provided. The Sea Java library encapsulates these concepts. Sea is used to easily build efficient and flexible low-level network clients and servers, and in particular as a basic communication substrate for Peer-to-Peer applications.

  5. Staged depressurization system

    DOEpatents

    Schulz, T.L.

    1993-11-02

    A nuclear reactor having a reactor vessel disposed in a containment shell is depressurized in stages using depressurizer valves coupled in fluid communication with the coolant circuit. At least one sparger submerged in the in-containment refueling water storage tank which can be drained into the containment sump communicates between one or more of the valves and an inside of the containment shell. The depressurizer valves are opened in stages, preferably at progressively lower coolant levels and for opening progressively larger flowpaths to effect depressurization through a number of the valves in parallel. The valves can be associated with a pressurizer tank in the containment shell, coupled to a coolant outlet of the reactor. At least one depressurization valve stage openable at a lowest pressure is coupled directly between the coolant circuit and the containment shell. The reactor is disposed in the open sump in the containment shell, and a further valve couples the open sump to a conduit coupling the refueling water storage tank to the coolant circuit for adding water to the coolant circuit, whereby water in the containment shell can be added to the reactor from the open sump. 4 figures.

  6. Staged depressurization system

    DOEpatents

    Schulz, Terry L.

    1993-01-01

    A nuclear reactor having a reactor vessel disposed in a containment shell is depressurized in stages using depressurizer valves coupled in fluid communication with the coolant circuit. At least one sparger submerged in the in-containment refueling water storage tank which can be drained into the containment sump communicates between one or more of the valves and an inside of the containment shell. The depressurizer valves are opened in stages, preferably at progressively lower coolant levels and for opening progressively larger flowpaths to effect depressurization through a number of the valves in parallel. The valves can be associated with a pressurizer tank in the containment shell, coupled to a coolant outlet of the reactor. At least one depressurization valve stage openable at a lowest pressure is coupled directly between the coolant circuit and the containment shell. The reactor is disposed in the open sump in the containment shell, and a further valve couples the open sump to a conduit coupling the refueling water storage tank to the coolant circuit for adding water to the coolant circuit, whereby water in the containment shell can be added to the reactor from the open sump.

  7. The March Toward Malaria Vaccines.

    PubMed

    Hoffman, Stephen L; Vekemans, Johan; Richie, Thomas L; Duffy, Patrick E

    2015-12-01

    In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of

  8. The march toward malaria vaccines.

    PubMed

    Hoffman, Stephen L; Vekemans, Johan; Richie, Thomas L; Duffy, Patrick E

    2015-11-27

    In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of

  9. The March Toward Malaria Vaccines

    PubMed Central

    Hoffman, Stephen L.; Vekemans, Johan; Richie, Thomas L.; Duffy, Patrick E.

    2016-01-01

    In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of

  10. Staged cascade fluidized bed combustor

    DOEpatents

    Cannon, Joseph N.; De Lucia, David E.; Jackson, William M.; Porter, James H.

    1984-01-01

    A fluid bed combustor comprising a plurality of fluidized bed stages interconnected by downcomers providing controlled solids transfer from stage to stage. Each stage is formed from a number of heat transfer tubes carried by a multiapertured web which passes fluidizing air to upper stages. The combustor cross section is tapered inwardly from the middle towards the top and bottom ends. Sorbent materials, as well as non-volatile solid fuels, are added to the top stages of the combustor, and volatile solid fuels are added at an intermediate stage.

  11. Pinworm Infection

    MedlinePlus

    ... the pinworm—egg, larva (immature stage), and mature worm—takes place inside the human body and requires ... barely noticeable. The movement of egg-laden female worms from your anus to deposit their eggs will ...

  12. Whole organism blood stage vaccines against malaria.

    PubMed

    Stanisic, Danielle I; Good, Michael F

    2015-12-22

    Despite a century of research focused on the development and implementation of effective control strategies, infection with the malaria parasite continues to result in significant morbidity and mortality worldwide. An effective malaria vaccine is considered by many to be the definitive solution. Yet, after decades of research, we are still without a vaccine that is capable of inducing robust, long lasting protection in naturally exposed individuals. Extensive sub-unit vaccine development focused on the blood stage of the malaria parasite has thus far yielded disappointing results. There is now a renewed focus on whole parasite vaccine strategies, particularly as they may overcome some of the inherent weaknesses deemed to be associated with the sub-unit approach. This review discusses the whole parasite vaccine strategy focusing on the blood stage of the malaria parasite, with an emphasis on recent advances and challenges in the development of killed and live attenuated vaccines.

  13. Genes expressed in grapevine leaves reveal latent wood infection by the fungal pathogen Neofusicoccum parvum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Detection of wood-infecting pathogens is often limited to the late stage of infection, when disease symptoms are obvious. Detection of the early stage of infection would benefit from identification of host-based markers in asymptomatic leaves. The fungus Neofusicoccum parvum (Botryosphaeria diebac...

  14. Dual stage check valve

    NASA Technical Reports Server (NTRS)

    Whitten, D. E. (Inventor)

    1973-01-01

    A dual stage seat valve head arrangement is described which consists of a primary sealing point located between a fixed orifice seat and a valve poppet, and a secondary sealing point between an orifice poppet and a valve poppet. Upstream of the valve orifice is a flexible, convoluted metal diaphragm attached to the orifice poppet. Downstream of the valve orifice, a finger spring exerts a force against the valve poppet, tending to keep the valve in a closed position. The series arrangement of a double seat and poppet is able to tolerate small particle contamination while minimizing chatter by controlling throttling or metering across the secondary seat, thus preserving the primary sealing surface.

  15. Nuclear Cryogenic Propulsion Stage

    NASA Technical Reports Server (NTRS)

    Houts, Michael G.; Borowski, S. K.; George, J. A.; Kim, T.; Emrich, W. J.; Hickman, R. R.; Broadway, J. W.; Gerrish, H. P.; Adams, R. B.

    2012-01-01

    The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progress made under the NCPS project could help enable both advanced NTP and advanced NEP.

  16. Chimpanzee sleep stages.

    NASA Technical Reports Server (NTRS)

    Freemon, F. R.; Mcnew, J. J.; Adey, W. R.

    1971-01-01

    The electroencephalogram and electro-oculogram of two unrestrained juvenile chimpanzees was monitored for 7 consecutive nights using telemetry methods. Of the sleeping time, 23% was spent in the rapid eye movement of REM type of sleep, whereas 8, 4, 15, and 10% were spent in non-REM stages 1 through 4, respectively. Seven to nine periods of REM sleep occurred per night. The average time from the beginning of one REM period to the beginning of the next was approximately 85 min.

  17. Two stages splicing system

    NASA Astrophysics Data System (ADS)

    Mudaber, Mohammad Hassan; Yusof, Yuhani

    2015-05-01

    The study of the biological process of deoxyribonucleic acid (DNA) splicing system in a translucent approach was investigated in 2012 by Yusof under the framework of formal language theory. In this work, the concepts of splicing system in two stages as well as splicing languages are mathematically and biologically discussed. Additionally, some theorems based on recognition site factor of initial strings at the existence of two initial strings and two rules are provided via Yusof-Goode (Y-G) approach. Besides, an example is also given in showing the biological meaning of the introduced concept.

  18. Vaccination in HIV-Infected Adults

    PubMed Central

    Wallace, Mark R.

    2014-01-01

    Abstract Vaccines are critical components for protecting HIV-infected adults from an increasing number of preventable diseases. However, missed opportunities for vaccination among HIV-infected persons persist, likely due to concerns regarding the safety and efficacy of vaccines, as well as the changing nature of vaccine guidelines. In addition, the optimal timing of vaccination among HIV-infected adults in regards to HIV stage and receipt of antiretroviral therapy remain important questions. This article provides a review of the current recommendations regarding vaccines among HIV-infected adults and a comprehensive summary of the evidence-based literature of the benefits and risks of vaccines among this vulnerable population. PMID:25029589

  19. Changes in Brain Function in Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Are Receiving Chemotherapy

    ClinicalTrials.gov

    2016-10-26

    Cognitive Side Effects of Cancer Therapy; Malignant Ovarian Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Choriocarcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Dysgerminoma; Ovarian Embryonal Carcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Mucinous Cystadenocarcinoma; Ovarian Polyembryoma; Ovarian Sarcoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  20. Upper stage technology evaluation studies

    NASA Technical Reports Server (NTRS)

    1972-01-01

    Studies to evaluate advanced technology relative to chemical upper stages and orbit-to-orbit stages are reported. The work described includes: development of LH2/LOX stage data, development of data to indicate stage sensitivity to engine tolerance, modified thermal routines to accommodate storable propellants, added stage geometries to computer program for monopropellant configurations, determination of the relative gain obtainable through improvement of stage mass fraction, future propulsion concepts, effect of ultrahigh chamber-pressure increases, and relative gains obtainable through improved mass fraction.

  1. [Endocrine abnormalities in HIV infections].

    PubMed

    Verges, B; Chavanet, P; Desgres, J; Kisterman, J P; Waldner, A; Vaillant, G; Portier, H; Brun, J M; Putelat, R

    The finding of endocrine gland lesions at pathological examination in AIDS and reports of several cases of endocrine disease in patients with this syndrome have prompted us to study endocrine functions in 63 patients (51 men, 12 women) with HIV-1 infection. According to the Center for Disease Control (CDC) classification system, 13 of these patients were stage CDC II, 27 stage CDC III and 23 stage CDC IV. We explored the adrenocortical function (ACTH, immediate tetracosactrin test) and the thyroid function (free T3 and T4 levels, TRH on TSH test) in all 63 patients. The hypothalamic-pituitary-gonadal axis (testosterone levels, LHRH test) and prolactin secretion (THR test) were explored in the 51 men. The results obtained showed early peripheral testicular insufficiency at stage CDC II and early pituitary gland abnormalities with hypersecretion of ACTH and prolactin also at stage CDC II. On the other hand, adrenocortical and pituitary abnormalities were not frequently found. The physiopathology of the endocrine abnormalities observed in HIV-1-infected patients remains unclear, but one may suspect that it involves interleukin-1 since this protein factor has recently been shown to stimulate the corticotropin-releasing hormone secretion and to act directly on the glycoprotein capsule of the virus (gp 120) whose structure is similar to that of some neurohormones.

  2. Approach to urinary tract infections

    PubMed Central

    Najar, M. S.; Saldanha, C. L.; Banday, K. A.

    2009-01-01

    Urinary tract infection (UTI) is the most common infection experienced by humans after respiratory and gastro-intestinal infections, and also the most common cause of both community-acquired and nosocomial infections for patients admitted to hospitals. For better management and prognosis, it is mandatory to know the possible site of infection, whether the infection is uncomplicated or complicated, re-infection or relapse, or treatment failure and its pathogenesis and risk factors. Asymptomatic bacteriuria is common in certain age groups and has different connotations. It needs to be treated and completely cured in pregnant women and preschool children. Reflux nephropathy in children could result in chronic kidney disease; otherwise, urinary tract infections do not play a major role in the pathogenesis of end-stage renal disease. Symptomatic urinary tract infections occur most commonly in women of child-bearing age. Cystitis predominates, but needs to be distinguished from acute urethral syndrome that affects both sexes and has a different management plan than UTIs. The prostatitis symptoms are much more common than bacterial prostatic infections. The treatment needs to be prolonged in bacterial prostatitis and as cure rates are not very high and relapses are common, the classification of prostatitis needs to be understood. The consensus conference convened by National Institute of Health added two more groups of patients, namely, chronic prostatitis/chronic pelvic pain syndrome and asymptomatic inflammatory prostatitis, in addition to acute and chronic bacterial prostatitis. Although white blood cells in urine signify inflammation, they do not always signify UTI. Quantitative cultures of urine provide definitive evidence of UTI. Imaging studies should be done 3-6 weeks after cure of acute infection to identify abnormalities predisposing to infection or renal damage or which may affect management. Treatment of cystitis in women should be a three-day course and if

  3. Plasmodium vivax trophozoite-stage proteomes

    PubMed Central

    Anderson, D.C.; Lapp, Stacey A.; Akinyi, Sheila; Meyer, Esmeralda V.S.; Barnwell, John W.; Korir-Morrison, Cindy; Galinski, Mary R.

    2015-01-01

    Plasmodium vivax is the causative infectious agent of 80–300 million annual cases of malaria. Many aspects of this parasite’s biology remain unknown. To further elucidate the interaction of P. vivax with its Saimiri boliviensis host, we obtained detailed proteomes of infected red blood cells, representing the trophozoite-enriched stage of development. Data from two of three biological replicate proteomes, emphasized here, were analyzed using five search engines, which enhanced identifications and resulted in the most comprehensive P. vivax proteomes to date, with 1375 P. vivax and 3209 S. boliviensis identified proteins. Ribosome subunit proteins were noted for both P. vivax and S. boliviensis, consistent with P. vivax’s known reticulocyte host–cell specificity. A majority of the host and pathogen proteins identified belong to specific functional categories, and several parasite gene families, while 33% of the P. vivax proteins have no reported function. Hemoglobin was significantly oxidized in both proteomes, and additional protein oxidation and nitration was detected in one of the two proteomes. Detailed analyses of these post-translational modifications are presented. The proteins identified here significantly expand the known P. vivax proteome and complexity of available host protein functionality underlying the host–parasite interactive biology, and reveal unsuspected oxidative modifications that may impact protein function. Biological significance Plasmodium vivax malaria is a serious neglected disease, causing an estimated 80 to 300 million cases annually in 95 countries. Infection can result in significant morbidity and possible death. P. vivax, unlike the much better-studied Plasmodium falciparum species, cannot be grown in long-term culture, has a dormant form in the liver called the hypnozoite stage, has a reticulocyte host–cell preference in the blood, and creates caveolae vesicle complexes at the surface of the infected reticulocyte

  4. Stage-selective inhibition of rodent malaria by cyclosporine.

    PubMed Central

    Murphy, J R; Baqar, S; Baker, R H; Roberts, E; Nickell, S P; Cole, G A

    1988-01-01

    The relative susceptibility of different developmental stages of Plasmodium berghei to cyclosporine was investigated in vivo. Within 12 h of receiving a single 25-mg/kg (body weight) dose of cyclosporine, mice with patent P. berghei infections uniformly exhibited a rapid fall in asexual parasite stages. Initially, ring forms and mature schizonts disappeared. Subsequently, trophozoites disappeared between 21 and 24 h, whereas gametocytes persisted for 36 h. In contrast, when cyclosporine was administered to mice 1 day before inoculation (100 mg/kg) with P. berghei sporozoites and for 2 consecutive days after inoculation (25 mg/kg), infections developed normally. When mice with patent infections were placed on prolonged cyclosporine therapy (25 mg/kg per day), parasitemia initially disappeared but often recrudesced. Recrudescent parasites were frequently resistant to cyclosporine (Csr). The Csr phenotype remained stable after serial passage of parasites in mice and after transmission through Anopheles stephensi mosquitoes, in which the capacity to produce oocysts was reduced. When infections of untreated mice were initiated with equal numbers of Csr and cyclosporine-susceptible (Css) parasites and then carried through two serial cycles of mosquito-to-mouse transmission without cyclosporine treatment, the Csr phenotype was lost. The results indicate that cyclosporine selectively inhibits asexual blood stages of P. berghei and favors the emergence of Csr parasites with diminished infectivity for mosquitoes. PMID:3288113

  5. Tinea Infections

    MedlinePlus

    Tinea is the name of a group of diseases caused by a fungus. Types of tinea include ringworm, athlete's foot and jock itch. These infections are ... depend on the affected area of the body: Ringworm is a red skin rash that forms a ...

