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Sample records for blood stage antigens

  1. Characterization of the Duffy-Binding-Like Domain of Plasmodium falciparum Blood-Stage Antigen 332

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    Sandra Nilsson

    2011-01-01

    Full Text Available Studies on Pf332, a major Plasmodium falciparum blood-stage antigen, have largely been hampered by the cross-reactive nature of antibodies generated against the molecule due to its high content of repeats, which are present in other malaria antigens. We previously reported the identification of a conserved domain in Pf332 with a high degree of similarity to the Duffy-binding-like (DBL domains of the erythrocyte-binding-like (EBL family. We here describe that antibodies towards Pf332-DBL are induced after repeated exposure to P. falciparum and that they are acquired early in life in areas of intense malaria transmission. Furthermore, a homology model of Pf332-DBL was found to be similar to the structure of the EBL-DBLs. Despite their similarities, antibodies towards Pf332-DBL did not display any cross-reactivity with EBL-proteins as demonstrated by immunofluorescence microscopy, Western blotting, and peptide microarray. Thus the DBL domain is an attractive region to use in further studies on the giant Pf332 molecule.

  2. Discovery of GAMA, a Plasmodium falciparum merozoite micronemal protein, as a novel blood-stage vaccine candidate antigen.

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    Arumugam, Thangavelu U; Takeo, Satoru; Yamasaki, Tsutomu; Thonkukiatkul, Amporn; Miura, Kazutoyo; Otsuki, Hitoshi; Zhou, Hong; Long, Carole A; Sattabongkot, Jetsumon; Thompson, Jennifer; Wilson, Danny W; Beeson, James G; Healer, Julie; Crabb, Brendan S; Cowman, Alan F; Torii, Motomi; Tsuboi, Takafumi

    2011-11-01

    One of the solutions for reducing the global mortality and morbidity due to malaria is multivalent vaccines comprising antigens of several life cycle stages of the malarial parasite. Hence, there is a need for supplementing the current set of malaria vaccine candidate antigens. Here, we aimed to characterize glycosylphosphatidylinositol (GPI)-anchored micronemal antigen (GAMA) encoded by the PF08_0008 gene in Plasmodium falciparum. Antibodies were raised against recombinant GAMA synthesized by using a wheat germ cell-free system. Immunoelectron microscopy demonstrated for the first time that GAMA is a microneme protein of the merozoite. Erythrocyte binding assays revealed that GAMA possesses an erythrocyte binding epitope in the C-terminal region and it binds a nonsialylated protein receptor on human erythrocytes. Growth inhibition assays revealed that anti-GAMA antibodies can inhibit P. falciparum invasion in a dose-dependent manner and GAMA plays a role in the sialic acid (SA)-independent invasion pathway. Anti-GAMA antibodies in combination with anti-erythrocyte binding antigen 175 exhibited a significantly higher level of invasion inhibition, supporting the rationale that targeting of both SA-dependent and SA-independent ligands/pathways is better than targeting either of them alone. Human sera collected from areas of malaria endemicity in Mali and Thailand recognized GAMA. Since GAMA in P. falciparum is refractory to gene knockout attempts, it is essential to parasite invasion. Overall, our study indicates that GAMA is a novel blood-stage vaccine candidate antigen.

  3. A Plasmodium vivax plasmid DNA- and adenovirus-vectored malaria vaccine encoding blood stage antigens AMA1 and MSP142 in a prime/boost heterologous immunization regimen partially protects Aotus monkeys against blood stage challenge.

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    Obaldia, Nicanor; Stockelman, Michael G; Otero, William; Cockrill, Jennifer A; Ganeshan, Harini; Abot, Esteban N; Zhang, Jianfeng; Limbach, Keith; Charoenvit, Yupin; Doolan, Denise L; Tang, De-Chu C; Richie, Thomas L

    2017-02-08

    Malaria is caused by parasites of the genus Plasmodium that are transmitted to humans by the bites of Anopheles mosquitoes. After the elimination of P. falciparum it is predicted that Plasmodium vivax will remain an important cause of morbidity and mortality outside of Africa, stressing the importance of developing a vaccine against malaria. In this study we assess the immunogenicity and protective efficacy of two P. vivax antigens, AMA1 and MSP142 in a recombinant DNA plasmid prime/adenoviral vector (Ad) boost regimen in Aotus monkeys. Groups of 4 to 5 monkeys were immunized with DNA alone, Ad alone, prime/boost regimens of each antigen, prime/boost with both antigens, and empty vector controls, and then subjected to blood stage challenge. The heterologous immunization regimen with the antigen pair was more protective than either antigen alone or both antigens delivered with a single vaccine platform, based on their ability to induced the longest pre-patent period and time to peak parasitemia; the lowest peak and mean parasitemia; the smallest area under the parasitemia curve and the highest self-cured rate. Overall, pre-challenge MSP1 antibody titers strongly correlated with decreased parasite burden. Nevertheless, a significant proportion of immunized animals developed anemia. In conclusion, P. vivax plasmid DNA/Ad5 vaccine encoding blood stage parasite antigens AMA1 and MSP142 in a heterologous prime/boost immunization regimen, provided significant protection against blood-stage challenge in Aotus monkeys, indicating the suitability of these antigens and regimen for further development.

  4. Distinct patterns of blood-stage parasite antigens detected by plasma IgG subclasses from individuals with different level of exposure to Plasmodium falciparum infections

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    Olesen, Cathrine Holm; Brahimi, Karima; Vandahl, Brian;

    2010-01-01

    ABSTRACT: BACKGROUND: In endemic regions naturally acquired immunity against Plasmodium falciparum develops as a function of age and exposure to parasite infections and is known to be mediated by IgG. The targets of protective antibodies remain to be fully defined. Several immunoepidemiological...... then gradually develop into protective response dominated by cytophilic IgG1 and IgG3 antibodies. METHODS: Naturally occurring IgG antibodies against P. falciparum blood-stage antigens were analysed from plasma samples collected from four groups of individuals differing in age and level of exposure to P....... falciparum infections. Western Blot profiling of blood-stage parasite antigens displaying reactivity with individual plasma samples in terms of their subclass specificities was conducted. Parasite antigens detected by IgG were grouped based on their apparent molecular sizes resolved by SDS-PAGE as high...

  5. Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya.

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    Bernhards R Ogutu

    Full Text Available The antigen, falciparum malaria protein 1 (FMP1, represents the 42-kDa C-terminal fragment of merozoite surface protein-1 (MSP-1 of the 3D7 clone of P. falciparum. Formulated with AS02 (a proprietary Adjuvant System, it constitutes the FMP1/AS02 candidate malaria vaccine. We evaluated this vaccine's safety, immunogenicity, and efficacy in African children.A randomised, double-blind, Phase IIb, comparator-controlled trial.The trial was conducted in 13 field stations of one mile radii within Kombewa Division, Nyanza Province, Western Kenya, an area of holoendemic transmission of P. falciparum. We enrolled 400 children aged 12-47 months in general good health.Children were randomised in a 1ratio1 fashion to receive either FMP1/AS02 (50 microg or Rabipur(R rabies vaccine. Vaccinations were administered on a 0, 1, and 2 month schedule. The primary study endpoint was time to first clinical episode of P. falciparum malaria (temperature >/=37.5 degrees C with asexual parasitaemia of >/=50,000 parasites/microL of blood occurring between 14 days and six months after a third dose. Case detection was both active and passive. Safety and immunogenicity were evaluated for eight months after first immunisations; vaccine efficacy (VE was measured over a six-month period following third vaccinations.374 of 400 children received all three doses and completed six months of follow-up. FMP1/AS02 had a good safety profile and was well-tolerated but more reactogenic than the comparator. Geometric mean anti-MSP-1(42 antibody concentrations increased from1.3 microg/mL to 27.3 microg/mL in the FMP1/AS02 recipients, but were unchanged in controls. 97 children in the FMP1/AS02 group and 98 controls had a primary endpoint episode. Overall VE was 5.1% (95% CI: -26% to +28%; p-value = 0.7.FMP1/AS02 is not a promising candidate for further development as a monovalent malaria vaccine. Future MSP-1(42 vaccine development should focus on other formulations and antigen constructs

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

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    Sumi Biswas

    Full Text Available 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

  7. Combining viral vectored and protein-in-adjuvant vaccines against the blood-stage malaria antigen AMA1: report on a phase 1a clinical trial.

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    Hodgson, Susanne H; Choudhary, Prateek; Elias, Sean C; Milne, Kathryn H; Rampling, Thomas W; Biswas, Sumi; Poulton, Ian D; Miura, Kazutoyo; Douglas, Alexander D; Alanine, Daniel Gw; Illingworth, Joseph J; de Cassan, Simone C; Zhu, Daming; Nicosia, Alfredo; Long, Carole A; Moyle, Sarah; Berrie, Eleanor; Lawrie, Alison M; Wu, Yimin; Ellis, Ruth D; Hill, Adrian V S; Draper, Simon J

    2014-12-01

    The development of effective vaccines against difficult disease targets will require the identification of new subunit vaccination strategies that can induce and maintain effective immune responses in humans. Here we report on a phase 1a clinical trial using the AMA1 antigen from the blood-stage Plasmodium falciparum malaria parasite delivered either as recombinant protein formulated with Alhydrogel adjuvant with and without CPG 7909, or using recombinant vectored vaccines--chimpanzee adenovirus ChAd63 and the orthopoxvirus MVA. A variety of promising "mixed-modality" regimens were tested. All volunteers were primed with ChAd63, and then subsequently boosted with MVA and/or protein-in-adjuvant using either an 8- or 16-week prime-boost interval. We report on the safety of these regimens, as well as the T cell, B cell, and serum antibody responses. Notably, IgG antibody responses primed by ChAd63 were comparably boosted by AMA1 protein vaccine, irrespective of whether CPG 7909 was included in the Alhydrogel adjuvant. The ability to improve the potency of a relatively weak aluminium-based adjuvant in humans, by previously priming with an adenoviral vaccine vector encoding the same antigen, thus offers a novel vaccination strategy for difficult or neglected disease targets when access to more potent adjuvants is not possible.

  8. Human T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT in acute malaria

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    Woodberry Tonia

    2009-06-01

    Full Text Available Abstract Background The Plasmodium purine salvage enzyme, hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT can protect mice against Plasmodium yoelii pRBC challenge in a T cell-dependent manner and has, therefore, been proposed as a novel vaccine candidate. It is not known whether natural exposure to Plasmodium falciparum stimulates HGXPRT T cell reactivity in humans. Methods PBMC and plasma collected from malaria-exposed Indonesians during infection and 7–28 days after anti-malarial therapy, were assessed for HGXPRT recognition using CFSE proliferation, IFNγ ELISPOT assay and ELISA. Results HGXPRT-specific T cell proliferation was found in 44% of patients during acute infection; in 80% of responders both CD4+ and CD8+ T cell subsets proliferated. Antigen-specific T cell proliferation was largely lost within 28 days of parasite clearance. HGXPRT-specific IFN-γ production was more frequent 28 days after treatment than during acute infection. HGXPRT-specific plasma IgG was undetectable even in individuals exposed to malaria for at least two years. Conclusion The prevalence of acute proliferative and convalescent IFNγ responses to HGXPRT demonstrates cellular immunogenicity in humans. Further studies to determine minimal HGXPRT epitopes, the specificity of responses for Plasmodia and associations with protection are required. Frequent and robust T cell proliferation, high sequence conservation among Plasmodium species and absent IgG responses distinguish HGXPRT from other malaria antigens.

  9. Western blot diagnosis of vivax malaria with multiple stage-specific antigens of the parasite

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    Son, Eui-Sun; Kim, Tong Soo; Nam, Ho-Woo

    2001-01-01

    Western blot analysis was performed to diagnose vivax malaria using stage-specific recombinant antigens. Genomic DNA from the whole blood of a malaria patient was used as templates to amplify the coding regions for the antigenic domains of circumsporozoite protein (CSP-1), merozoite surface protein (MSP-1), apical merozoite antigen (AMA-1), serine repeat antigen (SERA), and exported antigen (EXP-1) of Plasmodium vivax. Each amplified DNA fragment was inserted into a pGEX-4T plasmid to induce ...

  10. Antibody responses to a panel of Plasmodium falciparum malaria blood-stage antigens in relation to clinical disease outcome in Sudan

    DEFF Research Database (Denmark)

    Iriemenam, Nnaemeka C; Khirelsied, Atif H; Nasr, Amre;

    2009-01-01

    Despite many intervention programmes aimed at curtailing the scourge, malaria remains a formidable problem of human health. Immunity to asexual blood-stage of Plasmodium falciparum malaria is thought to be associated with protective antibodies of certain immunoglobulin classes and subclasses. We ...

  11. Recombinant viral-vectored vaccines expressing Plasmodium chabaudi AS apical membrane antigen 1: mechanisms of vaccine-induced blood-stage protection.

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    Biswas, Sumi; Spencer, Alexandra J; Forbes, Emily K; Gilbert, Sarah C; Holder, Anthony A; Hill, Adrian V S; Draper, Simon J

    2012-05-15

    Apical membrane Ag 1 (AMA1) is one of the leading candidate Ags for inclusion in a subunit vaccine against blood-stage malaria. However, the efficacy of Ab-inducing recombinant AMA1 protein vaccines in phase IIa/b clinical trials remains disappointing. In this article, we describe the development of recombinant human adenovirus serotype 5 and modified vaccinia virus Ankara vectors encoding AMA1 from the Plasmodium chabaudi chabaudi strain AS. These vectors, when used in a heterologous prime-boost regimen in BALB/c mice, are capable of inducing strong transgene-specific humoral and cellular immune responses. We show that this vaccination regimen is protective against a nonlethal P. chabaudi chabaudi strain AS blood-stage challenge, resulting in reduced peak parasitemias. The role of vaccine-induced, AMA1-specific Abs and T cells in mediating the antiparasite effect was investigated by in vivo depletion of CD4(+) T cells and adoptive-transfer studies into naive and immunodeficient mice. Depletion of CD4(+) T cells led to a loss of vaccine-induced protection. Adoptive-transfer studies confirmed that efficacy is mediated by both CD4(+) T cells and Abs functioning in the context of an intact immune system. Unlike previous studies, these results confirm that Ag-specific CD4(+) T cells, induced by a clinically relevant vaccine-delivery platform, can make a significant contribution to vaccine blood-stage efficacy in the P. chabaudi model. Given that cell-mediated immunity may also contribute to parasite control in human malaria, these data support the clinical development of viral-vectored vaccines that induce both T cell and Abs against Plasmodium falciparum blood-stage malaria Ags like AMA1.

  12. [Presence of Australia antigen in blood donors].

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    Gota, F

    1980-01-01

    The differential diagnosis of type A and B viral hepatitis is discussed and guidelines for the prevention of post-transfusional hospital hepatitis are proposed. Methods for the immunological demonstration of HBs antigen are illustrated, together with the respective positivity percentages in blood donors.

  13. Biofunctionalizing nanofibers with carbohydrate blood group antigens.

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    Barr, Katie; Kannan, Bhuvaneswari; Korchagina, Elena; Popova, Inna; Ryzhov, Ivan; Henry, Stephen; Bovin, Nicolai

    2016-11-01

    A rapid and simple method of biofunctionalising nylon, cellulose acetate, and polyvinyl butyral electrospun nanofibers with blood group glycans was achieved by preparing function-spacer-lipid constructs and simply contacting them to fibers with a piezo inkjet printer. A series of water dispersible amphipathic glycan-spacer constructs were synthesized representing a range ABO and related blood group antigens. After immediate contact of the amphipathic glycan-spacer constructs with nanofiber surfaces they self-assembled and were detectable by enzyme immunoassays with high sensitivity and specificity.

  14. The influence of Maloprim chemoprophylaxis on cellular and humoral immune responses to Plasmodium falciparum asexual blood stage antigens in schoolchildren living in a malaria endemic area of Mozambique

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    Hogh, B; Thompson, R; Lobo, V;

    1994-01-01

    antigens. The study was carried out in the Escola Primária de Lingamo, a primary school in a suburban area of Maputo, Mozambique. A cohort of 392 schoolchildren (aged 7-12 years) was randomly allocated to two equal groups, one receiving chemoprophylaxis with dapsone/pyrimethamine (Maloprim), the other...... assays in vitro. Anti-GLURP and anti-Pf155/RESA antibodies were detected by enzyme-linked immunosorbent assay (ELISA) and erythrocyte membrane immunofluorescence (EMIF), and total anti-P. falciparum antibodies were measured by indirect fluorescent antibody test (IFAT). Immunological reactivities were...

  15. The stage-specific in vitro efficacy of a malaria antigen cocktail provides valuable insights into the development of effective multi-stage vaccines.

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    Spiegel, Holger; Boes, Alexander; Kastilan, Robin; Kapelski, Stephanie; Edgue, Güven; Beiss, Veronique; Chubodova, Ivana; Scheuermayer, Matthias; Pradel, Gabriele; Schillberg, Stefan; Reimann, Andreas; Fischer, Rainer

    2015-10-01

    Multicomponent vaccines targeting different stages of Plasmodium falciparum represent a promising, holistic concept towards better malaria vaccines. Additionally, an effective vaccine candidate should demonstrate cross-strain specificity because many antigens are polymorphic, which can reduce vaccine efficacy. A cocktail of recombinant fusion proteins (VAMAX-Mix) featuring three diversity-covering variants of the blood-stage antigen PfAMA1, each combined with the conserved sexual-stage antigen Pfs25 and one of the pre-erythrocytic-stage antigens PfCSP_TSR or PfCelTOS, or the additional blood-stage antigen PfMSP1_19, was produced in Pichia pastoris and used to immunize rabbits. The immune sera and purified IgG were used to perform various assays determining antigen specific titers and in vitro efficacy against different parasite stages and strains. In functional in vitro assays we observed robust inhibition of blood-stage (up to 90%), and sexual-stage parasites (up to 100%) and biased inhibition of pre-erythrocytic parasites (0-40%). Cross-strain blood-stage efficacy was observed in erythrocyte invasion assays using four different P. falciparum strains. The quantification of antigen-specific IgGs allowed the determination of specific IC50 values. The significant difference in antigen-specific IC50 requirements, the direct correlation between antigen-specific IgG and the relative quantitative representation of antigens within the cocktail, provide valuable implementations for future multi-stage, multi-component vaccine designs.

  16. Tissue distribution of histo-blood group antigens

    DEFF Research Database (Denmark)

    Ravn, V; Dabelsteen, Erik

    2000-01-01

    carrier carbohydrate chains. Histo-blood group antigens are found in most epithelial tissues. Meanwhile, several factors influence the type, the amount, and the histological distribution of histoblood group antigens, i.e. the ABO, Lewis, and saliva-secretor type of the individual, and the cell- and tissue......The introduction of immunohistochemical techniques and monoclonal antibodies to specific carbohydrate epitopes has made it possible to study in detail the tissue distribution of histo-blood group antigens and related carbohydrate structures. The present paper summarizes the available data...... concerning the histological distribution of histo-blood group antigens and their precursor structures in normal human tissues. Studies performed have concentrated on carbohydrate antigens related to the ABO, Lewis, and TTn blood group systems, i.e. histo-blood group antigens carried by type 1, 2, and 3 chain...

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

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    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

  18. Western blot diagnosis of vivax malaria with multiple stage-specific antigens of the parasite.

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    Son, E S; Kim, T S; Nam, H W

    2001-06-01

    Western blot analysis was performed to diagnose vivax malaria using stage-specific recombinant antigens. Genomic DNA from the whole blood of a malaria patient was used as templates to amplify the coding regions for the antigenic domains of circumsporozoite protein (CSP-1), merozoite surface protein (MSP-1), apical merozoite antigen (AMA-1), serine repeat antigen (SERA), and exported antigen (EXP-1) of Plasmodium vivax. Each amplified DNA fragment was inserted into a pGEX-4T plasmid to induce the expression of GST fusion protein in Escherichia coli by IPTG. The bacterial cell extracts were separated on 10% SDS-PAGE followed by western blot analysis with patient sera which was confirmed by blood smear examination. When applied with patient sera, 147 (91.9%) out of 160 vivax malaria, 12 (92.3%) out of 13 falciparum malaria, and all 9 vivax/falciparum mixed malaria reacted with at least one antigen, while no reactions occurred with 20 normal uninfected sera. In the case of vivax malaria, CSP-1 reacted with 128 (80.0%) sera, MSP-1 with 102 (63.8%), AMA-1 with 128 (80.0%), SERA with 115 (71.9%), and EXP-1 with 89 (55.6%), respectively. We obtained higher detection rates when using 5 antigens (91.9%) rather than using each antigen solely (55.6-80%), a combination of 2 (76.3-87.5%), 3 (85.6-90.6%), or 4 antigens (89.4-91.3%). This method can be applied to serological diagnosis, mass screening in endemic regions, or safety test in transfusion of prevalent vivax malaria.

  19. Prostate-specific antigen (PSA) blood test

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    Prostate-specific antigen; Prostate cancer screening test; PSA ... special steps are needed to prepare for this test. ... Reasons for a PSA test: This test may be done to screen for prostate cancer. It is also used to follow people after prostate cancer ...

  20. [Blood groups - minuses and pluses. Do the blood group antigens protect us from infectious diseases?].

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    Czerwiński, Marcin

    2015-06-25

    Human blood can be divided into groups, which is a method of blood classification based on the presence or absence of inherited erythrocyte surface antigens that can elicit immune response. According to the International Society of Blood Transfusion, there are 341 blood group antigens collected in 35 blood group systems. These antigens can be proteins, glycoproteins or glycosphingolipids, and function as transmembrane transporters, ion channels, adhesion molecules or receptors for other proteins. The majority of blood group antigens is present also on another types of cells. Due to their localization on the surface of cells, blood group antigens can act as receptors for various pathogens or their toxins, such as protozoa (malaria parasites), bacteria (Helicobacter pylori, Vibrio cholerae and Shigella dysenteriae) and viruses (Noroviruses, Parvoviruses, HIV). If the presence of group antigen (or its variant which arised due to mutation) is beneficial for the host (e.g. because pathogens are not able to bind to the cells), the blood group may become a selection trait, leading to its dissemination in the population exposed to that pathogen. There are thirteen blood group systems that can be related to pathogen resistance, and it seems that the particular influence was elicit by malaria parasites. It is generally thought that the high incidence of blood groups such as O in the Amazon region, Fy(a-b-) in Africa and Ge(-) in Papua-New Guinea is the result of selective pressure from malaria parasite. This review summarizes the data about relationship between blood groups and resistance to pathogens.

  1. Antigen-driven focal inflammatory death of malaria liver stages

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    Ganchimeg eBayarsaikhan

    2015-02-01

    Full Text Available Multiple immunizations using live irradiated sporozoites, the infectious plasmodial stage delivered into the host skin during a mosquito bite, can elicit sterile immunity to malaria. CD8+ T cells seem to play an essential role in this protective immunity, since their depletion consistently abolishes sterilizing protection in several experimental models. So far, only a few parasite antigens are known to induce CD8+ T cell-dependent protection, but none of them can reach the levels of protection afforded by live attenuated parasites. Systematic attempts to identify novel antigens associated with this efficient cellular protection were so far unsuccessful. In addition, the precise mechanisms involved in the recognition and elimination of parasitized hepatocytes in vivo by CD8+ T cells still remain obscure. Recently, it has been shown that specific effector CD8+ T cells, after recognition of parasitized hepatocytes, recruit specific and non-specific activated CD8+ T cells to the site of infection, resulting in the formation of cellular clusters around and in the further elimination of intracellular parasites. The significance of this finding is discussed in the perspective of a general mechanism of antigen-dependent focalized inflammation and its consequences for the elimination of malaria liver stages.

  2. Prevalence of Rh, Duffy, Kell, Kidd & MNSs blood group antigens in the Indian blood donor population

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    R N Makroo

    2013-01-01

    Interpretation & conclusions: This study found the prevalence of the typed antigens among Indian blood donors to be statistically different to those in the Caucasian, Black and Chinese populations, but more similar to Caucasians than to the other racial groups.

  3. Duffy blood group antigens: structure, serological properties and function

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    Ewa Łukasik

    2016-03-01

    Full Text Available Duffy (Fy blood group antigens are located on seven-transmembrane glycoprotein expressed on erythrocytes and endothelial cells, which acts as atypical chemokine receptor (ACKR1 and malarial receptor. The biological role of the Duffy glycoprotein has not been explained yet. It is suggested that Duffy protein modulate the intensity of the inflammatory response. The Duffy blood group system consists of two major antigens, Fya and Fyb, encoded by two codominant alleles designated FY*A and FY*B which differ by a single nucleotide polymorphism (SNP at position 125G>A of the FY gene that results in Gly42Asp amino acid change in the Fya and Fyb antigens, respectively. The presence of antigen Fya and/or Fyb on the erythrocytes determine three Duffy-positive phenotypes: Fy(a+b-, Fy(a-b+ and Fy(a+b+, identified in Caucasian population. The Duffy-negative phenotype Fy(a-b-, frequent in Africans, but very rare in Caucasians, is defined by the homozygous state of FY*B-33 alleles. The FY*B-33 allele is associated with a SNP -33T>C in the promoter region of the FY gene, which suppresses erythroid expression of this gene without affecting its expression in other tissues. The FY*X allele, found in Caucasians, is correlated with weak expression of Fyb antigen. Fyx antigen differs from the native Fyb by the Arg89Cys and Ala100Thr amino acid substitutions due to SNPs: 265C>T and 298G>A in FY*B allele. The frequency of the FY alleles shows marked geographic disparities, the FY*B-33 allele is predominant in Africans, the FY*B in Caucasians, while the FY*A allele is dominant in Asians and it is the most prevalent allele globally. Tytuł główny Tak

  4. Red-blood-cell alloimmunisation in relation to antigens' exposure and their immunogenicity: a cohort study.

    NARCIS (Netherlands)

    Evers, D.; Middelburg, R.A.; Haas, M. de; Zalpuri, S.; Vooght, K.M. De; Kerkhof, D. van de; Visser, O; Pequeriaux, N.C.V.; Hudig, F.; Schonewille, H.; Zwaginga, J.J.; Bom, J.G. Van Der

    2016-01-01

    BACKGROUND: Matching donor red blood cells based on recipient antigens prevents alloimmunisation. Knowledge about the immunogenicity of red-blood-cell antigens can help optimise risk-adapted matching strategies. We set out to assess the immunogenicity of red-blood-cell antigens. METHODS: In an incid

  5. The distribution of blood group antigens in experimentally produced carcinomas of rat palate

    DEFF Research Database (Denmark)

    Reibel, J; Philipsen, H P; Fisker, A V;

    1986-01-01

    It has been shown previously that rat oral epithelia express antigens cross-reacting with antibodies against human blood group antigen B and its structural precursor, the H antigen (Type 2 chain). In the present study we investigated the expression of these antigens in malignant changes in the rat....... The blood group antigen staining pattern in experimentally produced verrucous carcinomas showed an almost normal blood group antigen expression. This may have diagnostic significance. Localized areas of hyperplastic palatal epithelium with slight dysplasia revealed loss of H antigen and the presence of B...

  6. Expression of blood group antigens A and B in pancreas of vertebrates

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    ELENKA GEORGIEVA

    2012-01-01

    Full Text Available The biological role of blood group antigens (BGA A and B in tissues of different vertebrates is still controversial. There are few investigations on vertebrate pancreas and no obvious explanation of their tissue expression. The aim of the present study is to follow and compare the pancreatic expression of BGA A and B in representatives of five vertebrate classes. The biotin-streptavidin-proxidase labeling system was used for immunohistochemical detection of BGA by monoclonal antibodies to human A and B antigens. The present study reveals specific immunoreactivity in acinar and epithelial cells of pancreatic efferent ducts in species free-living vertebrates. The immunoperoxidase staining shows antigenic heterogeneity in the cellular localization. The number of positive cells and the intensity of expression vary in different species. Endothelial cells are positive only in the pancreas of Emys orbicularis. The lack of BGA A and B in some species suggests that the expression of these antigens is dependent not only on the evolutionary level of the species, but mainly on some genetic control mechanisms. The production of BGA A and B and the variability in their cellular localization probably reflect the stage of cell differentiation and the mechanisms of pancreatic secretor function. The presence of histo BGA in endodermal acinar pancreatic cells confirms the assumption for the high antigenic stability and conservatism of these molecules in vertebrate histogenesis and evolution.

  7. Correlation between 'H' blood group antigen and Plasmodium falciparum invasion.

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    Pathak, Vrushali; Colah, Roshan; Ghosh, Kanjaksha

    2016-06-01

    The ABO blood group system is the most important blood group system in clinical practice. The relationship between Plasmodium falciparum and ABO blood groups has been studied for many years. This study was undertaken to investigate the abilities of different blood group erythrocytes to support in vitro growth of P. falciparum parasites. P. falciparum parasites of four different strains (3D7, 7G8, Dd2 and RKL9) were co-cultured with erythrocytes of blood group 'A', 'B', 'O' (n = 10 for each) and 'O(h)' (Bombay group) (n = 7) for 5 days. Statistically significant differences were observed on the fourth day among the mean percent parasitemias of 'O', non-'O' ('A' and 'B') and 'O(h)' group cultures. The parasitemias of four strains ranged from 12.23 to 14.66, 11.68 to 13.24, 16.89 to 22.3, and 7.37 to 11.27 % in 'A', 'B', 'O' and Bombay group cultures, respectively. As the expression of H antigen decreased from 'O' blood group to 'A' and 'B' and then to Bombay blood group, parasite invasion (percent parasitemia) also decreased significantly (p group erythrocytes were virtually converted to Bombay group-like erythrocytes by the treatment of anti-H lectins extracted from Ulex europaeus seeds. Mean percent parasitemia of lectin-treated cultures on the fourth day was significantly lower (p Bombay group erythrocyte cultures, thus further strengthening the hypothesis.

  8. Pattern of distribution of blood group antigens on human epidermal cells during maturation

    DEFF Research Database (Denmark)

    Dabelsteen, Erik; Buschard, Karsten; Hakomori, Sen-Itiroh

    1984-01-01

    The distribution in human epidermis of A, B, and H blood group antigens and of a precursor carbohydrate chain, N-acetyl-lactosamine, was examined using immunofluorescence staining techniques. The material included tissue from 10 blood group A, 4 blood group B, and 9 blood group O persons. Murine...... on the lower spinous cells whereas H antigen was seen predominantly on upper spinous cells or on the granular cells. Epithelia from blood group A or B persons demonstrated A or B antigens, respectively, but only if the tissue sections were trypsinized before staining. In such cases A or B antigens were found...... monoclonal antibodies were used to identify H antigen (type 2 chain) and N-acetyl-lactosamine. Human antisera were used to identify A and B antigens. In all groups N-acetyl-lactosamine and H antigen were found on the cell membranes of the spinous cell layer. N-acetyl-lactosamine was present mainly...

  9. Responses of synovial fluid and peripheral blood mononuclear cells to bacterial antigens and autologous antigen presenting cells.

    Science.gov (United States)

    Klasen, I S; Melief, M J; Swaak, T J; Severijnen, A J; Hazenberg, M P

    1993-01-01

    The specificity of T cells in the inflamed joints of patients with rheumatoid arthritis (RA) has been the subject of much study. Bacterial antigens are suspect in the aetiology of rheumatic diseases. The responsiveness of the mononuclear cell fraction of peripheral blood and synovial fluid of patients with RA and of patients with rheumatic diseases other than RA to bacterial antigens such as cell wall fragments of the anaerobic intestinal flora, cell wall fragments of Streptococcus pyogenes, intestinal flora derived peptidoglycan polysaccharide complexes, the 65 kilodalton protein of Mycobacterium tuberculosis, and muramyldipeptide was investigated. No significant difference in response was found to all these bacterial antigens in the synovial fluid of patients with RA compared with the responses in patients with other rheumatic diseases. The highest responsiveness in the synovial fluid of the patients with RA was to the streptococcal cell wall fragments and to the 65 kilodalton protein. Higher responses to several bacterial antigens in the synovial fluid of patients with RA were found compared with peripheral blood from the same patient group. The antigen presenting cell population of the synovial fluid in patients with RA and the patients with other rheumatic diseases was found to be stimulatory for autologous peripheral blood T cells even in the absence of antigen. This suggests an important role for the synovial antigen presenting cell in the aetiology of inflammatory joint diseases. PMID:8447692

  10. Can growth inhibition assays (GIA) predict blood-stage malaria vaccine efficacy?

    Science.gov (United States)

    Duncan, Christopher J A; Hill, Adrian V S; Ellis, Ruth D

    2012-06-01

    An effective vaccine against P. falciparum malaria remains a global health priority. Blood-stage vaccines are an important component of this effort, with some indications of recent progress. However only a fraction of potential blood-stage antigens have been tested, highlighting a critical need for efficient down-selection strategies. Functional in vitro assays such as the growth/invasion inhibition assays (GIA) are widely used, but it is unclear whether GIA activity correlates with protection or predicts vaccine efficacy. While preliminary data in controlled human malaria infection (CHMI) studies indicate a possible association between in vitro and in vivo parasite growth rates, there have been conflicting results of immunoepidemiology studies, where associations with exposure rather than protection have been observed. In addition, GIA-interfering antibodies in vaccinated individuals from endemic regions may limit assay sensitivity in heavily malaria-exposed populations. More work is needed to establish the utility of GIA for blood-stage vaccine development.

  11. Hierarchical phosphorylation of apical membrane antigen 1 is required for efficient red blood cell invasion by malaria parasites

    OpenAIRE

    Boris Prinz; Katherine L. Harvey; Louisa Wilcke; Ulrike Ruch; Klemens Engelberg; Laura Biller; Isabelle Lucet; Steffen Erkelenz; Dorothee Heincke; Tobias Spielmann; Christian Doerig; Conrad Kunick; Brendan S Crabb; Gilson, Paul R.; Gilberger, Tim W

    2016-01-01

    Central to the pathogenesis of malaria is the proliferation of Plasmodium falciparum parasites within human erythrocytes. Parasites invade erythrocytes via a coordinated sequence of receptor-ligand interactions between the parasite and host cell. One key ligand, Apical Membrane Antigen 1 (AMA1), is a leading blood-stage vaccine and previous work indicates that phosphorylation of its cytoplasmic domain (CPD) is important to its function during invasion. Here we investigate the significance of ...

  12. Surface antigen-negative hepatitis B virus infection in Dutch blood donors.

    Science.gov (United States)

    Lieshout-Krikke, R W; Molenaar-de Backer, M W A; van Swieten, P; Zaaijer, H L

    2014-01-01

    Hepatitis B virus (HBV) surface antigen (HBsAg) is a reliable marker for HBV infection, but HBsAg-negative forms of HBV infection occur. The introduction of HBV DNA screening of Dutch blood donors, which were not preselected for absence of HBV core antibodies, enabled the characterization of HBsAg-negative HBV infection in healthy persons and a comparison of the HBV genomes involved. The screening of 4.4 million Dutch blood donations identified 23 HBsAg-negative, HBV DNA-positive persons. Serological testing of the index donations, follow-up samples and archived earlier samples was performed to determine the nature of each HBV DNA-only case. Despite low viral loads HBV DNA could be sequenced in 14 out of 23 donors, allowing HBV genotyping and the analysis of mutations in the HBV surface gene. Four types of HBsAg-negative HBV infection were detected: infection in the early stage before occurrence of HBsAg; suppressed infection after vaccination; HBV genotype G infection with decreased HBsAg production; and chronic occult (HBsAg negative) HBV infection. In the donors with occult HBV genotype D infection the HBV surface gene showed multiple "escape" mutations in the HBsAg a-determinant and CTL epitopes, while in an occult genotype A case the surface gene showed no mutations. HBsAg-negative forms of HBV infection in healthy blood donors explain the ongoing transmission of HBV via blood transfusion, if donor screening is limited to HBsAg. The screening of blood donors for HBV DNA and HBV core antibodies seems to cover all stages and variants of HBV infection.

  13. Stem Cell Physics. Laser Manipulation of Blood Types: Laser-Stripping-Away of Red Blood Cell Surface Antigens

    Science.gov (United States)

    Stefan, V. Alexander

    2014-03-01

    A novel mechanism of importance for the transfusion medicine[2] is proposed. The interaction of ultrashort wavelength multilaser beams with the flowing blood thin films can lead to a conversion of blood types A, B, and AB into O type.[3] The stripping away of antigens is done by the scanning-multiple-lasers of a high repetition rate in the blue-purple frequency domain. The guiding-lasers are in the red-green frequency domain. The laser force, (parametric interaction with the antigen eigen-oscillation),[4] upon the antigen protein molecule must exceed its weight. Supported by Nikola Tesla Labs, La Jolla, CA.

  14. Bony metastases from breast cancer - a study of foetal antigen 2 as a blood tumour marker

    Directory of Open Access Journals (Sweden)

    Iles Ray K

    2010-05-01

    Full Text Available Abstract Background Foetal antigen 2 (FA-2, first isolated in the amniotic fluid, was shown to be the circulating form of the aminopropeptide of the alpha 1 chain of procollagen type I. Serum concentrations of FA-2 appeared to be elevated in a number of disorders of bone metabolism. This paper is the first report of its role as a marker of bone metabolism in metastatic breast cancer. Methods Serum FA-2 concentrations were measured by radioimmunoassay in 153 women with different stages of breast cancer and in 34 normal controls. Results Serum FA-2 was significantly elevated in women with bony metastases (p Conclusions FA-2 is a promising blood marker of bone metabolism. Further studies to delineate its role in the diagnosis and management of bony metastases from breast cancer are required.

  15. Cytokeratins and carcinoembryonic antigen in diagnosis, staging and prognosis of colorectal adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Luís C. Fernandes; Su B. Kim; Delcio Matos

    2005-01-01

    AIM: To evaluate the serum levels of cytokeratins and carcinoembryonic antigen (CEA) in diagnosis, staging and prognosis of patients with colorectal adenocarcinoma.METHODS: The sample consisted of 169 patients. One hundred blood donors formed the control group. Radical surgery was performed on 120 patients, with an average follow-up duration of 22.3 mo. Relapses occurred in 23individuals after an average of 18.09 mo. CEA was assayed via the Delfia(R) method with a limit of 5 ng/mL. Cytokeratins were assayed via the LIA-mat(R) TPA-M Prolifigen(R) method with a limit of 72 U/L.RESULTS: In the diagnosis of patients with colorectal adenocarcinoma, CEA showed a sensitivity of 56%, a specificity of 95%, a positive predictive value of 94%, a negative predictive value of 50% and an accuracy of 76.8%.TPA-M had a sensitivity of 70%, a specificity of 96%, a positive predictive value of 97%, a negative predictive value of 66% and an accuracy of 93.6%. The elevation of one of the markers was shown to have a sensitivity of 76.9%, a specificity of 91%, a positive predictive value of 93.5%, a negative predictive value of 70% and an accuracy of 83.6%.There was no variation in the levels of the markers according to the degree of cell differentiation while there was an elevation in their concentrations in accordance with the increase in neoplastic dissemination. There was a statistically significant difference between the patients with stage Ⅳ lesions and those with stages Ⅰ, Ⅱ and Ⅲ tumors.With regard to CEA, the averagelevel was 14.2 ng/mL in patients with stage Ⅰ lesions, 8.5 ng/mL in patients with stage Ⅱ lesions, 8.0 ng/mL in patients with stage Ⅲ lesions and 87.7 ng/mL in patients with stage Ⅳ lesions. In relation to TPA-M, the levels were 153.1 U/L in patients with stage Ⅰtumors, 106.5 U/L in patients with stage Ⅱ tumors, 136.3 U/L in patients with stage Ⅲ tumors and 464.3 U/L in patients with stage Ⅳ tumors. There was a statistical difference in

  16. Novel use of a radiolabelled antibody against stage specific embryonic antigen for the detection of occult abscesses in mammals

    Science.gov (United States)

    Thakur, Madhukar L.

    1990-01-01

    The invention discloses improved reagents containing antibodies against stage specific embryonic antigen-1 antibodies and improved methods for detection of occult abscess and inflammation using the improved reagents.

  17. ABO blood group antigens in oral mucosa. What is new?

    DEFF Research Database (Denmark)

    Dabelsteen, Erik

    2002-01-01

    which represent secondary gene products. They are synthesized in a stepwise fashion from a precursor by the action of different glycosyltransferases. In non-keratinized oral mucosa, a sequential elongation of the carbohydrates is associated with differentiation of epithelial cells, resulting...... in expression of precursors on basal cells and A/B antigens on spinous cells. Reduction or complete deletion of A/B antigen expression in oral carcinomas has been reported, a phenotypic change that is correlated with invasive and metastatic potential of the tumours and with the mortality rates of the patients....... Disappearance of the antigens is ascribed to the absence of A or B transferase gene expression. Several studies have shown that loss of A and B antigen expression is associated with increased cell motility, invasion in matrigel, and tumourigenecity in syngenic animals. In vivo studies of human oral wound...

  18. A whole parasite vaccine to control the blood stages of Plasmodium: the case for lateral thinking.

    Science.gov (United States)

    Good, Michael F

    2011-08-01

    Now, 27 years following the cloning of malaria antigens with the promise of the rapid development of a malaria vaccine, we face significant obstacles that are belatedly being addressed. Poor immunogenicity of subunit vaccine antigens and significant antigenic diversity of target epitopes represent major hurdles for which there are no clear strategies for a way forward within the current paradigm. Thus, a different paradigm - a vaccine that uses the whole organism - is now being examined. Although most advances in this approach relate to a vaccine for the pre-erythrocytic stages (sporozoites, liver stages), this opinion paper will outline the possibilities of developing a whole parasite vaccine for the blood stage and address some of the challenges for this strategy, which are entirely different to the challenges for a subunit vaccine. It is the view of the author that both vaccine paradigms should be pursued, but that success will come more quickly using the paranormal approach of exposing individuals to ultra-low doses of whole attenuated or killed parasites.

  19. Red blood cells as innovative antigen carrier to induce specific immune tolerance.

    Science.gov (United States)

    Cremel, Magali; Guérin, Nathalie; Horand, Françoise; Banz, Alice; Godfrin, Yann

    2013-02-25

    The route of administration, the dose of antigen as well as the type of antigen-presenting cells (APCs) targeted are important factors to induce immune tolerance. Despite encouraging results obtained in animal models, intravenous injection of soluble antigen is unsuccessful in human clinical trials on autoimmune disease due to inefficient antigen delivery. To improve antigen delivery, we used mouse red blood cells (RBCs) as antigen vehicles to specifically target APCs which are responsible for removal of senescent RBCs after phagocytosis. In this study, we demonstrated that antigen-delivery by RBCs induced a strong decrease in the humoral response compared with the ovalbumin (OVA) free form in mice. In addition, OVA-loaded RBC treated with [bis(sulphosuccinimidyl)] suberate (BS3), a chemical compound known to enhance RBC phagocytosis, induced an inhibition of antigen-specific T cell responses and an increase in the percentage of regulatory T cells. The state of tolerance induced is long lasting, antigen-specific and sufficiently robust to withstand immunization with antigen mixed with cholera toxin adjuvant. This RBC strategy, which does not abolish the immune system, constitutes an attractive approach for induction of tolerance compared to systemic immunosuppressant therapies already in use.

  20. Frequencies of red blood cell major blood group antigens and phenotypes in the Chinese Han population from Mainland China.

    Science.gov (United States)

    Yu, Y; Ma, C; Sun, X; Guan, X; Zhang, X; Saldanha, J; Chen, L; Wang, D

    2016-08-01

    Alloantibodies directed to red blood cell (RBC) antigens play an important role in alloimmune-mediated haemolytic transfusion reactions and haemolytic disease of the foetus and newborn. The frequencies and phenotypes of RBC antigens are different in populations from different geographic areas and races. However, the data on major blood group antigens in the Chinese Han population from Mainland China are still very limited; thus, we aimed to investigate them in this study. A total of 1412 unrelated voluntary Chinese Han blood donors were randomly recruited. All donors were typed for blood group antigens: D, C, c, E, e, C(w) , Jk(a) , Jk(b) ,M, N, S, s, Le(a) , Le(b) , K, k. Kp(a) , Kp(b) , Fy(a) , Fy(b) , Lu(a) , Lu(b) , P1 and Di(a) using serological technology. Calculations of antigen and phenotype frequencies were expressed as percentages and for allele frequencies under the standard assumption of Hardy-Weinberg equilibrium. Amongst the Rh antigens, D was the most common (98.94%) followed by e (92.28%), C (88.81%), c (58.43%), E (50.78%) and C(w) (0.07%) with DCe/DCe (R1 R1 , 40.72%) being the most common phenotype. In the Kell blood group system, k was present in 100% of the donors and a rare phenotype, Kp (a+b+), was found in 0.28% of the donors. For the Kidd and Duffy blood group systems, Jk (a+b+) and Fy (a+b-) were the most common phenotypes (44.05% and 84.35%, respectively). In the MNS blood group system, M+N+S-s+ (45.54%) was the most common, whereas M+N-S-s- and M-N+S-s- were not found. The rare Lu (a-b-) and Lu (a+b+) phenotypes were identified in 0.43% and 1.13% of the donors, respectively. Le(a) and Le(b) were seen in 17.92% and 63.03% of donors, respectively. The frequency of Di(a) was 4.75%, which was higher than in the Chinese population in Taiwan region or the Caucasian and Black populations (P frequencies of 24 blood group antigens in the Chinese Han population from Mainland China. The data can be helpful in creating a donor database for

  1. Acquisition of growth-inhibitory antibodies against blood-stage Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Fiona J McCallum

    Full Text Available BACKGROUND: Antibodies that inhibit the growth of blood-stage Plasmodium falciparum may play an important role in acquired and vaccine-induced immunity in humans. However, the acquisition and activity of these antibodies is not well understood. METHODS: We tested dialysed serum and purified immunoglobulins from Kenyan children and adults for inhibition of P. falciparum blood-stage growth in vitro using different parasite lines. Serum antibodies were measured by ELISA to blood-stage parasite antigens, extracted from P. falciparum schizonts, and to recombinant merozoite surface protein 1 (42 kDa C-terminal fragment, MSP1-42. RESULTS: Antibodies to blood-stage antigens present in schizont protein extract and to recombinant MSP1-42 significantly increased with age and were highly correlated. In contrast, growth-inhibitory activity was not strongly associated with age and tended to decline marginally with increasing age and exposure, with young children demonstrating the highest inhibitory activity. Comparison of growth-inhibitory activity among samples collected from the same population at different time points suggested that malaria transmission intensity influenced the level of growth-inhibitory antibodies. Antibodies to recombinant MSP1-42 were not associated with growth inhibition and high immunoglobulin G levels were poorly predictive of inhibitory activity. The level of inhibitory activity against different isolates varied. CONCLUSIONS: Children can acquire growth-inhibitory antibodies at a young age, but once they are acquired they do not appear to be boosted by on-going exposure. Inhibitory antibodies may play a role in protection from early childhood malaria.

  2. Prevalence of hepatitis B surface antigen (HBsAg) in blood donors from Bombay.

    Science.gov (United States)

    Satoskar, A; Ray, V

    1992-01-01

    Analysis of serum samples from 3104 blood donors from Bombay screened for hepatitis B surface antigen (HBsAg) by ELISA. HBsAg was detected in 4.7% of the subjects. Relatives showed a significantly higher prevalence of HBsAg than volunteer donors. There was no significant association between HBsAg positivity and a particular blood group.

  3. Synthetic TLR4 agonists enhance functional antibodies and CD4+ T-cell responses against the Plasmodium falciparum GMZ2.6C multi-stage vaccine antigen

    DEFF Research Database (Denmark)

    Baldwin, Susan L; Roeffen, Will; Singh, Susheel K;

    2016-01-01

    of the sexual-stage protein Pfs48/45-6C genetically fused to GMZ2, an asexual vaccine antigen in advanced clinical development. To select the most suitable vaccine formulation for downstream clinical studies, GMZ2.6C was tested with various immune modulators in different adjuvant formulations (stable emulsions......A subunit vaccine targeting both transmission and pathogenic asexual blood stages of Plasmodium falciparum, i.e., a multi-stage vaccine, could be a powerful tool to combat malaria. Here, we report production and characterization of the recombinant protein GMZ2.6C, which contains a fragment...

  4. Blood Group Antigen Recognition via the Group A Streptococcal M Protein Mediates Host Colonization

    Science.gov (United States)

    De Oliveira, David M. P.; Hartley-Tassell, Lauren; Everest-Dass, Arun; Day, Christopher J.; Dabbs, Rebecca A.; Ve, Thomas; Kobe, Bostjan; Nizet, Victor; Packer, Nicolle H.; Walker, Mark J.; Jennings, Michael P.

    2017-01-01

    ABSTRACT Streptococcus pyogenes (group A streptococcus [GAS]) is responsible for over 500,000 deaths worldwide each year. The highly virulent M1T1 GAS clone is one of the most frequently isolated serotypes from streptococcal pharyngitis and invasive disease. The oral epithelial tract is a niche highly abundant in glycosylated structures, particularly those of the ABO(H) blood group antigen family. Using a high-throughput approach, we determined that a strain representative of the globally disseminated M1T1 GAS clone 5448 interacts with numerous, structurally diverse glycans. Preeminent among GAS virulence factors is the surface-expressed M protein. M1 protein showed high affinity for several terminal galactose blood group antigen structures. Deletion mutagenesis shows that M1 protein mediates glycan binding via its B repeat domains. Association of M1T1 GAS with oral epithelial cells varied significantly as a result of phenotypic differences in blood group antigen expression, with significantly higher adherence to those cells expressing H antigen structures compared to cells expressing A, B, or AB antigen structures. These data suggest a novel mechanism for GAS attachment to host cells and propose a link between host blood group antigen expression and M1T1 GAS colonization. PMID:28119471

  5. Correlation of the Serum Level of Carcinoembryonic Antigen and Prolactin with Different Stages of Colorectal Carcinoma According to Dukes' Staging.

    Science.gov (United States)

    Rahman, M R; Sheikh, S H; Lima, I J; Islam, M R; Faisal, M; Islam, M S; Faruk, M O; Jalal, M T

    2016-01-01

    Carcinoembryonic antigen (CEA) is well established tumor marker for colorectal cancers worldwide. Recent studies show that serum prolactin level is also raised in colorectal cancers. The purpose of the study is to evaluate the correlation of serum CEA and Prolactin with Dukes' staging of colorectal carcinomas. Between January 2013 and June 2013, Serum CEA and Serum Prolactin were measured by radioimmunoassay from 103 patients who were histopathologically diagnosed as colorectal carcinomas. Evaluation of the stages of the colorectal cancers was done on the basis of preoperative investigations and postoperative histopathology and correlated with Preoperative Serum CEA and Serum Prolactin. Results were presented as median value, range and percentage. Male to female ratio was 1.4:1 with median age of 42.26 years (range 17-78 years). Most of the patients in this series presented with carcinoma rectum (42%). Most of the patients (52%) were found in Dukes' stage C and 27% and 15% cases were found as Dukes' stage B and Dukes' stage D respectively. Stage of the disease is directly proportionate to percentage of the patient with high serum prolactin except early stage (Dukes' A-50%, Dukes' B-28.6%, Dukes' C-33.3% & Dukes' D-46.7%). Similarly serum CEA level is directly proportionate to tumor stage (Dukes' A-0%, Dukes' B-32%, Dukes' C-40.7% & Dukes' D-74.7%). A preoperative high serum CEA value suggests advanced disease either locally or with distant metastasis. In contrast preoperative high serum prolactin (hyperprolactinaemia) did not suggest advanced disease as it can be elevated even in early stage of disease. Serum CEA and Serum Prolactin both are valuable tumor markers but serum CEA could not be replaced by serum Prolactin. Serum Prolactin may be a helpful marker in earlier stages of the colorectal cancer.

  6. Red Blood Cell Antigen Genotyping for Sickle Cell Disease, Thalassemia, and Other Transfusion Complications.

    Science.gov (United States)

    Fasano, Ross M; Chou, Stella T

    2016-10-01

    Since the discovery of the ABO blood group in the early 20th century, more than 300 blood group antigens have been categorized among 35 blood group systems. The molecular basis for most blood group antigens has been determined and demonstrates tremendous genetic diversity, particularly in the ABO and Rh systems. Several blood group genotyping assays have been developed, and 1 platform has been approved by the Food and Drug Administration as a "test of record," such that no phenotype confirmation with antisera is required. DNA-based red blood cell (RBC) phenotyping can overcome certain limitations of hemagglutination assays and is beneficial in many transfusion settings. Genotyping can be used to determine RBC antigen phenotypes in patients recently transfused or with interfering allo- or autoantibodies, to resolve discrepant serologic typing, and/or when typing antisera are not readily available. Molecular RBC antigen typing can facilitate complex antibody evaluations and guide RBC selection for patients with sickle cell disease (SCD), thalassemia, and autoimmune hemolytic anemia. High-resolution RH genotyping can identify variant RHD and RHCE in patients with SCD, which have been associated with alloimmunization. In the future, broader access to cost-efficient, high-resolution RBC genotyping technology for both patient and donor populations may be transformative for the field of transfusion medicine.

  7. Antibody to histo-blood group A antigen neutralizes HIV produced by lymphocytes from blood group A donors but not from blood group B or O donors

    DEFF Research Database (Denmark)

    Arendrup, M; Hansen, J E; Clausen, H;

    1991-01-01

    not inhibit the HTLV-IIIB/lyB or the HTLV-IIIB/lyO isolate. Specificity of the MAb-mediated inhibition was shown using A-antigen (tetrasaccharide). Thus, HIV infection of PBMC from donors with blood type A appears to induce expression of host-cell-encoded carbohydrate blood group A epitope on HIV which can...

  8. SMIM1 variants rs1175550 and rs143702418 independently modulate Vel blood group antigen expression

    Science.gov (United States)

    Christophersen, Mikael K.; Jöud, Magnus; Ajore, Ram; Vege, Sunitha; Ljungdahl, Klara W.; Westhoff, Connie M.; Olsson, Martin L.; Storry, Jill R.; Nilsson, Björn

    2017-01-01

    The Vel blood group antigen is expressed on the red blood cells of most individuals. Recently, we described that homozygosity for inactivating mutations in SMIM1 defines the rare Vel-negative phenotype. Still, Vel-positive individuals show great variability in Vel antigen expression, creating a risk for Vel blood typing errors and transfusion reactions. We fine-mapped the regulatory region located in SMIM1 intron 2 in Swedish blood donors, and observed a strong correlation between expression and rs1175550 as well as with a previously unreported tri-nucleotide insertion (rs143702418; C > CGCA). While the two variants are tightly linked in Caucasians, we separated their effects in African Americans, and found that rs1175550G and to a lesser extent rs143702418C independently increase SMIM1 and Vel antigen expression. Gel shift and luciferase assays indicate that both variants are transcriptionally active, and we identified binding of the transcription factor TAL1 as a potential mediator of the increased expression associated with rs1175550G. Our results provide insight into the regulatory logic of Vel antigen expression, and extend the set of markers for genetic Vel blood group typing. PMID:28084402

  9. Comparison of local Salmonella pullorum antigen with imported product in whole blood agglutination test

    Directory of Open Access Journals (Sweden)

    Priyani Medewewa

    Full Text Available Background: Salmonellosis is considered as one of the most important diseases in poultry as it causes devastating losses in chicken industry. Proper identification of the infected and carrier birds is required to control the disease among chickens. In field situation whole blood agglutination test is performed in order to identify carriers of Pullorum and Fowl typhoid particularly, in breeder operations. In this test, serum antibodies are detected by using a specially made antigen for this purpose. In Sri Lanka, three antigen products are used commonly in whole blood agglutination test. Objectives: This study was carried out to compare these two locally available S. Pullorum antigen products and to determine any difference in the efficacy. Methods:“Shaver Brown” commercial layer birds (70 in number were used in the experiment. Birds were inoculated orally with 1.8X109cfu/ml of S. Pullorum at 16 weeks age. After Three weeks post inoculation, blood was collected from each bird and Whole blood agglutination test was performed using both antigen products. Fifteen (15 inoculated hens were selected randomly and cloacal swabs were cultured on cultured Agar on same day of serum collected. Results: In this study, there was no significant difference observed between two antigens to detect carrier birds by whole blood agglutination test. Salmonella was not isolated from cloacal swabs since no observed excretion of Salmonella Pullorum through faces. All cloacal swabs gave negative results, when cultured on artificial Agar. Conclusion: Both antigen can be used effectively to detect carrier birds under the control program in country. [Vet World 2012; 5(9.000: 546-548

  10. Red cell antigen prevalence predicted by molecular testing in ethnic groups of South Texas blood donors.

    Science.gov (United States)

    Aranda, Lorena I; Smith, Linda A; Jones, Scott; Beddard, Rachel

    2015-01-01

    Alloimmunization to red blood cell antigens is seen in patients receiving chronic blood transfusion. Knowing the prevalence of blood group antigens of the different ethnicities of South Texas donors can provide better management of rare blood inventory for patients in this geographical area. A total of 4369 blood donors were tested and analyzed for various antigens in the following blood group systems: ABO, Rh, Kell, Duffy, Kidd, MNS, Lutheran, Dombrock, Landsteiner-Wiener, Diego, Colton, and Scianna. Donors tested to be group 0 or A were serologically tested for the Rh (C, E, c, e) antigens. Those that tested as presumably R1R1, R2R2, or Ror were then genotyped. Donors constituted three major ethnicities: black (18.3%), Hispanic (36.3%), and Caucasian (41.1%); ethnicities comprised of Asian, American Indian, multiracial, and other accounted for the remaining donors (4.3%). The most likely common Rh phenotype for each ethnicity is as follows: black -Ror (44.4%), Hispanic -R1R1 (59.0%), and Caucasian -R1R1 (38.9%). The prevalence of Kell, Duffy, and Kidd blood group system antigens in black and Caucasian donors is comparable with published reports for the entire U.S. The black South Texas donor population had an 8.8 percent increase in prevalence of the Fy(a+b-) phenotype as compared with these published reports; the Hispanic South Texas donor population had a prevalence of 36.1 percent of the Fy(a+b-) phenotype. Regarding the Diego blood group system, the Hispanic donor population in South Texas had a prevalence of 93.5 percent for the Di(a-b+) phenotype as compared with published reports for the entire U.S. (>99.9%). The Hispanic population had a prevalence of 7.9 percent of donors testing as M-N+S-s+ as compared with 20.2 percent and 15.6 percent for black and Caucasian donors, respectively. This study helped us determine the prevalence of each of the blood group antigens in the South Texas donor population to establish and maintain adequate rare inventory of

  11. Variation in antigenic determinants specific to the infective stage of Trypanosoma cruzi.

    Science.gov (United States)

    Wrightsman, R A; Leon, W; Manning, J E

    1986-08-01

    Monoclonal antibodies reactive with the surface antigens of the Peru strain of Trypanosoma cruzi were analyzed by Western blots and immunofluorescence assays to determine their reactivity with three life cycle stages and five strain isolates of T. cruzi. One monoclonal antibody, 7.6, recognized a 68-kilodalton (kDa) polypeptide in Western blots of Peru strain trypomastigotes, epimastigotes, and amastigotes. A 68-kDa polypeptide was also detected by monoclonal antibody 7.6 in trypomastigotes of the CL and Y strains and in the clonal isolates Esmeraldo clone 3 and Silvio X10 clone 1. Positive immunofluorescence results were obtained for all life cycle stages of the five strains that were reacted with monoclonal antibody 7.6, thus indicating that the antigen recognized by monoclonal antibody 7.6 is universally present in all T. cruzi strains tested. In contrast, monoclonal antibody 4.2 reacted with a polypeptide doublet of 90 and 105 kDa in Western blots of Peru strain trypomastigotes, but it did not detect these antigens in epimastigotes or amastigotes. The same polypeptide doublet of 90 and 105 kDa was also detected in Western blots of Y strain trypomastigotes; however, no bands were detected in blots of strain CL or isolate Silvio X10 clone 1 trypomastigotes. In blots of Esmeraldo clone 3 trypomastigotes, a single band of 130 kDa was detected by monoclonal antibody 4.2. In immunofluorescence assays of monoclonal antibody 4.2, positive reactions were obtained only with trypomastigotes of Peru, Y, and Esmeraldo clone 3 strains. Thus, monoclonal antibody 4.2 recognizes a trypomastigote-specific antigen which is not universally present on all strains of T. cruzi.

  12. Unique antigenic gene expression at different developmental stages of Trichinella pseudospiralis.

    Science.gov (United States)

    Wu, X P; Liu, X L; Wang, X L; Blaga, R; Fu, B Q; Liu, P; Bai, X; Wang, Z J; Rosenthal, B M; Shi, H N; Sandrine, L; Vallee, I; Boireau, P; Wang, F; Zhou, X N; Zhao, Y; Liu, M Y

    2013-05-20

    Parasite-induced and parasite-regulated larval capsule formation and host immunosuppression are two major characteristics that are unique in Trichinella spp. infections, but the molecule(s) and mechanism(s) that mediate these processes remain largely unknown. Trichinella pseudospiralis and Trichinella spiralis, are obviously different with respect to these two characteristics. A comparative study of these two species, in particular their antigen expression profiles at different developmental stages (the main molecules involved in the cross-talk or interaction between each parasite and its host), may help us better understand the parasite molecules and mechanisms involved. Here, we constructed cDNA libraries from T. pseudospiralis adults (Ad), newborn larvae (NBL) and muscle larvae (ML) mRNA and screened them with pig anti-T. pseudospiralis serum collected 26, 32 and 60 days post-infection (p.i.). The most abundant antigens were found to vary among life-cycle stages. Pyroglutamy peptidase 1-like and 6-phosphogluconolactonase-like genes predominated in the Ad stage and a serine protease (SS2-1-like gene) predominated in NBL similar to that observed in T. spiralis. Muscle larvae expressed proteasome activator complex subunit 3-like and 21 kDa excretory/secretory protein-like genes. This study indicated that parasites of two species may utilise different molecules and mechanisms for larvae capsule formation and host immunosuppression during their infections. Proteins of antigenic genes identified in this study may be also good candidates for diagnosis, treatment or vaccination for T. pseudospiralis infection, and also for the differential diagnosis of two species' infections.

  13. Human peripheral blood monocytes display surface antigens recognized by monoclonal antinuclear antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Holers, V.M.; Kotzin, B.L.

    1985-09-01

    The authors used monoclonal anti-nuclear autoantibodies and indirect immunofluorescence to examine normal human peripheral blood mononuclear leukocytes for the presence of cell surface nuclear antigens. Only one monoclonal anti-histone antibody (MH-2) was found to bind to freshly isolated PBL, staining approximately 10% of large cells. However, after cells were placed into culture for 16-24 h, a high percentage (up to 60%) of large-sized cells were recognized by an anti-DNA (BWD-1) and several different antihistone monoclonal antibodies (BWH-1, MH-1, and MH-2). These antibodies recognize separate antigenic determinants on chromatin and histones extracted from chromatin. The histone antigen-positive cells were viable, and the monoclonal antibodies could be shown to be binding to the cell surface and not to the nucleus. Using monoclonal antibodies specific for monocytes and T cells, and complement-mediated cytotoxicity, the cells bearing histone antigens were shown to be primarily monocytes. The appearance of histone and DNA antigen-positive cells was nearly completely inhibited by the addition of low concentrations of cycloheximide at initiation of the cultures. In contrast, little effect on the percentage of positive cells was detected if cells were exposed to high doses of gamma irradiation before culture. These data further support the existence of cell surface nuclear antigens on selected cell subsets, which may provide insight into the immunopathogenesis of systemic lupus erythematosus and related autoimmune diseases.

  14. Structure of ganglioside with CAD blood group antigen activity

    Energy Technology Data Exchange (ETDEWEB)

    Gillard, B.K.; Blanchard, D.; Cartron, J.P.; van Kuik, G.A.; Vliegenthart, J.F.G.; Marcus, D.M.

    1986-05-01

    The novel erythrocyte ganglioside which carries the blood group Cad determinant has been isolated, and its structure has been determined. The ganglioside contained Glu:Gal:GalNAc:GlcNAc in a molar ratio of 1.00:1.94:0.93:0.95. The ganglioside binds Helix pomatia lectin and its chromatographic mobility is similar to G/sub D3/. After treatment with ..beta..-hexosaminidase (human placenta HexA) the product migrated with sialosylparagloboside (SPG), no longer binds Helix lectin, and binds a human anti-SPG antibody. Treatment of this material with neuraminidase (V. cholera) yielded a product with the mobility of paragloboside that bound monoclonal antibody 1B2. NMR analysis revealed that the terminal GalNAc is linked ..beta..1-4 to Gal, and confirms the structure proposed previously: GalNAc..beta..1-4(NeuAc..cap alpha..2-3)Gal..beta..1-4GlcNAc..beta..1-3Gal..beta..1-4Glc-Cer. This structure is consistent with the previous demonstration that a compound with the same chromatographic mobility as the Cad ganglioside could be synthesized by enzymatic transfer of GalNAc to sialosylparagloboside.

  15. Passage of dietary antigens into the blood of children with coeliac disease. Quantification and size distribution of absorbed antigens

    DEFF Research Database (Denmark)

    Husby, S; Foged, N; Høst, A

    1987-01-01

    The uptake of ovalbumin (OA) from egg and beta-lactoglobulin (BLG) from cow's milk into the blood was investigated for seven hours after a test meal in five children with coeliac disease on a gluten free diet and after gluten challenge, and in five children with normal jejunal mucosa. Ovalbumin...... was detectable by ELISA in three of five coeliac children (maximal concentrations 8-178 ng/ml serum) and in five of five controls (maximal 4-91 ng/ml serum). Beta-lactoglobulin was detected in three of five coeliac children (maximal 0.6-6 ng/ml serum) and in two of five controls (maximal 0.5 and 50 ng/ml serum......). No clear relationship was seen between maximal antigen concentrations and titres of serum IgG or IgA antibodies determined by ELISA, or as percentage antigen binding in a Farr type radioimmunoassay. Ovalbumin and beta-lactoglobulin was seen in serum of all coeliac patients and controls by HPLC...

  16. Identification and Characterization of Peptide Mimics of Blood Group A Antigen

    Institute of Scientific and Technical Information of China (English)

    Zhaoming TANG; Lin WANG; Lihua HU; Yirong LI; Tianpen CUI; Juan XIONG; Lifang DOU

    2008-01-01

    In order to investigate peptide mimics of carbohydrate blood group A antigen, a phage display 12-met peptide library was screened with a monoclonal antibody against blood group A antigen, NaM87-1F6. The antibody-binding properties of the selected phage peptides were evaluated by phage ELISA and phage capture assay. The peptides were co-expressed as glutathione S-transferase (GST) fusion proteins. RBC agglutination inhibition assay was performed to assess the natural blood group A antigen-mimicking ability of the fusion proteins. The results showed that seven phage clones selected bound to NaM87-1F6 specifically, among which, 6 clones bore the same peptide sequence, EYWYCGMNRTGC and another harbored a different one QIWYERTLPFrF. The two peptides were successfully expressed at the N terminal of GST protein. Both of the fusion proteins inhibited the RBC agglutination mediated by anti-A serum in a concentration-dependent manner. These results suggested that the fusion proteins based on the selected peptides could mimic the blood group A an- tigen and might be used as anti-A antibody-adsorbing materials when immunoabsorption was applied in ABO incompatible transplantation.

  17. Prolonged antigen presentation is required for optimal CD8+ T cell responses against malaria liver stage parasites.

    Directory of Open Access Journals (Sweden)

    Ian A Cockburn

    2010-05-01

    Full Text Available Immunization with irradiated sporozoites is currently the most effective vaccination strategy against liver stages of malaria parasites, yet the mechanisms underpinning the success of this approach are unknown. Here we show that the complete development of protective CD8+ T cell responses requires prolonged antigen presentation. Using TCR transgenic cells specific for the malaria circumsporozoite protein, a leading vaccine candidate, we found that sporozoite antigen persists for over 8 weeks after immunization--a remarkable finding since irradiated sporozoites are incapable of replication and do not differentiate beyond early liver stages. Persisting antigen was detected in lymphoid organs and depends on the presence of CD11c+ cells. Prolonged antigen presentation enhanced the magnitude of the CD8+ T cell response in a number of ways. Firstly, reducing the time primed CD8+ T cells were exposed to antigen in vivo severely reduced the final size of the developing memory population. Secondly, fully developed memory cells expanded in previously immunized mice but not when transferred to naïve animals. Finally, persisting antigen was able to prime naïve cells, including recent thymic emigrants, to become functional effector cells capable of eliminating parasites in the liver. Together these data show that the optimal development of protective CD8+ T cell immunity against malaria liver stages is dependent upon the prolonged presentation of sporozoite-derived antigen.

  18. Human leucocyte antigens: their association with end-stage renal disease in Saudi patients awaiting transplantation.

    Science.gov (United States)

    Almogren, A; Shakoor, Z; Hamam, K D

    2012-01-01

    Most patients with chronic renal failure develop end-stage renal disease (ESRD) that requires renal transplantation. This study investigates the possible associations between human leucocyte antigen (HLA) Class I and Class II molecules with ESRD. Genotyping data (HLA) obtained between 2005 and 2009 on 235 unrelated Saudi patients (147 males, 88 females; mean age: 58 +/- 7 years) with ESRD awaiting renal transplantation were assessed retrospectively at the King Khalid University Hospital. Data were compared with the results on 60 normal, healthy, unrelated Saudi individuals (37 males and 23 females; mean age: 51 +/- 5 years). HLA Class I and Class II antigens were detected by lymphocytotoxicity and a polymerase chain reaction (PCR) method using DNA sequence-specific primers. Although present in small numbers, HLA Cw2 was found in significantly fewer patients (n = 11; 4.68%) compared to normal subjects (n = 9; 15%) and was found to confer protection against ESRD (P = 0.005; relative risk [RR]: 3.594, 95% confidence interval [CI]: 1.415-9.126). Among the HLA Class II antigens, HLA DQB1*03(8) was detected more frequently in the patient group (n = 65; 27.6%) than in the normal controls (n = 9; 15%) and was positively associated with risk of ESRD (P = 0.04; RR: 0.462, 95% CI: 0.215-0.991). No significant differences were observed between the two groups in respect of HLA-A2, HLA-B50(21), HLA-B51(5) and HLA-Cw7 (HLA Class I), and HLA-DRB1*04, HLA-DRB1*07 and HLA-DQB1*02 (HLA Class II). Occurrence of the most frequent HLA alleles was no different between the ESRD group and the controls. The protective role of HLA-Cw2 and the marginal susceptibility associated with HLA-DQBI*03(8) for ESRD requires further investigation.

  19. Rudimentary study on humanization of porcine red blood cells: Enzymatic removal of galactose-α1,3-galactose antigen from porcine red blood cell

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The serological and biochemical characterization of porcine red blood cells (pRBCs) are similar to human red blood cells. Porcine erythrocytes are considered as an alternative source for human blood transfusion. But there exist galactose-α1,3-galactose antigens (Galα1,3Galβ1, 4GalNAc-R, abbreviated αGal antigen) on pRBCs, which can induce anti-(Gal antibodies in human serum. The (Galepitopes are the major antigen responsible for hyperacute rejection in xenotransfusion. In this study, recombined soybean α-galactosidase (rSα-GalE) was usedto remove the (Gal antigens from pPRCs for humanization. The results showed that (Gal antigen was cleared by rSα-GalE and the structure and function of rSα-GalE treated pRBC were normal.

  20. Total and antigen-specific Ige levels in umbilical cord blood

    Directory of Open Access Journals (Sweden)

    Sybilski AJ

    2009-12-01

    Full Text Available Abstract The present study was conducted to learn whether the perinatal and environmental factors could influence the total and antigen-specific IgE levels in umbilical cord blood. Retrospective data were obtained from 173 mother-infant pairs. Total and specific (for children's food, wheat/grass and house dust mite-HDM cord blood IgE levels were determined using the immunoassay test. The total cord blood IgE was between 0.0-23.08 IU/ml (mean 0.55 ± 2.07 IU/ml; median 0.16 IU/ml. Total IgE levels were significantly higher in boys compared with girls (OR = 2.2; P = 0.007, and in newborns with complicated pregnancy (OR = 2.7; P = 0.003. A greater number of siblings correlated with increases in the total cord blood IgE (P

  1. Stage-specific embryonic antigen: determining expression in canine glioblastoma, melanoma, and mammary cancer cells

    Science.gov (United States)

    Ito, Daisuke

    2017-01-01

    The expression of stage-specific embryonic antigens (SSEAs) was determined in several types of canine cancer cells. Flow cytometry showed SSEA-1 expression in glioblastoma, melanoma, and mammary cancer cells, although none expressed SSEA-3 or SSEA-4. Expression of SSEA-1 was not detected in lymphoma, osteosarcoma, or hemangiosarcoma cell lines. Relatively stable SSEA-1 expression was observed between 24 and 72 h of culture. After 8 days in culture, sorted SSEA-1− and SSEA-1+ cells re-established SSEA-1 expression to levels comparable to those observed in unsorted cells. Our results document, for the first time, the expression of SSEA-1 in several canine cancer cell lines. PMID:27456773

  2. Development of blood-stages malaria vaccines%红内期疟疾疫苗的研究进展

    Institute of Scientific and Technical Information of China (English)

    陈琳; 黄复生

    2011-01-01

    目前发展疟疾疫苗仍然是防治和消灭疟疾感染的重要手段,红内期是疟原虫致病并引起临床症状的主要时期,发展有效的红内期疫苗不仅能减轻临床症状,还可降低血中配子体数量从而起到阻断传播作用.本文就目前红内期亚单位疫苗候选抗原及全虫疫苗的研究现状作一综述.%A key tool for control and elimination of malaria is an effective vaccine.The pathology and clinical symptoms of malaria are associated with the blood stages of the parasite's life cycle.The development of blood stage vaccines can reduce or clear the clinical symptoms and reduce the transmission through the mosquito vector.The review focuses only on advantages and challenges of candidate antigens of blood-stage subunit vaccine and whole blood-stage parasites vaccine.

  3. High prevalence of HIV p24 antigen among HIV antibody negative prospective blood donors in Ile-Ife, Nigeria.

    Science.gov (United States)

    Japhet, Margaret Oluwatoyin; Adewumi, Moses Olubusuyi; Adesina, Olufisayo Adeyemi; Donbraye, Emmanuel

    2016-01-01

    Blood transfusion service centers in Nigeria screen donated blood for markers of HIV infection using antibody- (Ab) based rapid test and in some centers, positives are re-tested using Ab-based ELISA. Paucity of data exists on p24 antigen prevalence among HIV Ab-negative donors in Nigeria. This study aims at detecting HIV p24 antigen among prospective blood donors in Osun State, Nigeria. Prospective blood donors negative for HIV antibodies using Determine test kit were re-tested using BIORAD GENSCREEN Ultra Ag-Ab ELISA kit, a fourth-generation ELISA kit that detects HIV antibodies/p24 antigen. Of the 169 HIV Ab-negative prospective donors, 10 (5.9%) were positive for HIV p24 antigen and 70% (7/10) of them were in the age range 18-30 years. Results of this study show that blood transfusion is still one of the major routes of HIV transmission in Nigeria and a higher proportion is among youth. Inclusion of p24 antigen testing into the blood donor screening will help reduce transfusion associated HIV in Nigeria if Nucleic Acid Testing (NAT) of all blood donor samples is not affordable; also, HIV enlightenment programs tailored toward youth may help reduce this rate among donors since more young people donate blood in low/middle-income countries than in high-income countries.

