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Sample records for foetal antigen presenting

  1. Foetal antigen 2 (FA2) in the stromal reaction induced by breast carcinoma

    DEFF Research Database (Denmark)

    Rasmussen, H B; Teisner, B; Andersen, J A

    1992-01-01

    An indirect immunoperoxidase technique was used to examine the distribution of foetal antigen 2 (FA2), a recently described basement membrane (BM)-associated antigen, in invasive breast carcinoma (n = 34), fibroadenoma (n = 5) and normal breast tissue (n = 5), and to compare its distribution...... with that of laminin and collagen type IV. In normal breast tissue, FA2 was detected in the intralobular stroma as a broad band around acini and ducts, but was not present in the interlobular stroma. In areas of carcinoma in situ, FA2 was present diffusely around and in close contact with the glandular elements......, the staining being more intense than that found around normal glandular structures. Two distinct patterns of FA2 distribution were found in adenocarcinomas of the breast. In the fibroblast reaction type, fibroblast staining dominated, whilst in the stromal reaction type, intense and extensive staining...

  2. Apple-peel atresia presenting as foetal intestinal obstruction ...

    African Journals Online (AJOL)

    Apple-peel atresia or Type 3 jejuno-ileal atresia (JIA) is an uncommon cause of foetal intestinal obstruction. Bowel obstruction in the foetus is diagnosed on the prenatal ultrasonography only in 50% cases. We report a case in which foetal intestinal obstruction was diagnosed on prenatal ultrasonography. The child showed ...

  3. Improving external cephalic version for foetal breech presentation.

    Science.gov (United States)

    Zandstra, H; Mertens, H J M M

    2013-01-01

    If success rate of external cephalic version (ECV) increases, the rate of primary caesarean sections -declines. The aims of this retrospective cohort study were to evaluate the ECV and to identify factors associated with the success rate of ECV for breech presentation at term. The second aim of this study was to analyse the outcome of labour of all patients with a foetus in breech near term. All women with a foetus in breech near or at term were included. Logistic regression analyses were -performed to identify the association between patient characteristics and success rate of ECV. The overall rate of successful ECV's was 19%. Foetal and maternal complications after ECV were negligible. BMI, type of breech and amount of amniotic fluid were significantly correlated with a successful ECV. The rate of primary caesarean sections for the group of patients who underwent an ECV was lower than the rate in the group who did not (52.9% vs. 79.6%). The rate of spontaneous deliveries was increased after ECV (36% versus 12%). After successful ECV the rate of spontaneous deliveries was 75%; after unsuccessful ECV 26.8%. The overall rate of successful ECV was low (19%). BMI, type of breech and amount of amniotic fluid were significantly correlated with a successful ECV. The rate of primary caesarean sections was significantly lower in patients with ECV (52.9% versus 79.6%). The rate of spontaneous deliveries was significantly higher (36% -versus 12%).

  4. Apple-peel atresia presenting as foetal intestinal obstruction

    Directory of Open Access Journals (Sweden)

    Ashok Yadavrao Kshirsagar

    2011-01-01

    Full Text Available Apple-peel atresia or Type 3 jejuno-ileal atresia (JIA is an uncommon cause of foetal intestinal obstruction. Bowel obstruction in the foetus is diagnosed on the prenatal ultrasonography only in 50% cases. We report a case in which foetal intestinal obstruction was diagnosed on prenatal ultrasonography. The child showed signs of intestinal obstruction on day one after birth, for which an exploratory laparotomy was performed. Type 3 JIA was found for which resection of atretic segments with jejuno-ascending colon anastomosis was preformed.