  6. Chlamydia Infections

    MedlinePlus

    ... PID). PID can cause permanent damage to your reproductive system. This can lead to long-term pelvic pain, infertility, and ectopic pregnancy. Women who have had chlamydia infections more than once are at higher risk of serious reproductive health complications. Men often don't have health ...

  7. Campylobacter Infections

    MedlinePlus

    ... Campylobacter is found in the intestines of many wild and domestic animals. The bacteria are passed in their feces (poop), which can lead to infection in humans via contaminated food, meats (especially chicken), water taken from contaminated sources (streams or rivers ...

  8. Fusarium Infection

    PubMed Central

    Muhammed, Maged; Anagnostou, Theodora; Desalermos, Athanasios; Kourkoumpetis, Themistoklis K.; Carneiro, Herman A.; Glavis-Bloom, Justin; Coleman, Jeffrey J.

    2013-01-01

    Abstract Fusarium species is a ubiquitous fungus that causes opportunistic infections. We present 26 cases of invasive fusariosis categorized according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria of fungal infections. All cases (20 proven and 6 probable) were treated from January 2000 until January 2010. We also review 97 cases reported since 2000. The most important risk factors for invasive fusariosis in our patients were compromised immune system, specifically lung transplantation (n = 6) and hematologic malignancies (n = 5), and burns (n = 7 patients with skin fusariosis), while the most commonly infected site was the skin in 11 of 26 patients. The mortality rates among our patients with disseminated, skin, and pulmonary fusariosis were 50%, 40%, and 37.5%, respectively. Fusarium solani was the most frequent species, isolated from 49% of literature cases. Blood cultures were positive in 82% of both current study and literature patients with disseminated fusariosis, while the remaining 16% had 2 noncontiguous sites of infection but negative blood cultures. Surgical removal of focal lesions was effective in both current study and literature cases. Skin lesions in immunocompromised patients should raise the suspicion for skin or disseminated fusariosis. The combination of medical monotherapy with voriconazole or amphotericin B and surgery in such cases is highly suggested. PMID:24145697

  9. Fungal Infections

    MedlinePlus

    ... it, you'll be saying bye-bye to fungi (say: FUN-guy). What Is a Fungal Infection? Fungi , the word for more than one fungus, can ... but of course, they're not!). Because the fungi that cause tinea (ringworm) live on different parts ...

  10. Modeling the Dynamics of Plasmodium vivax Infection and Hypnozoite Reactivation In Vivo

    PubMed Central

    Adekunle, Adeshina I.; Pinkevych, Mykola; McGready, Rose; Luxemburger, Christine; White, Lisa J.; Nosten, François; Cromer, Deborah; Davenport, Miles P.

    2015-01-01

    The dynamics of Plasmodium vivax infection is characterized by reactivation of hypnozoites at varying time intervals. The relative contribution of new P. vivax infection and reactivation of dormant liver stage hypnozoites to initiation of blood stage infection is unclear. In this study, we investigate the contribution of new inoculations of P. vivax sporozoites to primary infection versus reactivation of hypnozoites by modeling the dynamics of P. vivax infection in Thailand in patients receiving treatment for either blood stage infection alone (chloroquine), or the blood and liver stages of infection (chloroquine + primaquine). In addition, we also analysed rates of infection in a study in Papua New Guinea (PNG) where patients were treated with either artesunate, or artesunate + primaquine. Our results show that up to 96% of the P. vivax infection is due to hypnozoite reactivation in individuals living in endemic areas in Thailand. Similar analysis revealed the around 70% of infections in the PNG cohort were due to hypnozoite reactivation. We show how the age of the cohort, primaquine drug failure, and seasonality may affect estimates of the ratio of primary P. vivax infection to hypnozoite reactivation. Modeling of P. vivax primary infection and hypnozoite reactivation provides important insights into infection dynamics, and suggests that 90–96% of blood stage infections arise from hypnozoite reactivation. Major differences in infection kinetics between Thailand and PNG suggest the likelihood of drug failure in PNG. PMID:25780913

  11. Pancreatic Cancer Stage 2B

    MedlinePlus

    ... 2B Description: Stage IIB pancreatic cancer; drawing shows cancer in the pancreas and in nearby lymph nodes. Also shown are the bile duct, pancreatic duct, and duodenum. Stage IIB pancreatic cancer. Cancer has spread to nearby lymph nodes and ...

  12. Pancreatic Cancer Stage 2A

    MedlinePlus

    ... 2A Description: Stage IIA pancreatic cancer; drawing shows cancer in the pancreas and duodenum. The bile duct and pancreatic duct are also shown. Stage IIA pancreatic cancer. Cancer has spread to nearby tissue and organs ...

  13. Management of hepatitis C virus infection in HIV/HCV co-infected patients: Clinical review

    PubMed Central

    Singal, Ashwani K; Anand, Bhupinderjit S

    2009-01-01

    Nearly one fourth of individuals with human immunodeficiency virus (HIV) infection have hepatitis C virus (HCV) infection in the US and Western Europe. With the availability of highly active antiretroviral therapy and the consequent reduction in opportunistic infections, resulting in the prolongation of the life span of HIV-infected patients, HCV co-infection has emerged as a significant factor influencing the survival of HIV patients. Patients with HIV/HCV co-infection have a faster rate of fibrosis progression resulting in more frequent occurrences of cirrhosis, end-stage liver disease, and hepatocellular carcinoma. However, the mechanism of interaction between the two viruses is not completely understood. The treatment for HCV in co-infected patients is similar to that of HCV mono-infection; i.e., a combination of pegylated interferon and ribavirin. The presence of any barriers to anti-HCV therapy should be identified and eliminated in order to recruit all eligible patients. The response to treatment in co-infected patients is inferior compared to the response in patients with HCV mono-infection. The sustained virologic response rate is only 38% for genotype-1 and 75% for genotype-2 and -3 infections. Liver transplantation is no longer considered a contraindication for end-stage liver disease in co-infected patients. However, the 5 year survival rate is lower in co-infected patients compared to patients with HCV mono-infection (33% vs 72%, P = 0.07). A better understanding of liver disease in co-infected patients is needed to derive new strategies for improving outcome and survival. PMID:19673011

  14. Fungal nail infection

    MedlinePlus

    Nails - fungal infection; Onychomycosis; Infection - fungal - nails; Tinea unguium ... hair, nails, and outer skin layers. Common fungal infections include: Athlete's foot Jock itch Ringworm on the ...

  15. Viral infection

    PubMed Central

    Puigdomènech, Isabel; de Armas-Rillo, Laura; Machado, José-David

    2011-01-01

    Viruses have developed different survival strategies in host cells by crossing cell-membrane compartments, during different steps of their viral life cycle. In fact, the non-regenerative viral membrane of enveloped viruses needs to encounter the dynamic cell-host membrane, during early steps of the infection process, in which both membranes fuse, either at cell-surface or in an endocytic compartment, to promote viral entry and infection. Once inside the cell, many viruses accomplish their replication process through exploiting or modulating membrane traffic, and generating specialized compartments to assure viral replication, viral budding and spreading, which also serve to evade the immune responses against the pathogen. In this review, we have attempted to present some data that highlight the importance of membrane dynamics during viral entry and replicative processes, in order to understand how viruses use and move through different complex and dynamic cell-membrane structures and how they use them to persist. PMID:21966556

  16. Infective endocarditis.

    PubMed

    Cahill, Thomas J; Prendergast, Bernard D

    2016-02-27

    Infective endocarditis occurs worldwide, and is defined by infection of a native or prosthetic heart valve, the endocardial surface, or an indwelling cardiac device. The causes and epidemiology of the disease have evolved in recent decades with a doubling of the average patient age and an increased prevalence in patients with indwelling cardiac devices. The microbiology of the disease has also changed, and staphylococci, most often associated with health-care contact and invasive procedures, have overtaken streptococci as the most common cause of the disease. Although novel diagnostic and therapeutic strategies have emerged, 1 year mortality has not improved and remains at 30%, which is worse than for many cancers. Logistical barriers and an absence of randomised trials hinder clinical management, and longstanding controversies such as use of antibiotic prophylaxis remain unresolved. In this Seminar, we discuss clinical practice, controversies, and strategies needed to target this potentially devastating disease.

  17. Dermatophyte infections.

    PubMed

    Hainer, Barry L

    2003-01-01

    Dermatophytes are fungi that require keratin for growth. These fungi can cause superficial infections of the skin, hair, and nails. Dermatophytes are spread by direct contact from other people (anthropophilic organisms), animals (zoophilic organisms), and soil (geophilic organisms), as well as indirectly from fomites. Dermatophyte infections can be readily diagnosed based on the history, physical examination, and potassium hydroxide (KOH) microscopy. Diagnosis occasionally requires Wood's lamp examination and fungal culture or histologic examination. Topical therapy is used for most dermatophyte infections. Cure rates are higher and treatment courses are shorter with topical fungicidal allylamines than with fungistatic azoles. Oral therapy is preferred for tinea capitis, tinea barbae, and onychomycosis. Orally administered griseofulvin remains the standard treatment for tinea capitis. Topical treatment of onychomycosis with ciclopirox nail lacquer has a low cure rate. For onychomycosis, "pulse" oral therapy with the newer imidazoles (itraconazole or fluconazole) or allylamines (terbinafine) is considerably less expensive than continuous treatment but has a somewhat lower mycologic cure rate. The diagnosis of onychomycosis should be confirmed by KOH microscopy, culture, or histologic examination before therapy is initiated, because of the expense, duration, and potential adverse effects of treatment.

  18. Anthrax Infection

    PubMed Central

    Sweeney, Daniel A.; Hicks, Caitlin W.; Cui, Xizhong; Li, Yan

    2011-01-01

    Bacillus anthracis infection is rare in developed countries. However, recent outbreaks in the United States and Europe and the potential use of the bacteria for bioterrorism have focused interest on it. Furthermore, although anthrax was known to typically occur as one of three syndromes related to entry site of (i.e., cutaneous, gastrointestinal, or inhalational), a fourth syndrome including severe soft tissue infection in injectional drug users is emerging. Although shock has been described with cutaneous anthrax, it appears much more common with gastrointestinal, inhalational (5 of 11 patients in the 2001 outbreak in the United States), and injectional anthrax. Based in part on case series, the estimated mortalities of cutaneous, gastrointestinal, inhalational, and injectional anthrax are 1%, 25 to 60%, 46%, and 33%, respectively. Nonspecific early symptomatology makes initial identification of anthrax cases difficult. Clues to anthrax infection include history of exposure to herbivore animal products, heroin use, or clustering of patients with similar respiratory symptoms concerning for a bioterrorist event. Once anthrax is suspected, the diagnosis can usually be made with Gram stain and culture from blood or surgical specimens followed by confirmatory testing (e.g., PCR or immunohistochemistry). Although antibiotic therapy (largely quinolone-based) is the mainstay of anthrax treatment, the use of adjunctive therapies such as anthrax toxin antagonists is a consideration. PMID:21852539

  19. Infective endocarditis.

    PubMed

    Ferro, José M; Fonseca, Ana Catarina

    2014-01-01

    Infective endocarditis is a serious disease of the endocardium of the heart and cardiac valves, caused by a variety of infectious agents, ranging from streptococci to rickettsia. The proportion of cases associated with rheumatic valvulopathy and dental surgery has decreased in recent years, while endocarditis associated with intravenous drug abuse, prosthetic valves, degenerative valve disease, implanted cardiac devices, and iatrogenic or nosocomial infections has emerged. Endocarditis causes constitutional, cardiac and multiorgan symptoms and signs. The central nervous system can be affected in the form of meningitis, cerebritis, encephalopathy, seizures, brain abscess, ischemic embolic stroke, mycotic aneurysm, and subarachnoid or intracerebral hemorrhage. Stroke in endocarditis is an ominous prognostic sign. Treatment of endocarditis includes prolonged appropriate antimicrobial therapy and in selected cases, cardiac surgery. In ischemic stroke associated with infective endocarditis there is no indication to start antithrombotic drugs. In previously anticoagulated patients with an ischemic stroke, oral anticoagulants should be replaced by unfractionated heparin, while in intracranial hemorrhage, all anticoagulation should be interrupted. The majority of unruptured mycotic aneurysms can be treated by antibiotics, but for ruptured aneurysms, endovascular or neurosurgical therapy is indicated.

  20. Bevacizumab, Cisplatin, Radiation Therapy, and Fluorouracil in Treating Patients With Stage IIB, Stage III, Stage IVA, or Stage IVB Nasopharyngeal Cancer

    ClinicalTrials.gov

    2014-04-21

    Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx

  1. Oblimersen Sodium and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage I, Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

    ClinicalTrials.gov

    2012-10-11

    Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

  2. Evolution of Staged Versus Primary Closure of Gastroschisis

    PubMed Central

    Kidd, Joseph N.; Jackson, Richard J.; Smith, Samuel D.; Wagner, Charles W.

    2003-01-01

    Objective Since the introduction of a preformed silo to the authors’ practice in 1997, there has been a decrease in primary closure of gastroschisis. To clarify the impact of this change, the authors reviewed their results over the past 10 years. Methods From patient records, the authors abstracted the closure method, mechanical ventilation days, time to full feeds, mechanical and infectious complications, and length of stay. The authors compared groups using the Student t test and the Mann-Whitney test, as appropriate. Results Between 1993 and the present, 124 patients were identified. Between 1993 and 1997, 38 children presented with gastro-schisis. Thirty-two (84.2%) closures were primary and six (18.8%) were staged. After 1997, the authors treated 80 children with gastroschisis. There were 27 (33.8%) primary and 53 (66.2%) staged closures. Six patients with other lethal anomalies were excluded. Length of stay and ventilator days were higher for the staged closure group, but infection and mechanical complications were less common in the staged closure group. The time to full feeds did not differ. Conclusions A lower incidence of infection and complications related to abdominal compartment syndrome has made staged closure of gastroschisis more common in the authors’ practice. While it has resulted in a longer hospital stay, staged closure decreases the risk of long-term bowel dysfunction and need for reoperation. PMID:12796571

  3. Suramin inhibits EV71 infection.

    PubMed

    Wang, Yaxin; Qing, Jie; Sun, Yuna; Rao, Zihe

    2014-03-01

    Enterovirus-71 (EV71) is one of the major causative reagents for hand-foot-and-mouth disease. In particular, EV71 causes severe central nervous system infections and leads to numerous dead cases. Although several inactivated whole-virus vaccines have entered in clinical trials, no antiviral agent has been provided for clinical therapy. In the present work, we screened our compound library and identified that suramin, which has been clinically used to treat variable diseases, could inhibit EV71 proliferation with an IC50 value of 40 μM. We further revealed that suramin could block the attachment of EV71 to host cells to regulate the early stage of EV71 infection, as well as affected other steps of EV71 life cycle. Our results are helpful to understand the mechanism for EV71 life cycle and provide a potential for the usage of an approved drug, suramin, as the antiviral against EV71 infection.