  4. Blood group antigen studies using CdTe quantum dots and flow cytometry

    Directory of Open Access Journals (Sweden)

    Cabral Filho PE

    2015-07-01

    Full Text Available Paulo E Cabral Filho,1 Maria IA Pereira,1 Heloise P Fernandes,2 Andre A de Thomaz,3 Carlos L Cesar,3 Beate S Santos,4 Maria L Barjas-Castro,2 Adriana Fontes1 1Departamento de Biofísica e Radiobiologia, Universidade Federal de Pernambuco, Recife, Pernambuco, 2Centro de Hematologia e Hemoterapia, Universidade Estadual de Campinas, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, 3Departamento de Eletrônica Quântica, Instituto de Física Gleb Wataghin, Universidade Estadual de Campinas, Campinas, São Paulo, 4Departamento de Ciências Farmacêuticas, Universidade Federal de Pernambuco, Recife, PE, Brazil Abstract: New methods of analysis involving semiconductor nanocrystals (quantum dots [QDs] as fluorescent probes have been highlighted in life science. QDs present some advantages when compared to organic dyes, such as size-tunable emission spectra, broad absorption bands, and principally exceptional resistance to photobleaching. Methods applying QDs can be simple, not laborious, and can present high sensibility, allowing biomolecule identification and quantification with high specificity. In this context, the aim of this work was to apply dual-color CdTe QDs to quantify red blood cell (RBC antigen expression on cell surface by flow cytometric analysis. QDs were conjugated to anti-A or anti-B monoclonal antibodies, as well as to the anti-H (Ulex europaeus I lectin, to investigate RBCs of A1, B, A1B, O, A2, and Aweak donors. Bioconjugates were capable of distinguishing the different expressions of RBC antigens, both by labeling efficiency and by flow cytometry histogram profile. Furthermore, results showed that RBCs from Aweak donors present fewer amounts of A antigens and higher amounts of H, when compared to A1 RBCs. In the A group, the amount of A antigens decreased as A1 > A3 > AX = Ael, while H antigens were AX = Ael > A1. Bioconjugates presented stability and remained active for at least 6 months. In conclusion

  5. Acanthocheilonema viteae: Vaccination of jirds with irradiation-attenuated stage-3 larvae and with exported larval antigens

    Energy Technology Data Exchange (ETDEWEB)

    Lucius, R.; Textor, G.; Kern, A.; Kirsten, C. (Institut fuer Tropenhygiene, Heidelberg (West Germany))

    1991-08-01

    Jirds (Meriones unguiculatus) were immunized with irradiated (35 krad) stage-3 larvae (L3) of Acanthocheilonema viteae. The induced resistance against homologous challenge infection and the antibody response of the animals were studied. Immunization with 3, 2, or 1 dose of 50 irradiated L3 induced approximately 90% resistance. Immunization with a single dose of only 5 irradiated L3 resulted in 60.8% protection while immunization with a single dose of 25 L3 induced 94.1% protection. The protection induced with 3 doses of 50 irradiated L3 did not decrease significantly during a period of 6 months. Sera of a proportion, but not all resistant jirds, contained antibodies against the surface of vector derived L3 as defined by IFAT. No surface antigens of microfilariae or adult worms were recognized by the sera. Vaccinated animals had antibody responses against antigens in the inner organs of L3 and in the cuticle and reproductive organs of adult worms as shown by IFAT. Immunoblotting with SDS-PAGE-separated L3 antigens and L3-CSN revealed that all sera contained antibodies against two exported antigens of 205 and 68 kDa, and against a nonexported antigen of 18 kDa. The 205-kDa antigen easily degraded into fragments of 165, 140, 125, and 105 kDa which were recognized by resistant jird sera. Various antigens of adult worms, but relatively few antigens of microfilariae, were also recognized. To test the relevance of exported antigens of L3 to resistance, jirds were immunized with L3-CSN together with a mild adjuvant. This immunization induced 67.7% resistance against challenge infection and sera of the immunized animals recognized the 205- and 68-kDa antigens of L3.

  6. Is Stage-Specific Embryonic Antigen 4 a Marker for Human Ductal Stem/Progenitor Cells?

    Science.gov (United States)

    Kayali, Ayse; Lopez, Ana; Hayek, Alberto

    2012-01-01

    Abstract The presence of pancreatic stem cells (PnSCs) has not been firmly demonstrated in the human or animal pancreas. Previous reports have suggested that ductal and acinar structures in the exocrine pancreas can be a potential source of progenitor cells. More recently, immature insulin precursors in the periphery of human islets have been found to self-replicate and differentiate to endocrine cells in vitro. Transplantation of these cells under the kidney capsule improves the diabetic state in mice. The controversy surrounding where PnSCs reside could be resolved if a specific marker were to be found that allowed their identification, purification, and directed differentiation to endocrine cells. We have identified in human pancreas cells positive for the stage-specific embryonic antigen 4 (SSEA4), a stem cell marker. These cells also express ductal, pancreatic progenitor, and stem cell protein markers. Interestingly, some of the SSEA4+ cells scattered in the ducts do not show a ductal cell phenotype. SSEA4+-sorted cells formed aggregate-like spheres in culture and robustly differentiated to pancreatic hormone-expressing cells in conditions of high glucose concentration and B27 supplementation. We hypothesize that SSEA4+ cells or a subpopulation of those cells residing in the pancreatic ducts may be the elusive PnSCs, and in this case, SSEA4 may represent a potential surface antigen marker for human PnSCs. The discovery of specific markers for the identification and purification of human PnSCs would greatly facilitate studies aimed at the expansion of these cells and the development of targeting tools for their potential induction to insulin-producing cells. PMID:23515456

  7. Is stage-specific embryonic antigen 4 a marker for human ductal stem/progenitor cells?

    Science.gov (United States)

    Afrikanova, Ivka; Kayali, Ayse; Lopez, Ana; Hayek, Alberto

    2012-08-01

    The presence of pancreatic stem cells (PnSCs) has not been firmly demonstrated in the human or animal pancreas. Previous reports have suggested that ductal and acinar structures in the exocrine pancreas can be a potential source of progenitor cells. More recently, immature insulin precursors in the periphery of human islets have been found to self-replicate and differentiate to endocrine cells in vitro. Transplantation of these cells under the kidney capsule improves the diabetic state in mice. The controversy surrounding where PnSCs reside could be resolved if a specific marker were to be found that allowed their identification, purification, and directed differentiation to endocrine cells. We have identified in human pancreas cells positive for the stage-specific embryonic antigen 4 (SSEA4), a stem cell marker. These cells also express ductal, pancreatic progenitor, and stem cell protein markers. Interestingly, some of the SSEA4(+) cells scattered in the ducts do not show a ductal cell phenotype. SSEA4(+)-sorted cells formed aggregate-like spheres in culture and robustly differentiated to pancreatic hormone-expressing cells in conditions of high glucose concentration and B27 supplementation. We hypothesize that SSEA4(+) cells or a subpopulation of those cells residing in the pancreatic ducts may be the elusive PnSCs, and in this case, SSEA4 may represent a potential surface antigen marker for human PnSCs. The discovery of specific markers for the identification and purification of human PnSCs would greatly facilitate studies aimed at the expansion of these cells and the development of targeting tools for their potential induction to insulin-producing cells.

  8. Isolation, Cloning, Expression and Purification of Recombinant RhD Antigen from Cord Blood

    Directory of Open Access Journals (Sweden)

    M Habibi Roudkenar

    2008-09-01

    Full Text Available "nBackground: Rh (Rhesus is a highly complex blood group system in man deeply rooted in transfusion medicine. Isolation of RhD from cord blod, cloning and expression of recombinant RhD antigen in bacterial expression system was the aim of this study."nMethods: Total RNAs were extracted from cord blood (O+.  The quality of RNA was determined by electrophoresis. In or­der to obtain coding sequence of RhD antigen cDNA was synthesized and Rh D gene was amplified by RT-PCR. The iso­lated RhD gene was   cloned to pUC18 vector and transformed to DH5α. The confirmed construct was sub cloned into expres­sion vector, pBADgIII/A, and expressed in Top10 E.coli. The expressed protein was characterized by SDS-PAGE and western blot analysis. Antigenicity of the expressed protein was assessed by ELISA using commercially available hu­man anti-RhD polyclonal   antibody with   peroxidase conjugated goat anti-human IgG, IgM, IgA as secondary antibody. "nRe­sults: RhD gene was successfully cloned and expressed. The expected size of recombinant RhD protein was detected in SDS-PAGE, and confirmed by dot and western blot analysis. RhD antibody reacted with recombinant RhD antigen as well as with RhD polypeptide extracted from RBCs membrane."nConclusion: The recombinant RhD may be helpful to further investigate the molecular basis of RhD protein and could be applica­ble for production anti- D antibody in an animal model.

  9. Studies of the antigenicity and immunogenicity of bromelain-pretreated red blood cells.

    Science.gov (United States)

    Cox, K O; Baddams, H; Evans, A

    1977-02-01

    The effects of the proteolytic enzyme bromelain (Br) on the antigenicity and immunogenicity of sheep and mouse red blood cells (RBC) have been investigated. The results presented support the previous claim that there are antigens present on Br RBC that are not present in an exposed form on untreated RBC and that Br RBC have lost some of the antigens present on the surface of normal RBC. The susceptibility of Br RBC to osmotic lysis was very similar to that of normal RBC, implying that the modified RBC were not more fragile than normal RBC. Injection of mice with Br mouse-RBC did not increase the unusually high "background" number of cells producing IgM antibodies against Br mouse-RBC and mice did not mount delayed-type hypersensitivity reactions against Br mouse-RBC, either before or after sensitizing injections of Br mouse-RBC. However, mouse-RBC and Br mouse-RBC elicited similar antibody responses in rabbits and guinea pigs. Although mice appeared unresponsive to Br mouse-RBC injections, delayed-type hypersensitivity responses and antibody production in primary and secondary responses were of similar levels irrespective of whether sheep-RBC or Br sheep-RBC were used as immunogens. From these studies it appears that mice have B-cells producing antibodies against the "new" antigens on Br mouse-RBC, but there are no T-cells that respond to these antigens by way of "helper" activity in antibody production or by way of cell-mediated immune reactions.

  10. Paraneoplastic antigen Ma2 autoantibodies as specific blood biomarkers for detection of early recurrence of small intestine neuroendocrine tumors.

    Directory of Open Access Journals (Sweden)

    Tao Cui

    Full Text Available BACKGROUND: Small intestine neuroendocrine tumors (SI-NETs belong to a rare group of cancers. Most patients have developed metastatic disease at the time of diagnosis, for which there is currently no cure. The delay in diagnosis is a major issue in the clinical management of the patients and new markers are urgently needed. We have previously identified paraneoplastic antigen Ma2 (PNMA2 as a novel SI-NET tissue biomarker. Therefore, we evaluated whether Ma2 autoantibodies detection in the blood stream is useful for the clinical diagnosis and recurrence of SI-NETs. METHODOLOGY/PRINCIPAL FINDINGS: A novel indirect ELISA was set up to detect Ma2 autoantibodies in blood samples of patients with SI-NET at different stages of disease. The analysis was extended to include typical and atypical lung carcinoids (TLC and ALC, to evaluate whether Ma2 autoantibodies in the blood stream become a general biomarker for NETs. In total, 124 blood samples of SI-NET patients at different stages of disease were included in the study. The novel Ma2 autoantibody ELISA showed high sensitivity, specificity and accuracy with ROC curve analysis underlying an area between 0.734 and 0.816. Ma2 autoantibodies in the blood from SI-NET patients were verified by western blot and sequential immunoprecipitation. Serum antibodies of patients stain Ma2 in the tumor tissue and neurons. We observed that SI-NET patients expressing Ma2 autoantibody levels below the cutoff had a longer progression and recurrence-free survival compared to those with higher titer. We also detected higher levels of Ma2 autoantibodies in blood samples from TLC and ALC patients than from healthy controls, as previously shown in small cell lung carcinoma samples. CONCLUSION: Here we show that high Ma2 autoantibody titer in the blood of SI-NET patients is a sensitive and specific biomarker, superior to chromogranin A (CgA for the risk of recurrence after radical operation of these tumors.

  11. Preoperative serum squamous cell carcinoma antigen levels in clinical decision making for patients with early-stage cervical cancer

    NARCIS (Netherlands)

    Reesink-Peters, N; van der Velden, J; ten Hoor, KA; Boezen, HM; de Vries, EGE; Schilthuis, MS; Mourits, MJE; Nijman, HW; Aalders, JG; Hollema, H; Pras, E; Duk, JM; van der Zee, AGJ

    2005-01-01

    PURPOSE: To prevent morbidity associated with double modality treatment, early-stage cervical cancer patients should only be offered surgery when there is a low likelihood for adjuvant radiotherapy. We analyzed whether serum squamous cell carcinoma antigen (SCC-ag) analysis allows better preoperativ

  12. Distribution of ABO and rhesus (D blood group antigens among blood donors at a tertiary care teaching hospital blood bank in south India

    Directory of Open Access Journals (Sweden)

    Suresh B

    2015-04-01

    Full Text Available Background: The ABO and Rhesus (Rh blood group systems are important for transfusion of blood and its components, organ transplantation, genetic studies and in medico-legal issues. Despite the long list of several other blood groups discovered so far, the knowledge and distribution of ABO and Rh-D blood group are essential for effective management of blood bank inventory. Methods: We retrospectively studied the distribution of ABO and Rh blood group antigens in donors presenting to our tertiary care teaching hospital blood bank in south India during the period January 2007 to August 2014. Blood group was determined by commercially available standard monoclonal antisera by test tube agglutination technique. Results: A total of 49,110 donor samples were tested during the study period for ABO grouping and Rh-D typing. Out of these 96.9% were males. The frequency of O, B, A, AB and Bombay blood groups were 41.7%, 32.2% 20%, 6.1% and 0.03% respectively. Rh (D positive and negative blood groups were seen in 92.8% and 7.2% respectively. The allele frequencies of the I A , IB and IO alleles were 0.1398, 0.2148 and 0.6454 respectively. In case of Rh-D group, the calculated gene frequencies for ID and Id were 0.7321 and 0.2679 respectively. Conclusion: Knowledge of blood group systems as documented in the present study helps in efficient management of blood bank and transfusion services in emergencies.

  13. Soluble Plasmodium falciparum antigens contain carbohydrate moieties important for immune reactivity

    DEFF Research Database (Denmark)

    Jakobsen, P H; Theander, T G; Jensen, J B;

    1987-01-01

    The importance of carbohydrate moieties for the antigenicity of purified soluble Plasmodium falciparum antigens from the asexual blood stage was tested. Digestion of the soluble antigens with alpha-D-galactosidase clearly affected the ability of the antigen to react with malaria-immune sera from ....... The results might have important implications for the strategy of developing a malaria vaccine.......The importance of carbohydrate moieties for the antigenicity of purified soluble Plasmodium falciparum antigens from the asexual blood stage was tested. Digestion of the soluble antigens with alpha-D-galactosidase clearly affected the ability of the antigen to react with malaria-immune sera from...

  14. Chemoenzymatic Synthesis of a Type 2 Blood Group A Tetrasaccharide and Development of High-throughput Assays Enables a Platform for Screening Blood Group Antigen-cleaving Enzymes.

    Science.gov (United States)

    Kwan, David H; Ernst, Sabrina; Kötzler, Miriam P; Withers, Stephen G

    2015-08-01

    A facile enzymatic synthesis of the methylumbelliferyl β-glycoside of the type 2 A blood group tetrasaccharide in good yields is reported. Using this compound, we developed highly sensitive fluorescence-based high-throughput assays for both endo-β-galactosidase and α-N-acetylgalactosaminidase activity specific for the oligosaccharide structure of the blood group A antigen. We further demonstrate the potential to use this assay to screen the expressed gene products of metagenomic libraries in the search for efficient blood group antigen-cleaving enzymes.

  15. Diagnostic value of cancer-testis antigen mRNA in peripheral blood from hepatocellular carcinoma patients

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To evaluate the diagnostic value of cancer-testis antigen(CTA) mRNA in peripheral blood samples from hepatocellular carcinoma(HCC) patients.METHODS:Peripheral blood samples were taken from 90 patients with HCC before operation.Expression of melanoma antigen-1(MAGE-1),synovial sarcoma X breakpoint-1(SSX-1),and cancer-testis-associated protein of 11 kDa(CTp11) mRNA in peripheral blood mononuclear cells(PBMC) was tested by nested reverse transcriptspolymerase chain reaction(RT-PCR).Serum α-fetoprotein(AFP)...

  16. Expression of Lewisb blood group antigen in Helicobacterpylori does not interfere with bacterial adhesion property

    Institute of Scientific and Technical Information of China (English)

    Peng-Yuan Zheng; Jiesong Hua; Han-Chung Ng; Khay-Guan Yeoh; Ho Bow

    2003-01-01

    AIM: The finding that some Helicobacterpyloristrains expressLewis b (Leb) blood group antigen casts a doubt on the roleof Leb of human gastric epithelium being a receptor for-H.pylori. The aim of this study was to determine if expressionof Leb in H. Pyloriinterferes with bacterial adhesion property.METHODS: Bacterial adhesion to immobilized Leb onmicrotitre plate was performed in 63-H. Pyloristrains obtainedfrom Singapore using in vitro adherence assay. Expression ofLewis blood group antigens was determined by ELISA assay.RESULTS: Among 63 H. Pyloristrains, 28 expressed Lebantigen. In vitro adhesion assay showed that 78.6 % (22/28) of Leb-positive and 74.3 % (26/35) of Leb-negative-H.pyloriisolates were positive for adhesion to immobilized Lebcoated on microtitre plate (P=0.772). In addition, blockingof H. Pylori Leb by prior incubation with anti-Leb monoclonalantibody did not alter thebinding of the bacteria to solid-phase coated Leb.CONCLUSION: The present study suggests that expressionof Leb in H. Pyloridoes not interfere with the bacterialadhesion property. This result supports the notion that Lebpresent on human gastric epithelial cells is capable of beinga receptor for H.pylori.

  17. A modified PCR-SSP method for the identification of ABO blood group antigens.

    Science.gov (United States)

    Downing, J; Darke, C

    2003-08-01

    The ABO blood group antigens are carbohydrate molecules synthesized by the glycosyltransferases encoded by the ABO gene on chromosome 9. Kidney transplantation across the ABO barrier generally leads to rapid humoral graft rejection due to the presence of naturally occurring antibodies to the A and B antigens. We have developed a method for ABO typing our cadaveric organ donors by the polymerase chain reaction using sequence-specific primers (PCR-SSP). The method uses 12 primers in eight PCR mixtures and is performed under the same conditions as our routine HLA-A, B, C PCR-SSP typing. The PCR-SSP-based types of 166 regular blood donors and 148 cadaveric organ donors all showed total concordance with their serologically assigned ABO groups. Six individuals possessing the ABO A subgroups (A3, Ax and Aend) all typed as A1 by PCR-SSP, as expected. PCR-SSP is an appropriate method for ABO typing of cadaveric organ donors and, importantly, enables both ABO and HLA typing to be performed on the same DNA material.

  18. Differential expression of function-related antigens on blood monocytes in children with hemolytic uremic syndrome.

    Science.gov (United States)

    Fernández, Gabriela C; Ramos, María V; Gómez, Sonia A; Dran, Graciela I; Exeni, Ramón; Alduncín, Marta; Grimoldi, Irene; Vallejo, Graciela; Elías-Costa, Christian; Isturiz, Martín A; Palermo, Marina S

    2005-10-01

    Monocytes (Mo) mediate central functions in inflammation and immunity. Different subpopulations of Mo with distinct phenotype and functional properties have been described. Here, we investigate the phenotype and function of peripheral Mo from children with hemolytic uremic syndrome (HUS). For this purpose, blood samples from patients in the acute period of HUS (HUS AP) were obtained on admission before dialysis and/or transfusion. The Mo phenotypic characterization was performed on whole blood by flow cytometry, and markers associated to biological functions were selected: CD14 accounting for lipopolysaccharide (LPS) responsiveness, CD11b for adhesion, Fc receptor for immunoglobulin G type I (FcgammaRI)/CD64 for phagocytosis and cytotoxicity, and human leukocyte antigen (HLA)-DR for antigen presentation. Some of these functions were also determined. Moreover, the percentage of CD14+ CD16+ Mo was evaluated. We found that the entire HUS AP Mo population exhibited reduced CD14, CD64, and CD11b expression and decreased LPS-induced tumor necrosis factor production and Fcgamma-dependent cytotoxicity. HUS AP showed an increased percentage of CD14+ CD16+ Mo with higher CD16 and lower CD14 levels compared with the same subset from healthy children. Moreover, the CD14++ CD16- Mo subpopulation of HUS AP had a decreased HLA-DR expression, which correlated with severity. In conclusion, the Mo population from HUS AP patients presents phenotypic and functional alterations. The contribution to the pathogenesis and the possible scenarios that led to these changes are discussed.

  19. A novel method for rapid detection of Streptococcus pneumoniae antigens in blood.

    Science.gov (United States)

    Fukushima, Kiyoyasu; Kubo, Toru; Ehara, Naomi; Nakano, Reiji; Matsutake, Toyoshi; Ishimatu, Yuji; Tanaka, Yumi; Akamatsu, Suguru; Izumikawa, Koichi; Kohno, Shigeru

    2016-03-01

    In this study, we used "RAPIRUN(®)Streptococcus pneumoniae HS (otitis media/sinusitis) (RAPIRUN-HS)," a rapid S. pneumoniae antigen detection kit, to investigate methods for detecting S. pneumoniae antigens in blood of 32 bacterial pneumonia patients. We simultaneously performed PCR to detect S. pneumoniae in blood samples. The results of these tests were compared based on pneumonia severity, determined using the Pneumonia Severity Index (PSI) score classification. Four S. pneumoniae PCR-positive patients of the six severe pneumococcal pneumonia patients (PSI risk class IV/V) also tested positive using RAPIRUN-HS. Twenty-four mild to moderate pneumonia patients (PSI risk class I-III) were S. pneumoniae PCR-negative; of these, 21 tested negative using RAPIRUN-HS. The pneumococcal pneumonia patients testing positive using RAPIRUN-HS had low leukocyte counts and elevated C-reactive protein and procalcitonin levels, indicating that RAPIRUN-HS results were correlated with pneumonia severity. The time course evaluations of the laboratory tests for severe pneumococcal pneumonia patients showed that RAPIRUN-HS and S. pneumoniae PCR yielded positive results earlier than the changes in procalcitonin and IL-6. Thus, concomitant pneumococcal bacteremia was strongly suspected in patients testing positive using RAPIRUN-HS. In conclusion, RAPIRUN-HS may be useful for determining whether to admit patients into hospitals and selecting the appropriate antimicrobial agents.

  20. The prevalence of hepatitis B virus E antigen among Ghanaian blood donors

    Science.gov (United States)

    Rufai, Tanko; Mutocheluh, Mohamed; Kwarteng, Kwaku; Dogbe, Elliot

    2014-01-01

    Hepatitis B viral infection is an important clinical problem due to its worldwide distribution and potential of adverse sequelae, including hepatocellular carcinoma (HCC). We studied the prevalence of hepatitis B virus ‘e’ antigen (HBeAg) among individuals determined to be hepatitis B virus (HBV) surface antigen-positive and analyzed the gender/age category associated with more active HBV infection and whether alteration in the levels of alanine aminotransferase could be associated with HBeAg positivity. A total of 150 prospective blood donors who tested positive for hepatitis B surface antigen (HBsAg) at the blood transfusion center of the Komfo Anokye Teaching Hosptital (KATH), Kumasi were randomly selected for the study. The serum samples were further tested for HBsAg and HBeAg using a lateral flow immunochromatographic assay. Twenty (20) individuals were found to be HBeAg-positive giving an overall prevalence of 13.3%, of which 18 (15.5%) were males and 2 (5.9%) were females. Our results also revealed that the prevalence of HBeAg was higher in patients between the age group of 10-20 years and appeared to decrease with increase in age. There was no statistical difference between the HBeAg positive and negative individuals with respect to alanine aminotransferase (ALT) levels. We show for the first time that approximately 1/10 of HBV-infected individuals are HBeAg positive in the Ashanti Region of Ghana, suggestive of active viral replication and liver-cell infectivity thereby contributing to an increased HBV-transmission pool within the Ghanaian population. PMID:25018803

  1. BGMUT: NCBI dbRBC database of allelic variations of genes encoding antigens of blood group systems.

    Science.gov (United States)

    Patnaik, Santosh Kumar; Helmberg, Wolfgang; Blumenfeld, Olga O

    2012-01-01

    Analogous to human leukocyte antigens, blood group antigens are surface markers on the erythrocyte cell membrane whose structures differ among individuals and which can be serologically identified. The Blood Group Antigen Gene Mutation Database (BGMUT) is an online repository of allelic variations in genes that determine the antigens of various human blood group systems. The database is manually curated with allelic information collated from scientific literature and from direct submissions from research laboratories. Currently, the database documents sequence variations of a total of 1251 alleles of all 40 gene loci that together are known to affect antigens of 30 human blood group systems. When available, information on the geographic or ethnic prevalence of an allele is also provided. The BGMUT website also has general information on the human blood group systems and the genes responsible for them. BGMUT is a part of the dbRBC resource of the National Center for Biotechnology Information, USA, and is available online at http://www.ncbi.nlm.nih.gov/projects/gv/rbc/xslcgi.fcgi?cmd=bgmut. The database should be of use to members of the transfusion medicine community, those interested in studies of genetic variation and related topics such as human migrations, and students as well as members of the general public.

  2. P. falciparum and P. vivax Epitope-Focused VLPs Elicit Sterile Immunity to Blood Stage Infections.

    Directory of Open Access Journals (Sweden)

    David C Whitacre

    Full Text Available In order to design P. falciparum preerythrocytic vaccine candidates, a library of circumsporozoite (CS T and B cell epitopes displayed on the woodchuck hepatitis virus core antigen (WHcAg VLP platform was produced. To test the protective efficacy of the WHcAg-CS VLPs, hybrid CS P. berghei/P. falciparum (Pb/Pf sporozoites were used to challenge immunized mice. VLPs carrying 1 or 2 different CS repeat B cell epitopes and 3 VLPs carrying different CS non-repeat B cell epitopes elicited high levels of anti-insert antibodies (Abs. Whereas, VLPs carrying CS repeat B cell epitopes conferred 98% protection of the liver against a 10,000 Pb/Pf sporozoite challenge, VLPs carrying the CS non-repeat B cell eptiopes were minimally-to-non-protective. One-to-three CS-specific CD4/CD8 T cell sites were also fused to VLPs, which primed CS-specific as well as WHcAg-specific T cells. However, a VLP carrying only the 3 T cell domains failed to protect against a sporozoite challenge, indicating a requirement for anti-CS repeat Abs. A VLP carrying 2 CS repeat B cell epitopes and 3 CS T cell sites in alum adjuvant elicited high titer anti-CS Abs (endpoint dilution titer >1x10(6 and provided 80-100% protection against blood stage malaria. Using a similar strategy, VLPs were constructed carrying P. vivax CS repeat B cell epitopes (WHc-Pv-78, which elicited high levels of anti-CS Abs and conferred 99% protection of the liver against a 10,000 Pb/Pv sporozoite challenge and elicited sterile immunity to blood stage infection. These results indicate that immunization with epitope-focused VLPs carrying selected B and T cell epitopes from the P. falciparum and P. vivax CS proteins can elicit sterile immunity against blood stage malaria. Hybrid WHcAg-CS VLPs could provide the basis for a bivalent P. falciparum/P. vivax malaria vaccine.

  3. Screening of early antigen genes of adult-stage Trichinella spiralis using pig serum from different stages of early infection

    Science.gov (United States)

    The goal of this work was to identify novel, early antigens present in Trichinella spiralis. To this end, a cDNA library generated from 3-day old adult worms (Ad3) was immunologically screened using serum from a pig infected with 20,000 muscle larvae. The serum was obtained from multiple, time cours...

  4. OCCULT HEPATITIS B VIRUS INFECTION AMONG BLOOD DONORS WITH ANTIBODIES TO HEPATITIS B CORE ANTIGEN

    Directory of Open Access Journals (Sweden)

    A. Jafarzadeh

    2008-04-01

    Full Text Available Diagnosis of hepatitis B is routinely based on of serological assay of hepatitis B surface antigen (HBsAg. Occult hepatitis B virus (HBV infection is generally defined as the detection of HBV -DNA in the serum or tissues of subjects who have negative test for HBsAg. Transmission of HBV infection has been documented from HBsAg negative, anti-HBc positive blood and organ donors. The aim of this study was to determine the rate of occult HBV infection among HBsAg negative and anti-HBc positive blood donors of Rafsanjan blood transfusion center. ‎ Sera from 270 healthy blood donors who were negative for both HBsAg and anti-HCV, were tested for anti-HBc antibodies by use of ELISA technique. The samples that were negative for HBsAg but positive for anti-HBc markers also examined for the presence of HBV-DNA by polymerase chain reaction (PCR. ‎ Out of 270 HBsAg negative blood samples, 14 samples (5.18% were positive for anti-HBc antibodies. HBV-DNA was detected in 4/14 (28.57% of HBsAg negative and anti-HBc positive samples. Moreover, anti-HBs antibody was detected in 2/4 (50% of HBV-DNA positive samples. ‎ These results indicated that HBV-DNA found in the majority of HBsAg negative and anti-HBc-positive donors. In addition, the present study recommend the incorporation of routine anti-HBc screening of blood as a surrogate marker of occult HBV infection to prevent some transfusion-transmitted HBV infections.

  5. Stage and strain specific expression of the tandemly repeated 90 kDa surface antigen gene family in Trypanosoma cruzi.

    Science.gov (United States)

    Beard, C A; Wrightsman, R A; Manning, J E

    1988-04-01

    A recombinant cDNA library constructed in the expression vector lambda gtll using mRNA from the trypomastigote stage of Trypanosoma cruzi was screened with two monoclonal antibodies that have been shown to react with a 105 kDa and a 90 kDa surface antigen in trypomastigotes of the Peru and Y strains of T. cruzi. One recombinant lambda phage, designated Tcc-20, was reactive to both monoclonals. The beta-galactosidase/T. cruzi hybrid protein encoded in Tcc-20 is recognized by the monoclonal antibodies and by serum antibodies from mice infected with strains of T. cruzi which contain the 90 kDa antigen. Antibodies immunoselected from serum of mice infected with the Peru strain by adsorption to Tcc-20 fusion protein react specifically with a 90 kDa polypeptide in trypomastigote but not epimastigote lysates of T. cruzi. The mRNA complementary to the DNA insert in Tcc-20 is present only in those stages and strains of T. cruzi which express the 90 kDa surface antigen. These characteristics are strong evidence that the T. cruzi DNA fragment cloned into Tcc-20 encodes a portion of the 90 kDa surface antigen. The gene(s) which encodes this polypeptide is shown to be present in approximately 20 copies per haploid genome and most, and possibly all, of the copies are found in a tandemly linked multigene family.

  6. In vitro antigenic stimulation of peripheral blood and lymph node lymphocytes of sensitized guinea-pigs: the effect of a second administration of antigen in vivo

    Science.gov (United States)

    Housley, J.; Gell, P. G. H.

    1969-01-01

    Stimulation of DNA synthesis by a guinea-pig albumin—orthanilic acid conjugate (AO) and by tuberculin purified protein derivative (PPD) was obtained in in vitro cultures of peripheral blood and lymph node lymphocytes from guinea-pigs with delayed hypersensitivity to these antigens. Animals sensitized to both AO and PPD were given a further injection of 5 μg AO, intravenously, 8 hours before killing for in vitro studies. In these guinea-pigs, peripheral blood cultures, but not lymph node cultures, showed greater DNA synthesis in response to both AO and PPD than cultures from controls not given a further injection of AO. It is suggested that the further increase in DNA synthesis was due to non-specific lymphocyte `activation' following the interaction of antigen and specifically sensitized lymphocytes. PMID:5352364

  7. Identification of candidate antigens from adult stages of Toxocara canis for the serodiagnosis of human toxocariasis

    Directory of Open Access Journals (Sweden)

    Patrícia Longuinhos Peixoto

    2011-03-01

    Full Text Available In the present work, we identified adult Toxocara canis antigens through sodium dodecyl sulfate-polyacrylamide gel electrophoresis for potential use in human toxocariasis immunodiagnosis. The sensitivity and specificity of several semi-purified antigens, as well as their cross-reactivity with other parasitic infections, were assessed by IgM and IgG-enzime linked immunosorbent assay. Whilst we found that the crude extract of the parasite presented limited sensitivity, specificity and high cross-reactivity against other parasites, we identified 42, 58, 68 and 97-kDa semi-purified antigens as the most promising candidates for immunodiagnosis. Moreover, the 58 and 68-kDa antigens presented the lowest IgM cross-reactivity. When tested as a combination, a mixture of the 58 and 68-kDa antigens presented 100% sensitivity and specificity, as well as minor cross-reactivity. Although the combination of the 42, 58, 68 and 97-kDa antigens presented 100% sensitivity at a dilution of 1:40, the low specificity and high cross-reactivity observed suggested a limited use for diagnostic purposes. Our data suggested that the 58 and 68-kDa antigens might be most suitable for the immunodiagnosis of human toxocariasis.

  8. Antibody to histo-blood group A antigen neutralizes HIV produced by lymphocytes from blood group A donors but not from blood group B or O donors

    DEFF Research Database (Denmark)

    Arendrup, M; Hansen, J E; Clausen, H;

    1991-01-01

    for virus neutralization by the monoclonal antibody (MAb) AH16 directed against the blood group A epitope. MAb AH16 was previously shown to inhibit cell-free virus infection using HTLV-IIIB propagated in H9 cells. AH16 showed a concentration-dependent inhibition of the HTLV-IIIB/lyA isolate but did...... not inhibit the HTLV-IIIB/lyB or the HTLV-IIIB/lyO isolate. Specificity of the MAb-mediated inhibition was shown using A-antigen (tetrasaccharide). Thus, HIV infection of PBMC from donors with blood type A appears to induce expression of host-cell-encoded carbohydrate blood group A epitope on HIV which can......Three virus isolates HTLV-IIIB/lyA, HTLV-IIIB/lyB and HTLV-IIIB/lyO, obtained by passaging and propagating the HTLV-IIIB/H9 isolate in three separate cultures of mixed peripheral blood mononuclear cells (PBMC) from donors of blood type A, B or O, respectively, were tested for susceptibility...

  9. Cord Blood Derived CD4+CD25high T Cells Become Functional Regulatory T Cells upon Antigen Encounter

    Science.gov (United States)

    Mayer, Elisabeth; Bannert, Christina; Gruber, Saskia; Klunker, Sven; Spittler, Andreas; Akdis, Cezmi A.

    2012-01-01

    Background: Upon antigen exposure, cord blood derived T cells respond to ubiquitous environmental antigens by high proliferation. To date it remains unclear whether these “excessive” responses relate to different regulatory properties of the putative T regulatory cell (Treg) compartment or even expansion of the Treg compartment itself. Methods: Cord blood (>37 week of gestation) and peripheral blood (healthy controls) were obtained and different Treg cell subsets were isolated. The suppressive potential of Treg populations after antigen exposure was evaluated via functional inhibition assays ([3H]thymidine incorporation assay and CFSE staining) with or without allergen stimulation. The frequency and markers of CD4+CD25highFoxP3+ T cells were characterized by mRNA analysis and flow cytometry. Results: Cord blood derived CD4+CD25high cells did not show substantial suppressor capacity upon TCR activation, in contrast to CD4+CD25high cells freshly purified from adult blood. This could not be explained by a lower frequency of FoxP3+CD4+CD25highcells or FOXP3 mRNA expression. However, after antigen-specific stimulation in vitro, these cells showed strong proliferation and expansion and gained potent suppressive properties. The efficiency of their suppressive capacity can be enhanced in the presence of endotoxins. If T-cells were sorted according to their CD127 expression, a tiny subset of Treg cells (CD4+CD25+CD127low) is highly suppressive even without prior antigen exposure. Conclusion: Cord blood harbors a very small subset of CD4+CD25high Treg cells that requires antigen-stimulation to show expansion and become functional suppressive Tregs. PMID:22272233

  10. Atomic force microscopy measurements reveal multiple bonds between Helicobacter pylori blood group antigen binding adhesin and Lewis b ligand.

    Science.gov (United States)

    Parreira, P; Shi, Q; Magalhaes, A; Reis, C A; Bugaytsova, J; Borén, T; Leckband, D; Martins, M C L

    2014-12-01

    The strength of binding between the Helicobacter pylori blood group antigen-binding adhesin (BabA) and its cognate glycan receptor, the Lewis b blood group antigen (Le(b)), was measured by means of atomic force microscopy. High-resolution measurements of rupture forces between single receptor-ligand pairs were performed between the purified BabA and immobilized Le(b) structures on self-assembled monolayers. Dynamic force spectroscopy revealed two similar but statistically different bond populations. These findings suggest that the BabA may form different adhesive attachments to the gastric mucosa in ways that enhance the efficiency and stability of bacterial adhesion.

  11. The abundance and organization of polypeptides associated with antigens of the Rh blood group system.

    Science.gov (United States)

    Gardner, B; Anstee, D J; Mawby, W J; Tanner, M J; von dem Borne, A E

    1991-06-01

    Twelve murine monoclonal antibodies, which react with human red cells of common Rh phenotype but give weak or negative reactions with Rh null erythrocytes, were used in quantitative binding assays and competitive binding assays to investigate the abundance and organization of polypeptides involved in the expression of antigens of the Rh blood group system. Antibodies of the R6A-type (R6A, BRIC-69, BRIC-207) and the 2D10-type (MB-2D10, LA18.18, LA23.40) recognize related structures and 100,000-200,000 molecules of each antibody bind maximally to erythrocytes of common Rh phenotype. Antibodies of the BRIC-125 type (BRICs 32, 122, 125, 126, 168, 211) recognize structures that are unrelated to those recognized by R6A-type and 2D10-type antibodies and between 10,000 and 50,000 antibody molecules bind maximally to erythrocytes of the common Rh phenotype. The binding of antibodies of the R6A-type and the 2D10-type, but not of antibodies of the BRIC-125-type could be partially inhibited by human anti-D antibodies (polyclonal and monoclonal) and a murine anti-e-like antibody. These results are consistent with evidence (Moore & Green 1987; Avent et al., 1988b) that the Rh blood group antigens are associated with a complex that comprises two groups of related polypeptides of M(r) 30,000 and M(r) 35,000-100,000, respectively, and suggest that there are 1-2 x 10(5) copies of this complex per erythrocyte. The polypeptide recognized by antibodies of the BRIC-125 type is likely to be associated with this complex.

  12. Evolutionary analysis of HBV "S" antigen genetic diversity in Iranian blood donors: a nationwide study.

    Science.gov (United States)

    Pourkarim, Mahmoud Reza; Sharifi, Zohre; Soleimani, Ali; Amini-Bavil-Olyaee, Samad; Elsadek Fakhr, Ahmed; Sijmons, Steven; Vercauteren, Jurgen; Karimi, Gharib; Lemey, Philippe; Maes, Piet; Alavian, Seyed Moayed; Van Ranst, Marc

    2014-01-01

    The genetic diversity of the HBV S gene has a significant impact on the prophylaxis and treatment of hepatitis B infection. The effect of selective pressure on this genetic alteration has not yet been studied in Iranian blood donors. To explore HBV evolution and to analyze the effects and patterns of hepatitis B surface antigen (HBsAg) mutations on blood screening assays, 358 Iranian blood donors diagnosed as asymptomatic HBV carriers were enrolled in this nationwide study. Large S and partial S genes were amplified and sequenced. HBV (sub) genotypes and synonymous and nonsynonymous mutations were investigated. The impact of naturally occurring mutations on HBsAg ELISA results was explored. Phylogenetic analyses revealed that isolated strains were of genotype D. The dominant subgenotype/subtype was D1/ayw2. Deletions and naturally occurring stop codons in the pre-S1 and major hydrophilic region (MHR) were identified. In total, 32.8% of the studied strains harbored 195 single or multiple mutations in the MHR, the majority of which were located at the first loop of the "a determinant" domain. The ayw2 subtype showed a significant effect on the ELISA signal/cut-off value and carried fewer mutations in the MHR. Nonsynonymous/synonymous substitution value indicated that negative selection was the dominant evolutionary force in the HBV S gene. This nationwide study revealed that mutation frequency of HBsAg among Iranian blood donors was much higher than previous reports from the different local regions. These findings regarding the significant differences in reactivity of ELISA among different subtypes of HBV and its correlation with the number of mutations at the MHR will be valuable to public health authorities.

  13. ABH and Lewis antigen distributions in blood, saliva and gastric mucosa and H pylori infection in gastric ulcer patients

    Institute of Scientific and Technical Information of China (English)

    Luisa Caricio Martins; Juciclayton Tavares de Souza; Tereza Cristina de Oliveira Corvelo; Henrique Takeshi Oti; Rosane do Socorro Pompeu Loiola; Délia Cristina Figueira Aguiar; Katarine Ant(o)nia dos Santos Barile; Renata Kelly Costa do Amaral; Hivana Patricia Melo Barbosa; Amanda Alves Fecury

    2006-01-01

    AIM: To investigate the ABH and Lewis antigen expression in erythrocytes, saliva and gastric epithelium, as well as the association between H pylori and the presence of gastric epithelial lesions.METHODS: The distribution of ABH and Lewis blood group antigens in erythrocytes, saliva and gastric mucosa of H pylori-infected gastric ulcer patients was analyzed. Forty-two patients with gastric ulcer were studied,and fifty healthy individuals were used as control group.The blood group antigens were determined by direct hemagglutination, dot-ELISA and immunohistochemicai methods in erythrocytes, saliva and gastric mucosa specimens, respectively. Diagnosis for H pylori infection was performed by conventional optical microscopy and ELISA.RESULTS: A higher seroprevalence of IgG H pylori specific antibodies was observed in gastric ulcer patients (90%) compared to the control group (60%). We observed a significant increase of phenotypes O, A2 and Lewis b in H pylori-infected patients. The expression of these antigens had progressive alterations in areas of ulcerous lesions and intestinal metaplasia.CONCLUSION: ABH and Lewis blood group antigens are a good indicator for cellular alterations in the gastric epithelium.

  14. Quantifying cell binding kinetics mediated by surface-bound blood type B antigen to immobilized antibodies

    Institute of Scientific and Technical Information of China (English)

    LI BaoXia; CHEN Juan; LONG Mian

    2008-01-01

    Cell adhesion is crucial to many biological processes, such as inflammatory responses, tumor metastasis and thrombosis formation. Recently a commercial surface plasmon resonance (SPR)-based BIAcore biosensor has been extended to determine cell binding mediated by surface-bound biomolecular interactions. How such cell binding is quantitatively governed by kinetic rates and regulating factors, however, has been poorly understood. Here we developed a novel assay to determine the binding kinetics of surface-bound biomolecular interactions using a commercial BIAcore 3000 biosensor. Human red blood cells (RBCs) presenting blood group B antigen and CM5 chip bearing immobilized anti-B monoclonal antibody (mAb) were used to obtain the time courses of response unit, or sensorgrams, when flowing RBCs over the chip surface. A cellular kinetic model was proposed to correlate the sensorgrams with kinetic rates. Impacts of regulating factors, such as cell concentration,flow duration and rate, antibody-presenting level, as well as Ph value and osmotic pressure of suspending medium were tested systematically, which imparted the confidence that the approach can be applied to kinetic measurements of cell adhesion mediated by surface-bound biomolecular interactions.These results provided a new insight into quantifying cell binding using a commercial SPR-based BIAcore biosensor.

  15. Use of dried blood spots to define antibody response to the Strongyloides stercoralis recombinant antigen NIE.

    Science.gov (United States)

    Mounsey, Kate; Kearns, Therese; Rampton, Melanie; Llewellyn, Stacey; King, Mallory; Holt, Deborah; Currie, Bart J; Andrews, Ross; Nutman, Thomas; McCarthy, James

    2014-10-01

    An approach to improve the diagnosis of Strongyloides stercoralis infection is the use of serologic assays utilising the NIE antigen from S. stercoralis, with good diagnostic sensitivity and excellent specificity reported. Detection of antibody eluted from dried blood spots (DBS) has shown utility in large-scale seroepidemiological studies for a range of conditions and is appealing for use with children where sample collection is difficult. We adapted an existing NIE-enzyme linked immunosorbent assay (ELISA) for the testing of strongyloides antibody response on DBS, and evaluated it in a population screening and mass drug administration programme (MDA) for strongyloidiasis conducted in an Australian indigenous community. Study participants were treated with 200 μg/kg ivermectin (>15 kg) or 3× 400 mg albendazole (stercoralis NIE-DBS prior to MDA treatment, and 6 of 50 participants (12.0%) tested positive after treatment. These prevalence values are similar to those documented by standard serology in the same community. For 30 participants where a DBS was collected at both MDA 1 and 2, a significant decline in ELISA values was evident post treatment (0.12-0.02, p=0.0012). These results are in agreement with previous studies documenting the high seroprevalence of S. stercoralis in remote Australian Indigenous communities, and suggest that collection of dried blood spots may be a useful approach for field diagnosis of S. stercoralis seroprevalence.

  16. Analysis of GAGE, NY-ESO-1 and SP17 cancer/testis antigen expression in early stage non-small cell lung carcinoma

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Pøhl, Mette; Olsen, Karen E;

    2013-01-01

    NSCLC has shown promising results. However, little is known about the expression of other cancer/testis antigens in NSCLC. In the present study the expression of cancer/testis antigens GAGE, NY-ESO-1 and SP17 was investigated in patients with completely resected, early stage, primary NSCLC....

  17. Maternal ABO and rhesus blood group phenotypes and hepatitis B surface antigen carriage.

    Science.gov (United States)

    Lao, T T; Sahota, D S; Chung, M-K; Cheung, T K W; Cheng, Y K Y; Leung, T Y

    2014-11-01

    In view of a persistently high prevalence of hepatitis B surface antigen (HBsAg) carriage in our obstetric population, we examined the association between HBsAg carriage with maternal ABO and rhesus (Rh) blood group phenotypes determined at routine antenatal screening. In a retrospective study, the antenatal screening results of women booked for confinement between 1998 and 2011 in our hospital were examined for the relationship between HBsAg carriage with the ABO and rhesus blood groups, taking into account also the effects of advanced maternal age (≥ 35 years) and parity status (nulliparous or multiparous), and year of birth before or following the availability of the hepatitis B vaccine (1984). HBsAg carriage was found in 9.9%, 9.6%, 9.1% and 10.2% (P = 0.037) for group-A (n = 20 581 or 26.1%), -B (n = 20 744 or 26.4%), -AB (n = 5138 or 6.5%) and -O (n = 32 242 or 41.0%) among the 78705 women in the study cohort. Rhesus negativity was found in 0.6%, and HBsAg carriage was 12.3% and 9.8%, respectively, for the Rh-negative and Rh-positive women (P = 0.071). Carriage rate between group-O and non-O was influenced by nulliparity, age ≥ 35 years and Rh-positive status. Regression analysis indicated that group-B (P = 0.044, aOR = 1.062, 95% CI 1.002-1.127) and group-AB (P = 0.016, aOR = 1.134, 95% CI 1.024-1.256) were associated with HBsAg carriage. Blood groups-B and -AB are associated with increased hepatitis B virus (HBV) infection in our population, and further studies are warranted to elucidate the implications of this on the sequelae of HBV infection.

  18. The value of F-18 fluorodeoxyglucose positron emission tomography/computed tomography in asymptomatic examinees with unexplained elevated blood carcinoembryonic antigen levels

    Energy Technology Data Exchange (ETDEWEB)

    Li, Wenfeng [The First Affiliated Hospital of Wenzhou Medical University, Laboratory for Advanced Interdisciplinary Research, Institutes of Translational Medicine, Wenzhou (China); The First Affiliated Hospital of Wenzhou Medical University, Department of Radiation Oncology, Wenzhou (China); Yin, Weiwei [The First Affiliated Hospital of Wenzhou Medical University, Division of PET/CT, Department of Radiology, Wenzhou (China); Ou, Rongying [The First Affiliated Hospital of Wenzhou Medical University, Laboratory for Advanced Interdisciplinary Research, Institutes of Translational Medicine, Wenzhou (China); The First Affiliated Hospital of Wenzhou Medical University, Department of Gynaecology and Obstetrics, Wenzhou (China); Chen, Ting; Xiong, Lingling; Xu, Yunsheng [The First Affiliated Hospital of Wenzhou Medical University, Laboratory for Advanced Interdisciplinary Research, Institutes of Translational Medicine, Wenzhou (China); The First Affiliated Hospital of Wenzhou Medical University, Department of Dermatovenereology, Wenzhou (China); Cheng, Dezhi; Xie, Deyao [The First Affiliated Hospital of Wenzhou Medical University, Laboratory for Advanced Interdisciplinary Research, Institutes of Translational Medicine, Wenzhou (China); The First Affiliated Hospital of Wenzhou Medical University, Department of Cardiothoracic Surgery, Wenzhou (China); Zheng, Xiangwu; Zhao, Liang [The First Affiliated Hospital of Wenzhou Medical University, Laboratory for Advanced Interdisciplinary Research, Institutes of Translational Medicine, Wenzhou (China); The First Affiliated Hospital of Wenzhou Medical University, Division of PET/CT, Department of Radiology, Wenzhou (China); The First Affiliated Hospital of Wenzhou Medical University, Institutes of Intelligent and Molecular Imaging, Wenzhou (China)

    2016-04-15

    Cancer is still a clinical challenge, with many efforts invested in order to achieve timely detection. Unexplained elevated blood carcinoembryonic antigen levels are occasionally observed in an asymptomatic population and considered as a risk factor of cancers. The purpose of this study was to determine the validity of 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography (F-18 FDG-PET/CT) for detecting cancer in an asymptomatic population with an unexplained elevation in blood carcinoembryonic antigen (CEA) levels. This retrospective study included a total of 1920 asymptomatic examinees conducted from August 2011 through September 2013. The participants underwent CEA assay and conventional medical imaging (CEA-conventional), or CEA assay and F-18 FDG-PET/CT (CEA-PET/CT). The validity of conventional medical imaging and CEA-PET/CT scanning for detecting cancer and early-stage cancer in an asymptomatic population with an unexplained elevation in blood CEA levels were evaluated. Sensitivity, specificity, cancer detection rate, missed cancer detection rate, early-stage cancer detection rate, and early-stage cancer ratio using the CEA-PET/CT scanning were 96.6 %, 100 %, 10.4 %, 0.4 %, 3.7 %, and 34.5 %, respectively. In contrast, the corresponding values obtained using the conventional medical imaging were 50.6 % (P < 0.0001), 100 % (P > 0.9999), 50.6 % (P < 0.0001), 99.9 % (P = 0.055), 2.6 % (P < 0.0001), 2.5 % (P = 0.04), 0.7 % (P = 0.0004), and 14.5 % (P = 0.002), respectively. The F-18 FDG-PET/CT scanning significantly improved the validity of the cancer detection program in the asymptomatic population with an unexplained elevation in CEA levels. (orig.)

  19. Inhibition of histo-blood group antigen binding as a novel strategy to block norovirus infections.

    Directory of Open Access Journals (Sweden)

    Xu-Fu Zhang

    Full Text Available Noroviruses (NoVs are the most important viral pathogens that cause epidemic acute gastroenteritis. NoVs recognize human histo-blood group antigens (HBGAs as receptors or attachment factors. The elucidation of crystal structures of the HBGA-binding interfaces of a number of human NoVs representing different HBGA binding patterns opens a new strategy for the development of antiviral compounds against NoVs through rational drug design and computer-aided virtual screening methods. In this study, docking simulations and virtual screening were used to identify hit compounds targeting the A and B antigens binding sites on the surface of the capsid P protein of a GII.4 NoV (VA387. Following validation by re-docking of the A and B ligands, these structural models and AutoDock suite of programs were used to screen a large drug-like compound library (derived from ZINC library for inhibitors blocking GII.4 binding to HBGAs. After screening >2 million compounds using multistage protocol, 160 hit compounds with best predicted binding affinities and representing a number of distinct chemical classes have been selected for subsequent experimental validation. Twenty of the 160 compounds were found to be able to block the VA387 P dimers binding to the A and/or B HBGAs at an IC50<40.0 µM, with top 5 compounds blocking the HBGA binding at an IC50<10.0 µM in both oligosaccharide- and saliva-based blocking assays. Interestingly, 4 of the top-5 compounds shared the basic structure of cyclopenta [a] dimethyl phenanthren, indicating a promising structural template for further improvement by rational design.

  20. Crosstalk between ABO and Forssman (FORS) blood group systems: FORS1 antigen synthesis by ABO gene-encoded glycosyltransferases

    Science.gov (United States)

    Yamamoto, Miyako; Cid, Emili; Yamamoto, Fumiichiro

    2017-01-01

    A and B alleles at the ABO genetic locus specify A and B glycosyltransferases that catalyze the biosynthesis of A and B oligosaccharide antigens, respectively, of blood group ABO system which is important in transfusion and transplantation medicine. GBGT1 gene encodes Forssman glycolipid synthase (FS), another glycosyltransferase that produces Forssman antigen (FORS1). Humans are considered to be Forssman antigen-negative species without functional FS. However, rare individuals exhibiting Apae phenotype carry a dominant active GBGT1 gene and express Forssman antigen on RBCs. Accordingly, FORS system was recognized as the 31st blood group system. Mouse ABO gene encodes a cis-AB transferase capable of producing both A and B antigens. This murine enzyme contains the same GlyGlyAla tripeptide sequence as FSs at the position important for the determination of sugar specificity. We, therefore, transfected the expression construct into appropriate recipient cells and examined whether mouse cis-AB transferase may also exhibit FS activity. The result was positive, confirming the crosstalk between the ABO and FORS systems. Further experiments have revealed that the introduction of this tripeptide sequence to human A transferase conferred some, although weak, FS activity, suggesting that it is also involved in the recognition/binding of acceptor substrates, in addition to donor nucleotide-sugars. PMID:28134301

  1. Relationship between blood pressure variability and different renal function impairment stages in elderly hypertension patients

    Institute of Scientific and Technical Information of China (English)

    王云

    2014-01-01

    Objective To observe the change of blood pressure variability(BPV)in elderly hypertension patients,and to analyze the correlation between BPV and stages of renal function damage.Methods 127 elderly primary hypertensive patients with chronic kidney disease(CKD)were divided into three groups:stage 2 CKD group(aged 60-

  2. Functional expression of CD95/Fas Antigen and Bcl-2 on Cord blood Hematopoietic Progenitor Cells

    Institute of Scientific and Technical Information of China (English)

    马艳萍; 邹萍

    2002-01-01

    The cell-surface expression and functional status of the CD95/Fas antigen on primitive hematopoietic progenitors isolated from human cord blood (CB) were studied. The CD34+ cells freshly isolated from CB displayed low CD95 expression. The combinations of cytokines such as SCF+FL could up-regulate the expression of CD95 in vitro culture and tumor necrosis factor-e (TNF-α) and interon-γ (IFN-γ) further increased the CD95 expression induced by positive cytokines. The functional status of CD95-mediated apoptosis were analyzed by incubation of CD34+CB cells in the presence of anti-CD95 monoclonal antibodies (McAbs). The effects of anti-CD95 McAbs were measured by viable cell counting, flow cytometry, LTIC and CFU-C assays. A decrease of viable cells, CFUC and LTIC numbers were observed in the presence of anti-CD95 McAbs and TNF-α or IFN-γ.However, growth factor deprivation or the early-acting cytokine such as SCF and FL cross-linking to CD95 caused low apoptosis of CD34+ cells. The correlation of increased intracytoplasmic levels of bcl2 and the presence of CD95 on fresh CB CD34+ cells suggested that bcl-2 might be involved in protecting against CD95-mediated apoptosis of CB CD34+ cells.

  3. Detection of Leptospira interrogans DNA and antigen in fixed equine eyes affected with end-stage equine recurrent uveitis.

    Science.gov (United States)

    Pearce, Jacqueline W; Galle, Laurence E; Kleiboeker, Steve B; Turk, James R; Schommer, Susan K; Dubielizig, Richard R; Mitchell, William J; Moore, Cecil P; Giuliano, Elizabeth A

    2007-11-01

    Equine recurrent uveitis (ERU) is the most frequent cause of blindness in horses worldwide. Leptospira has been implicated as an etiologic agent in some cases of ERU and has been detected in fresh ocular tissues of affected horses. The objective of this study was to determine the presence of Leptospira antigen and DNA in fixed equine ocular tissues affected with end-stage ERU. Sections of eyes from 30 horses were obtained. Controls included 1) 10 normal equine eyes and 2) 10 equine eyes with a nonrecurrent form of uveitis. The experimental group consisted of 10 eyes diagnosed with ERU based on clinical signs and histologic lesions. Sections were subjected to immunohistochemical staining with an array of rabbit anti-Leptospira polyclonal antibodies. DNA extractions were performed by using a commercial kit designed for fixed tissue. Real-time PCR analysis was completed on extracted DNA. The target sequence for PCR was designed from alignments of available Leptospira 16S rDNA partial sequences obtained from GenBank. Two of 10 test samples were positive for Leptospira antigen by immunohistochemical assay. Zero of 20 controls were positive for Leptospira antigen. All test samples and controls were negative for Leptospira DNA by real-time PCR analysis. Leptospira was detected at a lower frequency than that previously reported for fresh ERU-affected aqueous humor and vitreous samples. Leptospira is not frequently detectable in fixed ocular tissues of horses affected with ERU when using traditional immunohistochemical and real-time PCR techniques.

  4. Blood splash in lambs-a preliminary study using the one-stage prothrombin time test.

    Science.gov (United States)

    Restall, D J

    1981-02-01

    Lambs from a flock in which a high incidence of blood splash had been detected were examined using the one-stage prothrombin test. For comparison lambs from a commercial slaughter line were also examined. All the affected lambs and 35·4% from the slaughter line had extended prothrombin times, and a relationship between extended prothrombin times and the occurrence of blood splash was established. Investigation of the pastures grazed by the affected flock showed the presence of coumarin producing plants and grasses. Some coumarin drugs prolong one-stage prothrombin times, and more importantly, induce capillary fragility, thus predisposing animals to blood splash.

  5. Prevalence of Diego blood group antigen and the antibody in three ethnic population groups in Klang valley of Malaysia

    Directory of Open Access Journals (Sweden)

    Cheong Tar Wei

    2013-01-01

    Full Text Available Background: Diego blood group antigen, Di(a, is very rare among Caucasians and Blacks, but relatively common among the South American Indians and Asians of Mongolian origin. The antibody to Di(a is clinically significant to cause hemolytic disease in a new-born or hemolytic transfusion reaction. Objectives: This study was designed to determine the prevalence of Di(a antigen among the blood donors from the three major ethnic groups in Klang Valley of Malaysia as well as to find an incidence of an antibody of the Diego antigen, anti-Di(a, in a tertiary care hospital to ascertain the need to include Di(a+ red cells for an antibody screen cell panel. Materials and Methods: Serological tests were performed by column agglutination technique using commercial reagents and following instruction as per kit insert. Results: Di(a antigen was found with a frequency of 2.1% among the Malaysians donors in three ethnic groups viz, Malay, Chinese and Indian. It was present among 1.25% of 401 Malay, 4.01% of Chinese and 0.88% of 114 Indian origin donors. None of the 1442 patients, including 703 antenatal outpatients, had anti-Di(a in serum. Conclusion: The prevalence of Di(a antigen was found among the donors of all the three ethnic background with varying frequency. Inclusion of Di(a+ red cells in routine antibody screening program would certainly help in detection of this clinically significant antibody and to provide safe blood transfusion in the Klang Valley, though the incidence of antibody appears to be very low in the region.

  6. Longitudinal microarray analysis of cell surface antigens on peripheral blood mononuclear cells from HIV+ individuals on highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Wang Bin

    2008-03-01

    Full Text Available Abstract Background The efficacy of highly active antiretroviral therapy (HAART determined by simultaneous monitoring over 100 cell-surface antigens overtime has not been attempted. We used an antibody microarray to analyze changes in the expression of 135 different cell-surface antigens overtime on PBMC from HIV+ patients on HAART. Two groups were chosen, one (n = 6 achieved sustainable response by maintaining below detectable plasma viremia and the other (n = 6 responded intermittently. Blood samples were collected over an average of 3 years and 5–8 time points were selected for microarray assay and statistical analysis. Results Significant trends over time were observed for the expression of 7 cell surface antigens (CD2, CD3epsilon, CD5, CD95, CD36, CD27 and CD28 for combined patient groups. Between groups, expression levels of 10 cell surface antigens (CD11a, CD29, CD38, CD45RO, CD52, CD56, CD57, CD62E, CD64 and CD33 were found to be differential. Expression levels of CD9, CD11a, CD27, CD28 and CD52, CD44, CD49d, CD49e, CD11c strongly correlated with CD4+ and CD8+ T cell counts, respectively. Conclusion Our findings not only detected markers that may have potential prognostic/diagnostic values in evaluating HAART efficacy, but also showed how density of cell surface antigens could be efficiently exploited in an array-like manner in relation to HAART and HIV-infection. The antigens identified in this study should be further investigated by other methods such as flow cytometry for confirmation as biological analysis of these antigens may help further clarify their role during HAART and HIV infection.

  7. The peripheral blood fibrocyte is a potent antigen-presenting cell capable of priming naive T cells in situ.

    Science.gov (United States)

    Chesney, J; Bacher, M; Bender, A; Bucala, R

    1997-06-10

    Recent studies have identified a novel population of blood-borne cells, termed fibrocytes, that have a distinct cell surface phenotype (collagen+/CD13(+)/CD34(+)/CD45(+)), rapidly enter sites of tissue injury, and synthesize connective tissue matrix molecules. We found by flow cytometry that purified human fibrocytes express each of the known surface components that are required for antigen presentation, including class II major histocompatability complex molecules (HLA-DP, -DQ, and -DR), the costimulatory molecules CD80 and CD86, and the adhesion molecules CD11a, CD54, and CD58. Human fibrocytes induced antigen-presenting cell-dependent T cell proliferation when cultured with specific antigen and this proliferative activity was significantly higher than that induced by monocytes and nearly as high as that induced by purified dendritic cells. Mouse fibrocytes also were found to express the surface components required for antigen presentation and to function as potent APCs in vitro. Mouse fibrocytes pulsed in vitro with the HIV-proteins p24 or gp120 and delivered to a site of cutaneous injury were found to migrate to proximal lymph nodes and to specifically prime naive T cells. These data suggest that fibrocytes play an early and important role in the initiation of antigen-specific immunity.

  8. Biochemical identification of the bovine blood group M' antigen as a major histocompatibility complex class I-like molecule

    DEFF Research Database (Denmark)

    Hønberg, L S; Larsen, B; Koch, C;

    1995-01-01

    . To elucidate the structural relationship between BoLA-A16 and blood group antigen M', immunoprecipitation experiments on red and white cell lysates isolated from M'-A16 positive and negative cattle were carried out. These results showed that M(r) 44,000 and M(r) 12000 polypeptides can be precipitated from both......Absorption and elution experiments showed that it was impossible to separate antibodies against blood group factor M' from antibodies against bovine lymphocyte antigen (BoLA) A16 in an antiserum showing haemolytic activity against M' as well as lymphocytotoxic activity against BoLA-A16...... red and white cells isolated from M'-A16 positive animals, whereas no bands were seen in M'-A16 negative animals in precipitations with the same antibody. Precipitation with a crossreacting human beta 2-microglobulin (beta 2-m) specific antibody confirmed a class-I-like structure associated with beta...

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

    Science.gov (United States)

    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.

  10. The Plasmodium falciparum blood stages acquire factor H family proteins to evade destruction by human complement.

    Science.gov (United States)

    Rosa, Thiago F A; Flammersfeld, Ansgar; Ngwa, Che J; Kiesow, Meike; Fischer, Rainer; Zipfel, Peter F; Skerka, Christine; Pradel, Gabriele

    2016-04-01

    The acquisition of regulatory proteins is a means of blood-borne pathogens to avoid destruction by the human complement. We recently showed that the gametes of the human malaria parasite Plasmodium falciparum bind factor H (FH) from the blood meal of the mosquito vector to assure successful sexual reproduction, which takes places in the mosquito midgut. While these findings provided a first glimpse of a complex mechanism used by Plasmodium to control the host immune attack, it is hitherto not known, how the pathogenic blood stages of the malaria parasite evade destruction by the human complement. We now show that the human complement system represents a severe threat for the replicating blood stages, particularly for the reinvading merozoites, with complement factor C3b accumulating on the surfaces of the intraerythrocytic schizonts as well as of free merozoites. C3b accumulation initiates terminal complement complex formation, in consequence resulting in blood stage lysis. To inactivate C3b, the parasites bind FH as well as related proteins FHL-1 and CFHR-1 to their surface, and FH binding is trypsin-resistant. Schizonts acquire FH via two contact sites, which involve CCP modules 5 and 20. Blockage of FH-mediated protection via anti-FH antibodies results in significantly impaired blood stage replication, pointing to the plasmodial complement evasion machinery as a promising malaria vaccine target.

  11. Study on the Frequent Expression of Rodgers and Chido, Red Blood Cell Antigens, in Iranian Healthy Population

    OpenAIRE

    Fatemeh Yari; Fatemeh Sabaghi; Nadia Bagheri; Maryam Zaman Vaziri; Maryam Sobhani; Zohreh Sharifi; Mahmoud Mahmoudian Shooshtari

    2009-01-01

    Rodgers (Rg) and Chido (Ch) are blood-group antigens and they determine the fourthcomponentof human complement C4. Rodgers and Chido are associated with two C4isotypes (C4A and C4B). In addition to genotype determination, study on expression ofRg and Chido could be useful in disease studies.DNA was extracted from the whole blood of 60 normal individuals. Then, PCR amplificationof C4d gene fragment was followed by restriction digestion. This studydemonstrated that the frequency of Ch and Rg in...

  12. Flow-induced detachment of red blood cells adhering to surfaces by specific antigen-antibody bonds.

    OpenAIRE

    Xia, Z; Goldsmith, H L; van de Ven, T G

    1994-01-01

    Fixed spherical swollen human red blood cells of blood type B adhering on a glass surface through antigen-antibody bonds to monoclonal mouse antihuman IgM, adsorbed or covalently linked on the surface, were detached by known hydrodynamic forces created in an impinging jet. The dynamic process of detachment of the specifically bound cells was recorded and analyzed. The fraction of adherent cells remaining on the surface decreased with increasing hydrodynamic force. For an IgM coverage of 0.26%...

  13. Secretion of protective antigens by tissue-stage nematode larvae revealed by proteomic analysis and vaccination-induced sterile immunity.

    Science.gov (United States)

    Hewitson, James P; Ivens, Al C; Harcus, Yvonne; Filbey, Kara J; McSorley, Henry J; Murray, Janice; Bridgett, Stephen; Ashford, David; Dowle, Adam A; Maizels, Rick M

    2013-08-01

    Gastrointestinal nematode parasites infect over 1 billion humans, with little evidence for generation of sterilising immunity. These helminths are highly adapted to their mammalian host, following a developmental program through successive niches, while effectively down-modulating host immune responsiveness. Larvae of Heligmosomoides polygyrus, for example, encyst in the intestinal submucosa, before emerging as adult worms into the duodenal lumen. Adults release immunomodulatory excretory-secretory (ES) products, but mice immunised with adult H. polygyrus ES become fully immune to challenge infection. ES products of the intestinal wall 4th stage (L4) larvae are similarly important in host-parasite interactions, as they readily generate sterile immunity against infection, while released material from the egg stage is ineffective. Proteomic analyses of L4 ES identifies protective antigen targets as well as potential tissue-phase immunomodulatory molecules, using as comparators the adult ES proteome and a profile of H. polygyrus egg-released material. While 135 proteins are shared between L4 and adult ES, 72 are L4 ES-specific; L4-specific proteins correspond to those whose transcription is restricted to larval stages, while shared proteins are generally transcribed by all life cycle forms. Two protein families are more heavily represented in the L4 secretome, the Sushi domain, associated with complement regulation, and the ShK/SXC domain related to a toxin interfering with T cell signalling. Both adult and L4 ES contain extensive but distinct arrays of Venom allergen/Ancylostoma secreted protein-Like (VAL) members, with acetylcholinesterases (ACEs) and apyrase APY-3 particularly abundant in L4 ES. Serum antibodies from mice vaccinated with L4 and adult ES react strongly to the VAL-1 protein and to ACE-1, indicating that these two antigens represent major vaccine targets for this intestinal nematode. We have thus defined an extensive and novel repertoire of H

  14. Secretion of protective antigens by tissue-stage nematode larvae revealed by proteomic analysis and vaccination-induced sterile immunity.

    Directory of Open Access Journals (Sweden)

    James P Hewitson

    2013-08-01

    Full Text Available Gastrointestinal nematode parasites infect over 1 billion humans, with little evidence for generation of sterilising immunity. These helminths are highly adapted to their mammalian host, following a developmental program through successive niches, while effectively down-modulating host immune responsiveness. Larvae of Heligmosomoides polygyrus, for example, encyst in the intestinal submucosa, before emerging as adult worms into the duodenal lumen. Adults release immunomodulatory excretory-secretory (ES products, but mice immunised with adult H. polygyrus ES become fully immune to challenge infection. ES products of the intestinal wall 4th stage (L4 larvae are similarly important in host-parasite interactions, as they readily generate sterile immunity against infection, while released material from the egg stage is ineffective. Proteomic analyses of L4 ES identifies protective antigen targets as well as potential tissue-phase immunomodulatory molecules, using as comparators the adult ES proteome and a profile of H. polygyrus egg-released material. While 135 proteins are shared between L4 and adult ES, 72 are L4 ES-specific; L4-specific proteins correspond to those whose transcription is restricted to larval stages, while shared proteins are generally transcribed by all life cycle forms. Two protein families are more heavily represented in the L4 secretome, the Sushi domain, associated with complement regulation, and the ShK/SXC domain related to a toxin interfering with T cell signalling. Both adult and L4 ES contain extensive but distinct arrays of Venom allergen/Ancylostoma secreted protein-Like (VAL members, with acetylcholinesterases (ACEs and apyrase APY-3 particularly abundant in L4 ES. Serum antibodies from mice vaccinated with L4 and adult ES react strongly to the VAL-1 protein and to ACE-1, indicating that these two antigens represent major vaccine targets for this intestinal nematode. We have thus defined an extensive and novel

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

    Science.gov (United States)

    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.

  16. Correlation of antigen-specific IFN-γ responses of fresh blood samples from Mycobacterium avium subsp. paratuberculosis infected heifers with responses of day-old samples co-cultured with IL-12 or anti-IL-10 antibodies

    DEFF Research Database (Denmark)

    Mikkelsen, Heidi; Aagaard, Claus; Nielsen, Søren Saxmose;

    2012-01-01

    Paratuberculosis is a chronic infection of the intestine of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). Early stage MAP infection can be detected by measuring cell-mediated immune responses using the interferon gamma (IFN-γ) assay. Whole blood samples are cultured...... to enhance IFN-γ responses of cultures stimulated with Johnin purified protein derivative (PPDj). Here we examined the correlation of IFN-γ production in response to PPDj and 15 recombinant antigens in day-old blood samples from heifers 10–21 months of age from a MAP infected herd with addition of either...

  17. Clinical significance of preoperative carcinoembryonic antigen level in patients with clinical stage IA non-small cell lung cancer

    Science.gov (United States)

    Suda, Takashi; Hachimaru, Ayumi; Tochii, Daisuke; Tochii, Sachiko; Takagi, Yasushi

    2017-01-01

    Background The objective of this study was to assess the preoperative serum carcinoembryonic antigen (CEA) level in patients with clinical stage IA non-small cell lung cancer (NSCLC) and to evaluate its clinical significance. Methods Between January 2005 and December 2014, a total of 378 patients with clinical stage IA NSCLC underwent complete resection with systematic node dissection. The survival rate was estimated starting from the date of surgery to the date of either death or the last follow-up by the Kaplan-Meier method. Univariate analyses by log-rank tests were used to determine prognostic factors. Cox proportional hazards ratios were used to identify independent predictors of poor prognosis. Clinicopathological predictors of lymph node metastases were evaluated by logistic regression analyses. Results The 5-year survival rate of patients with an elevated preoperative serum CEA level was significantly lower than that of patients with a normal CEA level (75.5% vs. 87.7%; P=0.02). However, multivariate analysis did not show the preoperative serum CEA level to be an independent predictor of poor prognosis. Postoperative pathological factors, including lymphatic permeation, visceral pleural invasion, and lymph node metastases, tended to be positive in patients with an elevated preoperative serum CEA level. In addition, the CEA level was a statistically significant independent clinical predictor of lymph node metastases. Conclusions The preoperative serum CEA level was not an independent predictor of poor prognosis in patients with pathological stage IA NSCLC but was an important clinical predictor of tumor invasiveness and lymph node metastases in patients with clinical stage IA NSCLC. Therefore, measurement of the preoperative serum CEA level should be considered even for patients with early-stage NSCLC.

  18. The Relationship between Apoptosis and the Expression of Proliferating Cell Nuclear Antigen and the Clinical Stages in Gastric Carcinoma

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The relationship between the apoptosis and the expression of proliferating cell nuclear antigen (PCNA) and the clinical stages in gastric cancers was studied. By using terminal deoxynucleotidyl transferase-mediated nick end labelling (TUNEL) technique and PCNA immunohistochemical staining, the apoptosis and the expression of PCNA in tissue of gastric carcinoma were assayed in situ, the index of apoptosis (AI), index of PCNA (PI) and the rate of AI/PI were calculated. AI and PI in gastric cancer tissues were (6.5±3.7) % and (49.8±15.9) % respectively, and the rate of AI/PI was 0.13±0.05, which were obviously different from those of normal gastric mucosa in paragastric cancer (P<0.01). With the advanced TNM stages of gastric carcinoma, the AI was decreased, PI was increased and the rate of AI/PI decreased in gastric carcinoma. There was significant difference in them between the gastric cancer tissues and normal gastric mucosa in pericarcinoma in TNM stage Ⅱ to Ⅳ (P<0.05). It was suggested that the decreased apoptotic cells and the increased proliferating cells were obviously related to the tumor genesis and tumor progression in gastric carcinoma. The AI, PI and the rate of AI/PI would become the prognostic factors in advanced gastric carcinoma.

  19. Phase 1 Trial of AMA1-C1/Alhydrogel plus CPG 7909: An Asexual Blood-Stage Vaccine for Plasmodium falciparum Malaria

    OpenAIRE

    Mullen, Gregory E. D.; Ellis, Ruth D; Kazutoyo Miura; Elissa Malkin; Caroline Nolan; Mhorag Hay; Michael P Fay; Allan Saul; Daming Zhu; Kelly Rausch; Samuel Moretz; Hong Zhou; Long, Carole A.; Miller, Louis H.; John Treanor

    2008-01-01

    BACKGROUND: Apical Membrane Antigen 1 (AMA1), a polymorphic merozoite surface protein, is a leading blood-stage malaria vaccine candidate. This is the first reported use in humans of an investigational vaccine, AMA1-C1/Alhydrogel, with the novel adjuvant CPG 7909. METHODS: A phase 1 trial was conducted at the University of Rochester with 75 malaria-naive volunteers to assess the safety and immunogenicity of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine. Participants were sequentially enroll...

  20. The O-Linked Glycome and Blood Group Antigens ABO on Mucin-Type Glycoproteins in Mucinous and Serous Epithelial Ovarian Tumors.

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    Varvara Vitiazeva

    Full Text Available Mucins are heavily O-glycosylated proteins where the glycosylation has been shown to play an important role in cancer. Normal epithelial ovarian cells do not express secreted mucins, but their abnormal expression has previously been described in epithelial ovarian cancer and may relate to tumor formation and progression. The cyst fluids were shown to be a rich source for acidic glycoproteins. The study of these proteins can potentially lead to the identification of more effective biomarkers for ovarian cancer.In this study, we analyzed the expression of the MUC5AC and the O-glycosylation of acidic glycoproteins secreted into ovarian cyst fluids. The samples were obtained from patients with serous and mucinous ovarian tumors of different stages (benign, borderline, malignant and grades. The O-linked oligosaccharides were released and analyzed by negative-ion graphitized carbon Liquid Chromatography (LC coupled to Electrospray Ionization tandem Mass Spectrometry (ESI-MSn. The LC-ESI-MSn of the oligosaccharides from ovarian cyst fluids displayed differences in expression of fucose containing structures such as blood group ABO antigens and Lewis-type epitopes.The obtained data showed that serous and mucinous benign adenomas, mucinous low malignant potential carcinomas (LMPs, borderline and mucinous low-grade carcinomas have a high level of blood groups and Lewis type epitopes. In contrast, this type of fucosylated structures were low abundant in the high-grade mucinous carcinomas or in serous carcinomas. In addition, the ovarian tumors that showed a high level of expression of blood group antigens also revealed a strong reactivity towards the MUC5AC antibody. To visualize the differences between serous and mucinous ovarian tumors based on the O-glycosylation, a hierarchical cluster analysis was performed using mass spectrometry average compositions (MSAC.Mucinous benign and LMPs along with mucinous low-grade carcinomas appear to be different from

  1. Whole blood interferon-gamma responses to mycobacterium tuberculosis antigens in young household contacts of persons with tuberculosis in Uganda.

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    Deborah A Lewinsohn

    Full Text Available BACKGROUND: Due to immunologic immaturity, IFN-gamma-producing T cell responses may be decreased in young children compared to adults, thus we hypothesized that IFN-gamma responses to mycobacterial antigens in household contacts exposed to Mycobacterium tuberculosis (Mtb would be impaired in young children relative to adults. The objective of this study was to compare whole blood IFN-gamma production in response to mycobacterial antigens between children and adults in Uganda. METHODOLOGY/PRINCIPAL FINDINGS: We studied household contacts of persons with culture-positive pulmonary tuberculosis (TB enrolled in a cohort study conducted in Kampala, Uganda. Whole blood IFN-gamma production in response to Mtb culture-filtrate antigens was measured by ELISA and compared between infants ( or =15 years old, n = 528. We evaluated the relationship between IFN-gamma responses and the tuberculin skin test (TST, and between IFN-gamma responses and epidemiologic factors that reflect exposure to Mtb, and the effect of prior BCG vaccination on IFN-gamma responses. Young household contacts demonstrated robust IFN-gamma responses comparable to those of adults that were associated with TST and known risk factors for infection. There was no effect of prior BCG immunization on the IFN-gamma response. CONCLUSIONS/SIGNIFICANCE: Young children in a TB endemic setting can mount robust IFN-gamma responses generally comparable to those of adults, and as in adults, these responses correlated with the TST and known epidemiologic risk factors for Mtb infection.