  5. Presentation of lipid antigens to T cells.

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    Mori, Lucia; De Libero, Gennaro

    2008-04-15

    T cells specific for lipid antigens participate in regulation of the immune response during infections, tumor immunosurveillance, allergy and autoimmune diseases. T cells recognize lipid antigens as complexes formed with CD1 antigen-presenting molecules, thus resembling recognition of MHC-peptide complexes. The biophysical properties of lipids impose unique mechanisms for their delivery, internalization into antigen-presenting cells, membrane trafficking, processing, and loading of CD1 molecules. Each of these steps is controlled at molecular and celular levels and determines lipid immunogenicity. Lipid antigens may derive from microbes and from the cellular metabolism, thus allowing the immune system to survey a large repertoire of immunogenic molecules. Recognition of lipid antigens facilitates the detection of infectious agents and the initiation of responses involved in immunoregulation and autoimmunity. This review focuses on the presentation mechanisms and specific recognition of self and bacterial lipid antigens and discusses the important open issues.

  6. Antigen Cross-Presentation of Immune Complexes

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    Platzer, Barbara; Stout, Madeleine; Fiebiger, Edda

    2014-01-01

    The ability of dendritic cells (DCs) to cross-present tumor antigens has long been a focus of interest to physicians, as well as basic scientists, that aim to establish efficient cell-based cancer immune therapy. A prerequisite for exploiting this pathway for therapeutic purposes is a better understanding of the mechanisms that underlie the induction of tumor-specific cytotoxic T-lymphocyte (CTL) responses when initiated by DCs via cross-presentation. The ability of humans DC to perform cross-presentation is of utmost interest, as this cell type is a main target for cell-based immunotherapy in humans. The outcome of a cross-presentation event is guided by the nature of the antigen, the form of antigen uptake, and the subpopulation of DCs that performs presentation. Generally, CD8α+ DCs are considered to be the most potent cross-presenting DCs. This paradigm, however, only applies to soluble antigens. During adaptive immune responses, immune complexes form when antibodies interact with their specific epitopes on soluble antigens. Immunoglobulin G (IgG) immune complexes target Fc-gamma receptors on DCs to shuttle exogenous antigens efficiently into the cross-presentation pathway. This receptor-mediated cross-presentation pathway is a well-described route for the induction of strong CD8+ T cell responses. IgG-mediated cross-presentation is intriguing because it permits the CD8− DCs, which are commonly considered to be weak cross-presenters, to efficiently cross-present. Engaging multiple DC subtypes for cross-presentation might be a superior strategy to boost CTL responses in vivo. We here summarize our current understanding of how DCs use IgG-complexed antigens for the efficient induction of CTL responses. Because of its importance for human cell therapy, we also review the recent advances in the characterization of cross-presentation properties of human DC subsets. PMID:24744762

  7. Harnessing Dendritic Cells for Tumor Antigen Presentation

    Energy Technology Data Exchange (ETDEWEB)

    Nierkens, Stefan [Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein 28, Nijmegen 6525 GA (Netherlands); Janssen, Edith M., E-mail: edith.janssen@cchmc.org [Division of Molecular Immunology, Cincinnati Children' s Hospital Research Foundation, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229 (United States)

    2011-04-26

    Dendritic cells (DC) are professional antigen presenting cells that are crucial for the induction of anti-tumor T cell responses. As a consequence, research has focused on the harnessing of DCs for therapeutic interventions. Although current strategies employing ex vivo-generated and tumor-antigen loaded DCs have been proven feasible, there are still many obstacles to overcome in order to improve clinical trial successes and offset the cost and complexity of customized cell therapy. This review focuses on one of these obstacles and a pivotal step for the priming of tumor-specific CD8{sup +} and CD4{sup +} T cells; the in vitro loading of DCs with tumor antigens.

  8. A scoring system predicting the clinical course of CLPB defect based on the foetal and neonatal presentation of 31 patients.