  4. Ten questions on prosthetic shoulder infection.

    PubMed

    Pinder, Elizabeth M; Ong, Joshua Cy; Bale, R Stephen; Trail, Ian A

    2016-07-01

    Prosthetic shoulder infection can cause significant morbidity secondary to pain and stiffness. Symptoms may be present for years before diagnosis because clinical signs are often absent and inflammatory markers may be normal. An emerging common culprit, Propionibacterium acnes, is hard to culture and so prolonged incubation is necessary. A negative culture result does not always exclude infection and new synovial fluid biochemical markers such as α defensin are less sensitive than for lower limb arthroplasty. A structured approach is necessary when assessing patients for prosthetic shoulder joint infection. This includes history, examination, serum inflammatory markers, plain radiology and aspiration and/or biopsy. A classification for the likelihood of prosthetic shoulder infection has been described based on culture, pre-operative and intra-operative findings. Treatment options include antibiotic suppression, debridement with component retention, one-stage revision, two-stage revision and excision arthroplasty. Revision arthroplasty is associated with the best outcomes. PMID:27583013

  5. Ten questions on prosthetic shoulder infection

    PubMed Central

    Pinder, Elizabeth M; Ong, Joshua CY; Bale, R Stephen

    2016-01-01

    Prosthetic shoulder infection can cause significant morbidity secondary to pain and stiffness. Symptoms may be present for years before diagnosis because clinical signs are often absent and inflammatory markers may be normal. An emerging common culprit, Propionibacterium acnes, is hard to culture and so prolonged incubation is necessary. A negative culture result does not always exclude infection and new synovial fluid biochemical markers such as α defensin are less sensitive than for lower limb arthroplasty. A structured approach is necessary when assessing patients for prosthetic shoulder joint infection. This includes history, examination, serum inflammatory markers, plain radiology and aspiration and/or biopsy. A classification for the likelihood of prosthetic shoulder infection has been described based on culture, pre-operative and intra-operative findings. Treatment options include antibiotic suppression, debridement with component retention, one-stage revision, two-stage revision and excision arthroplasty. Revision arthroplasty is associated with the best outcomes. PMID:27583013

  6. Frog Virus 3 DNA Replication Occurs in Two Stages

    PubMed Central

    Goorha, R.

    1982-01-01

    Viral DNA synthesis in frog virus 3 (FV3)-infected cells occurs both in the nucleus and in the cytoplasm (Goorha et al., Virology 84:32-51, 1978). Relationships between viral DNA molecules synthesized in these two compartments and their role in the virus replication were examined. The data presented here suggest that (i) FV3 DNA replicated in two stages and (ii) nucleus and cytoplasm were the sites of stages 1 and 2 of DNA replication, respectively. Stages 1 and 2 were further distinguished by their temporal appearance during infection and by the sizes of the replicating DNA as determined by sedimentation in neutral sucrose gradients. In stage 1, replicating molecules, between the size of unit and twice the unit length, were produced early in infection (2 h postinfection). In contrast, stage 2 of DNA replication occurred only after 3 h postinfection, and replicating molecules were large concatemers. Results of pulse-chase experiments showed that the concatemeric DNA served as the precursor for the production of mature FV3 DNA. Denaturation of concatemeric DNA with alkali or digestion with S1 nuclease reduced it to less than genome size molecules, indicating the presence of extensive single-stranded regions. Analysis of replicating DNA by equilibrium centrifugation in CsCl gradients after a pulse-chase suggested that these single-stranded regions were subsequently repaired. Based on these and previous data, a scheme of FV3 replication is presented. According to this scheme, FV3 utilizes the nucleus for early transcription and stage 1 of DNA replication. The viral DNA is then transported to the cytoplasm, where it participates in stage 2 DNA replication to form a concatemeric replication complex. The processing of concatemers to produce mature viral DNA and virus assembly also occurs in the cytoplasm. This mode of replication is strikingly different from any other known DNA virus. PMID:7109033

  7. Fish tapeworm infection

    MedlinePlus

    Fish tapeworm infection is an intestinal infection with the tapeworm parasite found in fish. ... The fish tapeworm ( Diphyllobothrium latum ) is the largest parasite that infects humans. Humans become infected when they eat raw ...

  8. Melanoma staging: facts and controversies.

    PubMed

    Forschner, Andrea; Eigentler, Thomas Kurt; Pflugfelder, Annette; Leiter, Ulrike; Weide, Benjamin; Held, Laura; Meier, Friedegund; Garbe, Claus

    2010-01-01

    The value of staging examinations remains controversial for the initial staging in melanoma patients at the time of the primary diagnosis and for surveillance. Issues concerning tumor recurrences and progression must be discussed separately for different risk groups. For low-risk patients (stage IA; tumor thickness less than 1 mm), staging examinations like sentinel lymph node biopsy (SLNB), blood tests, or imaging can generally be abandoned. Baseline staging with simple techniques is at the discretion of the physician. In intermediate-risk patients (stages IB and IIA), an initial staging examination involving SLNB and computed tomography (CT) scans is recommended. Further follow-up may be restricted to physical examinations, blood tests of tumor marker protein S100beta, and to lymph node ultrasonography. If findings are suspicious, further imaging procedures may be involved. In high-risk patients (stages IIB to III), an initial staging examination with CT is recommended, and regular follow-up every 6 months with whole body imaging by CT or magnetic resonance imaging seems useful. Physical examinations, blood tests of tumor marker protein S100beta, and lymph node ultrasound imaging should be routine. This intense follow-up may enable surgical treatments with complete removal of all recognizable metastases in about 15% to 25% of patients and improve their prognosis. The risk of recurrence or tumor progression is very high in stage IV patients, and their management is individualized. PMID:20541679

  9. Oral antibiotics are effective for highly resistant hip arthroplasty infections.

    PubMed

    Cordero-Ampuero, José; Esteban, Jaime; García-Cimbrelo, Eduardo

    2009-09-01

    Infected arthroplasties reportedly have a lower eradication rate when caused by highly resistant and/or polymicrobial isolates and in these patients most authors recommend intravenous antibiotics. We asked whether two-stage revision with interim oral antibiotics could eradicate these infections. We prospectively followed 36 patients (mean age, 71.8 years) with late hip arthroplasty infections. Combinations of oral antibiotics were prescribed according to cultures, biofilm, and intracellular effectiveness. The minimum followup was 1 year (mean, 4.4 years; range, 1-12 years). We presumed eradication in the absence of clinical, serologic, and radiographic signs of infection. Infection was eradicated in all 13 patients with highly resistant bacteria who completed a two-stage protocol (10 with methicillin-resistant Staphylococci) and in eight of 11 patients treated with only the first stage (and six of nine with methicillin-resistant Staphylococci). Infection was eradicated in six of six patients with polymicrobial isolates (of sensitive and/or resistant bacteria) who completed a two-stage protocol and in five of seven with polymicrobial isolates treated with only the first surgery. The Harris hip score averaged 88.1 (range, 70-98) in patients who underwent reimplantation and 56.8 (range, 32-76) in patients who underwent resection arthroplasty. Long cycles of combined oral antibiotics plus a two-stage surgical exchange appear a promising alternative for infections by highly resistant bacteria, methicillin-resistant Staphylococci, and polymicrobial infections.

  10. Paclitaxel and Carboplatin Before Radiation Therapy With Paclitaxel in Treating HPV-Positive Patients With Stage III-IV Oropharynx, Hypopharynx, or Larynx Cancer

    ClinicalTrials.gov

    2016-09-07

    Human Papilloma Virus Infection; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Larynx

  11. Protective efficacy and safety of liver stage attenuated malaria parasites

    PubMed Central

    Kumar, Hirdesh; Sattler, Julia Magdalena; Singer, Mirko; Heiss, Kirsten; Reinig, Miriam; Hammerschmidt-Kamper, Christiane; Heussler, Volker; Mueller, Ann-Kristin; Frischknecht, Friedrich

    2016-01-01

    During the clinically silent liver stage of a Plasmodium infection the parasite replicates from a single sporozoite into thousands of merozoites. Infection of humans and rodents with large numbers of sporozoites that arrest their development within the liver can cause sterile protection from subsequent infections. Disruption of genes essential for liver stage development of rodent malaria parasites has yielded a number of attenuated parasite strains. A key question to this end is how increased attenuation relates to vaccine efficacy. Here, we generated rodent malaria parasite lines that arrest during liver stage development and probed the impact of multiple gene deletions on attenuation and protective efficacy. In contrast to P. berghei strain ANKA LISP2(–) or uis3(–) single knockout parasites, which occasionally caused breakthrough infections, the double mutant lacking both genes was completely attenuated even when high numbers of sporozoites were administered. However, different vaccination protocols showed that LISP2(–) parasites protected better than uis3(–) and double mutants. Hence, deletion of several genes can yield increased safety but might come at the cost of protective efficacy. PMID:27241521

  12. Akabane virus infection.

    PubMed

    Kirkland, P D

    2015-08-01

    Akabane virus is a Culicoides-borne orthobunyavirus that is teratogenic to the fetus of cattle and small ruminant species. Depending upon the stage of gestation atwhich infection occurs, and the length of gestation of the mammalian host, a range of congenital defects may be observed. The developing central nervous system is usually the most severely affected, with hydranencephaly and arthrogryposis most frequently observed. Less commonly, some strains of Akabane virus can cause encephalitis in the neonate or, rarely, adult cattle. Akabane viruses are known to be widespread in temperate and tropical regions of Australia, Southeast Asia, the Middle East and some African countries. Disease is infrequently observed in regions where this virus is endemic and the presence of the virus remains unrecognised in the absence of serological surveillance. In some Asian countries, vaccines are used to minimise the occurrence of disease. PMID:26601444

  13. Staged membrane oxidation reactor system

    SciTech Connect

    Repasky, John Michael; Carolan, Michael Francis; Stein, VanEric Edward; Chen, Christopher Ming-Poh

    2013-04-16

    Ion transport membrane oxidation system comprising (a) two or more membrane oxidation stages, each stage comprising a reactant zone, an oxidant zone, one or more ion transport membranes separating the reactant zone from the oxidant zone, a reactant gas inlet region, a reactant gas outlet region, an oxidant gas inlet region, and an oxidant gas outlet region; (b) an interstage reactant gas flow path disposed between each pair of membrane oxidation stages and adapted to place the reactant gas outlet region of a first stage of the pair in flow communication with the reactant gas inlet region of a second stage of the pair; and (c) one or more reactant interstage feed gas lines, each line being in flow communication with any interstage reactant gas flow path or with the reactant zone of any membrane oxidation stage receiving interstage reactant gas.

  14. Staged membrane oxidation reactor system

    SciTech Connect

    Repasky, John Michael; Carolan, Michael Francis; Stein, VanEric Edward; Chen, Christopher Ming-Poh

    2014-05-20

    Ion transport membrane oxidation system comprising (a) two or more membrane oxidation stages, each stage comprising a reactant zone, an oxidant zone, one or more ion transport membranes separating the reactant zone from the oxidant zone, a reactant gas inlet region, a reactant gas outlet region, an oxidant gas inlet region, and an oxidant gas outlet region; (b) an interstage reactant gas flow path disposed between each pair of membrane oxidation stages and adapted to place the reactant gas outlet region of a first stage of the pair in flow communication with the reactant gas inlet region of a second stage of the pair; and (c) one or more reactant interstage feed gas lines, each line being in flow communication with any interstage reactant gas flow path or with the reactant zone of any membrane oxidation stage receiving interstage reactant gas.

  15. Staged membrane oxidation reactor system

    DOEpatents

    Repasky, John Michael; Carolan, Michael Francis; Stein, VanEric Edward; Chen, Christopher Ming-Poh

    2012-09-11

    Ion transport membrane oxidation system comprising (a) two or more membrane oxidation stages, each stage comprising a reactant zone, an oxidant zone, one or more ion transport membranes separating the reactant zone from the oxidant zone, a reactant gas inlet region, a reactant gas outlet region, an oxidant gas inlet region, and an oxidant gas outlet region; (b) an interstage reactant gas flow path disposed between each pair of membrane oxidation stages and adapted to place the reactant gas outlet region of a first stage of the pair in flow communication with the reactant gas inlet region of a second stage of the pair; and (c) one or more reactant interstage feed gas lines, each line being in flow communication with any interstage reactant gas flow path or with the reactant zone of any membrane oxidation stage receiving interstage reactant gas.

  16. Staged Repository Development Programmes

    SciTech Connect

    Isaacs, T

    2003-10-01

    Programs to manage and ultimately dispose of high-level radioactive wastes are unique from scientific and technological as well as socio-political aspects. From a scientific and technological perspective, high-level radioactive wastes remain potentially hazardous for geological time periods-many millennia-and scientific and technological programs must be put in place that result in a system that provides high confidence that the wastes will be isolated from the accessible environment for these many thousands of years. Of course, ''proof'' in the classical sense is not possible at the outset, since the performance of the system can only be known with assurance, if ever, after the waste has been emplaced for those geological time periods. Adding to this challenge, many uncertainties exist in both the natural and engineered systems that are intended to isolate the wastes, and some of the uncertainties will remain regardless of the time and expense in attempting to characterize the system and assess its performance. What was perhaps underappreciated in the early days of waste management and repository program development were the unique and intense reactions that the institutional, political, and public bodies would have to repository program development, particularly in programs attempting to identify and then select sites for characterization, design, licensing, and ultimate development. Reactions in most nations were strong, focused, unrelenting, and often successful in hindering, derailing, and even stopping national repository programs. The reasons for such reactions and the measures to successfully respond to them are still evolving and continue to be the focus of many national program and political leaders. Adaptive Staging suggests an approach to repository program development that reflects the unique challenges associated with the disposal of high-level radioactive waste. The step-wise, incremental, learn-as-you-go approach is intended to maximize the

  17. Carboplatin and Paclitaxel With or Without Cisplatin and Radiation Therapy in Treating Patients With Stage I, Stage II, Stage III, or Stage IVA Endometrial Cancer

    ClinicalTrials.gov

    2016-02-09

    Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer

  18. [Bacterial infections in AIDS (mycobacterial infections excluded): study of 100 cases].

    PubMed

    Zouiten, Fayçal; Rbia, Emna; Ben Said, Amel; Kanoun, Fakher; Ben Chaabane, Taoufik

    2003-02-01

    We report a retrospective study of 106 patients with bacterial infections from 322 patients infected with the human immunodeficiency virus (HIV) resulting in 33 percent. Epidemiological profile of bacterial infection in HIV patient is the same that observed in tunisian patient with HIV: a young male infected mainly by sexual route. Bacterial infection is located in the lungs in 38.3 percent, in the skin in 16.5 percent, in upper respiratory tract and oral in 12.7 percent, sexually transmitted disease and bacteremia are respectively found in 12 percent, bacterial genito-urinary tract infection in 5.3 percent, bacterial gastro-intestinal tact infection in 2.3 percent and meningitis in 0.8 percent. Bacterial infections occur at all stages in patients with HIV, but mainly in 77.7 percent at AIDS stage. Regardless the infectious site, granulocytes number is normal in 66 percent of cases. Bacterial investigation find a bacterial specie in 14.3 percent and a bacterial positive serology in 11.2 percent. Mortality caused by bacterial infection is found in 11.3 percent.