  2. Study on the Frequent Expression of Rodgers and Chido, Red Blood Cell Antigens, in Iranian Healthy Population

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    Fatemeh Yari

    2009-01-01

    Full Text Available Rodgers (Rg and Chido (Ch are blood-group antigens and they determine the fourthcomponentof human complement C4. Rodgers and Chido are associated with two C4isotypes (C4A and C4B. In addition to genotype determination, study on expression ofRg and Chido could be useful in disease studies.DNA was extracted from the whole blood of 60 normal individuals. Then, PCR amplificationof C4d gene fragment was followed by restriction digestion. This studydemonstrated that the frequency of Ch and Rg in Iranian healthy population was98.3 and 93.4 percent, respectively. Additionally, 6.6 percent of the studied populationshowed Chido-positive, Rodger-negative and 1.7 percent showed Rodger-positive,Chido-negative genotype. It may be concluded that upon receiving blood transfusion,6.6 and 1.7 percent of individuals could produce anti-Rg and anti-Ch antibodies, respectively.

  3. Whole blood assay to access T cell-immune responses to Mycobacterium tuberculosis antigens in healthy Brazilian individuals

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    Paulo RZ Antas

    2004-02-01

    Full Text Available The production of interferon gamma (IFNgamma guarantees effective T cell-mediated immunity against Mycobacterium tuberculosis infection. In the present study, we simply compare the in vitro immune responses to Mycobacterium antigens in terms of IFNg production in a total of 10 healthy Brazilian volunteers. Whole blood and mononuclear cells were cultivated in parallel with PPD, Ag85B, and M. bovis hsp65, and five-days supernatants were harvested for cytokine detection by ELISA. The inter-assay result was that the overall profile of agreement in response to antigens was highly correlated (r² = 0.9266; p = 0.0102. Potential analysis is in current progress to dictate the usefulness of this method to access the immune responses also in tuberculosis patients and its contacts.

  4. Comparison of three feline leukaemia virus (FeLV) point-of-care antigen test kits using blood and saliva.

    Science.gov (United States)

    Westman, Mark E; Malik, Richard; Hall, Evelyn; Sheehy, Paul A; Norris, Jacqueline M

    2017-02-01

    Feline leukaemia virus (FeLV) can be a challenging infection to diagnose due to a complex feline host-pathogen relationship and occasionally unreliable test results. This study compared the accuracy of three point-of-care (PoC) FeLV p27 antigen test kits commonly used in Australia and available commercially worldwide (SNAP FIV/FeLV Combo, Witness FeLV/FIV and Anigen Rapid FIV/FeLV), using detection of FeLV provirus by an in-house real-time polymerase chain reaction (qPCR) assay as the diagnostic gold standard. Blood (n=563) and saliva (n=419) specimens were collected from a population of cats determined to include 491 FeLV-uninfected and 72 FeLV-infected individuals (45 progressive infections [p27 and qPCR positive], 27 regressive infections [p27 negative, qPCR positive]). Sensitivity and specificity using whole blood was 63% and 94% for SNAP Combo, 57% and 98% for Witness, and 57% and 98% for Anigen Rapid, respectively. SNAP Combo had a significantly lower specificity using blood compared to the other two kits (P=0.004 compared to Witness, P=0.007 compared to Anigen Rapid). False-positive test results occurred with all three kits using blood, and although using any two kits in parallel increased specificity, no combination of kits completely eliminated the occurrence of false-positive results. We therefore recommend FeLV proviral PCR testing for any cat that tests positive with a PoC FeLV antigen kit, as well as for any cat that has been potentially exposed to FeLV but tests negative with a FeLV antigen kit, before final assignment of FeLV status can be made with confidence. For saliva testing, sensitivity and specificity was 54% and 100%, respectively, for all three test kits. The reduced sensitivity of saliva testing compared to blood testing, although not statistically significant, suggests saliva testing with the current generation of PoC FeLV antigen kits is unsuitable for screening large populations of cats, such as in shelters.

  5. [The prevalence of hepatitis C antibodies among volunteer blood donors with elevated blood transaminase and antibodies to the B virus core antigen].

    Science.gov (United States)

    Gavilán Carrasco, J C; González Santos, P; Rosario Díaz, E

    1996-05-01

    The use of non-specific markers before 1989 (increased serum transaminase values and antibodies to hepatitis B core antigen) as a screening method for blood donors in an attempt to decrease the incidence of post-transfusional non-A non-B hepatitis (currently hepatitis C virus) was a matter of controversy. To determine the impact of the use of these markers on the detection of blood donors infected with hepatitis C virus, a prospective study was undertaken in Málaga (1988-1989) with 5,003 volunteer donors with two objectives: a) to know the prevalence of these non-specific markers (anti-HBc and increased serum transaminase) and antibodies to HCV (anti-C100) in our blood donor population; b) to determine whether the presence of some of these non specific markers in blood donors was associated with a higher rate of virus C infection. The prevalence of antibodies to HCV in blood donors with increased serum transaminase and/or anti-HBc was significantly higher than the prevalence found among the general blood donor population.

  6. Prevalence of hepatitis B surface antigen & its subtypes in high risk group subjects & voluntary blood donors in Bombay.

    Science.gov (United States)

    Elavia, A J; Banker, D D

    1991-09-01

    HBsAg positive subjects belonging to high risk groups and voluntary blood donors were analysed for prevalence of HBsAg among various groups of subjects for ascertaining the carrier status among the voluntary blood donors, HBsAg subtype distribution, and association of HBsAg with blood groups and caste or religion. The prevalence of HBsAg varied from 2.02 per cent in voluntary blood donors to 58.38 per cent in patients of acute viral hepatitis. 70.5 per cent subjects had subtype 'ay' while 23.9 per cent of the subjects had subtype 'ad'. We also found compound 'ady' subtype in 5.6 per cent of our subjects. HBsAg/adr, a subtype not usually prevalent in India, was found in 30 of the 90 'ad' sera. Co-occurrence of HBsAg and anti-HBs was noted in 9 subjects. Homotypic anti-HBs was found to occur together mainly in voluntary blood donors, while heterotypic anti-HBs was found to occur together mainly multi-transfused patients. There was no significant correlation between HBsAg and blood group antigens and a relatively higher incidence of HBsAg among the Jain community was observed.

  7. Association between absolute blood eosinophil count and CKD stages among cardiac patients.

    Science.gov (United States)

    Ishii, Rui; Fujita, Shu-Ichi; Kizawa, Shun; Sakane, Kazushi; Morita, Hideaki; Ozeki, Michishige; Sohmiya, Koichi; Hoshiga, Masaaki; Ishizaka, Nobukazu

    2016-02-01

    Elevated eosinophil count was shown to be associated with the development of cholesterol embolization syndrome, a potentially life-threatening condition, after catheter-based procedures. We investigated the association between stages of chronic kidney disease (CKD) and the absolute eosinophil count (AEC) among cardiac patients. CKD stages were determined solely on the estimated glomerular filtration rate or requirement for hemodialysis. Eosinophilia is defined as an eosinophil count exceeding 500/μL. A total of 1022 patients were enrolled in the current study, and eosinophil counts (/μL) in the first through fourth eosinophil count quartiles were blood pressure, and total white blood cell count. Similarly, after adjustment for the same variables, eosinophilia was associated with severe renal dysfunction with an odds ratio of 2.60 (95 % confidence interval, 1.08-6.26, P count was positively associated with higher CKD stages among cardiology patients, some fraction of which might be related to subclinical cholesterol embolization.

  8. Patterns of human genetic variation inferred from comparative analysis of allelic mutations in blood group antigen genes.

    Science.gov (United States)

    Patnaik, Santosh Kumar; Blumenfeld, Olga O

    2011-03-01

    Comparative analysis of allelic variation of a gene sheds light on the pattern and process of its diversification at the population level. Gene families for which a large number of allelic forms have been verified by sequencing provide a useful resource for such studies. In this regard, human blood group-encoding genes are unique in that differences of cell surface traits among individuals and populations can be readily detected by serological screening, and correlation between the variant cell surface phenotype and the genotype is, in most cases, unequivocal. Here, we perform a comprehensive analysis of allelic forms, compiled in the Blood Group Antigen Gene Mutation database, of ABO, RHD/CE, GYPA/B/E and FUT1/2 gene families that encode the ABO, RH, MNS, and H/h blood group system antigens, respectively. These genes are excellent illustrative examples showing distinct mutational patterns among the alleles, and leading to speculation on how their origin may have been driven by recurrent but different molecular mechanisms. We illustrate how alignment of alleles of a gene may provide an additional insight into the DNA variation process and its pathways, and how this approach may serve to catalog alleles of a gene, simplifying the task and content of mutation databases.

  9. Action of adrenalin on the circulation of the murine Plasmodium developing stages, in different blood compartments

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    Bertani S.

    2004-12-01

    Full Text Available Adrenalin was used to investigate in vivo the circulation of the different stages of rodent Plasmodium present in the blood. A single dose of adrenalin injected to mice infected with P. yoelii resulted immediately in i a diminution of the parasitaemia of approximately 50 % in the peripheral large vessels (estimated in tail blood films, as well as in the capillaries (estimated in smears of blood collected from a fed Anopheles, and ii an increased parasitaemia in blood collected by cardiac puncture from the right heart. The numbers of young stages of P. yoelii in the peripheral blood were initially somewhat reduced but, unexpectedly, midterm trophozoites were preferentially expelled from the peripheral blood into major organs like the heart. With P. vinckei, parasitaemia decreased only when midterm trophozoites predominated, and with P. chabaudi no effect was observed at any time. We propose that midterm trophozoites, by their increased surface area, as compared to rings, and their flexibility which contrasts with the rigid schizonts, are particularly susceptible to haemodynamic perturbations.

  10. IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

    Science.gov (United States)

    Sebina, Ismail; James, Kylie R.; Soon, Megan S. F.; Best, Shannon E.; Montes de Oca, Marcela; Amante, Fiona H.; Thomas, Bryce S.; Beattie, Lynette; Souza-Fonseca-Guimaraes, Fernando; Smyth, Mark J.; Hertzog, Paul J.; Hill, Geoffrey R.; Engwerda, Christian R.

    2016-01-01

    Parasite-specific antibodies protect against blood-stage Plasmodium infection. However, in malaria-endemic regions, it takes many months for naturally-exposed individuals to develop robust humoral immunity. Explanations for this have focused on antigenic variation by Plasmodium, but have considered less whether host production of parasite-specific antibody is sub-optimal. In particular, it is unclear whether host immune factors might limit antibody responses. Here, we explored the effect of Type I Interferon signalling via IFNAR1 on CD4+ T-cell and B-cell responses in two non-lethal murine models of malaria, P. chabaudi chabaudi AS (PcAS) and P. yoelii 17XNL (Py17XNL) infection. Firstly, we demonstrated that CD4+ T-cells and ICOS-signalling were crucial for generating germinal centre (GC) B-cells, plasmablasts and parasite-specific antibodies, and likewise that T follicular helper (Tfh) cell responses relied on B cells. Next, we found that IFNAR1-signalling impeded the resolution of non-lethal blood-stage infection, which was associated with impaired production of parasite-specific IgM and several IgG sub-classes. Consistent with this, GC B-cell formation, Ig-class switching, plasmablast and Tfh differentiation were all impaired by IFNAR1-signalling. IFNAR1-signalling proceeded via conventional dendritic cells, and acted early by limiting activation, proliferation and ICOS expression by CD4+ T-cells, by restricting the localization of activated CD4+ T-cells adjacent to and within B-cell areas of the spleen, and by simultaneously suppressing Th1 and Tfh responses. Finally, IFNAR1-deficiency accelerated humoral immune responses and parasite control by boosting ICOS-signalling. Thus, we provide evidence of a host innate cytokine response that impedes the onset of humoral immunity during experimental malaria. PMID:27812214

  11. Effects of a structured treatment algorithm on blood pressure goal rates in both stage 1 and stage 2 hypertension.

    Science.gov (United States)

    Neutel, J M; Smith, D H G; Silfani, T N; Lee, Y; Weber, M A

    2006-04-01

    This study analysed the efficacy of an angiotensin receptor blocker-based treatment algorithm for achieving goal blood pressure (BP) in patients with stage 1 (systolic BP (SBP) 140-159 mmHg or diastolic BP (DBP) 90-99 mmHg) or stage 2 (SBP > or = 160 mmHg or DBP > or = 100 mmHg) hypertension. In this 24-week, open-label, multicentre study, patients followed a six-step algorithm until goal BP (mmHg) was attained. Initially, olmesartan medoxomil 20 mg/day was administered for 4 weeks. The regimen was modified every 4 weeks until goal BP was attained: increase olmesartan medoxomil to 40 mg/day; add hydrochlorothiazide (HCTZ) 12.5 mg/day; increase HCTZ to 25 mg/day; add amlodipine besylate 5 mg/day; increase amlodipine besylate to 10 mg/day. In patients with stage 1 hypertension, 80% (63/79) and 56% (44/79) achieved BP goals of mmHg and mmHg, respectively, with olmesartan medoxomil monotherapy (94% (74/79) and 89% (70/79) with olmesartan medoxomil/HCTZ double therapy, and 96% (76/79) and 98% (77/79) with addition of amlodipine besylate (triple therapy)). Mean SBP/DBP reductions were 16.7/11.6, 24.8/15.8, and 26.4/16.5 mmHg for mono-, double-, and triple-therapy, respectively. In patients with stage 2 hypertension, 42% (42/100) and 19% (19/100) achieved BP goals of mmHg and mmHg, respectively, with monotherapy (75% (75/100) and 54% (54/100) with double therapy, and 90% (90/100) and 81% (81/100) with triple-therapy). Mean SBP/DBP reductions in stage 2 patients were 18.4/10.0, 32.7/16.3, and 39.1/19.4 mmHg for mono-, double, and triple therapy, respectively. Overall, most patients with stage 1 or stage 2 hypertension achieved goal BP.

  12. Disruption of transitional stages in 24-h blood pressure in renal transplant recipients

    Directory of Open Access Journals (Sweden)

    Marcelo E Katz

    2012-03-01

    Full Text Available Patients with kidney replacement exhibit disrupted circadian rhythms. Most studies measuring blood pressure use the dipper/non-dipper classification, which does not consider analysis of transitional stages between low and high blood pressure, confidence intervals nor shifts in the time of peak, while assuming subjective onsets of night and day phases. In order to better understand the nature of daily variation of blood pressure in these patients, we analyzed 24h recordings from 41 renal transplant recipients using the non-symmetrical double-logistic fitting assessment which does not assume abruptness nor symmetry in ascending and descending stages of the blood pressure profile, and a cosine best-fitting regression method (Cosinor. Compared with matched controls, double-logistic fitting showed that the times for most of transitional stages (ascending systolic and descending systolic, diastolic and mean arterial pressure had a wider distribution along the 24 h. The proportion of individuals without daily blood pressure rhythm in the transplanted group was larger only for systolic arterial pressure, and the amplitude showed no significant difference. Furthermore, the transplant recipient group had a less pronounced slope in descending systolic and ascending mean blood pressure. Cosinor analysis confirmed the phase related changes, showing a wider distribution of times of peak (acrophases. We conclude that daily disruptions in renal transplant recipients can be explained not only by absence in diurnal variation, but also in changes in waveform-related parameters of the rhythm, and that distortions in the phase of the rhythm are the most consistent finding for the patients.

  13. Antigen induced production of υ-interferon ex vivo, in the peripheral blood of patients with active pulmonary tuberculosis

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    Z. M. Zagdyn

    2013-01-01

    Full Text Available Tuberculosis (TB is one of the most significant problems in the Russian Health Care. Russia remains on the list of the 22 countries with a high TB incidence and on the third place in the world with a high prevalence of Drug Resistant TB [1]. It is urgently needed to develop new TB diagnostic methods as well as effective measures of the specific TB prevention, including a development of the novel vaccines, so we have to know better about the most immunogenic antigens of Mycobacterium Tuberculosis. We studied the Interferon-Q production in the whole blood after stimulating immune response with different proteins of Mycobacterium Tuberculosis in patients with active TB. The study results permitted us to evaluate the immunogenicity of the previously known proteins (Ag85a и ESAT-6 in comparison to the recently identified ones (Rv2957, Rv2958c и Rv0447, analyzing simultaneously their relation to tuberculin, as well as to antigens of the different viruses (Human Immunodeficiency Virus, Cytomegalovirus, Epstein-Barr Virus, Influenza Virus. Protein Rv2958c, unlike protein ESAT-6, showed the high immunogenicity in comparison to tuberculin. The expressed immunogenicity of protein Rv2958c might be indicated a possible greatest specificity of immune response to this antigen in TB patients. Meanwhile, bacillary tuberculosis was strongly associated with low immune response to this protein. Also we were found statistical differences in immune responses of patients to the different Mycobacterium Tuberculosis antigens depending on the drug sensitivity. In addition it was interesting to know about a significantly low immune response of patients with Drug Resistant TB to protein pp65 CMV.

  14. Seroprevalence of hepatitis B e antigen (HBe antigen and B core antibodies (IgG anti-HBcore and IgM anti-HBcore among hepatitis B surface antigen positive blood donors at a Tertiary Centre in Nigeria

    Directory of Open Access Journals (Sweden)

    Akinbami Akinsegun A

    2012-03-01

    Full Text Available Abstract Background Hepatitis B virus (HBV is a common cause of liver disease throughout the world. HBV is transmitted through blood and other body fluids, including semen and saliva. Chronic replication of HBV virons is characterized by persistence circulation of HBsAg, HBeAg and HBV DNA; usually with anti-HBc and occasionally with anti-HBs. Aim: To determine the prevalence of HBeAg, IgG anti-HBcore and IgM anti-HBcore amongst HBsAg positive blood donors. These parameters are reflective of transmissibility and active hepatitis B infection. A cross sectional study was carried out at the blood donor clinics of Lagos State University Teaching Hospital Ikeja and Lagos University Teaching Hospital Idiaraba. A total of 267 donors were recruited to determine HBe antigen, IgG and IgM anti-HBcore antibodies amongst hepatitis BsAg positive donors. Five milliliters of blood was collected from those who tested positive to HBsAg screen during donation. The sera were subjected to enzyme linked immunosorbent assay (ELISA. Pearson chi-squared test was used for the analytical assessment. Findings A total number of 267 HBsAg positive blood donors were studied. A seroprevalence of 8.2% (22 of 267 HBeAg was obtained, 4 of 267 (1.5% were indeterminate while 241 (90.3% tested negative. Only 27 out of 267 donors (10.1% tested positive to IgM anti-HBcore, 234(87.6% tested negative, while 6(2.2% were indeterminate. A higher percentage of 60.7% (162 of 267 tested positive to IgG anti-HBcore, while 39.3% (105 of 267 tested negative. Conclusion There is a low seroprevalence rate of HBeAg-positive chronic hepatitis and relatively high IgG anti-HBcore and IgM anti-HBcore rates in South West Nigeria.

  15. Clinical significance of serum carbohydrate antigen 19-9 and its relationship with blood glucose in patients with type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    武秀玲

    2013-01-01

    Objective To study the relationship between serum carbohydrate antigen 19-9 (CA19-9) and blood glucose level in patients with type 2 diabetes (T2DM) .Methods Totally 784 T2DM patients and 197 healthy controls were enrolled in this study.Age,duration,body mass index (BMI) ,systolic blood pressure (SBP) ,diastolic blood pressure (DBP) ,levels of fasting blood glucose (FBG) ,postprandial blood glucose (PBG) ,hemoglobin A1c (HbA1c) ,total cholesterol (TC) ,triglyceride (TG) ,

  16. Circulating micro-RNAs as potential blood-based markers for early stage breast cancer detection.

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    Michael G Schrauder

    Full Text Available INTRODUCTION: MicroRNAs (miRNAs, miRs are a class of small, non-coding RNA molecules with relevance as regulators of gene expression thereby affecting crucial processes in cancer development. MiRNAs offer great potential as biomarkers for cancer detection due to their remarkable stability in blood and their characteristic expression in many different diseases. We investigated whether microarray-based miRNA profiling on whole blood could discriminate between early stage breast cancer patients and healthy controls. METHODS: We performed microarray-based miRNA profiling on whole blood of 48 early stage breast cancer patients at diagnosis along with 57 healthy individuals as controls. This was followed by a real-time semi-quantitative Polymerase Chain Reaction (RT-qPCR validation in a separate cohort of 24 early stage breast cancer patients from a breast cancer screening unit and 24 age matched controls using two differentially expressed miRNAs (miR-202, miR-718. RESULTS: Using the significance level of p<0.05, we found that 59 miRNAs were differentially expressed in whole blood of early stage breast cancer patients compared to healthy controls. 13 significantly up-regulated miRNAs and 46 significantly down-regulated miRNAs in our microarray panel of 1100 miRNAs and miRNA star sequences could be detected. A set of 240 miRNAs that was evaluated by radial basis function kernel support vector machines and 10-fold cross validation yielded a specificity of 78.8%, and a sensitivity of 92.5%, as well as an accuracy of 85.6%. Two miRNAs were validated by RT-qPCR in an independent cohort. The relative fold changes of the RT-qPCR validation were in line with the microarray data for both miRNAs, and statistically significant differences in miRNA-expression were found for miR-202. CONCLUSIONS: MiRNA profiling in whole blood has potential as a novel method for early stage breast cancer detection, but there are still challenges that need to be addressed to

  17. Chlorthalidone Plus Amiloride Reduces the Central Systolic Blood Pressure in Stage 1 Hypertension Patients

    Science.gov (United States)

    Fernandes, Leticia Aparecida Barufi; Cestario, Elizabeth do Espirito Santo; Cosenso-Martin, Luciana Neves; Vilela-Martin, Jose Fernando; Yugar-Toledo, Juan Carlos; Fuchs, Flavio Danni

    2016-01-01

    Background Hypertension reduction strategies use blood pressure in the brachial artery as the primary endpoint. Individuals who achieve the target blood pressure reduction with antihypertensive treatment have residual cardiovascular risk attributed to the difference in pressure between the aorta and brachial artery. Antihypertensive treatment affects the intrinsic properties of the vascular wall and arterial stiffness markers and consequently the central pressure. Recent publications stress the importance of adequate control of the central compared to peripheral blood pressure. Related clinical implications suggest that individuals with normal peripheral but high central blood pressure should not receive antihypertensive drugs that act on the central pressure. Therefore, they are at greater cardiovascular risk. The aim of the study was to evaluate the effect of treatment with a thiazide diuretic versus losartan on the central blood pressure in stage 1 hypertensive patients. Methods Twenty-five patients were randomized to the chlorthalidone 25 mg/amiloride 5 mg group (q.d.) and 25 patients received losartan 50 mg (b.i.d). The central systolic blood pressure (CSBP) and augmentation index (AIx 75) were assessed using applanation tonometry. The paired t-test was used to compare the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse pressure (PP), CSBP and AIx 75 between the thiazide and losartan groups at baseline and after 6 months of treatment. Results Significant reductions in CSBP (123.3 ± 14.2 vs. 113.4 ± 111.4, P = 0.0103) and AIx 75 (87.7 ± 9.6 vs. 83.8 ± 8.9, P = 0.0289) were observed after 6 months of drug treatment with chlorthalidone 25 mg/amiloride 5 mg (q.d.). The administration of losartan 50 mg (b.i.d) did not reduce the CSBP and there were insignificant changes in the AIx 75. Conclusions Six-month treatment of chlorthalidone/amiloride but not losartan reduces the CSBP and AIx 75 in adults with stage 1

  18. Stage-specific education/counseling intervention in women with elevated blood pressure.

    Science.gov (United States)

    Daley, Linda K; Fish, Anne F; Frid, David J; Mitchell, G Lynn

    2009-06-01

    Many women with elevated blood pressure who seek exercise opportunities require a flexible program with systematic follow-up. The study framework included motivational readiness (exercise stage of change) from the Transtheoretical Model and self-efficacy theory. This pilot study, which used a one-group repeated measures design, tested the feasibility of a stage-specific education/counseling intervention aimed at improving exercise outcomes in women with elevated blood pressure. Forty women completed a 2.5-hour session including prescription for moderate-vigorous exercise on their own, practice on equipment, maintenance of an exercise diary, and contracting; three follow-up calls (Weeks 1, 2, 3); a visit (Week 4); and a final call (Week 5). After the intervention, 85% of women moved to or remained in the action or maintenance stages of change, the highest levels of readiness; none relapsed. Exercise self-efficacy and benefits increased and barriers decreased (Pexercise performance. The intervention was feasible. Further testing is warranted using larger samples and including a control group.

  19. Human Platelet Antigen Alleles in 998 Taiwanese Blood Donors Determined by Sequence-Specific Primer Polymerase Chain Reaction

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    Shun-Chung Pai

    2013-01-01

    Full Text Available Polymorphism of human platelet antigens (HPAs leads to alloimmunizations and immune-mediated platelet disorders including fetal-neonatal alloimmune thrombocytopenia (FNAIT, posttransfusion purpura (PTP, and platelet transfusion refractoriness (PTR. HPA typing and knowledge of antigen frequency in a population are important in particular for the provision of HPA-matched blood components for patients with PTR. We have performed allele genotyping for HPA-1 through -6 and -15 among 998 platelet donors from 6 blood centers in Taiwan using sequence-specific primer polymerase chain reaction. The HPA allele frequency was 99.55, and 0.45% for HPA-1a and -1b; 96.49, and 3.51% for HPA-2a and -2b; 55.81, and 44.19% for HPA-3a and -3b; 99.75, and 0.25% for HPA-4a and -4b; 98.50, and 1.50% for HPA-5a and -5b; 97.75 and 2.25% for HPA-6a and -6b; 53.71 and 46.29% for HPA-15a and -15b. HPA-15b and HPA-3a, may be considered the most important, followed by HPA-2, -6, -1, -5, and -4 systems, as a cause of FNAIT, PTP, and PTR based on allele frequency. HPA-4b and HPA-5b role cannot be excluded based on their immunogenicity. A larger-scale study will now be conducted to confirm these hypotheses and to establish an apheresis donor database for the procurement of HPA-matched apheresis platelets for patients with PTR.

  20. Histo-blood group antigens in human fetal thymus and in thymomas

    DEFF Research Database (Denmark)

    Engel, P; Dabelsteen, Erik; Francis, D;

    1996-01-01

    -y, Le-x and sialyl-Le-x) of the ABO-histo-blood group system was investigated in 19 normal fetal thymuses (gestational age 16 to 39 weeks) and in 19 thymomas in order to study possible tumor-associated changes in the glycosylation pattern. The material was investigated by immunochemical stainings...

  1. Biosynthetic basis of incompatible histo-blood group A antigen expression

    DEFF Research Database (Denmark)

    David, L; Leitao, D; Sobrinho-Simoes, M

    1993-01-01

    , we have screened 31 cases of gastric tumors of phenotype O for the expression of blood group A gene-defined glycosyltransferase by immunohistology on frozen sections using newly developed monoclonal antibodies to the transferases. Three cases were positive, and transferase expression was confirmed...

  2. Decreased mitochondrial DNA content in blood samples of patients with stage I breast cancer

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    Fokas Emmanouil

    2009-12-01

    Full Text Available Abstract Background Alterations of mitochondrial DNA (mtDNA have been implicated in carcinogenesis. We developed an accurate multiplex quantitative real-time PCR for synchronized determination of mtDNA and nuclear DNA (nDNA. We sought to investigate whether mtDNA content in the peripheral blood of breast cancer patients is associated with clinical and pathological parameters. Methods Peripheral blood samples were collected from 60 patients with breast cancer and 51 age-matched healthy individuals as control. DNA was extracted from peripheral blood for the quantification of mtDNA and nDNA, using a one-step multiplex real-time PCR. A FAM labeled MGB probe and primers were used to amplify the mtDNA sequence of the ATP 8 gene, and a VIC labeled MGB probe and primers were employed to amplify the glyceraldehyde-3-phosphate-dehydrogenase gene. mtDNA content was correlated with tumor stage, menstruation status, and age of patients as well as lymph node status and the expression of estrogen receptor (ER, progesterone receptor (PR and Her-2/neu protein. Results The content of mtDNA in stage I breast cancer patients was significantly lower than in other stages (overall P = 0.023. Reduced mtDNA was found often in post menopausal cancer group (P = 0.024. No difference in mtDNA content, in regards to age (p = 0.564, lymph node involvement (p = 0.673, ER (p = 0.877, PR (p = 0.763, and Her-2/neu expression (p = 0.335, was observed. Conclusion Early detection of breast cancer has proved difficult and current detection methods are inadequate. In the present study, decreased mtDNA content in the peripheral blood of patients with breast cancer was strongly associated with stage I. The use of mtDNA may have diagnostic value and further studies are required to validate it as a potential biomarker for early detection of breast cancer.

  3. Blood platelet and monocyte activations and relation to stages of liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Anatol Panasiuk; Janusz Zak; Edwina Kasprzycka; Katarzyna Janicka; Danuta Prokopowicz

    2005-01-01

    AIM: Blood platelets (plt) and monocytes are the cells that play a crucial role in the pathogenesis of liver damage and liver cirrhosis (LC). In this paper, the analysis of mutual relationship between platelets and monocytes activation in LC was conducted.METHODS: Immunofluorescent flow cytometry was usedto measure the percentage of activated platelet populations(CD62P, CD63), the percentage of plt-monocyte aggregates (pma) (CD41/CD45), and activated monocytes (CD11b, CD14, CD16) in the blood of 20 volunteers and 40 patientswith LC. Platelet activation markers: sP-selectin, platelet factor 4 (PF4), beta-thromboglobulin (βTG) and monocyte chemotactic peptide-1 (MCP-1) were measured and compared in different stages of LC.RESULTS: Platelet activation with the increase in bothβTG serum concentration and elevation of plt population(CD62P and CD63 as well as MIF CD62P and CD63) is elevated as LC develops and thrombocytopenia rises. There is a positive correlation between medial intensityof fluorescence (MIF) CD62P and MIF CD63 in LC. We did not show any relationship between monocyte activation and pma level. SP-selectin concentration correlates positively with plt count and pma, and negatively with stage of plt activation and MIF CD62P and MIF CD63. There was no correlation between MCP-1 concentration andpit, monocyte activation as well as pma level in LC. CD16 monocytes and MIF CD16 populations are significantlyhigher in the end stage of LC. A positive correlation occurs between the value of CD11b monocyte population andMIF CD14 and MIF CD16 on monocytes in LC.CONCLUSION: Platelet and monocyte activation plays an important role in LC. Platelet activation stage does not influence monocyte activation and production of plt aggregates with monocytes in LC. With LC development, thrombocytopenia may be the result of plt consumption in platelet-monocyte aggregates.

  4. Cytotoxic T lymphocyte antigen-4 (CTLA-4 A49G polymorphism and autoimmune blood diseases

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    Faruk Aktürk

    2010-06-01

    Full Text Available Objective: The cytotoxic T lymphocyte associated antigen-4 (CTLA-4 is expressed on T lymphocytes, and inhibits the T-cell responses. In animal models, it has been shown that complete CTLA-4 deficiency was lethal due to massive infiltration of tissues by polyclonally proliferating lymphocytes. CTLA-4 A49G polymorphism, which has been suggested to reduce the inhibitory function of the CTLA-4 molecule, was found to be associated with various autoimmune diseases in recent studies. Material and Methods: In this study, we evaluated the frequency of CTLA-4 A49G polymorphism in 46 patients with autoimmune hemolytic anemia (AIHA, 62 patients with immune thrombocytopenic purpura (ITP, and 150 healthy individuals. Results: Allele frequencies and genotype distributions were similar in both ITP and AIHA patients compared to healthy individuals. In subgroup analysis, however, we found that in chronic lymphocytic leukemia (CLL patients with AIHA (n=4, all patients had CTLA-4 A49G polymorphism (3 had AG, 1 had GG. There was no significant statistical association between G allele and systemic lupus erythematosus (SLE or AIHA.Conclusion: These data suggest that CTLA-4 A49G polymorphism does not contribute to the pathogenesis of lymphoproliferative diseases itself, nor does it increase the risk of autoimmune complications in patients with lymphoproliferative disease.

  5. Evaluation of a Second Generation BOVIGAM Interferon Gamma (IFN-gamma) Assay with Alternative Antigens for Stimulation of Whole Blood Cultures

    Science.gov (United States)

    BOVIGAM®, a rapid laboratory assay, measures gamma interferon (IFN-gamma) production in whole blood samples after induction of a cell-mediated immune response (CMI) with M. bovis antigens. The test is widely used in the field and its excellent performance in TB eradication programs in many countries...

  6. Genome Sequence of Enterobacter cloacae Strain SENG-6, a Bacterium Producing Histo-Blood Group Antigen-Like Substances That Can Bind with Human Noroviruses.

    Science.gov (United States)

    Ishii, Satoshi; Amarasiri, Mohan; Hashiba, Satoshi; Yang, Peiyi; Okabe, Satoshi; Sano, Daisuke

    2016-01-01

    Enterobacter sp. strain SENG-6, isolated from healthy human feces, produces histo-blood group antigen (HBGA)-like substances that can bind with human noroviruses. Based on the genome sequence analysis, strain SENG-6 belongs to the species Enterobacter cloacae The genome sequence of this strain should help identify genes associated with the production of HBGA-like substances.

  7. Exercise maintains blood-brain barrier integrity during early stages of brain metastasis formation.

    Science.gov (United States)

    Wolff, Gretchen; Davidson, Sarah J; Wrobel, Jagoda K; Toborek, Michal

    2015-08-07

    Tumor cell extravasation into the brain requires passage through the blood-brain barrier, which is a highly protected microvascular environment fortified with tight junction (TJ) proteins. TJ integrity can be regulated under physiological and pathophysiological conditions. There is evidence that exercise can modulate oxidation status within the brain microvasculature and protect against tumor cell extravasation and metastasis formation. In order to study these events, mature male mice were given access to voluntary exercise on a running wheel (exercise) or access to a locked wheel (sedentary) for five weeks. The average running distance was 9.0 ± 0.2 km/day. Highly metastatic tumor cells (murine Lewis lung carcinoma) were then infused into the brain microvasculature through the internal carotid artery. Analyses were performed at early stage (48 h) and late stage (3 weeks) post tumor cell infusion. Immunohistochemical analysis revealed fewer isolated tumor cells extravasating into the brain at both 48 h and 3 weeks post surgery in exercised mice. Occludin protein levels were reduced in the sedentary tumor group, but maintained in the exercised tumor group at 48 h post tumor cell infusion. These results indicate that voluntary exercise may participate in modulating blood-brain barrier integrity thereby protecting the brain during metastatic progression.

  8. Red blood cell abnormalities and the pathogenesis of anemia in end-stage renal disease.

    Science.gov (United States)

    Georgatzakou, Hara T; Antonelou, Marianna H; Papassideri, Issidora S; Kriebardis, Anastasios G

    2016-08-01

    Anemia is the most common hematologic complication in end-stage renal disease (ESRD). It is ascribed to decreased erythropoietin production, shortened red blood cell (RBC) lifespan, and inflammation. Uremic toxins severely affect RBC lifespan; however, the implicated molecular pathways are poorly understood. Moreover, current management of anemia in ESRD is controversial due to the "anemia paradox" phenomenon, which underlines the need for a more individualized approach to therapy. RBCs imprint the adverse effects of uremic, inflammatory, and oxidative stresses in a context of structural and functional deterioration that is associated with RBC removal signaling and morbidity risk. RBCs circulate in hostile plasma by raising elegant homeostatic defenses. Variability in primary defect, co-morbidity, and therapeutic approaches add complexity to the pathophysiological background of the anemic ESRD patient. Several blood components have been suggested as biomarkers of anemia-related morbidity and mortality risk in ESRD. However, a holistic view of blood cell and plasma modifications through integrated omics approaches and high-throughput studies might assist the development of new diagnostic tests and therapies that will target the underlying pathophysiologic processes of ESRD anemia.

  9. Binding to histo-blood group antigen-expressing bacteria protects human norovirus from acute heat stress

    Directory of Open Access Journals (Sweden)

    Dan eLi

    2015-07-01

    Full Text Available This study aims to investigate if histo-blood group antigen (HBGA expressing bacteria have any protective role on human norovirus (NoV from acute heat stress. Eleven bacterial strains were included, belonging to Escherichia coli, Enterobacter cloacae, Enterobacter aerogenes, Clostridium difficile, Bifidobacterium adolescentis, and Bifidobacterium longum. HBGA expression of the bacteria as well as binding of human NoV virus-like particles (VLPs, GI.1 and GII.4 strains to the bacteria were detected by flow cytometry. NoV VLPs pre-incubated with HBGA expressing or non-HBGA expressing bacteria were heated and detected by both direct ELISA and porcine gastric mucin-binding assay. The NoV-binding abilities of the bacteria correlated well with their HBGA expression profiles. Two HBGA expressing E.coli (LMG8223 and LFMFP861, both GI.1 and GII.4 binders and one non-HBGA expressing E.coli (ATCC8739, neither GI.1 nor GII.4 binder were selected for the heat treatment test with NoV VLPs. Compared with the same cell numbers of non-HBGA expressing E.coli, the presence of HBGA-expressing E.coli could always maintain higher antigen integrity, as well as mucin-binding ability of NoV VLPs of both GI.1 and GII.4 after heat-treatment at 90°C for 2 min. These results indicate that HBGA-expressing bacteria may protect NoVs during the food processing treatments, thereby facilitating their transmission.

  10. Bacterial histo-blood group antigens contributing to genotype-dependent removal of human noroviruses with a microfiltration membrane.

    Science.gov (United States)

    Amarasiri, Mohan; Hashiba, Satoshi; Miura, Takayuki; Nakagomi, Toyoko; Nakagomi, Osamu; Ishii, Satoshi; Okabe, Satoshi; Sano, Daisuke

    2016-05-15

    We demonstrated the genotype-dependent removal of human norovirus particles with a microfiltration (MF) membrane in the presence of bacteria bearing histo-blood group antigens (HBGAs). Three genotypes (GII.3, GII.4, and GII.6) of norovirus-like particles (NoVLPs) were mixed with three bacterial strains (Enterobacter sp. SENG-6, Escherichia coli O86:K61:B7, and Staphylococcus epidermidis), respectively, and the mixture was filtered with an MF membrane having a nominal pore size of 0.45 μm. All NoVLP genotypes were rejected by the MF membrane in the presence of Enterobacter sp. SENG-6, which excreted HBGAs as extracellular polymeric substances (EPS). This MF membrane removal of NoVLPs was not significant when EPS was removed from cells of Enterobacter sp. SENG-6. GII.6 NoVLP was not rejected with the MF membrane in the presence of E. coli O86:K61:B7, but the removal of EPS of E. coli O86:K61:B7 increased the removal efficiency due to the interaction of NoVLPs with the exposed B-antigen in lipopolysaccharide (LPS) of E. coli O86:K61:B7. No MF membrane removal of all three genotypes was observed when S. epidermidis, an HBGA-negative strain, was mixed with NoVLPs. These results demonstrate that the location of HBGAs on bacterial cells is an important factor in determining the genotype-dependent removal efficiency of norovirus particles with the MF membrane. The presence of HBGAs in mixed liquor suspended solids from a membrane bioreactor (MBR) pilot plant was confirmed by immune-transmission electron microscopy, which implies that bacterial HBGAs can contribute to the genotype-dependent removal of human noroviruses with MBR using MF membrane.

  11. Insights into the biological features of the antigenic determinants recognized by four monoclonal antibodies in redia and adult stages of the liver fluke Fasciola hepatica.

    Science.gov (United States)

    Alba, Annia; Sánchez, Jorge; Hernández, Hilda; Mosqueda, Maryani; Rodríguez, Suanel Y; Capó, Virginia; Otero, Oscar; Alfonso, Carlos; Marcet, Ricardo; Sarracent, Jorge

    2016-09-01

    Fasciola hepatica is a digenean trematode which infects a wide variety of domestic animals and also humans. Previous studies have demonstrated that four monoclonal antibodies (Mabs) against the total extract of F. hepatica redia (named as 1E4, 6G11, 4E5 and 4G11) also recognized the excretion - secretion antigens (ES Ag) of adult parasites, which is a biologically-relevant mixture of molecules with functional roles during infection and immune evasion on definitive hosts. In the present report we describe the partial characterization of the epitopes recognized by these Mabs by heat treatment, mercaptoethanol reduction, pronase proteolysis and sodium peryodate oxidation, which suggested their predominant protein and conformational nature. Also, a comparative study using immunodetection assays on crude extracts and on histological sections of both rediae and adults of F. hepatica were performed to explore the expression pattern of the antigenic determinants in these developmental stages. From these experiments it was found that the Mabs reacted most likely with the same proteins of approximately 64 and 105 kDa present on both rediae and adult's extracts. However, the 1E4, 6G11 and 4E5 Mabs also recognized other molecules of the total extract of F. hepatica adults, a fact that constitutes an evidence of the antigenic variation between both stages and points at a certain biological relevance of the recognized antigenic determinants. Immunolocalization studies on histological sections revealed that all Mabs reacted with the tegument of F. hepatica in both rediae and adults stages, while the epitopes recognized by 1E4, 6G11 and 4E5 antibodies were also preferentially localized in the intestinal caeca and in different organs of the reproductive system of adult specimens. The immunogenicity of these antigenic determinants, their conserved status among different stages of the life cycle of F. hepatica and their presence in both tegument and ES Ag of adult parasites

  12. Corticosteroids decrease the expression of beta 2-microglobulin and histocompatibility antigens on human peripheral blood lymphocytes in vitro

    DEFF Research Database (Denmark)

    Hokland, M; Larsen, B; Heron, I

    1982-01-01

    . Both antigens were found to be decreased, dexamethasone typically in a concentration of 10-6 mol/l causing a decrease in surface beta 2-microglobulin of 15% after an incubation period of 24 hr. The expression of two other lymphocyte surface antigens, Igm and Thy antigens, measured in parallel with beta...

  13. Agglutinating mouse IgG3 compares favourably with IgMs in typing of the blood group B antigen: Functionality and stability studies.

    Science.gov (United States)

    Klaus, Tomasz; Bzowska, Monika; Kulesza, Małgorzata; Kabat, Agnieszka Martyna; Jemioła-Rzemińska, Małgorzata; Czaplicki, Dominik; Makuch, Krzysztof; Jucha, Jarosław; Karabasz, Alicja; Bereta, Joanna

    2016-08-03

    Mouse immunoglobulins M (IgMs) that recognize human blood group antigens induce haemagglutination and are used worldwide for diagnostic blood typing. Contrary to the current belief that IgGs are too small to simultaneously bind antigens on two different erythrocytes, we obtained agglutinating mouse IgG3 that recognized antigen B of the human ABO blood group system. Mouse IgG3 is an intriguing isotype that has the ability to form Fc-dependent oligomers. However, F(ab')2 fragments of the IgG3 were sufficient to agglutinate type B red blood cells; therefore, IgG3-triggered agglutination did not require oligomerization. Molecular modelling indicated that mouse IgG3 has a larger range of Fab arms than other mouse IgG subclasses and that the unique properties of mouse IgG3 are likely due to the structure of its hinge region. With a focus on applications in diagnostics, we compared the stability of IgG3 and two IgMs in formulated blood typing reagents using an accelerated storage approach and differential scanning calorimetry. IgG3 was much more stable than IgMs. Interestingly, the rapid decrease in IgM activity was caused by aggregation of the molecules and a previously unknown posttranslational proteolytic processing of the μ heavy chain. Our data point to mouse IgG3 as a potent diagnostic tool.

  14. Agglutinating mouse IgG3 compares favourably with IgMs in typing of the blood group B antigen: Functionality and stability studies

    Science.gov (United States)

    Klaus, Tomasz; Bzowska, Monika; Kulesza, Małgorzata; Kabat, Agnieszka Martyna; Jemioła-Rzemińska, Małgorzata; Czaplicki, Dominik; Makuch, Krzysztof; Jucha, Jarosław; Karabasz, Alicja; Bereta, Joanna

    2016-01-01

    Mouse immunoglobulins M (IgMs) that recognize human blood group antigens induce haemagglutination and are used worldwide for diagnostic blood typing. Contrary to the current belief that IgGs are too small to simultaneously bind antigens on two different erythrocytes, we obtained agglutinating mouse IgG3 that recognized antigen B of the human ABO blood group system. Mouse IgG3 is an intriguing isotype that has the ability to form Fc-dependent oligomers. However, F(ab′)2 fragments of the IgG3 were sufficient to agglutinate type B red blood cells; therefore, IgG3-triggered agglutination did not require oligomerization. Molecular modelling indicated that mouse IgG3 has a larger range of Fab arms than other mouse IgG subclasses and that the unique properties of mouse IgG3 are likely due to the structure of its hinge region. With a focus on applications in diagnostics, we compared the stability of IgG3 and two IgMs in formulated blood typing reagents using an accelerated storage approach and differential scanning calorimetry. IgG3 was much more stable than IgMs. Interestingly, the rapid decrease in IgM activity was caused by aggregation of the molecules and a previously unknown posttranslational proteolytic processing of the μ heavy chain. Our data point to mouse IgG3 as a potent diagnostic tool. PMID:27484487

  15. Cross-stage immunity for malaria vaccine development.

    Science.gov (United States)

    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.

  16. Anaemia in a phase 2 study of a blood stage falciparum malaria vaccine

    Directory of Open Access Journals (Sweden)

    Guindo Aldiouma

    2011-01-01

    Full Text Available Abstract Background A Phase 1-2b study of the blood stage malaria vaccine AMA1-C1/Alhydrogel was conducted in 336 children in Donéguébougou and Bancoumana, Mali. In the Phase 2 portion of the study (n = 300, no impact on parasite density or clinical malaria was seen; however, children who received the study vaccine had a higher frequency of anaemia (defined as haemoglobin Methods To further investigate the possible impact of vaccination on anaemia, additional analyses were conducted including patients from the Phase 1 portion of the study and controlling for baseline haemoglobin, haemoglobin types S or C, alpha-thalassaemia, G6PD deficiency, and age. A multiplicative intensity model was used, which generalizes Cox regression to allow for multiple events. Frailty effects for each subject were used to account for correlation of multiple anaemia events within the same subject. Intensity rates were calculated with reference to calendar time instead of time after randomization in order to account for staggered enrollment and seasonal effects of malaria incidence. Associations of anaemia with anti-AMA1 antibody were further explored using a similar analysis. Results A strong effect of vaccine on the incidence of anaemia (risk ratio [AMA1-C1 to comparator (Hiberix]= 2.01, 95% confidence interval [1.26,3.20] was demonstrated even after adjusting for baseline haemoglobin, haemoglobinopathies, and age, and using more sophisticated statistical models. Anti-AMA1 antibody levels were not associated with this effect. Conclusions While these additional analyses show a robust effect of vaccination on anaemia, this is an intensive exploration of secondary results and should, therefore, be interpreted with caution. Possible mechanisms of the apparent adverse effect on haemoglobin of vaccination with AMA1-C1/Alhydrogel and implications for blood stage vaccine development are discussed. The potential impact on malaria-associated anaemia should be closely

  17. Antigen-specific secretion of IFNγ and CXCL10 in whole blood assay detects Mycobacterium leprae infection but does not discriminate asymptomatic infection from symptomatic leprosy.

    Science.gov (United States)

    Hungria, Emerith Mayra; Freitas, Aline Araújo; Pontes, Maria Araci Andrade; Gonçalves, Heitor Sá; Sousa, Ana Lúcia Osório Maroccolo; Costa, Maurício Barcelos; Castilho, Mirian Lane Oliveira Rodrigues; Duthie, Malcolm S; Stefani, Mariane Martins Araújo

    2017-04-01

    To advance toward a whole blood assay (WBA)-based test capable of facilitating the diagnosis of paucibacillary (PB) leprosy, we evaluated a prototype in-tube WBA using combinations of Mycobacterium leprae antigens. Blood was collected from newly diagnosed untreated PB (n=38), multibacillary (MB) (n=30), healthy household contacts (HHC) of MB (n=27), and endemic controls (n=61) residing in Goiânia and Fortaleza, Brazil. Blood was incubated with M. leprae cell sonicate, recombinant proteins (46f+LID-1; ML0276+LID-1), or controls (phosphate-buffered saline, phytohemagglutinin, M. tuberculosis purified protein derivative). Antigen-specific IFNγ production was observed in 71-84% and 55% of PB and HHC, respectively. Antigen-specific CXCL10 levels were similarly assessed to determine if, unlike IFNγ, CXCL10 could differentiate PB from HHC with repeated exposure/asymptomatic M. leprae infection. The CXCL10 levels induced in response to M. leprae antigens could not, however, differentiate PB from HHC. Despite these limitations, the WBAs reported here still represent important tools for assessing M. leprae infection rates and evaluating the impact of control measures.

  18. The dynamics of naturally acquired immune responses to Plasmodium falciparum sexual stage antigens Pfs230 & Pfs48/45 in a low endemic area in Tanzania.

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    Teun Bousema

    Full Text Available BACKGROUND: Naturally acquired immune responses against sexual stages of P. falciparum can reduce the transmission of malaria from humans to mosquitoes. These antigens are candidate transmission-blocking vaccines but little is known about the acquisition of sexual stage immunity after exposure to gametocytes, or their longevity and functionality. We conducted a longitudinal study on functional sexual stage immune responses. METHODOLOGY/PRINCIPAL FINDINGS: Parasitaemic individuals (n = 116 were recruited at a health centre in Lower Moshi, Tanzania. Patients presented with gametocytes (n = 16, developed circulating gametocytes by day 7 (n = 69 or between day 7 and 14 (n = 10 after treatment or did not develop gametocytes (n = 21. Serum samples were collected on the first day of gametocytaemia and 28 and 84 days post-enrolment (or d7, 28, 84 after enrolment from gametocyte-negative individuals. Antibody responses to sexual stage antigens Pfs230 and Pfs48/45 were detected in 20.7% (72/348 and 15.2% (53/348 of the samples, respectively, and were less prevalent than antibodies against asexual stage antigens MSP-1(19 (48.1%; 137/285 and AMA-1 (52.4%; 129/246(p<0.001. The prevalence of anti-Pfs230 (p = 0.026 and anti-Pfs48/45 antibodies (p = 0.017 increased with longer duration of gametocyte exposure and had an estimated half-life of approximately 3 months. Membrane feeding experiments demonstrated a strong association between the prevalence and concentration of Pfs230 and Pfs48/45 antibodies and transmission reducing activity (TRA, p<0.01. CONCLUSIONS/SIGNIFICANCE: In a longitudinal study, anti-Pfs230 and Pfs48/45 antibodies developed rapidly after exposure to gametocytes and were strongly associated with transmission-reducing activity. Our data indicate that the extent of antigen exposure is important in eliciting functional transmission-reducing immune responses.

  19. Peripheral blood stem cell harvest in patients with limited stage small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Katakami, Nobuyuki; Takakura, Shunji; Fujii, Hiroshi; Nishimura, Takashi; Umeda, Bunichi [Kobe City General Hospital (Japan)

    2000-06-01

    Chemotherapy plus granulocyte colony-stimulating factor (G-CSF) induced mobilization of peripheral blood stem cells (PBSC) was performed in patients with limited stage small-cell lung cancer. Chemotherapy consisted of cisplatin/etoposide or cisplatin/adriamycin/etoposide. The amounts of CD34 positive cells and granulocyte-macrophage colony forming units (CFU-GM) collected during 2-3 courses of apheresis were 3.1{+-}2.9 x 10{sup 6}/kg (n=10) and 3.1{+-}1.5 x 10{sup 5}/kg (n=8) , respectively. Adequate amounts of PBSC were also harvested even in patients treated with concurrent chemoradiotherapy. Eight patients were successfully treated with high-dose chemotherapy consisting of ifosfamide, carboplatin and etoposide with PBSC transfusion. The patients'-bone marrow reconstruction was rapid and no treatment-related death was observed. (author)

  20. Comparison of Routine Method with Antibody and Antigen Ones for Diagnosing Giardia-Entamoeba Histolytica in Stool and Blood

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    Gharavi, MJ. (PhD

    2015-01-01

    Full Text Available Background and Objectives: Giardia lamblia and Entamoeba histolytica are the most prevalent human intestinal pathogenic protozoa, worldwide. The clinical features of Giardia infection are acute diarrhea, a chronic condition with continuous diarrhea and malabsorption. Entamoeba histolytica invade intestinal tract without any typical clinical indications, and it can involve liver and other organs too. Therefore, we aimed to study these protozoa by serological and parasitological methods. Material and Methods: In this comparative study, the stool and blood specimens were collected from 1025 patients selected via simple random sampling in three different laboratories located in Tehran and Karaj, Iran (2012. Formalin Detergent test was performed on all samples. Both serum and stool positive samples of this method were analyzed for antigen and antibodies related to Giardia lamblia and Entamoeba histolytica, respectively. Results: of 1025 stool specimens, 76 (4.7% were positive for Giardia lamblia and 19 (1.8% for Entamoeba histolytica using Formalin-detergent method. In ELISA, 81 (7.9% coproantibodies to Giardia lamblia and 24 (2.3% coproantibodies to Entamoeba histolytica, 78 (7.6% corproantigen for Giardia lamblia, and 5 (0.4% for Entamoeba histolytica were observed. circulatory antibodies to Entamoeba histlytica were detected in 22 cases (2.1% Conclusion: Sensitivity of microscopic method compared to serological methods is higher than 90%; therefore, Formalin-detergent method can be the best method for stool examination.

  1. Blood lactate minimum of rats during swimming test using three incremental stages

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    Mariana de Souza Sena

    2015-09-01

    Full Text Available AbstractThe purpose of this study was to determine the lactate minimum intensity (LMI by swimming LACmintest using three incremental stages (LACmintest3 and to evaluate its sensitivity to changes in aerobic fitness (AF. Twenty Wistar rats performed: LACmintest3 (1: induction of hyperlactacidemia and incremental phase (4%, 5% and 6.5% of bw; Constant loads tests on (2 and above (3 the LMI. Half of the animals were subjected to training with the individual LMI and the tests were performed again. The mean exercise load in LACmintest3 was 5.04 ± 0.13% bw at 5.08 ± 0.55 mmol L-1 blood lactate minimum (BLM. There was a stabilize and disproportionate increase of blood lactate in tests 2 and 3, respectively. After the training period, the mean BLM was lower in the trained animals. The LACmintest3 seems to be a good indicator of LMI and responsive to changes in AF in rats subjected to swim training.

  2. SOME BIOCHEMICAL BLOOD CONSTANTS EVOLUTION IN REPORT TO THE TRAINING SCHEDULE STAGE IN SPORT HORSES

    Directory of Open Access Journals (Sweden)

    FLAVIA BOCHIS

    2013-12-01

    Full Text Available To determine whether a clinical examination was adequate to assess the fitness of horses in a fence course riding, and to characterize the relationship between a clinical assessment of the horse's fitness, training schedule stage and its blood biochemistry, 22 horses were monitored before (S1, during training, immediately after warming-up (S2 and after an E level fence obstacle course ride (S3. The blood samples were taken from the jugular vein in the above three mentioned phases, for the determination of total protein (g/dl, nitrogen (mg/dl, glucose (mg/dl, lactic acid (nmol/l, calcium (mg/dl, cholesterol (mg/dl and phosphorus (mg/dl. The intend of the paper is to present the obtained results as a reference study for the appropriate use by clinicians, sport horses owners and trainers in view to have a solid base in evaluation, for the adequate protection of health and welfare of the jumper horses competitors.

  3. Blood Biomarkers Associated with Cognitive Decline in Early Stage and Drug-Naive Parkinson's Disease Patients.

    Directory of Open Access Journals (Sweden)

    Jose A Santiago

    Full Text Available Early diagnosis of Parkinson's disease (PD continues to be a major challenge in the field. The lack of a robust biomarker to detect early stage PD patients has considerably slowed the progress toward the development of potential therapeutic agents. We have previously evaluated several RNA biomarkers in whole blood from participants enrolled in two independent clinical studies. In these studies, PD patients were medicated, thus, expression of these biomarkers in de novo patients remains unknown. To this end, we tested ten RNA biomarkers in blood samples from 99 untreated PD patients and 101 HC nested in the cross-sectional Parkinson's Progression Markers Initiative by quantitative real-time PCR. One biomarker out of ten, COPZ1 trended toward significance (nominal p = 0.009 when adjusting for age, sex, and educational level. Further, COPZ1, EFTUD2 and PTBP1 mRNAs correlated with clinical features in PD patients including the Hoehn and Yahr scale, Movement Disorder Society revision of Unified Parkinson's Disease Rating Scale (MDS-UPDRS and Montreal Cognitive Assessment (MoCA score. Levels of EFTUD2 and PTBP1 were significantly higher in cognitively normal PD patients (PD-CN compared to cognitively impaired PD patients (PD-MCI. Interestingly, blood glucose levels were significantly higher in PD and PD-MCI patients (≥ 100 mg/dL, pre-diabetes compared to HC. Collectively, we report the association of three RNA biomarkers, COPZ1, EFTUD2 and PTBP1 with clinical features including cognitive decline in early drug-naïve PD patients. Further, our results show that drug-naïve PD and PD-MCI patients have glucose levels characteristic of pre-diabetes patients, suggesting that impaired glucose metabolism is an early event in PD. Evaluation of these potential biomarkers in a larger longitudinal study is warranted.

  4. Blood Biomarkers Associated with Cognitive Decline in Early Stage and Drug-Naive Parkinson's Disease Patients.

    Science.gov (United States)

    Santiago, Jose A; Potashkin, Judith A

    2015-01-01

    Early diagnosis of Parkinson's disease (PD) continues to be a major challenge in the field. The lack of a robust biomarker to detect early stage PD patients has considerably slowed the progress toward the development of potential therapeutic agents. We have previously evaluated several RNA biomarkers in whole blood from participants enrolled in two independent clinical studies. In these studies, PD patients were medicated, thus, expression of these biomarkers in de novo patients remains unknown. To this end, we tested ten RNA biomarkers in blood samples from 99 untreated PD patients and 101 HC nested in the cross-sectional Parkinson's Progression Markers Initiative by quantitative real-time PCR. One biomarker out of ten, COPZ1 trended toward significance (nominal p = 0.009) when adjusting for age, sex, and educational level. Further, COPZ1, EFTUD2 and PTBP1 mRNAs correlated with clinical features in PD patients including the Hoehn and Yahr scale, Movement Disorder Society revision of Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Montreal Cognitive Assessment (MoCA) score. Levels of EFTUD2 and PTBP1 were significantly higher in cognitively normal PD patients (PD-CN) compared to cognitively impaired PD patients (PD-MCI). Interestingly, blood glucose levels were significantly higher in PD and PD-MCI patients (≥ 100 mg/dL, pre-diabetes) compared to HC. Collectively, we report the association of three RNA biomarkers, COPZ1, EFTUD2 and PTBP1 with clinical features including cognitive decline in early drug-naïve PD patients. Further, our results show that drug-naïve PD and PD-MCI patients have glucose levels characteristic of pre-diabetes patients, suggesting that impaired glucose metabolism is an early event in PD. Evaluation of these potential biomarkers in a larger longitudinal study is warranted.

  5. Antigen Uptake during Different Life Stages of Zebrafish (Danio rerio) Using a GFP-Tagged Yersinia ruckeri

    DEFF Research Database (Denmark)

    Korbut, Rozalia; Mehrdana, Foojan; Kania, Per Walter;

    2016-01-01

    Immersion-vaccines (bacterins) are routinely used for aquacultured rainbow trout to protect against Yersinia ruckeri (Yr). During immersion vaccination, rainbow trout take up and process the antigens, which induce protection. The zebrafish was used as a model organism to study uptake mechanisms...... the gut was consistently a major uptake site. Zebrafish and rainbow trout tend to have similar uptake mechanisms following immersion or bath vaccination, which points towards zebrafish as a suitable model organism for this aquacultured species....... and subsequent antigen transport in fish. A genetically modified Yr was developed to constitutively express green fluorescent protein (GFP) and was used for bacterin production. Larval, juvenile and adult transparent zebrafish (tra:nac mutant) received a bath in the bacterin for up to 30 minutes. Samples were...

  6. Funções biológicas dos antígenos eritrocitários Biological functions of blood group antigens

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    Silvia L. Bonifácio

    2009-04-01

    Full Text Available Os antígenos de grupos sanguíneos eritrocitários são estruturas macromoleculares localizadas na superfície extracelular da membrana eritrocitária. Com o desenvolvimento de estudos moleculares, mais de 250 antígenos são conhecidos e estão organizados em 29 sistemas de grupos sanguíneos reconhecidos pela Sociedade Internacional de Transfusão Sanguínea (ISBT. Estudos têm revelado que os antígenos de grupo sanguíneo estão expressos na membrana eritrocitária com ampla diversidade estrutural, incluindo epítopos de carboidratos em glicoproteínas e/ou glicolipídios e em proteínas inseridas na membrana via um domínio, via domínios de multipassagem ou ligados a glicosilfosfatidinositol. Além das diversidades estruturais, muitas funções importantes têm sido associadas aos antígenos eritrocitários recentemente identificadas, podendo ser esquematicamente divididas em: estruturais, transportadores, receptores e moléculas de adesão, enzimas, proteínas controladoras do complemento e outras. Esta revisão tem como foco as funções potenciais das moléculas que expressam os antígenos eritrocitários.Erythrocyte blood group antigens are macromolecules structures located on the extracellular surface of the red blood cell membrane. The development of molecular studies allowed the recognition of more than 250 antigens by the International Society for Blood Transfusion (ISBT. These studies have also shown that blood group antigens are carried on red blood cell membrane of wide structural diversity, including carbohydrate epitopes on glycoproteins and/or glycolipids and on proteins inserted within the membrane via single or multi-pass transmembrane domains, or via glycosylphosphatidylinositol linkages. In addition, to their structural diversity, many important functions associated with blood group antigens have been recently identified and can be didactically divided into: structural proteins, transporters, receptors and adhesion

  7. Extensive release of an antigen associated with the sporogonic stages of myxobolus cerebralis (Myxozoa: Myxosporea) is detected by a heterologous antibody raised to Tetracapsuloides bryosalmonae (Myxozoa: Malacosporea).

    Science.gov (United States)

    Morris, David J; El-Matbouli, Mansour; Adams, Alexandra

    2004-06-01

    Monoclonal antibody B4 (mAb B4) was previously developed to the myxozoan parasite Tetracapsuloides bryosalmonae Canning, Curry, Feist, Longshaw et Okamura, 1999, the causative agent of proliferative kidney disease of salmonids, Here we describe the reaction of mAb B4 against Myxobolus cerebralis Hofer, 1903, the parasite that causes 'whirling disease' in salmonids. Tissues examined were collected from experimentally infected rainbow trout Oncorhynchus mykiss (Walbaum) and the aquatic oligochaete Tubifex tubifex (O.F. Müller), the two hosts involved in the life cycle of M. cerebralis. Paraffin sections of infected rainbow trout taken at 4 h and 3, 10, 17 and 54 days post-exposure to infective M. cerebralis actinospores were immunohistochemically stained with mAb B4. Longitudinal sections through infected T. tubifex sampled 120 days post-exposure to M. cerebralis myxospores were also examined using this method. The only phase of the M. cerebralis life cycle that expressed the mAb B4 antigen was during sporogenesis in the salmonid host. The immunohistochemical staining demonstrated that the antigen was released into the tissues surrounding the spore and sporogonic stages of the parasite. The localisation of the antigen was diffuse in the fish, suggesting that the possible effect of M. cerebralis infection is extensive through the head tissues and not limited to areas of cartilage destruction as previously thought.

  8. Apoptosis of granulocytes and lymphocytes in peripheral blood in rabbits infected with haemagglutinating and non-haemagglutinating antigenic variants of the RHD (rabbit haemorrhagic disease) virus.

    Science.gov (United States)

    Niedźwiedzka-Rystwej, P; Tokarz-Deptuła, B; Deptuła, W

    2013-01-01

    This paper attempts to study the dynamics of apoptosis of granulocytes and lymphocytes in peripheral blood in rabbits infected with haemagglutinating (Vt97, Triptis, Hartmannsdorf) and non-haemagglutinating (Pv97, 9905 RHDVa) antigenic variants of the RHD virus. The pathogenicity of those antigenic variants was also assessed by recording the mortality of the infected animals. The animals were infected with antigenic variants and blood was sampled at hour 0, 4, 8, 12, 24, 36 p.i. and the percentage of apoptotic granulocytes and lymphocytes was measured with the use of flow cytometry. The results of the study showed that apoptosis is included during RHDV infection, as the number of apoptotic granulocytes and lymphocytes increases throughout the experiment; depending on the antigenic variant, apoptosis joins in at 4-8-12 h p.i. and lasts until 24-36 h p.i. Furthermore, the mortality of rabbits infected with the examined strains of RHD virus varied from 30% to 100%. This study performed for the first time in this manner, indicates the importance of apoptosis during infection with the RHD virus.

  9. Correlation between the preoperative serum prostate specific antigen, Gleason score, and clinical staging with pathological outcome following robot-assisted radical prostatectomy: An Indian experience

    Directory of Open Access Journals (Sweden)

    P Singh

    2011-01-01

    Full Text Available Objectives: To correlate the preoperative serum prostate specific antigen (PSA, Gleason score, and clinical staging with pathological outcome following robot-assisted radical prostatectomy (RARP in Indian men with clinically localized cancer prostate. Materials and Methods: A prospective study analysis was done for 166 consecutive patients of prostate cancer who underwent RARP at our center from June 2006 to October 2009. Preoperative workup included serum PSA, biopsy Gleason score, and clinical staging. The preoperative parameters were correlated with final Gleason score, capsular penetration, seminal vesicle involvement, and lymph node status on final histopathology. Results: The mean age was 64 years (range: 50-76 years with mean and median PSA of 17.98 ng/ml (range: 0.3-68.3 ng/ml and 12.1 ng/ml, respectively. With increase in preoperative Gleason score, chance of organ confinement decreases (P=0.002 and capsular penetration increases (P=0.004 linearly. With increasing serum PSA, there is linear decrease in trend of organ-confined disease (P=0.03 and increased chances of seminal vesicle involvement (P=0.02. Patients with higher clinical stage have less probability of localized disease (P=0.007 and more chances of capsular penetration (P=0.04 and seminal vesicle involvement (P=0.004. Conclusion: Our data suggest that patients with higher preoperative serum PSA, Gleason score, and clinical stage have more chances of advanced pathological stage following RARP.

  10. Premalignant and malignant oral lesions are associated with changes in the glycosylation pattern of carbohydrates related to ABH blood group antigens

    DEFF Research Database (Denmark)

    Dabelsteen, Erik; Clausen, H; Holmstrup, P

    1988-01-01

    The distribution of carbohydrate structures related to the ABO(H) blood group antigen system was studied in biopsies from eight squamous cell carcinomas, and eight erythroplakias with epithelial dysplasia. Twenty oral lesions without histological evidence of malignancy (13 lichen planus lesions...... and 7 homogeneous leukoplakias) were also examined. The distribution of Lex, Ley, H type 2 chain, and N-acetyllactosamine, all type 2 chain carbohydrate structures, was investigated by immunohistological staining using monoclonal antibodies with selected specificity. The histological pattern...

  11. Stage-specific immunity to Taenia taeniaeformis infection in mice. A histological study of the course of infection in mice vaccinated with either oncosphere or metacestode antigens.

    Science.gov (United States)

    Bøgh, H O; Lightowlers, M W; Sullivan, N D; Mitchell, G F; Rickard, M D

    1990-03-01

    The course of Taenia taeniaeformis infection in mice previously vaccinated with antigens prepared from either oncosphere (TtO) or metacestode (TtM) was followed by histological examination of livers from mice killed at various times post-infection (p.i.). Distinctly different immune responses occurred in the two groups. Very few cysts were seen at any stage of infection in TtO-vaccinated mice and most of those which were present appeared histologically similar to cysts in control mice. In TtM-vaccinated mice many cysts were present from early in infection but histologically it was apparent that most were dying from 15 days p.i. because the tegument had lost its integrity, and degranulated polymorphonuclear leucocytes were present inside the parasites. These findings support earlier suggestions that stage-specific antigens are expressed in oncospheres and metacestodes. Parasites developing normally were surrounded by a halo of alcian blue staining amorphous acellular material. This material appeared to act as a barrier to attack by host inflammatory cells, and disappearance of this layer signalled death of the parasite. The possibility that the gut acted as a barrier to delay migration of oncospheres to the liver in vaccinated mice was investigated, but no evidence for this could be found.

  12. Biomarkers for early and late stage chronic allograft nephropathy by proteogenomic profiling of peripheral blood.

    Directory of Open Access Journals (Sweden)

    Sunil M Kurian

    Full Text Available BACKGROUND: Despite significant improvements in life expectancy of kidney transplant patients due to advances in surgery and immunosuppression, Chronic Allograft Nephropathy (CAN remains a daunting problem. A complex network of cellular mechanisms in both graft and peripheral immune compartments complicates the non-invasive diagnosis of CAN, which still requires biopsy histology. This is compounded by non-immunological factors contributing to graft injury. There is a pressing need to identify and validate minimally invasive biomarkers for CAN to serve as early predictors of graft loss and as metrics for managing long-term immunosuppression. METHODS: We used DNA microarrays, tandem mass spectroscopy proteomics and bioinformatics to identify genomic and proteomic markers of mild and moderate/severe CAN in peripheral blood of two distinct cohorts (n = 77 total of kidney transplant patients with biopsy-documented histology. FINDINGS: Gene expression profiles reveal over 2400 genes for mild CAN, and over 700 for moderate/severe CAN. A consensus analysis reveals 393 (mild and 63 (moderate/severe final candidates as CAN markers with predictive accuracy of 80% (mild and 92% (moderate/severe. Proteomic profiles show over 500 candidates each, for both stages of CAN including 302 proteins unique to mild and 509 unique to moderate/severe CAN. CONCLUSIONS: This study identifies several unique signatures of transcript and protein biomarkers with high predictive accuracies for mild and moderate/severe CAN, the most common cause of late allograft failure. These biomarkers are the necessary first step to a proteogenomic classification of CAN based on peripheral blood profiling and will be the targets of a prospective clinical validation study.

  13. Kinetics of cytokine expression in bovine PBMCs and whole blood after in vitro stimulation with foot-and-mouth disease virus (FMDV) antigen.

    Science.gov (United States)

    Dar, Pervaiz A; Hajam, Irshad A; Suryanarayana, Velavurthy S; Kishore, Subodh; Kondabattula, Ganesh

    2015-03-01

    The interest in analysing antigen-specific cytokine responses has substantially increased in recent years, in part due to their use in assessing vaccine efficacy. In the present study, the kinetics of IL-2, IL-4 and IFN-γ expression was determined in bovine PBMCs by real-time PCR and in whole blood by cytokine-release assay after in vitro stimulation with recall foot-and-mouth disease virus (FMDV) antigen. The results showed that the cytokine mRNA of IL-2 and IFN-γ in PBMCs were induced early (peak induction at 6 h), whereas the IL-4 mRNA showed delayed induction (peaked at 24 h). In contrast, the kinetics of cytokine proteins in whole blood was different and required the accumulation of the proteins before being optimally detected. The peak accumulation of cytokine protein in whole blood was recorded at 72 h for IL-2 and IL-4, and 96 h for IFN-γ. The findings of this study are of importance when selecting an optimal time points for measuring antigen-specific cytokine expression in cattle.

  14. Comparison of real-time PCR and antigen assays for detection of hepatitis E virus in blood donors.

    Science.gov (United States)

    Vollmer, T; Knabbe, C; Dreier, J

    2014-06-01

    Hepatitis E virus (HEV) infection is recognized as an emerging and often undiagnosed disease in industrialized countries, with asymptomatic infections actually occurring in blood donors. Sensitive detection of HEV-RNA is crucial for diagnosis and monitoring of disease progression. We evaluated the analytical sensitivity and performance of three HEV RT-PCR assays (RealStar HEV reverse transcription-PCR [RT-PCR], hepatitis@ceeramTools, and ampliCube HEV RT-PCR) for screening of individuals for HEV infections (ID-nucleic acid amplification technology [ID-NAT]) and for blood donor pool screening (minipool-NAT [MP-NAT]). RNA was extracted using NucliSens easyMAG (ID-NAT) and a high-volume extraction protocol (4.8 ml, chemagic Viral 5K, MP-NAT). Three NAT assays were evaluated for ID-NAT but only two assays for MP-NAT due to inhibition of the ampliCube HEV RT-PCR kit using the corresponding RNA extract. Assays provided good analytical sensitivity, ranging from 37.8 to 180.1 IU/ml (ID-NAT) and from 4.7 to 91.2 IU/ml (MP-NAT). The applicability of HEV antigen (HEV-Ag) screening was compared to that of RT-PCR screening and detection of HEV-IgM antibodies using seroconversion panels of 10 HEV genotype 3-infected individuals. Four individuals revealed a positive HEV-Ag detection result, with corresponding viremias ranging from 1.92 E + 03 to 2.19 E + 05 IU/ml, while the progression of HEV-Ag followed that of HEV viremia. The other six individuals showed no presence of HEV-Ag although the corresponding viremias were also in the range of >1.0 E + 03. Anti-HEV-IgM antibodies were detectable in seven donors; one donor presented parallel positivities of HEV-Ag and anti-HEV IgM. The evaluated NAT methods present powerful tools providing sensitive HEV detection. Application of HEV-Ag or anti-HEV IgM screening is currently inferior for the early detection of HEV infection due to the decreased sensitivity compared to NAT methods.

  15. Blood biochemical changes in lambs infected with normal and gamma irradiated third stage larvae of Dictyocaulus filaria

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    Bhat, T.K.; Dhar, D.N.; Bansal, G.C.; Sharma, R.L. (Indian Veterinary Research Inst., Srinagar (India). Regional Centre)

    1984-09-01

    Primary infections with normal third stage larvae of Dictyocaulus filaria at a dose of 150 1/kg caused significant decrease in the levels of haemoglobin, blood glucose, serum total proteins, serum albumin, albumin/globulin ratio and increase in levels of total globulins and lactate dehydrogenase (LDH) activity in lambs. Almost similar changes in the above blood constituents excepting for haemoglobin, blood glucose and LDH activity were noticed in lambs immunised with two doses of gamma irradiation larvae and subsequently challenged with normal larvae of D. filaria at a dose of 150 1/kg. In both the infected groups, serum calcium, inorganic phosphorus, malate dehydrogenase and alkaline phosphatase activities were, however, not affected.

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

    Science.gov (United States)

    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

  17. Mechanisms of protective immunity against asexual blood stages of Plasmodium falciparum in the experimental host Saimiri

    Directory of Open Access Journals (Sweden)

    J. Gysin

    1992-01-01

    Full Text Available In the Saimiri monkey, an experimental host for human malaria, acquired protection against Plasmodium falciparum blood stages depends on the IgG antibody populations developed. In vivo protective anti-falciparum activity of IgG antibodies is correlated with the in vivo opsonizing activity promoting phagocytosis of parasited red bloood cells. In contrast, non protective antibodies inhibit this mechanism by competing at the target level. A similar phenomenon can be and human infection. Anti-cytoadherent and anti-rosette antibodies developed by Saimiri and humans prevent the development of physiopathological events like cerebral malaria which can also occur in this experimental host. Furthermore, transfer to protective human anti-falciparum IgG antibodies into infected Saimiri monkeys exerts an anti parasite activity as efficient as that observed when it is transfered into acute falciparum malaria patients, making the Saimiri an even more attractive host. Studies on the role of immunocompetent cells in the protective immune reponse are still in their infancy, however the existance of a restricted polymorphism of MHC II class molecules in the Saimiri confers additional theoretical and practical importance to this model.

  18. Fcγ receptor antigen targeting potentiates cross-presentation by human blood and lymphoid tissue BDCA-3+ dendritic cells.

    Science.gov (United States)

    Flinsenberg, Thijs W H; Compeer, Ewoud B; Koning, Dan; Klein, Mark; Amelung, Femke J; van Baarle, Debbie; Boelens, Jaap Jan; Boes, Marianne

    2012-12-20

    The reactivation of human cytomegalovirus (HCMV) poses a serious health threat to immune compromised individuals. As a treatment strategy, dendritic cell (DC) vaccination trials are ongoing. Recent work suggests that BDCA-3(+) (CD141(+)) subset DCs may be particularly effective in DC vaccination trials. BDCA-3(+) DCs had however been mostly characterized for their ability to cross-present antigen from necrotic cells. We here describe our study of human BDCA-3(+) DCs in elicitation of HCMV-specific CD8(+) T-cell clones. We show that Fcgamma-receptor (FcγR) antigen targeting facilitates antigen cross-presentation in several DC subsets, including BDCA-3(+) DCs. FcγR antigen targeting stimulates antigen uptake by BDCA-1(+) rather than BDCA-3(+) DCs. Conversely, BDCA-3(+) DCs and not BDCA-1(+) DCs show improved cross-presentation by FcγR targeting, as measured by induced release of IFNγ and TNF by antigen-specific CD8(+) T cells. FcγR-facilitated cross-presentation requires antigen processing in both an acidic endosomal compartment and by the proteasome, and did not induce substantial DC maturation. FcγRII is the most abundantly expressed FcγR on both BDCA-1(+) and BDCA-3(+) DCs. Furthermore we show that BDCA-3(+) DCs express relatively more stimulatory FcγRIIa than inhibitory FcγRIIb in comparison with BDCA-1(+) DCs. These studies support the exploration of FcγR antigen targeting to BDCA-3(+) DCs for human vaccination purposes.