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    Pronicka, Ewa; Ropacka-Lesiak, Mariola; Trubicka, Joanna; Pajdowska, Magdalena; Linke, Markus; Ostergaard, Elsebet; Saunders, Carol; Horsch, Sandra; van Karnebeek, Clara; Yaplito-Lee, Joy; Distelmaier, Felix; Õunap, Katrin; Rahman, Shamima; Castelle, Martin; Kelleher, John; Baris, Safa; Iwanicka-Pronicka, Katarzyna; Steward, Colin G; Ciara, Elżbieta; Wortmann, Saskia B

    2017-11-01

    Recently, CLPB deficiency has been shown to cause a genetic syndrome with cataracts, neutropenia, and 3-methylglutaconic aciduria. Surprisingly, the neurological presentation ranges from completely unaffected to patients with virtual absence of development. Muscular hypo- and hypertonia, movement disorder and progressive brain atrophy are frequently reported. We present the foetal, peri- and neonatal features of 31 patients, of which five are previously unreported, using a newly developed clinical severity scoring system rating the clinical, metabolic, imaging and other findings weighted by the age of onset. Our data are illustrated by foetal and neonatal videos. The patients were classified as having a mild (n = 4), moderate (n = 13) or severe (n = 14) disease phenotype. The most striking feature of the severe subtype was the neonatal absence of voluntary movements in combination with ventilator dependency and hyperexcitability. The foetal and neonatal presentation mirrored the course of disease with respect to survival (current median age 17.5 years in the mild group, median age of death 35 days in the severe group), severity and age of onset of all findings evaluated. CLPB deficiency should be considered in neonates with absence of voluntary movements, respiratory insufficiency and swallowing problems, especially if associated with 3-methylglutaconic aciduria, neutropenia and cataracts. Being an important differential diagnosis of hyperekplexia (exaggerated startle responses), we advise performing urinary organic acid analysis, blood cell counts and ophthalmological examination in these patients. The neonatal presentation of CLPB deficiency predicts the course of disease in later life, which is extremely important for counselling.

  9. Foetal and neonatal alloimmune thrombocytopaenia

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    Kaplan Cecile

    2006-10-01

    Full Text Available Abstract Foetal/neonatal alloimmune thrombocytopaenia (NAIT results from maternal alloimmunisation against foetal platelet antigens inherited from the father and different from those present in the mother, and usually presents as a severe isolated thrombocytopaenia in otherwise healthy newborns. The incidence has been estimated at 1/800 to 1/1 000 live births. NAIT has been considered to be the platelet counterpart of Rh Haemolytic Disease of the Newborn (RHD. Unlike RHD, NAIT can occur during a first pregnancy. The spectrum of the disease may range from sub-clinical moderate thrombocytopaenia to life-threatening bleeding in the neonatal period. Mildly affected infants may be asymptomatic. In those with severe thrombocytopaenia, the most common presentations are petechiae, purpura or cephalohaematoma at birth, associated with major risk of intracranial haemorrhage (up to 20% of reported cases, which leads to death or neurological sequelae. Alloimmune thrombocytopaenia is more often unexpected and is usually diagnosed after birth. Once suspected, the diagnosis is confirmed by demonstration of maternal antiplatelet alloantibodies directed against a paternal antigen inherited by the foetus/neonate. Post-natal management involves transfusion of platelets devoid of this antigen, and should not be delayed by biological confirmation of the diagnosis (once the diagnosis is suspected, especially in case of severe thrombocytopaenia. Prompt diagnosis and treatment are essential to reduce the chances of death and disability due to haemorrhage. Due to the high rate of recurrence and increased severity of the foetal thrombocytopaenia in successive pregnancies, antenatal therapy should be offered. However, management of high-risk pregnancies is still a matter of discussion.

  10. Antigen Presentation Keeps Trending in Immunotherapy Resistance.

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    Kalbasi, Anusha; Ribas, Antoni

    2018-04-19

    Through a gain-of-function kinome screen, MEX3B was identified as a mediator of resistance to T-cell immunotherapy not previously identified using CRISPR-based screens. MEX3B is a posttranscriptional regulator of HLA-A, validating the critical role of tumor-intrinsic antigen presentation in T-cell immunotherapy and indicating a new putative molecular target. Clin Cancer Res; 24(14); 1-3. ©2018 AACR. See related article by Huang et al., p. xxxx . ©2018 American Association for Cancer Research.