  19. Second stage gasifier in staged gasification and integrated process

    SciTech Connect

    Liu, Guohai; Vimalchand, Pannalal; Peng, Wan Wang

    2015-10-06

    A second stage gasification unit in a staged gasification integrated process flow scheme and operating methods are disclosed to gasify a wide range of low reactivity fuels. The inclusion of second stage gasification unit operating at high temperatures closer to ash fusion temperatures in the bed provides sufficient flexibility in unit configurations, operating conditions and methods to achieve an overall carbon conversion of over 95% for low reactivity materials such as bituminous and anthracite coals, petroleum residues and coke. The second stage gasification unit includes a stationary fluidized bed gasifier operating with a sufficiently turbulent bed of predefined inert bed material with lean char carbon content. The second stage gasifier fluidized bed is operated at relatively high temperatures up to 1400.degree. C. Steam and oxidant mixture can be injected to further increase the freeboard region operating temperature in the range of approximately from 50 to 100.degree. C. above the bed temperature.

  20. Infective endocarditis.

    PubMed

    Holland, Thomas L; Baddour, Larry M; Bayer, Arnold S; Hoen, Bruno; Miro, Jose M; Fowler, Vance G

    2016-01-01

    Infective endocarditis (IE) is a rare, life-threatening disease that has long-lasting effects even among patients who survive and are cured. IE disproportionately affects those with underlying structural heart disease and is increasingly associated with health care contact, particularly in patients who have intravascular prosthetic material. In the setting of bacteraemia with a pathogenic organism, an infected vegetation may form as the end result of complex interactions between invading microorganisms and the host immune system. Once established, IE can involve almost any organ system in the body. The diagnosis of IE may be difficult to establish and a strategy that combines clinical, microbiological and echocardiography results has been codified in the modified Duke criteria. In cases of blood culture-negative IE, the diagnosis may be especially challenging, and novel microbiological and imaging techniques have been developed to establish its presence. Once diagnosed, IE is best managed by a multidisciplinary team with expertise in infectious diseases, cardiology and cardiac surgery. Antibiotic prophylaxis for the prevention of IE remains controversial. Efforts to develop a vaccine that targets common bacterial causes of IE are ongoing, but have not yet yielded a commercially available product. PMID:27582414

  1. [Norovirus infections].

    PubMed

    Stock, Ingo

    2007-10-01

    During the last winter season, there was the hitherto largest norovirus gastroenteritis epidemic in Germany. Noroviruses are genetically highly variable, non-enveloped viruses with a single-stranded, positive sense RNA genome. They are the major cause of epidemic non-bacterial gastroenteritis worldwide, and have been identified as the cause of more than 70% of outbreaks and approximately half of all gastroenteritis outbreaks. Noroviruses also are frequently involved in sporadic cases of gastroenteritis. Typically, norovirus-associated enteritis is characterized by the sudden onset of vomiting and watery diarrhoea, frequently accompanied by several unspecific symptoms, e. g. abdominal pain, anorexia, malaise, headache, and low-grade fever. Diarrhoea without emesis as well as asymptomatic infections is also common. With few exceptions, diseases due to noroviruses are self-limited and the illness duration is restricted to a few days. Noroviruses are transmitted primarily from person-to-person by the faecal-oral route, but airborne transmission also occurs. Contamination of food and water represent important sources for human infection. Treatment ofnorovirus gastroenteritis is usually symptomatic and comprises a sufficient fluid and electrolyte substitution. There is no specific antiviral therapy. For prophylaxis, obeying of common hygienic rules in canteen kitchens and community institutions is regarded to be sufficient. Food with high risk of contamination should be cooked thoroughly. Because of the high stability of noroviruses to several environmental conditions, disinfection should be performed applying disinfectants with proven activity against noroviruses.

  2. Raoultella ornithinolytica: An unusual pathogen for prosthetic joint infection.

    PubMed

    Seng, Piseth; Theron, Françoise; Honnorat, Estelle; Prost, Didier; Fournier, Pierre-Edouard; Stein, Andreas

    2016-01-01

    We herein report the first case of a prosthetic joint infection caused by Raoultella ornithinolytica in an immunocompetent patient. The clinical outcome was favorable after a two-stage prosthetic exchange and a six-month course of antimicrobial therapy.

  3. Ecopathology of ranaviruses infecting amphibians.

    PubMed

    Miller, Debra; Gray, Matthew; Storfer, Andrew

    2011-11-01

    Ranaviruses are capable of infecting amphibians from at least 14 families and over 70 individual species. Ranaviruses infect multiple cell types, often culminating in organ necrosis and massive hemorrhaging. Subclinical infections have been documented, although their role in ranavirus persistence and emergence remains unclear. Water is an effective transmission medium for ranaviruses, and survival outside the host may be for significant duration. In aquatic communities, amphibians, reptiles and fish may serve as reservoirs. Controlled studies have shown that susceptibility to ranavirus infection and disease varies among amphibian species and developmental stages, and likely is impacted by host-pathogen coevolution, as well as, exogenous environmental factors. Field studies have demonstrated that the likelihood of epizootics is increased in areas of cattle grazing, where aquatic vegetation is sparse and water quality is poor. Translocation of infected amphibians through commercial trade (e.g., food, fish bait, pet industry) contributes to the spread of ranaviruses. Such introductions may be of particular concern, as several studies report that ranaviruses isolated from ranaculture, aquaculture, and bait facilities have greater virulence (i.e., ability to cause disease) than wild-type isolates. Future investigations should focus on the genetic basis for pathogen virulence and host susceptibility, ecological and anthropogenic mechanisms contributing to emergence, and vaccine development for use in captive populations and species reintroduction programs.

  4. Infections in liver transplant recipients.

    PubMed

    Romero, Fabian A; Razonable, Raymund R

    2011-04-27

    Liver transplantation is a standard life-saving procedure for the treatment of many end-stage liver diseases. The success of this procedure may be limited by infectious complications. In this article, we review the contemporary state of infectious complications during the post-operative period, with particular emphasis on those that occur most commonly during the first 6 mo after liver transplantation. Bacteria, and less commonly Candida infections, remain the predominant pathogens during the immediate post-operative period, especially during the first month, and infections caused by drug-resistant strains are emerging. Infections caused by cytomegalovirus and Aspergillus sp. present clinically during the "opportunistic" period characterized by intense immunosuppression. As newer potent immunosuppressive therapies with the major aim of reducing allograft rejection are developed, one potential adverse effect is an increase in certain infections. Hence, it is essential for liver transplant centers to have an effective approach to prevention that is based on predicted infection risk, local antimicrobial resistance patterns, and surveillance. A better understanding of the common and most important infectious complications is anticipated to lead to improvements in quality of life and survival of liver transplant recipients.

  5. Ecopathology of Ranaviruses Infecting Amphibians

    PubMed Central

    Miller, Debra; Gray, Matthew; Storfer, Andrew

    2011-01-01

    Ranaviruses are capable of infecting amphibians from at least 14 families and over 70 individual species. Ranaviruses infect multiple cell types, often culminating in organ necrosis and massive hemorrhaging. Subclinical infections have been documented, although their role in ranavirus persistence and emergence remains unclear. Water is an effective transmission medium for ranaviruses, and survival outside the host may be for significant duration. In aquatic communities, amphibians, reptiles and fish may serve as reservoirs. Controlled studies have shown that susceptibility to ranavirus infection and disease varies among amphibian species and developmental stages, and likely is impacted by host-pathogen coevolution, as well as, exogenous environmental factors. Field studies have demonstrated that the likelihood of epizootics is increased in areas of cattle grazing, where aquatic vegetation is sparse and water quality is poor. Translocation of infected amphibians through commercial trade (e.g., food, fish bait, pet industry) contributes to the spread of ranaviruses. Such introductions may be of particular concern, as several studies report that ranaviruses isolated from ranaculture, aquaculture, and bait facilities have greater virulence (i.e., ability to cause disease) than wild-type isolates. Future investigations should focus on the genetic basis for pathogen virulence and host susceptibility, ecological and anthropogenic mechanisms contributing to emergence, and vaccine development for use in captive populations and species reintroduction programs. PMID:22163349

  6. Multiple stage miniature stepping motor

    DOEpatents

    Niven, William A.; Shikany, S. David; Shira, Michael L.

    1981-01-01

    A stepping motor comprising a plurality of stages which may be selectively activated to effect stepping movement of the motor, and which are mounted along a common rotor shaft to achieve considerable reduction in motor size and minimum diameter, whereby sequential activation of the stages results in successive rotor steps with direction being determined by the particular activating sequence followed.

  7. A Model of Moral Stages

    ERIC Educational Resources Information Center

    Reed, Don Collins

    2008-01-01

    The argument of this paper focuses on the relationship between cognitive structures and structures of interaction. It contends that there is still a place in moral development theory and research for a concept of moral stages. The thesis, in short, is that moral stages are not structures of thought. They are structures of action encoded in…

  8. The Theatre Student: Stage Violence.

    ERIC Educational Resources Information Center

    Katz, Albert M.

    Stage violence is a complex art which, when conceived inventively, approached with professional care and respect, and practiced with patience and energy, can be the highlight of a scene or of an entire play. This book is designed for amateurs who have not had the benefit of formal training in stage violence. Chapters discuss falling (the…

  9. Stage fluctuations of Wisconsin lakes

    USGS Publications Warehouse

    House, Leo B.

    1985-01-01

    This report describes lake-stage fluctuations of 83 gaged lakes in Wisconsin and presents techniques for estimating stage fluctuation at ungaged lakes. Included are stage information at 83 lakes and stage-frequency data for 32 of these lakes that had sufficient record for analysis. Lakes are classified by a hydrologic-topographic lake classification scheme as ground-water flowthrough (GWF) lakes, surface-water drainage (SWD) lakes, and surface-water flow-through (SWF) lakes. Lakes within the same class were found to have similar water-level fluctuations. The lake-stage records indicate that most annual maximums occur during the months of May and June for all three classes. Annual minimum lake levels generally occur in September for surface-water drainage lakes, in March for surface-water flowthrough lakes, and in November for ground-water flow-through lakes. Data for each lake include location, period of water-level record, hydrologic classification, drainage area, surface area, lake volume, maximum depth, long-term mean stage and its standard deviation, maximum and minimum observed lake stage, and the average annual lake-stage fluctuation.

  10. Writing Stages: A Developmental Hierarchy.

    ERIC Educational Resources Information Center

    Milner, Joseph O.

    The developmental stages of writing can be related to Jean Piaget's final three stages of development (preoperational, concrete operational, and formal operational) and to the narrative, descriptive, explanative, analytical, and artistic rhetorical modes. As the child enters kindergarten or the first grade, narrative blooms. By this age most young…

  11. Lung Cancer Staging and Prognosis.

    PubMed

    Woodard, Gavitt A; Jones, Kirk D; Jablons, David M

    2016-01-01

    The seventh edition of the non-small cell lung cancer (NSCLC) TNM staging system was developed by the International Association for the Staging of Lung Cancer (IASLC) Lung Cancer Staging Project by a coordinated international effort to develop data-derived TNM classifications with significant survival differences. Based on these TNM groupings, current 5-year survival estimates in NSLCC range from 73 % in stage IA disease to 13 % in stage IV disease. TNM stage remains the most important prognostic factor in predicting recurrence rates and survival times, followed by tumor histologic grade, and patient sex, age, and performance status. Molecular prognostication in lung cancer is an exploding area of research where interest has moved beyond TNM stage and into individualized genetic tumor analysis with immunohistochemistry, microarray, and mutation profiles. However, despite intense research efforts and countless publications, no molecular prognostic marker has been adopted into clinical use since most fail in subsequent cross-validation with few exceptions. The recent interest in immunotherapy for NSCLC has identified new biomarkers with early evidence that suggests that PD-L1 is a predictive marker of a good response to new immunotherapy drugs but a poor prognostic indicator of overall survival. Future prognostication of outcomes in NSCLC will likely be based on a combination of TNM stage and molecular tumor profiling and yield more precise, individualized survival estimates and treatment algorithms. PMID:27535389

  12. Impact of chronic kidney disease stage on lower-extremity arthroplasty.

    PubMed

    Deegan, Brian F; Richard, Raveesh D; Bowen, Thomas R; Perkins, Robert M; Graham, Jove H; Foltzer, Michael A

    2014-07-01

    End-stage renal disease and dialysis is commonly associated with poor outcomes after joint replacement surgery. The goal of this study was to evaluate postoperative complications in patients with less advanced chronic kidney disease undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA). Patients who underwent THA or TKA between 2004 and 2011 with stage 1, 2, or 3 chronic kidney disease were retrospectively reviewed via an electronic medical record. The authors compared 377 patients who had stage 1 to 2 chronic kidney disease with 402 patients who had stage 3 chronic kidney disease. No significant differences in 90-day readmission or revision rates were found between the stage 1 to 2 and stage 3 patient groups. For patients with stage 3 chronic kidney disease, the overall mortality rate was greater than that in patients with stage 1 to 2 chronic kidney disease. However, when adjusted for comorbid disease, no significant increases were seen in joint infection, readmission, or early revision between patients with stage 1 to 2 chronic kidney disease vs patients with stage 3 chronic kidney disease. The overall incidence of infection was high (3.5%) but far less than reported for patients with end-stage renal disease, dialysis, and kidney transplant. In conclusion, patients with stage 1, 2, or 3 chronic kidney disease may have a higher than expected rate of prosthetic joint infection (3.5%) after total joint arthroplasty. Patients with stage 3 chronic kidney disease are at higher risk for postoperative mortality compared with those with lesser stages of kidney disease.

  13. Impact of chronic kidney disease stage on lower-extremity arthroplasty.

    PubMed

    Deegan, Brian F; Richard, Raveesh D; Bowen, Thomas R; Perkins, Robert M; Graham, Jove H; Foltzer, Michael A

    2014-07-01

    End-stage renal disease and dialysis is commonly associated with poor outcomes after joint replacement surgery. The goal of this study was to evaluate postoperative complications in patients with less advanced chronic kidney disease undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA). Patients who underwent THA or TKA between 2004 and 2011 with stage 1, 2, or 3 chronic kidney disease were retrospectively reviewed via an electronic medical record. The authors compared 377 patients who had stage 1 to 2 chronic kidney disease with 402 patients who had stage 3 chronic kidney disease. No significant differences in 90-day readmission or revision rates were found between the stage 1 to 2 and stage 3 patient groups. For patients with stage 3 chronic kidney disease, the overall mortality rate was greater than that in patients with stage 1 to 2 chronic kidney disease. However, when adjusted for comorbid disease, no significant increases were seen in joint infection, readmission, or early revision between patients with stage 1 to 2 chronic kidney disease vs patients with stage 3 chronic kidney disease. The overall incidence of infection was high (3.5%) but far less than reported for patients with end-stage renal disease, dialysis, and kidney transplant. In conclusion, patients with stage 1, 2, or 3 chronic kidney disease may have a higher than expected rate of prosthetic joint infection (3.5%) after total joint arthroplasty. Patients with stage 3 chronic kidney disease are at higher risk for postoperative mortality compared with those with lesser stages of kidney disease. PMID:24992055

  14. Spatial spread of the Hantavirus infection

    NASA Astrophysics Data System (ADS)

    Reinoso, José A.; de la Rubia, F. Javier

    2015-03-01

    The spatial propagation of Hantavirus-infected mice is considered a serious threat for public health. We analyze the spatial spread of the infected mice by including diffusion in the stage-dependent model for Hantavirus infection recently proposed by Reinoso and de la Rubia [Phys. Rev. E 87, 042706 (2013), 10.1103/PhysRevE.87.042706]. We consider a general scenario in which mice propagate in fronts from their refugia to the surroundings and find an expression for the speed of the front of infected mice. We also introduce a depletion time that measures the time scale for an appreciable impoverishment of the environment conditions and show how this new situation may change the spreading of the infection significantly.