  19. Increased expression of TLR-2, COX-2, and SOD-2 genes in the peripheral blood leukocytes of opisthorchiasis patients induced by Opisthorchis viverrini antigen.

    Science.gov (United States)

    Yongvanit, Puangrat; Thanan, Raynoo; Pinlaor, Somchai; Sithithaworn, Paiboon; Loilome, Watcharin; Namwat, Nisana; Techasen, Anchalee; Dechakhamphu, Somkid

    2012-05-01

    Re-infection with liver fluke, Opisthorchis viverrini, increases proinflammatory molecules involved in inflammation-mediated disease and carcinogenesis in an animal model. To clarify whether these genes respond to parasite antigen in peripheral blood leukocytes (PBL) of opisthorchiasis patients, we examined the transcriptional level of oxidant-generating (toll-like receptor 2 (TLR-2), nuclear factor-kappa B (NF-KB), and cyclooxygenase 2 (COX-2)), anti-oxidant-generating (manganese superoxide dismutase 2 (SOD-2) and catalase (CAT)), proinflammatory cytokine (interleukin (IL)-1β), and anti-inflammatory cytokine (IL-10), in PBL exposed to parasite antigen in O. viverrini-infected patients compared with healthy individuals in an in vitro experiment. After O. viverrini antigen-treated PBL, quantitative RT-PCR analysis revealed that increased expression of cytokines and oxidant-generating genes in PBL was similar between O. viverrini-infected and healthy groups. Interestingly, compared with healthy subjects, increase of TLR-2, COX-2, and SOD-2 and decreased CAT mRNA expression levels were observed in O. viverrini-infected group. The results indicate that O. viverrini antigen induces upregulation of TLR-2, COX-2, and SOD-2 and downregulation of CAT genes in opisthorchiasis patients, suggesting that imbalance of oxidant/anti-oxidant transcripts during re-infection may be involved in the inflammatory-driven carcinogenesis. These molecules may be used as the chemopreventive target for intervention of opisthorchiasis patients in an endemic area.

  20. Strategies for the identification of T cell-recognized tumor antigens in hematological malignancies for improved graft-versus-tumor responses after allogeneic blood and marrow transplantation.

    Science.gov (United States)

    Zilberberg, Jenny; Feinman, Rena; Korngold, Robert

    2015-06-01

    Allogeneic blood and marrow transplantation (allo-BMT) is an effective immunotherapeutic treatment that can provide partial or complete remission for patients with hematological malignancies. Mature donor T cells in the donor inoculum play a central role in mediating graft-versus-tumor (GVT) responses by destroying residual tumor cells that persist after conditioning regimens. Alloreactivity towards minor histocompatibility antigens (miHA), which are varied tissue-related self-peptides presented in the context of major histocompatibility complex (MHC) molecules on recipient cells, some of which may be shared on tumor cells, is a dominant factor for the development of GVT. Potentially, GVT can also be directed to tumor-associated antigens or tumor-specific antigens that are more specific to the tumor cells themselves. The full exploitation of allo-BMT, however, is greatly limited by the development of graft-versus-host disease (GVHD), which is mediated by the donor T cell response against the miHA expressed in the recipient's cells of the intestine, skin, and liver. Because of the significance of GVT and GVHD responses in determining the clinical outcome of patients, miHA and tumor antigens have been intensively studied, and one active immunotherapeutic approach to separate these two responses has been cancer vaccination after allo-BMT. The combination of these two strategies has an advantage over vaccination of the patient without allo-BMT because his or her immune system has already been exposed and rendered unresponsive to the tumor antigens. The conditioning for allo-BMT eliminates the patient's existing immune system, including regulatory elements, and provides a more permissive environment for the newly developing donor immune compartment to selectively target the malignant cells. Utilizing recent technological advances, the identities of many human miHA and tumor antigenic peptides have been defined and are currently being evaluated in clinical and basic

  1. Strategies for the Identification of T Cell–Recognized Tumor Antigens in Hematological Malignancies for Improved Graft-versus-Tumor Responses after Allogeneic Blood and Marrow Transplantation

    Science.gov (United States)

    Zilberberg, Jenny; Feinman, Rena; Korngold, Robert

    2015-01-01

    Allogeneic blood and marrow transplantation (allo-BMT) is an effective immunotherapeutic treatment that can provide partial or complete remission for patients with hematological malignancies. Mature donor T cells in the donor inoculum play a central role in mediating graft-versus-tumor (GVT) responses by destroying residual tumor cells that persist after conditioning regimens. Alloreactivity towards minor histocompatibility antigens (miHA), which are varied tissue-related self-peptides presented in the context of major histocompatibility complex (MHC) molecules on recipient cells, some of which may be shared on tumor cells, is a dominant factor for the development of GVT. Potentially, GVT can also be directed to tumor-associated antigens or tumor-specific antigens that are more specific to the tumor cells themselves. The full exploitation of allo-BMT, however, is greatly limited by the development of graft-versus-host disease (GVHD), which is mediated by the donor T cell response against the miHA expressed in the recipient’s cells of the intestine, skin, and liver. Because of the significance of GVT and GVHD responses in determining the clinical outcome of patients, miHA and tumor antigens have been intensively studied, and one active immunotherapeutic approach to separate these two responses has been cancer vaccination after allo-BMT. The combination of these two strategies has an advantage over vaccination of the patient without allo-BMT because his or her immune system has already been exposed and rendered unresponsive to the tumor antigens. The conditioning for allo-BMT eliminates the patient’s existing immune system, including regulatory elements, and provides a more permissive environment for the newly developing donor immune compartment to selectively target the malignant cells. Utilizing recent technological advances, the identities of many human miHA and tumor antigenic peptides have been defined and are currently being evaluated in clinical and basic

  2. Outcomes of peripheral blood stem cell transplantation in patients from human leukocyte antigen matched or mismatched unrelated donors

    Institute of Scientific and Technical Information of China (English)

    Cao Tingting; Li Yanfen; Wang Quanshun; Li Honghua; Bo Jian; Zhao Yu; Jing Yu

    2014-01-01

    Background Allogeneic peripheral blood stem cell transplantation from unrelated donors (UR-PBSCT) is an alternative treatment for many hematologic diseases due to lack of human leukocyte antigen (HLA)-identical sibling donors.This study aimed to evaluate the impact of the degree of the HLA match on the clinical efficacy of UR-PBSCT.Methods Patients who underwent UR-PBSCT from September 2003 to September 2012 were retrospectively investigated.They were divided into three groups according to high-resolution molecular typing.SPSS version 17.0 was used to analysis and compare the statistics of engraftment,incidence of GVHD,other complications and survival among the groups.Results One hundred and eleven patients received UR-PBSCT,60 of them with an HLA matched donor (10/10),36 of them with a one locus mismatched donor (9/10),and 15 of them with a two loci mismatched donor (8/10).Similar basic characteristics were found in the three groups.No differences were found in engraftment of myeloid cells or platelets in the three groups (P>0.05).Two-year cumulative incidence of relapse,overall survival (OS) and disease-free survival (DFS) among those three groups were similar (P>0.05).The cumulative incidence of 100-day Ⅲ-Ⅳ aGVHD in the HLA matched group and the one HLA locus mismatched group were significantly lower than that in the two HLA loci mismatched group (3.3%,8.6%,and 26.7%,P=0.009).The occurrence rate of new pulmonary infections in the HLA matched group was lower than in the two HLA mismatched groups (26.67%,52.78%,and 41.18%,P=0.035).The cumulative incidence of 100-day and 2-year transplantation related mortality (TRM) in two HLA loci mismatched group was higher than in the HLA matched group and in the one HLA locus mismatched group,(8.4%,11.8% and 33.3%,P=0.016) and (12.3%,18.7% and 47.5%,P=0.002).Conclusions HLA mismatch will not significantly impact the engraftment or 2-year survival after UR-PBSCT,but two mismatched HLA loci may

  3. Nebivolol reduces central blood pressure in stage I hypertensive patients: experimental single cohort study

    Directory of Open Access Journals (Sweden)

    Renan Oliveira Vaz-de-Melo

    Full Text Available CONTEXT AND OBJECTIVES: Assessment of central blood pressure (BP has grown substantially over recent years because evidence has shown that central BP is more relevant to cardiovascular outcomes than peripheral BP. Thus, different classes of antihypertensive drugs have different effects on central BP despite similar reductions in brachial BP. The aim of this study was to investigate the effect of nebivolol, a β-blocker with vasodilator properties, on the biochemical and hemodynamic parameters of hypertensive patients.DESIGN AND SETTING: Experimental single cohort study conducted in the outpatient clinic of a university hospital.METHODS: Twenty-six patients were recruited. All of them underwent biochemical and hemodynamic evaluation (BP, heart rate (HR, central BP and augmentation index before and after 3 months of using nebivolol.RESULTS: 88.5% of the patients were male; their mean age was 49.7 ± 9.3 years and most of them were overweight (29.6 ± 3.1 kg/m2 with large abdominal waist (102.1 ± 7.2 cm. There were significant decreases in peripheral systolic BP (P = 0.0020, diastolic BP (P = 0.0049, HR (P < 0.0001 and central BP (129.9 ± 12.3 versus 122.3 ± 10.3 mmHg; P = 0.0083 after treatment, in comparison with the baseline values. There was no statistical difference in the augmentation index or in the biochemical parameters, from before to after the treatment.CONCLUSIONS: Nebivolol use seems to be associated with significant reduction of central BP in stage I hypertensive patients, in addition to reductions in brachial systolic and diastolic BP.

  4. Phase 1 trial of the Plasmodium falciparum blood stage vaccine MSP1(42-C1/Alhydrogel with and without CPG 7909 in malaria naive adults.

    Directory of Open Access Journals (Sweden)

    Ruth D Ellis

    Full Text Available BACKGROUND: Merozoite surface protein 1(42 (MSP1(42 is a leading blood stage malaria vaccine candidate. In order to induce immune responses that cover the major antigenic polymorphisms, FVO and 3D7 recombinant proteins of MSP1(42 were mixed (MSP1(42-C1. To improve the level of antibody response, MSP1(42-C1 was formulated with Alhydrogel plus the novel adjuvant CPG 7909. METHODS: A Phase 1 clinical trial was conducted in healthy malaria-naïve adults at the Center for Immunization Research in Washington, D.C., to evaluate the safety and immunogenicity of MSP1(42-C1/Alhydrogel +/- CPG 7909. Sixty volunteers were enrolled in dose escalating cohorts and randomized to receive three vaccinations of either 40 or 160 microg protein adsorbed to Alhydrogel +/- 560 microg CPG 7909 at 0, 1 and 2 months. RESULTS: Vaccinations were well tolerated, with only one related adverse event graded as severe (Grade 3 injection site erythema and all other vaccine related adverse events graded as either mild or moderate. Local adverse events were more frequent and severe in the groups receiving CPG. The addition of CPG enhanced anti-MSP1(42 antibody responses following vaccination by up to 49-fold two weeks after second immunization and 8-fold two weeks after the third immunization when compared to MSP1(42-C1/Alhydrogel alone (p<0.0001. After the third immunization, functionality of the antibody was tested by an in vitro growth inhibition assay. Inhibition was a function of antibody titer, with an average of 3% (range -2 to 10% in the non CPG groups versus 14% (3 to 32% in the CPG groups. CONCLUSION/SIGNIFICANCE: The favorable safety profile and high antibody responses induced with MSP1(42-C1/Alhydrogel + CPG 7909 are encouraging. MSP1(42-C1/Alhydrogel is being combined with other blood stage antigens and will be taken forward in a formulation adjuvanted with CPG 7909. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00320658.

  5. Non-major histocompatibility complex-restricted cytotoxic activity of blood mononuclear cells stimulated with secreted mycobacterial proteins and other mycobacterial antigens

    DEFF Research Database (Denmark)

    Ravn, P; Pedersen, B K

    1994-01-01

    Several observations indicate that non-major histocompatibility complex (MHC)-restricted cytotoxicity, mediated for example by natural killer cells and lymphokine-activated killer cells, may serve as an important antimicrobial defense mechanism. The purpose of the present study was to investigate...... the influences of different mycobacterial antigens on non-MHC-restricted cytotoxicity and further to investigate the ways by which various lymphocyte subpopulations contribute to the development of this cytotoxicity. Non-MHC-restricted cytotoxicity was induced following stimulation of mononuclear cells...... the influence of CD4+ cells on the development of non-MHC-restricted cytotoxicity, blood mononuclear cells were depleted of CD4+ cells before antigen stimulation. When mononuclear cells were incubated with purified protein derivative or short-term culture filtrate in the absence of CD4+ cells, cytotoxic...

  6. In vivo approaches reveal a key role for DCs in CD4+ T cell activation and parasite clearance during the acute phase of experimental blood-stage malaria.

    Directory of Open Access Journals (Sweden)

    Henrique Borges da Silva

    2015-02-01

    Full Text Available Dendritic cells (DCs are phagocytes that are highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP of the spleen, which is a major site for the control of blood-borne infections such as malaria. However, the dynamics of splenic DCs during Plasmodium infections are poorly understood, limiting our knowledge regarding their protective role in malaria. Here, we used in vivo experimental approaches that enabled us to deplete or visualize DCs in order to clarify these issues. To elucidate the roles of DCs and marginal zone macrophages in the protection against blood-stage malaria, we infected DTx (diphtheria toxin-treated C57BL/6.CD11c-DTR mice, as well as C57BL/6 mice treated with low doses of clodronate liposomes (ClLip, with Plasmodium chabaudi AS (Pc parasites. The first evidence suggesting that DCs could contribute directly to parasite clearance was an early effect of the DTx treatment, but not of the ClLip treatment, in parasitemia control. DCs were also required for CD4+ T cell responses during infection. The phagocytosis of infected red blood cells (iRBCs by splenic DCs was analyzed by confocal intravital microscopy, as well as by flow cytometry and immunofluorescence, at three distinct phases of Pc malaria: at the first encounter, at pre-crisis concomitant with parasitemia growth and at crisis when the parasitemia decline coincides with spleen closure. In vivo and ex vivo imaging of the spleen revealed that DCs actively phagocytize iRBCs and interact with CD4+ T cells both in T cell-rich areas and in the RP. Subcapsular RP DCs were highly efficient in the recognition and capture of iRBCs during pre-crisis, while complete DC maturation was only achieved during crisis. These findings indicate that, beyond their classical role in antigen presentation, DCs also contribute to the direct elimination of iRBCs during acute Plasmodium infection.

  7. In Vivo Approaches Reveal a Key Role for DCs in CD4+ T Cell Activation and Parasite Clearance during the Acute Phase of Experimental Blood-Stage Malaria

    Science.gov (United States)

    Borges da Silva, Henrique; Fonseca, Raíssa; Cassado, Alexandra dos Anjos; Machado de Salles, Érika; de Menezes, Maria Nogueira; Langhorne, Jean; Perez, Katia Regina; Cuccovia, Iolanda Midea; Ryffel, Bernhard; Barreto, Vasco M.; Marinho, Cláudio Romero Farias; Boscardin, Silvia Beatriz; Álvarez, José Maria; D’Império-Lima, Maria Regina; Tadokoro, Carlos Eduardo

    2015-01-01

    Dendritic cells (DCs) are phagocytes that are highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP) of the spleen, which is a major site for the control of blood-borne infections such as malaria. However, the dynamics of splenic DCs during Plasmodium infections are poorly understood, limiting our knowledge regarding their protective role in malaria. Here, we used in vivo experimental approaches that enabled us to deplete or visualize DCs in order to clarify these issues. To elucidate the roles of DCs and marginal zone macrophages in the protection against blood-stage malaria, we infected DTx (diphtheria toxin)-treated C57BL/6.CD11c-DTR mice, as well as C57BL/6 mice treated with low doses of clodronate liposomes (ClLip), with Plasmodium chabaudi AS (Pc) parasites. The first evidence suggesting that DCs could contribute directly to parasite clearance was an early effect of the DTx treatment, but not of the ClLip treatment, in parasitemia control. DCs were also required for CD4+ T cell responses during infection. The phagocytosis of infected red blood cells (iRBCs) by splenic DCs was analyzed by confocal intravital microscopy, as well as by flow cytometry and immunofluorescence, at three distinct phases of Pc malaria: at the first encounter, at pre-crisis concomitant with parasitemia growth and at crisis when the parasitemia decline coincides with spleen closure. In vivo and ex vivo imaging of the spleen revealed that DCs actively phagocytize iRBCs and interact with CD4+ T cells both in T cell-rich areas and in the RP. Subcapsular RP DCs were highly efficient in the recognition and capture of iRBCs during pre-crisis, while complete DC maturation was only achieved during crisis. These findings indicate that, beyond their classical role in antigen presentation, DCs also contribute to the direct elimination of iRBCs during acute Plasmodium infection. PMID:25658925

  8. Protection from experimental cerebral malaria with a single dose of radiation-attenuated, blood-stage Plasmodium berghei parasites.

    Directory of Open Access Journals (Sweden)

    Noel J Gerald

    Full Text Available BACKGROUND: Whole malaria parasites are highly effective in inducing immunity against malaria. Due to the limited success of subunit based vaccines in clinical studies, there has been a renewed interest in whole parasite-based malaria vaccines. Apart from attenuated sporozoites, there have also been efforts to use live asexual stage parasites as vaccine immunogens. METHODOLOGY AND RESULTS: We used radiation exposure to attenuate the highly virulent asexual blood stages of the murine malaria parasite P. berghei to a non-replicable, avirulent form. We tested the ability of the attenuated blood stage parasites to induce immunity to parasitemia and the symptoms of severe malaria disease. Depending on the mouse genetic background, a single high dose immunization without adjuvant protected mice from parasitemia and severe disease (CD1 mice or from experimental cerebral malaria (ECM (C57BL/6 mice. A low dose immunization did not protect against parasitemia or severe disease in either model after one or two immunizations. The protection from ECM was associated with a parasite specific antibody response and also with a lower level of splenic parasite-specific IFN-γ production, which is a mediator of ECM pathology in C57BL/6 mice. Surprisingly, there was no difference in the sequestration of CD8+ T cells and CD45+ CD11b+ macrophages in the brains of immunized, ECM-protected mice. CONCLUSIONS: This report further demonstrates the effectiveness of a whole parasite blood-stage vaccine in inducing immunity to malaria and explicitly demonstrates its effectiveness against ECM, the most pathogenic consequence of malaria infection. This experimental model will be important to explore the formulation of whole parasite blood-stage vaccines against malaria and to investigate the immune mechanisms that mediate protection against parasitemia and cerebral malaria.

  9. Can perfusion CT assessment of primary colorectal adenocarcinoma blood flow at staging predict for subsequent metastatic disease? A pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Goh, Vicky [Mount Vernon Hospital, Paul Strickland Scanner Centre, Northwood (United Kingdom); Halligan, Steve [University College Hospital, Department of Academic Radiology, London (United Kingdom); Wellsted, David M. [University of Hertfordshire, Health Research and Development Support Unit, Hatfield (United Kingdom); Bartram, Clive I. [St Mark' s Hospital, Intestinal Imaging Centre, Harrow (United Kingdom)

    2009-01-15

    We aimed to determine whether perfusion CT measurements at colorectal cancer staging may predict for subsequent metastatic relapse. Fifty two prospective patients underwent perfusion CT at staging to estimate tumour blood flow, blood volume, mean transit time, and permeability surface area product. Patients considered metastasis free and suitable for surgery underwent curative resection subsequently. At final analysis, a median of 48.6 months post-surgery, patients were divided into those who remained disease free, and those with subsequent metastases. Vascular parameters for these two groups were compared using t-testing, and receiver operator curve analysis was performed to determine the sensitivity and specificity of these vascular parameters for predicting metastases. Thirty seven (71%) patients underwent curative surgery; data were available for 35: 26 (74%) remained disease free; 9 (26%) recurred (8 metastatic, 1 local). Tumour blood flow differed significantly between disease-free and metastatic patients (76.0 versus 45.7 ml/min/100 g tissue; p=0.008). With blood flow <64 ml/min/100 g tissue, sensitivity and specificity (95% CI) for development of metastases were 100% (60-100%) and 73% (53-87%), respectively. Our preliminary findings suggest that primary tumour blood flow might potentially be a useful predictor warranting further study. (orig.)

  10. [Seasonal changes in the blood coagulating and anticoagulating system indices in men at the preclinical stage of ischemic heart disease].

    Science.gov (United States)

    Andreenko, G V; Panchenko, V M; Liutova, L V; Lisina, A N; Karabasova, M A

    1980-03-01

    Examination of 52 males (aged 23 to 40 years) in the preclinical stage of ischemic heart disease revealed seasonal differences in the values of the blood coagulation and anticoagulation systems: in the spring, there was an increase in blood coagulation activity displayed by growth of the concentration of fibrinogen and soluble fibrin and a reduction in the amount of the plasminogen activator. The authors suggest conducting preventive treatment of patients in the spring, the most unfavourable season in respect of the effect of the pathogenetic factors.

  11. Countermeasures of Blood of Patients with ABO Disease Weakened Blood Group Antigens%血液病患者ABO血型抗原减弱及其输血对策

    Institute of Scientific and Technical Information of China (English)

    陈鹏

    2014-01-01

    Objective To analyze the causes of decreased blood ABO in patients with blood group antigens and puts forward the corresponding countermeasures of blood transfusion. Methods The diagnosis and treatment of 30 cases in our hospital were col ected and the weakening of the ABO blood group antigen blood disease patients as the observation group, 30 cases of blood group antigen expression of the normal patients were selected as control group, summarize the cause of weakening of the ABO blood group antigen and puts forward the corresponding Countermeasures of blood transfusion. Results The results showed that, the observation group with 10 patients with red blood cel s and antiserum reaction and reverse typing discrepancies, including 7 cases of type A and type B in 3 cases, 2 patients were type, the rest 18 patients al type O. At the same time, the observation group in 2 patients with non hemolytic in hemolytic cases, accounting for 6.67%of the total, the control group had 4 cases, accounting for 13.33%of the total, two groups of patients increased hemoglobin close degree. Conclusion The patients with blood diseases mainly concentrated in myelodysplastic syndrome and acute and chronic non lymphocytic leukemia, by entering the same blood type has good clinical ef ect in the treatment of such patients, can ef ectively promote the functional recovery of the antigen, and promote the rehabilitation of patients.%目的分析血液病患者ABO血型抗原减弱的原因并提出相应的输血对策。方法收集我院诊治的30例ABO血型抗原减弱的血液病患者设为观察组,另选同期的30例血型抗原正常表达患者设为对照组,总结ABO血型抗原减弱的原因并提出相应的输血对策。结果研究结果显示,观察组中有10例患者红细胞与抗血清反应中出现与反定型不符,包括7例A型和3例B型,有2例患者为正定型,其余18例患者全部为O型。同时,观察组中有2例患者在溶血性情况中出

  12. Transfection of B7-1 cDNA empowers antigen presentation of blood malignant cells for activation of anti-tumor T cells

    Institute of Scientific and Technical Information of China (English)

    克晓燕; 贾丽萍; 王晶; 王德炳

    2003-01-01

    Objective To define roles of B7-1 co-stimulation factor expressed in human malignant cell lines in mediating anti-tumor T cell immune responses. Methods Examining human leucocyte antigen (HLA) and B7 expressions on 8 human blood malignancies cell lines by flow cytometry. Transfecting B7-1 gene to B7-1 negative (B7*!-) Raji and B7*!- Jurkat cell lines by liposome, and comparing the potencies of blood malignant cell lines in the induction of T cell activation by examination of T cell cytokine mRNAs before and after transfection using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Results High level of HLA Ⅰ and Ⅱ molecules were expressed in most human blood malignant cell lines examined, and the co-stimulatory factor B7-2 was also highly expressed. In contrast, another member of B7 family: B7-1 was either not expressed or very limitedly expressed in most of these hematopoietic malignant cell lines. Most importantly, transfection of B7-1 gene to B7*!-. Raji and B7*!-. Jurkat cell lines made these cell lines better antigen presenting cells for stimulation of anti-tumor T cell activation, which was demonstrated by up regulation of expression of T cell cytokines IL-2, IL-4 and INF-γ mRNAs after incubation of these tumor cells with T cells for 24 h. Conclusions B7 co-stimulation plays an important role in anti-tumor immunity. Transfection of B7-1 gene to the human hematopoietic malignant cell lines that are deficient in the B7-1 expression empowers their antigen presentation potency for activation of anti-tumor T cells. Our results suggested that repairing the deficiency of B7-1 co-stimulatory pathway in tumor cells might be a novel immunotherapeutic approach for human hematopoietic malignancies.

  13. Red blood cell calcium homeostasis in patients with end-stage renal disease

    Energy Technology Data Exchange (ETDEWEB)

    Gafter, U.; Malachi, T.; Barak, H.; Djaldetti, M.; Levi, J. (Hasharon Hospital, Petah-Tiqva (Israel))

    1989-09-01

    Low cell calcium level is essential for preservation of red blood cell (RBC) membrane deformability and survival. RBCs from patients with end-stage renal disease (ESRD) demonstrate reduction in membrane deformability, possibly as a result of increased RBC cellular calcium level. To evaluate calcium homeostasis in RBCs from patients with ESRD, we measured cell calcium level, basal and calmodulin-stimulated calcium-stimulated Mg-dependent ATPase (CaATPase) activity, and calcium 45 efflux were measured before and after hemodialysis. The in vitro effect of uremic plasma and of urea on CaATPase activity of normal RBCs was tested, and 45Ca influx into RBCs of patients undergoing hemodialysis also was determined. A morphologic evaluation of red cells from patients with ESRD was performed with a scanning electron microscope. RBC calcium level in patients (mean +/- SEM 21.2 +/- 2.8 mumol/L of cells; n = 28) was higher than in controls (4.9 +/- 0.3 mumol/L of cells; n = 24; p less than 0.001). Hemodialysis had no effect on cell calcium level. Both basal and calmodulin-stimulated RBC CaATPase activities in patients with ESRD (n = 9) were reduced by approximately 50% (p less than 0.01), but after hemodialysis, enzyme activity returned to normal. 45Ca efflux from calcium-loaded cells, which was 2574.0 +/- 217.0 mumol/L of cells per 0.5 hours before hemodialysis, increased to 3140.7 +/- 206.8 mumol/L of cells per 0.5 hours after hemodialysis (p less than 0.005). In vitro incubation of normal RBCs with uremic plasma depressed CaATPase activity, but incubation with urea had no effect. RBCs of patients with ESRD revealed increased 45Ca influx, 7.63 +/- 1.15 mumol/L of cells per hour versus 4.61 +/- 0.39 mumol/L of cells per hour (p less than 0.025). RBCs of patients revealed a high incidence of spherocytosis and echynocytosis, which correlated with a high cell calcium level (r = 0.894, p less than 0.01).

  14. Correlative BOLD MR imaging of stages of synovitis in a rabbit model of antigen-induced arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Doria, Andrea S. [Hospital for Sick Children, Department of Diagnostic Imaging, Toronto (Canada); University of Toronto, Department of Medical Imaging, Toronto (Canada); Crawley, Adrian [University of Toronto, Department of Medical Imaging, Toronto (Canada); Toronto Western Hospital, Department of Medical Imaging, Toronto (Canada); Gahunia, Harpal; Rayner, Tammy; Tassos, Vivian; Zhong, Anguo [Hospital for Sick Children, Department of Diagnostic Imaging, Toronto (Canada); Moineddin, Rahim [Family and Community Medicine, Department of Public Health, Toronto (Canada); Pritzker, Kenneth; Mendes, Maria; Jong, Roland [Mount Sinai Hospital, Department of Pathology and Laboratory Medicine, Toronto (Canada); Salter, Robert B. [Hospital for Sick Children, Department of Orthopedic Surgery, Toronto (Canada)

    2012-01-15

    Because of the ability of blood-oxygen-level-dependent (BOLD) MRI to assess blood oxygenation changes within the microvasculature, this technique holds potential for evaluating early perisynovial changes in inflammatory arthritis. To evaluate the feasibility of BOLD MRI to detect interval perisynovial changes in knees of rabbits with inflammatory arthritis. Rabbit knees were injected with albumin (n=9) or saline (n=6) intra-articularly, or were not injected (control knees, n=9). Except for two rabbits (albumin-injected, n=2 knees; saline-injected, n=2 knees) that unexpectedly died on days 7 and 21 of the experiment, respectively, all other animals were scanned with BOLD MRI on days 0, 1, 7, 14, 21 and 28 after induction of arthritis. T2*-weighted gradient-echo MRI was performed during alternate 30 s of normoxia/hyperoxia. BOLD MRI measurements were compared with clinical, laboratory and histological markers. Percentage of activated voxels was significantly greater in albumin-injected knees than in contralateral saline-injected knees (P=0.04). For albumin-injected knees (P < 0.05) and among different categories of knees (P=0.009), the percentage of activated BOLD voxels varied over time. A quadratic curve for on-and-off BOLD difference was delineated for albumin- and saline-injected knees over time (albumin-injected, P=0.047; saline-injected, P=0.009). A trend toward a significant difference in synovial histological scores between albumin-injected and saline-injected knees was noted only for acute scores (P=0.07). As a proof of concept, BOLD MRI can depict perisynovial changes during progression of experimental arthritis. (orig.)

  15. Histo-blood group ABO antigen in oral potentially malignant lesions and squamous cell carcinoma--genotypic and phenotypic characterization

    DEFF Research Database (Denmark)

    Gao, Shan; Bennett, Erik Paul; Reibel, Jesper

    2004-01-01

    to establish the ABO genotype. Total and patchy loss of A/B antigen expression was found in 24/32 carcinomas, 6/7 leukoplakias with severe dysplasia, 12/17 leukoplakias with mild and moderate dysplasia, and 6/17 leukoplakias without dysplasia. Specific A/B allele loss was found in 8/24 cases with carcinoma...

  16. Effect of the pre-erythrocytic candidate malaria vaccine RTS,S/AS01E on blood stage immunity in young children

    DEFF Research Database (Denmark)

    Bejon, Philip; Cook, Jackie; Bergmann-Leitner, Elke

    2011-01-01

    -linked immunosorbent assay, antibodies to 4 Plasmodium falciparum merozoite antigens (AMA-1, MSP-1(42), EBA-175, and MSP-3) and by growth inhibitory activity (GIA) using 2 parasite clones (FV0 and 3D7) at 4 times on 860 children who were randomized to receive with RTS,S/AS01(E) or a control vaccine. Results. Antibody......(See the article by Greenhouse et al, on pages 19-26.) Background. RTS,S/AS01(E) is the lead candidate malaria vaccine and confers pre-erythrocytic immunity. Vaccination may therefore impact acquired immunity to blood-stage malaria parasites after natural infection. Methods. We measured, by enzyme...... concentrations to AMA-1, EBA-175, and MSP-1(42) decreased with age during the first year of life, then increased to 32 months of age. Anti-MSP-3 antibody concentrations gradually increased, and GIA gradually decreased up to 32 months. Vaccination with RTS,S/AS01(E) resulted in modest reductions in AMA-1, EBA-175...

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

    Science.gov (United States)

    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

  18. Effect of artificial colloids on blood coagulation during shock stage of severe burn injury

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jian-jun; XING Nan; CHEN Jiong; SHI Jian-wu; SU Guo-liang

    2013-01-01

    Background There are controversies about the use of artificial colloids.This research was aimed to determine the effect of various artificial colloids on blood coagulation in the shock stage of severe burn injury.Methods Totally,18 female Ba-Ma mini-pigs were subjected to a 40% total body surface third-degree flame burn under anesthesia.Resuscitation therapy was applied 2 hours after the injury,using the burn shock fluid resuscitation formula commonly accepted in the surgical treatment of burns.The Ba-Ma mini-pigs were randomly assigned to three groups (six pigs in each group):succinylated gelatin group (the artificial colloid used was succinylated gelatin Injection),hydroxyethyl starch group (the artificial colloid used was hydroxyethyl starch (130/0.4)),and allogeneic plasma group (the colloid used was allogeneic plasma).Blood samples were collected from the animals prior to the burn injury and again at intervals of 4,8,24 and 48 hours post-injury.The platelet count (PLT),prothrombin time (PT),international normalized ratio (INR),activated partial thromboplastin time (APTT),and fibrinogen (Fib) were measured,followed by a statistical analysis of all results.Results The PLT of succinylated gelatin group and hydroxyethyl starch group at intervals of 24 and 48 hours were (124.3±52.7),(78.8±16.4)×109/L and (159.0±62.8),(87.3±32.0)×109/L respectively.But in the allogeneic plasma group at intervals of 8,24,and 48 hours were (234.3±52.6),(136.0±47.4),(75.8±31.0)×109/L.The decrease were all statistically significant (P <0.05,P <0.01) when compared to pre-burn ((383.3±77.9),(382.7±65.7),(381.0±49.4)×109/L).The PLT among the three groups,at all the time points,had no statistical difference (P >0.05).Compared to pre-burn ((10.8±0.9),(11.4±0.8),(10.6±0.7) seconds),the PT of succinylated gelatin group and hydroxyethyl starch group at 24 hours were (14.5±1.5) and (16.2±1.3) seconds,whereas in the allogeneic plasma group at 8 and 24 hours the PT were

  19. In Vitro Differentiation of Insulin Secreting Cells from Mouse Bone Marrow Derived Stage-Specific Embryonic Antigen 1 Positive Stem Cells

    Directory of Open Access Journals (Sweden)

    Morteza Abouzaripour

    2016-02-01

    Full Text Available Objective: Bone marrow has recently been recognized as a novel source of stem cells for the treatment of wide range of diseases. A number of studies on murine bone marrow have shown a homogenous population of rare stage-specific embryonic antigen 1 (SSEA-1 positive cells that express markers of pluripotent stem cells. This study focuses on SSEA-1 positive cells isolated from murine bone marrow in an attempt to differentiate them into insulin-secreting cells (ISCs in order to investigate their differentiation potential for future use in cell therapy. Materials and Methods: This study is an experimental research. Mouse SSEA-1 positive cells were isolated by Magnetic-activated cell sorting (MACS followed by characterization with flow cytometry. Induced SSEA-1 positive cells were differentiated into ISCs with specific differentiation media. In order to evaluate differentiation quality and analysis, dithizone (DTZ staining was use, followed by reverse transcription polymerase chain reaction (RT-PCR, immunocytochemistry and insulin secretion assay. Statistical results were analyzed by one-way ANOVA. Results: The results achieved in this study reveal that mouse bone marrow contains a population of SSEA-1 positive cells that expresses pluripotent stem cells markers such as SSEA-1, octamer-binding transcription factor 4 (OCT-4 detected by immunocytochemistry and C-X-C chemokine receptor type 4 (CXCR4 and stem cell antigen-1 (SCA-1 detected by flow cytometric analysis. SSEA-1 positive cells can differentiate into ISCs cell clusters as evidenced by their DTZ positive staining and expression of genes such as Pdx1 (pancreatic transcription factors, Ngn3 (endocrine progenitor marker, Insulin1 and Insulin2 (pancreaticβ-cell markers. Additionally, our results demonstrate expression of PDX1 and GLUT2 protein and insulin secretion in response to a glucose challenge in the differentiated cells. Conclusion: Our study clearly demonstrates the potential of SSEA-1

  20. Non-invasive assessment of pulmonary blood supply after staged repair of pulmonary atresia.

    OpenAIRE

    Del Torso, S.; Kelly, M J; Kalff, V; Stellin, G; Mee, R B; Venables, A W

    1985-01-01

    Radionuclide studies were performed to determine pulmonary blood flow in six children who had undergone surgery for pulmonary atresia, ventricular septal defect, and hypoplastic pulmonary arteries with or without major aortopulmonary collateral arteries. Lung blood flow was assessed from both particle perfusion lung scans and the pulmonary and systemic phase of a radionuclide dynamic flow study. Five patients had perfusion defects identified on the particle perfusion lung scan. In three of th...

  1. Structural Analysis of Histo-Blood Group Antigen Binding Specificity in a Norovirus GII.4 Epidemic Variant: Implications for Epochal Evolution

    Energy Technology Data Exchange (ETDEWEB)

    Shanker, Sreejesh; Choi, Jae-Mun; Sankaran, Banumathi; Atmar, Robert L.; Estes, Mary K.; Prasad, B.V. Venkataram (Baylor); (LBNL)

    2012-03-23

    Susceptibility to norovirus (NoV), a major pathogen of epidemic gastroenteritis, is associated with histo-blood group antigens (HBGAs), which are also cell attachment factors for this virus. GII.4 NoV strains are predominantly associated with worldwide NoV epidemics with a periodic emergence of new variants. The sequence variations in the surface-exposed P domain of the capsid protein resulting in differential HBGA binding patterns and antigenicity are suggested to drive GII.4 epochal evolution. To understand how temporal sequence variations affect the P domain structure and contribute to epochal evolution, we determined the P domain structure of a 2004 variant with ABH and secretor Lewis HBGAs and compared it with the previously determined structure of a 1996 variant. We show that temporal sequence variations do not affect the binding of monofucosyl ABH HBGAs but that they can modulate the binding strength of difucosyl Lewis HBGAs and thus could contribute to epochal evolution by the potentiated targeting of new variants to Lewis-positive, secretor-positive individuals. The temporal variations also result in significant differences in the electrostatic landscapes, likely reflecting antigenic variations. The proximity of some of these changes to the HBGA binding sites suggests the possibility of a coordinated interplay between antigenicity and HBGA binding in epochal evolution. From the observation that the regions involved in the formation of the HBGA binding sites can be conformationally flexible, we suggest a plausible mechanism for how norovirus disassociates from salivary mucin-linked HBGA before reassociating with HBGAs linked to intestinal epithelial cells during its passage through the gastrointestinal tract.

  2. Comprehensive analysis of blood group antigen binding to classical and El Tor cholera toxin B-pentamers by NMR.

    Science.gov (United States)

    Vasile, Francesca; Reina, José J; Potenza, Donatella; Heggelund, Julie E; Mackenzie, Alasdair; Krengel, Ute; Bernardi, Anna

    2014-08-01

    Cholera is a diarrheal disease responsible for the deaths of thousands, possibly even hundreds of thousands of people every year, and its impact is predicted to further increase with climate change. It has been known for decades that blood group O individuals suffer more severe symptoms of cholera compared with individuals with other blood groups (A, B and AB). The observed blood group dependence is likely to be caused by the major virulence factor of Vibrio cholerae, the cholera toxin (CT). Here, we investigate the binding of ABH blood group determinants to both classical and El Tor CTB-pentamers using saturation transfer difference NMR and show that all three blood group determinants bind to both toxin variants. Although the details of the interactions differ, we see no large differences between the two toxin genotypes and observe very similar binding constants. We also show that the blood group determinants bind to a site distinct from that of the primary receptor, GM1. Transferred NOESY data confirm that the conformations of the blood group determinants in complex with both toxin variants are similar to those of reported X-ray and solution structures. Taken together, this detailed analysis provides a framework for the interpretation of the epidemiological data linking the severity of cholera infection and an individual's blood group, and brings us one step closer to understanding the molecular basis of cholera blood group dependence.

  3. Clinical Observation in 45 Cases of Hemorrhagic Apoplexy of the Acute Stage Treated by Promoting Blood Circulation and Removing Blood Stasis

    Institute of Scientific and Technical Information of China (English)

    孙国柱

    2003-01-01

    To explore the therapeutic effects of the method of promoting blood circulation and removing blood stasis on hemorrhagic apoplexy of acute stage, 45 cases were treated by the method and observed for their conscious state and motor function, which were compared with 40 cases treated with regular western drugs. The results showed that the effective rate in the treated group was 82.2% and that in control group 60% with a significant difference (P<0.05) between the two groups. In the treated group, the scores of the conscious state and the motor function after treatment were elevated dramatically (P<0.01), indicating a much better effect in the treated group than in the control group.

  4. Genetic diversity through human leukocyte antigen typing in end-stage renal disease patients and prospective donors of North India

    Directory of Open Access Journals (Sweden)

    Mohit Chowdhry

    2016-01-01

    Full Text Available As the incidence of end-stage renal disease (ESRD is rapidly increasing, the demand for dialysis and transplantation has dramatically increased, which has led to concerns about the availability and equitable allocation of kidneys for transplantation. The distribution of HLA-A, B and DR alleles in 148 renal transplant recipients and 191 live related prospective donors from 2009 to 2010 were analyzed. Allele frequencies and haplotype frequencies were calculated in recipients and donors. The prospective donors were further analyzed on the basis of their relationship to the patients and according to the sex ratio. A significant female preponderance was noted in the prospective donor population, most of whom were either siblings or parents of the recipients. On the contrary, the recipient population predominantly comprised of males. The most frequent HLA-A, HLA-B, HLA-DRB1 alleles in renal transplant patients were HLA-AFNx0111, AFNx0102, AFNx0101, AFNx0124; HLA-BFNx0135, BFNx0140, BFNx0144, BFNx0115, BFNx0152, and HLA-DRB1FNx0115, DRB1FNx0107, DRB1FNx0113, DRB1FNx0111 respectively. The most frequent HLA-A, HLA-B, HLA-DRB1 alleles in prospective donors were HLA-AFNx0102, AFNx0111, AFNx0133, AFNx0124; HLA-BFNx0135, BFNx0144, BFNx0140, BFNx0115 and HLA-DRB1FNx0115, DRB1FNx0107, DRB1FNx0111, DRB1FNx0113 respectively. AFNx0111-BFNx0135, AFNx0102-DRB1FNx0115, BFNx0140-DRB1FNx0115 were the most common HLA A-B , HLA A-DR, HLA B-DR haplotypes respectively in renal transplant patients, whereas, AFNx0111-BFNx0135, AFNx0111-DRB1FNx0115, BFNx0144-DRB1FNx0107 were the most common haplotypes in renal donors. In three locus haplotype, HLA-AFNx0102-BFNx0140-DRB1FNx0115 was the most frequent haplotype in patients, whereas, in prospective renal donors HLA-AFNx0133-BFNx0144-DRB1FNx0107 was the most frequent haplotype.

  5. Chemopreventive effect of resveratrol, sesamol, sesame oil and sunflower oil in the Epstein-Barr virus early antigen activation assay and the mouse skin two-stage carcinogenesis.

    Science.gov (United States)

    Kapadia, Govind J; Azuine, Magnus A; Tokuda, Harukuni; Takasaki, Midori; Mukainaka, Teruo; Konoshima, Takao; Nishino, Hoyoku

    2002-06-01

    Resveratrol, sesamol, sesame oil and sunflower oil are known natural dietary components with intrinsic cancer chemopreventive potentials. As a part of our study of dietary constituents as potential cancer chemopreventive agents, we have assessed the anti-cancer potentials of these products in the promotion stage of cancer development employing the in vitro Epstein-Barr virus early antigen activation assay induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). Further, we studied the activities of these compounds in the brine shrimp cytotoxicity assay as well as on the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging bioassay with a view to comparing some of the mechanisms of their anti-cancer activity. Finally, we compared the observed chemoprotective capabilities of the four products in the in vivo 7,12 dimethylbenz(a)anthracene initiated and TPA-promoted mouse skin two-stage carcinogenesis protocols. All the products tested showed a profound inhibitory effect on the Epstein-Barr virus early antigen induction using Raji cells. Comparatively, sesame oil was the most potent followed by sesamol and then resveratrol. Only sesamol and resveratrol showed a remarkable cytotoxic activity in the brine shrimp lethality assays as well as profound free radical scavenging activity in the DPPH bioassay. In both test systems, sesamol exhibited a more remarkable activity than resveratrol while sesame oil and sunflower oil did not exhibit any appreciable activity even at the highest concentrations tested (4000 microg ml(-1) ). In our in vivo assay at a 50-fold molar ratio to TPA, sesamol offered 50% reduction in mouse skin papillomas at 20 weeks after promotion with TPA. Under an identical molar ratio to TPA, resveratrol offered a 60% reduction in the papillomas in mouse at 20 weeks. Thus sesamol seems to be an almost equally potent chemopreventive agent. Sesame oil and sunflower oil offered 20 and 40% protection, respectively, in the mouse

  6. No evidence for a direct effect of von Willebrand factor's ABH blood group antigens on von Willebrand factor clearance

    NARCIS (Netherlands)

    Groeneveld, D J; van Bekkum, T; Cheung, K L; Dirven, R J; Castaman, G; Reitsma, P H; van Vlijmen, B; Eikenboom, J

    2015-01-01

    BACKGROUND: One of the major determinants of von Willebrand factor (VWF) plasma levels is ABO blood group status, and individuals with blood group O have ~ 25% lower plasma levels. The exact mechanism behind this relationship remains unknown, although effects on clearance have been postulated. OBJEC

  7. Blood groups systems

    Directory of Open Access Journals (Sweden)

    Ranadhir Mitra

    2014-01-01

    Full Text Available International Society of Blood Transfusion has recently recognized 33 blood group systems. Apart from ABO and Rhesus system, many other types of antigens have been noticed on the red cell membranes. Blood grouping and cross-matching is one of the few important tests that the anaesthesiologist orders during perioperative period. Hence, a proper understanding of the blood group system, their clinical significance, typing and cross-matching tests, and current perspective are of paramount importance to prevent transfusion-related complications. Nonetheless, the knowledge on blood group system is necessary to approach blood group-linked diseases which are still at the stage of research. This review addresses all these aspects of the blood groups system.

  8. Male microchimerism at high levels in peripheral blood mononuclear cells from women with end stage renal disease before kidney transplantation.

    Directory of Open Access Journals (Sweden)

    Laetitia Albano

    Full Text Available Patients with end stage renal diseases (ESRD are generally tested for donor chimerism after kidney transplantation for tolerance mechanism purposes. But, to our knowledge, no data are available on natural and/or iatrogenic microchimerism (Mc, deriving from pregnancy and/or blood transfusion, acquired prior to transplantation. In this context, we tested the prevalence of male Mc using a real time PCR assay for DYS14, a Y-chromosome specific sequence, in peripheral blood mononuclear cells (PBMC from 55 women with ESRD, prior to their first kidney transplantation, and compared them with results from 82 healthy women. Male Mc was also quantified in 5 native kidney biopsies obtained two to four years prior to blood testing and in PBMC from 8 women collected after female kidney transplantation, several years after the initial blood testing. Women with ESRD showed statistically higher frequencies (62% and quantities (98 genome equivalent cells per million of host cells, gEq/M of male Mc in their PBMC than healthy women (16% and 0.3 gEq/M, p<0.00001 and p = 0.0005 respectively. Male Mc was increased in women with ESRD whether they had or not a history of male pregnancy and/or of blood transfusion. Three out of five renal biopsies obtained a few years prior to the blood test also contained Mc, but no correlation could be established between earlier Mc in a kidney and later presence in PBMC. Finally, several years after female kidney transplantation, male Mc was totally cleared from PBMC in all women tested but one. This intriguing and striking initial result of natural and iatrogenic male Mc persistence in peripheral blood from women with ESRD raises several hypotheses for the possible role of these cells in renal diseases. Further studies are needed to elucidate mechanisms of recruitment and persistence of Mc in women with ESRD.

  9. Male microchimerism at high levels in peripheral blood mononuclear cells from women with end stage renal disease before kidney transplantation.

    Science.gov (United States)

    Albano, Laetitia; Rak, Justyna M; Azzouz, Doua F; Cassuto-Viguier, Elisabeth; Gugenheim, Jean; Lambert, Nathalie C

    2012-01-01

    Patients with end stage renal diseases (ESRD) are generally tested for donor chimerism after kidney transplantation for tolerance mechanism purposes. But, to our knowledge, no data are available on natural and/or iatrogenic microchimerism (Mc), deriving from pregnancy and/or blood transfusion, acquired prior to transplantation. In this context, we tested the prevalence of male Mc using a real time PCR assay for DYS14, a Y-chromosome specific sequence, in peripheral blood mononuclear cells (PBMC) from 55 women with ESRD, prior to their first kidney transplantation, and compared them with results from 82 healthy women. Male Mc was also quantified in 5 native kidney biopsies obtained two to four years prior to blood testing and in PBMC from 8 women collected after female kidney transplantation, several years after the initial blood testing. Women with ESRD showed statistically higher frequencies (62%) and quantities (98 genome equivalent cells per million of host cells, gEq/M) of male Mc in their PBMC than healthy women (16% and 0.3 gEq/M, ppregnancy and/or of blood transfusion. Three out of five renal biopsies obtained a few years prior to the blood test also contained Mc, but no correlation could be established between earlier Mc in a kidney and later presence in PBMC. Finally, several years after female kidney transplantation, male Mc was totally cleared from PBMC in all women tested but one. This intriguing and striking initial result of natural and iatrogenic male Mc persistence in peripheral blood from women with ESRD raises several hypotheses for the possible role of these cells in renal diseases. Further studies are needed to elucidate mechanisms of recruitment and persistence of Mc in women with ESRD.

  10. Meningitis Caused by Toscana Virus Is Associated with Strong Antiviral Response in the CNS and Altered Frequency of Blood Antigen-Presenting Cells

    Directory of Open Access Journals (Sweden)

    Stefania Varani

    2015-11-01

    Full Text Available Toscana virus (TOSV is a Phlebotomus-transmitted RNA virus and a frequent cause of human meningitis and meningoencephalitis in Southern Europe during the summer season. While evidence for TOSV-related central nervous system (CNS cases is increasing, little is known about the host defenses against TOSV. We evaluated innate immune response to TOSV by analyzing frequency and activation of blood antigen-presenting cells (APCs and cytokine levels in plasma and cerebrospinal fluid (CSF from patients with TOSV neuroinvasive infection and controls. An altered frequency of different blood APC subsets was observed in TOSV-infected patients, with signs of monocytic deactivation. Nevertheless, a proper or even increased responsiveness of toll-like receptor 3 and 7/8 was observed in blood APCs of these patients as compared to healthy controls. Systemic levels of cytokines remained low in TOSV-infected patients, while levels of anti-inflammatory and antiviral mediators were significantly higher in CSF from TOSV-infected patients as compared to patients with other infectious and noninfectious neurological diseases. Thus, the early host response to TOSV appears effective for viral clearance, by proper response to TLR3 and TLR7/8 agonists in peripheral blood and by a strong and selective antiviral and anti-inflammatory response in the CNS.

  11. Autologous peripheral blood stem cell transplantation in tumor-stage mycosis fungoides: predictors of disease-free survival.

    Science.gov (United States)

    Russell-Jones, R; Child, F; Olavarria, E; Whittaker, S; Spittle, M; Apperley, J

    2001-09-01

    Nine patients with mycosis fungoides (age range 27-67) underwent autologous peripheral blood stem cell transplantation (PBSCT). All patients had tumor-stage disease, and four had lymph node involvement. Eight patients exhibited a peripheral blood T cell clone using PCR/SSCP analysis of the TCR gamma gene, six prior to harvest and two at the time of harvest. Mobilization of CD34+ stem cells was achieved with etoposide and G-CSF. Harvested cells were positively selected for CD34. After negative selection for CD4 and CD8, only two samples became PCR negative. Conditioning prior to reinfusion of stem cells was achieved with various combinations of total skin electron beam (TSEB), total body irradiation (TBI), and chemotherapy, depending upon the patient's prior exposure to radiotherapy. One patient failed to engraft and died of candidal septicemia 15 days posttransplant. The other eight patients achieved complete remission, but this was short-lived in four (median disease-free survival [DFS] = 2 months) and prolonged in three (median DFS 11 months). Those with a short DFS were distinguished by rapid tumor onset prior to transplant but not by stage at transplant. Loss of a detectable T cell clone after manipulation of the harvest did not discriminate between the two groups, but rapid relapsers had been subjected to a greater degree of T cell depletion, possibly indicating a compromised cytotoxic response post-PBSCT. The median survival of the cohort is four years from tumor onset, 15 months from PBSCT, and 27 months from the date a peripheral blood clone was first detected in the presence of tumor-stage disease. Rapid relapse was associated with poor overall survival. Our data demonstrate the value of PBSCT for inducing remission in tumor-stage mycosis fungoides. Reinfusion of neoplastic cells could be avoided by harvesting stem cells at an earlier stage in the disease process, preferably before a T cell clone is detectable in the peripheral blood. Alternatively T cell

  12. PSA Nadir of <0.5 ng/mL Following Brachytherapy for Early-Stage Prostate Adenocarcinoma is Associated With Freedom From Prostate-Specific Antigen Failure

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Eric C. [Department of Radiation Oncology, Mount Sinai Medical Center, New York, NY (United States); Stone, Nelson N. [Department of Radiation Oncology, Mount Sinai Medical Center, New York, NY (United States); Department of Urology, Mount Sinai Medical Center, New York, NY (United States); Stock, Richard G., E-mail: Richard.Stock@mountsinai.org [Department of Radiation Oncology, Mount Sinai Medical Center, New York, NY (United States)

    2012-06-01

    Purpose: Because limited information exists regarding whether the rate or magnitude of PSA decline following brachytherapy predicts long-term clinical outcomes, we evaluated whether achieving a prostate-specific antigen (PSA) nadir (nPSA) <0.5 ng/mL following brachytherapy is associated with decreased PSA failure and/or distant metastasis. Methods and Materials: We retrospectively analyzed our database of early-stage prostate adenocarcinoma patients who underwent brachytherapy, excluding those receiving androgen-deprivation therapy and those with <2 years follow-up. Median and mean pretreatment PSA were 6 ng/mL and 7.16 ng/mL, respectively. By clinical stage, 775 were low risk ({<=}T2a), 126 were intermediate risk (T2b), and 20 were high risk (>T2b). By Gleason score, 840 were low risk ({<=}6), 71 were intermediate risk (7), and 10 were high risk (>7). Patients were treated with brachytherapy only (I-125, n = 779, or Pd-103, n = 47), or brachytherapy + external-beam radiation therapy (n = 95). Median follow-up was 6.3 years. We noted whether nPSA <0.5 ng/mL was achieved and the time to achieve this nadir and tested for associations with pretreatment risk factors. We also determined whether this PSA endpoint was associated with decreased PSA failure or distant metastasis. Results: Absence of high-risk factors in clinical stage ({<=}T2b), Gleason score ({<=}7), and pretreatment PSA ({<=}20 ng/mL) was significantly associated with achieving nPSA <0.5 ng/mL. By Kaplan-Meier analysis, patients achieving nPSA <0.5 ng/mL had significantly higher long-term freedom from biochemical failure (FFBF) than nonresponders (5-year FFBF: 95.2 {+-} 0.8% vs. 71.5 {+-} 6.7%; p < 0.0005). Among responders, those who achieved nPSA <0.5 ng/mL in {<=}5 years had higher FFBF than those requiring >5 years (5-year FFBF: 96.7 {+-} 0.7% vs. 80.8 {+-} 4.6%; p < 0.0005). On multivariate analysis, patients who achieved nPSA <0.5 ng/mL in {<=}5 years had significantly higher FFBF than other

  13. Interruption of the blood-stage cycle of the malaria parasite, Plasmodium chabaudi, by protein tyrosine kinase inhibitors

    Directory of Open Access Journals (Sweden)

    M.L. Gazarini

    2003-11-01

    Full Text Available Malaria is a devastating disease caused by a unicellular protozoan, Plasmodium, which affects 3.7 million people every year. Resistance of the parasite to classical treatments such as chloroquine requires the development of new drugs. To gain insight into the mechanisms that control Plasmodium cell cycle, we have examined the effects of kinase inhibitors on the blood-stage cycle of the rodent malaria parasite, Plasmodium chabaudi. In vitro incubation of red blood cells for 17 h at 37ºC with the inhibitors led to a decrease in the percent of infected cells, compared to control treatment, as follows: genistein (200 µM - 75%, staurosporine (1 µM - 58%, R03 (1 µM - 75%, and tyrphostins B44 (100 µM - 66% and B46 (100 µM - 68%. All these treatments were shown to retard or prevent maturation of the intraerythrocytic parasites. The diverse concentration ranges at which these inhibitors exert their effects give a clue as to the types of signals that initiate the transitions between the different developmental stages of the parasite. The present data support our hypothesis that the maturation of the intraerythrocytic cycle of malaria parasites requires phosphorylation. In this respect, we have recently reported a high Ca2+ microenvironment surrounding the parasite within red blood cells. Several kinase activities are modulated by Ca2+. The molecular identification of the targets of these kinases could provide new strategies against malaria.

  14. Mature dendritic cells generated from patient-derived peripheral blood monocytes in one-step culture using streptococcal preparation OK-432 exert an enhanced antigen-presenting capacity.

    Science.gov (United States)

    Naito, Kei; Ueda, Yuji; Itoh, Tsuyoshi; Fuji, Nobuaki; Shimizu, Keiji; Yano, Yutaro; Yamamoto, Yoshiki; Imura, Kenichiro; Kohara, Junji; Iwamoto, Arihiro; Shiozaki, Atsushi; Tamai, Hidemasa; Shimizu, Takeshi; Mazda, Osam; Yamagishi, Hisakazu

    2006-06-01

    Dendritic cells (DCs) have been shown to be potent in inducing cytotoxic T cell (CTL) response leading to the efficient anti-tumor effect in active immunotherapy. Myeloid DCs are conventionally generated from human peripheral blood monocytes in the presence of interleukin (IL)-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF). Streptococcal preparation OK-432, which is known to be a multiple cytokine inducer, has been extensively studied as to its maturation effects on immature DCs using an in vitro culture system. The purpose of this study was to examine whether it could be possible to generate mature DCs directly from peripheral monocytes using OK-432. We specifically focused on the possibility that recombinant cytokines, which are considered to be essential for in vitro DC generation, could be substituted by OK-432. Human peripheral monocytes, which were obtained from patients with advanced cancer, were cultured with IL-4 and OK-432 for 7 days. Cultured cells were compared with DCs generated in the presence of IL-4 and GM-CSF with or without OK-432 with regard to the surface phenotype as well as the antigen-presenting capacity. As a result, the culture of monocytes in the presence of IL-4 followed by the addition of OK-432 on day 4 (IL-4/OK-DC) induced cells with a fully mature DC phenotype. Functional assays also demonstrated that IL-4/OK-DCs had a strong antigen-presenting capacity determined by their enhanced antigen-specific CTL response and exerted a Th1-type T cell response which is critical for the induction of anti-tumor response. In conclusion, human peripheral blood monocytes cultured in the presence of IL-4 and OK-432 without exogenous GM-CSF demonstrated a fully mature DC phenotype and strong antigen-presenting capacity. This one-step culture protocol allows us to generate fully mature DCs directly from monocytes in 7 days and thus, this protocol can be applicable for DC-based anti-tumor immunotherapy.

  15. Ontology-based Malaria Parasite Stage and Species Identification from Peripheral Blood Smear Images

    NARCIS (Netherlands)

    Makkapati, V.; Rao, R.

    2011-01-01

    The diagnosis and treatment of malaria infection requires detectingthe presence of malaria parasite in the patient as well as identification of the parasite species. We present an image processing-basedapproach to detect parasites in microscope images of blood smear andan ontology-based classificati

  16. Longitudinal observations on circadian blood pressure variation in chronic kidney disease stages 3-5

    DEFF Research Database (Denmark)

    Elung-Jensen, Thomas; Strandgaard, Svend; Kamper, Anne-Lise

    2008-01-01

    BACKGROUND: It has been suggested that status as a 'non-dipper' determined from 24-h blood pressure (BP) recordings is associated with increased risk of end-organ damage but little is known about the consistency of dipper status in renal patients. The present post hoc analysis evaluated dipper...

  17. [Identification of blood donors capable of transmitting P. falciparum. Use of homologous antigenic preparations ready for use].

    Science.gov (United States)

    Deroff, P; Reguer, M; Simitzis, A M; Boudon, A; Saleun, J P

    1982-09-01

    The smears of P. falciparum parasited blood ready to be employed, that we have tested in indirect immunofluorescence to detect blood donors who can be at the origin of post transfusional paludism, seem to offer a very important progress to us for the improvement of transfusion security. Their routine use can be recommended because their easy way of using allows their adoption by very many transfusion centers.

  18. EFFECT OF PLANT LECTINS ON HUMAN BLOOD GROUP ANTIGENS WITH SPECIAL FOCUS ON PLANT FOODS AND JUICES

    Directory of Open Access Journals (Sweden)

    B. Venkata Raman

    2012-04-01

    Full Text Available Different plant lectins have been studied for lectin binding activity on ABO blood group system individually to study their suitability for consumption. 45% of plants were found to show blood group agglutination activity against A, B, AB and O groups. These results showed more suitability for consumption of investigated plants and their products to entire human population. Data also alarming human to be more careful about the plant lectins reacting with blood groups as the similar reactions may possibly happen at mucosal surface of the gut. In fact, chemical composition on RBC may similar with mucosal cell surfaces of human gastrointestinal tract. In our investigation results reveal that 27 percent of plant extracts showed activity against A, 38 percent of plant extracts for B, 45 percent plant extracts on AB and 45 percent of plants on O group blood populations of human beings. Further, O blood group humans have shown more significant activity (10 different plants than A, B and AB. Hence, these double blind placebo studies are very promising and would give better results for suitability and digestibility of foods taking either as staple foods or juices, and also several health benefits for controlling the diet intake, based on the blood group type.

  19. Efficacy of combination therapy with amlodipine besylate/benazepril hydrochloride for lowering systolic blood pressure in stage 2 hypertension.

    Science.gov (United States)

    Neutel, Joel M; Smith, David H G; Weber, Michael A; Schofield, Lesley; Purkayastha, Das; Gatlin, Marjorie

    2006-01-01

    The Systolic Evaluation of Lotrel Efficacy and Comparative Therapies (SELECT) study compared daily treatment with combination amlodipine besylate/benazepril hydrochloride 5/20 mg, amlodipine besylate 5 mg, and benazepril hydrochloride 20 mg in 505 patients aged 55 years of age or older with stage 2 hypertension (systolic blood pressure [BP] > or =160 and or =60 and < or =100 mm Hg). BP and pulse pressure were assessed by conventional office BP measurements and 24-hour ambulatory BP monitoring. In this analysis, combination therapy was associated with significantly greater reductions in mean 24-hour BP, pulse pressure, and mean ambulatory BP during various time intervals compared with either monotherapy in the intent-to-treat population, in those with isolated and predominantly systolic hypertension, and in dippers and nondippers. Adverse event rates were low and similar in all treatment groups. This study demonstrated that combination therapy is superior to monotherapy in older patients with stage 2 systolic hypertension and is well tolerated.

  20. Antigenicity, Immunogenicity and Protective Efficacy of Three Proteins Expressed in the Promastigote and Amastigote Stages of Leishmania infantum against Visceral Leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Vivian Tamietti Martins

    Full Text Available In the present study, two Leishmania infantum hypothetical proteins present in the amastigote stage, LiHyp1 and LiHyp6, were combined with a promastigote protein, IgE-dependent histamine-releasing factor (HRF; to compose a polyproteins vaccine to be evaluated against L. infantum infection. Also, the antigenicity of the three proteins was analyzed, and their use for the serodiagnosis of canine visceral leishmaniasis (CVL was evaluated. The LiHyp1, LiHyp6, and HRF DNA coding sequences were cloned in prokaryotic expression vectors and the recombinant proteins were purified. When employed in ELISA assays, all proteins were recognized by sera from visceral leishmaniasis (VL dogs, and presented no cross-reactivity with either sera from dogs vaccinated with a Brazilian commercial vaccine, or sera of Trypanosoma cruzi-infected or Ehrlichia canis-infected animals. In addition, the antigens were not recognized by antibodies from non-infected animals living in endemic or non-endemic areas for leishmaniasis. The immunogenicity and protective efficacy of the three proteins administered in the presence of saponin, individually or in combination (composing a polyproteins vaccine, were evaluated in a VL murine model: BALB/c mice infected with L. infantum. Spleen cells from mice inoculated with the individual proteins or with the polyproteins vaccine plus saponin showed a protein-specific production of IFN-γ, IL-12, and GM-CSF after an in vitro stimulation, which was maintained after infection. These animals presented significant reductions in the parasite burden in different evaluated organs, when compared to mice inoculated with saline or saponin. The decrease in parasite burden was associated with an IL-12-dependent production of IFN-γ against parasite total extracts (produced mainly by CD4+ T cells, correlated to the induction of parasite proteins-driven NO production. Mice inoculated with the recombinant protein-based vaccines showed also high levels of

  1. Antigenicity, Immunogenicity and Protective Efficacy of Three Proteins Expressed in the Promastigote and Amastigote Stages of Leishmania infantum against Visceral Leishmaniasis

    Science.gov (United States)

    Martins, Vivian Tamietti; Chávez-Fumagalli, Miguel Angel; Lage, Daniela Pagliara; Duarte, Mariana Costa; Garde, Esther; Costa, Lourena Emanuele; da Silva, Viviane Gomes; Oliveira, Jamil Silvano; de Magalhães-Soares, Danielle Ferreira; Teixeira, Santuza Maria Ribeiro; Fernandes, Ana Paula; Soto, Manuel; Tavares, Carlos Alberto Pereira; Coelho, Eduardo Antonio Ferraz

    2015-01-01

    In the present study, two Leishmania infantum hypothetical proteins present in the amastigote stage, LiHyp1 and LiHyp6, were combined with a promastigote protein, IgE-dependent histamine-releasing factor (HRF); to compose a polyproteins vaccine to be evaluated against L. infantum infection. Also, the antigenicity of the three proteins was analyzed, and their use for the serodiagnosis of canine visceral leishmaniasis (CVL) was evaluated. The LiHyp1, LiHyp6, and HRF DNA coding sequences were cloned in prokaryotic expression vectors and the recombinant proteins were purified. When employed in ELISA assays, all proteins were recognized by sera from visceral leishmaniasis (VL) dogs, and presented no cross-reactivity with either sera from dogs vaccinated with a Brazilian commercial vaccine, or sera of Trypanosoma cruzi-infected or Ehrlichia canis-infected animals. In addition, the antigens were not recognized by antibodies from non-infected animals living in endemic or non-endemic areas for leishmaniasis. The immunogenicity and protective efficacy of the three proteins administered in the presence of saponin, individually or in combination (composing a polyproteins vaccine), were evaluated in a VL murine model: BALB/c mice infected with L. infantum. Spleen cells from mice inoculated with the individual proteins or with the polyproteins vaccine plus saponin showed a protein-specific production of IFN-γ, IL-12, and GM-CSF after an in vitro stimulation, which was maintained after infection. These animals presented significant reductions in the parasite burden in different evaluated organs, when compared to mice inoculated with saline or saponin. The decrease in parasite burden was associated with an IL-12-dependent production of IFN-γ against parasite total extracts (produced mainly by CD4+ T cells), correlated to the induction of parasite proteins-driven NO production. Mice inoculated with the recombinant protein-based vaccines showed also high levels of parasite

  2. Crystallography of a Lewis-binding norovirus, elucidation of strain-specificity to the polymorphic human histo-blood group antigens.

    Directory of Open Access Journals (Sweden)

    Yutao Chen

    2011-07-01

    Full Text Available Noroviruses, an important cause of acute gastroenteritis in humans, recognize the histo-blood group antigens (HBGAs as host susceptible factors in a strain-specific manner. The crystal structures of the HBGA-binding interfaces of two A/B/H-binding noroviruses, the prototype Norwalk virus (GI.1 and a predominant GII.4 strain (VA387, have been elucidated. In this study we determined the crystal structures of the P domain protein of the first Lewis-binding norovirus (VA207, GII.9 that has a distinct binding property from those of Norwalk virus and VA387. Co-crystallization of the VA207 P dimer with Le(y or sialyl Le(x tetrasaccharides showed that VA207 interacts with these antigens through a common site found on the VA387 P protein which is highly conserved among most GII noroviruses. However, the HBGA-binding site of VA207 targeted at the Lewis antigens through the α-1, 3 fucose (the Lewis epitope as major and the β-N-acetyl glucosamine of the precursor as minor interacting sites. This completely differs from the binding mode of VA387 and Norwalk virus that target at the secretor epitopes. Binding pocket of VA207 is formed by seven amino acids, of which five residues build up the core structure that is essential for the basic binding function, while the other two are involved in strain-specificity. Our results elucidate for the first time the genetic and structural basis of strain-specificity by a direct comparison of two genetically related noroviruses in their interaction with different HBGAs. The results provide insight into the complex interaction between the diverse noroviruses and the polymorphic HBGAs and highlight the role of human HBGA as a critical factor in norovirus evolution.

  3. Magnetic Nanovectors for the Development of DNA Blood-Stage Malaria Vaccines

    Directory of Open Access Journals (Sweden)

    Fatin M. Nawwab Al-Deen

    2017-02-01

    Full Text Available DNA vaccines offer cost, flexibility, and stability advantages, but administered alone have limited immunogenicity. Previously, we identified optimal configurations of magnetic vectors comprising superparamagnetic iron oxide nanoparticles (SPIONs, polyethylenimine (PEI, and hyaluronic acid (HA to deliver malaria DNA encoding Plasmodium yoelii (Py merozoite surface protein MSP119 (SPIONs/PEI/DNA + HA gene complex to dendritic cells and transfect them with high efficiency in vitro. Herein, we evaluate their immunogenicity in vivo by administering these potential vaccine complexes into BALB/c mice. The complexes induced antibodies against PyMSP119, with higher responses induced intraperitoneally than intramuscularly, and antibody levels further enhanced by applying an external magnetic field. The predominant IgG subclasses induced were IgG2a followed by IgG1 and IgG2b. The complexes further elicited high levels of interferon gamma (IFN-γ, and moderate levels of interleukin (IL-4 and IL-17 antigen-specific splenocytes, indicating induction of T helper 1 (Th1, Th2, and Th17 cell mediated immunity. The ability of such DNA/nanoparticle complexes to induce cytophilic antibodies together with broad spectrum cellular immunity may benefit malaria vaccines.

  4. Magnetic Nanovectors for the Development of DNA Blood-Stage Malaria Vaccines

    Science.gov (United States)

    Al-Deen, Fatin M. Nawwab; Xiang, Sue D.; Ma, Charles; Wilson, Kirsty; Coppel, Ross L.; Selomulya, Cordelia; Plebanski, Magdalena

    2017-01-01

    DNA vaccines offer cost, flexibility, and stability advantages, but administered alone have limited immunogenicity. Previously, we identified optimal configurations of magnetic vectors comprising superparamagnetic iron oxide nanoparticles (SPIONs), polyethylenimine (PEI), and hyaluronic acid (HA) to deliver malaria DNA encoding Plasmodium yoelii (Py) merozoite surface protein MSP119 (SPIONs/PEI/DNA + HA gene complex) to dendritic cells and transfect them with high efficiency in vitro. Herein, we evaluate their immunogenicity in vivo by administering these potential vaccine complexes into BALB/c mice. The complexes induced antibodies against PyMSP119, with higher responses induced intraperitoneally than intramuscularly, and antibody levels further enhanced by applying an external magnetic field. The predominant IgG subclasses induced were IgG2a followed by IgG1 and IgG2b. The complexes further elicited high levels of interferon gamma (IFN-γ), and moderate levels of interleukin (IL)-4 and IL-17 antigen-specific splenocytes, indicating induction of T helper 1 (Th1), Th2, and Th17 cell mediated immunity. The ability of such DNA/nanoparticle complexes to induce cytophilic antibodies together with broad spectrum cellular immunity may benefit malaria vaccines.

  5. [Early stages of development of Trypanosoma rotatorium (Mayer, 1843) from peripheral blood and internal organs of Anurans Bufo bufo (Linnaeus) and Rana sp. (Anura)].

    Science.gov (United States)

    Malysheva, M N

    2014-01-01

    The data on the fauna of trypanosomes of Anura of the Leningrad Province are given. The initial development stages of Trypanosoma rotatorium in peripheral blood and internal organs of the frog are described for the first time.

  6. Induction of multi-antigen multi-stage immune responses against Plasmodium falciparum in rhesus monkeys, in the absence of antigen interference, with heterologous DNA prime/poxvirus boost immunization.

    Science.gov (United States)

    Jiang, George; Charoenvit, Yupin; Moreno, Alberto; Baraceros, Maria F; Banania, Glenna; Richie, Nancy; Abot, Steve; Ganeshan, Harini; Fallarme, Victoria; Patterson, Noelle B; Geall, Andrew; Weiss, Walter R; Strobert, Elizabeth; Caro-Aquilar, Ivette; Lanar, David E; Saul, Allan; Martin, Laura B; Gowda, Kalpana; Morrissette, Craig R; Kaslow, David C; Carucci, Daniel J; Galinski, Mary R; Doolan, Denise L

    2007-10-09

    The present study has evaluated the immunogenicity of single or multiple Plasmodium falciparum (Pf) antigens administered in a DNA prime/poxvirus boost regimen with or without the poloxamer CRL1005 in rhesus monkeys. Animals were primed with PfCSP plasmid DNA or a mixture of PfCSP, PfSSP2/TRAP, PfLSA1, PfAMA1 and PfMSP1-42 (CSLAM) DNA vaccines in PBS or formulated with CRL1005, and subsequently boosted with ALVAC-Pf7, a canarypox virus expressing the CSLAM antigens. Cell-mediated immune responses were evaluated by IFN-gamma ELIspot and intracellular cytokine staining, using recombinant proteins and overlapping synthetic peptides. Antigen-specific and parasite-specific antibody responses were evaluated by ELISA and IFAT, respectively. Immune responses to all components of the multi-antigen mixture were demonstrated following immunization with either DNA/PBS or DNA/CRL1005, and no antigen interference was observed in animals receiving CSLAM as compared to PfCSP alone. These data support the down-selection of the CSLAM antigen combination. CRL1005 formulation had no apparent effect on vaccine-induced T cell or antibody responses, either before or after viral boost. In high responder monkeys, CD4+IL-2+ responses were more predominant than CD8+ T cell responses. Furthermore, CD8+ IFN-gamma responses were detected only in the presence of detectable CD4+ T cell responses. Overall, this study demonstrates the potential for multivalent Pf vaccines based on rational antigen selection and combination, and suggests that further formulation development to increase the immunogenicity of DNA encoded antigens is warranted.

  7. STUDY ON PERIPHERAL BLOOD MONONUCLEAR CELL(PBMC) PROLIFERATIVE RESPONSES TO DIFFERENT HCV ANTIGENS IN PATIENTS WITH HEPATITIS C

    Institute of Scientific and Technical Information of China (English)

    窦骏; 刘克洲; 陈智; 沃建尔; 何南祥; 徐陈槐; 章明太; 王信子

    1999-01-01

    To explore the cellular immune function in patients with hepatitis C and study the HCV pathogenic mechanism and immune protection effect against HCV infection in host. PBMC proliferative responses in vitro to HCV synthetic peptides (Cp9, Ns4) and recombinant HCV proteins (C,E1 ,E2 ,NS3) were evaluated in 21 patients with chronic hepatitis C and 3 patients with acute hepatitis C. Phenotypic characteristics of proliferating cells in PBMC were detected by FACS after PBMC were stimulated with HCV antigens. Results showed that lymphoproliferative responses of PBMC from patients with hepatitis C to synthetic peptides (Cp9, NS4) and rccombinant proteins (C,E1 ,E2 and NS3) were detected and its stimulation index(SI) were 1.69±0.51, 1. 61±0.54, 1. 68±0.58,1. 49±0.44, 1.44±0.44 and 1. 33±0. 33 respectively. Two out of three patients with acute hepatitis C had efficient lymphoproliferative response to HCV antigens (SI≥2. 1) and their serum HCV-RNA were seroconversion and serum ALT values were returned to normal when studied. Phenotype analysis showed that phenotypic characteristics of proliferating cells was CD4+ lymphocytes and CD8+ lymphocytes proliferative responses was less than that of CD4+ lymphocytes. The results indicate that PBMC from patients with hepatitis C exist proliferative responses to different HCV antigens. CD4+ lymphocytes proliferative response is greater than that of CD8+ lymphocytes. The efficient lymphoproliferative responses to HCV antigens in patients with acute hepatitis C suggests that the patients possibly have a good clinical prognosis.%为探讨丙型肝炎(HC)病人细胞免疫功能和丙型肝炎病毒(HCV)的致病机制及机体对其免疫保护作用,收集24例HC病人(急性3例,慢性21例),用3H-TdR掺入法研究病人外周血单个核细胞(PBMC)对不同HCV抗原增殖反应,并用流式细胞仪(FACS)检测了PBMC中CD4+、CD8+淋巴细胞亚群在HCV抗原刺激后的变化.结果:HC病人PBMC对HCV合成肽CP9,NS

  8. [The diagnosis, treatment and prevention of early stages of cerebral blood flow insufficiency].

    Science.gov (United States)

    Martynov, Iu S; Girich, T I; Kuntsevich, G I; Sokov, E L; Malkova, E V; Borisova, N F; Nozdriukhina, N V; Shuvakhina, N A

    1998-01-01

    Biomicroscopy of bulbar conjuctiva as well as oencephalography were quite informative for discovery of subclinical manifestations of disorders of cerebral circulation (DCC). That conclusion resulted from the observation of 133 patients with early forms of vascular pathology of brain. Besides, to find the early signs, it was also worth while to perform some biochemical studies (coagulogram, studies of both rheologic properties and lipids of blood). In order to establish discirculatory encephalopathy it was also expedient to use ultrasonic dopplerography and electroencephalography. Efficiency of some medical-prophylactic measures (normalization of the diet, weight, muscular activity, administration of antiatherosclerotic drugs) that prevented the progression of aorta's stenosis was also demonstrated.