  11. Endothelial cells present antigens in vivo

    Directory of Open Access Journals (Sweden)

    Tellides George

    2004-03-01

    Full Text Available Abstract Background Immune recognition of vascular endothelial cells (EC has been implicated in allograft rejection, protection against pathogens, and lymphocyte recruitment. However, EC pervade nearly all tissues and predominate in none, complicating any direct test of immune recognition. Here, we examined antigen presentation by EC in vivo by testing immune responses against E. coli β-galactosidase (β-gal in two lines of transgenic mice that express β-gal exclusively in their EC. TIE2-lacZ mice express β-gal in all EC and VWF-lacZ mice express β-gal in heart and brain microvascular EC. Results Transgenic and congenic wild type FVB mice immunized with β-gal expression vector DNA or β-gal protein generated high titer, high affinity antisera containing comparable levels of antigen-specific IgG1 and IgG2a isotypes, suggesting equivalent activation of T helper cell subsets. The immunized transgenic mice remained healthy, their EC continued to express β-gal, and their blood vessels showed no histological abnormalities. In response to β-gal in vitro, CD4+ and CD8+ T cells from immunized transgenic and FVB mice proliferated, expressed CD25, and secreted IFN-γ. Infection with recombinant vaccinia virus encoding β-gal raised equivalent responses in transgenic and FVB mice. Hearts transplanted from transgenic mice into FVB mice continued to beat and the graft EC continued to express β-gal. These results suggested immunological ignorance of the transgene encoded EC protein. However, skin transplanted from TIE2-lacZ onto FVB mice lost β-gal+ EC and the hosts developed β-gal-specific antisera, demonstrating activation of host immune effector mechanisms. In contrast, skin grafted from TIE2-lacZ onto VWF-lacZ mice retained β-gal+ EC and no antisera developed, suggesting a tolerant host immune system. Conclusion Resting, β-gal+ EC in transgenic mice tolerize specific lymphocytes that would otherwise respond against β-gal expressed by EC within

  12. Subsequent pregnancy outcome after previous foetal death

    NARCIS (Netherlands)

    Nijkamp, J. W.; Korteweg, F. J.; Holm, J. P.; Timmer, A.; Erwich, J. J. H. M.; van Pampus, M. G.

    Objective: A history of foetal death is a risk factor for complications and foetal death in subsequent pregnancies as most previous risk factors remain present and an underlying cause of death may recur. The purpose of this study was to evaluate subsequent pregnancy outcome after foetal death and to

  13. Ultraviolet light-induced suppression of antigen presentation

    International Nuclear Information System (INIS)

    Spellman, C.W.; Tomasi, T.B.

    1983-01-01

    Ultraviolet (UV) light irradiation of animals results in the development of specific T suppressor cells that inhibit antitumor immune responses. It is thought that suppression may arise as a consequence of altered antigen presentation by UV-irradiated epidermal cells. This hypothesis is based on evidence demonstrating that specific lymphoid tissues from UV-irradiated hosts exhibit impaired antigen-presenting function and that animals cannot be contact sensitized when antigens are applied to a UV-irradiated skin site. Langerhans cells of the skin are likely candidates as targets of UV-induced defects in antigen presentation as they bear Fc and C3b receptors, express Ia antigens, are of bone marrow origin, and are capable of presenting antigen in vitro. We speculate on the possible clinical usefulness of UV-induced tolerance to specific antigens such as those encountered in monoclonal antibody therapy and tissue transplantation

  14. Dissecting antigen processing and presentation routes in dermal vaccination strategies

    NARCIS (Netherlands)