  15. Alteration of cell cycle progression by Sindbis virus infection

    SciTech Connect

    Yi, Ruirong; Saito, Kengo; Isegawa, Naohisa; Shirasawa, Hiroshi

    2015-07-10

    We examined the impact of Sindbis virus (SINV) infection on cell cycle progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero. Cell cycle analyses showed that SINV infection is able to alter the cell cycle progression in both HeLa and Vero cells, but differently, especially during the early stage of infection. SINV infection affected the expression of several cell cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells and caused HeLa cells to accumulate in S phase during the early stage of infection. Monitoring SINV replication in HeLa and Vero cells expressing cell cycle indicators revealed that SINV which infected HeLa cells during G{sub 1} phase preferred to proliferate during S/G{sub 2} phase, and the average time interval for viral replication was significantly shorter in both HeLa and Vero cells infected during G{sub 1} phase than in cells infected during S/G{sub 2} phase. - Highlights: • SINV infection was able to alter the cell cycle progression of infected cancer cells. • SINV infection can affect the expression of cell cycle regulators. • SINV infection exhibited a preference for the timing of viral replication among the cell cycle phases.

  16. Multi-stage wax hydrocracking

    SciTech Connect

    Lipinski, J.J.; Nye, J.R.; Soudek, M.

    1991-02-19

    This patent describes improvement in a process for the shape selective catalytic dewaxing of a wax containing feed. It consists of at least one of atmospheric gas oil and vacuum gas oil by passing the feed with about 1000 to 5000 standard cubic feet per barrel of hydrogen over a dewaxing catalyst comprising a shape selective zeolite to produce a dewaxed product and wherein the hydrogen is added to retard catalyst aging. The improvement comprises conducting the dewaxing reaction in at least two states, with a first stage containing at least 20 wt. % of the dewaxing catalyst and in at least one second stage containing at least 20 wt. % of the dewaxing catalyst and adding at least a portion of the hydrogen downstream of the first stage reactor wherein the total hydrogen to the second stage is greater than the total hydrogen to the first stage.

  17. Subminiature infrared detector translation stage

    NASA Astrophysics Data System (ADS)

    Bell, Alan D.

    1989-11-01

    This paper describes a precision subminiature three-axis translation stage used in the GOES Sounder to provide positional adjustment of 12 cooled infrared detectors. Four separate translation stages and detectors are packaged into a detector mechanism which has an overall size of 0.850 x 1.230 x 0.600 inches. Each translation stage is capable of + or - 0.015 inch motion in the X and Y axes and +0.050/-0.025 inch motion in the Z axis with a sensitivity of 0.0002 inches. The function of the detector translation stage allows real time detector signal peaking during Sounder alignment. The translation stage operates in a cryogenic environment under a 10 to the -6th torr vacuum.

  18. Subminiature infrared detector translation stage

    NASA Technical Reports Server (NTRS)

    Bell, Alan D.

    1989-01-01

    This paper describes a precision subminiature three-axis translation stage used in the GOES Sounder to provide positional adjustment of 12 cooled infrared detectors. Four separate translation stages and detectors are packaged into a detector mechanism which has an overall size of 0.850 x 1.230 x 0.600 inches. Each translation stage is capable of + or - 0.015 inch motion in the X and Y axes and +0.050/-0.025 inch motion in the Z axis with a sensitivity of 0.0002 inches. The function of the detector translation stage allows real time detector signal peaking during Sounder alignment. The translation stage operates in a cryogenic environment under a 10 to the -6th torr vacuum.

  19. Radical Hysterectomy for Early Stage Cervical Cancer: Laparoscopy Versus Laparotomy

    PubMed Central

    McBee, William C.; Richard, Scott D.; Edwards, Robert P.

    2011-01-01

    Objectives: Gynecologic oncologists have recently begun using laparoscopic techniques to treat early stage cervical cancer. We evaluated a single institution's experience of laparoscopic radical hysterectomy and staging compared with laparotomy. Methods: A retrospective chart review identified stage IA2 and IB1 cervical cancer patients who underwent laparoscopic radical hysterectomy and pelvic lymph node dissection from July 2003 to April 2009. A 2:1 cohort of patients treated with laparotomy were matched by stage. Results: Nine laparoscopic patients (3 stage IA2, 6 stage IB1) with 18 matched controls (6 and 12) were identified. Demographics for each group were similar. None had positive margins or lymph nodes. An average of 11.2 vs.13.9 pelvic lymph nodes (P=0.237) were removed. Average operating time was 231.7 vs. 207.2 minutes (P=0.434), and average estimated blood loss was 161.1 vs. 394.4mL (P=0.059). Average length of stay was 2.9 vs. 5.5 days (P=0.012). No transfusions or operative complications were noted in the laparoscopic group vs. 3 each in the open group (P=0.194). No laparoscopic patients and 5 open patients had a postoperative wound infection (P=0.079). No recurrences were noted. Conclusions: Laparoscopic radical hysterectomy is a feasible alternative to laparotomy for early stage cervical cancer. Similar surgical outcomes are achieved with significantly less morbidity. PMID:21902978

  20. Stage measurement at gaging stations

    USGS Publications Warehouse

    Sauer, Vernon B.; Turnipseed, D. Phil

    2010-01-01

    Stream and reservoir stage are critical parameters in the computation of stream discharge and reservoir volume, respectively. In addition, a record of stream stage is useful in the design of structures that may be affected by stream elevation, as well as for the planning for various uses of flood plains. This report describes equipment and methodology for the observation, sensing, and recording of stage in streams and reservoirs. Although the U.S. Geological Survey (USGS) still uses the traditional, basic stilling-well float system as a predominant gaging station, modern electronic stage sensors and water-level recorders are now commonly used. Bubble gages coupled with nonsubmersible pressure transducers eliminate the need for stilling wells. Submersible pressure transducers have become common in use for the measurement of stage in both rivers and lakes. Furthermore, noncontact methods, such as radar, acoustic, and laser methods of sensing water levels, are being developed and tested, and in the case of radar, are commonly used for the measurement of stage. This report describes commonly used gaging-station structures, as well as the design and operation of gaging stations. Almost all of the equipment and instruments described in this report will meet the accuracy standard set by the USGS Office of Surface Water (OSW) for the measurement of stage for most applications, which is ?0.01 foot (ft) or 0.2 percent of the effective stage. Several telemetry systems are used to transmit stage data from the gaging station to the office, although satellite telemetry has become the standard. These telemetry systems provide near real-time stage data, as well as other information that alerts the hydrographer to extreme or abnormal events, and instrument malfunctions.

  1. Anolunula in Fingernails among Patients Infected with HIV.

    PubMed

    Gahalaut, Pratik; Mishra, Nitin; Chauhan, Sandhya; Ali, Mir Mubashir; Rastogi, Madhur Kant; Thakur, Richa

    2014-01-01

    Lunula is the white, half-moon shaped area seen in proximal ends of some nails. Though a few studies have described the nail changes that can occur in association with HIV infection, none of these paid much attention to lunula. Aims and Objectives. To study the lunula in fingernails among HIV infected patients. Materials and Methods. An observational, cross-sectional study to record presence of lunula in 168 HIV-positive patients and compare it with age and sex matched 168 healthy HIV-negative control. Anolunula (absence of lunula) in HIV-positive patients was correlated with CD4 counts, stages of HIV infection, time since patient was diagnosed as HIV-positive, and status of antiretroviral therapy. Results. Anolunula was present in significantly more fingernails in HIV-positive patients compared to HIV-negative controls. There was a highly significant difference for total anolunula (anolunula in all fingernails) in study and control group. Incidence of total anolunula was directly proportional to the stage of HIV infection, increasing progressively as the HIV infection advances from stage 1 to stage 4. Conclusion. Absence of lunula is related to not only HIV infection per se but also the stages of HIV infection.

  2. Spatiotemporal dynamics of HIV infection

    NASA Astrophysics Data System (ADS)

    Strain, Matthew Carl

    during the primary or chronic stages of HIV infection. The nonlinear clearance of HIV DNA therefore predicts lifelong virus production, even in treated patients. Collectively, these results demonstrate that important features of the spatiotemporal dynamics of HIV infection both in vitro and in vivo are best explained with explicit spatial models.

  3. Complications of radical hysterectomy: clinical experience of 115 early stage cervical cancers.

    PubMed

    Zorlu, C G; Aydoğlu, T; Ergün, Y; Kuşçu, E; Cobanoğlu, O; Koçak, S

    1998-01-01

    We evaluated the clinical experience of 115 women with early stage cervical cancer who had been operated in our Gynecologic Oncology Clinic. Of these, 85 were in stage I, and 30 in stage II. Intraoperative complications occurred in 16 patients including 3 cases concerning bladder, 1 ureter, 1 aorta, 5 v.cava inferior, 1 internal iliac a., 3 internal iliac v., 1 obturator nerve and 1 rectovaginal septum hematoma formation. Postoperative complications were observed in 38 patients. These were 14 bladder dysfunctions, 10 lymphocyst formations, 6 urinary infections, 12 wound infections, 3 pelvic infections, 2 eviscerations and 1 incisional hernia. However, no death occurred due to intraoperative or postoperative complications. Pelvic lymph node metastases were observed in 32 patients of whom 17 had only unilateral involvement, most often in the obturator region. Para-aortic lymph node metastases were diagnosed in 4 patients, all of whom were in stage II.

  4. Liver-Stage Specific Response among Endemic Populations: Diet and Immunity

    PubMed Central

    Dalai, Sarat Kumar; Yadav, Naveen; Patidar, Manoj; Patel, Hardik; Singh, Agam Prasad

    2015-01-01

    Developing effective anti-malarial vaccine has been a challenge for long. Various factors including complex life cycle of parasite and lack of knowledge of stage specific critical antigens are some of the reasons. Moreover, inadequate understanding of the immune responses vis-à-vis sterile protection induced naturally by Plasmodia infection has further compounded the problem. It has been shown that people living in endemic areas take years to develop protective immunity to blood stage infection. But hardly anyone believes that immunity to liver-stage infection could be developed. Various experimental model studies using attenuated parasite suggest that liver-stage immunity might exist among endemic populations. This could be induced because of the attenuation of parasite in liver by various compounds present in the diet of endemic populations. PMID:25852693

  5. How Is Kaposi Sarcoma Staged?

    MedlinePlus

    ... the lungs is a particularly bad sign. I (immune system) status The immune status is assessed using a ... in healthy people but affect people with suppressed immune systems) or thrush (a fungal infection in the mouth). ...

  6. Virology, Immunology, and Clinical Course of HIV Infection.

    ERIC Educational Resources Information Center

    McCutchan, J. Allen

    1990-01-01

    Presents overview of medical aspects of human immunodeficiency virus Type 1 (HIV-1) disease. Addresses structure and replication of virus, current methods for detecting HIV-1 in infected persons, effects of the virus on immune system, and clinical course of HIV-1 disease. Emphasizes variable causes of progression through HIV-1 infection stages;…

  7. Adenovirus infection reverses the antiviral state induced by human interferon.

    PubMed

    Feduchi, E; Carrasco, L

    1987-04-01

    HeLa cells treated with human lymphoblastoid interferon do not synthesize poliovirus proteins. The antiviral state against poliovirus is reversed if cells are previously infected with adenovirus type 5. A late gene product seems to be involved in this reversion, since no effect is observed at early stages of infection or in the presence of aphidicolin.

  8. Analysis of the transmission of Trypanosoma cruzi infection through hosts and vectors.

    PubMed

    Fabrizio, María C; Schweigmann, Nicolás J; Bartoloni, Norberto J

    2016-08-01

    Calculating epidemiological measures of infection by Trypanosoma cruzi, the causative agent of Chagas disease, is complex, because it involves several species, different stages of infection in humans and multiple transmission routes. Using the next-generation matrix method, we analysed a model which considers the three stages of human infection, triatomines and dogs (the main domestic reservoirs of T. cruzi when triatomines are present) and the main transmission routes. We derived R 0 and type-reproduction numbers T. We deduced formulas for the number of new infections generated through each transmission route by each infected individual. We applied our findings in Argentine Gran Chaco. The expressions achieved allowed quantifying the high infectivity of dogs and emphasizing the epidemiological importance of the long and asymptomatic chronic indeterminate stage in humans in the spread of the infection. According to the model, it is expected that one infected human infects 21 triatomines, that 100 infected triatomines are necessary to infect one human and 34 to infect a dog, and that each dog infects on average one triatomine per day. Our results may allow quantifying the effect of control measures on infected humans, triatomines and dogs (or other highly infected vertebrate) or on a specific route of transmission, in other scenarios. PMID:27039662

  9. Analysis of the transmission of Trypanosoma cruzi infection through hosts and vectors.

    PubMed

    Fabrizio, María C; Schweigmann, Nicolás J; Bartoloni, Norberto J

    2016-08-01

    Calculating epidemiological measures of infection by Trypanosoma cruzi, the causative agent of Chagas disease, is complex, because it involves several species, different stages of infection in humans and multiple transmission routes. Using the next-generation matrix method, we analysed a model which considers the three stages of human infection, triatomines and dogs (the main domestic reservoirs of T. cruzi when triatomines are present) and the main transmission routes. We derived R 0 and type-reproduction numbers T. We deduced formulas for the number of new infections generated through each transmission route by each infected individual. We applied our findings in Argentine Gran Chaco. The expressions achieved allowed quantifying the high infectivity of dogs and emphasizing the epidemiological importance of the long and asymptomatic chronic indeterminate stage in humans in the spread of the infection. According to the model, it is expected that one infected human infects 21 triatomines, that 100 infected triatomines are necessary to infect one human and 34 to infect a dog, and that each dog infects on average one triatomine per day. Our results may allow quantifying the effect of control measures on infected humans, triatomines and dogs (or other highly infected vertebrate) or on a specific route of transmission, in other scenarios.

  10. Circulating immune cell subpopulations in pestivirus persistently infected calves and non-infected calves varying in immune status.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Circulating immune cell subpopulations in cattle representing varying stages of immune status categorized as; colostrum deprived (CD), receiving colostrum (COL), colostrum plus vaccination (VAC) and persistently infected with a pestivirus (PI) were compared. The PI calves were infected with a HoBi-...

  11. Circulating immune cell subpopulations in pestivirus persistently infected calves and non-infected calves varying in immune status [Abstract

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The circulating immune cell subpopulations in cattle representing varying stages of immune status categorized as; colostrum deprived (CD), receiving colostrum (COL), colostrum plus vaccination (VAC) and persistently infected with a pestivirus (PI) were compared. The PI calves were infected with a H...

  12. Distribution of potato spindle tuber viroid in reproductive organs of petunia during its developmental stages.

    PubMed

    Matsushita, Yosuke; Tsuda, Shinya

    2014-09-01

    Embryo infection is important for efficient seed transmission of viroids. To identify the major pattern of seed transmission of viroids, we used in situ hybridization to histochemically analyze the distribution of Potato spindle tuber viroid (PSTVd) in each developmental stage of petunia (flowering to mature seed stages). In floral organs, PSTVd was present in the reproductive tissues of infected female × infected male and infected female × healthy male but not of healthy female × infected male before embryogenesis. After pollination, PSTVd was detected in the developed embryo and endosperm in all three crosses. These findings indicate that PSTVd is indirectly delivered to the embryo through ovule or pollen during the development of reproductive tissues before embryogenesis but not directly through maternal tissues as cell-to-cell movement during embryogenesis.