  9. Comparative testing of six antigen-based malaria vaccine candidates directed toward merozoite-stage Plasmodium falciparum

    DEFF Research Database (Denmark)

    Arnot, David E; Cavanagh, David R; Remarque, Edmond J;

    2008-01-01

    Immunogenicity testing of Plasmodium falciparum antigens being considered as malaria vaccine candidates was undertaken in rabbits. The antigens compared were recombinant baculovirus MSP-1(19) and five Pichia pastoris candidates, including two versions of MSP-1(19), AMA-1 (domains I and II), AMA-1...

  10. Evidence for an amoeba-like infectious stage of ichthyophonus sp. and description of a circulating blood stage: a probable mechanism for dispersal within the fish host

    Science.gov (United States)

    Kocan, Richard; LaPatra, Scott; Hershberger, Paul

    2013-01-01

    Small amoeboid cells, believed to be the infectious stage of Ichthyophonus sp., were observed in the bolus (stomach contents) and tunica propria (stomach wall) of Pacific staghorn sculpins and rainbow trout shortly after they ingested Ichthyophonus sp.–infected tissues. By 24–48 hr post-exposure (PE) the parasite morphed from the classically reported multinucleate thick walled schizonts to 2 distinct cell types, i.e., a larger multinucleate amoeboid cell surrounded by a narrow translucent zone and a smaller spherical cell surrounded by a “halo” and resembling a small schizont. Both cell types also appeared in the tunica propria, indicating that they had recently penetrated the columnar epithelium of the stomach. No Ichthyophonus sp. pseudo-hyphae (“germination tubes”) were observed in the bolus or penetrating the stomach wall. Simultaneously, Ichthyophonus sp. was isolated in vitro from aortic blood, which was consistently positive from 6 to 144 hr PE, then only intermittently for the next 4 wk. Small PAS-positive cells observed in blood cultures grew into colonies consisting of non-septate tubules (pseudo-hyphae) terminating in multinucleated knob-like apices similar to those seen in organ explant cultures. Organ explants were culture positive every day; however, typical Ichthyophonus sp. schizonts were not observed histologically until 20–25 days PE. From 20 to 60 days PE, schizont diameter increased from ≤25 μm to ≥82 μm. Based on the data presented herein, we are confident that we have resolved the life cycle of Ichthyophonus sp. within the piscivorous host.

  11. Plasmodium falciparum SERA5 plays a non-enzymatic role in the malarial asexual blood-stage lifecycle.

    Science.gov (United States)

    Stallmach, Robert; Kavishwar, Manoli; Withers-Martinez, Chrislaine; Hackett, Fiona; Collins, Christine R; Howell, Steven A; Yeoh, Sharon; Knuepfer, Ellen; Atid, Avshalom J; Holder, Anthony A; Blackman, Michael J

    2015-04-01

    The malaria parasite Plasmodium falciparum replicates in an intraerythrocytic parasitophorous vacuole (PV). The most abundant P. falciparum PV protein, called SERA5, is essential in blood stages and possesses a papain-like domain, prompting speculation that it functions as a proteolytic enzyme. Unusually however, SERA5 possesses a Ser residue (Ser596) at the position of the canonical catalytic Cys of papain-like proteases, and the function of SERA5 or whether it performs an enzymatic role is unknown. In this study, we failed to detect proteolytic activity associated with the Ser596-containing parasite-derived or recombinant protein. However, substitution of Ser596 with a Cys residue produced an active recombinant enzyme with characteristics of a cysteine protease, demonstrating that SERA5 can bind peptides. Using targeted homologous recombination in P. falciparum, we substituted Ser596 with Ala with no phenotypic consequences, proving that SERA5 does not perform an essential enzymatic role in the parasite. We could also replace an internal segment of SERA5 with an affinity-purification tag. In contrast, using almost identical targeting constructs, we could not truncate or C-terminally tag the SERA5 gene, or replace Ser596 with a bulky Arg residue. Our findings show that SERA5 plays an indispensable but non-enzymatic role in the P. falciparum blood-stage life cycle.

  12. L3L4ES antigen and secretagogues induce histamine release from porcine peripheral blood basophils after Ascaris suum infection

    Science.gov (United States)

    The aim of this paper was to investigate the role of porcine basophils in protective immunity. Experimental pigs were infected with 1,000 Ascaris suum eggs daily for 21 days. Control pigs were maintained helminth-free. Circulating porcine basophils were isolated from the anti-coagulated whole blood ...

  13. Phase 1 trial of AMA1-C1/Alhydrogel plus CPG 7909: an asexual blood-stage vaccine for Plasmodium falciparum malaria.

    Directory of Open Access Journals (Sweden)

    Gregory E D Mullen

    Full Text Available BACKGROUND: Apical Membrane Antigen 1 (AMA1, a polymorphic merozoite surface protein, is a leading blood-stage malaria vaccine candidate. This is the first reported use in humans of an investigational vaccine, AMA1-C1/Alhydrogel, with the novel adjuvant CPG 7909. METHODS: A phase 1 trial was conducted at the University of Rochester with 75 malaria-naive volunteers to assess the safety and immunogenicity of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine. Participants were sequentially enrolled and randomized within dose escalating cohorts to receive three vaccinations on days 0, 28 and 56 of either 20 microg of AMA1-C1/Alhydrogel+564 microg CPG 7909 (n = 15, 80 microg of AMA1-C1/Alhydrogel (n = 30, or 80 microg of AMA1-C1/Alhydrogel+564 microg CPG 7909 (n = 30. RESULTS: Local and systemic adverse events were significantly more likely to be of higher severity with the addition of CPG 7909. Anti-AMA1 immunoglobulin G (IgG were detected by enzyme-linked immunosorbent assay (ELISA, and the immune sera of volunteers that received 20 microg or 80 microg of AMA1-C1/Alhydrogel+CPG 7909 had up to 14 fold significant increases in anti-AMA1 antibody concentration compared to 80 microg of AMA1-C1/Alhydrogel alone. The addition of CPG 7909 to the AMA1-C1/Alhydrogel vaccine in humans also elicited AMA1 specific immune IgG that significantly and dramatically increased the in vitro growth inhibition of homologous parasites to levels as high as 96% inhibition. CONCLUSION/SIGNIFICANCE: The safety profile of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine is acceptable, given the significant increase in immunogenicity observed. Further clinical development is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov NCT00344539.

  14. Expression of stage-specific embryonic antigen-4 (SSEA-4) defines spontaneous loss of epithelial phenotype in human solid tumor cells.

    Science.gov (United States)

    Sivasubramaniyan, Kavitha; Harichandan, Abhishek; Schilbach, Karin; Mack, Andreas F; Bedke, Jens; Stenzl, Arnulf; Kanz, Lothar; Niederfellner, Gerhard; Bühring, Hans-Jörg

    2015-08-01

    Stage-specific embryonic antigen-4 (SSEA-4) is a glycosphingolipid, which is overexpressed in some cancers and has been linked to disease progression. However, little is known about the functions of SSEA-4 and the characteristics of SSEA-4 expressing tumor cells. Our studies identified SSEA-4 expression on a subpopulation of cells in many solid tumor cell lines but not in leukemic cell lines. Fluorescence-activated cell sorting-sorted SSEA-4(+) prostate cancer cells formed fibroblast-like colonies with limited cell-cell contacts, whereas SSEA-4(-) cells formed cobblestone-like epithelial colonies. Only colonies derived from SSEA-4(+) cells were enriched for pluripotent embryonic stem cell markers. Moreover, major epithelial cell-associated markers Claudin-7, E-cadherin, ESRP1 and GRHL2 were down-regulated in the SSEA-4(+) fraction of DU145 and HCT-116 cells. Similar to cell lines, SSEA-4(+) primary prostate tumor cells also showed down-regulation of epithelial cell-associated markers. In addition, they showed up-regulation of epithelial-to-mesenchymal transition as well as mesenchymal markers. Furthermore, SSEA-4(+) cells escape from adhesive colonies spontaneously and form invadopodia-like migratory structures, in which SSEA-4, cortactin as well as active pPI3K, pAkt and pSrc are enriched and colocalized. Finally, SSEA-4(+) cells displayed strong tumorigenic ability and stable knockdown of SSEA-4 synthesis resulted in decreased cellular adhesion to different extracellular matrices. In conclusion, we introduce SSEA-4 as a novel marker to identify heterogeneous, invasive subpopulations of tumor cells. Moreover, increased cell-surface SSEA-4 expression is associated with the loss of cell-cell interactions and the gain of a migratory phenotype, suggesting an important role of SSEA-4 in cancer invasion by influencing cellular adhesion to the extracellular matrix.

  15. [The comparison of concentration of endogenous ethanol blood serum in alcoholics and in non-alcoholics at different stages of abstinence].

    Science.gov (United States)

    Lukaszewicz, A; Markowski, T; Pawlak, D

    1997-01-01

    In this report the concentration of endogenous ethanol in blood serum in alcoholics at different stages of abstinence and in non-alcoholics was studied. 36 people--26 alcoholics and 10 non-alcoholics were examined and gas chromatography was used. It was revealed that the longer the period of abstinence in alcoholics, the lower the concentration of endogenous ethanol in blood serum. Moreover, the alcoholics showed a higher concentration of endogenous ethanol in blood serum as compared to non-alcoholics.

  16. Improving blood pressure control in end stage renal disease through a supportive educative nursing intervention.

    Science.gov (United States)

    Kauric-Klein, Zorica

    2012-01-01

    Hypertension in patients on hemodialysis (HD) contributes significantly to their morbidity and mortality. This study examined whether a supportive nursing intervention incorporating monitoring, goal setting, and reinforcement can improve blood pressure (BP) control in a chronic HD population. A randomized controlled design was used and 118 participants were recruited from six HD units in the Detroit metro area. The intervention consisted of (1) BP education sessions; (2) a 12-week intervention, including monitoring, goal setting, and reinforcement; and (3) a 30-day post-intervention follow-up period. Participants in the treatment were asked to monitor their BP, sodium, and fluid intake weekly for 12 weeks in weekly logs. BP, fluid and sodium logs were reviewed weekly with the researcher to determine if goals were met or not met. Reinforcement was given for goals met and problem solving offered when goals were not met. The control group received standard care. Both systolic and diastolic BPs were significantly decreased in the treatment group.

  17. Distinct kinetics of memory B-cell and plasma-cell responses in peripheral blood following a blood-stage Plasmodium chabaudi infection in mice.

    Directory of Open Access Journals (Sweden)

    Eunice W Nduati

    Full Text Available B cell and plasma cell responses take place in lymphoid organs, but because of the inaccessibility of these organs, analyses of human responses are largely performed using peripheral blood mononuclear cells (PBMC. To determine whether PBMC are a useful source of memory B cells and plasma cells in malaria, and whether they reflect Plasmodium-specific B cell responses in spleen or bone marrow, we have investigated these components of the humoral response in PBMC using a model of Plasmodium chabaudi blood-stage infections in C57BL/6 mice. We detected memory B cells, defined as isotype-switched IgD(- IgM(- CD19(+ B cells, and low numbers of Plasmodium chabaudi Merozoite Surface Protein-1 (MSP1-specific memory B cells, in PBMC at all time points sampled for up to 90 days following primary or secondary infection. By contrast, we only detected CD138(+ plasma cells and MSP1-specific antibody-secreting cells within a narrow time frame following primary (days 10 to 25 or secondary (day 10 infection. CD138(+ plasma cells in PBMC at these times expressed CD19, B220 and MHC class II, suggesting that they were not dislodged bone-marrow long-lived plasma cells, but newly differentiated migratory plasmablasts migrating to the bone marrow; thus reflective of an ongoing or developing immune response. Our data indicates that PBMC can be a useful source for malaria-specific memory B cells and plasma cells, but extrapolation of the results to human malaria infections suggests that timing of sampling, particularly for plasma cells, may be critical. Studies should therefore include multiple sampling points, and at times of infection/immunisation when the B-cell phenotypes of interest are likely to be found in peripheral blood.

  18. Using a genomic assay for the detection of SNPs of Knops blood group antigens leads to the identification of two caucasians homozygous for the SNP associated with the knops SL3 antigen

    DEFF Research Database (Denmark)

    Jakobsen, M. A.; Sprogoe, U.

    2015-01-01

    an allele frequency of 4828 A at 4.3%. Both of the patients were homozygous for 4828 T>A (p.1610Thr), suggesting them to be Sl3-. This was later confirmed serologically for one of the patients, because the patient's red cells were found to be compatible with a panreacting antibody from the only other person...... previously described to be Sl3- (personal communication from the International Blood Group Reference Laboratory in Bristol). * Number indicates the nucleotide position of the CR1 gene. Conclusion: In this study, we have set up a genomic assay for identifying the antigens in the Knops system. We found...... was homozygous for 4801 A>G (p.1601Gly) associated with Sl2+ (the rest were all homozygous for 4801 A). The Sl2+ donor was also Mc(a-b+). With regard to Sl3, we found 9 out of 105 (8.6%) donors to be heterozygous for 4828 T>A, and 96 of 105 (91.4%) to be homozygous for 4828 T (p.1610Ser). These numbers yields...

  19. Prevalence of Weak D Antigen In Western Indian Population

    Directory of Open Access Journals (Sweden)

    Tanvi Sadaria

    2015-12-01

    Full Text Available Introduction: Discovery of Rh antigens in 1939 by Landsteiner and Weiner was the revolutionary stage in blood banking. Of these antigens, D, which decides Rh positivity or negativity, is the most antigenic. A problem is encountered when an individual has a weakened expression of D (Du, i.e., fewer numbers of D antigens on red cell membrane. Aims and Objectives: To know the prevalence of weak D in Indian population because incidence varies in different population. To determine the risk of alloimmunization among Rh D negative patients who receives the blood of weak D positive donors. Material and Methods: Rh grouping of 38,962 donors who came to The Department of Immunohematology and Blood Transfusion of Civil Hospital, Ahmedabad from 1st January 2013 to 30th September 2014 was done using the DIAGAST (Automated Grouping. The samples that tested negative for D antigen were further analysed for weak D (Du by indirect antiglobulin test using blend of Ig G and Ig M Anti D. This was done using Column agglutination method in ID card (gel card. Results: The total number of donors studied was 38,962. Out of these 3360(8.6% were tested Rh D negative. All Rh D negative donors were tested for weak D (Du. 22 (0.056% of total donors and 0.65% of Rh negative donors turned out to be weak D (Du positive. Conclusion: The prevalence of weak D (Du in Western Indian population is 0.056 %, So the risk of alloimmunization in our setting due to weak D (Du antigen is marginal. But, testing of weak D antigen is necessary in blood bank because weak D antigen is immunogenic and can produce alloimmunization if transfused to Rh D negative subjects.

  20. Increased red blood cell distribution width associates with cancer stage and prognosis in patients with lung cancer.

    Directory of Open Access Journals (Sweden)

    Yasuko Koma

    Full Text Available BACKGROUND: Red cell distribution width (RDW, one of many routinely examined parameters, shows the heterogeneity in erythrocyte size. We investigated the association of RDW levels with clinical parameters and prognosis of lung cancer patients. METHODS: Clinical and laboratory data from 332 patients with lung cancer in a single institution were retrospectively studied by univariate analysis. Kaplan-Meier survival analysis and Cox proportional hazard models were used to examine the effect of RDW on survival. RESULTS: THE RDW LEVELS WERE DIVIDED INTO TWO GROUPS: high RDW (>=15%, n=73 vs. low RDW, n=259 (<15%. Univariate analysis showed that there were significant associations of high RDW values with cancer stage, performance status, presence of other disease, white blood cell count, hemoglobin, mean corpuscular volume, platelet count, albumin level, C-reactive protein level, and cytokeratin 19 fragment level. Kruskal-Wallis tests revealed an association of RDW values with cancer stage in patients irrespective of comorbidity (patient with/without comorbidity: p<0.0001, patient without comorbidity: p<0.0001. Stages I-IV lung cancer patients with higher RDW values had poorer prognoses than those with lower RDW values (Wilcoxon test: p=0.002. In particular, the survival rates of stage I and II patients (n=141 were lower in the high RDW group (n=19 than in the low RDW group (n=122 (Wilcoxon test: p<0.001. Moreover, multivariate analysis showed higher RDW is a significant prognostic factor (p=0.040. CONCLUSION: RDW is associated with several factors that reflect inflammation and malnutrition in lung cancer patients. Moreover, high levels of RDW are associated with poor survival. RDW might be used as a new and convenient marker to determine a patient's general condition and to predict the mortality risk of lung cancer patients.

  1. IPP-rich milk protein hydrolysate lowers blood pressure in subjects with stage 1 hypertension, a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Kloek Joris

    2010-11-01

    Full Text Available Abstract Background Milk derived peptides have been identified as potential antihypertensive agents. The primary objective was to investigate the effectiveness of IPP-rich milk protein hydrolysates (MPH on reducing blood pressure (BP as well as to investigate safety parameters and tolerability. The secondary objective was to confirm or falsify ACE inhibition as the mechanism underlying BP reductions by measuring plasma renin activity and angiotensin I and II. Methods We conducted a randomized, placebo-controlled, double blind, crossover study including 70 Caucasian subjects with prehypertension or stage 1 hypertension. Study treatments consisted of daily consumption of two capsules MPH1 (each containing 7.5 mg Isoleucine-Proline-Proline; IPP, MPH2 (each containing 6.6 mg Methionine-Alanine-Proline, 2.3 mg Leucine-Proline-Proline, 1.8 mg IPP, or placebo (containing cellulose for 4 weeks. Results In subjects with stage 1 hypertension, MPH1 lowered systolic BP by 3.8 mm Hg (P = 0.0080 and diastolic BP by 2.3 mm Hg (P = 0.0065 compared with placebo. In prehypertensive subjects, the differences in BP between MPH1 and placebo were not significant. MPH2 did not change BP significantly compared with placebo in stage I hypertensive or prehypertensive subjects. Intake of MPHs was well tolerated and safe. No treatment differences in hematology, clinical laboratory parameters or adverse effects were observed. No significant differences between MPHs and placebo were found in plasma renin activity, or angiotensin I and II. Conclusions MPH1, containing IPP and no minerals, exerts clinically relevant BP lowering effects in subjects with stage 1 hypertension. It may be included in lifestyle changes aiming to prevent or reduce high BP. Trial registration ClinicalTrials.gov NCT00471263

  2. Towards Developing a Malaria Vaccine Based on CD4 T Cell Mediated Immunity in Blood Stage of Malaria Infection

    Institute of Scientific and Technical Information of China (English)

    徐沪济

    2004-01-01

    Twenty-one years after malaria antigens were first cloned a vaccine still appears to be a long way off. There have been periods of great excitement and in model systems subunit vaccine homologues can induce robust protection. However, significant challenges exist concerning antigenic variation and polymorphism, immunological non-respons-iveness to individual vaccine antigens, parasite-induced apoptosis of immune effector and memory cells and immune deviation as a result of maternal immtmity and alterations of dendritic cell function.

  3. Microglial MHC antigen expression after ischemic and kainic acid lesions of the adult rat hippocampus

    DEFF Research Database (Denmark)

    Finsen, B.R.; Jørgensen, Martin Balslev; Diemer, Nils Henrik

    1993-01-01

    Leukocyte common antigen, macrophages, blood-brain barrier, neural degeneration, fascia dentata, neuropathology......Leukocyte common antigen, macrophages, blood-brain barrier, neural degeneration, fascia dentata, neuropathology...

  4. Blood

    Science.gov (United States)

    ... Also, blood is either Rh-positive or Rh-negative. So if you have type A blood, it's either A positive or A negative. Which type you are is important if you need a blood transfusion. And your Rh factor could be important ...

  5. Preoperative Monocyte-to-Lymphocyte Ratio in Peripheral Blood Predicts Stages, Metastasis, and Histological Grades in Patients with Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Jiangdong Xiang

    2017-02-01

    dehydrogenase were found between the low-MLR group (MLR ≤ 0.23 and the high-MLR group (MLR > 0.23. Correspondingly, dramatic differences were observed between the two groups in OS. CONCLUSION: Our results show that the peripheral blood MLR before surgery could be a significant predictor of advanced stages, advanced pathologic grades, and positive lymphatic metastasis in ovarian cancer patients.

  6. Nucleated red blood cells and early EEG: predicting Sarnat stage and two year outcome.

    LENUS (Irish Health Repository)

    Walsh, B H

    2012-01-31

    AIMS: Hypoxic Ischaemic Encephalopathy (HIE) causes characteristic changes of the electroencephalogram (EEG), and a raised Nucleated Red Blood Cell (NRBC) count compared to controls. We wished to examine whether combining these markers could improve their ability to predict HIE severity in the first 24h. METHODS: Term infants with HIE were recruited. NRBC count and continuous multi-channel EEG were recorded within the first 24h. Neurological assessment was carried out at 24 months. A control population with NRBC counts in the first 24h was recruited. RESULTS: 44 infants with HIE and 43 control infants were recruited. Of the HIE population 39 completed a 2 year follow-up. The median NRBC count differed significantly between the controls and those with HIE (3\\/100 WBC [range of 0-11] vs 12.3\\/100 WBC [0-240]) (p<0.001). Within the HIE population the median NRBC count was significantly greater in infants with moderate\\/severe HIE than mild (16\\/100 WBC [range of 0-240] vs 8\\/100 WBC [1-23]) (p=0.016), and among infants with abnormal outcome compared to normal (21.3\\/100 WBC [1-239.8] vs 8.3\\/100 WBC [0-50])(p=0.03). The predictive ability of EEG changed with time post-delivery, therefore results are given at both 12 and 24h of age. At both time points the combined marker had a stronger correlation than EEG alone; with HIE severity (12h: r=0.661 vs r=0.622), (24h: r=0.645 vs r=0.598), and with outcome at 2 years (12h: r=0.756 vs r=0.652), (24h: r=0.802 vs r=0.746). CONCLUSION: Combining early EEG and NRBC count to predict HIE severity and neurological outcome, improved the predictive ability of either in isolation.

  7. CD8+ T cells from a novel T cell receptor transgenic mouse induce liver-stage immunity that can be boosted by blood-stage infection in rodent malaria.

    Science.gov (United States)

    Lau, Lei Shong; Fernandez-Ruiz, Daniel; Mollard, Vanessa; Sturm, Angelika; Neller, Michelle A; Cozijnsen, Anton; Gregory, Julia L; Davey, Gayle M; Jones, Claerwen M; Lin, Yi-Hsuan; Haque, Ashraful; Engwerda, Christian R; Nie, Catherine Q; Hansen, Diana S; Murphy, Kenneth M; Papenfuss, Anthony T; Miles, John J; Burrows, Scott R; de Koning-Ward, Tania; McFadden, Geoffrey I; Carbone, Francis R; Crabb, Brendan S; Heath, William R

    2014-05-01

    To follow the fate of CD8+ T cells responsive to Plasmodium berghei ANKA (PbA) infection, we generated an MHC I-restricted TCR transgenic mouse line against this pathogen. T cells from this line, termed PbT-I T cells, were able to respond to blood-stage infection by PbA and two other rodent malaria species, P. yoelii XNL and P. chabaudi AS. These PbT-I T cells were also able to respond to sporozoites and to protect mice from liver-stage infection. Examination of the requirements for priming after intravenous administration of irradiated sporozoites, an effective vaccination approach, showed that the spleen rather than the liver was the main site of priming and that responses depended on CD8α+ dendritic cells. Importantly, sequential exposure to irradiated sporozoites followed two days later by blood-stage infection led to augmented PbT-I T cell expansion. These findings indicate that PbT-I T cells are a highly versatile tool for studying multiple stages and species of rodent malaria and suggest that cross-stage reactive CD8+ T cells may be utilized in liver-stage vaccine design to enable boosting by blood-stage infections.

  8. Detailed analysis of immunologic effects of the cytotoxic T lymphocyte-associated antigen 4-blocking monoclonal antibody tremelimumab in peripheral blood of patients with melanoma

    Directory of Open Access Journals (Sweden)

    Gualberto Antonio

    2008-05-01

    Full Text Available Abstract Background CTLA4-blocking antibodies induce tumor regression in a subset of patients with melanoma. Analysis of immune parameters in peripheral blood may help define how responses are mediated. Methods Peripheral blood from HLA-A*0201-positive patients with advanced melanoma receiving tremelimumab (formerly CP-675,206 at 10 mg/kg monthly was repeatedly sampled during the first 4 cycles. Samples were analyzed by 1 tetramer and ELISPOT assays for reactivity to CMV, EBV, MART1, gp100, and tyrosinase; 2 activation HLA-DR and memory CD45RO markers on CD4+/CD8+ cells; and 3 real-time quantitative PCR of mRNA for FoxP3 transcription factor, preferentially expressed by T regulatory cells. The primary endpoint was difference in MART1-specific T cells by tetramer assay. Immunological data were explored for significant trends using clustering analysis. Results Three of 12 patients eligible for immune monitoring had tumor regression lasting > 2 years without relapse. There was no significant change in percent of MART1-specific T cells by tetramer assay. Additionally, there was no generalized trend toward postdosing changes in other antigen-specific CD8+ cell populations, FoxP3 transcripts, or overall changes in surface expression of T-cell activation or memory markers. Unsupervised hierarchical clustering based on immune monitoring data segregated patients randomly. However, clustering according to T-cell activation or memory markers separated patients with clinical response and most patients with inflammatory toxicity into a common subgroup. Conclusion Administration of CTLA4-blocking antibody tremelimumab to patients with advanced melanoma results in a subset of patients with long-lived tumor responses. T-cell activation and memory markers served as the only readout of the pharmacodynamic effects of this antibody in peripheral blood. Clinical trial registration number NCT00086489

  9. Biosynthesis of GDP-fucose and other sugar nucleotides in the blood stages of Plasmodium falciparum.

    Science.gov (United States)

    Sanz, Sílvia; Bandini, Giulia; Ospina, Diego; Bernabeu, Maria; Mariño, Karina; Fernández-Becerra, Carmen; Izquierdo, Luis

    2013-06-01

    Carbohydrate structures play important roles in many biological processes, including cell adhesion, cell-cell communication, and host-pathogen interactions. Sugar nucleotides are activated forms of sugars used by the cell as donors for most glycosylation reactions. Using a liquid chromatography-tandem mass spectrometry-based method, we identified and quantified the pools of UDP-glucose, UDP-galactose, UDP-N-acetylglucosamine, GDP-mannose, and GDP-fucose in Plasmodium falciparum intraerythrocytic life stages. We assembled these data with the in silico functional reconstruction of the parasite metabolic pathways obtained from the P. falciparum annotated genome, exposing new active biosynthetic routes crucial for further glycosylation reactions. Fucose is a sugar present in glycoconjugates often associated with recognition and adhesion events. Thus, the GDP-fucose precursor is essential in a wide variety of organisms. P. falciparum presents homologues of GDP-mannose 4,6-dehydratase and GDP-L-fucose synthase enzymes that are active in vitro, indicating that most GDP-fucose is formed by a de novo pathway that involves the bioconversion of GDP-mannose. Homologues for enzymes involved in a fucose salvage pathway are apparently absent in the P. falciparum genome. This is in agreement with in vivo metabolic labeling experiments showing that fucose is not significantly incorporated by the parasite. Fluorescence microscopy of epitope-tagged versions of P. falciparum GDP-mannose 4,6-dehydratase and GDP-L-fucose synthase expressed in transgenic 3D7 parasites shows that these enzymes localize in the cytoplasm of P. falciparum during the intraerythrocytic developmental cycle. Although the function of fucose in the parasite is not known, the presence of GDP-fucose suggests that the metabolite may be used for further fucosylation reactions.

  10. Mitochondrial peroxidase TPx-2 is not essential in the blood and insect stages of Plasmodium berghei

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    Masuda-Suganuma Hirono

    2012-11-01

    Full Text Available Abstract Background Malaria parasites actively proliferate in the body of their vertebrate and insect hosts, and are subjected to the toxic effects of reactive oxygen species. The antioxidant defenses of malaria parasites are considered to play essential roles in their survival and are thus considered promising targets for intervention. We sought to identify the cellular function of thioredoxin peroxidase-2 (TPx-2, which is expressed in the mitochondria, by disrupting the TPx-2 gene (pbtpx-2 of the rodent malaria parasite Plasmodium berghei. Findings In three independent experiments, two disruptant populations (TPx-2 KO and three wild-type parasite populations with pyrimethamine resistance (dhfr-ts/mt at the DHFR-TS locus and intact pbtpx-2 (TPx-2 WT were obtained and cloned. Null expression of TPx-2 in the KO population was confirmed by RT-PCR and Western blot analyses. The TPx-2 KO parasite developed normally in mouse erythrocytes and multiplied at a rate similar to that of the TPx-2 WT parasite during the experimental period. The peak period of gametocytemia was delayed by 1 day in the TPx-2 KO compared with that of the TPx-2 WT and the parent parasite, however, the highest gametocyte number was comparable. The number of midgut oocysts in the TPx-2 KO at 14 days post feeding was comparable to that of the TPx-2 WT. Conclusions The present finding suggests that mitochondrial Prx TPx-2 is not essential for asexual and the insect stage development of the malaria parasite.

  11. Subcompartmentalisation of proteins in the rhoptries correlates with ordered events of erythrocyte invasion by the blood stage malaria parasite.

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    Elizabeth S Zuccala

    Full Text Available Host cell infection by apicomplexan parasites plays an essential role in lifecycle progression for these obligate intracellular pathogens. For most species, including the etiological agents of malaria and toxoplasmosis, infection requires active host-cell invasion dependent on formation of a tight junction - the organising interface between parasite and host cell during entry. Formation of this structure is not, however, shared across all Apicomplexa or indeed all parasite lifecycle stages. Here, using an in silico integrative genomic search and endogenous gene-tagging strategy, we sought to characterise proteins that function specifically during junction-dependent invasion, a class of proteins we term invasins to distinguish them from adhesins that function in species specific host-cell recognition. High-definition imaging of tagged Plasmodium falciparum invasins localised proteins to multiple cellular compartments of the blood stage merozoite. This includes several that localise to distinct subcompartments within the rhoptries. While originating from the same organelle, however, each has very different dynamics during invasion. Apical Sushi Protein and Rhoptry Neck protein 2 release early, following the junction, whilst a novel rhoptry protein PFF0645c releases only after invasion is complete. This supports the idea that organisation of proteins within a secretory organelle determines the order and destination of protein secretion and provides a localisation-based classification strategy for predicting invasin function during apicomplexan parasite invasion.

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

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    Lydie Béniguel

    2004-01-01

    Full Text Available 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.

  13. Serological and molecular identification of H Antigen deficiency and the physical and chemical functions of H deficient red blood cells%红细胞H抗原缺陷型鉴定及其理化功能研究

    Institute of Scientific and Technical Information of China (English)

    何子毅; 邹文涛; 胡应明; 钟炽辉; 刘仁强; 王德文; 刘赴平

    2013-01-01

    Objective To study the serology, molecular biology, typing characteristics, and physical and chemical func-tions of H antigen-deficient red blood cells. Methods H antigen deficiency was identified by serological method,ABO and para- Bombay genotype was determined by SSP-PCR. Erythrocyte osmotic fragility test,and deformability test for H Antigen-deficient red blood cell were conducted. Cross matching tests, simulating blood recipient and donor,were also performed. Results A total of six blood donors were identified as H antigen-deficient by serological methods, among which 3 cases were h3 homozygous,one h4 homozygous,one h1h3 heterozygotes,and the last not determined. The osmotic fragility and the deformability of H antigen-deficient red blood cells were below those of H antigen normal cells. As a blood recipient, the major cross match showed stronger agglutination with A or B type RBCs, compared to O type RBCs. As a blood donor, the major cross match were negative with some recipients,and positive with others. Conclusion H antigen deficient RBCs do not react with anti-H,anti-H1/H can be detected in H deficient serum,ABO genes were normal. The osmotic fragility and the deformability of H antigen-deficient type RBCs were lower than those of H antigen normal cells. As a receipt,receiving 0 type blood,is safer than A type or B type blood. While as a donor,if cross match is non-reactive,H deficient RBCs could be transfused to 0 type recipient.%目的 研究红细胞H抗原缺陷型血清学及分子生物学分型特点及其理化功能.方法 采用血型血清学鉴定H抗原缺陷型、SSP-PCR进行ABO基因分型,采用红细胞渗透脆性试验、变形性试验检测H抗原缺陷型红细胞理化功能,模拟作为受血者或供血者进行交叉配血试验.结果 6名献血者血样经血清学方法确定为H抗原缺陷型,类孟买基因分型其中3例为h3纯合子,1例为h4纯合子,1例为h1h3杂合子,1例基因分型不确定;H抗原缺陷型红

  14. Differential miRNA Expression in the Liver of Balb/c Mice Protected by Vaccination during Crisis of Plasmodium chabaudi Blood-Stage Malaria

    Science.gov (United States)

    Dkhil, Mohamed A.; Al-Quraishy, Saleh A.; Abdel-Baki, Abdel-Azeem S.; Delic, Denis; Wunderlich, Frank

    2017-01-01

    MicroRNAs are increasingly recognized as epigenetic regulators for outcome of diverse infectious diseases and vaccination efficacy, but little information referring to this exists for malaria. This study investigates possible effects of both protective vaccination and P. chabaudi malaria on the miRNome of the liver as an effector against blood-stage malaria using miRNA microarrays and quantitative PCR. Plasmodium chabaudi blood-stage malaria takes a lethal outcome in female Balb/c mice, but a self-healing course after immunization with a non-infectious blood-stage vaccine. The liver robustly expresses 71 miRNA species at varying levels, among which 65 miRNA species respond to malaria evidenced as steadily increasing or decreasing expressions reaching highest or lowest levels toward the end of the crisis phase on day 11 p.i. in lethal malaria. Protective vaccination does not affect constitutive miRNA expression, but leads to significant (p malaria.

  15. Regional immune responses with stage-specific antigen recognition profiles develop in lymph nodes of pigs following Ascaris suum larval migration

    DEFF Research Database (Denmark)

    Jungersen, Gregers; Eriksen, Lizzie; Nansen, P.;

    2001-01-01

    The early life-cycle of the pig round worm, Ascaris suum, involves well-defined larval development in the liver; lungs and finally the small intestine. Distinct regional immune responses to larval antigens of A. suum were observed in the draining lymph nodes of immunized and challenged pigs during...... larval migration. This was reflected in a transient enlargement of the stimulated lymph nodes, due to increases in numbers of B cells and CD4 T cells, and the production of A. suum-specific antibody by antibody secreting cell (ASC) cultures. Larval antigen recognition pattern of antibodies in serum, bile...

  16. Antigen Uptake during Different Life Stages of Zebrafish (Danio rerio) Using a GFP-Tagged Yersinia ruckeri

    DEFF Research Database (Denmark)

    Korbut, Rozalia; Mehrdana, Foojan; Kania, Per Walter;

    2016-01-01

    and subsequent antigen transport in fish. A genetically modified Yr was developed to constitutively express green fluorescent protein (GFP) and was used for bacterin production. Larval, juvenile and adult transparent zebrafish (tra:nac mutant) received a bath in the bacterin for up to 30 minutes. Samples were......Immersion-vaccines (bacterins) are routinely used for aquacultured rainbow trout to protect against Yersinia ruckeri (Yr). During immersion vaccination, rainbow trout take up and process the antigens, which induce protection. The zebrafish was used as a model organism to study uptake mechanisms...

  17. Blood group change in acute myeloid leukemia

    Science.gov (United States)

    Nambiar, Rakul K.; Prakash, N. P.; Vijayalakshmi, K.

    2017-01-01

    Blood group antigens are either sugars or proteins found attached to the red blood cell membrane. ABO blood group antigens are the most clinically important antigens because they are the most immunogenic. As red blood cell antigens are inherited traits, they are usually not altered throughout the life of an individual. There have been occasional case reports of ABO blood group antigen change in malignant conditions. We report two such cases of ABO antigen alteration associated with acute myeloid leukemia. These patients had suppression of their blood group antigens during their leukemic phase, and the antigens were reexpressed when the patients attained remission.

  18. Rapid detection of dendritic cell and monocyte disorders using CD4 as a lineage marker of the human peripheral blood antigen presenting cell compartment

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    Laura eJardine

    2013-12-01

    Full Text Available Dendritic cells (DCs and monocytes are critical regulators and effectors of innate and adaptive immune responses. Monocyte expansion has been described in many pathological states while monocyte and DC deficiency syndromes are relatively recent additions to the catalogue of human primary immunodeficiency disorders. Clinically applicable screening tests to diagnose and monitor these conditions are lacking. Conventional strategies for identifying human DCs and monocytes have been based on the use of a lineage gate to exclude lymphocytes, thus preventing simultaneous detection of DCs, monocytes and lymphocyte subsets. Here we demonstrate that CD4 is a reliable lineage marker for the human peripheral blood antigen presenting cell compartment that can be used to identify DCs and monocytes in parallel with lymphocytes. Based on this principle, simple modification of a standard lymphocyte phenotyping assay permits simultaneous enumeration of four lymphocyte and five DC/monocyte populations from a single sample. This approach is applicable to clinical samples and facilitates the diagnosis of DC and monocyte disorders in a wide range of clinical settings, including genetic deficiency, neoplasia and inflammation.

  19. Novel association of ABO histo-blood group antigen with soluble ICAM-1: results of a genome-wide association study of 6,578 women.

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    Guillaume Paré

    2008-07-01

    Full Text Available While circulating levels of soluble Intercellular Adhesion Molecule 1 (sICAM-1 have been associated with diverse conditions including myocardial infarction, stroke, malaria, and diabetes, comprehensive analysis of the common genetic determinants of sICAM-1 is not available. In a genome-wide association study conducted among 6,578 participants in the Women's Genome Health Study, we find that three SNPs at the ICAM1 (19p13.2 locus (rs1799969, rs5498 and rs281437 are non-redundantly associated with plasma sICAM-1 concentrations at a genome-wide significance level (P<5x10(-8, thus extending prior results from linkage and candidate gene studies. We also find that a single SNP (rs507666, P = 5.1x10(-29 at the ABO (9q34.2 locus is highly correlated with sICAM-1 concentrations. The novel association at the ABO locus provides evidence for a previously unknown regulatory role of histo-blood group antigens in inflammatory adhesion processes.

  20. Antigen specificity determines anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn.

    Science.gov (United States)

    Sonneveld, Myrthe E; Koelewijn, Joke; de Haas, Masja; Admiraal, Jon; Plomp, Rosina; Koeleman, Carolien A M; Hipgrave Ederveen, Agnes L; Ligthart, Peter; Wuhrer, Manfred; van der Schoot, C Ellen; Vidarsson, Gestur

    2017-02-01

    Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. HDFN is most often caused by anti-D but may also occur due to anti-K, -c- or -E. We recently found N-linked glycosylation of anti-D to be skewed towards low fucosylation, thereby increasing the affinity to IgG-Fc receptor IIIa and IIIb, which correlated with HDFN disease severity. Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. Anti-c, -E and -K show - independent of the event that had led to immunisation - a different kind of Fc-glycosylation compared to that of the total IgG fraction, but with less pronounced differences compared to anti-D. High Fc-galactosylation and sialylation of anti-c correlated with HDFN disease severity, while low anti-K Fc-fucosylation correlated with severe fetal anaemia. IgG-Fc glycosylation of anti-RBC antibodies is shaped depending on the antigen. These features influence their clinical potency and may therefore be used to predict severity and identify those needing treatment.

  1. Blood levels of vitamin D and early stage breast cancer prognosis: a systematic review and meta-analysis.

    Science.gov (United States)

    Rose, April A N; Elser, Christine; Ennis, Marguerite; Goodwin, Pamela J

    2013-10-01

    Vitamin D regulates expression of genes important in development and progression of breast cancer. The association of vitamin D with breast cancer outcomes among breast cancer patients is controversial. We conducted a systematic review and meta-analysis of this association in early stage breast cancer outcome. We searched MEDLINE (1982-May 1, 2013), the American Society of Clinical Oncology (2009-2012), and the San Antonio Breast Cancer Symposium (2010-2012) for abstracts, using the following keywords: "breast cancer" and "prognosis" or "survival", and "vitamin D" or" calcitriol" to identify studies reporting the associations of blood vitamin D levels (drawn close to diagnosis) with breast cancer outcomes. Meta-analyses were performed using an inverse-variance weighted fixed-effects model with Stata Version 12. Eight studies including 5,691 patients were identified. Vitamin D deficiency was variably categorized across studies; a median of 36.8 % of patients were classified as deficient. Low vitamin D levels were associated with a pooled hazard ratio of 2.13 (95 % CI 1.64-2.78) and 1.76 (95 % CIs 1.35-2.30) for recurrence (six studies) and death (four studies), respectively, with no evidence of significant heterogeneity across studies. There was potential evidence of a publication bias in studies examining associations with death (but not in those examining associations with recurrence). These findings support an association of low levels of vitamin D with increased risk of recurrence and death in early stage breast cancer patients. Given the observational nature of the included studies, it cannot be concluded that this association is causal. Further research is warranted to investigate the potential beneficial effects of vitamin D in breast cancer.

  2. A NEW METHOD OF SINGLE-STAGE ISLAND PLASTY BY TWO BONE AUTOGRAFTS WITH BLOOD SUPPLY IN PATIENTS WITH PSEUDOARTHROSIS OF BOTH FOREARM BONES

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    R. M. Tikhilov

    2010-01-01

    Full Text Available The applied topographic-anatomic studies prepared in 14 fixed and 16 unfixed preparations of upper extremity allowed to precise the details of radius blood supply with reference to possibilities of formation of bone autografts with blood supply. Due to this fact the novel method of single-stage bone plasty for pseudoarthrosis of both forearm bones was developed and successfully approved in clinic. This method proposes the formation of two periosteal-cortical grafts with blood supply and small muscle cuff in distal and middle one-thirds of radius simultaneously.

  3. Conformational dynamics and antigenicity in the disordered malaria antigen merozoite surface protein 2.

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    Christopher A MacRaild

    Full Text Available Merozoite surface protein 2 (MSP2 of Plasmodium falciparum is an abundant, intrinsically disordered protein that is GPI-anchored to the surface of the invasive blood stage of the malaria parasite. Recombinant MSP2 has been trialled as a component of a malaria vaccine, and is one of several disordered proteins that are candidates for inclusion in vaccines for malaria and other diseases. Nonetheless, little is known about the implications of protein disorder for the development of an effective antibody response. We have therefore undertaken a detailed analysis of the conformational dynamics of the two allelic forms of MSP2 (3D7 and FC27 using NMR spectroscopy. Chemical shifts and NMR relaxation data indicate that conformational and dynamic properties of the N- and C-terminal conserved regions in the two forms of MSP2 are essentially identical, but significant variation exists between and within the central variable regions. We observe a strong relationship between the conformational dynamics and the antigenicity of MSP2, as assessed with antisera to recombinant MSP2. Regions of increased conformational order in MSP2, including those in the conserved regions, are more strongly antigenic, while the most flexible regions are minimally antigenic. This suggests that modifications that increase conformational order may offer a means to tune the antigenicity of MSP2 and other disordered antigens, with implications for vaccine design.

  4. Conformational Dynamics and Antigenicity in the Disordered Malaria Antigen Merozoite Surface Protein 2

    Science.gov (United States)

    Andrew, Dean; Krishnarjuna, Bankala; Nováček, Jiří; Žídek, Lukáš; Sklenář, Vladimír; Richards, Jack S.; Beeson, James G.; Anders, Robin F.; Norton, Raymond S.

    2015-01-01

    Merozoite surface protein 2 (MSP2) of Plasmodium falciparum is an abundant, intrinsically disordered protein that is GPI-anchored to the surface of the invasive blood stage of the malaria parasite. Recombinant MSP2 has been trialled as a component of a malaria vaccine, and is one of several disordered proteins that are candidates for inclusion in vaccines for malaria and other diseases. Nonetheless, little is known about the implications of protein disorder for the development of an effective antibody response. We have therefore undertaken a detailed analysis of the conformational dynamics of the two allelic forms of MSP2 (3D7 and FC27) using NMR spectroscopy. Chemical shifts and NMR relaxation data indicate that conformational and dynamic properties of the N- and C-terminal conserved regions in the two forms of MSP2 are essentially identical, but significant variation exists between and within the central variable regions. We observe a strong relationship between the conformational dynamics and the antigenicity of MSP2, as assessed with antisera to recombinant MSP2. Regions of increased conformational order in MSP2, including those in the conserved regions, are more strongly antigenic, while the most flexible regions are minimally antigenic. This suggests that modifications that increase conformational order may offer a means to tune the antigenicity of MSP2 and other disordered antigens, with implications for vaccine design. PMID:25742002

  5. Pattern of pre-existing IgG subclass responses to a panel of asexual stage malaria antigens reported during the lengthy dry season in Daraweesh, Sudan

    DEFF Research Database (Denmark)

    Nasr, A; Iriemenam, N C; Troye-Blomberg, M;

    2011-01-01

    The anti-malarial IgG immune response during the lengthy and dry season in areas of low malaria transmission as in Eastern Sudan is largely unknown. In this study, ELISA was used for the measurement of pre-existing total IgG and IgG subclasses to a panel of malaria antigens, MSP2-3D7, MSP2-FC27, ...

  6. Mechanisms of immune protection in the asexual blood stage infection by Plasmodium falciparum: analysis by in vitro and ex-vivo assays

    Directory of Open Access Journals (Sweden)

    Jurg Gysin

    1992-01-01

    Full Text Available Mechanisms of immune protection against the asexual blood stage infection by Plasmodium falciparum are reviewed. Recent studies of two independent lines of research developed at the Institute Pasteur, in humans and primate infections clearly indicate an obligatory interaction of antibodies and effector cells to express the anti-parasitic effect.

  7. Study on the Soluble Protein Antigens Derived from Four Developmental Stages of Periplaneta fuliginosa%黑胸大蠊不同发育阶段可溶性蛋白抗原的分析

    Institute of Scientific and Technical Information of China (English)

    徐绍锐; 汪世平; 李文凯; 吴仕筠; 吕志跃; 彭选楚; 何卓

    2004-01-01

    目的了解黑胸大蠊的不同发育阶段蛋白质抗原的免疫生化特性.方法采用十十烷基硫酸钠聚丙烯酰胺凝胶电泳(SDS-PAGE)对黑胸大蠊不同发育阶段可溶性蛋白质组分进行分离鉴定并通过酶联免疫印迹(ELIB)技术分析不同发育阶段抗原的免疫学特性.结果四种抗原蛋白经SDS-PAGE后银染色,均得到清晰的蛋白显色带.卵抗原、若虫抗原、雄成虫抗原、雌成虫抗原分别可见13、28、26、41条蛋白区带,其中主带分别为2、10、10、13条,分子量大多位于10~97kDa范围.具有免疫原性的蛋白质大多分布在43kDa以上分子量范围,四种抗原组分相互之间有交叉抗原的存在.结论不同发育阶段黑胸大蠊的蛋白质组分从卵-若虫-成虫出现次第增多现象并趋于复杂化,这对研究黑胸大蠊的发育生物学特征具有一定的潜在意义.%Objective To provide experimental data for further studies on the immunobiochemical characteristics of the protein antigens from Periplaneta fuliginosa at different developmental stages. Method Four groups of soluble protein antigens of the P. filiginosa, namely, egg antigens, nymph antigens, male and female adult antigens, were analyzed with SDS-PAGE and ELIB. Results Stripes of the studied antigens were clearly displayed by silver staining after SDS-PAGE. The egg antigens, nymph antigens, male and female adult antigens revealed 13, 28, 26 and 41 bands,respectively, of which 2, 10, 10 and 13 major bands were found in the respective groups. Most protein components varied in a molecular weight range of 10 ~ 97kDa. The ELIB analysis showed that proteins with immunogenic activity were mainly distributed in a molecular weight range of higher than 43kDa. The ELIB result also showed an existence of common antigenic components among these groups. Conclusions With the development of the cockroach from egg to adult, the P. fuliginosa protein components are increasingly aggrandized in

  8. Development of an artificial-antigen-presenting-cell-based assay for the detection of low-frequency virus-specific CD8(+) T cells in whole blood, with application for measles virus.

    Science.gov (United States)

    Ndhlovu, Zaza M; Angenendt, Monika; Heckel, Diana; Schneck, Jonathan P; Griffin, Diane E; Oelke, Mathias

    2009-07-01

    Evaluation of the immune responses induced by childhood vaccines requires measurement of T-cell, as well as antibody, responses. However, cellular immune responses are often not analyzed because of technical hurdles and the volume of blood required. Therefore, a sensitive and specific assay for antigen-specific T cells that utilizes a small volume of blood would facilitate new vaccine evaluation. We developed a novel assay for quantifying virus-specific CD8(+) T cells that combines the use of HLA-A2 immunoglobulin-based artificial antigen-presenting cells (aAPCs) for stimulation of antigen-specific CD8(+) T cells in whole blood with quantitative real-time reverse transcription-PCR (qRT-PCR) to detect gamma interferon (IFN-gamma) mRNA. This assay was optimized using a well-established cytomegalovirus (CMV) CD8(+) T-cell system. The aAPC-qRT-PCR assay had comparable sensitivity to intracellular cytokine staining (ICS) in detecting CMV-specific CD8(+) T cells with a detection limit of less than 0.004%. The assay was applied to the detection of low-frequency measles virus (MV)-specific CD8(+) T cells by stimulating blood from five MV-immune HLA-A*0201 donors with four different MV-specific peptides (MV peptide aAPCs). Stimulation with three of the MV peptide aAPCs resulted in significant increases in IFN-gamma mRNA ranging from 3.3- to 13.5-fold. Our results show that the aAPC-qRT-PCR assay is highly sensitive and specific and can be standardized for screening MV-specific CD8(+) T cells in vaccine trials. The technology should be transferable to analysis of CD8(+) T-cell responses to other antigens.

  9. Clinical application of Sleeping Beauty and artificial antigen presenting cells to genetically modify T cells from peripheral and umbilical cord blood.

    Science.gov (United States)

    Huls, M Helen; Figliola, Matthew J; Dawson, Margaret J; Olivares, Simon; Kebriaei, Partow; Shpall, Elizabeth J; Champlin, Richard E; Singh, Harjeet; Cooper, Laurence J N

    2013-02-01

    The potency of clinical-grade T cells can be improved by combining gene therapy with immunotherapy to engineer a biologic product with the potential for superior (i) recognition of tumor-associated antigens (TAAs), (ii) persistence after infusion, (iii) potential for migration to tumor sites, and (iv) ability to recycle effector functions within the tumor microenvironment. Most approaches to genetic manipulation of T cells engineered for human application have used retrovirus and lentivirus for the stable expression of CAR(1-3). This approach, although compliant with current good manufacturing practice (GMP), can be expensive as it relies on the manufacture and release of clinical-grade recombinant virus from a limited number of production facilities. The electro-transfer of nonviral plasmids is an appealing alternative to transduction since DNA species can be produced to clinical grade at approximately 1/10(th) the cost of recombinant GMP-grade virus. To improve the efficiency of integration we adapted Sleeping Beauty (SB) transposon and transposase for human application(4-8). Our SB system uses two DNA plasmids that consist of a transposon coding for a gene of interest (e.g. 2(nd) generation CD19-specific CAR transgene, designated CD19RCD28) and a transposase (e.g. SB11) which inserts the transgene into TA dinucleotide repeats(9-11). To generate clinically-sufficient numbers of genetically modified T cells we use K562-derived artificial antigen presenting cells (aAPC) (clone #4) modified to express a TAA (e.g. CD19) as well as the T cell costimulatory molecules CD86, CD137L, a membrane-bound version of interleukin (IL)-15 (peptide fused to modified IgG4 Fc region) and CD64 (Fc-γ receptor 1) for the loading of monoclonal antibodies (mAb)(12). In this report, we demonstrate the procedures that can be undertaken in compliance with cGMP to generate CD19-specific CAR(+) T cells suitable for human application. This was achieved by the synchronous electro-transfer of

  10. Acquired hemoglobin variants and exposure to glucose-6-phosphate dehydrogenase deficient red blood cell units during exchange transfusion for sickle cell disease in a patient requiring antigen-matched blood.

    Science.gov (United States)

    Raciti, Patricia M; Francis, Richard O; Spitalnik, Patrice F; Schwartz, Joseph; Jhang, Jeffrey S

    2013-08-01

    Red blood cell exchange (RBCEx) is frequently used in the management of patients with sickle cell disease (SCD) and acute chest syndrome or stroke, or to maintain target hemoglobin S (HbS) levels. In these settings, RBCEx is a category I or II recommendation according to guidelines on the use of therapeutic apheresis published by the American Society for Apheresis. Matching donor red blood cells (RBCs) to recipient phenotypes (e.g., C, E, K-antigen negative) can decrease the risk of alloimmunization in patients with multi-transfused SCD. However, this may select for donors with a higher prevalence of RBC disorders for which screening is not performed. This report describes a patient with SCD treated with RBCEx using five units negative for C, E, K, Fya, Fyb (prospectively matched), four of which were from donors with hemoglobin variants and/or glucose-6-phosphate dehydrogenase (G6PD) deficiency. Pre-RBCEx HbS quantification by high performance liquid chromatography (HPLC) demonstrated 49.3% HbS and 2.8% hemoglobin C, presumably from transfusion of a hemoglobin C-containing RBC unit during a previous RBCEx. Post-RBCEx HPLC showed the appearance of hemoglobin G-Philadelphia. Two units were G6PD-deficient. The patient did well, but the consequences of transfusing RBC units that are G6PD-deficient and contain hemoglobin variants are unknown. Additional studies are needed to investigate effects on storage, in-vivo RBC recovery and survival, and physiological effects following transfusion of these units. Post-RBCEx HPLC can monitor RBCEx efficiency and detect the presence of abnormal transfused units.

  11. Crystal Structures of GII.10 and GII.12 Norovirus Protruding Domains in Complex with Histo-Blood Group Antigens Reveal Details for a Potential Site of Vulnerability

    Energy Technology Data Exchange (ETDEWEB)

    Hansman, Grant S.; Biertümpfel, Christian; Georgiev, Ivelin; McLellan, Jason S.; Chen, Lei; Zhou, Tongqing; Katayama, Kazuhiko; Kwong, Peter D. (NIH); (NIID-Japan)

    2011-10-10

    Noroviruses are the dominant cause of outbreaks of gastroenteritis worldwide, and interactions with human histo-blood group antigens (HBGAs) are thought to play a critical role in their entry mechanism. Structures of noroviruses from genogroups GI and GII in complex with HBGAs, however, reveal different modes of interaction. To gain insight into norovirus recognition of HBGAs, we determined crystal structures of norovirus protruding domains from two rarely detected GII genotypes, GII.10 and GII.12, alone and in complex with a panel of HBGAs, and analyzed structure-function implications related to conservation of the HBGA binding pocket. The GII.10- and GII.12-apo structures as well as the previously solved GII.4-apo structure resembled each other more closely than the GI.1-derived structure, and all three GII structures showed similar modes of HBGA recognition. The primary GII norovirus-HBGA interaction involved six hydrogen bonds between a terminal {alpha}fucose1-2 of the HBGAs and a dimeric capsid interface, which was composed of elements from two protruding subdomains. Norovirus interactions with other saccharide units of the HBGAs were variable and involved fewer hydrogen bonds. Sequence analysis revealed a site of GII norovirus sequence conservation to reside under the critical {alpha}fucose1-2 and to be one of the few patches of conserved residues on the outer virion-capsid surface. The site was smaller than that involved in full HBGA recognition, a consequence of variable recognition of peripheral saccharides. Despite this evasion tactic, the HBGA site of viral vulnerability may provide a viable target for small molecule- and antibody-mediated neutralization of GII norovirus.

  12. H-2g, a glucose analog of blood group H antigen, mediates monocyte recruitment in vitro and in vivo via IL-8/CXCL8

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    Rabquer BJ

    2012-09-01

    Full Text Available Bradley J Rabquer,1,2 Yong Hou,1 Jeffrey H Ruth,1 Wei Luo,1 Daniel T Eitzman,1 Alisa E Koch,3,1 Mohammad A Amin11University of Michigan Medical School, Department of Internal Medicine, Ann Arbor, MI, USA; 2Albion College, Biology Department, Albion, MI, USA; 3VA Medical Service, Department of Veterans Affairs, Ann Arbor, MI, USAObjective: Monocyte (MN recruitment is an essential inflammatory component of many autoimmune diseases, including rheumatoid arthritis (RA. In this study we investigated the ability of 2-fucosyllactose (H-2g, a glucose analog of blood group H antigen to induce MN migration in vivo and determined if H-2g-induced interleukin-8 (IL-8/CXCL8 plays a role in MN ingress in RA.Methods: Sponge granuloma and intravital microscopy assays were performed to examine H-2g-induced in vivo MN migration and rolling, respectively. MNs were stimulated with H-2g, and the production of IL-8/CXCL8 was assessed by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. Lastly, in vitro MN migration assays and an in vivo RA synovial tissue severe combined immunodeficiency mouse model were used to determine the role of IL-8/CXCL8 in H-2g-induced MN migration.Results: In vivo, H-2g induced significantly greater MN migration compared to phosphate buffered saline. Intravital microscopy revealed that H-2g mediates MN migration in vivo by inducing MN rolling. In addition, H-2g induced MN production of IL-8/CXCL8, a process that was dependent on Src kinase. Moreover, we found that H-2g mediated MN migration in vitro, and in vivo migration was inhibited by a neutralizing anti-IL-8/CXCL8 antibody.Conclusion: These findings suggest that H-2g mediates MN recruitment in vitro and in vivo (in part via IL-8/CXCL8.Keywords: inflammation, rheumatoid arthritis, chemokine, migration

  13. Standardized Serum-Free Cryomedia Maintain Peripheral Blood Mononuclear Cell Viability, Recovery, and Antigen-Specific T-Cell Response Compared to Fetal Calf Serum-Based Medium

    Science.gov (United States)

    Schulz, Julia C.; Kemp-Kamke, Beatrice; Zimmermann, Heiko; von Briesen, Hagen

    2011-01-01

    The ability to analyze cryopreserved peripheral blood mononuclear cells (PBMCs) from biobanks for antigen-specific T-cell immunity is necessary to evaluate responses to immune-based therapies. Comprehensive studies have demonstrated that the quality of frozen PBMCs is critical and the maintenance of cell viability and functionality by using appropriate cryopreservation techniques is a key to the successful outcome of assays using PBMCs. Different cryomedia additives affect cell viability. The most common additive is fetal calf serum (FCS), although it is widely known that each FCS lot has to be tested before usage to prevent nonspecific stimulation of T-cells. Also, shipping of samples containing FCS is critical because of many import restrictions. Often, dimethyl sulfoxide (DMSO) is added as a cryoprotectant. However, DMSO concentration has to be reduced significantly because of its toxic effect on cells at room temperature. Therefore, we have developed freezing approaches to minimize cytotoxicity of cryoprotectants and maintain T-cell functionality. We compared different additives to the widely used FCS and found bovine serum albumin fraction V to be an appropriate substitute for the potentially immune-modulating FCS. We also found that DMSO concentration can be reduced by the addition of hydroxyethyl starch. Using our serum-free cryomedia, the PBMC recovery was more than 83% and the PBMC viability was more than 98%. Also, the T-cell functionality measured by enzyme-linked immunospot (ELISpot) was optimal after cryopreservation with our new cryomedia. On the basis of our experimental results, we could finally design 2 different, fully working cryomedia that are standardized, serum free, and manufactured under GMP conditions. PMID:21977240

  14. CEA blood test

    Science.gov (United States)

    Carcinoembryonic antigen blood test ... A blood sample is needed . ... When the needle is inserted to draw blood, some people feel moderate pain. Others feel only a prick or stinging sensation. Afterward, there may be some throbbing or a slight bruise. ...

  15. Comparison of Measurements of Autoantibodies to Glutamic Acid Decarboxylase and Islet Antigen-2 in Whole Blood Eluates from Dried Blood Spots Using the RSR-Enzyme Linked Immunosorbent Assay Kits and In-House Radioimmunoassays

    Directory of Open Access Journals (Sweden)

    Anders Persson

    2010-01-01

    Full Text Available To evaluate the performance of dried blood spots (DBSs with subsequent analyses of glutamic acid decarboxylase (GADA and islet antigen-2 (IA-2A with the RSR-ELISAs, we selected 80 children newly diagnosed with type 1 diabetes and 120 healthy women. DBSs from patients and controls were used for RSR-ELISAs while patients samples were analysed also with in-house RIAs. The RSR-ELISA-GADA performed well with a specificity of 100%, albeit sensitivity (46% was lower compared to in RIA (56%; P=.008. No prozone effect was observed after dilution of discrepant samples. RSR-ELISA-IA-2A achieved specificity of 69% and sensitivity was lower (59% compared with RIA (66%; P<.001. Negative or low positive patients and control samples in the RSR-ELISA-IA-2A increased after dilution. Eluates from DBS can readily be used to analyse GADA with the RSR-ELISA, even if low levels of autoantibodies were not detected. Some factor could disturb RSR-ELISA-IA-2A analyses.

  16. Cytokine responses of CD4+ T cells during a Plasmodium chabaudi chabaudi (ER blood-stage infection in mice initiated by the natural route of infection

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    Butcher Geoffrey

    2007-06-01

    Full Text Available Abstract Background Investigation of host responses to blood stages of Plasmodium spp, and the immunopathology associated with this phase of the life cycle are often performed on mice infected directly with infected red blood cells. Thus, the effects of mosquito bites and the pre-erythrocytic stages of the parasite, which would be present in natural infection, are ignored In this paper, Plasmodium chabaudi chabaudi infections of mice injected directly with infected red blood cells were compared with those of mice infected by the bites of infected mosquitoes, in order to determine whether the courses of primary infection and splenic CD4 T cell responses are similar. Methods C57Bl/6 mice were injected with red blood cells infected with P. chabaudi (ER or infected via the bite of Anopheles stephensi mosquitoes. Parasitaemia were monitored by Giemsa-stained thin blood films. Total spleen cells, CD4+ T cells, and cytokine production (IFN-γ, IL-2, IL-4, IL-10 were analysed by flow cytometry. In some experiments, mice were subjected to bites of uninfected mosquitoes prior to infectious bites in order to determine whether mosquito bites per se could affect a subsequent P. chabaudi infection. Results P. chabaudi (ER infections initiated by mosquito bite were characterized by lower parasitaemia of shorter duration than those observed after direct blood challenge. However, splenomegaly was comparable suggesting that parasitaemia alone does not account for the increase in spleen size. Total numbers of CD4 T cells and those producing IFN-γ, IL-10 and IL-2 were reduced in comparison to direct blood challenge. By contrast, the reduction in IL-4 producing cells was less marked suggesting that there is a proportionally lower Th1-like response in mice infected via infectious mosquitoes. Strikingly, pre-exposure to bites of uninfected mosquitoes reduced the magnitude and duration of the subsequent mosquito-transmitted infection still further, but enhanced the

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

    Science.gov (United States)

    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

  18. The Use of a New CellCollector to Isolate Circulating Tumor Cells from the Blood of Patients with Different Stages of Prostate Cancer and Clinical Outcomes - A Proof-of-Concept Study

    Science.gov (United States)

    Theil, Gerit; Fischer, Kersten; Weber, Ekkehard; Medek, Rita; Hoda, Raschid; Lücke, Klaus; Fornara, Paolo

    2016-01-01

    Background and Methods Circulating tumor cells (CTCs) constitute a useful approach for personalized medicine. Nevertheless, the isolation of these cells remains very challenging because they rarely circulate in the blood. Another current problem is the cancer-specific characterization of these cells, which requires a method that allows for the molecular and immunocytochemical profiling of all captured cells. The purpose of our proof of concept study was to investigate the use of a medical wire (CellCollector, GILUPI) to isolate CTCs in the blood of prostate cancer (PCa) patients, which allowed CTCs to be counted and molecularly characterized. Forty-three PCa patients in different stages and 11 control subjects were studied. Some randomized samples were used to detect tumor-associated transcripts, such as prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA) and epidermal growth factor receptor (EGFR), in the isolated CTCs. Results The mean CTC counts were 4.6 CTCs [range, 0–8] in patients with localized PCa, 16.8 CTCs [range, 10–25] in patients with locally advanced PCa, and 26.8 CTCs [range, 0–98] in patients with metastatic PCa. The median follow-up time was 24 months, and there was a significant difference in the cancer-specific survival rates. Patients with CTC counts under 5 CTCs lived significantly longer (p = 0.035) than patients with more than 5 CTCs. We also demonstrated that the captured CTCs could be molecularly characterized. We detected tumor-associated transcripts of EGFR and PSMA in patients with metastatic PCa in 42.8% and 14.3% of the analyzed samples, respectively. Conclusion Our results indicate that the sensitive isolation and molecular characterization of CTCs can be achieved ex vivo using the wire. Patients with more than 5 CTCs had a mortality risk that was 7.0 times greater that of those with fewer than 5 CTCs (hazard ratio 7.0 95%, CI 1.1–29.39). This proof of concept was required for the approval of the use of

  19. Comparison of the antibody responses to Plasmodium vivax and Plasmodium falciparum antigens in residents of Mandalay, Myanmar

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    Kim Yeon-Joo

    2011-08-01

    Full Text Available Abstract Background The aim of this study was to investigate the profile of antibodies against several antigens of Plasmodium vivax and Plasmodium falciparum in Mandalay, Myanmar. Methods Malaria parasites were identified by microscopic examination. To test the antibodies against P. vivax and P. falciparum in sera, an indirect immunofluorescence antibody test (IFAT was performed using asexual blood parasite antigens. An enzyme-linked immunosorbent assay (ELISA was performed with circumsporozoite protein (CSP, Pvs25 and Pvs28 recombinant proteins of transmission-blocking vaccine candidates for P. vivax, and liver stage specific antigen-1 and -3 (PfLSA-1, PfLSA-3 for P. falciparum. Results Fourteen patients among 112 were found to be infected with P. vivax and 26 with P. falciparum by thick smear examination. Twenty-three patients were found to be infected with P. vivax, 19 with P. falciparum and five with both by thin smear examination. Blood samples were divided into two groups: Group I consisted of patients who were positive for infection by microscopic examination, and Group II consisted of those who showed symptoms, but were negative in microscopic examination. In P. falciparum, IgG against the blood stage antigen in Group I (80.8% was higher than in Group II (70.0%. In P. vivax, IgG against the blood stage antigen in Group I (53.8% was higher than in Group II (41.7%. However, the positivity rate of the PvCSP VK210 subtype in Group II (40.0% was higher than in Group I (23.1%. Similarly for the PvCSP VK247 subtype, Group II (21.7% was higher than that for Group I (9.6%. A similar pattern was observed in the ELISA using Pvs25 and Pvs28: positive rates of Group II were higher than those for Group I. However, those differences were not shown significant in statistics. Conclusions The positive rates for blood stage antigens of P. falciparum were higher in Group I than in Group II, but the positive rates for antigens of other stages (PfLSA-1 and -3

  20. Increased SOCS expression in peripheral blood mononuclear cells of end stage renal disease patients is related to inflammation and dialysis modality.

    Science.gov (United States)

    Rastmanesh, M Mehdi; Braam, Branko; Joles, Jaap A; Boer, Peter; Bluyssen, Hans A R

    2009-01-05

    Inflammation is a characteristic of cardiovascular disease and is increased in end-stage renal disease. Suppressors of cytokine signaling (SOCS) inhibit and reflect activation of intracellular inflammatory pathways. We hypothesized that SOCS expression in peripheral blood mononuclear cells of end stage renal disease patients is increased. Whether SOCS expression in peripheral blood mononuclear cells is related to inflammation, dialysis, and dialysis modality was investigated. Monocytes and lymphocytes were isolated from peripheral blood mononuclear cells of patients not on dialysis (n=8), on peritoneal dialysis (n=8), on hemodialysis (n=14) and of healthy control (n=15) subjects. SOCS expression was assessed by real-time quantitative PCR and plasma cytokines by ELISA. In end stage renal disease patients monocyte SOCS1, and lymphocyte SOCS1 and cytokine-inducible SH2 containing protein-1 (CIS-1) gene expression were increased along with increased plasma levels of interleukin (IL)-6, tumor necrosis factor (TNF)alpha ,and C-reactive protein (CRP). Monocyte SOCS1 correlated with IL-6. Lymphocyte CIS-1 was increased in non-dialysis and peritoneal dialysis but not in hemodialysis patients. Lymphocyte CIS-1 in peritoneal dialysis patients correlated with plasma TNFalpha. Despite the relatively low number of patients studied we observed increased expression of SOCS1 in both monocytes and lymphocytes, and of CIS-1 solely in lymphocytes of the patients. SOCS expression was related to increased systemic inflammation, illustrated by a significant correlation between monocyte SOCS1 and plasma IL-6. SOCS expression in peripheral blood mononuclear cells was also affected by hemodialysis, indicated by increased lymphocyte CIS-1 in non-dialysis and peritoneal dialysis but not in hemodialysis patients. We suggest that increased SOCS expression in peripheral blood mononuclear cells of end stage renal disease patients reflects whether and to which extent systemic inflammation

  1. Relationship between the Increased Haemostatic Properties of Blood Platelets and Oxidative Stress Level in Multiple Sclerosis Patients with the Secondary Progressive Stage

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    Agnieszka Morel

    2015-01-01

    Full Text Available Multiple sclerosis (MS is the autoimmune disease of the central nervous system with complex pathogenesis, different clinical courses and recurrent neurological relapses and/or progression. Despite various scientific papers that focused on early stage of MS, our study targets selective group of late stage secondary progressive MS patients. The presented work is concerned with the reactivity of blood platelets in primary hemostasis in SP MS patients. 50 SP MS patients and 50 healthy volunteers (never diagnosed with MS or other chronic diseases were examined to evaluate the biological activity of blood platelets (adhesion, aggregation, especially their response to the most important physiological agonists (thrombin, ADP, and collagen and the effect of oxidative stress on platelet activity. We found that the blood platelets from SP MS patients were significantly more sensitive to all used agonists in comparison with control group. Moreover, the platelet hemostatic function was advanced in patients suffering from SP MS and positively correlated with increased production of O2-∙ in these cells, as well as with Expanded Disability Status Scale. We postulate that the increased oxidative stress in blood platelets in SP MS may be primarily responsible for the altered haemostatic properties of blood platelets.

  2. Immunodetection of Helicobacter sp. and the associated expression of ABO blood group antigens in the gastric mucosa of captive and free-living New World primates in the Amazon region

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    Délia Cristina Figueira Aguiar

    2011-12-01

    Full Text Available The histo-blood group ABH antigens were first described in humans. These antigens are only present on erythrocytes from great apes and humans, while in more primitive animals they are found in tissues and body fluids. The ABH antigens are mainly distributed in tissues exposed to the external environment and potentially serve as ligands for pathogens or inhibitors of tissue connections. The objective of this paper was two-fold: (i to determine the presence of Helicobacter sp. in the gastric mucosa of 16 captive and 24 free-living New World monkeys and (ii to evaluate the presence of histopathological alterations related to bacterial infection and the associated expression of ABH antigens in the tissue. Stomach tissues from 13 species of monkey were assessed using haematoxylin-eosin and modified Gram staining (Hucker methods. An immunohistochemical analysis of the tissue revealed the presence of infectious bacteria that were characteristic of the genus Helicobacter sp. The results demonstrate that various species of monkey might be naturally infected with the Helicobacter sp. and that there is an increased susceptibility to infection. This study serves as a comparative analysis of infection between human and non-human primates and indicates the presence of a new species of Helicobacter.

  3. Malaria parasite-synthesized heme is essential in the mosquito and liver stages and complements host heme in the blood stages of infection.

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    Viswanathan Arun Nagaraj

    Full Text Available Heme metabolism is central to malaria parasite biology. The parasite acquires heme from host hemoglobin in the intraerythrocytic stages and stores it as hemozoin to prevent free heme toxicity. The parasite can also synthesize heme de novo, and all the enzymes in the pathway are characterized. To study the role of the dual heme sources in malaria parasite growth and development, we knocked out the first enzyme, δ-aminolevulinate synthase (ALAS, and the last enzyme, ferrochelatase (FC, in the heme-biosynthetic pathway of Plasmodium berghei (Pb. The wild-type and knockout (KO parasites had similar intraerythrocytic growth patterns in mice. We carried out in vitro radiolabeling of heme in Pb-infected mouse reticulocytes and Plasmodium falciparum-infected human RBCs using [4-(14C] aminolevulinic acid (ALA. We found that the parasites incorporated both host hemoglobin-heme and parasite-synthesized heme into hemozoin and mitochondrial cytochromes. The similar fates of the two heme sources suggest that they may serve as backup mechanisms to provide heme in the intraerythrocytic stages. Nevertheless, the de novo pathway is absolutely essential for parasite development in the mosquito and liver stages. PbKO parasites formed drastically reduced oocysts and did not form sporozoites in the salivary glands. Oocyst production in PbALASKO parasites recovered when mosquitoes received an ALA supplement. PbALASKO sporozoites could infect mice only when the mice received an ALA supplement. Our results indicate the potential for new therapeutic interventions targeting the heme-biosynthetic pathway in the parasite during the mosquito and liver stages.

  4. Comparative effect of fixed dose combination of Amlodipine + Bisoprolol versus Amlodipine and Bisoprolol alone on blood pressure in stage-2 essential hypertensive patients.

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    Shirure PA,Tadvi NA, Bajait CS, Baig MS, Gade PR

    2012-09-01

    Full Text Available Background: Employment of low dose combinations of two antihypertensives, with different mode of action has gained acceptance worldwide for the treatment of mild to moderate hypertension. However, most studies in hypertensive disease have focused on monotherapy. The combination therapy in the treatment of hypertension is largely extrapolated from these monotherapy studies. Objectives: To study and compare the effect of amlodipine, bisoprolol and fixed dose combination of amlodipine + bisoprolol on blood pressure in stage-2 essential hypertensive patients. Methods: The present study was carried out in Department of Pharmacology in collaboration with Department of Medicine at Government Medical College and Hospital, Aurangabad. Results and Conclusion : Amlodipine + bisoprolol in fixed dose combination have showed significant blood pressure control in patients of stage-2 essential hypertension and the antihypertensive effect was greater than individual monotherapy study groups.

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

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    Orban, Agnes; Albuquerque, Inês S; Butykai, Adam; Kezsmarki, Istvan; Hänscheid, Thomas

    2015-01-01

    Global research efforts have been focused on the simultaneous improvement of the efficiency and sensitivity of malaria diagnosis in resource-limited settings and for the active case detection of asymptomatic infections. A recently developed magneto-optical (MO) method allows the high-sensitivity detection of malaria pigment (hemozoin) crystals in blood via their magnetically induced rotational motion. The evaluation of the method using synthetic $\\beta$-hematin crystals and P. falciparum in vitro cultures implies its potential for in-field diagnosis. Here, we study the performance of the method in monitoring the in vivo onset and progression of the blood stage infection using a malaria mouse model. We found that the MO method can detect the first generation of intraerythrocytic parasites at the ring stage 61-66 hours after sporozoite injection demonstrating better sensitivity than light microscopy and flow cytometry. MO measurements performed after treatment of severe P. berghei infections show that the clear...

  6. A high force of plasmodium vivax blood-stage infection drives the rapid acquisition of immunity in papua new guinean children.

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    Cristian Koepfli

    Full Text Available BACKGROUND: When both parasite species are co-endemic, Plasmodium vivax incidence peaks in younger children compared to P. falciparum. To identify differences in the number of blood stage infections of these species and its potential link to acquisition of immunity, we have estimated the molecular force of blood-stage infection of P. vivax ((molFOB, i.e. the number of genetically distinct blood-stage infections over time, and compared it to previously reported values for P. falciparum. METHODS: P. vivax (molFOB was estimated by high resolution genotyping parasites in samples collected over 16 months in a cohort of 264 Papua New Guinean children living in an area highly endemic for P. falciparum and P. vivax. In this cohort, P. vivax episodes decreased three-fold over the age range of 1-4.5 years. RESULTS: On average, children acquired 14.0 new P. vivax blood-stage clones/child/year-at-risk. While the incidence of clinical P. vivax illness was strongly associated with mol FOB (incidence rate ratio (IRR = 1.99, 95% confidence interval (CI95 [1.80, 2.19], (molFOB did not change with age. The incidence of P. vivax showed a faster decrease with age in children with high (IRR = 0.49, CI95 [0.38, 0.64] p<0.001 compared to those with low exposure (IRR = 0.63, CI95[0.43, 0.93] p = 0.02. CONCLUSION: P. vivax (molFOB is considerably higher than P. falciparum (molFOB (5.5 clones/child/year-at-risk. The high number of P. vivax clones that infect children in early childhood contribute to the rapid acquisition of immunity against clinical P. vivax malaria.

  7. Novel measurement of blood velocity profile using translating-stage optical method and theoretical modeling based on non-Newtonian viscosity model

    Science.gov (United States)

    Kim, Chang-Beom; Lim, Jaeho; Hong, Hyobong; Kresh, J. Yasha; Wootton, David M.