    Platteel, Anouk C M; Henri, Sandrine; Zaiss, Dietmar M; Sijts, Alice J A M

    2017-01-01

    The skin is an attractive site for vaccination due to its accessibility and presence of immune cells surveilling this barrier. However, knowledge of antigen processing and presentation upon dermal vaccination is sparse. In this study we determined antigen processing routes that lead to CD8(+) T cell

  15. Antigen processing and remodeling of the endosomal pathway: requirements for antigen cross-presentation.

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    Compeer, Ewoud Bernardus; Flinsenberg, Thijs Willem Hendrik; van der Grein, Susanna Geertje; Boes, Marianne

    2012-01-01

    Cross-presentation of endocytosed antigen as peptide/class I major histocompatibility complex complexes plays a central role in the elicitation of CD8(+) T cell clones that mediate anti-viral and anti-tumor immune responses. While it has been clear that there are specific subsets of professional antigen presenting cells capable of antigen cross-presentation, identification of mechanisms involved is still ongoing. Especially amongst dendritic cells (DC), there are specialized subsets that are highly proficient at antigen cross-presentation. We here present a focused survey on the cell biological processes in the endosomal pathway that support antigen cross-presentation. This review highlights DC-intrinsic mechanisms that facilitate the cross-presentation of endocytosed antigen, including receptor-mediated uptake, maturation-induced endosomal sorting of membrane proteins, dynamic remodeling of endosomal structures and cell surface-directed endosomal trafficking. We will conclude with the description of pathogen-induced deviation of endosomal processing, and discuss how immune evasion strategies pertaining endosomal trafficking may preclude antigen cross-presentation.

  16. Antigen processing and remodeling of the endosomal pathway: requirements for antigen cross-presentation.

    Directory of Open Access Journals (Sweden)

    Ewoud Bernardus Compeer

    2012-03-01

    Full Text Available The cross-presentation of endocytosed antigen as peptide/class I MHC complexes plays a central role in the elicitation of CD8+ T cell clones that mediate anti-viral and anti-tumor immune responses. While it has been clear that there are specific subsets of professional antigen presenting cells (APC capable of antigen cross-presentation, description of mechanisms involved is still ongoing. Especially amongst dendritic cells (DC, there are specialized subsets that are highly proficient at antigen cross-presentation. We here present a focused survey on the cell biological processes in the endosomal pathway that support antigen cross-presentation. This review highlight DC-intrinsic mechanisms that facilitate the cross-presentation of endocytosed antigen, including receptor-mediated uptake, recycling and maturation including the sorting of membrane proteins, dynamic remodeling of endosomal structures and cell-surface directed endosomal trafficking. We will conclude with description of pathogen-induced deviation of endosomal processing, and discuss how immune evasion strategies pertaining endosomal trafficking may preclude antigen cross-presentation.

  17. The Antigen Presenting Cells Instruct Plasma Cell Differentiation

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    Wei eXu

    2014-01-01

    Full Text Available The professional antigen presenting cells (APCs, including many subsets of dendritic cells and macrophages, not only mediate prompt but nonspecific response against microbes, but also bridge the antigen-specific adaptive immune response through antigen presentation. In the latter, typically activated B cells acquire cognate signals from T helper cells in the germinal center of lymphoid follicles to differentiate into plasma cells, which generate protective antibodies. Recent advances have revealed that many APC subsets provide not only signal 1 (the antigen, but also signal 2 to directly instruct the differentiation process of plasma cells in a T cell-independent manner. Herein, the different signals provided by these APC subsets to direct B cell proliferation, survival, class switching and terminal differentiation are discussed. We furthermore propose that the next generation of vaccines for boosting antibody response could be designed by targeting APCs.