  13. Listeria Infections (For Parents)

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Listeria Infections KidsHealth > For Parents > Listeria Infections Print A ... to Call the Doctor en español Listeriosis About Listeria Listeria infections (known as listeriosis ) are rare. When ...

  14. Infections and Pregnancy

    MedlinePlus

    If you are pregnant, an infection can be more than just a problem for you. Some infections can be dangerous to your baby. You can help yourself avoid infections: Don't eat raw or undercooked meat Don' ...

  15. Chlamydial infections - male

    MedlinePlus

    Chlamydia infection in males is an infection of the urethra (the tube that drains urine from the ... and passes through the penis). This type of chlamydia infection is passed from one person to another ...

  16. Cognitive Development and Group Stages.

    ERIC Educational Resources Information Center

    Saidla, Debie D.

    1990-01-01

    Attempts to integrate Perry's (1970) scheme of the cognitive development of college students with a model of group development adapted by Waldo (1985) based on Tuckman's (1965) formulation of developmental group stages. (Author)

  17. Evaluating the Stage Learning Hypothesis.

    ERIC Educational Resources Information Center

    Thomas, Hoben

    1980-01-01

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

  18. Two stage to orbit design

    NASA Technical Reports Server (NTRS)

    1991-01-01

    A preliminary design of a two-stage to orbit vehicle was conducted with the requirements to carry a 10,000 pound payload into a 300 mile low-earth orbit using an airbreathing first stage, and to take off and land unassisted on a 15,000 foot runway. The goal of the design analysis was to produce the most efficient vehicle in size and weight which could accomplish the mission requirements. Initial parametric analysis indicated that the weight of the orbiter and the transonic performance of the system were the two parameters that had the largest impact on the design. The resulting system uses a turbofan ramjet powered first stage to propel a scramjet and rocket powered orbiter to the stage point of Mach 6 to 6.5 at an altitude of 90,000 ft.

  19. Two stage liquefaction of coal

    DOEpatents

    Neuworth, Martin B.

    1981-01-01

    A two stage coal liquefaction process and apparatus comprising hydrogen donor solvent extracting, solvent deashing, and catalytic hydrocracking. Preferrably, the catalytic hydrocracking is performed in an ebullating bed hydrocracker.

  20. Congenital Toxoplasmosis in Chronically Infected and Subsequently Challenged Ewes

    PubMed Central

    dos Santos, Thaís Rabelo; Faria, Gabriela da Silva Magalhães; Guerreiro, Bruna Martins; dal Pietro, Nathalia Helena Pereira da Silva; Lopes, Welber Daniel Zanetti; da Silva, Helenara Machado; Garcia, João Luis; Luvizotto, Maria Cecília Rui; Bresciani, Katia Denise Saraiva; da Costa, Alvimar José

    2016-01-01

    This experiment studied congenital transmission in sheep experimentally infected with oocysts of Toxoplasma gondii and reinfected at one of three stages of pregnancy. Twenty ewes were experimentally infected with T. gondii strain ME49 (day 0). After the T. gondii infection became chronic (IFAT≤512), the ewes were allocated with rams for coverage. After the diagnosis of pregnancy, these ewes were allocated into four experimental groups (n = 5): I-reinfected with T. gondii on the 40th day of gestation (DG); II-reinfected on DG 80; III-reinfected on DG 120; and IV-saline solution on DG 120 (not reinfected). Five ewes (IFAT<64) were kept as negative controls (uninfected, group V), therefore in groups I-III were infected prior to pregnancy and re-infected during pregnancy, group IV was only infected prior to pregnancy, and group V was not infected. Parasitism by T. gondii was investigated (histopathology, immunohistochemistry, mouse bioassay and PCR) in mothers and lambs tissue. All ewes produced lambs serologically positive for T. gondii. The results of the mouse bioassay, immunohistochemistry and PCR assays revealed the presence of T. gondii in all 20 sheep and their lambs. The congenital transmission of T. gondii was associated with fetal loss and abnormalities in persistently infected sheep and in ewes infected and subsequently reinfected by this protozoan. Therefore, congenital T. gondii infection was common when ewes were chronically infected prior to pregnancy, with or without reinfection during at various stages of gestation. PMID:27788185

  1. Staged regenerative sorption heat pump

    NASA Technical Reports Server (NTRS)

    Jones, Jack A. (Inventor)

    1995-01-01

    A regenerative adsorbent heat pump process and system for cooling and heating a space. A sorbent is confined in a plurality of compressors of which at least four are first stage and at least four are second stage. The first stage operates over a first pressure region and the second stage over a second pressure region which is higher than the first. Sorbate from the first stage enters the second stage. The sorbate loop includes a condenser, expansion valve, evaporator and the compressors. A single sorbate loop can be employed for single-temperature-control such as air conditioning and heating. Two sorbate loops can be used for two-temperature-control as in a refrigerator and freezer. The evaporator temperatures control the freezer and refrigerator temperatures. Alternatively the refrigerator temperature can be cooled by the freezer with one sorbate loop. A heat transfer fluid is circulated in a closed loop which includes a radiator and the compressors. Low temperature heat is exhausted by the radiator. High temperature heat is added to the heat transfer fluid entering the compressors which are desorbing vapor. Heat is transferred from compressors which are sorbing vapor to the heat transfer fluid, and from the heat transfer fluid to the compressors which are desorbing vapor. Each compressor is subjected to the following phases, heating to its highest temperature, cooling down from its highest temperature, cooling to its lowest temperature, and warming up from its lowest temperature. The phases are repeated to complete a cycle and regenerate heat.

  2. Crew Launch Vehicle Upper Stage

    NASA Technical Reports Server (NTRS)

    Davis, D. J.; Cook, J. R.

    2006-01-01

    The Agency s Crew Launch Vehicle (CLV) will be the first human rated space transportation system developed in the United States since the Space Shuttle. The CLV will utilize existing Shuttle heritage hardware and systems combined with a "clean sheet design" for the Upper Stage. The Upper Stage element will be designed and developed by a team of NASA engineers managed by the Marshall Space Flight Center (MSFC) in Huntsville, Alabama. The team will design the Upper Stage based on the Exploration Systems Architecture Study (ESAS) Team s point of departure conceptual design as illustrated in the figure below. This concept is a self-supporting cylindrical structure, approximately 1 15 feet long and 216 inches in diameter. While this "clean-sheet" upper stage design inherently carries more risk than utilizing a modified design, the approach also has many advantages. This paper will discuss the advantages and disadvantages of pursuing a "clean-sheet" design for the new CLV Upper Stage as well as describe in detail the overall design of the Upper Stage and its integration into NASA s CLV.

  3. Postembryonic stages of Nucellicola holmanae Lamb et al., 1996 (copepoda, poecilostomatoida), an endoparasite of the dog whelk Nucella lapillus (gastropoda)

    NASA Astrophysics Data System (ADS)

    Lamb, E. J.; Boxshall, G. A.; Mill, P. J.; Grahame, J.

    1998-06-01

    The external morphology of the first three larval stages of Nucellicola holmanae is described. These stages were cultured from eggs found with the adults in the viscera of dog whelks collected from Robin Hood's Bay, North Yorkshire. The nauplius develops within the whelk. It moults to a metanauplius which is released as a free-swimming stage. The metanauplius moults to a free copepodid stage which exhibits a combination of characters typical of the first, second and third copepodid stages of other poecilostomatoid copepods. The infective copepodid stage which locates and penetrates the host is visible through the integument of this free-swimming copepodid.

  4. Assessment of causal prophylactic activity in Plasmodium berghei yoelii and its value for the development of new antimalarial drugs*

    PubMed Central

    Fink, E.

    1974-01-01

    The causal prophylactic activity of several reference and experimental antimalarial compounds was assessed in sporozoite-induced infections of NMRI mice with Plasmodium berghei yoelii (strain 17X). The animals were inoculated with 10 000 sporozoites per mouse and treated once 2-4 hours later. The test system has proved to be very suitable in experiments involving more than 3 000 mice. The infection rate in 448 untreated controls was 97.3%. Lowering the sporozoite content of the inoculum to 1 000 or 100 sporozoites markedly reduced the rate (65.1% and 32.7%). In experiments with primaquine the causal prophylactic activity was also influenced by the time of drug administration before or after sporozoite inoculation. No causal prophylactic effect was demonstrable with quinine, chloroquine, amodiaquine, amopyroquine, RC-12, or B 505. Primaquine was active, but pamaquine and pentaquine were only sporadically active. The pre-erythrocytic stages of P. b. yoelii were only slightly sensitive to dapsone, sulfadiazine, and sulformethoxine; they were 10-100 times more susceptible to proguanil, cycloguanil, and pyrimethamine. The experimental 6-aminoquinolines NI 147/36, NI 187/82, and BA 138/111 and the 7-chlorolincomycin derivative U 24729 were also studied. Experiments in which curative activity against blood-induced infections of P. b. yoelii was evaluated showed that the causal prophylactics act more specifically against the pre-erythrocytic than against the erythrocytic forms. This specificity was most pronounced among the DHFR-inhibitors, whose outstanding activity may be explained by the fact that the rate of multiplication of the pre-erythrocytic forms of P. b. yoelii is greater than that of other plasmodia used hitherto; it is also greater than the rate shown by the malaria parasites of man and that of the erythrocytic forms of P. b. yoelii itself. We believe that this feature will render P. b. yoelii very useful for determination of the causal prophylactic activity

  5. Acute cytomegalovirus (CMV) infection

    MedlinePlus

    CMV mononucleosis; Cytomegalovirus (CMV) ... Infection with cytomegalovirus (CMV) is very common. The infection is spread by: Blood transfusions Organ transplants Respiratory droplets Saliva Sexual contact ...

  6. Fungal infections of the orbit

    PubMed Central

    Mukherjee, Bipasha; Raichura, Nirav Dilip; Alam, Md. Shahid

    2016-01-01

    Fungal infections of the orbit can lead to grave complications. Although the primary site of inoculation of the infective organism is frequently the sinuses, the patients can initially present to the ophthalmologist with ocular signs and symptoms. Due to its varied and nonspecific clinical features, especially in the early stages, patients are frequently misdiagnosed and even treated with steroids which worsen the situation leading to dire consequences. Ophthalmologists should be familiar with the clinical spectrum of disease and the variable presentation of this infection, as early diagnosis and rapid institution of appropriate therapy are crucial elements in the management of this invasive sino-orbital infection. In this review, relevant clinical, microbiological, and imaging findings are discussed along with the current consensus on local and systemic management. We review the recent literature and provide a comprehensive analysis. In the immunocompromised, as well as in healthy patients, a high index of suspicion must be maintained as delay in diagnosis of fungal pathology may lead to disfiguring morbidity or even mortality. Obtaining adequate diagnostic material for pathological and microbiological examination is critical. Newer methods of therapy, particularly oral voriconazole and topical amphotericin B, may be beneficial in selected patients. PMID:27380972

  7. [HIV infection : Test and treatment].

    PubMed

    Rockstroh, J K; Wasmuth, J-C

    2016-08-01

    In Europe depending on the country 15-80 % of all individuals infected with human immunodeficiency virus (HIV) are either not aware of the diagnosis or are diagnosed later. An early HIV diagnosis could, however, considerably improve the prognosis of individuals infected with HIV and decrease the risk of new infections; therefore, in the presence of indicator diseases, such as sexually transmitted diseases, oral thrush, herpes zoster and lymphoma, the performance of a HIV test is of utmost importance. A newly diagnosed HIV infection represents an indication for starting antiretroviral combination therapy independent of the clinical stage or CD4 cell count. A decline of the viral burden to below the limit of detection and subsequent continuous suppression of viral replication can prevent transition from HIV to acquired immune deficiency syndrome (AIDS) and if started early enough a normal life expectancy can be achieved. Challenges which remain in HIV therapy are the lifelong daily intake of medication and the complex long-term adverse effects. PMID:27368530

  8. Infective endocarditis.

    PubMed

    Herregods, M-C

    2011-01-01

    Despite the progress in medicine, infectious endocarditis is often diagnosed late, as its symptomatology is subject to a high variability. The clinical features are usually atypical. Since the introduction of the Duke criteria, clinical, bacteriological and echocardiographical findings are being integrated, allowing an earlier definitive diagnosis. The incidence remains practically stable. The decrease in post-rheumatic valvular heart disease at population level is compensated by an increase in degenerative valvular heart disease as predisposing factor. Moreover, the share of patients with intravascular foreign material is increasing. Endocarditis is usually characterized by a complicated development. About half of the patients develop heart failure as a consequence of the destruction of the affected valve with serious valvular insufficiency. One third of the patients present cerebral or peripheral embolization. Embolization predominantly occurs at the beginning, until the first two weeks of antibiotic treatment. Abscess formation occurs more frequently than is suspected based on echographical examinations. Particularly a Staphylococcus aureus infection in the presence of an artificial valve leads to extravalvular extension with abscess formation around the artificial valve. Treatment should be initiated promptly. High doses of antibiotics, tailored to the microorganism and the valve type (native or artificial valve), are administered intravenously during four, or more frequently, six weeks. In more than half of the patients cardiac surgery is also required. As soon as an indication for cardiac surgery is present, the operation should not be postponed. Experience learns that a smaller risk is associated with an early intervention. The operation is performed in a technically easier way. Eventually, also the total duration of hospitalization is shorter. Despite the available antibiotics and the technical progress in cardiac surgery, mortality remains high. This is

  9. Enteric pathogens through life stages

    PubMed Central

    Kolling, Glynis; Wu, Martin; Guerrant, Richard L.

    2012-01-01

    Enteric infections and diarrheal diseases constitute pervasive health burdens throughout the world, with rates being highest at the two ends of life. During the first 2–3 years of life, much of the disease burden may be attributed to infection with enteric pathogens including Salmonella, rotavirus, and many other bacterial, viral, and protozoan organisms; however, infections due to Clostridium difficile exhibit steady increases with age. Still others, like Campylobacter infections in industrialized settings are high in early life (<2 years old) and increase again in early adulthood (called the “second weaning” by some). The reasons for these differences undoubtedly reside in part in pathogen differences; however, host factors including the commensal intestinal microbial communities, immune responses (innate and acquired), and age-dependant shifts likely play important roles. Interplay of these factors is illustrated by studies examining changes in human gut microbiota with inflammatory bowel disease and irritable bowel syndrome. Recent gut microbial surveys have indicated dramatic shifts in gut microbial population structure from infants to young adults to the elders. An understanding of the evolution of these factors and their interactions (e.g., how does gut microbiota modulate the “inflamm-aging” process or vice versa) through the human life “cycle” will be important in better addressing and controlling these enteric infections and their consequences for both quality and quantity of life (often assessed as disability adjusted life-years or “DALYs”). PMID:22937528

  10. Backward elastic light scattering of malaria infected red blood cells

    NASA Astrophysics Data System (ADS)

    Lee, Seungjun; Lu, Wei

    2011-08-01

    We investigated the backward light scattering pattern of healthy and malaria (Plasmodium falciparum) parasitized red blood cells. The spectrum could clearly distinguish between predominant ring stage infected blood cells and healthy blood cells. Further, we found that infected samples mixed with different stages of P. falciparum showed different signals, suggesting that even variance in parasite stages could also be detected by the spectrum. These results together with the backward scattering technique suggest the potential of non-invasive diagnosis of malaria through light scattering of blood cells near the surface of human body, such as using eyes or skin surface.