    2015-07-01

    Detailed knowledge of the blood velocity distribution over the cross-sectional area of a microvessel is important for several reasons: (1) Information about the flow field velocity gradients can suggest an adequate description of blood flow. (2) Transport of blood components is determined by the velocity profiles and the concentration of the cells over the cross-sectional area. (3) The velocity profile is required to investigate volume flow rate as well as wall shear rate and shear stress which are important parameters in describing the interaction between blood cells and the vessel wall. The present study shows the accurate measurement of non-Newtonian blood velocity profiles at different shear rates in a microchannel using a novel translating-stage optical method. Newtonian fluid velocity profile has been well known to be a parabola, but blood is a non-Newtonian fluid which has a plug flow region at the centerline due to yield shear stress and has different viscosities depending on shear rates. The experimental results were compared at the same flow conditions with the theoretical flow equations derived from Casson non-Newtonian viscosity model in a rectangular capillary tube. And accurate wall shear rate and shear stress were estimated for different flow rates based on these velocity profiles. Also the velocity profiles were modeled and compared with parabolic profiles, concluding that the wall shear rates were at least 1.46-3.94 times higher than parabolic distribution for the same volume flow rate.

  8. 多重PCR筛选K、Ytb血型抗原的方法研究%Development of a multiplex polymerase chain reaction system for screening low-frequency blood group antigens K and Ytb

    Institute of Scientific and Technical Information of China (English)

    谢莉; 贺云蕾; 库热西江; 叶璐夷; 朱自严

    2014-01-01

    Objective A multiplex PCR system for screening rare blood group antigens K and Ytb was constructed to study the distribution of the two blood groups in a Uygur population in Xinjiang,China.Methods Sequence-specific primers (SSP) were designed based on single nucleotide polymorphism sites of KEL and ACHE alleles encoding the two blood group antigens.The system was designed for simultaneously detecting the two antigens by optimizing the PCR reaction.Three hundred and sixty-two randomly selected healthy individuals were screened.Products of PCR were further analyzed for heterozygnsity.Results The system was set up successfully.No KK sample was identified and 9 K+k+,41 Yt (a+b+),4 Yt (a-b +) were found among the 362 samples.Conclusion The established PCR-SSP based multiple PCR system is efficient to screen the rare blood group antigens K and Ytb.The information of rare blood donors obtained from the screening can be used to improve the capability of compatible transfusion.%目的 建立筛选稀有血型抗原K、Ytb的多重PCR体系,了解这两种血型抗原在维吾尔族人群中的分布情况.方法 针对血型抗原K、Ytb的编码基因KEL和ACHE单核苷酸多态性位点设计序列特异性引物,通过优化PCR反应条件,构建可同时检测K、Ytb血型抗原的多重PCR体系,用该体系对362份新疆维吾尔族随机献血者样本进行相应抗原筛选,并对筛选到的稀有样本进行杂合性分析.结果 成功构建可同时检测低频血型抗原K、Ytb的多重PCR体系,362份维吾尔族样本中共检出9例K+k+,41例Yt(a+b+),4例Yt(a-b+).结论 建立的检测K、Ytb血型抗原的多重PCR体系简便有效.通过筛选所获得的维吾尔族稀有血型数据,可为临床输注配合性血液提供参考资料.

  9. ION-EXCHANGE IMMUNOAFFINITY PURIFICATION OF A RECOMBINANT BACULOVIRUS PLASMODIUM-FALCIPARUM APICAL MEMBRANE ANTIGEN, PF83/AMA-1

    NARCIS (Netherlands)

    NARUM, DL; WELLING, GW; THOMAS, AW

    1993-01-01

    A two-step purification regime has been developed for a quantitatively minor, putatively transmembrane, M(r) 83 000, apical membrane blood stage vaccine candidate antigen of Plasmodium falciparum (PF83/AMA-1), that has been expressed as a full-length baculovirus recombinant protein, PF83-FG8-1. The

  10. COLONOSCOPY AND CARCINOEMBRYONIC ANTIGEN VARIATIONS

    Directory of Open Access Journals (Sweden)

    Rita G SOUSA

    2014-03-01

    Full Text Available Context Colonoscopy is essential for synchronous and metachronous cancer detection. Carcinoembryonic antigen is a colorectal cancer tumor marker, important as a follow-up tool in patients with previous colorectal cancer. False-positive carcinoembryonic antigen elevation results in multiples exams and in patient anxiety. In literature, there is reference to transient carcinoembryonic antigen increase with colonoscopy. Objective To evaluate the influence of bowel preparation and colonoscopy in carcinoembryonic antigen blood levels. Methods We prospectively studied subjects that underwent routine colonoscopy in our institution. Blood samples were collected (1 before bowel cleaning, (2 before colonoscopy and (3 immediately after colonoscopy. Blood carcinoembryonic antigen levels were determined by “Sandwich” immunoassay. The statistical methods used were the paired t-test and ANOVA. Results Thirty-seven patients (22M/15F were included; age range 28-84 (mean 56 years. Mean carcinoembryonic antigen values were 1.9, 2 and 1.8 for (1, (2 and (3, respectively. An increase in value (2 compared with (1 was observed in 20/37 patients (P = 0.018, mainly in younger patients and in patients requiring more endoluminal interventions. In 29/37 patients, the CEA value decreased from (2 to (3 (P = 1.3x10-7. Conclusions A trend for carcinoembryonic antigen increase after bowel cleaning was observed, especially in younger patients and in patients with more endoluminal interventions, but without clinical meaning.

  11. Relationship of gelatinases-tight junction proteins and blood-brain barrier permeability in the early stage of cerebral ischemia and reperfusion

    Institute of Scientific and Technical Information of China (English)

    Haolin Xin; Wenzhao Liang; Jing Mang; Lina Lin; Na Guo; Feng Zhang; Zhongxin Xu

    2012-01-01

    Gelatinases matrix metalloproteinase-2 and matrix metalloproteinase-9 have been shown to mediate claudin-5 and occludin degradation, and play an important regulatory role in blood-brain barrier permeability. This study established a rat model of 1.5-hour middle cerebral artery occlusion with reperfusion. Protein expression levels of claudin-5 and occludin gradually decreased in the early stage of reperfusion, which corresponded to the increase of the gelatinolytic activity of matrix metalloproteinase-2 and matrix metalloproteinase-9. In addition, rats that received treatment with matrix metalloproteinase inhibitor N-[(2R)-2-(hydroxamidocarbonylmethyl)-4-methylpenthanoyl]-L- tryptophan methylamide (GM6001) showed a significant reduction in Evans blue leakage and an inhibition of claudin-5 and occludin protein degradation in striatal tissue. These data indicate that matrix metalloproteinase-2 and matrix metalloproteinase-9-mediated claudin-5 and occludin degradation is an important reason for blood-brain barrier leakage in the early stage of reperfusion. The leakage of the blood-brain barrier was present due to gelatinases-mediated degradation of claudin-5 and occludin proteins. We hypothesized that the timely closure of the structural component of the blood-brain barrier (tight junction proteins) is of importance.

  12. Non-major histocompatibility complex-restricted cytotoxic activity of blood mononuclear cells stimulated with secreted mycobacterial proteins and other mycobacterial antigens

    DEFF Research Database (Denmark)

    Ravn, P; Pedersen, B K

    1994-01-01

    Several observations indicate that non-major histocompatibility complex (MHC)-restricted cytotoxicity, mediated for example by natural killer cells and lymphokine-activated killer cells, may serve as an important antimicrobial defense mechanism. The purpose of the present study was to investigate...... the influences of different mycobacterial antigens on non-MHC-restricted cytotoxicity and further to investigate the ways by which various lymphocyte subpopulations contribute to the development of this cytotoxicity. Non-MHC-restricted cytotoxicity was induced following stimulation of mononuclear cells......+ cells proliferated and expressed interleukin-2 receptors following stimulation with mycobacterial antigens. Depletion studies after antigen stimulation showed that the cytotoxic effector cells were CD16+ CD56+ and CD4-; the CD4+ cells alone did not mediate non-MHC-restricted cytotoxicity. To evaluate...

  13. Detection of nuclear and membrane antigens by liquid-based cytology following long-term storage of d1 cells, karpas cells, and peripheral blood mononuclear cells.

    Science.gov (United States)

    Zappacosta, Roberta; Aiello, Francesca B; D'Antuono, Tommaso; Procopio, Antonio D; Durum, Scott K; Conti, Pio; Rosini, Sandra

    2011-01-01

    Immunofluorescence is the most frequently utilized technique to analyze protein expression. Fixed immunofluorescent cell suspensions, however, can only be stored for a week. We investigated whether liquid-based cytology could be used to detect antigens in cultured cells after a long storage period. Murine and human cells were fixed in PreservCyt solution, stored for various periods, and then used to perform an automated immunocytochemical analysis. Phosphorylation of the nuclear transcription factor Stat-5 induced by IL-7 was detected up to 4 months after IL-7 stimulation. Simultaneous nuclear positivity for the proliferation index MIB-1 and membrane positivity for the CD30 antigen were evident three months after fixation. Liquid-based cytology thus ensures long-lasting nuclear and membrane antigen immunoreactivity and permits the storage of cells from laborious experiments at room temperature for future analyses.

  14. Enhancing blockade of Plasmodium falciparum erythrocyte invasion: assessing combinations of antibodies against PfRH5 and other merozoite antigens.

    Directory of Open Access Journals (Sweden)

    Andrew R Williams

    Full Text Available No vaccine has yet proven effective against the blood-stages of Plasmodium falciparum, which cause the symptoms and severe manifestations of malaria. We recently found that PfRH5, a P. falciparum-specific protein expressed in merozoites, is efficiently targeted by broadly-neutralizing, vaccine-induced antibodies. Here we show that antibodies against PfRH5 efficiently inhibit the in vitro growth of short-term-adapted parasite isolates from Cambodia, and that the EC(50 values of antigen-specific antibodies against PfRH5 are lower than those against PfAMA1. Since antibody responses elicited by multiple antigens are speculated to improve the efficacy of blood-stage vaccines, we conducted detailed assessments of parasite growth inhibition by antibodies against PfRH5 in combination with antibodies against seven other merozoite antigens. We found that antibodies against PfRH5 act synergistically with antibodies against certain other merozoite antigens, most notably with antibodies against other erythrocyte-binding antigens such as PfRH4, to inhibit the growth of a homologous P. falciparum clone. A combination of antibodies against PfRH4 and basigin, the erythrocyte receptor for PfRH5, also potently inhibited parasite growth. This methodology provides the first quantitative evidence that polyclonal vaccine-induced antibodies can act synergistically against P. falciparum antigens and should help to guide the rational development of future multi-antigen vaccines.

  15. Preoperative serum carcinoembryonic antigen, albumin and age are supplementary to UICC staging systems in predicting survival for colorectal cancer patients undergoing surgical treatment

    Directory of Open Access Journals (Sweden)

    Kuo Chao-Hung

    2009-08-01

    Full Text Available Abstract Background The aim of this study was to determine influence of prognostic factors in addition to UICC staging systems, on cancer-specific and overall survival rates for patients with colorectal cancer (CRC undergoing surgical treatment. Methods Between January 1996 and December 2006, a total of 1367 CRC patients who underwent surgical treatment in Kaohsiung Medical University Hospital were analyzed. We retrospectively investigated clinicopathologic features of these patients. All patients were followed up intensively, and their outcomes were investigated completely. Results Of 1367 CRC patients, there were seven hundred and fifty-seven males (55.4% and 610 (44.6% females. The median follow-up period was 60 months (range, 3–132 months. A multivariate analysis identified that low serum albumin level (P = 0.011, advanced UICC stage (P P P P P Conclusion Preoperative serum albumin level, CEA level and age could prominently affect postoperative outcome of CRC patients undergoing surgical treatment. In addition to conventional UICC staging system, it might be imperative to take these additional characteristics of factors into account in CRC patients prior to surgical treatment.

  16. Characterization of WbiQ: An {alpha}1,2-fucosyltransferase from Escherichia coli O127:K63(B8), and synthesis of H-type 3 blood group antigen

    Energy Technology Data Exchange (ETDEWEB)

    Pettit, Nicholas; Styslinger, Thomas; Mei, Zhen; Han, Weiqing; Zhao, Guohui [Departments of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210 (United States); Wang, Peng George, E-mail: Wang.892@osu.edu [Departments of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210 (United States)

    2010-11-12

    Research highlights: {yields} WbiQ is an {alpha}1,2-fucosyltransferase from Escherichia coli O127. {yields} WbiQ demonstrates strict substrate specificity for the Gal-{beta}1,3-GalNAc acceptor. {yields} WbiQ was used to synthesize milligram scale of the H-type 3 blood group antigen. -- Abstract: Escherichia coli O127:K63(B8) possesses high human blood group H (O) activity due to its O-antigen repeating unit structure. In this work, the wbiQ gene from E. coli O127:K63(B8) was expressed in E. coli BL21 (DE3) and purified as a fusion protein containing an N-terminal GST affinity tag. Using the GST-WbiQ fusion protein, the wbiQ gene was identified to encode an {alpha}1,2-fucosyltransferase using a radioactivity based assay, thin-layer chromatography assay, as well confirming product formation by using mass spectrometry and NMR spectroscopy. The fused enzyme (GST-WbiQ) has an optimal pH range from 6.5 to 7.5 and does not require the presence of a divalent metal to be enzymatically active. WbiQ displays strict substrate specificity, displaying activity only towards acceptors that contain Gal-{beta}1,3-GalNAc-{alpha}-OR linkages; indicating that both the Gal and GalNAc residues are vital for enzymatic activity. In addition, WbiQ was used to prepare the H-type 3 blood group antigen, Fuc-{alpha}1,2-Gal-{beta}1,3-GalNAc-{alpha}-OMe, on a milligram scale.

  17. 浅析血液生化检测各阶段质控对策%Analysis of the various stages of quality control blood biochemical detection countermeasures

    Institute of Scientific and Technical Information of China (English)

    王光让; 李婷; 刘宁

    2013-01-01

    Objective To investigate the effects of the various stages of quality control sample pass rate of biochemical tests of blood. Methods Patients in February 2013 -2014 February 422 routine blood biochemical examination of the hospital for the study. order by patients admitted to hospital will be divided into a control group (n = 211) and experimental group (n = 211). The control group received routine blood chemistry testing. Experimental group at all stages of biochemical strict quality control testing. Compare two samples of blood biochemical test pass rate case. Results The control group of blood samples biochemical detection rate of 84.36% passing (178/211), the experimental group 98.58% (208/211), blood biochemistry experimental group was significantly higher pass rate specimens (P <0.01). Conclusion The various stages of quality control can significantly improve the pass rate of clinical specimens of blood biochemical tests provide a reliable basis for clinical diagnosis and treatment.%目的:探讨各阶段质控对血液生化检测标本合格率的影响。方法选取我院2013年2月至2013年8月422例行血生化检查的患者作为研究对象。按患者入院顺序,将其分为对照组(n=211)和实验组(n=211)。对照组接受常规血生化检测。实验组对血生化检测的各个阶段进行严格质控。对比两组血生化检测标本合格率情况。结果对照组血生化检测标本合格率84.36%(178/211),实验组98.58%(208/211),实验组血生化检测标本合格率显著高于对照组(P<0.01)。结论各阶段质控可显著提高临床血生化检测标本的合格率,为临床诊断及治疗提供可靠依据。

  18. Complete blood counts, liver function tests, and chest x-rays as routine screening in early-stage breast cancer: value added or just cost?

    Science.gov (United States)

    Louie, Raphael J; Tonneson, Jennifer E; Gowarty, Minda; Goodney, Philip P; Barth, Richard J; Rosenkranz, Kari M

    2015-11-01

    Current National Comprehensive Cancer Network guidelines for breast cancer staging include pre-treatment complete blood count (CBC) and liver function tests (LFT) to screen for occult metastatic disease. To date, the relevance of these tests in detecting metastatic disease in asymptomatic women with early-stage breast cancer (Stage I/II) has not been demonstrated. Although chest x-rays are no longer recommended in the NCCN guidelines, many centers continue to include this imaging as part of their screening process. We aim to determine the clinical and financial impact of these labs and x-rays in the evaluation of early-stage breast cancer patients. A single institution IRB-approved retrospective chart review was conducted of patients with biopsy-proven invasive breast cancer treated from January 1, 2005–December 31, 2009. We collected patient demographics, clinical and pathologic staging, chest x-ray, CBC, and LFT results at the time of referral. Patients were stratified according to radiographic stage at the time of diagnosis. We obtained Medicare reimbursement fees for cost analysis. From 2005 to 2009, 1609 patients with biopsy-proven invasive breast cancer were treated at our institution. Of the 1082 patients with radiographic stage I/II disease, 27.3 % of patients had abnormal CBCs. No additional testing was performed to evaluate these abnormalities. In the early-stage population, 24.7 % of patients had elevated LFTs, resulting in 84 additional imaging studies. No metastatic disease was detected. The cost of CBC, LFTs and chest x-rays was $110.20 per patient, totaling $106,410.99. Additional tests prompted by abnormal results cost $58,143.30 over the five-year period. We found that pre-treatment CBCs, LFTs, and chest x-rays did not improve detection of occult metastatic disease but resulted in additional financial costs. Avoiding routine ordering of these tests would save the US healthcare system $25.7 million annually.

  19. Antigen Export Reduces Antigen Presentation and Limits T Cell Control of M. tuberculosis.

    Science.gov (United States)

    Srivastava, Smita; Grace, Patricia S; Ernst, Joel D

    2016-01-13

    Persistence of Mycobacterium tuberculosis results from bacterial strategies that manipulate host adaptive immune responses. Infected dendritic cells (DCs) transport M. tuberculosis to local lymph nodes but activate CD4 T cells poorly, suggesting bacterial manipulation of antigen presentation. However, M. tuberculosis antigens are also exported from infected DCs and taken up and presented by uninfected DCs, possibly overcoming this blockade of antigen presentation by infected cells. Here we show that the first stage of this antigen transfer, antigen export, benefits M. tuberculosis by diverting bacterial proteins from the antigen presentation pathway. Kinesin-2 is required for antigen export and depletion of this microtubule-based motor increases activation of antigen-specific CD4 T cells by infected cells and improves control of intracellular infection. Thus, although antigen transfer enables presentation by bystander cells, it does not compensate for reduced antigen presentation by infected cells and represents a bacterial strategy for CD4 T cell evasion.

  20. Expression of variant surface antigens by Plasmodium falciparum parasites in the peripheral blood of clinically immune pregnant women indicates ongoing placental infection

    DEFF Research Database (Denmark)

    Ofori, Michael F; Staalsoe, Trine; Bam, Victoria

    2003-01-01

    Placenta-sequestered Plasmodium falciparum parasites that cause pregnancy-associated malaria (PAM) in otherwise clinically immune women express distinct variant surface antigens (VSA(PAM)) not expressed by parasites in nonpregnant individuals. We report here that parasites from the peripheral blo...

  1. Incubation of whole blood at 39°C augments gamma interferon (IFN-γ)-induced protein 10 and IFN-γ responses to Mycobacterium tuberculosis antigens

    DEFF Research Database (Denmark)

    Aabye, Martine G; Ravn, Pernille; Johansen, Isik S

    2011-01-01

    A rarely challenged dogma in cell-mediated immune (CMI) assays is the incubation temperature, 37°C. Fever augments proinflammatory immune responses in vivo, and the aim of this study was to explore whether incubation at fever-range temperature could increase antigen-specific biomarker responses. ...

  2. Prospective evaluation of a whole-blood test using Mycobacterium tuberculosis-specific antigens ESAT-6 and CFP-10 for diagnosis of active tuberculosis

    DEFF Research Database (Denmark)

    Ravn, Pernille; Munk, Martin E; Andersen, Ase B

    2005-01-01

    A new immunodiagnostic test based on the Mycobacterium tuberculosis-specific antigens CFP-10/ESAT-6(QFT-RD1) has been launched as an aid in the diagnosis of latent tuberculosis (TB) infection (LTBI). The aim of this study was to evaluate this test for the diagnosis of active TB. Eighty-two patien...

  3. Stable solid-phase Rh antigen.

    Science.gov (United States)

    Yared, M A; Moise, K J; Rodkey, L S

    1997-12-01

    Numerous investigators have attempted to isolate the Rh antigens in a stable, immunologically reactive form since the discovery of the Rh system over 56 years ago. We report here a successful and reproducible approach to solubilizing and adsorbing the human Rh antigen(s) to a solid-phase matrix in an antigenically active form. Similar results were obtained with rabbit A/D/F red blood cell antigens. The antigen preparation was made by dissolution of the red blood cell membrane lipid followed by fragmentation of the residual cytoskeleton in an EDTA solution at low ionic strength. The antigenic activity of the soluble preparations was labile in standard buffers but was stable in zwitterionic buffers for extended periods of time. Further studies showed that the antigenic activity of these preparations was enhanced, as was their affinity for plastic surfaces, in the presence of acidic zwitterionic buffers. Adherence to plastic surfaces at low pH maintained antigenic reactivity and specificity for antibody was retained. The data show that this approach yields a stable form of antigenically active human Rh D antigen that could be used in a red blood cell-free assay for quantitative analysis of Rh D antibody and for Rh D antibody immunoadsorption and purification.

  4. Flow Cytometric Analysis of T, B, and NK Cells Antigens in Patients with Mycosis Fungoides

    Science.gov (United States)

    Yazıcı, Serkan; Bülbül Başkan, Emel; Budak, Ferah; Oral, Barbaros; Adim, Şaduman Balaban; Ceylan Kalin, Zübeyde; Özkaya, Güven; Aydoğan, Kenan; Saricaoğlu, Hayriye; Tunali, Şükran

    2015-01-01

    We retrospectively analyzed the clinicopathological correlation and prognostic value of cell surface antigens expressed by peripheral blood mononuclear cells in patients with mycosis fungoides (MF). 121 consecutive MF patients were included in this study. All patients had peripheral blood flow cytometry as part of their first visit. TNMB and histopathological staging of the cases were retrospectively performed in accordance with International Society for Cutaneous Lymphomas/European Organization of Research and Treatment of Cancer (ISCL/EORTC) criteria at the time of flow cytometry sampling. To determine prognostic value of cell surface antigens, cases were divided into two groups as stable and progressive disease. 17 flow cytometric analyses of 17 parapsoriasis (PP) and 11 analyses of 11 benign erythrodermic patients were included as control groups. Fluorescent labeled monoclonal antibodies were used to detect cell surface antigens: T cells (CD3+, CD4+, CD8+, TCRαβ+, TCRγδ+, CD7+, CD4+CD7+, CD4+CD7−, and CD71+), B cells (HLA-DR+, CD19+, and HLA-DR+CD19+), NKT cells (CD3+CD16+CD56+), and NK cells (CD3−CD16+CD56+). The mean value of all cell surface antigens was not statistically significant between parapsoriasis and MF groups. Along with an increase in cases of MF stage statistically significant difference was found between the mean values of cell surface antigens. Flow cytometric analysis of peripheral blood cell surface antigens in patients with mycosis fungoides may contribute to predicting disease stage and progression. PMID:26788525

  5. Flow Cytometric Analysis of T, B, and NK Cells Antigens in Patients with Mycosis Fungoides

    Directory of Open Access Journals (Sweden)

    Serkan Yazıcı

    2015-01-01

    Full Text Available We retrospectively analyzed the clinicopathological correlation and prognostic value of cell surface antigens expressed by peripheral blood mononuclear cells in patients with mycosis fungoides (MF. 121 consecutive MF patients were included in this study. All patients had peripheral blood flow cytometry as part of their first visit. TNMB and histopathological staging of the cases were retrospectively performed in accordance with International Society for Cutaneous Lymphomas/European Organization of Research and Treatment of Cancer (ISCL/EORTC criteria at the time of flow cytometry sampling. To determine prognostic value of cell surface antigens, cases were divided into two groups as stable and progressive disease. 17 flow cytometric analyses of 17 parapsoriasis (PP and 11 analyses of 11 benign erythrodermic patients were included as control groups. Fluorescent labeled monoclonal antibodies were used to detect cell surface antigens: T cells (CD3+, CD4+, CD8+, TCRαβ+, TCRγδ+, CD7+, CD4+CD7+, CD4+CD7−, and CD71+, B cells (HLA-DR+, CD19+, and HLA-DR+CD19+, NKT cells (CD3+CD16+CD56+, and NK cells (CD3−CD16+CD56+. The mean value of all cell surface antigens was not statistically significant between parapsoriasis and MF groups. Along with an increase in cases of MF stage statistically significant difference was found between the mean values of cell surface antigens. Flow cytometric analysis of peripheral blood cell surface antigens in patients with mycosis fungoides may contribute to predicting disease stage and progression.

  6. A novel Pfs38 protein complex on the surface of Plasmodium falciparum blood-stage merozoites

    DEFF Research Database (Denmark)

    Paul, Gourab; Deshmukh, Arunaditya; Kaur, Inderjeet;

    2017-01-01

    BACKGROUND: The Plasmodium genome encodes for a number of 6-Cys proteins that contain a module of six cysteine residues forming three intramolecular disulphide bonds. These proteins have been well characterized at transmission as well as hepatic stages of the parasite life cycle. In the present s...

  7. T-cell depletion and autologous stem cell transplantation in the management of tumour stage mycosis fungoides with peripheral blood involvement.

    Science.gov (United States)

    Olavarria, E; Child, F; Woolford, A; Whittaker, S J; Davis, J G; McDonald, C; Chilcott, S; Spittle, M; Grieve, R J; Stewart, S; Apperley, J F; Russell-Jones, R

    2001-09-01

    Nine patients with tumour stage mycosis fungoides (MF) have been entered into a pilot study of T-cell depletion and autologous stem cell transplantation (SCT). Eight patients had detectable rearrangements of the T-cell receptor (TCR) gamma-gene demonstrated by polymerase chain reaction (PCR)/single-stranded conformation polymorphism (SSCP) in the peripheral blood. The median age was 47 years and the median duration of disease before SCT was 61 months; Peripheral blood progenitor cells were mobilized using high-dose etoposide (1.6 g/m2) and granulocyte colony-stimulating factor (G-CSF). The apheresis products underwent rigorous T-cell depletion with immunomagnetic methods. Double CD34-positive and CD4/CD8-negative selection achieved a median reduction of 3.89 log of T cells. All nine patients have been transplanted. Conditioning included carmustine (BCNU), etoposide and melphalan (BEM) in seven patients and total body irradiation plus etoposide or melphalan in two. Eight patients engrafted promptly and one patient died of septicaemia. All survivors entered complete remission. Seven patients have relapsed at a median of 7 months (2-14) post SCT. However, most patients have relapsed into a less aggressive stage, which has responded to conventional therapy. Four out of seven evaluable patients had detectable TCR rearrangements in the T-cell depleted graft. A T-cell clone was also detected in the peripheral blood before relapse in four cases. Autologous SCT is feasible, safe and can result in complete remission in a significant proportion of patients with tumour stage mycosis fungoides. Despite a short relapse-free survival, most patients achieved good disease control at the time of relapse.

  8. A randomized controlled trial comparing the effects of yoga with an active control on ambulatory blood pressure in individuals with prehypertension and stage 1 hypertension.

    Science.gov (United States)

    Hagins, Marshall; Rundle, Andrew; Consedine, Nathan S; Khalsa, Sat Bir S

    2014-01-01

    The purpose of this study was to compare the effects of yoga with an active control (nonaerobic exercise) in individuals with prehypertension and stage 1 hypertension. A randomized clinical trial was performed using two arms: (1) yoga and (2) active control. Primary outcomes were 24-hour day and night ambulatory systolic and diastolic blood pressures. Within-group and between-group analyses were performed using paired t tests and repeated-measures analysis of variance (time × group), respectively. Eighty-four participants enrolled, with 68 participants completing the trial. Within-group analyses found 24-hour diastolic, night diastolic, and mean arterial pressure all significantly reduced in the yoga group (-3.93, -4.7, -4.23 mm Hg, respectively) but no significant within-group changes in the active control group. Direct comparisons of the yoga intervention with the control group found a single blood pressure variable (diastolic night) to be significantly different (P=.038). This study has demonstrated that a yoga intervention can lower blood pressure in patients with mild hypertension. Although this study was not adequately powered to show between-group differences, the size of the yoga-induced blood pressure reduction appears to justify performing a definitive trial of this intervention to test whether it can provide meaningful therapeutic value for the management of hypertension.

  9. Azilsartan medoxomil plus chlorthalidone reduces blood pressure more effectively than olmesartan plus hydrochlorothiazide in stage 2 systolic hypertension.

    Science.gov (United States)

    Cushman, William C; Bakris, George L; White, William B; Weber, Michael A; Sica, Domenic; Roberts, Andrew; Lloyd, Eric; Kupfer, Stuart

    2012-08-01

    Azilsartan medoxomil, an effective, long-acting angiotensin II receptor blocker, is a new treatment for hypertension that is also being developed in fixed-dose combinations with chlorthalidone, a potent, long-acting thiazide-like diuretic. We compared once-daily fixed-dose combinations of azilsartan medoxomil/chlorthalidone force titrated to a high dose of either 40/25 mg or 80/25 mg with a fixed-dose combination of the angiotensin II receptor blocker olmesartan medoxomil plus the thiazide diuretic hydrochlorothiazide force titrated to 40/25 mg. The design was a randomized, 3-arm, double-blind, 12-week study of 1071 participants with baseline clinic systolic blood pressure 160 to 190 mm Hg and diastolic blood pressure ≤119 mm Hg. Patients had a mean age of 57 years; 59% were men, 73% were white, and 22% were black. At baseline, mean clinic blood pressure was 165/96 mm Hg and 24-hour mean blood pressure was 150/88 mm Hg. Changes in clinic (primary end point) and ambulatory systolic blood pressures at week 12 were significantly greater in both azilsartan medoxomil/chlorthalidone arms than in the olmesartan/hydrochlorothiazide arm (Pblood pressure (mean±SE) were -42.5±0.8, -44.0±0.8, and -37.1±0.8 mm Hg, respectively. Changes in 24-hour ambulatory systolic blood pressure were -33.9±0.8, -36.3±0.8, and -27.5±0.8 mm Hg, respectively. Adverse events leading to permanent drug discontinuation occurred in 7.9%, 14.5%, and 7.1% of the groups given azilsartan medoxomil/chlorthalidone 40/25 mg, azilsartan medoxomil/chlorthalidone 80/25 mg, and olmesartan/hydrochlorothiazide 40/25 mg, respectively. This large, forced-titration study has demonstrated superior antihypertensive efficacy of azilsartan medoxomil/chlorthalidone fixed-dose combinations compared with the maximum approved dose of olmesartan/hydrochlorothiazide.

  10. Targeting Angiotensin II Type-1 Receptor (AT1R) Inhibits the Harmful Phenotype of Plasmodium-Specific CD8+ T Cells during Blood-Stage Malaria

    Science.gov (United States)

    Silva-Filho, João L.; Caruso-Neves, Celso; Pinheiro, Ana A. S.

    2017-01-01

    CD8+ T-cell response is critical in the pathogenesis of cerebral malaria during blood-stage. Our group and other have been shown that angiotensin II (Ang II) and its receptor AT1 (AT1R), a key effector axis of renin-angiotensin system (RAS), have immune regulatory effects on T cells. Previously, we showed that inhibition of AT1R signaling protects mice against the lethal disease induced by Plasmodium berghei ANKA infection However, most of the Ang II/AT1R actions were characterized by using only pharmacological approaches, the effects of which may not always be due to a specific receptor blockade. In addition, the mechanisms of action of the AT1R in inducing the pathogenic activity of Plasmodium-specific CD8+ T cells during blood-stage were not determined. Here, we examined how angiotensin II/AT1R axis promotes the harmful response of Plasmodium-specific CD8+ T-cell during blood-stage by using genetic and pharmacological approaches. We evaluated the response of wild-type (WT) and AT1R−/− Plasmodium-specific CD8+ T cells in mice infected with a transgenic PbA lineage expressing ovalbumin; and in parallel infected mice receiving WT Plasmodium-specific CD8+ T cells were treated with losartan (AT1R antagonist) or captopril (ACE inhibitor). Both, AT1R−/− OT-I cells and WT OT-I cells from losartan- or captopril-treated mice showed lower expansion, reduced IL-2 production and IL-2Rα expression, lower activation (lower expression of CD69, CD44 and CD160) and lower exhaustion profiles. AT1R−/− OT-I cells also exhibit lower expression of the integrin LFA-1 and the chemokine receptors CCR5 and CXCR3, known to play a key role in the development of cerebral malaria. Moreover, AT1R−/− OT-I cells produce lower amounts of IFN-γ and TNF-α and show lower degranulation upon restimulation. In conclusion, our results show the pivotal mechanisms of AT1R-induced harmful phenotype of Plasmodium-specific CD8+ T cells during blood-stage malaria. PMID:28261571

  11. Staged treatment of a blood blister-like aneurysm with stent-assisted coiling followed by flow diverter in-stent insertion. A case report.

    Science.gov (United States)

    Princiotta, C; Dall'olio, M; Cirillo, L; Leonardi, M

    2011-09-01

    Blood blister-like aneurysms (BBLA) are rare lesions sometimes difficult to recognize and in most cases associated with diffuse subarachnoid haemorrhage and severe clinical conditions. BBLA are life-threatening because they tend to enlarge rapidly and to rebleed, and no consensus has so far been reached on the best management strategy. We describe a patient with a BBLA in the right ICA treated successful by a two-stage embolization procedure first with coils and an open cell stent (Neuroform 3) and later by further coil placement and insertion of a flow-diverting stent (Silk).

  12. The Plasmodium falciparum var gene transcription strategy at the onset of blood stage infection in a human volunteer

    DEFF Research Database (Denmark)

    Wang, Christian W; Hermsen, Cornelus C; Sauerwein, Robert W;

    2009-01-01

    The var genes encode a family of adhesion receptor proteins, Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), which profoundly influence malaria pathogenesis. Only a single var gene is transcribed and one PfEMP1 expressed per P.falciparum parasite. Here we present the in vivo...... transcript distribution of var genes in a P. falciparum-infected non-immune individual and show that the initial expression of PfEMP1 is based on a strategy that allows all or most variants of PfEMP1s to be expressed by the parasite population at the onset of the blood stage infection....

  13. Flow cytometric readout based on Mitotracker Red CMXRos staining of live asexual blood stage malarial parasites reliably assesses antibody dependent cellular inhibition

    DEFF Research Database (Denmark)

    Jogdand, Prajakta S; Singh, Susheel K; Christiansen, Michael;

    2012-01-01

    ABSTRACT: BACKGROUND: Functional in vitro assays could provide insights into the efficacy of malaria vaccine candidates. For estimating the anti-parasite effect induced by a vaccine candidate, an accurate determination of live parasite count is an essential component of most in vitro bioassays...... asynchronous and tightly synchronized asexual blood stage cultures of Plasmodium falciparum were stained with CMXRos and subjected to detection by flow cytometry and fluorescence microscopy. The parasite counts obtained by flow cytometry were compared to standard microscopic counts obtained through examination...

  14. A Novel Synthetic TLR-4 Agonist Adjuvant Increases the Protective Response to a Clinical-Stage West Nile Virus Vaccine Antigen in Multiple Formulations.

    Science.gov (United States)

    Van Hoeven, Neal; Joshi, Sharvari Waghmare; Nana, Ghislain Ismael; Bosco-Lauth, Angela; Fox, Christopher; Bowen, Richard A; Clements, David E; Martyak, Timothy; Parks, D Elliot; Baldwin, Susan; Reed, Steven G; Coler, Rhea N

    2016-01-01

    West Nile virus (WNV) is a mosquito-transmitted member of the Flaviviridae family that has emerged in recent years to become a serious public health threat. Given the sporadic nature of WNV epidemics both temporally and geographically, there is an urgent need for a vaccine that can rapidly provide effective immunity. Protection from WNV infection is correlated with antibodies to the viral envelope (E) protein, which encodes receptor binding and fusion functions. Despite many promising E-protein vaccine candidates, there are currently none licensed for use in humans. This study investigates the ability to improve the immunogenicity and protective capacity of a promising clinical-stage WNV recombinant E-protein vaccine (WN-80E) by combining it with a novel synthetic TLR-4 agonist adjuvant. Using the murine model of WNV disease, we find that inclusion of a TLR-4 agonist in either a stable oil-in-water emulsion (SE) or aluminum hydroxide (Alum) formulation provides both dose and dosage sparing functions, whereby protection can be induced after a single immunization containing only 100 ng of WN-80E. Additionally, we find that inclusion of adjuvant with a single immunization reduced viral titers in sera to levels undetectable by viral plaque assay. The enhanced protection provided by adjuvanted immunization correlated with induction of a Th1 T-cell response and the resultant shaping of the IgG response. These findings suggest that inclusion of a next generation adjuvant may greatly enhance the protective capacity of WNV recombinant subunit vaccines, and establish a baseline for future development.

  15. CisAB01血型分子机制及红细胞表面抗原表达的研究%Study of molecular mechanism and antigen expression of CisAB01 blood group

    Institute of Scientific and Technical Information of China (English)

    邓刚; 许德义; 梁伟; 贺云蕾; 黄丹丹; 郭雯玉; 张日

    2015-01-01

    Objective To explore the molecular mechanism of CisAB01 subtype in the ABO blood group system,and to investigate the expression of A and B antigens in red blood cells (RBCs).Methods For 5 unrelated individuals with the CisAB phenotype,the molecular basis for the blood type was studied with serological assay,DNA sequencing and haplotype analysis.Bioinformatics analysis was carried out to investigate the changes in structure and function of relevant enzymes.Expression of A and B antigens in RBCs of CisAB01 was detected by flow cytometry.Results All of the 5 samples were found to have a CisAB01 subtype.The underlying mutations,467C>T and 803G>C in exon 7,have resulted in replacement of amino acid P156L and G268A.The mean fluorescence intensity (MFI) of A antigen in CisAB01 cases was 135,while the control group was 172.The B antigens in CisAB01 cases (MFI =38) showed significant decrease in MFI compared with the control group (MFI=164).Conclusion 803G>C mutation of the ABO gene probably underlies the CisAB01 subtype.Fluorescence intensity of A antigens in CisAB01 subtype cases is slightly lower than the normal type,while the B antigen was significantly lower.%目的 研究ABO血型系统CisAB01亚型的分子机制,并探讨该亚型红细胞表面A和B抗原的表达情况.方法 对5例ABO血型正反定型不符的无偿献血者或患者,通过血清学技术、ABO基因直接测序及TA克隆单体型分析对该血型进行相关研究.应用相关生物学软件对突变位点引起的酶结构和功能变化进行分析,并采用流式细胞术分析红细胞表面A和B抗原的表达情况,同时取正常AB型血的献血者80名作为对照.结果 发现5例CisAB01亚型,该亚型ABO基因第7外显子467C>T、803G>C突变,分别引起多肽链P156L和G268A替换.5例标本红细胞表面A抗原平均荧光强度(mean fluorescenceintensity,MFI)为135,对照组A抗原MFI则为172;5例标本红细胞表面B抗原MFI为38,对照组B抗原MFI则为164.

  16. Impacts of acupuncture on blood pressure and hematoma in patients of cerebral hemorrhage at the early stage

    Institute of Scientific and Technical Information of China (English)

    陶文强

    2014-01-01

    Objective To explore the therapeutic effect of acupuncture for hypertensive cerebral hemorrhage at the early stage.Methods Fifty-four cases of small-amount cerebral hemorrhage were randomized into an acupuncture group and a conventional treatment group,27 cases in each.In the conventional treatment group,special care,oxygen therapy,nerve nutrition and symptomatic support were applied.If necessary,dehydrant and hypotensive drugs were prescribed for antihypertension,or surgery

  17. Three-dimensional visualisation of developmental stages of an apicomplexan fish blood parasite in its invertebrate host

    Directory of Open Access Journals (Sweden)

    Hayes Polly M

    2011-11-01

    Full Text Available Abstract Background Although widely used in medicine, the application of three-dimensional (3D imaging to parasitology appears limited to date. In this study, developmental stages of a marine fish haemogregarine, Haemogregarina curvata (Apicomplexa: Adeleorina, were investigated in their leech vector, Zeylanicobdella arugamensis; this involved 3D visualisation of brightfield and confocal microscopy images of histological sections through infected leech salivary gland cells. Findings 3D assessment demonstrated the morphology of the haemogregarine stages, their spatial layout, and their relationship with enlarged host cells showing reduced cellular content. Haemogregarine meronts, located marginally within leech salivary gland cells, had small tail-like connections to the host cell limiting membrane; this parasite-host cell interface was not visible in two-dimensional (2D light micrographs and no records of a similar connection in apicomplexan development have been traced. Conclusions This is likely the first account of the use of 3D visualisation to study developmental stages of an apicomplexan parasite in its invertebrate vector. Elucidation of the extent of development of the haemogregarine within the leech salivary cells, together with the unusual connections between meronts and the host cell membrane, illustrates the future potential of 3D visualisation in parasite-vector biology.

  18. Estimated aortic blood pressure based on radial artery tonometry underestimates directly measured aortic blood pressure in patients with advancing chronic kidney disease staging and increasing arterial stiffness

    DEFF Research Database (Denmark)

    Carlsen, Rasmus K; Peters, Christian D; Khatir, Dinah S;

    2016-01-01

    we compared invasive aortic systolic BP (SBP) with estimated central SBP obtained by radial artery tonometry and examined the influence of renal function and arterial stiffness on this relationship. We evaluated 83 patients with stage 3 to 5 CKD (mean estimated glomerular filtration rate [eGFR] 30 ml......% confidence interval -14.9 to -11.4) mm Hg. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (cf-PWV) and was significantly increased in CKD patients compared with (versus) control patients (mean 10.7 vs. 9.3 m/s). The difference in BP significantly increased 1.0 mm Hg for every 10 ml....../min decrease in eGFR and by 1.6 mm Hg per 1 m/s increase in cfPWV. Using multivariate regression analysis including both eGFR and cfPWV, the difference between estimated central and invasive aortic SBP was significantly increased by 0.7 mm Hg. For the entire cohort brachial SBP significantly better reflected...

  19. 抗体筛查细胞抗原涵盖范围与电子配血技术的安全应用%Application of antibody screening cell antigen coverage and electronic matching of blood

    Institute of Scientific and Technical Information of China (English)

    刘家瑞; 王远杰; 冯宁; 李红梅; 冯俊程

    2013-01-01

    Objective To study the significance of antibody screening cell antigen range in the electronic matching technology security application.Methods ABO/RhD of blood donor and blood recipient were detect with blood type and antibody.The blood matching were used by electronic matching technology and polybrene crossmatch.Results Of 22,790 blood samples of patients,there were 164 cases with positive antibody screening (0.72%).Of 15740 blood donor blood samples,there were 11 cases with positive antibody screening (0.07 %).Of 22,540 blood samples in line with the rules of the electronic distribution of blood,the implementation of electronic matching of blood ABO / RhD blood group incompatibility was not found by the computer.Of 22534 blood samples with blood compatible,6 blood samples polybrene crossmatch was incompatible with the main side and found no secondary side incompatible.6 blood samples spectrum cell antibody specific identification of all the MNS system anti-Mur,missed rate of 0.027%.Conclusion Clinical antibody screening cells only serological crossmatch,whose antibody missing rate is relatively high,which cannot fully protect the security of the technology of the electronic matching of blood.%目的 探讨抗体筛查细胞抗原涵盖范围在保障电子配血技术安全应用中的意义.方法 分别对供受血者进行ABO/RhD血型检测以及抗体筛查.患者二次血型鉴定结果一致,抗体筛查结果阴性,按电子配血规则进行电子配血,同时采用凝聚胺法对供受血者进行传统血清学交叉配血平行试验,分析抗体筛查细胞抗原涵盖范围与不规则抗体漏检情况以及对电子配血技术安全应用的影响.结果 22790份患者血样,抗体筛查阳性164例,阳性率0.72%.15740份供血者血样,抗体筛查阳性11例,占0.07%.22540份血样均符合电子配血规则,由计算机实施电子配血未发现ABO/RhD血型不相容.用凝聚胺法进行传统血清学

  20. Regulatory T cells in dogs with multicentric lymphoma: peripheral blood quantification at diagnosis and after initial stage chemotherapy

    Directory of Open Access Journals (Sweden)

    T.D. Munhoz

    2016-02-01

    Full Text Available Lymphoma is the most common hematopoietic malignancy in dogs and one of the most frequent among all neoplastic diseases in this species. It can occur in several anatomical locations with distinct histological and immunophenotypes. Depending on the host immune response towards the tumor, prognosis information could be collected. Because its well established immunosuppressant, antitumor activity, the function of regulatory T cells (Tregs in canine neoplasias has been investigated. In this study, we sought to quantify, using flow cytometry, the Tregs subpopulation in peripheral blood of healthy dogs (10 and in those diagnosed with type-B (14 and type-T (8 multicentric lymphoma before (at diagnosis and after the first cycle (5-week of 19-week Madison-Wisconsin (MW protocol of chemotherapy. Our results indicated that dogs with lymphoma showed higher percentage of Tregs (18,84±2,56 when compared to healthy dogs (4,70±0,50 (P0,05. There was no difference in Tregs percentage between B-type (17,45±2,77 and T-type (21,27±5,27 lymphoma (P>0,05. With this, we conclude that canine lymphoma increases Tregs in the peripheral blood and the MW protocol of chemotherapy reduces this cell subpopulation to control values.

  1. Glycoprotein and Glycan in Tissue and Blood Samples of Patients With Stage IB-IVA Cervical Cancer Undergoing Surgery to Remove Pelvic and Abdominal Lymph Nodes

    Science.gov (United States)

    2016-10-26

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  2. Two-stage cyclic enzymatic amplification method for ultrasensitive electrochemical assay of microRNA-21 in the blood serum of gastric cancer patients.

    Science.gov (United States)

    Li, Bingchen; Liu, Fei; Peng, Yuanyuan; Zhou, Yunlei; Fan, Wenxuan; Yin, Huanshun; Ai, Shiyun; Zhang, Xiansheng

    2016-05-15

    MicroRNA (miRNA) is riveting nowadays due to its close relevance to human malignancies. Exploiting a fast and convenient biosensor for sensitive and specific detecting miRNA is necessary and it has significant meaning for oncology. In this work, to understand the relationship between miRNA-21 and gastric cancer, we employ T4 RNA ligase 2 to initiate specific ligation reaction depending on the sequence of target RNA, and T7 exonuclease to catalyze the first stage cyclic enzymatic amplification method (CEAM) specifically, which also resting on the target RNA sequence, and the second stage CEAM to further amplify the response resulting from the initial target RNA. Our two-stage CEAM strategy can detect miRNA-21 as low as 0.36fM with remarkable specificity, and most importantly, it can be used to inspect the expression level of miRNA-21 in blood serum of gastric cancer patients. This will offer new perspective for figuring out the pathways of miRNA-21 involving in cancer.

  3. Expression of proliferating cell nuclear antigen and CD44 variant exon 6 in primary tumors and corresponding lymph node metastases of colorectal carcinoma with Dukes'stage C or D

    Institute of Scientific and Technical Information of China (English)

    Ji-Cheng Zhang; Zuo-Ren Wang; Yan-Juan Cheng; Ding-Zhong Yang; Jing-Sen Shi; Ai-Lin Liang; Ning-Na Liu; Xiao-Min Wang

    2003-01-01

    AIM: To study changes in characteristics of colorectal carcinoma during the metastatic process and to investigate the correlation between cell proliferation activity and metastatic ability of patients with Dukes′ stage C or D.METHODS: Formalin fixed and paraffin embedded materials of primary tumors and corresponding lymph node metastases resected from 56 patients with Dukes′ stage C or D of colorectal carcinoma were stained immunohistochemically with proliferating cell nuclear antigen (PCNA) and CD44variant exon 6 (CD44v6).RESULTS: Thirty-one of 56 patients (55.4 %) expressed PCNA in the primary sites and 36 of 56 patients (64.3 %)expressed PCNA in the metastatic lymph nodes. A significant relation in PCNA expression was observed between the primary site and the metastatic lymph node (0.010<P<0.025).Forty-one of 56 patients (73.2 %) expressed CD44v6 in the primary site and 39 of 56 patients (69.6 %) expressed CD44v6 in the metastatic lymph node. There was also an significant relationship of CD44v6 between the primary site and the metastatic lymph node (0.005<P<0.010). No difference was observed between expression of CD44v6 and PCNA in the primary site (0.250<P<0.500).CONCLUSION: This study partially demonstrates that tumor cells in metastatic lymph node of colorectal carcinoma still possess cell proliferation activity and metastatic ability of tumor cells in primary site. There may be no association between cell proliferation activity and metastatic ability in colorectal carcinoma.

  4. Polymorphisms in B Cell Co-Stimulatory Genes Are Associated with IgG Antibody Responses against Blood-Stage Proteins of Plasmodium vivax.

    Directory of Open Access Journals (Sweden)

    Gustavo C Cassiano

    Full Text Available The development of an effective immune response can help decrease mortality from malaria and its clinical symptoms. However, this mechanism is complex and has significant inter-individual variation, most likely owing to the genetic contribution of the human host. Therefore, this study aimed to investigate the influence of polymorphisms in genes involved in the costimulation of B-lymphocytes in the naturally acquired humoral immune response against proteins of the asexual stage of Plasmodium vivax. A total of 319 individuals living in an area of malaria transmission in the Brazilian Amazon were genotyped for four SNPs in the genes CD40, CD40L, BLYS and CD86. In addition, IgG antibodies against P. vivax apical membrane antigen 1 (PvAMA-1, Duffy binding protein (PvDBP and merozoite surface protein 1 (PvMSP-119 were detected by ELISA. The SNP BLYS -871C>T was associated with the frequency of IgG responders to PvAMA-1 and PvMSP-119. The SNP CD40 -1C>T was associated with the IgG response against PvDBP, whereas IgG antibody titers against PvMSP-119 were influenced by the polymorphism CD86 +1057G>A. These data may help to elucidate the immunological aspects of vivax malaria and consequently assist in the design of malaria vaccines.

  5. Oncogenic cancer/testis antigens

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Andersen, Mads H; Ditzel, Henrik J

    2015-01-01

    Recent developments have set the stage for immunotherapy as a supplement to conventional cancer treatment. Consequently, a significant effort is required to further improve efficacy and specificity, particularly the identification of optimal therapeutic targets for clinical testing. Cancer....../testis antigens are immunogenic, highly cancer-specific, and frequently expressed in various types of cancer, which make them promising candidate targets for cancer immunotherapy, including cancer vaccination and adoptive T-cell transfer with chimeric T-cell receptors. Our current understanding of tumor...... immunology and immune escape suggests that targeting oncogenic antigens may be beneficial, meaning that identification of cancer/testis antigens with oncogenic properties is of high priority. Recent work from our lab and others provide evidence that many cancer/testis antigens, in fact, have oncogenic...

  6. Prospective evaluation of a whole-blood test using Mycobacterium tuberculosis-specific antigens ESAT-6 and CFP-10 for diagnosis of active tuberculosis

    DEFF Research Database (Denmark)

    Ravn, Pernille; Munk, Martin E; Andersen, Ase B;

    2005-01-01

    A new immunodiagnostic test based on the Mycobacterium tuberculosis-specific antigens CFP-10/ESAT-6(QFT-RD1) has been launched as an aid in the diagnosis of latent tuberculosis (TB) infection (LTBI). The aim of this study was to evaluate this test for the diagnosis of active TB. Eighty-two patients...... in a specificity of 60%. However, 80% (8/10) of these had risk-factors for TB, indicating latent infection in this group. In healthy controls, only 3% (1/39) were QFT-RD1 positive. In conclusion, the QFT-RD1 test is sensitive for diagnosis of TB, especially in patients with negative microscopy and culture....... The accuracy of the QFT-RD1 test will vary with the prevalence of LTBI. We suggest that the QFT-RD1 test could be a very useful supplementary tool for the diagnosis of TB....

  7. [Anti-alpha-gliadin antibodies. Sensitivity, specificity and correlation with blood xylose test in the 3 diagnostic stages of celiac disease in children].

    Science.gov (United States)

    Ventura, A; Florean, P; Trevisan, M; Not, T; Perticarari, S; Quadrifoglio, F; Torre, G; Cauci, S

    1987-01-01

    The specificity and sensibility of IgA and IgG alfagliadin antibody test (AaGA) for screening, diagnosis and follow-up of childhood coeliac disease has been evaluated. We have compared AaGA test to D-xylose blood test and at last we have examined the false positive and negative results given by the test. Two groups of subjects were considered: 1) 90 children with untreated coeliac disease (21 newly diagnosed (I stage), 50 in gluten withdrawal (II stage), 19 in challenge (III stage); 2) 255 disease controls including: 157 healthy controls; 31 children with gastroenterological disorders other than coeliac disease; 31 children with food allergy and atopic dermatitis; 36 children with "constitutional" short stature (without GH deficiency and with normal intestinal mucosa). The sensibility of AaGA test in the first stage of coeliac disease has been of 95.2% for the IgG class antibody and 90.4% for the IgA class; on the other hand the showed a specificity of 83.6% for IgG class antibody and 96.9% for IgA class. In only two newly diagnosed coeliac children we have found false negative results: in the first case the patient was IgA-deficient, in the second the age was above 3 years. AaGA IgA resulted positive only in the 12.9% of the group of gastroenterological and atopic controls; particularly most cases were affected by multiple food allergies and two patients by chronic autoimmune disease of small intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Compromised Blood-Brain Barrier Competence in Remote Brain Areas in Ischemic Stroke Rats at Chronic Stage

    Science.gov (United States)

    Garbuzova-Davis, Svitlana; Haller, Edward; Williams, Stephanie N.; Haim, Eithan D.; Tajiri, Naoki; Hernandez-Ontiveros, Diana G.; Frisina-Deyo, Aric; Boffeli, Sean M.; Sanberg, Paul R.; Borlongan, Cesario V.

    2014-01-01

    Stroke is a life threatening disease leading to long-term disability in stroke survivors. Cerebral functional insufficiency in chronic stroke might be due to pathological changes in brain areas remote from initial ischemic lesion, i.e. diaschisis. Previously, we showed that the damaged blood-brain barrier (BBB) was implicated in subacute diaschisis. The present study investigated BBB competence in chronic diaschisis using a transient middle cerebral artery occlusion (tMCAO) rat model. Our results demonstrated significant BBB damage mostly in the ipsilateral striatum and motor cortex in rats at 30 days after tMCAO. The BBB alterations were also determined in the contralateral hemisphere via ultrastructural and immunohistochemical analyses. Major BBB pathological changes in contralateral remote striatum and motor cortex areas included: (1) vacuolated endothelial cells containing large autophagosomes, (2) degenerated pericytes displaying mitochondria with cristae disruption, (3) degenerated astrocytes and perivascular edema, (4) Evans Blue extravasation, and (5) appearance of parenchymal astrogliosis. Importantly, discrete analyses of striatal and motor cortex areas revealed significantly higher autophagosome accumulation in capillaries of ventral striatum and astrogliosis in dorsal striatum in both cerebral hemispheres. These widespread microvascular alterations in ipsilateral and contralateral brain hemispheres suggest persistent and/or continued BBB damage in chronic ischemia. The pathological changes in remote brain areas likely indicate chronic ischemic diaschisis, which should be considered in the development of treatment strategies for stroke. PMID:24610730

  9. Conformational analysis of thioglycoside derivatives of histo-blood group ABH antigens using an ab initio-derived reparameterization of MM4: implications for design of non-hydrolysable mimetics

    Science.gov (United States)

    Strino, Francesco; Lii, Jenn-Huei; Gabius, Hans-Joachim; Nyholm, Per-Georg

    2009-12-01

    Histo-blood group ABH antigens serve as recognition sites for infectious microorganisms and tissue lectins in intercellular communication, e.g. in tumor progression. Thus, they are of interest as a starting point for drug design. In this respect, potent non-hydrolysable derivatives such as thioglycosides are of special interest. As prerequisite to enable estimations of ligand properties relative to their natural counterparts, conformational properties of the thioglycosidic derivatives of ABH trisaccharides and their disaccharide units were calculated using systematic and filtered systematic searches with the MM4 force field. Parameters for the glycosidic torsions of thioglycosides were independently derived from ab initio calculations. The resulting energy deviations required a reparameterization of MM4 to a new parameter set called MM4R. The data sets obtained using MM4R reveal that the thioglycosides have somewhat increased levels of flexibility about the major low-energy conformations shared with the corresponding O-glycosides. In the trisaccharides, the thiosubstitution of the Gal[NAc]α1-3Gal linkage leads to a preference for a conformation which is the secondary minimum of the natural counterparts. This conformation also generates contacts between the N-acetyl group and the fucose moiety in the blood group A derivative. Calculations further indicate that thiosubstitution of only the Fucα1-2Gal linkage does not affect the conformational preferences compared to the natural trisaccharide. Thiosubstitution of both linkages in the trisaccharide results in increased flexibility but the favored conformation of the natural trisaccharides is preferred. The study suggests that thioglycoside derivatives of ABH antigens could have pharmaceutical interest as ligands of lectins and other carbohydrate-binding proteins.

  10. Diagnostic significance of DNA and antibodies against capsid antigens of anti-Epstein–Barr virus antibodies levels in blood plasma of nasopharyngeal carcinoma patients from non-endemic region

    Directory of Open Access Journals (Sweden)

    V. E. Gurtsevich

    2015-01-01

    Full Text Available Epstein–Barr virus (EBV, a representative of the herpesvirus family, is the etiological agent for a number of benign and malignant human neoplasms. Among the latter, the nasopharyngeal carcinoma (NPC occupies a special place. In NPC development EBV plays a key role stimulating the progression of the pathological process from precancerous lesions to the cancer development. For most NPC patients, elevated levels of humoral IgG and IgA antibodies against capsid and early EBV antigens are characteristic and their antibody titers rise to high levels long before the diagnosis of cancer. Using this phenomenon, virus-specific antibodies are used for many years as markers for NPC screening, especially in cases of undiagnosed primary lesion. In recent years, in endemic for NPC regions (South China, South-East Asia a great attention has been paid to the use of quantitative determination of EBV DNA copies in the blood plasma of patients with NPC as a method of early cancer detection and monitoring.The aim of this study was to compare clinical significance of EBV DNA and humoral antibodies levels in blood plasma of NPC patients in non-endemic region, Russia. The results obtained indicate that both markers DNA / EBV and IgA antibodies against capsid EBV antigens can be successfully used for diagnosis of NPC in non-endemic region. However, in comparison with the virus-specific antibody titers, the viral DNA levels in the patients plasma are more sensitive and specific as NPC marker reflecting the efficacy of the therapy, and the state of remission or relapse.

  11. Antigen-induced cytokine and chemokine release test for tuberculosis infection using adsorption of stimulated whole blood on filter paper and multiplex analysis

    DEFF Research Database (Denmark)

    Skogstrand, Kristin; Thysen, Anna H; Jørgensen, Charlotte S

    2012-01-01

    of inflammatory markers in samples from suspected MTI patients confirmed the IFN-γ findings in the QFT. IL-2, GM-CSF, IL-5, and IL-1β were also found as useful markers for MTI. We were not able to distinguish between active tuberculosis and latent MTI. Conclusion: Applying blood on filter paper after incubation...

  12. Hepatitis B virus screening in contacts of blood donors with antibodies against core protein (anti-HBc, but without surface antigen (HBsAg

    Directory of Open Access Journals (Sweden)

    Hildenete Monteiro Fortes

    2006-03-01

    Full Text Available To increase blood safety Brazil introduced screening for anti-HBc among blood donors in 1993. There was a decrease in the hepatitis B virus (HBV transmission, but this measure identified a great number of HBsAg-negative, anti-HBc-positive donors. Surveillance policy determines that contacts of HBV carriers should be screened to HBV markers, but there is no recommendation about how to guide contacts of HBsAg-negative, anti-HBc-positive donors. Aiming to evaluate whether the contacts of this group are at greater risk for HBV infection, a cross-sectional study was performed to compare prevalence of HBV infection between contacts of HBsAg-positive blood donors (group I and contacts of HBsAg-negative, anti-HBc-positive donors (group II. Contacts were submitted to a questionnaire and blood tests for HBV markers. In group I (n = 143, 53 (37.1% were anti-HBc-positive and 11 (7.7% were HBsAg-positive. In group II (n = 111, there were 9 and 0.9%, respectively. HBV exposure was associated with group I, sexual activity, blood transfusion, being one of the donor's parents, and living for more than ten years with the donor. Regarding the families as sample units, it was more common to find at least one member with HBV markers (p < 0.05 among the families of group I compared to group II. Contacts of HBsAg-negative, anti-HBc-positive individuals presented a much lower risk of having already been exposed to HBV and there is no need to screen them for HBV in low to moderate prevalence populations.

  13. Regional cerebral blood flow in acute stage ischemic cerebrovascular disease by xenon-133 inhalation and single photon emission computerized tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kurokawa, Hiroyuki (Akita Univ. (Japan). School of Medicine)

    1989-03-01

    During the period from February 1984 through June 1985, single photon emission computerized tomography (SPECT) with xenon-133 inhalation method has been performed for the measurement of regional cerebral blood flow (rCBF) during the first 48 hours of onset of cerebral infarction (n=71) and transient ischemic attack (n=21). X-ray CT (CT) and carotid arteriography were concurrently performed in all the patients. In repeated studies performed for 15 normal volunteers, rCBF measurement by SPECT was found reproducible. Mean values of rCBF for the right and left cerebral hemispheres were 60.3{plus minus}6.52 and 61.8{plus minus}6.91 ml/100 g/min, respectively. For cerebral infarction, ischemic foci corresponding to clinical symptoms were detected more frequently on SPECT than on CT (93% vs 63%). In all of the evaluable 35 patients with cerebral infarction, rCBF within the first 8 hours of onset was decreased: 31.0 ml/100 g/min for the internal carotid artery (ICA) occlusion and 36.0 ml/100 g/min for the middle cerebral artery (MCA) occlusion. Crossed cerebellar diaschisis was observed in 50% (9/18) for ICA occlusion and 37% (14/38) for MCA occlusion. For transient ischemic attack, there was no significant difference in the detection of ischemic foci between SPECT and CT (38% vs 43%). In detecting small foci especially in the deep regions such as the basal ganglia, SPECT was inferior to CT. Mean rCBF for transient ischemic attack tended to be lower than the normal rCBF (50.7 ml/100 g/min for the right cerebral hemisphere and 50.6 ml/100 g/min for the left cerebral hemisphere). SPECT may aid in predicting prognosis and chosing treatment strategy, as well as in determining cerebral hemodynamics. (N.K.).

  14. Proteomic and genetic analyses demonstrate that Plasmodium berghei blood stages export a large and diverse repertoire of proteins.

    Science.gov (United States)

    Pasini, Erica M; Braks, Joanna A; Fonager, Jannik; Klop, Onny; Aime, Elena; Spaccapelo, Roberta; Otto, Thomas D; Berriman, Matt; Hiss, Jan A; Thomas, Alan W; Mann, Matthias; Janse, Chris J; Kocken, Clemens H M; Franke-Fayard, Blandine

    2013-02-01

    Malaria parasites actively remodel the infected red blood cell (irbc) by exporting proteins into the host cell cytoplasm. The human parasite Plasmodium falciparum exports particularly large numbers of proteins, including proteins that establish a vesicular network allowing the trafficking of proteins onto the surface of irbcs that are responsible for tissue sequestration. Like P. falciparum, the rodent parasite P. berghei ANKA sequesters via irbc interactions with the host receptor CD36. We have applied proteomic, genomic, and reverse-genetic approaches to identify P. berghei proteins potentially involved in the transport of proteins to the irbc surface. A comparative proteomics analysis of P. berghei non-sequestering and sequestering parasites was used to determine changes in the irbc membrane associated with sequestration. Subsequent tagging experiments identified 13 proteins (Plasmodium export element (PEXEL)-positive as well as PEXEL-negative) that are exported into the irbc cytoplasm and have distinct localization patterns: a dispersed and/or patchy distribution, a punctate vesicle-like pattern in the cytoplasm, or a distinct location at the irbc membrane. Members of the PEXEL-negative BIR and PEXEL-positive Pb-fam-3 show a dispersed localization in the irbc cytoplasm, but not at the irbc surface. Two of the identified exported proteins are transported to the irbc membrane and were named erythrocyte membrane associated proteins. EMAP1 is a member of the PEXEL-negative Pb-fam-1 family, and EMAP2 is a PEXEL-positive protein encoded by a single copy gene; neither protein plays a direct role in sequestration. Our observations clearly indicate that P. berghei traffics a diverse range of proteins to different cellular locations via mechanisms that are analogous to those employed by P. falciparum. This information can be exploited to generate transgenic humanized rodent P. berghei parasites expressing chimeric P. berghei/P. falciparum proteins on the surface of

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

    Science.gov (United States)

    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.

  16. No effect of human serum and erythrocytes enriched in n-3 fatty acids by oral intake on Plasmodium falciparum blood stage parasites in vitro

    DEFF Research Database (Denmark)

    Abu-Zeid, Y A; Hansen, H S; Jakobsen, P H;

    1993-01-01

    To examine the effect of n-3 polyunsaturated fatty acids (n-3 PUFA) on the erythrocytic growth of Plasmodium falciparum, serum and erythrocytes were separated from blood of a healthy donor before and after he had taken fish oil capsules for 8 days. Such intake supplied an amount of eicosapentaenoic...... acid (EPA, 20:5n-3) of 3.5 g/d and docosahexaenoic acid (DHA, 22:6n-3) of 2.5 g/d and 24 mg/d of total tocopherol. Post-intake fish oil serum (post-s) and erythrocytes (post-e) were tested in vitro for inhibitory activity against blood stages of P. falciparum compared with pre-intake serum (pre......-s) and pre-intake erythrocyte (pre-e). Also the effect of EPA and arachidonic acid (AA, 20:4n-6) on the erythrocytic growth of P. falciparum was tested using in vitro assays. The results show that both post-s and post-e had no antimalarial activity on P. falciparum. No differential antimalarial effect...

  17. Elevated global cerebral blood flow, oxygen extraction fraction and unchanged metabolic rate of oxygen in young adults with end-stage renal disease: an MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Gang; Lou, Yaxian; Pan, Zhiying; Liu, Ya [Medical School of Nanjing University, Department of Medical Imaging, Jinling Hospital, Nanjing, Jiangsu (China); Nanjing University of Aeronautics and Astronautics, College of Aivil Aviation, Nanjing, Jiangsu (China); Wen, Jiqiu; Li, Xue; Zhang, Zhe [Medical School of Nanjing University, National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing, Jiangsu (China); Lu, Hanzhang [University of Texas Southwestern Medical Center, Advanced Imaging Research Center, Dallas, TX (United States); Liu, Wei [Siemens Shenzhen Magnetic Resonance Ltd., Shenzhen, Guangdong (China); Liu, Hui [Siemens MR NEA Collaboration, Siemens Ltd., Shanghai (China); Chen, Huijuan; Kong, Xiang; Luo, Song; Jiang, Xiaolu; Zhang, Zongjun; Zhang, Long Jiang; Lu, Guang Ming [Medical School of Nanjing University, Department of Medical Imaging, Jinling Hospital, Nanjing, Jiangsu (China)

    2016-06-15

    To noninvasively assess global cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO{sub 2}) in young adults with end-stage renal disease (ESRD). Thirty-six patients and 38 healthy volunteers were included and took part in MR examinations, blood and neuropsychological tests. CBF and OEF were measured by phase-contrast and T2-relaxation-under-spin-tagging MRI techniques, respectively. CMRO{sub 2} was computed from CBF, OEF and hematocrit according to Fick's principle. Correlations were performed between MR measurements, blood biochemistry measurements and neuropsychological test scores. Compared with controls, ESRD patients had elevated CBF (72.9 ± 12.5 vs. 63.8 ± 8.5 ml min{sup -1} 100 g{sup -1}, P < 0.001), elevated OEF (47.2 ± 10.2 vs. 35.8 ± 5.4 %, P < 0.001), but unaffected CMRO{sub 2} (199.5 ± 36.4 vs. 193.8 ± 28.6 μmol O{sub 2} min{sup -1} 100 g{sup -1}, P = 0.879). Hematocrit negatively correlated with CBF (r = -0.640, P < 0.001) and OEF (r = -0.701, P < 0.001), but not with CMRO{sub 2}. Altered neuropsychological test scores of ESRD patients were associated with OEF and CBF, but not with CMRO{sub 2}. There were weak relationships between eGFR and hematocrit (r = 0.308, P = 0.068) or CBF (r = 0.318, P = 0.059). Our findings suggested that anaemic young adults with ESRD may afford higher CBF and OEF to maintain a normal CMRO{sub 2}. Despite this compensatory process, however, cognitive function was still impaired and its severity was correlated with their CBF and OEF abnormality. (orig.)

  18. Prevalence of Serologic Hepatitis B Markers in Blood Donors From Puebla, Mexico: The Association of Relatively High Levels of Anti-Core Antibodies With the Detection of Surface Antigen and Genomic DNA

    Directory of Open Access Journals (Sweden)

    Sosa-Jurado

    2016-06-01

    Full Text Available Background The hepatitis B virus (HBV causes chronic hepatitis, hepatic cirrhosis, and hepatocellular carcinoma. Surface antigen (HBsAg detection is a definitive test that can confirm HBV infection, while the presence of antibodies against the core protein (anti-HBc suggests either a previous or ongoing infection or occult hepatitis B infection (OBI. Objectives The aim of the present study was to determine the prevalence of anti-HBc and HBsAg in blood donors. Further, the study aimed to estimate the anti-HBc level at which HBV DNA is detected in putative OBI cases, as well as to search for mutations in the “a” determinant associated with the non-detection of HBsAg in serum. Patients and Methods We conducted a cross-sectional study from 2003–2009. The study included 120,552 blood donors from the state of Puebla, Mexico. Different commercial systems based on microparticles (enzymatic (MEIA or chemiluminescent (CMIA were used to determine the HBsAg and anti-HBc levels. For the detection of HBV DNA, a nested polymerase chain reaction (nested PCR was used and the genotypes were determined using Sanger sequencing. Results Of the 120,552 blood donors, 1437 (1.19%, 95% CI: 1.12 - 1.26 were reactive to anti-HBc, while 82 (0.066%, 95% CI: 0.053 - 0.079 were reactive to HBsAg. Some 156 plasma samples collected in 2009 from anti-HBc-positive/HBsAg-negative blood donors were submitted for HBV DNA detection in a search for probable OBI. Viral DNA was detected in 27/156 (17.3%, 95% CI: 11.5 - 23.1. Our results show an association between HBV DNA or HBsAg and anti-HBc S/CO levels ≥ 4.0. All DNA samples were identified as genotype H and some “a” determinant mutations were identified, although none corresponded to mutations previously reported to hinder the detection of HBsAg by commercial immunoassays. Conclusions We observed that as the anti-HBc levels increase, there is a higher prevalence of the viral protein HBsAg in blood donors. Samples testing

  19. Changes in IgE- and Antigen-dependent histamine-release in peripheral blood of Schistosoma mansoni-infected Ugandan fishermen after treatment with praziquantel

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    Kazibwe Francis

    2004-04-01

    Full Text Available Abstract Background Parasite-specific IgE levels correlate with human resistance to reinfection with Schistosoma spp. after chemotherapy. Although the role of eosinophils in schistosomiasis has been the focus of a great deal of important research, the involvement of other Fcε receptor-bearing cells, such as mast cells and basophils, has not been investigated in relation to human immunity to schistosomes. Chemotherapy with praziquantel (PZQ kills schistosomes living in an in vivo blood environment rich in IgE, eosinophils and basophils. This releases parasite Ags that have the potential to cross-link cell-bound IgE. However, systemic hypersensitivity reactions are not induced by treatment. Here, we describe the effects of schistosomiasis, and its treatment, on human basophil function by following changes in total cellular histamine and in vitro histamine-release induced by schistosome Ags or anti-IgE, in blood samples from infected Ugandan fishermen, who are continuously exposed to S. mansoni infection, before and 1-day and 21-days after PZQ treatment. Results There was a significant increase in the total cellular histamine in blood samples at 1-day post-treatment, followed by a very significant further increase by 21-days post-treatment. In vitro histamine-release induced by S. mansoni egg (SEA or worm (SWA Ags or anti-IgE antibody, was significantly reduced 1-day post-treatment. The degree of this reduction correlated with pre-treatment infection intensity. Twenty-1-days post-treatment, SEA-induced histamine-release was still significantly lower than at pretreatment. Histamine-release was not correlated to plasma concentrations of total or parasite-specific IgE, nor to specific IgG4 plasma concentrations. Conclusion The biology of human blood basophils is modulated by S. mansoni infection and praziquantel treatment. Infection intensity-dependent suppression of basophil histamine-release, histamine-dependent resistance to infection, and

  20. Frequent detection of CXCR4-using viruses among Brazilian blood donors with HIV-1 long-standing infection and unknown clinical stage: Analysis of massive parallel sequencing data

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    Rodrigo Pessôa

    2016-03-01

    Full Text Available The determination of viral tropism is critically important and highly recommended to guide therapy with the CCR5 antagonist, which does not inhibit the effect of X4-tropic viruses. Here, we report the prevalence of HIV-1×4 HIV strains in 84 proviral DNA massively parallel sequencing “MPS” data from well-defined non-recently infected first-time Brazilian blood donors. The MPS data covering the entire V3 region of the env gene was extracted from our recently generated HIV-1 genomes sequenced by a paired-end protocol (Illumina. Of the 84 MPS data samples, 63 (75% were derived from donors with long-standing infection and 21 (25% were lacking stage information. HIV‐1 tropism was inferred using Geno2pheno (g2p [454] algorithm (FPR=1%, 2.5%, and 3.75%. Among the 84 data samples for which tropism was defined by g2p2.5%, 13 (15.5% participants had detectable CXCR4-using viruses in their MPS reads. Mixed infections with R5 and X4 were observed in 11.9% of the study subjects and minority X4 viruses were detected in 7 (8.3% of participants. Nine of the 63 (14.3% subjects with LS infection were predicted by g2p 2.5% to harbor proviral CXCR4-using viruses. Our findings of a high proportion of blood donors (15.5% harboring CXCR4-using viruses in PBMCs may indicate that this phenomenon is common. These findings may have implications for clinical and therapeutic aspects and may benefit individuals who plan to receive CCR5 antagonists.

  1. Laser Doppler flowmeter study on regional cerebral blood flow in early stage after standard superficial temporal artery-middle cerebral artery bypass surgery for moyamoya disease

    Institute of Scientific and Technical Information of China (English)

    GESANG Dun-zhu; ZHANG Dong; ZHAO Ji-zong; WANG Shuo; ZHAO Yuan-li; WANG Rong; SUN Jian-jun; MENG Ze

    2009-01-01

    Background Standard superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery is an effective treatment for moyamoya disease, but recent evidence suggests that postoperative cerebral hyperperfusion can occur. In this study, the trendline of changes in regional cerebral blood flow (rCBF) after surgery were continually monitored near the site of anastomosis in order to investigate both the efficacy of the procedure for improving rCBF and the possible riskof hyperperfusion.Methods Standard STA-MCA bypass surgery was performed on 13 patients, rCBF was measured continually using laser Doppler flowmetry (LDF) until the 5th day after the operation with the LDF probe implanted adjacent to the area of the anastomosis. The trendline of rCBF changes postoperatively was recorded for the analysis performed using SPSS 13.0.Results The baseline LDF value of cortical rCBF was (84.68±14.39) perfusion unit (PU), which was linear relative to absolute perfusion volume before anastomosis and (88.90±11.26) PU immediately after anastomosis (P >0.05). The value changed significantly from before to after anastomosis (P 0.05).Conclusions STA-MCA anastomosis improves the cerebral blood supply significantly in the early stage after surgery,however, the risk of symptomatic hyperperfusion may exist, which may possibly occur on the 1st day and 5th day after surgery. A LDF is useful for postoperative monitoring for both the efficacy of bypass and possible risk of neurologic deterioration or bleeding from hyperperfusion.

  2. Iyengar Yoga versus Enhanced Usual Care on Blood Pressure in Patients with Prehypertension to Stage I Hypertension: a Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Debbie L. Cohen

    2011-01-01

    Full Text Available The prevalence of prehypertension and Stage 1 hypertension continues to increase despite being amenable to non-pharmacologic interventions. Iyengar yoga (IY has been purported to reduce blood pressure (BP though evidence from randomized trials is lacking. We conducted a randomized controlled trial to assess the effects of 12 weeks of IY versus enhanced usual care (EUC (based on individual dietary adjustment on 24-h ambulatory BP in yoga-naïve adults with untreated prehypertension or Stage 1 hypertension. In total, 26 and 31 subjects in the IY and EUC arms, respectively, completed the study. There were no differences in BP between the groups at 6 and 12 weeks. In the EUC group, 24-h systolic BP (SBP, diastolic BP (DBP and mean arterial pressure (MAP significantly decreased by 5, 3 and 3 mmHg, respectively, from baseline at 6 weeks (P < .05, but were no longer significant at 12 weeks. In the IY group, 24 h SBP was reduced by 6 mmHg at 12 weeks compared to baseline (P = .05. 24 h DBP (P < .01 and MAP (P < .05 decreased significantly each by 5 mmHg. No differences were observed in catecholamine or cortisol metabolism to explain the decrease in BP in the IY group at 12 weeks. Twelve weeks of IY produces clinically meaningful improvements in 24 h SBP and DBP. Larger studies are needed to establish the long term efficacy, acceptability, utility and potential mechanisms of IY to control BP.