  18. The antigen presenting cells instruct plasma cell differentiation.

    Science.gov (United States)

    Xu, Wei; Banchereau, Jacques

    2014-01-06

    The professional antigen presenting cells (APCs), including many subsets of dendritic cells and macrophages, not only mediate prompt but non-specific response against microbes, but also bridge the antigen-specific adaptive immune response through antigen presentation. In the latter, typically activated B cells acquire cognate signals from T helper cells in the germinal center of lymphoid follicles to differentiate into plasma cells (PCs), which generate protective antibodies. Recent advances have revealed that many APC subsets provide not only "signal 1" (the antigen), but also "signal 2" to directly instruct the differentiation process of PCs in a T-cell-independent manner. Herein, the different signals provided by these APC subsets to direct B cell proliferation, survival, class switching, and terminal differentiation are discussed. We furthermore propose that the next generation of vaccines for boosting antibody response could be designed by targeting APCs.

  19. Effective antigen presentation to helper T cells by human eosinophils.

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    Farhan, Ruhaifah K; Vickers, Mark A; Ghaemmaghami, Amir M; Hall, Andrew M; Barker, Robert N; Walsh, Garry M

    2016-12-01

    Although eosinophils are inflammatory cells, there is increasing attention on their immunomodulatory roles. For example, murine eosinophils can present antigen to CD4 + T helper (Th) cells, but it remains unclear whether human eosinophils also have this ability. This study determined whether human eosinophils present a range of antigens, including allergens, to activate Th cells, and characterized their expression of MHC class II and co-stimulatory molecules required for effective presentation. Human peripheral blood eosinophils purified from non-allergic donors were pulsed with the antigens house dust mite extract (HDM), Timothy Grass extract (TG) or Mycobacterium tuberculosis purified protein derivative (PPD), before co-culture with autologous CD4 + Th cells. Proliferative and cytokine responses were measured, with eosinophil expression of HLA-DR/DP/DQ and the co-stimulatory molecules CD40, CD80 and CD86 determined by flow cytometry. Eosinophils pulsed with HDM, TG or PPD drove Th cell proliferation, with the response strength dependent on antigen concentration. The cytokine responses varied with donor and antigen, and were not biased towards any particular Th subset, often including combinations of pro- and anti-inflammatory cytokines. Eosinophils up-regulated surface expression of HLA-DR/DP/DQ, CD80, CD86 and CD40 in culture, increases that were sustained over 5 days when incubated with antigens, including HDM, or the major allergens it contains, Der p I or Der p II. Human eosinophils can, therefore, act as effective antigen-presenting cells to stimulate varied Th cell responses against a panel of antigens including HDM, TG or PPD, an ability that may help to determine the development of allergic disease. © 2016 John Wiley & Sons Ltd.

  20. ONCOLYTIC VIRUS-MEDIATED REVERSAL OF IMPAIRED TUMOR ANTIGEN PRESENTATION

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    Shashi Ashok Gujar

    2014-04-01

    Full Text Available Anti-tumor immunity can eliminate existing cancer cells and also maintain a constant surveillance against possible relapse. Such an antigen-specific adaptive response begins when tumor-specific T cells become activated. T cell activation requires two signals on antigen presenting cells (APCs: antigen presentation through MHC molecules and co-stimulation. In the absence of one or both of these signals, T cells remain inactivated or can even become tolerized. Cancer cells and their associated microenvironment strategically hinder the processing and presentation of tumor antigens and consequently prevent the development of anti-tumor immunity. Many studies, however, demonstrate that interventions that overturn tumor-associated immune evasion mechanisms can establish anti-tumor immune responses of therapeutic potential. One such intervention is oncolytic virus (OV-based anti-cancer therapy. Here we discuss how OV-induced immunological events override tumor-associated antigen presentation impairment and promote appropriate T cell:APC interaction. Detailed understanding of this phenomenon is pivotal for devising the strategies that will enhance the efficacy of OV-based anti-cancer therapy by complementing its inherent oncolytic

  1. The systems biology of MHC class II antigen presentation

    NARCIS (Netherlands)