  11. Saturn IB First Stage (S-IB Stage) at MSFC

    NASA Technical Reports Server (NTRS)

    1965-01-01

    Marshall Space Flight Center (MSFC) workers lower S-IB-200D, a dynamic test version of the Saturn IB launch vehicle's first stage (S-IB stage), into the Center's Dynamic Test Stand on January 12, 1965. Test Laboratory persornel assembled a complete Saturn IB to test the structural soundness of the launch vehicle. Developed by the MSFC as an interim vehicle in MSFC's 'building block' approach to Saturn rocket development, the Saturn IB utilized Saturn I technology to further develop and refine large boosters and the Apollo spacecraft capabilities required for the manned lunar missions.

  12. Saturn IB First Stage (S-IB Stage) at MSFC

    NASA Technical Reports Server (NTRS)

    1965-01-01

    Workers at the Marshall Space Flight Center (MSFC) begin hoisting S-IB-200D, a dynamic test version of the Saturn IB launch vehicle's first stage (S-IB stage), into the Center's Dynamic Test Stand on January 11, 1965. Test Laboratory persornel assembled a complete Saturn IB to test the structural soundness of the launch vehicle. Developed by the MSFC as an interim vehicle in MSFC's 'building block' approach to Saturn rocket development, the Saturn IB utilized Saturn I technology to further develop and refine large boosters and the Apollo spacecraft capabilities required for the manned lunar missions.

  13. Size Does Matter: Staging of Silene latifolia Floral Buds for Transcriptome Studies

    PubMed Central

    Toh, Su San; Perlin, Michael H.

    2015-01-01

    Dioecious plants in the Caryophyllaceae family are susceptible to infection by members of the anthericolous smut fungi. In our studies of the Silene latifolia/Microbotryum lychnidis-dioicae pathosystem, we were interested in characterizing the plant-pathogen interaction at the molecular level before and during teliosporogenesis. This takes place during floral bud development, and we hoped to capture the interaction by Illumina Next-Gen RNA-Sequencing. Using previous literature that documented the stages of the floral buds for S. latifolia, we examined the floral buds from plants grown and infected under growth chamber conditions, using the disserting microscope to determine the stage of floral buds based on the morphology. We compiled the information and determined the size of floral buds that correspond to the desired stages of development for tissue collection, for the purpose of RNA-sequencing. This offers a practical approach for researchers who require a large number of floral buds/tissue categorized by stages of development, ascertaining whether infected/uninfected buds are at comparable stages of development and whether this also holds true for male vs. female buds. We also document our experience in infecting the plants and some of the unusual morphologies we observed after infection. PMID:26378529

  14. Two-Stage Centrifugal Fan

    NASA Technical Reports Server (NTRS)

    Converse, David

    2011-01-01

    Fan designs are often constrained by envelope, rotational speed, weight, and power. Aerodynamic performance and motor electrical performance are heavily influenced by rotational speed. The fan used in this work is at a practical limit for rotational speed due to motor performance characteristics, and there is no more space available in the packaging for a larger fan. The pressure rise requirements keep growing. The way to ordinarily accommodate a higher DP is to spin faster or grow the fan rotor diameter. The invention is to put two radially oriented stages on a single disk. Flow enters the first stage from the center; energy is imparted to the flow in the first stage blades, the flow is redirected some amount opposite to the direction of rotation in the fixed stators, and more energy is imparted to the flow in the second- stage blades. Without increasing either rotational speed or disk diameter, it is believed that as much as 50 percent more DP can be achieved with this design than with an ordinary, single-stage centrifugal design. This invention is useful primarily for fans having relatively low flow rates with relatively high pressure rise requirements.

  15. Three stages of medical dialogue.

    PubMed

    Abramovitch, H; Schwartz, E

    1996-06-01

    The negative consequences of physicians' failure to establish and maintain personal relationships with patients are at the heart of the "humanistic crisis" in medicine. To resolve this crisis, a new model of doctor-patient interaction is proposed, based on the ideas of Martin Buber's philosophy of dialogue. This model shows how the physician may successfully combine the personal (I-Thou) and impersonal (I-It) aspects of medicine in three stages. These "Three Stages of Medical Dialogue" include: 1. An Initial Personal Meeting stage, which initiates the doctor-patient relationship and involves mutual confirmation; 2. An Examination stage, which requires a shift from a personal to an impersonal style of interaction; 3. An Integration Through Dialogue or "Healing Through Meeting" Stage, which involves the integration of the impersonal medical data into the ongoing dialogue between doctor and patient, as a basis for shared decision-making. The use of the model, as well as common failures of doctor-patient dialogue are discussed.

  16. Stage Separation Performance Analysis Project

    NASA Technical Reports Server (NTRS)

    Chen, Yen-Sen; Zhang, Sijun; Liu, Jiwen; Wang, Ten-See

    2001-01-01

    Stage separation process is an important phenomenon in multi-stage launch vehicle operation. The transient flowfield coupled with the multi-body systems is a challenging problem in design analysis. The thermodynamics environment with burning propellants during the upper-stage engine start in the separation processes adds to the complexity of the-entire system. Understanding the underlying flow physics and vehicle dynamics during stage separation is required in designing a multi-stage launch vehicle with good flight performance. A computational fluid dynamics model with the capability to coupling transient multi-body dynamics systems will be a useful tool for simulating the effects of transient flowfield, plume/jet heating and vehicle dynamics. A computational model using generalize mesh system will be used as the basis of this development. The multi-body dynamics system will be solved, by integrating a system of six-degree-of-freedom equations of motion with high accuracy. Multi-body mesh system and their interactions will be modeled using parallel computing algorithms. Adaptive mesh refinement method will also be employed to enhance solution accuracy in the transient process.

  17. [The efficiency of combined therapy of herpes virus infection in HIV infected patients].

    PubMed

    Papuashvili, M N; Shchelkanov, M Iu

    2004-01-01

    The target of the case study was to investigate the efficiency of an alternative combined therapy scheme of herpes simplex infections versus the routine therapy by acyclovir or famvir as applicable to HIV-infected patients. leukinferon was shown to induce the antoherpetic acyclovir efficiency. The use of the latter concurrently with cycloferon for the treatment of infections provoked by herpes simple virus-1 (HSV-1) and HSV-2 in HIV-infected patients prolongs the remission period in case of the above opportunistic infections. The leukinferon anti-herpetic efficiency is, obviously, related with the phagocytosis stimulation and with its positive influence exerted on hemopoiesis. The combined therapy can be stated to be most effective in HIV, clinical stages B1 and 2.

  18. A Sporozoite- and Liver Stage-expressed Tryptophan-rich Protein Plays an Auxiliary Role in Plasmodium Liver Stage Development and Is a Potential Vaccine Candidate*

    PubMed Central

    Jaijyan, Dabbu Kumar; Singh, Himanshu; Singh, Agam Prasad

    2015-01-01

    The liver stages of the malaria parasite are clinically silent and constitute ideal targets for causal prophylactic drugs and vaccines. Cellular and molecular events responsible for liver stage development are poorly characterized. Here, we show that sporozoite, liver stage tryptophan-rich protein (SLTRiP) forms large multimers. Mice immunized with a purified recombinant SLTRiP protein gave high antibody titers in both inbred and outbred mice. Immunized mice showed highly significant levels of protection upon challenge with sporozoites and exhibited 10,000-fold fewer parasite 18S-rRNA copy numbers in their livers. The protection offered by immunization with SLTRiP came mainly from T-cells, and antibodies had little role to play despite their high titers. Immunofluorescence assays showed that SLTRiP is expressed in the sporozoite and early to late liver stages of malaria parasites. SLTRiP protein is exported to the cytosol of infected host cells during the early hours of parasite infection. Parasites deficient in SLTRiP were moderately defective in liver stage parasite development. A transcriptome profile of SLTRiP-deficient parasite-infected hepatocytes highlighted that SLTRiP interferes with multiple pathways in the host cell. We have demonstrated a role for SLTRiP in sporozoites and the liver stage of malaria parasites. PMID:25960542

  19. Helicobacter pylori infection and related gastrointestinal diseases.

    PubMed

    Makola, Diklar; Peura, David A; Crowe, Sheila E

    2007-07-01

    Helicobacter pylori has been implicated in the pathogenesis of a number of digestive tract disorders, such as chronic active gastritis, peptic ulceration, gastric cancer, and mucosa-associated lymphoid tissue lymphoma. Disease outcome is dependent on many factors, including bacterial genotype, host physiology and genetics, and environmental factors such as diet. Researchers continue to explore the complexities of H. pylori infection, seeking to explain why some individuals have asymptomatic infection, whereas others experience clinical disease. The importance of treating H. pylori infection in patients with gastrointestinal problems has been confirmed in recent years, with clinical trials showing that cure of infection can prevent duodenal ulcer and, to a lesser extent, gastric ulcer recurrence; cure early stage mucosa-associated lymphoid tissue lymphoma; and reduce the chances of developing gastric cancer in high-risk individuals.

  20. Programmatic Implications of Acute and Early HIV Infection.

    PubMed

    Suthar, Amitabh B; Granich, Reuben M; Kato, Masaya; Nsanzimana, Sabin; Montaner, Julio S G; Williams, Brian G

    2015-11-01

    Human immunodeficiency virus (HIV) infection includes acute, early, chronic, and late stages. Acute HIV infection lasts approximately 3 weeks and early HIV infection, which includes acute HIV infection, lasts approximately 7 weeks. Many testing and blood screening algorithms detect HIV antibodies about 3 weeks after HIV infection. Incidence estimates are based on results of modeling, cohort studies, surveillance, and/or assays. Viral load is the key modifiable risk factor for HIV transmission and peaks during acute and early HIV infection. Empirical evidence characterizing the impact of acute and early HIV infection on the spread of the HIV epidemic are limited. Time trends of HIV prevalence collected from concentrated and generalized epidemics suggest that acute and early HIV infection may have a limited role in population HIV transmission. Collectively, these data suggest that acute and early HIV infection is relatively short and does not currently require fundamentally different programmatic approaches to manage the HIV/AIDS epidemic in most settings. Research and surveillance will inform which epidemic contexts and phases may require tailored strategies for these stages of HIV infection.

  1. Who Gets Fungal Infections?

    MedlinePlus

    ... infections can also happen in people without weak immune systems Fungal infections that are not life-threatening, such ... likely to cause an infection. People with weak immune systems Infections that happen because a person’s immune system ...

  2. Fusarium infections of the skin.

    PubMed

    Gupta, Aditya K.; Baran, Robert; Summerbell, Richard C.

    2000-04-01

    Fusarium species are ubiquitous and may be found in the soil, air and on plants. Fusarium species can cause mycotoxicosis in humans following ingestion of food that has been colonized by the fungal organism. In humans, Fusarium species can also cause disease that is localized, focally invasive or disseminated. The pathogen generally affects immunocompromised individuals with infection of immunocompetent persons being rarely reported. Localized infection includes septic arthritis, endophthalmitis, osteomyelitis, cystitis and brain abscess. In these situations relatively good response may be expected following appropriate surgery and oral antifungal therapy. Disseminated infection occurs when two or more noncontiguous sites are involved. Over eighty cases have been reported, many of which had a hematologic malignancy including neutropenia. The species most commonly involved include Fusarium solani, Fusarium oxysporum, and Fusarium moniliforme (also termed F. verticillioides). The diagnosis of Fusarium infection may be made on histopathology, gram stain, mycology, blood culture, or serology. Portals of entry of disseminated infection include the respiratory tract, the gastrointestinal tract, and cutaneous sites.The skin can be an important and an early clue to diagnosis since cutaneous lesions may be observed at an early stage of the disease and in about seventy-five cases of disseminated Fusarium infection. Typical skin lesions may be painful red or violaceous nodules, the center of which often becomes ulcerated and covered by a black eschar. The multiple necrotizing lesions are often observed on the trunk and the extremities. Onychomycosis most commonly due to F. oxysporum or F. solani has been reported. The onychomycosis may be of several types: distal and lateral subungual (DLSO), white superficial (WSO), and proximal subungual (PSO). In proximal subungual onychomycosis there may be associated leukonychia and/or periungual inflammation. Patients with Fusarium

  3. Deconvoluting heme biosynthesis to target blood-stage malaria parasites.

    PubMed

    Sigala, Paul A; Crowley, Jan R; Henderson, Jeffrey P; Goldberg, Daniel E

    2015-07-14

    Heme metabolism is central to blood-stage infection by the malaria parasite Plasmodium falciparum. Parasites retain a heme biosynthesis pathway but do not require its activity during infection of heme-rich erythrocytes, where they can scavenge host heme to meet metabolic needs. Nevertheless, heme biosynthesis in parasite-infected erythrocytes can be potently stimulated by exogenous 5-aminolevulinic acid (ALA), resulting in accumulation of the phototoxic intermediate protoporphyrin IX (PPIX). Here we use photodynamic imaging, mass spectrometry, parasite gene disruption, and chemical probes to reveal that vestigial host enzymes in the cytoplasm of Plasmodium-infected erythrocytes contribute to ALA-stimulated heme biosynthesis and that ALA uptake depends on parasite-established permeability pathways. We show that PPIX accumulation in infected erythrocytes can be harnessed for antimalarial chemotherapy using luminol-based chemiluminescence and combinatorial stimulation by low-dose artemisinin to photoactivate PPIX to produce cytotoxic reactive oxygen. This photodynamic strategy has the advantage of exploiting host enzymes refractory to resistance-conferring mutations.

  4. Deconvoluting heme biosynthesis to target blood-stage malaria parasites

    PubMed Central

    Sigala, Paul A; Crowley, Jan R; Henderson, Jeffrey P; Goldberg, Daniel E

    2015-01-01

    Heme metabolism is central to blood-stage infection by the malaria parasite Plasmodium falciparum. Parasites retain a heme biosynthesis pathway but do not require its activity during infection of heme-rich erythrocytes, where they can scavenge host heme to meet metabolic needs. Nevertheless, heme biosynthesis in parasite-infected erythrocytes can be potently stimulated by exogenous 5-aminolevulinic acid (ALA), resulting in accumulation of the phototoxic intermediate protoporphyrin IX (PPIX). Here we use photodynamic imaging, mass spectrometry, parasite gene disruption, and chemical probes to reveal that vestigial host enzymes in the cytoplasm of Plasmodium-infected erythrocytes contribute to ALA-stimulated heme biosynthesis and that ALA uptake depends on parasite-established permeability pathways. We show that PPIX accumulation in infected erythrocytes can be harnessed for antimalarial chemotherapy using luminol-based chemiluminescence and combinatorial stimulation by low-dose artemisinin to photoactivate PPIX to produce cytotoxic reactive oxygen. This photodynamic strategy has the advantage of exploiting host enzymes refractory to resistance-conferring mutations. DOI: http://dx.doi.org/10.7554/eLife.09143.001 PMID:26173178

  5. Deconvoluting heme biosynthesis to target blood-stage malaria parasites.

    PubMed

    Sigala, Paul A; Crowley, Jan R; Henderson, Jeffrey P; Goldberg, Daniel E

    2015-01-01

    Heme metabolism is central to blood-stage infection by the malaria parasite Plasmodium falciparum. Parasites retain a heme biosynthesis pathway but do not require its activity during infection of heme-rich erythrocytes, where they can scavenge host heme to meet metabolic needs. Nevertheless, heme biosynthesis in parasite-infected erythrocytes can be potently stimulated by exogenous 5-aminolevulinic acid (ALA), resulting in accumulation of the phototoxic intermediate protoporphyrin IX (PPIX). Here we use photodynamic imaging, mass spectrometry, parasite gene disruption, and chemical probes to reveal that vestigial host enzymes in the cytoplasm of Plasmodium-infected erythrocytes contribute to ALA-stimulated heme biosynthesis and that ALA uptake depends on parasite-established permeability pathways. We show that PPIX accumulation in infected erythrocytes can be harnessed for antimalarial chemotherapy using luminol-based chemiluminescence and combinatorial stimulation by low-dose artemisinin to photoactivate PPIX to produce cytotoxic reactive oxygen. This photodynamic strategy has the advantage of exploiting host enzymes refractory to resistance-conferring mutations. PMID:26173178

  6. Vaginal Yeast Infections (For Parents)

    MedlinePlus

    ... Can I Help a Friend Who Cuts? Vaginal Yeast Infections KidsHealth > For Teens > Vaginal Yeast Infections Print ... side effect of taking antibiotics. What Is a Yeast Infection? A yeast infection is a common infection ...