  3. Plasmodium vivax merozoite surface protein-3 (PvMSP3: expression of an 11 member multigene family in blood-stage parasites.

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    Jianlin Jiang

    Full Text Available BACKGROUND: Three members of the Plasmodium vivax merozoite surface protein-3 (PvMSP3 family (PvMSP3-α, PvMSP3-β and PvMSP3-γ were initially characterized and later shown to be part of a larger highly diverse family, encoded by a cluster of genes arranged head-to-tail in chromosome 10. PvMSP3-α and PvMSP3-β have become genetic markers in epidemiological studies, and are being evaluated as vaccine candidates. This research investigates the gene and protein expression of the entire family and pertinent implications. METHODOLOGY/PRINCIPAL FINDINGS: A 60 kb multigene locus from chromosome 10 in P. vivax (Salvador 1 strain was studied to classify the number of pvmsp3 genes present, and compare their transcription, translation and protein localization patterns during blood-stage development. Eleven pvmsp3 paralogs encode an N-terminal NLRNG signature motif, a central domain containing repeated variable heptad sequences, and conserved hydrophilic C-terminal features. One additional ORF in the locus lacks these features and was excluded as a member of the family. Transcripts representing all eleven pvmsp3 genes were detected in trophozoite- and schizont-stage RNA. Quantitative immunoblots using schizont-stage extracts and antibodies specific for each PvMSP3 protein demonstrated that all but PvMSP3.11 could be detected. Homologs were also detected by immunoblot in the closely related simian species, P. cynomolgi and P. knowlesi. Immunofluorescence assays confirmed that eight of the PvMSP3s are present in mature schizonts. Uniquely, PvMSP3.7 was expressed exclusively at the apical end of merozoites. CONCLUSION/SIGNIFICANCE: Specific proteins were detected representing the expression of 10 out of 11 genes confirmed as members of the pvmsp3 family. Eight PvMSP3s were visualized surrounding merozoites. In contrast, PvMSP3.7 was detected at the apical end of the merozoites. Pvmsp3.11 transcripts were present, though no corresponding protein was detected

  4. Rheumatoid arthritis and its association with HLA-DR antigens. I. Cell mediated immune response against connective tissue antigens.

    Science.gov (United States)

    Vullo, C M; Pesoa, S A; Onetti, C M; Riera, C M

    1987-04-01

    HLA-DR antigens and cellular sensitivity to native bovine type I and type II collagen and proteoglycans were examined in patients with classic rheumatoid arthritis (RA) and normal individuals. Fifty eight percent of patients with RA (n = 88) and 28% of normals (n = 52) were DR4+ (pc less than 0.01). DR4 phenotype was significantly increased in patients with severe disease stages (III-IV), as defined by the ARA criteria, in contrast to those showing mild disease stages (I-II) (p less than 0.05). Furthermore, peripheral blood mononuclear cells from 55 patients and 30 controls were evaluated for the in vitro production of leukocyte inhibitory factor in response to native type I and type II collagen and proteoglycans. By using this assay, cells from the arthritic group exhibited a statistically significant response when stimulated with native type I collagen and proteoglycans. The cellular immune response was not associated with any particular HLA-DR antigens, or to the disease stage or severity.

  5. Protection of aouts monkeys after immunization with recombinant antigens of Plasmodium falciparum

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    Burhard Enders

    1992-01-01

    Full Text Available The genus Aotus spp. (owl monkey is one of the WHO recommended experimental models for Plasmodium falciparum blood stage infection, especially relevant for vaccination studies with asexual blood stage antigens of this parasite. For several immunization trials with purified recombinant merozoite/schizont antigens, the susceptible Aouts kenotypes II, III, IV and VI were immunized with Escherichia coli derived fusion proteins containg partial sequences of the proteins MSAI (merozoite surface antigen I, SERP (serine-strech protein and HRPII (histidine alanine rich protein II as well as with a group of recombinant antigens obtained by an antiserum raised against a protective 41 kD protein band. The subcutaneous application (3x of the antigen preparations was carried out in intact animals followed by splenectomy prior to challange, in order to increase the susceptibility of the experimental hosts to the parasite. A partial sequence of HRPII, the combination of three different fusion proteins of the 41 kD group and mixture of two sequences of SERP in the presence of the modified Al(OH3 adjuvant conferred significant protection against a challange infection with P. falciparum blood stages (2-5 x 10 (elevado a sexta potência i. RBC. Monkey immunized with the MS2-fusion protein carrying the N-terminal part of the 195 kD precursor of the major merozoite surface antigens induced only marginal protection showing some correlation between antibody titer and degree of parasitaemia. Based on the protective capacity of these recombinant antigens we have expressed two hybrid proteins (MS2/SERP/HRPII and SERP/MSAI/HRPII in E. coli containing selected partial sequences of SERP, HRPII and MSAI. Antibodies raised against both hybrid proteins in rabbits and Aotus monkeys recognize the corresponding schizont polypeptides. In two independent immunization trials using 13 animals (age 7 months to 3 years we could show that immunization of Aotus monkeys with either of the

  6. Phase 1 study in malaria naive adults of BSAM2/Alhydrogel®+CPG 7909, a blood stage vaccine against P. falciparum malaria.

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    Ruth D Ellis

    Full Text Available A Phase 1 dose escalating study was conducted in malaria naïve adults to assess the safety, reactogenicity, and immunogenicity of the blood stage malaria vaccine BSAM2/Alhydrogel®+ CPG 7909. BSAM2 is a combination of the FVO and 3D7 alleles of recombinant AMA1 and MSP1(42, with equal amounts by weight of each of the four proteins mixed, bound to Alhydrogel®, and administered with the adjuvant CPG 7909. Thirty (30 volunteers were enrolled in two dose groups, with 15 volunteers receiving up to three doses of 40 µg total protein at Days 0, 56, and 180, and 15 volunteers receiving up to three doses of 160 µg protein on the same schedule. Most related adverse events were mild or moderate, but 4 volunteers experienced severe systemic reactions and two were withdrawn from vaccinations due to adverse events. Geometric mean antibody levels after two vaccinations with the high dose formulation were 136 µg/ml for AMA1 and 78 µg/ml for MSP1(42. Antibody responses were not significantly different in the high dose versus low dose groups and did not further increase after third vaccination. In vitro growth inhibition was demonstrated and was closely correlated with anti-AMA1 antibody responses. A Phase 1b trial in malaria-exposed adults is being conducted.Clinicaltrials.gov NCT00889616.

  7. Early stage carcinoma of the uterine cervix. Effects of intracavitary radium treatment on lymphoid cells in blood and pelvic lymph nodes

    Energy Technology Data Exchange (ETDEWEB)

    Onsrud, M.; Grahm, I.; Gaudernack, G.

    Sixteen patients with early stage carcinoma of the uterine cervix treated with primary radical hysterectomy and pelvic lymphadenectomy were compared with 17 patients who four to six weeks before the operation received intracavitary treatment with radium. The calculated radiation dose to the pelvic wall was approximately 10 Gy. The distribution of lymphoid cells in blood and pelvic lymph nodes was studied by an indirect immunoflourescence technique using monoclonal antibodies. The radium treated group showed a significant reduction of circulating OKT4+ (T helper) and OKT8+ (T suppressor/cytotoxic) lymphocytes. The number of Leu7+ (natural killer) cells and 1D5+ cells (monocytes) was not changed, but the ratio between monocytes and T cells was increased after radium therapy. In cell suspensions obtained from the pelvic lymph nodes, the radium treatment induced a significant reduction of the OKT4+ cell fraction. It is concluded that this low dose rate regimen of intracavitary treatment induces changes in the immune system which are of the same type as those seen after external field irradiation.

  8. Red blood cell alloimmunization after blood transfusion

    NARCIS (Netherlands)

    Schonewille, Henk

    2008-01-01

    Current pretransfusion policy requires the patients’ serum to be tested for the presence of irregular red blood cell antibodies. In case of an antibody, red blood cells lacking the corresponding antigen are transfused after an antiglobulin crossmatch. The aim of the studies in this thesis is primari

  9. Genetic polymorphism of Babesia bovis merozoite surface antigens-2 (MSA-2) isolates from bovine blood and Rhipicephalus annulatus ticks in Israel.

    Science.gov (United States)

    Molad, T; Fleiderovitz, L; Leibovich, B; Wolkomirsky, R; Erster, O; Roth, A; Mazuz, M L; Markovics, A; Shkap, V

    2014-09-15

    This study demonstrated the genetic diversity among MSA-2c, MSA-2a1 and MSA-2b proteins of Babesia bovis isolates obtained from bovine blood and Rhipicephalus annulatus tick samples. The least identities that were observed among the deduced amino acid sequences of MSA-2c, MSA-2a1 and MSA-2b were 55, 63, and 71%, respectively. During the study four B. bovis calves, aged about 1 month, were found to be infected with virulent field strains and developed babesiosis. Probably, the calves had received insufficient antibodies, or the antibodies raised against the vaccine strain did not cross-protect against virulent field isolates. The complete msa-2 locus from the Israeli B. bovis vaccine strain and two field isolates were characterized. Similarly to the Australian strains and isolates, the msa-2 loci of the examined Israeli strain and isolates had only two msa-2 genes - msa-2c and msa-2a/b - located between msa-2c and orfB. Several of the examined samples, contained different MSA-2 genotypes concurrently. No obvious geographical relationships among isolates from various regions of Israel were established. Moreover, in the phylogenetic analyses, the Israeli deduced MSA-2 amino acid sequences of the three examined genes were clustered together with sequences derived from other countries, proving that the msa-2 gene sequences of B. bovis shared the same genetic characters worldwide. The present study clearly showed that the MSA-2 proteins of B. bovis isolates from Israel were genetically distinct from the vaccine strains. Thus, further research will be needed in order to understand the genetic diversity mechanisms of B. bovis, and the immunological responses of the infected animals.

  10. 第四代HIV抗原抗体检测试剂在血液筛查中的应用%Application of 4th generation reagents for the detection of HIV antigen and antibody in blood screening

    Institute of Scientific and Technical Information of China (English)

    陈尚良; 郑欣; 曾月婷; 廖扬勋; 梁洁贞; 余文潮; 李结敏; 梁丽婷; 梁剑锋

    2014-01-01

    目的:研究第四代HIV抗原抗体检测试剂在血液筛查中的应用价值。方法对第四代HIV抗原抗体检测试剂进行灵敏度和重复性实验;分别采用第三代HIV抗体检测试剂和第四代HIV抗原抗体检测试剂对血液样本进行初复检,对第三代试剂检测阴性第四代试剂检测阳性的样本采用HIV核酸检测方法进行确认。结果第四代HIV抗原抗体检测试剂最低抗原检出浓度为1.25 U/mL,孔间精密度为3.2%;2009年10月~2011年3月,共筛查样本23480例,其中13例第三代试剂结果阴性而第四代试剂结果阳性,经HIV核酸检测的方法进行确认,全部结果均为阴性。结论在血液筛查中引入第四代HIV检测试剂的试剂功效尚待进一步验证,在已经广泛开展HIV抗体检测的基础上,引入第四代HIV抗原抗体检测试剂还是引入核酸检测具有更好的成本效益比,是一个值得待探讨的课题。%Objective To study the application of 4th-generation HIV reagents for detecting HIV antigens and antibodies in blood screening. Methods The sensitivity and repeatability experiments were tested respectively. All samples were detected by 3th-generation HIV reagents for only detecting HIV antibody and 4th-generation HIV reagents for detecting HIV antigens and antibodies, respectively, and the samples which were positive in 4th-generation HIV reagents detecting but negative in 3th-generation HIV reagents were confirmed by HIV nucleic acid detections. Results The minimum detectable concentration of HIV antigen was 1.25 U/mL and the precision was 3.2%for 4th-generation HIV reagent. In tolal 23 480 samples had been screened from October 2009 to March 2011, 13 samples were positive in 4th-generation HIV reagent detecting but negative in HIV 3th-generation HIV reagent, all of them were confired negative by HIV nucleic acid detection. Conclusion The efficacy of HIV detection attribute to applying 4th-generation HIV reagent

  11. Umbilical cord blood regulatory T-cell expansion and functional effects of tumor necrosis factor receptor family members OX40 and 4-1BB expressed on artificial antigen-presenting cells.

    Science.gov (United States)

    Hippen, Keli L; Harker-Murray, Paul; Porter, Stephen B; Merkel, Sarah C; Londer, Aryel; Taylor, Dawn K; Bina, Megan; Panoskaltsis-Mortari, Angela; Rubinstein, Pablo; Van Rooijen, Nico; Golovina, Tatiana N; Suhoski, Megan M; Miller, Jeffrey S; Wagner, John E; June, Carl H; Riley, James L; Blazar, Bruce R

    2008-10-01

    Previously, we showed that human umbilical cord blood (UCB) regulatory T cells (Tregs) could be expanded approximately 100-fold using anti-CD3/28 monoclonal antibody (mAb)-coated beads to provide T-cell receptor and costimulatory signals. Because Treg numbers from a single UCB unit are limited, we explored the use of cell-based artificial antigen-presenting cells (aAPCs) preloaded with anti-CD3/28 mAbs to achieve higher levels of Treg expansion. Compared with beads, aAPCs had similar expansion properties while significantly increasing transforming growth factor beta (TGF-beta) secretion and the potency of Treg suppressor function. aAPCs modified to coexpress OX40L or 4-1BBL expanded UCB Tregs to a significantly greater extent than bead- or nonmodified aAPC cultures, reaching mean expansion levels exceeding 1250-fold. Despite the high expansion and in contrast to studies using other Treg sources, neither OX40 nor 4-1BB signaling of UCB Tregs reduced in vitro suppression. UCB Tregs expanded with 4-1BBL expressing aAPCs had decreased levels of proapoptotic bim. UCB Tregs expanded with nonmodified or modified aAPCs versus beads resulted in higher survival associated with increased Treg persistence in a xeno-geneic graft-versus-host disease lethality model. These data offer a novel approach for UCB Treg expansion using aAPCs, including those coexpressing OX40L or 4-1BBL.

  12. Human infection with Wuchereria bancrofti in Matara, Sri Lanka: the use, in parallel, of an ELISA to detect filaria-specific IgG4 in urine and of ICT card tests to detect filarial antigen in whole blood.

    Science.gov (United States)

    Weerasooriya, M V; Itoh, M; Mudalige, M P S; Qiu, X-G; Kimura, E; Gunawardena, N K; Fujimaki, Y

    2003-03-01

    The ICT card test to detect circulating filarial antigen and an ELISA that detects filaria-specific urinary IgG(4) were each used to screen 473 subjects from a community in Sri Lanka where Wuchereria bancrofti is endemic. When the ICT test was used as the gold standard, the ELISA was found to have a sensitivity of 91.2%. However, far more of the subjects were found ELISA-positive than ICT-positive (76.5% v. 31.1%). The youngest children studied (aged 1-10 years) were similar to the adult subjects in terms of the prevalence of antigenaemia (33.8%) and the prevalence (72.1%) and concentration of filaria-specific IgG(4) in their urine. Therefore, especially as urine samples are easier, less painful and safer to collect than blood samples, the ELISA may be particularly useful to screen very young and school-age children, to estimate current levels of transmission in a particular area.

  13. Study of Interference Treatment by Xuesaitong (血塞通) Soft Capsule on Patients of Nephrosis Syndrome with Qi Deficiency and Blood Stasis during Dose Reducing Stage of Corticosteroid

    Institute of Scientific and Technical Information of China (English)

    吕勇; 王亿平; 张莉

    2004-01-01

    Objective: To observe the effect of Xuesaitong (血塞通, XST) soft capsule in interference treatment on patients of nephrosis syndrome (NS) during corticosteroid (CS) dose reducing stage. Methods:Seventy-one NS patients applying prednisone and initiating dose reducing stage were randomized into trial group and control group. On the basis of conventional prednisone dose reduction of both groups, the trial group was given additionally XST, and the treatment course ended with the reduction to maintenance dose. In the course of observation, those who did not comply with the criteria of observation were excluded. Before and after the dose reduction, TCM syndrome scoring, 24 hrs urinary protein amount, blood β2-microglobulin (β2-MG), urinary β2-MG, blood fibrinogen (Fbg), plasma prothrombin time (PT), blood lipid, etc. were observed. Results: The trial group of XST could obviously lower their urinary protein amount and blood lipid level (P<0.05 or P<0.01), markedly improve the blood coagulation parameters (P<0.01), improve the TCM syndrome and CS induced adverse reaction (P<0.05 or P<0.01), also obviously reduced the recurrence rate of NS (P<0.05). Conclusion: XST could obviously improve the clinical symptoms and renal impairment parameters in NS patients during CS dose reduction stage, improve the CS induced adverse reaction and prevent the recurrence of NS.

  14. THE RHEOLOGICAL PROPERTIES OF BLOOD IN THE MOST ACUTE STAGE OF ISCHEMIC STROKE AND THEIR RELATION TO THE SEVERITY OF NEUROLOGICAL IMPAIRMENT

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    M. N. Azhermacheva

    2013-01-01

    Full Text Available The study evaluated the rheological parameters of blood: blood viscosity, plasma viscosity, hematocrit, red blood cell aggregation and deformability. The severity of the patients was assessed by clinical scales:Glasgowcoma scale, the scale NIHSS, Barthel index. The study found that in the acute phase of ischemic stroke increased blood viscosity by increasing red blood cell aggregation and reduced erythrocyte deformability. The increase in the viscosity of the blood in acute ischemic stroke is accompanied by increased severity of neurological disorders.

  15. ABO blood group A antigen expression in A201 allele analysis of activity%ABO血型A201等位基因表达A抗原活性的分析

    Institute of Scientific and Technical Information of China (English)

    曾学平; 王恭; 陆理; 李涛; 冯学冠

    2014-01-01

    目的:研究ABO血型A201等位基因表达A抗原活性。方法运用血型血清学方法对1家2代3人的唾液及血液标本的ABO血型进行检测;运用Identifiler法医基因分析试剂盒作为亲缘关系鉴定;PCR扩增ABO基因后,对所有外显子做DNA测序分析,运用PCR-RFLP法进行同步检测A201等位基因中的序列变异。结果亲缘关系鉴定在Identifiler的15个遗传标记系统中显示,父母可以将所有的等位基因提供给子女,确定具有亲缘关系;然而运用不同来源的3份抗体对ABO血型进行检验时,却出现了正定型否定了母子关系,反定型无法排除母子关系的现象。3个标本ABO基因的测序:父、母、子的基因型分别为O01/O01、A201/B101及A201/O01,符合反定型结果,这就说明A201等位基因在A表型及AB表型中表达的A抗原活性差异显著。运用PCR-RFLP法可将A201等位基因中的2个主要变异点1059-1061delC和467C/T。结论 ABO血型A201基因在AB及A表型中表达A抗原活性,可由于检测抗体不同出现一定的差异;基因测序与PCR-RFLP法进行同步分析能够快速简便的鉴定A201等位基因中的1059-1061delC和467C/T。%Objective To study the ABO blood group A antigen expression in A201 allele activity. Methods Using serological methods, a two-generation three human saliva and blood samples were used to detect ABO blood. Forensic genetic analysis using Identifiler kit was used as kinship identification including PCR amplification ABO gene,exons do for all DNA sequencing,PCR-RFLP method using synchronous detection of sequence variation A201 allele. Results Identification of the genetic relationship of 15 genetic markers was performed using Identifiler system, which shows that parents can have all the alleles,be available to children determined to have kinship. However,after the use of three different sources of ABO blood group antibodies,they appeared the mother-child relationship was

  16. Safety and Reproducibility of a Clinical Trial System Using Induced Blood Stage Plasmodium vivax Infection and Its Potential as a Model to Evaluate Malaria Transmission

    Science.gov (United States)

    Elliott, Suzanne; Sekuloski, Silvana; Sikulu, Maggy; Hugo, Leon; Khoury, David; Cromer, Deborah; Davenport, Miles; Sattabongkot, Jetsumon; Ivinson, Karen; Ockenhouse, Christian; McCarthy, James

    2016-01-01

    Background Interventions to interrupt transmission of malaria from humans to mosquitoes represent an appealing approach to assist malaria elimination. A limitation has been the lack of systems to test the efficacy of such interventions before proceeding to efficacy trials in the field. We have previously demonstrated the feasibility of induced blood stage malaria (IBSM) infection with Plasmodium vivax. In this study, we report further validation of the IBSM model, and its evaluation for assessment of transmission of P. vivax to Anopheles stephensi mosquitoes. Methods Six healthy subjects (three cohorts, n = 2 per cohort) were infected with P. vivax by inoculation with parasitized erythrocytes. Parasite growth was monitored by quantitative PCR, and gametocytemia by quantitative reverse transcriptase PCR (qRT-PCR) for the mRNA pvs25. Parasite multiplication rate (PMR) and size of inoculum were calculated by linear regression. Mosquito transmission studies were undertaken by direct and membrane feeding assays over 3 days prior to commencement of antimalarial treatment, and midguts of blood fed mosquitoes dissected and checked for presence of oocysts after 7–9 days. Results The clinical course and parasitemia were consistent across cohorts, with all subjects developing mild to moderate symptoms of malaria. No serious adverse events were reported. Asymptomatic elevated liver function tests were detected in four of six subjects; these resolved without treatment. Direct feeding of mosquitoes was well tolerated. The estimated PMR was 9.9 fold per cycle. Low prevalence of mosquito infection was observed (1.8%; n = 32/1801) from both direct (4.5%; n = 20/411) and membrane (0.9%; n = 12/1360) feeds. Conclusion The P. vivax IBSM model proved safe and reliable. The clinical course and PMR were reproducible when compared with the previous study using this model. The IBSM model presented in this report shows promise as a system to test transmission-blocking interventions

  17. Flow cytometric readout based on Mitotracker Red CMXRos staining of live asexual blood stage malarial parasites reliably assesses antibody dependent cellular inhibition

    Directory of Open Access Journals (Sweden)

    Jogdand Prajakta S

    2012-07-01

    Full Text Available Abstract Background Functional in vitro assays could provide insights into the efficacy of malaria vaccine candidates. For estimating the anti-parasite effect induced by a vaccine candidate, an accurate determination of live parasite count is an essential component of most in vitro bioassays. Although traditionally parasites are counted microscopically, a faster, more accurate and less subjective method for counting parasites is desirable. In this study mitochondrial dye (Mitotracker Red CMXRos was used for obtaining reliable live parasite counts through flow cytometry. Methods Both asynchronous and tightly synchronized asexual blood stage cultures of Plasmodium falciparum were stained with CMXRos and subjected to detection by flow cytometry and fluorescence microscopy. The parasite counts obtained by flow cytometry were compared to standard microscopic counts obtained through examination of Giemsa-stained thin smears. A comparison of the ability of CMXRos to stain live and compromised parasites (induced by either medium starvation or by anti-malarial drug treatment was carried out. Finally, parasite counts obtained by CMXRos staining through flow cytometry were used to determine specific growth inhibition index (SGI in an antibody-dependent cellular inhibition (ADCI assay. Results Mitotracker Red CMXRos can reliably detect live intra-erythrocytic stages of P. falciparum. Comparison between staining of live with compromised parasites shows that CMXRos predominantly stains live parasites with functional mitochondria. Parasite counts obtained by CMXRos staining and flow cytometry were highly reproducible and can reliably determine the ability of IgG from hyper-immune individuals to inhibit parasite growth in presence of monocytes in ADCI assay. Further, a dose-dependent parasite growth inhibitory effect could be detected for both total IgG purified from hyper-immune sera and affinity purified IgGs against the N-terminal non-repeat region of GLURP

  18. Determination of carcinoembryonic antigen levels in peripheral and draining venous blood in patients with colorectal carcinoma Determinação dos níveis do antígeno carcinoembriônico no sangue periférico e no efluente venoso em doentes com carcinoma colorretal

    Directory of Open Access Journals (Sweden)

    Jaques Waisberg

    2004-06-01

    Full Text Available BACKGROUND: The problem of the relationship between blood carcinoembryonic antigen (CEA levels and tissue CEA content in colorectal carcinoma, and the mechanisms for CEA release from tumor cells in tissue adjacent to the neoplasm is important to understanding the biology of colorectal carcinoma. It has not been adequately explained whether CEA in the peripheral blood is drained mainly by portal system blood or by the lymphatic system, or indeed by both systems. AIM: To study the behavior of CEA levels in peripheral blood (CEA-p and venous effluent blood (CEA-d among patients with colorectal tumors, who underwent curative operation. METHOD: A total of 28 patients were studied (12 male [42.9%] and 16 female [57.1%], mean age 66.1 years [range: 43 - 84]. Immediately after laparotomy, peripheral venous blood was extracted by antecubital venous puncture and venous effluent blood was collected from the main drainage vein of the lesions. Values of CEA-p, CEA-d and the gradient between CEA-d and CEA-p that were less than 5.0 ng/mL were considered normal. RESULTS: Eight (28.6% patients were stage A in Duke's classification, nine (32.1% stage B and 11 (39.3% stage C. The neoplasm was located in the rectum of 14 patients (50.0%, in the transverse colon in five (17.9%, in the sigmoid in four (14.3%, in the cecum and/or ascending colon in three (10.7%, and in the descending colon in two (7.1%. The histopathological examination revealed well-differentiated adenocarcinoma in all the patients. Only one patient (3.6%, Duke's classification stage C, presented neoplasm with venous invasion. The gradient between the CEA-p and CEA-d levels were normal in 25 patients (88.3% and high in three (10.7%. The mean value for CEA-p was 3.8 ± 4.1 ng/mL (0.1-21.1 ng/mL and for the drained CEA (CEA-d it was 4.5 ± 4.3 ng/mL (0.3-20.2 ng/mL, without significant difference between these values. There was a significant difference between the mean value for CEA-p and CEA-d levels

  19. Técnica para obtenção do aparelho geniturinário e dosagem do PSA (Prostate Specific Antigen no hamster sírio, Mesocricetus auratus Technique for collecting blood for PSA (Prostate Specific Antigen dosing and genitourinary system obtaining in syrian hamster, Mesocricetus auratus

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    Dimas José Araújo Vidigal

    2004-12-01

    ículas seminais e testículos. Observou-se nos Hamsters adultos (n=20, setenta por cento de alterações nos anexos sexuais a saber: um caso (5% de processo supurativo das vesículas seminais, um caso (5% de processo inflamatório isolado das vesículas seminais, um caso (5% de Processo inflamatório das vesículas seminais, HBP e prostatite concomitante e um caso (5% de infarto testicular e prostatite. Onze animais (55%, dos Hamsters adultos, apresentaram HBP (Hiperplasia Benigna da Próstata. Conclusão: A técnica cirúrgica descrita mostrou-se eficiente para a obtenção dos orgãos e estruturas do aparelho geniturinário, estudo histológico desses orgãos e dosagem do PSA no Hamster Sírio, Mesocricetus auratus.Purpose: To explain the available technique in collecting blood for PSA (Prostate Specific Antigen dosing and the genitourinary system extracting from Syrian Hamster, Mesocricetus auratus, and correspond PSA findings to anexed sexual histologic changes. Methods: Thirty (n=30 Hamsters were used in the experiment: ten (n=10 animals were on the average age of 47,5 days on the decease mourent, being qualified as young and twenty ( n=20 animals over the age of one year were qualified as adults. After being under chetamina cloridate and diazepam anesthesia, on the superior abdomen level, c. 1,5mL to 2,0mL of blood were collected for total PSA dosing though ELISA method, with human antigen. They died after blood extracting. After verifying the animal death, laparatomy was carried out, extracting in complete monoblock the genitourinary system for a histologic study of sexual anexes. A PSA correlation was set with the found histologic changes. Results: An excellent anesthesian plan was obtained after shooting chetamina cloridate and diazepam intraperitoneum on the animals, that made possible to collect blood through the cava vein trans-derm via to the superior abdomen for the PSA dosing. The animal died after blood collecting. Laparatomy was carried out with the complete

  20. A pilot randomised trial of induced blood-stage Plasmodium falciparum infections in healthy volunteers for testing efficacy of new antimalarial drugs.

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    James S McCarthy

    Full Text Available BACKGROUND: Critical to the development of new drugs for treatment of malaria is the capacity to safely evaluate their activity in human subjects. The approach that has been most commonly used is testing in subjects with natural malaria infection, a methodology that may expose symptomatic subjects to the risk of ineffective treatment. Here we describe the development and pilot testing of a system to undertake experimental infection using blood stage Plasmodium falciparum parasites (BSP. The objectives of the study were to assess the feasibility and safety of induced BSP infection as a method for assessment of efficacy of new drug candidates for the treatment of P. falciparum infection. METHODS AND FINDINGS: A prospective, unblinded, Phase IIa trial was undertaken in 19 healthy, malaria-naïve, male adult volunteers who were infected with BSP and followed with careful clinical and laboratory observation, including a sensitive, quantitative malaria PCR assay. Volunteers were randomly allocated to treatment with either of two licensed antimalarial drug combinations, artemether-lumefantrine (A/L or atovaquone-proguanil (A/P. In the first cohort (n = 6 where volunteers received ∼360 BSP, none reached the target parasitemia of 1,000 before the day designated for antimalarial treatment (day 6. In the second and third cohorts, 13 volunteers received 1,800 BSP, with all reaching the target parasitemia before receiving treatment (A/L, n = 6; A/P, n = 7 The study demonstrated safety in the 19 volunteers tested, and a significant difference in the clearance kinetics of parasitemia between the drugs in the 13 evaluable subjects, with mean parasite reduction ratios of 759 for A/L and 17 for A/P (95% CI 120-4786 and 7-40 respectively; p<0.01. CONCLUSIONS: This system offers a flexible and safe approach to testing the in vivo activity of novel antimalarials. TRIAL REGISTRATION: ClinicalTrials.gov NCT01055002.

  1. Cerebral blood flow of patients with age-associated memory impairment and the early stage of Alzheimer`s disease. A study by SPECT using the ARG method

    Energy Technology Data Exchange (ETDEWEB)

    Ishiwata, Akiko; Kitamura, Shin; Nagazumi, Atushi; Terashi, Akiro [Nippon Medical School, Tokyo (Japan)

    1998-04-01

    In order to further understand the pathology of Alzheimer`s disease (AD), we have utilized image analysis in diagnosing the early stages of AD in patients with cognitive disorders. CT and MRI, however, have not been feasible since only atrophy is seen and it is difficult to differentiate the changes in AD from age associated changes. In this study we tried to determine whether regional cerebral blood flow (rCBF) measurements using single photon emission CT (SPECT) are feasible for the early diagnosis of AD. Regional CBF (rCBF) was measured using SPECT in three subject groups: Age-associated memory impairment (AAMI, n=9), mild AD (n=16), and normal aged patients (mean age=68.3; n=20). The subjects were then observed for three years. The region of interest (ROI) for the medial temporal lobe was set at OM-30deg to cover the maximum area of the hippocampus. The absolute values of rCBF in the frontal, temporal, and parietal lobes and the cerebellum were significantly lower in the mild AD subjects than in the normal aged subjects. A significant decrease in rCBF was also seen in the medial temporal lobe in both the AD and the AAMI subjects compared to the normal controls. During the three years of follow up, no cases of dementia were seen in the AAMI subjects. However, there were two patients who appeared to have difficulty in adapting to daily life due to amnesia, one with a decrease in rCBF of the medial temporal lobe on the second SPECT, and the other showing a low rCBF the first time. This study suggests that AAMI subjects may comprise both AD and normal subjects. Therefore a more prospective study is needed. (author)

  2. Nitric oxide synthetic pathway and cGMP levels are altered in red blood cells from end-stage renal disease patients.

    Science.gov (United States)

    Di Pietro, Natalia; Giardinelli, Annalisa; Sirolli, Vittorio; Riganti, Chiara; Di Tomo, Pamela; Gazzano, Elena; Di Silvestre, Sara; Panknin, Christina; Cortese-Krott, Miriam M; Csonka, Csaba; Kelm, Malte; Ferdinandy, Péter; Bonomini, Mario; Pandolfi, Assunta

    2016-06-01

    Red blood cells (RBCs) enzymatically produce nitric oxide (NO) by a functional RBC-nitric oxide synthase (RBC-NOS). NO is a vascular key regulatory molecule. In RBCs its generation is complex and influenced by several factors, including insulin, acetylcholine, and calcium. NO availability is reduced in end-stage renal disease (ESRD) and associated with endothelial dysfunction. We previously demonstrated that, through increased phosphatidylserine membrane exposure, ESRD-RBCs augmented their adhesion to human cultured endothelium, in which NO bioavailability decreased. Since RBC-NOS-dependent NO production in ESRD is unknown, this study aimed to investigate RBC-NOS levels/activation, NO production/bioavailability in RBCs from healthy control subjects (C, N = 18) and ESRD patients (N = 27). Although RBC-NOS expression was lower in ESRD-RBCs, NO, cyclic guanosine monophosphate (cGMP), RBC-NOS Serine1177 phosphorylation level and eNOS/Calmodulin (CaM)/Heat Shock Protein-90 (HSP90) interaction levels were higher in ESRD-RBCs, indicating increased enzyme activation. Conversely, following RBCs stimulation with insulin or ionomycin, NO and cGMP levels were significantly lower in ESRD- than in C-RBCs, suggesting that uremia might reduce the RBC-NOS response to further stimuli. Additionally, the activity of multidrug-resistance-associated protein-4 (MRP4; cGMP-membrane transporter) was significantly lower in ESRD-RBCs, suggesting a possible compromised efflux of cGMP across the ESRD-RBCs membrane. This study for the first time showed highest basal RBC-NOS activation in ESRD-RBCs, possibly to reduce the negative impact of decreased NOS expression. It is further conceivable that high NO production only partially affects cell function of ESRD-RBCs maybe because in vivo they are unable to respond to physiologic stimuli, such as calcium and/or insulin.

  3. Long-term oral calcium supplementation reduces diastolic blood pressure in end stage renal disease. A randomized, double-blind, placebo controlled study.

    Science.gov (United States)

    Petersen, L J; Rudnicki, M; Højsted, J

    1994-01-01

    Previous studies suggest that oral calcium supply reduces blood pressure in patients with mild to moderate hypertension. The aim of this study was to determine whether oral calcium supply reduces blood pressure in patients undergoing haemodialysis. The study was randomized, double-blind, and placebo controlled. Eleven patients received two grams of calcium per day and 12 patients received placebo. Three patients (one from the calcium group and two from the placebo group) dropped out within the first month. The groups were comparable at inclusion regarding blood pressure, weight, and serum values. Blood pressure measurements were auscultatory with a mercury manometer and diastolic blood pressure was measured as Korotkoff phase V. At inclusion a significant positive correlation between serum phosphate and blood pressure was found. After a study period of six months a significant reduction in diastolic blood pressure was found between the two groups (p < 0.05), but no difference was found in systolic blood pressure. The reduction in diastolic blood pressure was 6.9 mmHg of the pretreatment level in the calcium group. In conclusion, the treatment of secondary hyperparathyroidism with oral calcium gives good benefits in the regulation of diastolic blood pressure. A well controlled phosphate homeostasis may also be of importance for the control of blood pressure in haemodialysis patients.

  4. Estimated aortic blood pressure based on radial artery tonometry underestimates directly measured aortic blood pressure in patients with advancing chronic kidney disease staging and increasing arterial stiffness.

    Science.gov (United States)

    Carlsen, Rasmus K; Peters, Christian D; Khatir, Dinah S; Laugesen, Esben; Bøtker, Hans Erik; Winther, Simon; Buus, Niels H

    2016-10-01

    Central blood pressure (BP) can be assessed noninvasively based on radial tonometry and may potentially be a better predictor of clinical outcome than brachial BP. However, the validity of noninvasively obtained estimates has never been examined in patients with chronic kidney disease (CKD). Here we compared invasive aortic systolic BP (SBP) with estimated central SBP obtained by radial artery tonometry and examined the influence of renal function and arterial stiffness on this relationship. We evaluated 83 patients with stage 3 to 5 CKD (mean estimated glomerular filtration rate [eGFR] 30 ml/min/1.73 m(2)) and 41 controls without renal disease undergoing scheduled coronary angiography. BP in the ascending aorta was measured through the angiography catheter and simultaneously estimated using radial tonometry. The mean difference between estimated central and aortic SBP was -13.2 (95% confidence interval -14.9 to -11.4) mm Hg. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (cf-PWV) and was significantly increased in CKD patients compared with (versus) control patients (mean 10.7 vs. 9.3 m/s). The difference in BP significantly increased 1.0 mm Hg for every 10 ml/min decrease in eGFR and by 1.6 mm Hg per 1 m/s increase in cfPWV. Using multivariate regression analysis including both eGFR and cfPWV, the difference between estimated central and invasive aortic SBP was significantly increased by 0.7 mm Hg. For the entire cohort brachial SBP significantly better reflected invasive SBP than estimated SBP. Thus, tonometry-based estimates of central BP progressively underestimate invasive central SBP with decreasing renal function and increasing arterial stiffness in CKD patients.

  5. Oral lipid-based nanoformulation of tafenoquine enhanced bioavailability and blood stage antimalarial efficacy and led to a reduction in human red blood cell loss in mice

    Directory of Open Access Journals (Sweden)

    Melariri P

    2015-02-01

    Full Text Available Paula Melariri,1 Lonji Kalombo,2 Patric Nkuna,2 Admire Dube,2,3 Rose Hayeshi,2 Benhards Ogutu,4,5 Liezl Gibhard,6 Carmen deKock,6 Peter Smith,6 Lubbe Wiesner,6 Hulda Swai2 1Polymers and Composites, Material Science and Manufacturing, Council for Scientific and Industrial Research, Port Elizabeth, South Africa; 2Polymer and Composites, Material Science and Manufacturing, Council for Scientific and Industrial Research, Pretoria, South Africa; 3School of Pharmacy, University of the Western Cape, Bellville, South Africa; 4Centre for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya; 5Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya; 6Division of Pharmacology, University of Cape Town Medical School, Groote Schuur Hospital, Cape Town, South Africa Abstract: Tafenoquine (TQ, a new synthetic analog of primaquine, has relatively poor bioavailability and associated toxicity in glucose-6-phosphate dehydrogenase (G6PD-deficient individuals. A microemulsion formulation of TQ (MTQ with sizes <20 nm improved the solubility of TQ and enhanced the oral bioavailability from 55% to 99% in healthy mice (area under the curve 0 to infinity: 11,368±1,232 and 23,842±872 min·µmol/L for reference TQ and MTQ, respectively. Average parasitemia in Plasmodium berghei-infected mice was four- to tenfold lower in the MTQ-treated group. In vitro antiplasmodial activities against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum indicated no change in half maximal inhibitory concentration, suggesting that the microemulsion did not affect the inherent activity of TQ. In a humanized mouse model of G6PD deficiency, we observed reduction in toxicity of TQ as delivered by MTQ at low but efficacious concentrations of TQ. We hereby report an enhancement in the solubility, bioavailibility, and efficacy of TQ against blood stages of Plasmodium parasites without a corresponding increase in toxicity

  6. Inhibitory monoclonal antibody against a (myristylated) small-molecular-weight antigen from Plasmodium falciparum associated with the parasitophorous vacuole membrane.

    Science.gov (United States)

    Kara, U A; Stenzel, D J; Ingram, L T; Bushell, G R; Lopez, J A; Kidson, C

    1988-04-01

    A small-molecular-weight antigen that occurs in asexual blood stages in synchronized cultures of Plasmodium falciparum was detected by a monoclonal antibody which inhibits parasite growth in vitro. This antigen, QF116, showed a molecular weight of 15,000 in parasite strain FCR-3K+ from The Gambia and 19,000 in strain FCQ-27 from Papua New Guinea. The protein did not show significant glycosylation by galactose or glucosamine labeling but was found to be acylated by myristic acid. By using immunogold labeling and electron microscopy, the location of the antigen could be attributed to the parasitophorous vacuole membrane and to inclusions and vesicles residing within the cytoplasm of the erythrocyte host cell.

  7. Identification and screening the mimic epitopes of human Rh(D)blood type antigens%人Rh(D)血型抗原模拟表位的筛选和鉴定

    Institute of Scientific and Technical Information of China (English)

    卞茂红; 沈际佳; 刘淼; 许伟; 杨鹏; 刘淑均; 钟涛

    2008-01-01

    Objective To screen the mimic epitopes of Rh(D)blood group antigens and identify their immunity from phage display peptide library.Methods A twelve mer phage peptide library was biopanned with anti-Rh(D)monoclonal antibody immobilized on plastic surface.After three round panning,thirty-five clones were randomly selected and positive clones were identified by ELISA and cross-reaction,followed by antibody competition inhibition assay and DNA sequencing to obtain the mimic epitopes of Rh (D)blood type antigens.The target phage clones were characterized and the antigenicity was analyzed by Western blot.Results After the third round screening,phages were enriched,and eleven positive clones were obtained.According to sequencing and competition inhibition analysis,the same"-WP-Q-"structure existed in seven of the eleven clones,and they had more than 40%inhibition ratio.The other clones had no same characteristics with low inhibition ratio possibly due to non-specific binding.Western blot analysis indicated that these phage clones could be specifically recognized by the anti-Rh(D)serum and they shared the same antigenicity of Rh(D)protein.Conclusions Rh(D)mimotope of"-WP-Q-"structure is successfully obtained by phage peptide library screening with anti-Rh(D)monoelonal antibody.The results lay the foundation for further exploration of pathogenesis and vaccine development of Rh(D)hemolytic diseases of newborn.%目的 从噬菌体随机肽库中筛选人Rh(D)血型抗原模拟表位,并对其免疫学活性进行鉴定.方法 以抗Rh(D)单克隆抗体作为固相筛选分子,对噬菌体随机十二肽库进行3轮"吸附-洗脱-扩增"筛选过程,随机挑选35个克隆,经噬菌体ELISA和交叉反应试验,确定阳性克隆,再对这些克隆进行DNA序列测定和抗体竞争抑制试验,以获取人Rh(D)血型抗原模拟表位.然后采用蛋白质免疫印迹法(Western blot)对所获噬菌体进行鉴定和抗原性分析.结果 经过3轮淘洗

  8. The antibody approach of labeling blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.

    1992-12-31

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are critically assessed and evaluated.

  9. The antibody approach of labeling blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.

    1991-01-01

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are criticality assessed and evaluated.

  10. The antibody approach of labeling blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.

    1991-12-31

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are criticality assessed and evaluated.

  11. Contrasting Patterns of Serologic and Functional Antibody Dynamics to Plasmodium falciparum Antigens in a Kenyan Birth Cohort

    Science.gov (United States)

    Malhotra, Indu; Wang, Xuelie; Babineau, Denise; Yeo, Kee Thai; Anderson, Timothy; Kimmel, Rhonda J.; Angov, Evelina; Lanar, David E.; Narum, David; Dutta, Sheetij; Richards, Jack; Beeson, James G.; Crabb, Brendan S.; Cowman, Alan F.; Horii, Toshihiro; Muchiri, Eric; Mungai, Peter L.; King, Christopher L.; Kazura, James W.

    2015-01-01

    IgG antibodies to Plasmodium falciparum are transferred from the maternal to fetal circulation during pregnancy, wane after birth, and are subsequently acquired in response to natural infection. We examined the dynamics of malaria antibody responses of 84 Kenyan infants from birth to 36 months of age by (i) serology, (ii) variant surface antigen (VSA) assay, (iii) growth inhibitory activity (GIA), and (iv) invasion inhibition assays (IIA) specific for merozoite surface protein 1 (MSP1) and sialic acid-dependent invasion pathway. Maternal antibodies in each of these four categories were detected in cord blood and decreased to their lowest level by approximately 6 months of age. Serologic antibodies to 3 preerythrocytic and 10 blood-stage antigens subsequently increased, reaching peak prevalence by 36 months. In contrast, antibodies measured by VSA, GIA, and IIA remained low even up to 36 months. Infants sensitized to P. falciparum in utero, defined by cord blood lymphocyte recall responses to malaria antigens, acquired antimalarial antibodies at the same rate as those who were not sensitized in utero, indicating that fetal exposure to malaria antigens did not affect subsequent infant antimalarial responses. Infants with detectable serologic antibodies at 12 months of age had an increased risk of P. falciparum infection during the subsequent 24 months. We conclude that serologic measures of antimalarial antibodies in children 36 months of age or younger represent biomarkers of malaria exposure rather than protection and that functional antibodies develop after 36 months of age in this population. PMID:26656119

  12. Differential regulation of toll-like receptor-2, toll-like receptor-4, CD16 and human leucocyte antigen-DR on peripheral blood monocytes during mild and severe dengue fever.

    Science.gov (United States)

    Azeredo, Elzinandes L; Neves-Souza, Patrícia C; Alvarenga, Allan R; Reis, Sônia R N I; Torrentes-Carvalho, Amanda; Zagne, Sonia-Maris O; Nogueira, Rita M R; Oliveira-Pinto, Luzia M; Kubelka, Claire F

    2010-06-01

    Dengue fever (DF), a public health problem in tropical countries, may present severe clinical manifestations as result of increased vascular permeability and coagulation disorders. Dengue virus (DENV), detected in peripheral monocytes during acute disease and in in vitro infection, leads to cytokine production, indicating that virus-target cell interactions are relevant to pathogenesis. Here we investigated the in vitro and in vivo activation of human peripheral monocytes after DENV infection. The numbers of CD14(+) monocytes expressing the adhesion molecule intercellular adhesion molecule 1 (ICAM-1) were significantly increased during acute DF. A reduced number of CD14(+) human leucocyte antigen (HLA)-DR(+) monocytes was observed in patients with severe dengue when compared to those with mild dengue and controls; CD14(+) monocytes expressing toll-like receptor (TLR)2 and TLR4 were increased in peripheral blood from dengue patients with mild disease, but in vitro DENV-2 infection up-regulated only TLR2. Increased numbers of CD14(+) CD16(+) activated monocytes were found after in vitro and in vivo DENV-2 infection. The CD14(high) CD16(+) monocyte subset was significantly expanded in mild dengue, but not in severe dengue. Increased plasma levels of tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin (IL)-18 in dengue patients were inversely associated with CD14(high) CD16(+), indicating that these cells might be involved in controlling exacerbated inflammatory responses, probably by IL-10 production. We showed here, for the first time, phenotypic changes on peripheral monocytes that were characteristic of cell activation. A sequential monocyte-activation model is proposed in which DENV infection triggers TLR2/4 expression and inflammatory cytokine production, leading eventually to haemorrhagic manifestations, thrombocytopenia, coagulation disorders, plasmatic leakage and shock development, but may also produce factors that act in

  13. Blood Donation Population Human Platelet Antigen of 1~5 System Gene Polymorphism Distribution Characteristics%献血人群人类血小板抗原1~5系统基因多态性分布特点

    Institute of Scientific and Technical Information of China (English)

    徐向华

    2015-01-01

    目的:探讨献血人群人类血小板抗原1~5系统基因多态性分布特点。方法采用聚合酶链-序列特异性引物技术(PCR-SSP)对200例无血缘关系的健康献血者进行HPA-1-5系统基因分型,分别计算献血人群的基因型及基因频率,分析其基因的多态性分布特点。结果该研究中献血人群HPA-1a、2a、3a、4a、5a基因频率分别为:0.942、0.741、0.926、0.945、0.773,HPA-1b、2b、3b、4b、5b基因频率分别为:0.058、0.286、0.084、0.045、0.227,各系统均呈多态性分布, ab杂合子依次为64和30例,-2bb4例;HPA-3和-15高度杂合,aa基因型依次为112和80例,很多献血人群属于bb基因型。结论该地区献血人群HPA-1-5系统基因均呈多态性分布,以HPA-3、-2和-5的a与b基因杂合率较高。%Objective To investigate the blood donation population human platelet antigen of 1 ~ 5 system gene polymorphism distribution characteristics.Methods Polymerase chain - sequence specific primers (PCR SSP) technology to the health of 200 cases of unrelated donors to HPA genotyping-1-5 system, gene frequency and genotype of the blood donation population are calculated respectively, analyze its gene polymorphism distribution characteristics.Results The study of blood donation population HPA - 1 a、2 a、3 a、4 a、5 a gene frequency are: 0.942、0.741、0.926、 0.741、0.926,HPA - 1 b、2 b、3 b、4 b、5 b gene frequencies are: 0.058、 0.286、0.084、0.286、0.084, are distributed in each system are polymorphism, ab heterozygous for 64 and 30 cases, in turn - 2 bb4 cases; HPA - 3 and 15 highly heterozygous, aa genotype was followed by 242 and 210, many line but people belong to the bb genotype. Conclusion This area crowd HPA - 1-5 blood donation system in gene polymorphism distribution of HPA - 3, 2 and 5 a and b gene hybrid rate is higher.

  14. Immune reactivity in early life stages of sea-cage cultured Pacific bluefin tuna naturally infected with blood flukes from genus Cardicola (Trematoda: Aporocotylidae).

    Science.gov (United States)

    Pennacchi, Ylenia; Shirakashi, Sho; Nowak, Barbara F; Bridle, Andrew R

    2016-11-01

    Pacific bluefin tuna (PBT), Thunnus orientalis, due to its high average price on the market is an economically valuable fish species. Infections by blood flukes from the genus Cardicola (Trematoda: Aporocotylidae) represent a growing concern for the cage culture of bluefin tuna in Japan, Australia and Southern Europe. The accumulation of numerous Cardicola eggs in the fish gills causes severe pathology that has been linked to mortality in PBT juveniles up to one year old. The only effective treatment used to mitigate the infection is the oral administration of the antihelminthic drug praziquantel (PZQ) to the affected fish. However, with the need to minimise therapeutic drug use in aquaculture it is hoped that immunoprophylaxis can provide a future alternative to protect the PBT juveniles against Cardicola infection. Currently, little is known of the host immune response to these parasites and of their infection dynamics. In this study, using real-time qPCR we aimed to quantitatively detect C. orientalis and C. opisthorchis DNA within the gills and heart of cultured PBT juveniles and to investigate the host immune response at the transcriptional level in the gills. The research focused mainly during early stages of infection soon after young PBT were transferred to culture cages (from 14 to 77 days post-transfer). An increase (up to 11-fold) of immune-related genes, namely IgM, MHC-I, TCR-β and IL-1β was observed in the PBT gills infected with Cardicola spp. (28-77 days post-transfer). Furthermore, IgM (19-fold increase) and MHC-I (11.5-fold increase) transcription was strongly up-regulated in gill samples of PBT infected with C. orientalis relative to uninfected fish but not in fish infected with C. opisthorchis. Cardicola-specific DNA was first detected in the host 14 days post-transfer (DPT) to sea-cages which was 55 days earlier than the first detection of parasite eggs and adults by microscopy. Oral administration of PZQ did not have an immediate effect

  15. The dysfunction of CD4(+CD25(+ regulatory T cells contributes to the abortion of mice caused by Toxoplasma gondii excreted-secreted antigens in early pregnancy.

    Directory of Open Access Journals (Sweden)

    Jin-ling Chen

    Full Text Available Toxoplasma gondii is an opportunistic intracellular parasite that is highly prevalent in human and warm-blooded animals throughout the world, leading to potentially severe congenital infections. Although the abortion caused by T. gondii is believed to be dependent on the timing of maternal infection during pregnancy, the mechanism remains unclear. This study was focused on the effects of T. gondii excreted-secreted antigens on pregnant outcomes and CD4(+CD25(+ Foxp3(+ regulatory T cells at different stages of pregnancy. The results showed that in mice the frequency and suppressive function of CD4(+CD25(+ regulatory cells were diminished after injection of T. gondii excreted-secreted antigens at early and intermediate stages of pregnancy. The abortion caused by T. gondii excreted-secreted antigens at early pregnancy could be partly prevented by adoptively transferring of CD4(+CD25(+ cells from the mice injected with T. gondii excreted-secreted antigens at late pregnancy, but not from the mice with the same treatment at early pregnancy. Furthermore, T. gondii excreted-secreted antigens induced apoptosis of CD4(+CD25(+ regulatory cells of mice in early and intermediate stages of pregnancy by down-regulating their Bcl-2 expressions and Bcl-2/Bax ratio. This study provides new insights into the mechanism that T. gondii infection is the high risk factor for abortion in early pregnancy.

  16. CLINICAL OBSERVATION ABOUT THE EFFECT OF BLOOD-LETTING OF JING-POINTS ON CEREBRAL BLOOD FLOW IN STROKE PATIENTS AT THE EARLY STAGE AND EXPERIMENTAL STUDY ON ITS MECHANISMS IN THE RABBIT

    Institute of Scientific and Technical Information of China (English)

    WANG Xiuyun; REN Shusheng; GUO Yi; ZHOU Guoping; ZHOU Zhiliang; PAN Rongqing; XU Tangping; LI Qing; WANG Xin; REN Huanzhong

    2002-01-01

    In this paper,the authors sum their research resuits about the effect of blood-letting of Jing(Well)-point on cerebral blood flow both in stroke patients and in experimental cerebral ischemia,cerebral hematoma and hypertension rabbits.In 30cases of stroke (cerebral hemorrhage and cerebral infarction)patients,blood flow state of the anterior cerebral artery(ACA),middle cerebral artery(MCA)and the posterior cerebral artery (PCA), and the blood flow velocity of the bilateral vertebral artery (VA)and the basil artery(BA)are determined before and afterpricking blood of the Twelve Jing-points.In experimental cerebral ischernia (by occlusion of the common carotid ertery) rabbits ,cerebral hematoma model rabbits and intravenous injection of noradrenaline induced hypertension rabbits, rheoencephalogram(REC) is detected before and after blood letting of the twelve"Jing -points.In these 30stroke patients,ultrasound Doppler examination's results show that in 22 cases (73.33%) whose blood flow velocity decreases,after blood-letting of the 12 Jing-points, it ncreases significantly(P< 0.01); in the rest 8 cases (26.67%) whose blood flow velocity speeds up,after treatment,it decreases evidently(P<tly (P< 0.01), showing a good dual-directional regulative effect of blood -letting therapy.In experimental cerebral ischemia rabbits,cerebral hematoma rabbits and hypertension rabbits whose REG lowers in the amplitude apparently ( P < 0.01 ), after blood letting stimulation of the 12 Jing-points, it increases at different degrees.Three patterns of stimulation as blood letting stimulation, pain stimulation and Jing-point stimulation, also the 3factors of blood-letting,may contribute to their effect on improvement of the cerebral blood flow.Somatic affterent nerve,sympathetic nerve of the vasular wall,central cholinergic nerve(M receptors)and adrenergic nerve (α receptors) participate in the effect of blood letting on cerebral blood flow.

  17. Blood group genotyping: from patient to high-throughput donor screening

    NARCIS (Netherlands)

    B. Veldhuisen; C.E. van der Schoot; M. de Haas

    2009-01-01

    Blood group antigens, present on the cell membrane of red blood cells and platelets, can be defined either serologically or predicted based on the genotypes of genes encoding for blood group antigens. At present, the molecular basis of many antigens of the 30 blood group systems and 17 human platele

  18. Blood Types

    Science.gov (United States)

    ... maternity. Learn About Blood Blood Facts and Statistics Blood Components Whole Blood and Red Blood Cells Platelets Plasma ... About Blood Blood Facts and Statistics Blood Types Blood Components What Happens to Donated Blood Blood and Diversity ...

  19. Kinetics of antigen specific and non-specific polyclonal B-cell responses during lethal Plasmodium yoelii malaria

    Directory of Open Access Journals (Sweden)

    Laurence Rolland

    1992-06-01

    Full Text Available In order to study the kinetics and composition of the polyclonal B-cell activation associated to malaria infection, antigen-specific and non-specific B-cell responses were evaluated in the spleens of mice infected with Plasmodium yoelii 17 XL or injected with lysed erythrocytes or plasma from P. yoelii infected mice or with P. falciparum culture supernatants. Spleen/body weigth ratio, numbers of nucleated spleen cells and Immunoglobulin-containing and Immunoglobulin-secreting cells increased progressively during the course of infection,in parallel to the parasitemia. A different pattern of kinetics was observed when anti-sheep red blood cell and anti-trinitrophenylated-sheep red blood cell plaque forming cells response were studied: maximum values were observed at early stages of infection, whereas the number of total Immunoglobulin-containing and Immunoglobulin-secreting cells were not yet altered. Conversely, at the end of infection, when these latter values reached their maximum, the anti-sheep red blood cell and anti-trinitrophenylated-sheep red blood cell specific responses were normal or even infranormal. In mice injected with Plasmodium-derived material, a higher increase in antigen-specific PFC was observed, as compared to the increase of Immunoglobulin-containing and Immunoglobulin-secreting cell numbers. This suggested a "preferential" (antigen-plus mitogen-induced stimulation of antigen-specific cells rather than a generalized non-specific (mitogen-induced triggering of B-lymphocytes. On the basis of these and previous results, it is suggested that polyclonal B-cell activation that takes place during the course of infection appears as a result of successive waves of antigen-specific B-cell activation.

  20. Find out the Target IOP while Different Blood Pressure in Advanced Stage Glaucoma%晚期青光眼在不同血压段时靶眼压的选择

    Institute of Scientific and Technical Information of China (English)

    晏兴云; 贺平; 刘静

    2016-01-01

    目的:探讨晚期青光眼在不同血压段时病程的进展规律 ,并找出在不同血压段时的治疗靶眼压.方法:长期随访晚期青光眼患者的血压及眼压值 ,并分别做视野检查 ,通过A G IS评分法判断病程的进展.并统计出不同血压时的治疗靶眼压值.结果:随访血压越低 ,视野受损进展越快.当视野无进展时 ,血压越低 ,其随访眼压也越低.血压与目标眼压之间呈近似线性关系.结论:低血压是晚期青光眼病程中的危险因素之一.晚期青光眼患者对靶眼压的选择应根据不同血压段来选择.%Objective:To explore progress rule of advanced stage glaucoma and find out the target intraocular pressure in different blood pressure .Methods:Long term follow-up the intraocular pressure and blood pressure .Judge the course of glaucoma by AGIS .find out the target intraocular pressure in different blood pressure .Results:For the lower blood pressure ,impaired vision progress more quickly .When vision without progress ,the lower blood pressure ,the lower intraocular pressure there has been approximate linear relationship between blood pressure and the target intraocular pressure .Conclusion:Low blood pressure is one of the risk factors of adanced glaucoma progression .The target in-traocular pressure should be selected according to different blood pressure .

  1. 丙型肝炎病毒核心抗原检测技术在安全输血中的应用价值%Technique of detection of hepatitis c virus core antigen used in safety blood transfusion

    Institute of Scientific and Technical Information of China (English)

    纪勇平; 周斌; 麻海勇; 孙爱华

    2015-01-01

    目的 探讨丙型肝炎病毒(HCV)核心抗原酶联免疫吸附技术(HCV-cAg ELISA)筛查献血员感染HCV的可行性.方法 将183份抗-HCV阳性、6370份抗-HCV阴性(包括120份伴HBsAg阳性)献血员进行HCV RT-PCR和HCV-cAgELISA检测.结果 抗-HCV阳性和抗-HCV阴性血清HCV RNA和HCV-cAg检测结果符合率分别为92.34%和99.97%.6370份抗-HCV阴性且不伴HBsAg阳性血清HCV-cAg阳性3份,其中1份HCV RNA阳性.HCV RNA拷贝数的上升与HCV-cAg阳性检出率上升呈正相关.结论 HCV-cAg ELISA敏感性与HCV RT-PCR类似,具有简便、快速、可靠优点,较适用于安全输血中献血者的血液筛检.%Objective To evaluate the feasibility to screen donor with hepatitis C virus (HCV) infection by HCV core antigen ELISA (HCV-cAgELISA).Methods 183 anti-HCV positive,6370 anti-HCV negative (including 120 specimens with HbsAg +) serum specimens by using HCV-cAgELISA and HCV RT-PCR methods.Results Comparing with HCV RT-PCR,the detection results of HCV-cAgELISA consistency were 92.34% in anti-HCV positive serum specimens and 99.97% in anti-HCV negative serum specimens,respectively.In 6370 anti-HCV negative specimens,1 serum sample was positive HCV RNA identification in 3 serum specimens which were positive for HCV-cAgELISA.HCV RNA copies and HCV-cAg positive rate was a positive correlation.Conclusion Sensitivity of HCVcAg ELISA is silllilar to HCV RT-PCR.HCVcAgELISA is a simple,fast,and reliable memod to screen donor with HCV infection in blood transfusion medicine.

  2. Human leukocyte antigen supertype matching after myeloablative hematopoietic cell transplantation with 7/8 matched unrelated donor allografts: a report from the Center for International Blood and Marrow Transplant Research

    Science.gov (United States)

    Lazaryan, Aleksandr; Wang, Tao; Spellman, Stephen R.; Wang, Hai-Lin; Pidala, Joseph; Nishihori, Taiga; Askar, Medhat; Olsson, Richard; Oudshoorn, Machteld; Abdel-Azim, Hisham; Yong, Agnes; Gandhi, Manish; Dandoy, Christopher; Savani, Bipin; Hale, Gregory; Page, Kristin; Bitan, Menachem; Reshef, Ran; Drobyski, William; Marsh, Steven GE; Schultz, Kirk; Müller, Carlheinz R.; Fernandez-Viña, Marcelo A.; Verneris, Michael R.; Horowitz, Mary M.; Arora, Mukta; Weisdorf, Daniel J.; Lee, Stephanie J.

    2016-01-01

    The diversity of the human leukocyte antigen (HLA) class I and II alleles can be simplified by consolidating them into fewer supertypes based on functional or predicted structural similarities in epitope-binding grooves of HLA molecules. We studied the impact of matched and mismatched HLA-A (265 versus 429), -B (230 versus 92), -C (365 versus 349), and -DRB1 (153 versus 51) supertypes on clinical outcomes of 1934 patients with acute leukemias or myelodysplasia/myeloproliferative disorders. All patients were reported to the Center for International Blood and Marrow Transplant Research following single-allele mismatched unrelated donor myeloablative conditioning hematopoietic cell transplantation. Single mismatched alleles were categorized into six HLA-A (A01, A01A03, A01A24, A02, A03, A24), six HLA-B (B07, B08, B27, B44, B58, B62), two HLA-C (C1, C2), and five HLA-DRB1 (DR1, DR3, DR4, DR5, DR9) supertypes. Supertype B mismatch was associated with increased risk of grade II–IV acute graft-versus-host disease (hazard ratio =1.78, P=0.0025) compared to supertype B match. Supertype B07-B44 mismatch was associated with a higher incidence of both grade II–IV (hazard ratio=3.11, P=0.002) and III–IV (hazard ratio=3.15, P=0.01) acute graft-versus-host disease. No significant associations were detected between supertype-matched versus -mismatched groups at other HLA loci. These data suggest that avoiding HLA-B supertype mismatches can mitigate the risk of grade II–IV acute graft-versus-host disease in 7/8-mismatched unrelated donor hematopoietic cell transplantation when multiple HLA-B supertype-matched donors are available. Future studies are needed to define the mechanisms by which supertype mismatching affects outcomes after alternative donor hematopoietic cell transplantation. PMID:27247320

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

    Directory of Open Access Journals (Sweden)

    Alexander Boes

    Full Text Available 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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    Boes, Alexander; Spiegel, Holger; 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.

  6. Identification and characterization of Tu88, an antigenic gene from Theileria uilenbergi.

    Science.gov (United States)

    Lu, Yizhu; Wang, Yuefeng; Li, Youquan; Gou, Huitian; Luo, Jianxun; Yin, Hong; Liu, Zhijie

    2015-06-01

    Theileria uilenbergi is a pathogen that causes ovine theileriosis. Prevention and control of theileriosis relies on its diagnosis at early stages of occurrence and requires understanding of proteins with antigenic properties from the pathogen. Despite its prevalence in China, only a few molecules with antigenic properties have been characterized from T. uilenbergi. In this study, we identified a cDNA named Tu88 by immunoscreening a T. uilenbergi merozoite cDNA library with T. uilenbergi-positive sera from infected sheep. Recombinant Tu88 (rTu88) expressed in bacteria reacted strongly with the positive sera of T. uilenbergi in western blot analysis indicating its potential as an antigen. Southern blot analysis showed that it is a single copy gene. Protein localization by immunostaining blood smears from an infected sheep demonstrated the presence of native Tu88 in merozoites. These findings suggest that Tu88 is a potential candidate antigen for the development of a sero-diagnostic tool.

  7. Screening peptide mimotopes of blood group B carbohydrate antigen using phage display peptide library%随机十二肽噬菌体展示文库筛选血型B抗原模拟多肽的实验研究

    Institute of Scientific and Technical Information of China (English)

    李许锋; 罗敏; 邹建军; 岑东芝; 何克菲; 张积仁

    2011-01-01

    OBJECTIVE: To screen peptide mimotopes of blood group B carbohydrate antigen with high affinity for blood group B monoclonal antibody which can replace carbohydrate antigen using a phage display peptide library, and find a new tool for application of blood group B carbohydrate antigen. METHODS: A 12-mer phage peptide library was screened for 3 rounds by using a blood group B monoclonal antibody as target protein according to such a procedure as “adsorbing,eluting and amplification”, and positive clones were selected randomly,confirmed by sandwich ELISA, single strand DNA was extracted from these positive clones and sequenced, and the mimic peptides were deduced by the DNA sequence. RESULTS: After 3 rounds of effective bio-panning, two major mimic peptides with high affinity for target protein were obtained, one peptide sequence was TKNMLSLPVGPG,the other one was HSLKHTQMSYSS. CONCLUSION: The resuits shows that the motif identified through a 12- mer phage display peptide library can be mimiced and may be a substitute for blood group B antigen.%目的:筛选出替代血型B抗原的模拟多肽,用多肽抗原替代糖类抗原.方法:抗血型B抗原的单克隆抗体作为固相筛选靶分子,对随机十二肽噬菌体展示文库进行生物淘选(bio-panning),经包被-结合-洗脱-扩增等循环3轮,对筛选的克隆ELISA鉴定,并通过剂量依赖实验验证其结合特异性.最后提取DNA测序,确定模拟肽氨基酸序列.结果:3轮筛选结束,得到2个亲和力较强的十二肽序列TKNMLSL-PVGPG和HSLKHTQMSYSS.结论:经过生物筛选得到模拟多肽序列,利用噬菌体展示技术筛选糖类抗原的模拟肽具有可行性,为糖类抗原的研究提供一种新思路.

  8. Application Research forTrichinella spiralis Excretory-secretory Antigens from Different Growth Stages in Immunologic Diagnosis%旋毛虫不同发育时期排泄分泌物抗原在免疫学诊断中的应用研究

    Institute of Scientific and Technical Information of China (English)

    吴秀萍; 孙召金; 翟铖铖; 刘晓雷; 唐斌; 刘明远

    2016-01-01

    [目的]系统了解并比较旋毛虫不同发育时期排泄分泌物(ES)抗原的免疫学特性,探索可用于临床检测出栏猪旋毛虫感染的血清学诊断技术。[方法]分别以旋毛虫肠道期10 h肌幼虫(10 h ML)、肠道期30 h成虫(30 h Ad)、3 d成虫(Ad3)、6 d成虫与新生幼虫混合(Ad6+NBL)以及肌幼虫(ML)五个不同发育时期的ES作为包被抗原,应用ELISA方法,检测感染不同剂量、不同天数的猪血清中的抗旋毛虫抗体IgM和IgG水平,绘制抗体消长规律曲线并进行数据分析。[结果]10 h ML ES和ML ES作为包被抗原适合检测不同感染剂量、感染35 d之前的猪抗旋毛虫IgM抗体,低剂量感染10 d左右可以检出,高剂量感染5 d也可以检出;Ad3 ES作为包被抗原对高剂量感染35 d之前的猪抗旋毛虫IgM抗体检测敏感;Ad3和ML的ES作为包被抗原可检测不同剂量、感染35 d之后的猪抗旋毛虫IgG抗体,其中Ad3 ES抗原检测低剂量感染的效果优于ML ES抗原。[结论]肠道期肌幼虫、成虫和肌幼虫的ES抗原可用于检测旋毛虫的早期感染,成虫和肌幼虫的ES抗原可用于检测出栏猪的旋毛虫感染。本研究为进一步合理有效利用旋毛虫不同发育时期的ES抗原,建立更有效的检测屠宰动物旋毛虫感染的方法提供了重要理论基础和参考。%[Objective]To systematically understand and compare the immunological characters of theTrichinella spiralis excretory-secretory(ES)antigens from different growth stages,so as to explore the serological diagnosis techniques which could be applied to slaughter pigs infected withTrichinella spiralis. [Methods]ES antigens from 10-hour muscle larvae at intestinal stage(10 h ML),30-hour adult at intestinal stage(30 h Ad),3-day adult at adult stage(Ad3),6-day adult and newborn larvae stage(Ad6+NBL),and muscle larvae(ML)ofT.spiralis were used as coating antigen,then the serum of infected pigs in

  9. [The biological reaction of inflammation, methylglyoxal of blood plasma, functional and structural alterations in elastic type arteries at the early stage of hypertension disease].

    Science.gov (United States)

    Titov, V N; Dmitriev, V A; Oshchepkov, E V; Balakhonova, T V; Tripoten', M I; Shiriaeva, Iu K

    2012-08-01

    The article deals with studying of the relationship between biologic reaction of inflammation with glycosylation reaction and content of methylglyoxal in blood serum. The positive correlation between pulse wave velocity and content of methylglyoxal, C-reactive protein in intercellular medium and malleolar brachial index value was established. This data matches the experimental results concerning involvement of biological reaction of inflammation into structural changes of elastic type arteries under hypertension disease, formation of arteries' rigidity and increase of pulse wave velocity. The arterial blood pressure is a biological reaction of hydrodynamic pressure which is used in vivo by several biological functions: biological function of homeostasis, function of endoecology, biological function of adaptation and function of locomotion. The biological reaction of hydrodynamic (hydraulic) pressure is a mode of compensation of derangement of several biological functions which results in the very high rate of hypertension disease in population. As a matter of fact, hypertension disease is a syndrome of lingering pathological compensation by higher arterial blood pressure of the biological functions derangements occurring in the distal section at the level of paracrine cenoses of cells. The arterial blood pressure is a kind of in vivo integral indicator of deranged metabolism. The essential hypertension disease pathogenically is a result of the derangement of three biological functions: biological function of homeostasis, biological function of trophology - nutrition (biological reaction of external feeding - exotrophia) and biological function of endoecology. In case of "littering" of intercellular medium in vivo with nonspecific endogenic flogogens a phylogenetically earlier activation of biological reactions of excretion, inflammation and hydrodynamic arterial blood pressure occur. In case of derangement of biological function of homeostasis, decreasing of

  10. 恶性肿瘤病人血液检查与临床分期及转移的相关性研究%The associations between blood indexes with clinical pathological stages and metastasis conditions in malignant tumor patients

    Institute of Scientific and Technical Information of China (English)

    赵晶; 游舟

    2011-01-01

    Objective To investigate the difference and relevance of complete blood count, coagulation test, albumin and globulins in different clinical pathological stages and metastasis conditions in patients with malignant tumors. Methods The complete blood count, coagulation test, albumin and globulins were compared and the relevant study was performed in patients of different clinical pathological stages and with or without metastasis. Results The different pathological stages, hemoglobin, red blood cell count, fibrinogen and white blood cell count were significantly different (P< 0. 05). The fibrinogen and white blood cell count were significantly relevant with clinical stages(r=0. 244, P<0. 05 and r=0. 220,P<0.05). The white blood cell count was significantly higher in patients with metastasis and was significantly relevant with it (r=0. 202,P<0. 05). Conclusion The fibrinogen and white blood cell count are significantly relevant with clinical pathological stages of malignant tumors, and white blood cell count is of prognostic values for them.%目的 研究恶性肿瘤患者的血常规、凝血功能及血白蛋白、球蛋白等指标在不同分期及有无转移的情况下的差异及相关性,并探讨其临床意义.方法 按不同分期及有无转移对胃癌、乳腺癌、食道癌、肾癌及肺癌等101例恶性肿瘤患者的血常规、凝血功能及血白蛋白、球蛋白等指标进行比较并进行相关性分析.结果 恶性肿瘤不同分期各指标中红细胞、血红蛋白、FIB(纤维蛋白原)及白细胞计数有明显差异(P<0.05),其中FIB含量及白细胞计数与分期明显相关(r=0.244,P<0.05;r=0.220,P<0.05);在有及无转移的情况下仅白细胞计数的差异有统计学意义(P<0.05),且明显具有相关性(r=0.202,P<0.05).结论 FIB及白细胞计数与恶性肿瘤患者的临床分期密切相关,且后者对于患者的预后具有预测价值.

  11. Comparison of Excretory-Secretory and Somatic Antigens of Ornithobilharzia turkestanicum in Agar Gel Diffusion Test

    Directory of Open Access Journals (Sweden)

    H Miranzadeh

    2008-12-01

    Full Text Available Background: Ornithobilharziosis as one of the parasitic infections may give rise to serious economic problems in animal husbandry. The Aim of the study was to prepare and compare the somatic and excretory-secretory (ES antigens of O. tur­kestanicum in gel diffusion test. Methods: Excretory-secretory (ES and somatic antigens of Ornithobilharzia turkestanicum were prepared from collected worms from mesentric blood vessels of infected sheep. The laboratory bred rabbits were immunized with antigens and then antisera were prepared. The reaction of antigens and antisera was observed in gel diffusion test. Results: ES antigens of this species showed positive reaction with antisera raised against ES and also somatic antigens. Somatic antigens also showed positive reaction with antisera raised against somatic and also ES antigens. Conclusion: The antigenicity of O. turkestanicum ES and somatic antigens is the same in gel diffusion test.

  12. CRISPR-Cas9-modified pfmdr1 protects Plasmodium falciparum asexual blood stages and gametocytes against a class of piperazine-containing compounds but potentiates artemisinin-based combination therapy partner drugs.

    Science.gov (United States)

    Ng, Caroline L; Siciliano, Giulia; Lee, Marcus C S; de Almeida, Mariana J; Corey, Victoria C; Bopp, Selina E; Bertuccini, Lucia; Wittlin, Sergio; Kasdin, Rachel G; Le Bihan, Amélie; Clozel, Martine; Winzeler, Elizabeth A; Alano, Pietro; Fidock, David A

    2016-08-01

    Emerging resistance to first-line antimalarial combination therapies threatens malaria treatment and the global elimination campaign. Improved therapeutic strategies are required to protect existing drugs and enhance treatment efficacy. We report that the piperazine-containing compound ACT-451840 exhibits single-digit nanomolar inhibition of the Plasmodium falciparum asexual blood stages and transmissible gametocyte forms. Genome sequence analyses of in vitro-derived ACT-451840-resistant parasites revealed single nucleotide polymorphisms in pfmdr1, which encodes a digestive vacuole membrane-bound ATP-binding cassette transporter known to alter P. falciparum susceptibility to multiple first-line antimalarials. CRISPR-Cas9 based gene editing confirmed that PfMDR1 point mutations mediated ACT-451840 resistance. Resistant parasites demonstrated increased susceptibility to the clinical drugs lumefantrine, mefloquine, quinine and amodiaquine. Stage V gametocytes harboring Cas9-introduced pfmdr1 mutations also acquired ACT-451840 resistance. These findings reveal that PfMDR1 mutations can impart resistance to compounds active against asexual blood stages and mature gametocytes. Exploiting PfMDR1 resistance mechanisms provides new opportunities for developing disease-relieving and transmission-blocking antimalarials.

  13. Clonal T cell receptor gamma-chain gene rearrangement by PCR-based GeneScan analysis in the skin and blood of patients with parapsoriasis and early-stage mycosis fungoides.

    Science.gov (United States)

    Klemke, Claus-Detlev; Dippel, Edgar; Dembinski, Antje; Pönitz, Nina; Assaf, Chalid; Hummel, Michael; Stein, Harald; Goerdt, Sergij

    2002-07-01

    Cutaneous T cell lymphoma (CTCL) and reactive T cell skin diseases represent opposite ends of a spectrum of diseases ranging from overtly malignant to persistently benign. Within this spectrum, the parapsoriasis group is not clearly defined regarding malignant potential. In contrast to consistent findings in advanced-stage CTCL, clonality analysis of parapsoriasis has produced conflicting results in previous studies. As T cell receptor gamma-chain polymerase chain reaction GeneScan analysis (TCR-gamma-PCR-GSA) stands out by its sensitivity, its accuracy in size determination of PCR products, its capacity to identify false positives by repeated analysis and its easy applicability, this approach was used to analyse the clonality status of 41 patients with borderline T cell lymphoproliferative skin diseases, including parapsoriasis (n=27) and early-stage mycosis fungoides (MF) (n=14). A monoclonal T cell infiltrate was demonstrated by repeated TCR-gamma-PCR-GSA in lesional skin specimens in 19.2% of parapsoriasis patients and in 66.6% of early-stage MF cases (p=0.013). In peripheral blood, a monoclonal T cell population was found in a similar percentage of parapsoriasis and of early-stage MF patients (26.7% versus 12.5%; p=0.611). A detailed analysis of parapsoriasis subentities, namely small and large plaque parapsoriasis, and parapsoriasis lichenoides, revealed monoclonality in 2(6)/2(5), 3(14)/2(8) and 0(6)/0/(3) of the skin and peripheral blood specimens, respectively. The high detection rate of false positive cases by repeated analysis (20-37.5%) provides a corrected perspective for the high rates of dominant T cell clones found by others in the peripheral blood of such patients. From the results obtained, three major conclusions can be drawn: firstly, CTCL is clearly associated with detection of monoclonality, even in its early stages; secondly, monoclonality is not a prerequisite for potential CTCL precursor entities; and thirdly, recirculating malignant T

  14. Effect of surgical castration of bull calves at different stages of maturity with or without analgesia on the acute phase response (APR) and complete blood count (CBC)

    Science.gov (United States)

    The study objective was to determine if surgical castration at birth or weaning impacts the acute phase response (APR) or complete blood counts (CBC) and whether concurrent administration of an oral analgesic (meloxicam) ameliorates inflammation. Bull calves (n=29) from the University of Arkansas re...