    Paul, Petra

    2012-01-01

    Major histocompatibility class II molecules (MHC class II) are one of the key regulators of adaptive immunity because of their specific expression by professional antigen presenting cells (APC). They present peptides derived from endocytosed material to T helper lymphocytes. Consequently, MHC class

  2. Intersection of autophagy with pathways of antigen presentation.

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    Patterson, Natalie L; Mintern, Justine D

    2012-12-01

    Traditionally, macroautophagy (autophagy) is viewed as a pathway of cell survival. Autophagy ensures the elimination of damaged or unwanted cytosolic components and provides a source of cellular nutrients during periods of stress. Interestingly, autophagy can also directly intersect with, and impact, other major pathways of cellular function. Here, we will review the contribution of autophagy to pathways of antigen presentation. The autophagy machinery acts to modulate both MHCI and MHCII antigen presentation. As such autophagy is an important participant in pathways that elicit host cell immunity and the elimination of infectious pathogens.

  3. Can resting B cells present antigen to T cells

    International Nuclear Information System (INIS)

    Ashwell, J.D.; DeFranco, A.L.; Paul, W.E.; Schwartz, R.H.

    1985-01-01

    Antigen stimulation of T lymphocytes can occur only in the presence of an antigen-presenting cell (APC). An ever-increasing number of cell types have been found to act as APCs; these include macrophages, splenic and lymph node dendritic cells, and Langerhans cells of the skin. Although activated B lymphocytes and B cell lymphomas are known to serve as APCs, it has been generally believed that resting B cells cannot perform this function. However, in recent studies the authors have found that resting B cells can indeed present soluble antigen to T cell clones as well as to antigen-primed T cells. The previous difficulty in demonstrating this activity can be explained by the finding that, in contrast to macrophages and dendritic cells, the antigen-presenting ability of resting B cells is very radiosensitive. Macrophages are usually irradiated with 2000-3300 rads to prevent them from incorporating [ 3 H]thymidine in the T cell proliferation assay. Resting B cells, however, begin to lose presenting function at 1500 rads and have completely lost this activity at 3300 rads. It was also possible to distinguish two distinct T cell clonal phenotypes when resting B cells were used as APCs on the basis of two different assays (T cell proliferation, and B cell proliferation resulting from T cell activation). The majority of T cell clones tested were capable of both proliferating themselves and inducing the proliferation of B cells. Some T cells clones, however, could not proliferate in the presence of antigen and B cell APCs, although they were very good at inducing the proliferation of B cells

  4. Modulation of antigen presenting cell functions during chronic HPV infection

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    Abate Assefa Bashaw

    2017-12-01

    Full Text Available High-risk human papillomaviruses (HR-HPV infect basal keratinocytes, where in some individuals they evade host immune responses and persist. Persistent HR-HPV infection of the cervix causes precancerous neoplasia that can eventuate in cervical cancer. Dendritic cells (DCs are efficient in priming/cross-priming antigen-specific T cells and generating antiviral and antitumor cytotoxic CD8+ T cells. However, HR-HPV have adopted various immunosuppressive strategies, with modulation of DC function crucial to escape from the host adaptive immune response. HPV E6 and E7 oncoproteins alter recruitment and localization of epidermal DCs, while soluble regulatory factors derived from HPV-induced hyperplastic epithelium change DC development and influence initiation of specific cellular immune responses. This review focuses on current evidence for HR-HPV manipulation of antigen presentation in dendritic cells and escape from host immunity.