  7. Staged sacrectomy--an adaptive approach.

    PubMed

    Ramamurthy, Rajaraman; Bose, Jagadish Chandra; Muthusamy, Vimalakannan; Natarajan, Mayilvahanan; Kunjithapatham, Deiveegan

    2009-09-01

    Object Sacral tumors are commonly diagnosed late and therefore present at an advanced stage. The late presentation makes curative surgery technically demanding. Sacrectomy is fraught with a high local recurrence rate and potential complications: deep infection; substantial blood loss; large-bone and soft-tissue defects; bladder, bowel, and sexual dysfunction; spinopelvic nonunion; and gait disturbance. The aim of this study was to analyze the complications and morbidity of sacrectomy and the modifications meant to reduce the morbidity. Methods This is a retrospective study of the patients who underwent sacrectomy between February 1997 and September 2008 in the Department of Surgical Oncology, Government Royapettah Hospital, Kilpauk Medical College, in Chennai, Tamilnadu, India. Sacrectomy was performed using 1 of the following approaches: posterior approach, abdominolateral approach, or abdominosacral approach, either as sequential or staged operations. The morbidity rate after the sequential and staged abdominosacral approaches was analyzed. Functional assessment was made based on the Enneking functional scoring system. The results were analyzed and survival analysis was done using the Kaplan-Meier method (with SPSS software). Results Nineteen patients underwent sacrectomy, of which 12 operations were partial, 3 were subtotal, and 4 were total sacrectomy. Histological diagnosis included giant cell tumor, chordoma, chondroblastoma, adenocarcinoma of rectum, and retroperitoneal sarcoma. The giant cell tumor was the most common tumor in this series, followed by chordoma. The patients' mean age at diagnosis was 32 years. There were 10 male and 9 female patients. Fortyseven percent of patients had bowel and bladder disturbances postoperatively, and 57.89% of patients had wound complications. The median follow-up duration was 24 months (range 2-140 months). The 5-year overall survival rate was 70.4%, and the 5-year disease-free survival rate was 65% (based on the Kaplan

  8. [Infection and urinary lithiasis].

    PubMed

    Bruyere, F; Traxer, O; Saussine, C; Lechevallier, E

    2008-12-01

    Urinary infection is a risk factor for lithiasis. Urinary tract infection is a factor of gravity of urinary stone. The stone can exist before the infection which colonizes the stone, infected stone. The infection can be the cause of the stone, infectious stone (struvite stone). Infectious stones can be secondary to a non urinary infectious agent, oxalobacter formigenes (OF) and nanobacteria. The first-line treatment of struvite stone is percutaneous surgery. Perioperative antibiotics, renal urines and stone cultures are obligatory. PMID:19033073

  9. Tecovirimat for smallpox infections.

    PubMed

    Bolken, T C; Hruby, D E

    2010-02-01

    SIGA Technologies, Inc. is a small biotech company committed to developing novel products for the prevention and treatment of serious viral diseases, with an emphasis on products to combat outbreaks that could result from bioterrorism. With government support, SIGA has developed the necessary infrastructure to successfully advance new antiviral drugs from the discovery stage through to licensing. Currently, there is a need to develop safe and effective inhibitors for poxvirus-induced diseases such as smallpox caused by variola, which is a potential biological warfare agent. Likewise emerging zoonotic infections due to cowpox virus and monkeypox virus require the development of effective countermeasures. Tecovirimat, also known as ST-246, has shown efficacy in all small animal and nonhuman primate prophylaxis and therapeutic efficacy models of poxvirus-induced disease tested to date. Phase I clinical trials and new drug application-enabling toxicology studies have been completed with tecovirimat. A phase II clinical study is being run and SIGA has initiated commercial scale-up manufacturing and preparation for the pivotal safety and efficacy studies. SIGA is committed to getting approval for tecovirimat and supplying it to the Strategic National Stockpile, the Department of Defense and global health authorities. PMID:20393639

  10. Histopathology and cellular response in Enteromyxum leei (Myxozoa) infections of Diplodus puntazzo (Teleostei).

    PubMed

    Alvarez-Pellitero, Pilar; Palenzuela, Oswaldo; Sitjá-Bobadilla, Ariadna

    2008-06-01

    Enteromyxum leei is an intestinal parasite responsible for serious outbreaks in Mediterranean sharpsnout sea bream Diplodus puntazzo. E. leei infection was experimentally transmitted to healthy D. puntazzo (R) by cohabitation with infected donor fish. Haematological changes and histopathological damage were evaluated in relation to the course of infection. The prevalence of infection in R fish was 100% from day 10 post-exposure (p.e.) onwards, and the infection intensity and histopathological damage increased progressively. Different developmental stages were found in the infected intestines, including proliferative (stages 1-3) and sporogonic (stages 4 and 5) stages. Intestinal damage consisted of vacuolation, necrosis, detachment and sloughing of epithelium, and was correlated with the progression of the infection and with the development of the parasite. Sporogonic stages appeared from day 20 p.e. onwards. Initially, D. puntazzo seems to counteract the infection through the increase in leucocyte numbers, respiratory burst activity, haematopoietic activity and MMC. Two types of eosinophilic granular cells (EGC1 and EGC2) were detected in the intestinal epithelium and lamina propria. EGC1 numbers decreased with the progression of infection, whereas an increase in EGC2 occurred, mainly in the lamina propria. The involvement of the cellular immunity in the response of D. puntazzo to E. leei was demonstrated. The depletion of this response at a certain point of the infection could contribute to the high virulence of this myxozoan in this fish species. PMID:18373973

  11. A clinical staging system and treatment guidelines for maxillary osteoradionecrosis in irradiated nasopharyngeal carcinoma patients

    SciTech Connect

    Cheng, S.-J.; Lee, J.-J.; Ting, L.-L.; Tseng, I.-Y.; Chang, H.-H.; Chen, H.-M.; Kuo, Y.-S.; Hahn, L.-J.; Kok, S.-H. . E-mail: kok@ha.mc.ntu.edu.tw

    2006-01-01

    Purpose: To develop a clinical staging system for maxillary osteoradionecrosis (ORN) in irradiated nasopharyngeal carcinoma (NPC) patients. Methods and Materials: The data of maxillary ORN cases among 1,758 irradiated NPC patients were analyzed. A staging system based on the degrees of bone exposure (E), infection (I), and bleeding (B) was developed. Correlations between various clinical parameters and stages of maxillary ORN and relationships between treatment modalities and outcomes at each stage were evaluated. Cumulative success of treatment and risk factors that affect treatment outcomes were analyzed. Results: The incidence of maxillary ORN was 2.7% (48/1,758). TNM stage of NPC (p < 0.001), radiation dose (p = 0.029), and tooth extraction (p < 0.001) appeared to have significant influences on disease severity. Success rates between conservative therapy and surgical treatment were not significantly different for Stage I ORN but differed significantly for Stage II (p = 0.013) and Stage III (p = 0.008) lesions. Grade 3 infection and bleeding significantly jeopardized treatment success (p = 0.043 and 0.015, respectively). The risk ratios of treatment failure for Grade 3 infection and bleeding were 2.523 (p = 0.034) and 3.141 (p = 0.027), respectively. Conclusions: More serious maxillary ORN tended to occur in cases with more advanced NPC, higher radiation dose, and history of tooth extraction. Surgical treatment was usually required in Stage II and III ORN. The grades of infection and bleeding are important factors in guidance of treatment and prediction of outcomes.

  12. Bloodstream infections in HIV-infected patients.

    PubMed

    Taramasso, Lucia; Tatarelli, Paola; Di Biagio, Antonio

    2016-04-01

    In the combined antiretroviral therapy era, HIV-infected patients remain a vulnerable population for the onset of bloodstream infections (BSI). Worldwide, nontyphoid salmonellae, Streptococcus pneumoniae, Escherichia coli, Staphylococcus aureus and coagulase negative staphylococci are the most important pathogens. Intravenous catheter associated infection, skin-soft tissue infection and endocarditis are associated with Gram-positive bacteremia. Among the Gram-negative, nontyphoidal Salmonella have been previously correlated to sepsis. Other causes of BSI in HIV-infected patients are mycobacteria and fungi. Mycobacteria constitute a major cause of BSI in limited resource countries. Fungal BSI are not frequent and among them Cryptococcus neoformans is the most common life-threatening infection. The degree of immunosuppression remains the key prognostic factor leading to the development of BSI. PMID:26950194

  13. Drama for Classroom and Stage.

    ERIC Educational Resources Information Center

    Johnson, Albert and Bertha

    This book with a three-part format contains information which the would-be thespian needs to know for maximum enjoyment and success in stage activities. The first part, "Heritage," traces the history and development of the theater from primitive ritual through the drama of classical Greece and Rome, the Renaissance, and modern Europe and America,…

  14. Stage 2--Information Seeking Strategies

    ERIC Educational Resources Information Center

    Elsenberg, Michael B.

    2005-01-01

    A brief overview of one Big6 stage by Mike Eisenberg, followed by articles by two exemplary Big6 teachers, Barbara Jansen and Rob Darrow, offering practical uses of the Big6 in elementary and secondary situations is presented. The two-part nature of information seeking strategies that includes brainstorming and choosing is emphasized.

  15. The Beginning Stages of Reading.

    ERIC Educational Resources Information Center

    Wilkie, Fiona, Comp.

    Noting that in the beginning stages of reading it is helpful for children to be surrounded by the written word and to be read to by adults, this article offers brief encapsulations of and responses to five articles about beginning reading and reading readiness. The five articles are as follows: (1) "Three-Year-Olds in Their Reading Corner" by…

  16. Ares I Stage Separation Test

    NASA Technical Reports Server (NTRS)

    2007-01-01

    Under the goals of the Vision for Space Exploration, Ares I is a chief component of the cost-effective space transportation infrastructure being developed by NASA's Constellation Program. This transportation system will safely and reliably carry human explorers back to the moon, and then onward to Mars and other destinations in the solar system. The Ares I effort includes multiple project element teams at NASA centers and contract organizations around the nation, and is managed by the Exploration Launch Projects Office at NASA's Marshall Space Flight Center (MFSC). ATK Launch Systems near Brigham City, Utah, is the prime contractor for the first stage booster. ATK's subcontractor, United Space Alliance of Houston, is designing, developing and testing the parachutes at its facilities at NASA's Kennedy Space Center in Florida. NASA's Johnson Space Center in Houston hosts the Constellation Program and Orion Crew Capsule Project Office and provides test instrumentation and support personnel. Together, these teams are developing vehicle hardware, evolving proven technologies, and testing components and systems. Their work builds on powerful, reliable space shuttle propulsion elements and nearly a half-century of NASA space flight experience and technological advances. Ares I is an inline, two-stage rocket configuration topped by the Crew Exploration Vehicle, its service module, and a launch abort system. In this HD video image, an Ares I x-test involves the upper stage separating from the first stage. This particular test was conducted at the NASA Langley Research Center in July 2007. (Highest resolution available)

  17. Multi-stage flash degaser

    DOEpatents

    Rapier, P.M.

    1980-06-26

    A multi-stage flash degaser is incorporated in an energy conversion system having a direct-contact, binary-fluid heat exchanger to remove essentially all of the noncondensable gases from geothermal brine ahead of the direct-contact binary-fluid heat exchanger in order that the heat exchanger and a turbine and condenser of the system can operate at optimal efficiency.

  18. All the World's a Stage

    ERIC Educational Resources Information Center

    Stanistreet, Paul

    2011-01-01

    Open Stages is Britain's biggest amateur theatre project, a hugely ambitious scheme to bring the professional and amateur theatre worlds together. It is a learning project but, as the Royal Shakespeare Company's Ian Wainwright tells this author, it is not only the amateurs who are learning. Wainwright states that the amateur and professional…

  19. Stage I: Development of VOICE.

    ERIC Educational Resources Information Center

    Echternacht, Gary J.; And Others

    The initial stages of test development of the Vocational and Occupational Interest Choice Examination (VOICE), developed for Air Force recruiters, are described. Reviewed are a number of relevant occupational interest inventories from which a pool of 400 items was drawn corresponding to eight career fields: general accounting, administration,…

  20. Disseminated Mycobacterium abscessus Infection Following Septic Arthritis

    PubMed Central

    Fukui, Shoichi; Sekiya, Noritaka; Takizawa, Yasunobu; Morioka, Hiroshi; Kato, Hirofumi; Aono, Akio; Chikamatsu, Kinuyo; Mitarai, Satoshi; Kobayashi, Satomi; Kamei, Satoshi; Setoguchi, Keigo

    2015-01-01

    Abstract Mycobacterium abscessus is a rapidly growing mycobacterium found mainly in patients with respiratory or cutaneous infections, but it rarely causes disseminated infections. Little is known about the clinical characteristics, treatment, and prognosis of disseminated M abscessus infection. A 75-year-old Japanese woman who had been treated for 17 years with a corticosteroid for antisynthetase syndrome with antithreonyl-tRNA synthetase antibody developed swelling of her right elbow. X-ray of her right elbow joint showed osteolysis, and magnetic resonance imaging revealed fluid in her right elbow joint. M abscessus grew in joint fluid and blood cultures. She was diagnosed with a disseminated M abscessus infection following septic arthritis. Antimicrobial treatment by clarithromycin, amikacin, and imipenem/cilastatin combined with surgical debridement was administered. Although blood and joint fluid cultures became negative 1 week later, the patient died at 6 weeks from starting antimicrobial treatment. We reviewed 34 cases of disseminated M abscessus infections from the literature. Most of the patients had immunosuppressive backgrounds such as transplantation, use of immunosuppressive agents, hematological malignancy, and end stage renal disease. The duration from onset of symptoms to diagnosis was over 3 months in half of the cases. All fatal cases had positive blood cultures or use of immunosuppressive agents. Clinicians should bear in mind that mycobacterial infections including M abscessus are one of the differential diagnoses in patients with subacute arthritis and soft tissue infections. PMID:26020393