  15. Blood type biochemistry and human disease.

    Science.gov (United States)

    Ewald, D Rose; Sumner, Susan C J

    2016-11-01

    Associations between blood type and disease have been studied since the early 1900s when researchers determined that antibodies and antigens are inherited. In the 1950s, the chemical identification of the carbohydrate structure of surface antigens led to the understanding of biosynthetic pathways. The blood type is defined by oligosaccharide structures, which are specific to the antigens, thus, blood group antigens are secondary gene products, while the primary gene products are various glycosyltransferase enzymes that attach the sugar molecules to the oligosaccharide chain. Blood group antigens are found on red blood cells, platelets, leukocytes, plasma proteins, certain tissues, and various cell surface enzymes, and also exist in soluble form in body secretions such as breast milk, seminal fluid, saliva, sweat, gastric secretions, urine, and amniotic fluid. Recent advances in technology, biochemistry, and genetics have clarified the functional classifications of human blood group antigens, the structure of the A, B, H, and Lewis determinants and the enzymes that produce them, and the association of blood group antigens with disease risks. Further research to identify differences in the biochemical composition of blood group antigens, and the relationship to risks for disease, can be important for the identification of targets for the development of nutritional intervention strategies, or the identification of druggable targets. WIREs Syst Biol Med 2016, 8:517-535. doi: 10.1002/wsbm.1355 For further resources related to this article, please visit the WIREs website.

  16. Antigen loading on dendritic cells affects the lell function in stimulating T cells.

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To study the effect of antigen loading on dendritic cells (DC). Methods: DCs collected from peripheral blood monocytes were loaded with a tumor antigen from XG-7 cell line. These DCs were then co-cultured with allogeneic T cells and were compared with those DCs without antigen exposure.

  17. Human Blood Autoantibodies in the Detection of Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Ola H Negm

    Full Text Available Colorectal cancer (CRC is the second most common malignancy in the western world. Early detection and diagnosis of all cancer types is vital to improved prognosis by enabling early treatment when tumours should be both resectable and curable. Sera from 3 different cohorts; 42 sera (21 CRC and 21 matched controls from New York, USA, 200 sera from Pittsburgh, USA (100 CRC and 100 controls and 20 sera from Dundee, UK (10 CRC and 10 controls were tested against a panel of multiple tumour-associated antigens (TAAs using an optimised multiplex microarray system. TAA specific IgG responses were interpolated against the internal IgG standard curve for each sample. Individual TAA specific responses were examined in each cohort to determine cutoffs for a robust initial scoring method to establish sensitivity and specificity. Sensitivity and specificity of combinations of TAAs provided good discrimination between cancer-positive and normal serum. The overall sensitivity and specificity of the sample sets tested against a panel of 32 TAAs were 61.1% and 80.9% respectively for 6 antigens; p53, AFP, K RAS, Annexin, RAF1 and NY-CO16. Furthermore, the observed sensitivity in Pittsburgh sample set in different clinical stages of CRC; stage I (n = 19, stage II (n = 40, stage III (n = 34 and stage IV (n = 6 was similar (73.6%, 75.0%, 73.5% and 83.3%, respectively, with similar levels of sensitivity for right and left sided CRC. We identified an antigen panel of sufficient sensitivity and specificity for early detection of CRC, based upon serum profiling of autoantibody response using a robust multiplex antigen microarray technology. This opens the possibility of a blood test for screening and detection of early colorectal cancer. However this panel will require further validation studies before they can be proposed for clinical practice.

  18. MHC structure and function – antigen presentation. Part 1

    Science.gov (United States)

    Goldberg, Anna Carla; Rizzo, Luiz Vicente

    2015-01-01

    The setting for the occurrence of an immune response is that of the need to cope with a vast array of different antigens from both pathogenic and non-pathogenic sources. When the first barriers against infection and innate defense fail, adaptive immune response enters the stage for recognition of the antigens by means of extremely variable molecules, namely immunoglobulins and T-cell receptors. The latter recognize the antigen exposed on cell surfaces, in the form of peptides presented by the HLA molecule. The first part of this review details the central role played by these molecules, establishing the close connection existing between their structure and their antigen presenting function. PMID:25807245

  19. Short communication: amino acid supplementation and stage of lactation alter apparent utilization of nutrients by blood neutrophils from lactating dairy cows in vitro

    Science.gov (United States)

    Glutamine is the preferred AA used by polymorphonuclear leukocytes (PMN) during the inflammatory response. However, the effect of other AA on bovine PMN response during inflammation and how this is altered by stage of lactation has not been fully elucidated. The objective of this study was to dete...

  20. [The influence of N-stearoylethanolamine on the activity of antioxidant enzymes and on the level of stable NO metabolites in the rat testes and blood plasma at the early stages of streptozotocine-induced diabetes].

    Science.gov (United States)

    Gorid'ko, T M; Kosiakova, H V; Berdyshev, A H; Bazylians'ka, V R; Margitych, V M; Gula, N M

    2012-01-01

    The influence of N-stearoylethanolamine was investigated on the activity of enzymes of antioxidant protection and content of stable metabolites of nitric oxide (NO) in the testes and plasma of rats at the early stages of development of streptozotocine-induced diabetes mellitus. It was shown that the activity of superoxide dismutase, catalase is reduced in the plasma and testes of animals with streptozotocin-induced (50 mg/kg) diabetes (blood glucose 8-10 mmol/L). A significant increase in the amount of nitrite and nitrate anions was revealed in the plasma of rats, while only the level of nitrite was significantly changed in the testes of animals. The per os administration of the NSE aqueous suspension in a dose of 50 mg/kg during 10 days to the rats with induced diabetes contributed to the normalization of catalase activity in the testis, which correlated with a decrease in the amount of TBA-reacting products and activity of superoxide dismutase and catalase in the blood plasma of animals; the use of NSE also contributed to the reduction of nitrite content in the gonads and to normalization of both nitrite and nitrate in the blood plasma of rats. The NSE administration to intact animals caused an increase in superoxide dismutase activity and significantly reduced the content of stable NO metabolites in the blood plasma of animals.

  1. Eosinofil Sel Penyaji Antigen

    Directory of Open Access Journals (Sweden)

    Safari Wahyu Jatmiko

    2015-04-01

    Full Text Available Sel eosinofil merupakan jenis sel lekosit yang terlibat dalam berbagai patogenesis penyakit. Sel eosinofil pada awalnya dikenal sebagai sel efektor  dari sistem imunitas alamiah. Akan tetapi, kemampuan sel eosinofil dalam memfagositosis patogen menimbulkan dugaan bahwa sel eosinofil ikut berperan sebagai sel penyaji antigen. Hal ini dianalogikan dengan sel makrofag dan sel dendritik yang bisa memfagositosis dan menyajikan antigen sebagai hasil dari degradasi patogen yang difagositosis. Untuk menjawab permasalahan ini, penulis melakukan penelusuran artikel tentang eosinofil sebagai sel penyaji antigen melalui US National Library of Medicine National Institute of Healthdengan kata kunci eoshinophil dan antigen presenting cell. Hasil penelusuran adalah ditemukannya 10 artikel yang relevan dengan topik. Hasil dari sintesis kesepuluh jurnal tersebut adalah sel eosinofil mampu berperan sebagai sel penyaji antigen yang profesional (professionalantigenpresentng cell

  2. Performance of calibration standards for antigen quantitation with flow cytometry.

    Science.gov (United States)

    Lenkei, R; Gratama, J W; Rothe, G; Schmitz, G; D'hautcourt, J L; Arekrans, A; Mandy, F; Marti, G

    1998-10-01

    In the frame of the activities initiated by the Task Force for Antigen Quantitation of the European Working Group on Clinical Cell Analysis (EWGCCA), an experiment was conducted to evaluate microbead standards used for quantitative flow cytometry (QFCM). An unified window of analysis (UWA) was established on three different instruments (EPICS XL [Coulter Corporation, Miami, FL], FACScan and FACS Calibur [Becton Dickinson, San Jose, CA]) with QC3 microbeads (FCSC, PR). By using this defined fluorescence intensity scale, the performance of several monoclonal antibodies directed to CD3, CD4, and CD8 (conjugated and unconjugated), from three manufacturers (BDIS, Coulter [Immunotech], and DAKO) was tested. In addition, the QIFI system (DAKO) and QuantiBRITE (BDIS), and a method of relative fluorescence intensity (RFI, method of Giorgi), were compared. mAbs reacting with three more antigens, CD16, CD19, and CD38 were tested on the FACScan instrument. Quantitation was carried out using a single batch of cryopreserved peripheral blood leukocytes, and all tests were performed as single color analyses. Significant correlations were observed between the antibody-binding capacity (ABC) values of the same CD antigen measured with various calibrators and with antibodies differing in respect to vendor, labeling and possible epitope recognition. Despite the significant correlations, the ABC values of most monoclonal antibodies differed by 20-40% when determined by the different fluorochrome conjugates and different calibrators. The results of this study indicate that, at the present stage of QFCM consistent ABC values may be attained between laboratories provided that a specific calibration system is used including specific calibrators, reagents, and protocols.

  3. Regional cerebral blood flow in acute stage with ischemic cerebrovascular disease by xenon-133 inhalation and single photon emission computerized tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kurokawa, Hiroyuki; Iino, Katsuro; Kojima, Hisashi; Saito, Hitoshi; Suzuki, Mikio; Watanabe, Kazuo; Kato, Toshiro

    1987-05-01

    Single photon emission computed tomography (SPECT) with xenon-133 inhalation method was undertaken within 48 hr after the onset in 68 patients with ischemic cerebrovascular disease. The results for regional cerebral blood flow (rCBF) were compared with concurrently available computed tomography (CT) scans. In patients with cerebral infarction, SPECT detected ischemic lesions earlier than CT, with the detectability being 92 %. The area with a decreased blood flow, as seen on SPECT, was more extensive than the low density area on CT, with a concomitant decrease in blood flow in the contralateral cerebral hemisphere. Crossed cerebellar diaschisis was associated with stenosis of the internal carotid artery in 50 % (7/14), and with stenosis of the middle cerebral artery in 35 % (9/26). Abnormal SPECT findings were seen in 47 % (8/17) of the patients with transient ischemic attack (TIA). Five TIA patients had a decreased rCBF on SPECT, which was not provided by CT scans. On the contrary, small infarct lesions in the cerebral basal ganglia, as observed in 4 patients, was not detected by SPECT, but detected by CT. This may imply the limitations of SPECT in the detection of deep-seated lesions of the cerebrum. The results led to the conclusion that SPECT can be performed safely even in acute, seriously ill patients to know changes in rCBF because it is noninvasive and is capable of being repeated in a short time. (Namekawa, K.).

  4. A Phase 1 study of the blood-stage malaria vaccine candidate AMA1-C1/Alhydrogel with CPG 7909, using two different formulations and dosing intervals.

    Science.gov (United States)

    Ellis, Ruth D; Mullen, Gregory E D; Pierce, Mark; Martin, Laura B; Miura, Kazutoyo; Fay, Michael P; Long, Carole A; Shaffer, Donna; Saul, Allan; Miller, Louis H; Durbin, Anna P

    2009-06-24

    A Phase 1 study was conducted in 24 malaria naïve adults to assess the safety and immunogenicity of the recombinant protein vaccine apical membrane antigen 1-Combination 1 (AMA1-C1)/Alhydrogel with CPG 7909 in two different formulations (phosphate buffer and saline), and given at two different dosing schedules, 0 and 1 month or 0 and 2 months. Both formulations were well tolerated and frequency of local reactions and solicited adverse events was similar among the groups. Peak antibody levels in the groups receiving CPG 7909 in saline were not significantly different than those receiving CPG 7909 in phosphate. Peak antibody levels in the groups vaccinated at a 0,2 month interval were 2.52-fold higher than those vaccinated at a 0,1 month interval (p=0.037, 95% CI 1.03, 4.28). In vitro growth inhibition followed the antibody level: median inhibition was 51% (0,1 month interval) versus 85% (0,2 month interval) in antibody from samples taken 2 weeks post-second vaccination (p=0.056).

  5. 早期脓毒症大鼠脑氧代谢与乳酸的变化%Preliminary study of cerebral oxygen metabolism and change of blood lactate in early stage of sepsis in rats

    Institute of Scientific and Technical Information of China (English)

    钱欣; 郑峥; 汤罗嘉; 陈锋

    2011-01-01

    Objective To observe the change of cerebral oxygen metablism and the level of blood lactate in early stage of sepsis in rats.Method Sixty-four SD rats were randomly(random number)divided into septic group and control group.The sepsis model of rat was made by lipopolysaccharide (LPS,10 mg/kg)injected intra-abdominally,and rats of control group were treated with the same amount of physiological saline instead.And each group was further divided into 4 sub-groups of4 h,6 h,12 h and 24 h after treatment.At each interval,blood samples were obtained via jugular vein for detecting blood oxygen saturation (Sjv02)and blood lactate(LA).The blood oxygen saturation(Sa02)of ventral aorta was also measured.Arteriovenous oxygen content difference (AVD02) and oxygen extraction fraction (OEF) were studied.These four variables were analyzed and compared between two groups.Results The AVD02 and OEF in sepsis group were higher than those in control groups of 3 h,6 h and 12 h (P0.05).LA in sepsis group was higher than that in control group in each interval (P0.05).脓毒症组各时间点LA含量与对照组相比均有不同程度升高,差异具有统计学意义(P<0.05).结论 脓毒症早期可出现脑贯注及脑氧摄取的增强;Sjv02,AVDO2,OEF结合LA水平的监测,能更准确的评估脓毒症早期脑供氧、耗氧和脑贯注状态.

  6. Liver-Stage Specific Response among Endemic Populations: Diet and Immunity

    Science.gov (United States)

    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

  7. New diagnostic antigens for early trichinellosis: the excretory-secretory antigens of Trichinella spiralis intestinal infective larvae.

    Science.gov (United States)

    Sun, Ge Ge; Liu, Ruo Dan; Wang, Zhong Quan; Jiang, Peng; Wang, Li; Liu, Xiao Lin; Liu, Chun Yin; Zhang, Xi; Cui, Jing

    2015-12-01

    The excretory-secretory (ES) antigens from Trichinella spiralis muscle larvae (ML) are the most commonly used diagnostic antigens for trichinellosis, but anti-Trichinella IgG antibodies cannot be detected until 2-3 weeks after infection; there is an obvious window period between Trichinella infection and antibody positivity. Intestinal infective larvae (IIL) are the first invasive stage during Trichinella infection, and their ES antigens are firstly exposed to the immune system and might be the early diagnostic markers of trichinellosis. The aim of this study was to evaluate the early diagnostic values of IIL ES antigens for trichinellosis. The IIL were collected from intestines of infected mice at 6 h postinfection (hpi), and IIL ES antigens were prepared by incubation for 18 h. Anti-Trichinella IgG antibodies in mice infected with 100 ML were detectable by ELISA with IIL ES antigens as soon as 10 days postinfection (dpi), but ELISA with ML ES antigens did not permit detection of infected mice before 12 dpi. When the sera of patients with trichinellosis at 19 dpi were assayed, the sensitivity (100 %) of ELISA with IIL ES antigens was evidently higher than 75 % of ELISA with ML ES antigens (P < 0.05) The specificity (96.86 %) of ELISA with IIL ES antigens was also higher than 89.31 % of ELISA with ML ES antigens (P < 0.05). The IIL ES antigens provided a new source of diagnostic antigens and could be considered as a potential early diagnostic antigen for trichinellosis.

  8. Peripheral blood lymphocytes from low-grade squamous intraepithelial lesions patients recognize vaccine antigens in the presence of activated dendritic cells, and produced high levels of CD8 + IFNγ + T cells and low levels of IL-2 when induced to proliferate

    Directory of Open Access Journals (Sweden)

    Hernández-Montes Jorge

    2012-05-01

    Full Text Available Abstract Background Most infections with human papillomavirus (HPV are resolved without clinical intervention, but a minority evolves into chronic lesions of distinct grades, including cervical-uterine cancer. It is known that in most cases the immune system mediates elimination of HPV infection. However, the mechanism of immune evasion leading to HPV persistence and development of early cervical lesions is not fully understood. The aim of the present work was to evaluate the potential of peripheral blood leukocytes (PBL from low-grade squamous intraepithelial lesions (LSIL patients to be activated ex-vivo by vaccine antigens, the participation of cytotoxic lymphocytes and regulatory T cells, and to determine the secretion of Th1 and Th2 cytokines mediated by stimulation of T cell receptors. Results We found that PBL from LSIL patients showed a significantly lower proliferation rate to vaccine antigens as compared to that of healthy donors, even though there was not a difference in the presence of antibodies to those antigens in sera from both groups. We did not find differences in either the frequency of CD4 + CD25 + FoxP3+ in PBL, or the levels of IL-4, IL-5 and IL-10 in plasma or conditioned media from PBL incubated with TcR agonists in vitro, between the two groups. However, we detected a lower production of IL-2 and a higher proportion of CD8 + IFNγ + cells in PBL from LSIL patients as compared with PBL from normal donors. We also observed that PBL from patients infected by HPV-16 and −18 were not able to proliferate in the presence of soluble HPV antigens added to the culture; however, a high level of proliferation was attained when these antigens were presented by activated dendritic cells. Conclusions Our results suggest that the immunodeficiency reported in LSIL patients could be due to the inability of specific cytotoxic T lymphocytes that for some unknown reason are present but unable to mount a response when

  9. [Characteristics of the indicators of the blood coagulation and fibrinolysis systems in the pre-clinical stage of ischemic heart disease].

    Science.gov (United States)

    Andreenko, G V; Panchenko, V M; Lisina, A N; Liutova, L V

    1978-10-01

    Signs of dysfunction of the coagulation system and fibrinolysis were determined in 45 healthy young individuals who had such risk factors in relation to ischemic heart disease as arterial hypertension, hypercholesterolemia, smoking, aggravated heredity, permanent emotional overstress, etc. These signs were manifested by a tendency to augmentation of blood coagulation and compensatory activation of fibrinolysis. Ischemic-type changes were detected on the ECG after a physical load. It is assumed that dysfunction of the coagulation system and fibrinolysis is an additional risk factor in relation to ischemic heart disease, while derangement of compensatory fibrinolysis tension with the subsequent tension of its components may lead to the development of coronary thrombosis.

  10. Increased P-35, EBI3 Transcripts and Other Treg Markers in Peripheral Blood Mononuclear Cells of Breast Cancer Patients with Different clinical Stages

    Directory of Open Access Journals (Sweden)

    Maryam Hamidinia

    2015-06-01

    Full Text Available Purpose: Currently, cancer as a major problem around the world threatens human health and has a high incidence in developing countries. Many reports have indicated that patients suffering from cancer demonstrate decreased antitumor immune responses as well as a high prevalence of T regulatory population. It has been reported that Foxp3+Tregs exert suppression by cell contact-dependent mechanisms which are mediated by soluble factors such as immunosuppressive cytokines like IL-10, TGF-​B and IL-35. Consequently there is a great need to identify prognostic and diagnostic biomarkers of regulatory T cells for vaccine and drug development. Methods: In this study IL-10, TGF-B, IL-35 and Foxp3 mRNA gene expression has been measured in peripheral blood of 40 breast cancer patients and 40 normal age-matched women using quantitative real-time PCR (qRT-PCR method with Master Mix reaction containing SYBER Green. GAPDH gene was used as housekeeping gene. Results: Our data demonstrated a significant up-regulation of IL-10, TGF-​B, P35, EBI3 and Foxp3 gene expression in patients’ peripheral blood compared to normal healthy controls (p<0.05. Conclusion: The data suggests that the immune system is suppressed in breast cancer patients, which may be due to elevated Treg cells population. These results may be useful for diagnostic or therapeutic purposes. However it may require more investigations

  11. CONFIRMATION OF HEREDITARY TYROSINEMIA TYPE 1 IN NEONATAL STAGE USING SPECTROPHOTOMETRIC MICROASSAY BASED ON THE DETERMINATION OF SUCCINYLACETONE LEVEL IN DRIED-BLOOD SPOTS

    Directory of Open Access Journals (Sweden)

    Gautam Kumar

    2014-05-01

    Full Text Available Hereditary Tyrosinemia Type 1 (HT1 is a metabolic disorder below to the class of autosomal recessive inheritance caused by the dearth of enzyme fumaryl acetoacetase the last enzyme in the tyrosine catabolic pathway . Affected individuals show increased tyrosine and succinyl acetone concentration (SA in blood. Patients also excrete increased concentration of SA in urine. The disorder is characterized by progressive liver disease and renal tubular defects with accompanying hypophosphatemic rickets. Symptoms of HT1 usually appear in the first few months of life and include failure to gain weight and grow at the expected rate, diarrhea, vomiting, yellowing of the skin and whites of the eyes (jaundice. It may also lead to liver and kidney failure and an increased risk of liver cancer. Liver transplantation is the only effective treatment for hereditary tyrosinemia type 1. In the present study, Succinyl Acetone is measured by using its inhibitory property on d-aminolaevulinate dehydratase enzyme for the diagnosis of HT1 in dried blood spots.

  12. H-deficient Bombay and para-Bombay red blood cells are most strongly agglutinated by the galactophilic lectins of Aplysia and Pseudomonas aeruginosa that detect I and P1 antigens.

    Science.gov (United States)

    Gilboa-Garber, N; Sudakevitz, D; Levene, C; Rahimi-Levene, N; Yahalom, V

    2006-01-01

    The galactophilic lectins Aplysia gonad lectin (AGL) and Pseudomonas aeruginosa lectin (PA-IL), which detect human I and P1 RBC antigens, were examined for hemagglutination of H+ (group O and B) and H-deficient (Bombay and para-Bombay phenotype) RBCs. The results were compared with those obtained using two other galactophilic lectins, Maclura pomifera lectin (MPL) and Arachis hypogaea (peanut) agglutinin (PNA), which share T-antigen affinity, and two fucose-binding H-specific lectins, Ulex europaeus (UEA-I) and Pseudomonas aeruginosa lectin (PA-IIL), as well as with those achieved with anti-I serum. The results revealed that, in contrast to UEA-I and PA-IIL, which preferentially agglutinated H+ RBCs, and to MPL and PNA, which similarly agglutinated all examined RBCs, AGL, PA-IL, and the anti-I serum agglutinated the H-deficient RBCs more strongly than did the H+ RBCs. These findings could be attributed to increased levels of I and P1 antigens on those RBCs resulting from the use of the free common H-type 2 precursor for their synthesis. Since both PA-IL and PA-IIL are regarded as potential pathogen adhesins, it would be interesting to statistically compare the sensitivities of individuals of H+ and H-deficient RBC populations to P. aeruginosa infections.

  13. Qi and removing blood stasis in treating early stage cirrhosis%益气化瘀法治疗早期肝硬化

    Institute of Scientific and Technical Information of China (English)

    叶思文

    2012-01-01

      目的:就益气化瘀法治疗早期肝硬化进行探讨。方法:选取三个案例进行分析,将益气健脾,活血化瘀辨证治疗肝硬化。结果:案例1:服上方治疗3个月后病愈。随访至今未见再发。案例2诸症悉除,复查肝功能,肝胆脾彩超均属正常范围。后用上方加减研末冲服月余,以巩固疗效,随访1年未见再发。案例3诸症悉除,复查肝功能及肝胆脾彩超,其中彩超示:脾脏肿大,余项均属正常范围。后用上方加减蜜丸服药月余,病告痊愈,随访2年未见再发。结论:臌胀为临床四大疑难重症之一,其病机为肝脾肾三脏功能失调,气、血、水停于腹中,本虚标实,虚实夹杂的病理过程。%  Objective:Yiqi Huayu method treatment early time liver cirrhosis of. Methods:a total of three cases were analyzed, the Qi of the spleen, promoting blood circulation to remove blood stasis syndrome differentiation and treatment of liver cirrhosis. Results:the case of 1: served 3 months after the treatment was over. Up to now no longer hair. 2 cases are in addition to all disease, the liver function, liver spleen ultrasound within the normal range. After using the above addition and subtraction grind end each month, in order to consolidate the curative effect, follow-up of 1 years again. 3 cases are in addition to all disease, the liver function and liver spleen ultrasound, including ultrasonography indicated: enlargement of spleen, the remainder were within normal range. After taking over addition and subtraction pill month, disease to cure, follow-up of 2 years showed no recurrence. Conclusion:swelling for clinical four severe problems, its pathogenesis is spleen kidney three dirty function disorders, gas, blood, water stop in the abdomen, the superficial, inclusion of actual pathological process.

  14. Blood sugar test - blood

    Science.gov (United States)

    ... blood glucose level ( hypoglycemia ) may be due to: Hypopituitarism (a pituitary gland disorder) Underactive thyroid gland or ... tonic-clonic seizure Glucagon blood test Glucagonoma Hyperthyroidism Hypopituitarism Hypothyroidism Insulinoma Low blood sugar Multiple endocrine neoplasia ( ...

  15. Relationship of prognosis and body temperature and white blood cell count in peripheral blood in early stage of patients of cerebral hemorrhage%急性脑出血患者早期体温变化及外周血白细胞计数与预后的关系

    Institute of Scientific and Technical Information of China (English)

    杨春永; 孙京莉

    2011-01-01

    目的 探讨急性脑出血患者早期体温变化及外周血白细胞计数与预后的关系.方法 将77例脑出血患者按体温与外周血白细胞计数分别分成发热组与不发热组;白细胞数正常组与白细胞数增高组;白细胞数轻度增高组与显著增高组,观察各组死亡率并进行统计学分析.结果 发热组死亡率(67.3%)高于不发热组的死亡率(20.0%)(P<0.01);白细胞数正常组死亡率(32.4%)低于白细胞数增高组的死亡率(67.4%)(P<0.01);白细胞数轻度增高组死亡率(43.5%)低于显著白细胞数增高组的死亡率(95.0%)(P<0.01).结论 根据急性脑出血患者早期体温变化及外周血白细胞计数可对预后做出较为准确的判断,且方法简单、易行,有很高的临床应用价值.%Objective To investigate the relationship of prognosis and body temperature and white blood cell count in peripheral blood in early stage of patients of cerebral hemorrhage. Methods Seventy-seven patients of cerebral hemorrhage were divided into fever group and normal temperature group, white blood cell count increasing group and normal white blood cell count group, white blood cell minimal increasing group and white blood cell increasing significantly group. Mortality of each group were calculated and compared. Results The mortality of fever group and normal temperature group was 67. 3% and 20.0% . There was significant difference between two groups ( P < 0. 01). The mortality of white blood cell count increasing group and normal white blood cell count group was 32.4% and 67.4%. There was significantly difference between two group ( P < 0.01). The mortality of white blood cell minimal increasing group and white blood cell increasing significantly group was 43. 5% and 95.0%. There was significantly difference in two group (P <0.01). Conclusion It would determine the prognosis by study body temperature and white blood cell count in peripheral blood in early stage of

  16. Antigen-specific lymphocyte transformation in patients with recent yersiniosis.

    Science.gov (United States)

    Vuento, R

    1983-04-01

    Lymphocyte transformation in patients with recent yersiniosis was studied. A micromethod using washed blood cells and Yersinia enterocolitica antigen was employed. The washed blood cells were incubated in the presence of various dilutions of heat-treated whole bacteria; these proved as antigen superior to gentamicin- or formalin-treated bacteria. Patients with recent yersiniosis had a significantly higher response against Yersinia antigen as compared to 20 healthy controls, who had either no response or a low response. No difference could be observed in responses against PPD or streptokinase-streptodornase, or in the mitogen responses between these two groups. A marked cross-reaction was observed between Yersinia and Escherichia coli antigen. The results show that patients with recent yersiniosis develop lymphocyte transformation response against Yersinia. Lymphocyte transformation test can be used in the study of host responses against infecting Yersinia in patients with different clinical pictures of yersiniosis.

  17. Application of monoclonal antibody against granulocytes of scallop Chlamys farreri on granulocytes occurrence at different developmental stages and antigenic cross-reactivity of granulocytes in five other bivalve species.

    Science.gov (United States)

    Xing, Jing; Tang, Xiaoqian; Ni, Yongqing; Zhan, Wenbin

    2014-01-01

    A monoclonal antibody (MAb) 6H7 raised specifically against granulocytes of scallop (Chlamys farreri) was employed to observe granulocyte occurrence successively in blastulae, gastrulae, trochophore larvae, D-shape larvae, umbo-veliger larvae and creeping larvae of C. farreri by immunohistochemistry assay contrasted with H&E stain using semi-thin sections. Moreover, the reactivity of the MAb with granulocytes of C. farreri, Bay scallop Argopecten irradians, Japanese scallop Patinopecten yessoensis, Blue mussel Mytilus edulis, Pacific oyster Crassostrea gigas and Manila clam Ruditapes philippinarum, was detected by immunofluorescence assay (IFA) with differential interference contrast and fluorescent microscopy and flow cytometric immunofluorescence assay (FCIFA). The results showed that positive signals were first observed at D-shape larval stage, about 28 h post fertilization, after that, umbo-veliger larvae exhibited the positive cells with a diameter of 3-5 μm distributed in velum, digestive gland and esophagus. Then in creeping larvae, the number of positive cells increased with average diameter of 5-7 μm, and widely distributed in foot, digestive gland, gills and adductor muscles. No positive signal was found in blastulae, gastrulae and trochophore larvae. The results of IFA and FCIFA showed MAb 6H7 reacted to granulocytes of C. farreri, A. irradians, P. yessoensis and C. gigas, and the positive percentage reactivity were 53 ± 2.5%, 15 ± 2.5%, 12 ± 2.1% and 19 ± 2.1%, respectively, however, no cross-reaction was detected in hemocytes of R. philippinarum and M. edulis.

  18. Amino acid efflux by asexual blood-stage Plasmodium falciparum and its utility in interrogating the kinetics of hemoglobin endocytosis and catabolism in vivo.

    Science.gov (United States)

    Dalal, Seema; Klemba, Michael

    2015-06-01

    The endocytosis and catabolism of large quantities of host cell hemoglobin is a hallmark of the intraerythrocytic asexual stage of the human malaria parasite Plasmodium falciparum. It is known that the parasite's production of amino acids from hemoglobin far exceeds its metabolic needs. Here, we show that P. falciparum effluxes large quantities of certain non-polar (Ala, Leu, Val, Pro, Phe, Gly) and polar (Ser, Thr, His) amino acids to the external medium. That these amino acids originate from hemoglobin catabolism is indicated by the strong correlation between individual amino acid efflux rates and their abundances in hemoglobin, and the ability of the food vacuole falcipain inhibitor E-64d to greatly suppress efflux rates. We then developed a rapid, sensitive and precise method for quantifying flux through the hemoglobin endocytic-catabolic pathway that is based on leucine efflux. Optimization of the method involved the generation of a novel amino acid-restricted RPMI formulation as well as the validation of D-norvaline as an internal standard. The utility of this method was demonstrated by characterizing the effects of the phosphatidylinositol-3-kinase inhibitors wortmannin and dihydroartemisinin on the kinetics of Leu efflux. Both compounds rapidly inhibited Leu efflux, which is consistent with a role for phosphtidylinositol-3-phosphate production in the delivery of hemoglobin to the food vacuole; however, wortmannin inhibition was transient, which was likely due to the instability of this compound in culture medium. The simplicity, convenience and non-invasive nature of the Leu efflux assay described here makes it ideal for characterizing the in vivo kinetics of hemoglobin endocytosis and catabolism, for inhibitor target validation studies, and for medium-throughput screens to identify novel inhibitors of cytostomal endocytosis.

  19. Specific CTL response of anti-leukemia induced by leukemia antigen loading with cord blood DCs in vitro%白血病细胞抗原负载脐血DCs体外诱导抗白血病特异性CTLs应答研究

    Institute of Scientific and Technical Information of China (English)

    刘芯; 谭丽; 谭获

    2014-01-01

    Objective:To investigate the feasibility of inducing specific cytotoxic T lymphocytes by cord blood in vitro. Methods:Mononuclear cells from 10 induced samples of cord blood were differentiated into dendritic cells ( DCs) by cytokines in vitro, and DCs cells were loading with freeze-thaw antigen of U937 at the same time. Homologous cord blood T lymphocytes activated by mature cells generated cytotoxic T lymphocytes ( CLTs) for the experiment of lethal effect. The killing activity was assayed with MTT method. Results: Mature DCs with typical morphology and function were cultivated from 10 samples of cord blood. As effector cell DC-CTLs were induced through DCs, the target ratio was compared amongU937 cell line group, K562 cell line group and the control group. It showed that the highest killing rate was in U937 group (P<0.05). Conclusion: DCs cells of cord blood loaded with specific antigen have specific killing effect.%目的:探讨体外诱导脐血产生特异性细胞毒淋巴细胞的可行性。方法:通过体外联合细胞因子体外诱导10份脐血单个核细胞分化为树突状细胞( dendritic cells,DCs),同时让DCs细胞负载U937冻融抗原;使成熟DCs刺激同源的脐血T淋巴细胞生成细胞毒性T细胞( cytotoxic T lymphocytes,CTLs)从而进行杀伤效应实验。 MTT法测定杀伤活性。结果:10份脐血标本均可培养出形态典型、功能成熟的DCs。经DCs诱导效应细胞DC-CTLs,在不同效靶比对U937细胞系、K562细胞株和对照组中,杀伤率以U937组最高( P<0.05)。结论:特定抗原负载的脐血DCs细胞有特异性的杀伤效应。

  20. Expression of Lewisa, Sialyl Lewisa, Lewisx, Sialyl Lewisx, Antigens as Prognostic Factors in Patients with Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Tohru Nakagoe

    2000-01-01

    Full Text Available BACKGROUND: Altered expression of blood group-related carbohydrate antigens such as sialyl Lewis (Lex antigen in tumours is associated with tumour progression behaviour and subsequent prognosis. However, the prognostic value of the expression of Le-related antigens in colorectal tumours remains unclear.

  1. Co-incubation with IL-18 potentiates antigen-specific IFN-γ response in a whole-blood stimulation assay for measurement of cell-mediated immune responses in pigs experimentally infected with Lawsonia intracellularis

    DEFF Research Database (Denmark)

    Riber, Ulla; Boesen, Henriette Toft; Jakobsen, Jeanne Toft

    2011-01-01

    The whole-blood interferon-gamma (IFN-γ) assay is a quantitative in-vitro assay for a direct read out of Ag-specific cell-mediated immune (CMI) responses to infectious diseases. The IFN-γ assay is robust in severe intracellular infections like Brucella or mycobacteria, but more difficult to evalu......The whole-blood interferon-gamma (IFN-γ) assay is a quantitative in-vitro assay for a direct read out of Ag-specific cell-mediated immune (CMI) responses to infectious diseases. The IFN-γ assay is robust in severe intracellular infections like Brucella or mycobacteria, but more difficult...

  2. Staging of moyamoya disease by perfusion SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Kuwabara, Yasuo [Kyushu Univ., Fukuoka (Japan). Hospital; Matsushima, Toshio; Fukui, Masashi

    2001-04-01

    Staging of moyamoya disease, based on angiography and PET have already been established. The authors have established staging of moyamoya disease based on perfusion SPECT, that can be summarized as follows: Stage I, no abnormality is seen at rest or after acetazolamide loading; Stage II, no abnormality is seen at rest, however, a decreased response (blood flow increase rate: <15%) is seen to acetazolamide loading (a, a decreased response is seen only in the frontal lobe; b, a decreased response is seen in regions other than the frontal lobe; and c, a decreased response is seen throughout the cerebrum); Stage III, localized decrease in blood flow (blood flow decrease compared with peripheral tissue: {>=}15%) and marked decrease in response to acetazolamide (blood flow increase rate: <5%) are seen at rest. In Stage III, CT and MRI show no abnormal findings or only mild lesions of the white matter; and Stage IV, multiple decreases in blood flow are seen at rest, and CT and MRI reveal infarctions and severe atrophy at the same sites. The above staging does not require determination of cerebral blood flow, and thus it can be used in children, in whom cerebral blood flow determination is difficult. The authors performed 99m-Tc ECD perfusion SPECT in 25 patients with moyamoya disease for the staging, and compared staging based on angiography with staging based on perfusion SPECT. The results did not show a correlation between the 2 staging methods. A problem inherent in the staging of moyamoya disease based on perfusion SPECT is that the relationship between cerebral blood flow and cerebral radioactivity concentrations may differ depending on the drug used to determine cerebral blood flow. Thus, although the present staging system does not depend on any specific radioactive drug to determine cerebral blood flow, further investigation is necessary to identify a more appropriate drug than those in current use. (K.H.)

  3. T-cell response to p53 tumor-associated antigen in patients with colorectal carcinoma.

    Science.gov (United States)

    Bueter, Marco; Gasser, Martin; Schramm, Nicolai; Lebedeva, Tatiana; Tocco, Georges; Gerstlauer, Christiane; Grimm, Martin; Nichiporuk, Ekaterina; Thalheimer, Andreas; Thiede, Arnulf; Meyer, Detlef; Benichou, Gilles; Waaga-Gasser, Ana Maria

    2006-02-01

    Despite the radical surgical resection performed in patients with colorectal carcinoma, there is a high rate of tumor recurrence. Over an observation period of 3 years, 18% of the patients in our collective suffered a tumor relapse with local or distinct metastases after initial R0-resection. Some evidence suggests that this may be due to suppression of anti-tumor responses, a phenomenon that might be attributed to regulatory T cells. The aim of our study was to investigate the tumor-specific immune response depending on the UICC stage of patients with colorectal cancer. The cellular immune responses against defined antigens that are overexpressed in most of the patients with colorectal cancer were characterized. For this purpose, the tumor suppressor gene, p53, was chosen as the tumor-associated antigen that exhibits mutations and overexpression in up to 60% of colorectal carcinoma. We observed that p53 induced both IFN-gamma and IL-10 secretion. The predominance of IL-10 production indicated that regulatory T cells directly participate in modulating the anti-tumor immune response. IL-10 levels in the blood as well as the expression of regulatory T-cell specific genes at the tumor site correlate with the UICC stage of the disease. These results may provide an explanation for the poor prognosis and increased recurrence rate in patients with advanced carcinoma.

  4. Modulation of antigenicity of mycelial antigens during developmental cycle of Karnal bunt (Tilletia indica) of wheat.

    Science.gov (United States)

    Rai, G; Kumar, A; Singh, A; Garg, G K

    2000-05-01

    Indirect enzyme linked immunosorbent assays (ELISA) were developed using polyclonal antibodies against soluble cytoplasmic (SCA) and insoluble cell wall antigens (ICWA) for monitoring modulation of mycelial antigens during growth cycle of T. indica. With SCA, continuous decrease in ELISA reactivity was observed in maturing fungus cultures, suggesting that SCA were expressed predominantly during early vegetative phase and their decreasing role was apparent as the fungus matures possibly towards sporogenous mycelium. In case of ICWA, the reaction profile showed an increase up to exponential phase of growth probably due to increase in the cell division and branching of mycelium. But later, ICWA antibody reactivity was decreased which may be due to conversion of mycelial phase to sporogenous phase, a quiescent stage of growth. Characterization of changes in antigenic configuration during developmental cycle of Tilletia indica by these antibodies could prove to be useful in identification of developmentally related and virulence marker(s).

  5. Well staged

    Energy Technology Data Exchange (ETDEWEB)

    Budd, Godfrey

    2011-06-15

    Packers Plus Energy Services Inc. has commercially launched QuickFRAC, a multi-stage completition system which can fracture four to five isolated stages in one treatment and set up a record of 23-stage slickwater frac in less than 10 hours. It could take up to 40 days to do 100 fracture treatments with other systems. This technology makes it possible to distribute fluid at each port thanks to the limited entry system. In order to make multiple isolated stages within one treatment zone, each zone includes multiple QuickPORT sleeves with packers on either side. The other technology which made this possible is the repeater port system, it allows them to perform more frac stages. This technology could be useful in the future since the need for stages will be doubling soon with microdarcy shale oil extraction which is more difficult than gas.

  6. A single point in protein trafficking by Plasmodium falciparum determines the expression of major antigens on the surface of infected erythrocytes targeted by human antibodies.

    Science.gov (United States)

    Chan, Jo-Anne; Howell, Katherine B; Langer, Christine; Maier, Alexander G; Hasang, Wina; Rogerson, Stephen J; Petter, Michaela; Chesson, Joanne; Stanisic, Danielle I; Duffy, Michael F; Cooke, Brian M; Siba, Peter M; Mueller, Ivo; Bull, Peter C; Marsh, Kevin; Fowkes, Freya J I; Beeson, James G

    2016-11-01

    Antibodies to blood-stage antigens of Plasmodium falciparum play a pivotal role in human immunity to malaria. During parasite development, multiple proteins are trafficked from the intracellular parasite to the surface of P. falciparum-infected erythrocytes (IEs). However, the relative importance of different proteins as targets of acquired antibodies, and key pathways involved in trafficking major antigens remain to be clearly defined. We quantified antibodies to surface antigens among children, adults, and pregnant women from different malaria-exposed regions. We quantified the importance of antigens as antibody targets using genetically engineered P. falciparum with modified surface antigen expression. Genetic deletion of the trafficking protein skeleton-binding protein-1 (SBP1), which is involved in trafficking the surface antigen PfEMP1, led to a dramatic reduction in antibody recognition of IEs and the ability of human antibodies to promote opsonic phagocytosis of IEs, a key mechanism of parasite clearance. The great majority of antibody epitopes on the IE surface were SBP1-dependent. This was demonstrated using parasite isolates with different genetic or phenotypic backgrounds, and among antibodies from children, adults, and pregnant women in different populations. Comparisons of antibody reactivity to parasite isolates with SBP1 deletion or inhibited PfEMP1 expression suggest that PfEMP1 is the dominant target of acquired human antibodies, and that other P. falciparum IE surface proteins are minor targets. These results establish SBP1 as part of a critical pathway for the trafficking of major surface antigens targeted by human immunity, and have key implications for vaccine development, and quantifying immunity in populations.

  7. Antigen-specific immune reactions to ischemic stroke

    Directory of Open Access Journals (Sweden)

    Xabier eUrra

    2014-09-01

    Full Text Available Brain proteins are detected in the CSF and blood of stroke patients and their concentration is related to the extent of brain damage. Antibodies against brain antigens develop after stroke, suggesting a humoral immune response to the brain injury. Furthermore, induced immune tolerance is beneficial in animal models of cerebral ischemia. The presence of circulating T cells sensitized against brain antigens, and antigen presenting cells (APCs carrying brain antigens in draining lymphoid tissue of stroke patients support the notion that stroke might induce antigen-specific immune responses. After stroke, brain proteins that are normally hidden from the periphery, inflammatory mediators, and danger signals can exit the brain through several efflux routes. They can reach the blood after leaking out of the damaged blood-brain barrier or following the drainage of interstitial fluid to the dural venous sinus, or reach the cervical lymph nodes through the nasal lymphatics following CSF drainage along the arachnoid sheaths of nerves across the nasal submucosa. The route and mode of access of brain antigens to lymphoid tissue could influence the type of response. Central and peripheral tolerance prevents autoimmunity, but the actual mechanisms of tolerance to brain antigens released into the periphery in the presence of inflammation, danger signals, and APCs, are not fully characterized. Stroke does not systematically trigger autoimmunity, but under certain circumstances, such as pronounced systemic inflammation or infection, autoreactive T cells could escape the tolerance controls. Further investigation is needed to elucidate whether antigen-specific immune events could underlie neurological complications impairing stroke outcome.

  8. Trading stages

    DEFF Research Database (Denmark)

    Steiner, Uli; Tuljapurkar, Shripad; Coulson, Tim

    2012-01-01

    Interest in stage-and age structured models has recently increased because they can describe quantitative traits such as size that are left out of age-only demography. Available methods for the analysis of effects of vital rates on lifespan in stage-structured models have not been widely applied ...... examples. Much of our approach relies on trading of time and mortality risk in one stage for time and risk in others. Our approach contributes to the new framework of the study of age- and stage-structured biodemography....

  9. Relationship between prostate specific antigen related variables and Gleason score and clinical stage of prostate cancer%前列腺特异性抗原相关变数与前列腺癌Gleason评分及临床分期的关系

    Institute of Scientific and Technical Information of China (English)

    王道元; 乔保平; 孙如坤; 辛航; 王雷阳

    2012-01-01

    目的:探讨前列腺特异性抗原(PSA)相关变数与前列腺癌病理分级及临床分期的关系.方法:回顾性分析125例经穿刺活检病理证实为前列腺癌患者的临床资料,采用Spearman相关分析探讨游离PSA(FPSA)、FPSA比率(F/TPSA)、PSA密度(PSAD)与Gleason评分及临床分期的关系.结果:FPSA与前列腺癌Gleason评分呈正相关(rS=0.499,P<0.001),与临床分期呈负相关(rS=-0.300,P<0.001);PSAD与前列腺癌Gleason评分呈正相关(rS=0.616,P<0.001),与临床分期无相关性(rS=-0.128,P=0.155);F/TPSA与前列腺癌Gleason评分呈弱相关(rS=0.182,P=0.042),与临床分期呈负相关(rS=-0.417,P<0.001).结论:FPSA可作为前列腺癌病理分级和临床分期的参考指标;而PSAD可作为前列腺癌病理分级的参考指标,F/TPSA可作为前列腺癌临床分期的参考指标.%Aim : To explore the relationship between prostate specific antigen related variables and Gleason score and clinical stage in patients with prostate cancer. Methods: The clinical data from 125 cases of prostate cancer diagnosed by biopsies were collected, and the correlation of FPSA , F/TPSA and PSAD with Gleason score and clinical stage was analyzed. Results: FPSA was positively correlated with Gleason score ( rs =0. 499 , P < 0. 001 ) , but negatively correlated with clinical stage ( rs = - 0. 300 , P < 0. 001) for prostate cancer patients ; PSAD was also positively correlated with Gleason score ( rs = 0. 616 ,P < 0. 001 ) , but not correlated with clinical stage ( rs = - 0. 128 ,P = 0. 155 ) for prostate cancer patients; F/TPSA was negatively correlated with clinical stage ( rs = -0.417,P<0. 001 ) , but weakly correlated with Gleason score ( rs = 0. 182 ,P = 0. 042) for prostate cancer patients. Conclusion ;FPSA could be used as a reference index in pathological grading and clinical staging for prostate cancer patients ; PSAD could be used as a reference index in pathological grading and F/TPSA could be used as a reference

  10. Plasmodium vivax antigen discovery based on alpha-helical coiled coil protein motif.

    Directory of Open Access Journals (Sweden)

    Nora Céspedes

    Full Text Available Protein α-helical coiled coil structures that elicit antibody responses, which block critical functions of medically important microorganisms, represent a means for vaccine development. By using bioinformatics algorithms, a total of 50 antigens with α-helical coiled coil motifs orthologous to Plasmodium falciparum were identified in the P. vivax genome. The peptides identified in silico were chemically synthesized; circular dichroism studies indicated partial or high α-helical content. Antigenicity was evaluated using human sera samples from malaria-endemic areas of Colombia and Papua New Guinea. Eight of these fragments were selected and used to assess immunogenicity in BALB/c mice. ELISA assays indicated strong reactivity of serum samples from individuals residing in malaria-endemic regions and sera of immunized mice, with the α-helical coiled coil structures. In addition, ex vivo production of IFN-γ by murine mononuclear cells confirmed the immunogenicity of these structures and the presence of T-cell epitopes in the peptide sequences. Moreover, sera of mice immunized with four of the eight antigens recognized native proteins on blood-stage P. vivax parasites, and antigenic cross-reactivity with three of the peptides was observed when reacted with both the P. falciparum orthologous fragments and whole parasites. Results here point to the α-helical coiled coil peptides as possible P. vivax malaria vaccine candidates as were observed for P. falciparum. Fragments selected here warrant further study in humans and non-human primate models to assess their protective efficacy as single components or assembled as hybrid linear epitopes.

  11. Cancer and blood coagulation.

    Science.gov (United States)

    Boccaccio, C; Medico, E

    2006-05-01

    In human patients, blood coagulation disorders often associate with cancer, even in its early stages. Recently, in vitro and in vivo experimental models have shown that oncogene expression, or inactivation of tumour suppressor genes, upregulate genes that control blood coagulation. These studies suggest that activation of blood clotting, leading to peritumoral fibrin deposition, is instrumental in cancer development. Fibrin can indeed build up a provisional matrix, supporting the invasive growth of neoplastic tissues and blood vessels. Interference with blood coagulation can thus be considered as part of a multifaceted therapeutic approach to cancer.

  12. Identification, characterization and antigenicity of the Plasmodium vivax rhoptry neck protein 1 (PvRON1

    Directory of Open Access Journals (Sweden)

    Patarroyo Manuel E

    2011-10-01

    Full Text Available Abstract Background Plasmodium vivax malaria remains a major health problem in tropical and sub-tropical regions worldwide. Several rhoptry proteins which are important for interaction with and/or invasion of red blood cells, such as PfRONs, Pf92, Pf38, Pf12 and Pf34, have been described during the last few years and are being considered as potential anti-malarial vaccine candidates. This study describes the identification and characterization of the P. vivax rhoptry neck protein 1 (PvRON1 and examine its antigenicity in natural P. vivax infections. Methods The PvRON1 encoding gene, which is homologous to that encoding the P. falciparum apical sushi protein (ASP according to the plasmoDB database, was selected as our study target. The pvron1 gene transcription was evaluated by RT-PCR using RNA obtained from the P. vivax VCG-1 strain. Two peptides derived from the deduced P. vivax Sal-I PvRON1 sequence were synthesized and inoculated in rabbits for obtaining anti-PvRON1 antibodies which were used to confirm the protein expression in VCG-1 strain schizonts along with its association with detergent-resistant microdomains (DRMs by Western blot, and its localization by immunofluorescence assays. The antigenicity of the PvRON1 protein was assessed using human sera from individuals previously exposed to P. vivax malaria by ELISA. Results In the P. vivax VCG-1 strain, RON1 is a 764 amino acid-long protein. In silico analysis has revealed that PvRON1 shares essential characteristics with different antigens involved in invasion, such as the presence of a secretory signal, a GPI-anchor sequence and a putative sushi domain. The PvRON1 protein is expressed in parasite's schizont stage, localized in rhoptry necks and it is associated with DRMs. Recombinant protein recognition by human sera indicates that this antigen can trigger an immune response during a natural infection with P. vivax. Conclusions This study shows the identification and characterization of

  13. Lamivudinbehandling af en hepatitis Bs- antigen-positiv patient med reaktiv artritis

    DEFF Research Database (Denmark)

    Borup, Christian; Siboni, Anders

    2008-01-01

    A 46-year-old man who was HBs antigen positive since childhood had painful talocrural arthritis that was considered re-active to HBs antigen. Lamivudine treatment was started and HBV-DNA disappeared from the blood, and the joint swellings disappeared. HBe antibody disappeared after eight months. ...

  14. Molecular characterization of antigen-peptide pulsed dendritic cells: immature dendritic cells develop a distinct molecular profile when pulsed with antigen peptide.

    Directory of Open Access Journals (Sweden)

    Amy X Yang

    Full Text Available As dendritic cells (DCs are the most potent professional antigen-presenting cells, they are being tested as cancer vaccines for immunotherapy of established cancers. Although numerous studies have characterized DCs by their phenotype and function, few have identified potential molecular markers of antigen presentation prior to vaccination of host. In this study we generated pre-immature DC (piDC, immature DC (iDC, and mature DC (mDC from human peripheral blood monocytes (PBMC obtained from HLA-A2 healthy donors, and pulsed them with human papillomavirus E7 peptide (p11-20, a class I HLA-A2 binding antigen. We then characterized DCs for cell surface phenotype and gene expression profile by microarray technology. We identified a set of 59 genes that distinguished three differentiation stages of DCs (piDC, iDC and mDC. When piDC, iDC and mDC were pulsed with E7 peptide for 2 hrs, the surface phenotype did not change, however, iDCs rather than mDCs showed transcriptional response by up-regulation of a set of genes. A total of 52 genes were modulated in iDC upon antigen pulsing. Elongation of pulse time for iDCs to 10 and 24 hrs did not significantly bring further changes in gene expression. The E7 peptide up-modulated immune response (KPNA7, IGSF6, NCR3, TREM2, TUBAL3, IL8, NFKBIA, pro-apoptosis (BTG1, SEMA6A, IGFBP3 and SRGN, anti-apoptosis (NFKBIA, DNA repair (MRPS11, RAD21, TXNRD1, and cell adhesion and cell migration genes (EPHA1, PGF, IL8 and CYR61 in iDCs. We confirmed our results by Q-PCR analysis. The E7 peptide but not control peptide (PADRE induced up-regulation of NFKB1A gene only in HLA-A2 positive iDCs and not in HLA-A2 negative iDCs. These results suggest that E7 up-regulation of genes is specific and HLA restricted and that these genes may represent markers of antigen presentation and help rapidly assess the quality of dendritic cells prior to administration to the host.

  15. The chicken erythrocyte-specific MHC antigen. Characterization and purification of the B-G antigen by monoclonal antibodies

    DEFF Research Database (Denmark)

    Salomonsen, J; Skjødt, K; Crone, M

    1987-01-01

    Mouse monoclonal antibodies with B-G antigen (major histocompatibility complex class IV) specificity were obtained after immunization with erythrocytes or partially purified B-G antigen. The specificities of the hybridoma antibodies were determined by precipitation of B-G antigens from 125I...... of purified B-G antigen with Endoglycosidase-F or trifluoromethanesulfonic acid. Two-way sequential immunoprecipitation studies of erythrocyte membrane extracts with anti-B-G alloantisera and monoclonal antibodies revealed only one population of B-G molecules. Pulse-chase experiments have shown B...... from the affinity chromatography step was 3-4 micrograms B-G/ml blood, calculated from Coomassie-stained SDS-PAGE of B-G using ovalbumin standards. The monoclonal antibodies were also used to identify the B-G (class IV) precipitation arc in crossed immunoelectrophoresis. No common precipitate...

  16. Taenia taeniaeformis: immunoprecipitation analysis of the protein antigens of oncospheres and larvae.

    Science.gov (United States)

    Bowtell, D D; Mitchell, G F; Anders, R F; Lightowlers, M W; Rickard, M D

    1983-12-01

    Biosynthetically or exogenously labeled proteins and immunoprecipitated protein antigens of established 28-day-old larvae of Taenia taeniaeformis were compared with proteins and antigens of infective oncospheres using single and two-dimensional gel electrophoresis. Immunoprecipitation was carried out using sera from infected mice and mouse antisera raised to larvae or oncospheres, and emphasis was placed on identifying antigens common to both oncospheres and larvae. Two major larval antigens of Mr 40,000 and 200,000, designated Tt40 and Tt200, are common to somatic larval preparations and oncospheres. Additionally, two major oncosphere antigens of Mr 55,000 and 60,000, designated Tt55 and Tt60, are also present in larval excretory and secretory (i.e., ES or exoantigen) products. Information obtained from these immunoprecipitation analyses will facilitate isolation and production of common as well as stage-specific protein antigens in the development of defined-antigen vaccines in this model system of cysticercosis.

  17. 2株间日疟原虫18S rDNA的克隆及其同源性分析%Cloning and homology analysis of blood stage 18S rDNA of two Plasmodium vivax isolates

    Institute of Scientific and Technical Information of China (English)

    高世同; 李晓恒; 耿艺介; 黄达娜; 谢旭; 梅树江; 张仁利

    2013-01-01

    目的 克隆间日疟原虫河南分离株与湖北分离株红内期18S rDNA,并进行同源性分析.方法 采用PCR方法从间日疟患者血样DNA中扩增间日疟原虫18S rDNA,纯化后与pGEM-Teasy质粒连接,转化大肠埃希氏菌JM109;阳性克隆质粒经双酶切鉴定后,进行序列测定,采用BLAST和MEGA4生物软件分析同源性. 结果 间日疟原虫18S rDNA扩增片段大小为998 bp;阳性克隆重组质粒经双酶切鉴定,与预期结果相符;序列测定结果显示,河南、湖北2分离株间日疟原虫18S rDNA序列完全相同,与GenBank中报道的12株间日疟原虫相同序列进行比对,其同源性均大于99%;用邻位连接法(neigh-bor-joining,NJ)和非加权组平均法(UPGMA)2种方法构建系统发生树发现,河南分离株、湖北分离株与间日疟原虫X13926.1株遗传距离小,同属一个分支.结论 克隆了间日疟原虫河南与湖北分离株红内期18S rDNA,该基因序列在不同地理株间遗传稳定.%Objective To clone and homology analyze the sequences of blood stage 18S rRNA-encoding gene fragment of two P.vivax isolates from Henan and Hubei provinces in China.Methods The 18S rDNA fragments were amplified by PCR from the DNA extracted from two P.vivax infection blood samples.After purification,the gene fragments were ligated with plasmid pGEM-Teasy to construct recombinant plasmids,and transformed into E.coli JM109.Positive clones were identified by double enzymes digestion methods.The sequences of inserted 18S rDNA fragments were finally determined and analyzed with BLAST and MEGA4 biological software.Results The amplified 18S rDNA fragments of two isolates were about 998 bp in length,and the 18S rDNA sequence of Henan isolate was same as that of Hubei isolate.As aligned with the corresponding sequences of twelve P.vivax strains deposited in the GenBank database,the indentity of nucleotides was more than 99% respectively.Based on the 18S rDNA sequence,phylogenetic analysis with

  18. Genetic diversity and antigenicity variation of Babesia bovis merozoite surface antigen-1 (MSA-1) in Thailand.

    Science.gov (United States)

    Tattiyapong, Muncharee; Sivakumar, Thillaiampalam; Takemae, Hitoshi; Simking, Pacharathon; Jittapalapong, Sathaporn; Igarashi, Ikuo; Yokoyama, Naoaki

    2016-07-01

    Babesia bovis, an intraerythrocytic protozoan parasite, causes severe clinical disease in cattle worldwide. The genetic diversity of parasite antigens often results in different immune profiles in infected animals, hindering efforts to develop immune control methodologies against the B. bovis infection. In this study, we analyzed the genetic diversity of the merozoite surface antigen-1 (msa-1) gene using 162 B. bovis-positive blood DNA samples sourced from cattle populations reared in different geographical regions of Thailand. The identity scores shared among 93 msa-1 gene sequences isolated by PCR amplification were 43.5-100%, and the similarity values among the translated amino acid sequences were 42.8-100%. Of 23 total clades detected in our phylogenetic analysis, Thai msa-1 gene sequences occurred in 18 clades; seven among them were composed of sequences exclusively from Thailand. To investigate differential antigenicity of isolated MSA-1 proteins, we expressed and purified eight recombinant MSA-1 (rMSA-1) proteins, including an rMSA-1 from B. bovis Texas (T2Bo) strain and seven rMSA-1 proteins based on the Thai msa-1 sequences. When these antigens were analyzed in a western blot assay, anti-T2Bo cattle serum strongly reacted with the rMSA-1 from T2Bo, as well as with three other rMSA-1 proteins that shared 54.9-68.4% sequence similarity with T2Bo MSA-1. In contrast, no or weak reactivity was observed for the remaining rMSA-1 proteins, which shared low sequence similarity (35.0-39.7%) with T2Bo MSA-1. While demonstrating the high genetic diversity of the B. bovis msa-1 gene in Thailand, the present findings suggest that the genetic diversity results in antigenicity variations among the MSA-1 antigens of B. bovis in Thailand.

  19. The Indian blood group system.

    Science.gov (United States)

    Xu, Q

    2011-01-01

    The Indian blood group system (ISBT: IN/023) consists of two antithetical antigens: In(a) (IN1), which is present in approximately 10 percent of some Arab populations and in 3 percent of Bombay Indians, and its allelic antigen In(b) (IN2), an antigen of high incidence in all populations. In 2007, two new high-incidence antigens were identified as belonging to the IN blood group system, namely IN3 (INFI) and IN4 (INJA). The antigens in this system are located on CD44, a single-pass membrane glycoprotein that is encoded by the CD44 gene on chromosome 11 at position p13. The biologic function of CD44 is as a leukocyte homing receptor and cellular adhesion molecule. The In(a) and In(b) polymorphism represents a 252G>C substitution of CD44, encoding R46P, and lack of IN3 and IN4 results from homozygosity for mutations encoding H85Q and T163R in the CD44 gene. The high-frequency antigen AnWj (901009) has not been assigned to the Indian system, but either is located on an isoform of CD44 or is closely associated with it.

  20. International Society of Blood Transfusion Working Party on red cell immunogenetics and blood group terminology: Cancun report (2012).

    Science.gov (United States)

    Storry, J R; Castilho, L; Daniels, G; Flegel, W A; Garratty, G; de Haas, M; Hyland, C; Lomas-Francis, C; Moulds, J M; Nogues, N; Olsson, M L; Poole, J; Reid, M E; Rouger, P; van der Schoot, E; Scott, M; Tani, Y; Yu, L-C; Wendel, S; Westhoff, C; Yahalom, V; Zelinski, T

    2014-07-01

    The International Society of Blood Transfusion Working Party on red cell immunogenetics and blood group terminology convened during the International congress in Cancun, July 2012. This report details the newly identified antigens in existing blood group systems and presents three new blood group systems.

  1. Pediatric patient with Bombay blood group: A rare case report

    Directory of Open Access Journals (Sweden)

    Sudeshna Bhar (Kundu

    2015-01-01

    Full Text Available Bombay blood group is a rare blood group in which there is the absence of H antigen and presence of anti-H antibodies. At the time of blood grouping, this blood group mimics O blood group due to the absence of H antigen, but it shows incompatibility with O group blood during cross matching. Serum grouping or reverse grouping are essential for confirmation of the diagnosis. Patients carrying this blood group can receive blood only from a person with this blood group. Reported cases of anesthesia in the pediatric patient with Bombay blood group are relatively rare. Here, we present successful anesthetic management along with intraoperative blood transfusion in a pediatric patient with Bombay blood group posted for ovarian cystectomy.

  2. Pediatric patient with Bombay blood group: A rare case report.

    Science.gov (United States)

    Bhar Kundu, Sudeshna; De, Anisha; Saha, Anindita; Bhattacharyya, Chiranjib

    2015-01-01

    Bombay blood group is a rare blood group in which there is the absence of H antigen and presence of anti-H antibodies. At the time of blood grouping, this blood group mimics O blood group due to the absence of H antigen, but it shows incompatibility with O group blood during cross matching. Serum grouping or reverse grouping are essential for confirmation of the diagnosis. Patients carrying this blood group can receive blood only from a person with this blood group. Reported cases of anesthesia in the pediatric patient with Bombay blood group are relatively rare. Here, we present successful anesthetic management along with intraoperative blood transfusion in a pediatric patient with Bombay blood group posted for ovarian cystectomy.

  3. Staging atmospheres

    DEFF Research Database (Denmark)

    Bille, Mikkel; Bjerregaard, Peter; Sørensen, Tim Flohr

    2015-01-01

    The article introduces the special issue on staging atmospheres by surveying the philosophical, political and anthropological literature on atmosphere, and explores the relationship between atmosphere, material culture, subjectivity and affect. Atmosphere seems to occupy one of the classic...... localities of tensions between matter and the immaterial, the practical and the ideal, and subject and object. In the colloquial language there can, moreover, often seem to be something authentic or genuine about atmosphere, juxtaposing it to staging, which is implied to be something simulated or artificial....... This introduction seeks to outline how a number of scholars have addressed the relationship between staged atmospheres and experience, and thus highlight both the philosophical, social and political aspects of atmospheres...

  4. Cancer testis antigen and immunotherapy

    Directory of Open Access Journals (Sweden)

    Krishnadas DK

    2013-04-01

    Full Text Available Deepa Kolaseri Krishnadas, Fanqi Bai, Kenneth G Lucas Department of Pediatrics, Division of Hematology/Oncology, University of Louisville, KY, USA Abstract: The identification of cancer testis (CT antigens has been an important advance in determining potential targets for cancer immunotherapy. Multiple previous studies have shown that CT antigen vaccines, using both peptides and dendritic cell vaccines, can elicit clinical and immunologic responses in several different tumors. This review details the expression of melanoma antigen family A, 1 (MAGE-A1, melanoma antigen family A, 3 (MAGE-A3, and New York esophageal squamous cell carcinoma-1 (NY-ESO-1 in various malignancies, and presents our current understanding of CT antigen based immunotherapy. Keywords: cancer testis antigens, immunotherapy, vaccine

  5. Primary immunization-like response without hepatitis following transfusion of HBeAg-positive blood

    DEFF Research Database (Denmark)

    Gluud, C; Aldershvile, J; Kryger, P;

    1983-01-01

    An accidental transfusion of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) positive whole blood was given to a 19-yr-old male, bleeding after tonsillectomy. Serum obtained from the patient before the transfusion revealed no hepatitis B antigens or antibodies. After...... the transfusion the patient became HBsAg-positive, cleared this antigen and developed antibodies to both HBsAg and HBeAg. The transfusion blood was positive for total antibody and IgM antibody to hepatitis B core antigen (HBcAg). The patient's blood became positive for these antibodies after the transfusion...

  6. Effect of perioperative blood transfusions on long term graft outcomes in renal transplant patients.

    LENUS (Irish Health Repository)

    O'Brien, Frank J

    2012-06-01

    It is established that blood transfusions will promote sensitization to human leucocyte antigen (HLA) antigens, increase time spent waiting for transplantation and may lead to higher rates of rejection. Less is known about how perioperative blood transfusion influence patient and graft outcome. This study aims to establish if there is an association between perioperative blood transfusion and graft or patient survival.

  7. Intranasal sensitization with Blomia Tropicalis antigens induces allergic responses in mice characterized by elevated antigen-specific and non-specific serum ige and peripheral blood eosinophil counts Sensibilização intranasal com antígenos de Blomia tropicalis induz respostas alérgicas em camundos caracterizadas pela elevada contagem de soro IgE antígeno-específico e não específico e de eosinófilos no sangue periférico

    Directory of Open Access Journals (Sweden)

    Fumiko Takeda

    2004-02-01

    Full Text Available In order to evaluate the potential allergenicity of Blomia tropicalis (Bt antigen, IgE production of both specific and non-specific for Bt antigen was monitored in BALB/c mice after exposure to the antigen by nasal route. It was evidenced that B. tropicalis contains a functional allergen in its components. The allergenic components, however, when administered intranasally without any adjuvant, did not function to induce IgE response within a short period. On the other hand, intranasal inoculation of Bt antigens augmented serum IgE responses in mice pretreated by a subcutaneous priming injection of the same antigens. Inoculation of Bt antigen without subcutaneous priming injections induced IgE antibody production only when the antigen was continuously administered for a long period of over 24 weeks. Even when the priming injection was absent, the Bt antigen inoculated with cholera toxin (CT as a mucosal adjuvant also significantly augmented the Bt antigen-specific IgE responses depending on the dose of CT co-administered. The present study also demonstrated that Bt antigen/CT-inoculated mice showed increased non-specific serum IgE level and peripheral blood eosinophil rates without noticeable elevations of the total leukocyte counts. The immunoblot analysis demonstrated 5 main antigenic components reactive to IgE antibodies induced. These components at about 44-64 kDa position were considered to be an important candidate antigen for diagnosis of the mite-related allergy.Para avaliar a capacidade alergizante do antígeno da Blomia tropicalis (Bt a produção de IgE específica e não específica a antígeno Bt foi monitorada em camundongos BALB/c após exposição ao antígeno por via nasal. Foi evidenciado que Bt contem um alérgeno funcional em seus componentes. Os componentes alergênicos entretanto, quando administrados por via intra-nasal, sem qualquer adjuvante, não induzem resposta IgE durante um pequeno período. Por outro lado, a inocula

  8. Blood smear

    Science.gov (United States)

    ... some red blood cells shaped like spheres ( hereditary spherocytosis ) Increased breakdown of RBCs Presence of RBCs with ... normal Red blood cells, elliptocytosis Red blood cells, spherocytosis Acute lymphocytic leukemia - photomicrograph Red blood cells, multiple ...

  9. Blood culture

    Science.gov (United States)

    Culture - blood ... A blood sample is needed . The site where blood will be drawn is first cleaned with an antiseptic such ... organism from the skin getting into (contaminating) the blood sample and causing a false-positive result (see ...

  10. Blood Thinners

    Science.gov (United States)

    If you have some kinds of heart or blood vessel disease, or if you have poor blood flow to your brain, your doctor may recommend that you take a blood thinner. Blood thinners reduce the risk of heart ...

  11. Blood transfusions

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000431.htm Blood transfusions To use the sharing features on this ... several sources of blood which are described below. Blood From the Public (Volunteer Blood Donation) The most ...

  12. Low cost tuberculosis vaccine antigens in capsules: expression in chloroplasts, bio-encapsulation, stability and functional evaluation in vitro.

    Directory of Open Access Journals (Sweden)

    Priya Saikumar Lakshmi

    Full Text Available Tuberculosis (TB caused by Mycobacterium tuberculosis is one of the leading fatal infectious diseases. The development of TB vaccines has been recognized as a major public health priority by the World Health Organization. In this study, three candidate antigens, ESAT-6 (6 kDa early secretory antigenic target and Mtb72F (a fusion polyprotein from two TB antigens, Mtb32 and Mtb39 fused with cholera toxin B-subunit (CTB and LipY (a cell wall protein were expressed in tobacco and/or lettuce chloroplasts to facilitate bioencapsulation/oral delivery. Site-specific transgene integration into the chloroplast genome was confirmed by Southern blot analysis. In transplastomic leaves, CTB fusion proteins existed in soluble monomeric or multimeric forms of expected sizes and their expression levels varied depending upon the developmental stage and time of leaf harvest, with the highest-level of accumulation in mature leaves harvested at 6PM. The CTB-ESAT6 and CTB-Mtb72F expression levels reached up to 7.5% and 1.2% of total soluble protein respectively in mature tobacco leaves. Transplastomic CTB-ESAT6 lettuce plants accumulated up to 0.75% of total leaf protein. Western blot analysis of lyophilized lettuce leaves stored at room temperature for up to six months showed that the CTB-ESAT6 fusion protein was stable and preserved proper folding, disulfide bonds and assembly into pentamers for prolonged periods. Also, antigen concentration per gram of leaf tissue was increased 22 fold after lyophilization. Hemolysis assay with purified CTB-ESAT6 protein showed partial hemolysis of red blood cells and confirmed functionality of the ESAT-6 antigen. GM1-binding assay demonstrated that the CTB-ESAT6 fusion protein formed pentamers to bind with the GM1-ganglioside receptor. The expression of functional Mycobacterium tuberculosis antigens in transplastomic plants should facilitate development of a cost-effective and orally deliverable TB booster vaccine with potential

  13. Low cost tuberculosis vaccine antigens in capsules: expression in chloroplasts, bio-encapsulation, stability and functional evaluation in vitro.

    Science.gov (United States)

    Lakshmi, Priya Saikumar; Verma, Dheeraj; Yang, Xiangdong; Lloyd, Bethany; Daniell, Henry

    2013-01-01

    Tuberculosis (TB) caused by Mycobacterium tuberculosis is one of the leading fatal infectious diseases. The development of TB vaccines has been recognized as a major public health priority by the World Health Organization. In this study, three candidate antigens, ESAT-6 (6 kDa early secretory antigenic target) and Mtb72F (a fusion polyprotein from two TB antigens, Mtb32 and Mtb39) fused with cholera toxin B-subunit (CTB) and LipY (a cell wall protein) were expressed in tobacco and/or lettuce chloroplasts to facilitate bioencapsulation/oral delivery. Site-specific transgene integration into the chloroplast genome was confirmed by Southern blot analysis. In transplastomic leaves, CTB fusion proteins existed in soluble monomeric or multimeric forms of expected sizes and their expression levels varied depending upon the developmental stage and time of leaf harvest, with the highest-level of accumulation in mature leaves harvested at 6PM. The CTB-ESAT6 and CTB-Mtb72F expression levels reached up to 7.5% and 1.2% of total soluble protein respectively in mature tobacco leaves. Transplastomic CTB-ESAT6 lettuce plants accumulated up to 0.75% of total leaf protein. Western blot analysis of lyophilized lettuce leaves stored at room temperature for up to six months showed that the CTB-ESAT6 fusion protein was stable and preserved proper folding, disulfide bonds and assembly into pentamers for prolonged periods. Also, antigen concentration per gram of leaf tissue was increased 22 fold after lyophilization. Hemolysis assay with purified CTB-ESAT6 protein showed partial hemolysis of red blood cells and confirmed functionality of the ESAT-6 antigen. GM1-binding assay demonstrated that the CTB-ESAT6 fusion protein formed pentamers to bind with the GM1-ganglioside receptor. The expression of functional Mycobacterium tuberculosis antigens in transplastomic plants should facilitate development of a cost-effective and orally deliverable TB booster vaccine with potential for long

  14. Nanovaccines for Malaria Using Plasmodium falciparum Antigen Pfs25 Attached Gold Nanoparticles

    OpenAIRE

    Kumar, Rajesh; Ray, Paresh C; Datta, Dibyadyuti; Bansal, Geetha P.; Angov, Evelina; Kumar, Nirbhay

    2015-01-01

    Malaria transmission-blocking vaccines (TBV) targeting sexual stages of the parasite represent an ideal intervention to reduce the burden of the disease and eventual elimination at the population level in endemic regions. Immune responses against sexual stage antigens impair the development of parasite inside the mosquitoes. Target antigens identified in Plasmodium falciparum include surface proteins Pfs230 and Pfs48/45 in male and female gametocytes and Pfs25 expressed in zygotes and ookinet...

  15. Duffy blood group system and the malaria adaptation process in humans

    OpenAIRE

    Gledson Barbosa de Carvalho; Glauber Barbosa de Carvalho

    2011-01-01

    Malaria is an acute infectious disease caused by the protozoa of the genus Plasmodium. The antigens of the Duffy Blood Group System, in addition to incompatibilities in transfusions and hemolytic disease of the newborn, are of great interest in medicine due to their association with the invasion of red blood cells by the parasite Plasmodium vivax. For invasions to occur an interaction between the parasites and antigens of the Duffy Blood Group System is necessary. In Caucasians six antigens a...

  16. CpG oligodeoxynucleotides with crude parasite antigens reduce worm recovery in Opisthorchis viverrini infected hamsters.

    Science.gov (United States)

    Kaewraemruaen, Chamraj; Sermswan, Rasana W; Wongratanacheewin, Surasakdi

    2016-12-01

    Opisthorchis viverrini, a human liver fluke, is still an endemic parasitic infection in Thailand and nearly all countries in Southeast Asia. O. viverrini induces a chronic stage of infection in hamsters. During the first 2 weeks of infection, Th1 inducing cytokine, IL-12, increased but was down regulated in chronic infection. In this study it was found that unmethylated-CpG ODN (oligodeoxynucleotides) 1826 increased hamster mononuclear cell proliferation and stimulated IFN-γ production in vitro. The IFN-γ levels in hamster sera were significantly increased in hamsters injected with CpG ODN 1826 alone or plus crude somatic antigens (CSAg). Further investigation using the flow cytometer found that CD4(+)T cells and IFN-γ(+) CD4(+)T cells (Th1-like cells) in the hamster blood were significantly increased. The role of these cells in the protective responses in hamsters was evaluated by challenging with 25 metacercaria and observation for 3 months. The number of worms recovered was significantly reduced in the hamsters injected with CpG ODN 1826 with CSAg, but not in CpG ODN 1826 alone groups when compared to PBS control. The percent of reduction in hamsters against this parasite were 32.95% and 21.49% in the CpG ODN 1826 with CSAg and CpG ODN 1826 alone. This study indicates that CpG ODN 1826 plus parasite antigens elicit a Th1-like response that leads to the enhancement of worm reduction.

  17. HLA-antigen frequencies in patients with a Plummer-Vinson stricture.

    Science.gov (United States)

    Middleton, D; Logan, J S; Magennis, B P; Nelson, S D

    1978-09-01

    Factors of individual susceptibility seem to be involved in the occurrence of Plummer-Vinson stricture, which is a permanent stricture of the cervical esophagus associated with long continued iron deficiency. Fifty female patients with Plummer-Vinson stricture were HLA typed and the antigen frequencies were compared with those of 75 female blood donors from the same geographic area and of the same race. A comparison was also made with the HLA antigen frequencies of a group of 200 blood donors (75 female and 125