  5. Unusual antigen presentation offers new insight into HIV vaccine design.

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    McMichael, Andrew J; Picker, Louis J

    2017-06-01

    Recent findings with a rhesus monkey cytomegalovirus based simian immunodeficiency virus vaccine have identified strong CD8+ T cell responses that are restricted by MHC-E. Also mycobacteria specific CD8+ T cells, that are MHC-E restricted, have been identified. MHC-E therefore can present a wide range of epitope peptides to CD8+ T cells, alongside its well defined role in presenting a conserved MHC-class I signal peptide to the NKG2A/C-CD94 receptor on natural killer cells. Here we explore the antigen processing pathways involved in these atypical T cell responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Granulocytes: New Members of the Antigen-Presenting Cell Family

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    Ang Lin

    2017-12-01

    Full Text Available Granulocytes, the most abundant types of leukocytes, are the first line of defense against pathogen invasion. However, the plasticity and diversity of granulocytes have been increasingly revealed, especially with regard to their versatile functions in orchestrating adaptive immune responses. A substantial body of recent evidence demonstrates that granulocytes can acquire the function as antigen-presenting cells under pathological or inflammatory conditions. In addition, they can acquire surface expression of MHC class II and costimulatory molecules as well as T cell stimulatory behavior when cultured with selected cytokines. The classic view of granulocytes as terminally differentiated, short-lived phagocytes is therefore changing to phenotypically and functionally heterogeneous cells that are engaged in cross-talk with other leukocyte populations and provide an additional link between innate and adaptive immunity. In this brief review, we summarize the current knowledge on the antigen-presenting capacity of granulocyte subsets (neutrophils, eosinophils, and basophils. Underlying mechanisms, relevant physiological significance and potential controversies are also discussed.

  7. Bioengineering of Artificial Antigen Presenting Cells and Lymphoid Organs.

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    Wang, Chao; Sun, Wujin; Ye, Yanqi; Bomba, Hunter N; Gu, Zhen

    2017-01-01

    The immune system protects the body against a wide range of infectious diseases and cancer by leveraging the efficiency of immune cells and lymphoid organs. Over the past decade, immune cell/organ therapies based on the manipulation, infusion, and implantation of autologous or allogeneic immune cells/organs into patients have been widely tested and have made great progress in clinical applications. Despite these advances, therapy with natural immune cells or lymphoid organs is relatively expensive and time-consuming. Alternatively, biomimetic materials and strategies have been applied to develop artificial immune cells and lymphoid organs, which have attracted considerable attentions. In this review, we survey the latest studies on engineering biomimetic materials for immunotherapy, focusing on the perspectives of bioengineering artificial antigen presenting cells and lymphoid organs. The opportunities and challenges of this field are also discussed.

  8. A role for NADPH oxidase in antigen presentation

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    Gail J Gardiner

    2013-09-01

    Full Text Available The nicotinamide adenine dinucleotide phosphate (NADPH oxidase expressed in phagocytes is a multi-subunit enzyme complex that generates superoxide (O2.-. This radical is an important precursor of hydrogen peroxide (H2O2 and other reactive oxygen species (ROS needed for microbicidal activity during innate immune responses. Inherited defects in NADPH oxidase give rise to chronic granulomatous disease (CGD, a primary immunodeficiency characterized by recurrent infections and granulomatous inflammation. Interestingly, CGD, CGD carrier status, and oxidase gene polymorphisms have all been associated with autoinflammatory and autoimmune disorders, suggesting a potential role for NADPH oxidase in regulating adaptive immune responses. Here, NADPH oxidase function in antigen processing and presentation is reviewed. NADPH oxidase influences dendritic cell (DC crosspresentation by major histocompatibility complex class I molecules (MHC-I through regulation of the phagosomal microenvironment, while in B lymphocytes, NADPH oxidase alters epitope selection by major histocompatibility complex class II molecules (MHC-II.

  9. A scoring system predicting the clinical course of CLPB defect based on the foetal and neonatal presentation of 31 patients

    DEFF Research Database (Denmark)

    Pronicka, Ewa; Ropacka-Lesiak, Mariola; Trubicka, Joanna

    2017-01-01

    Recently, CLPB deficiency has been shown to cause a genetic syndrome with cataracts, neutropenia, and 3-methylglutaconic aciduria. Surprisingly, the neurological presentation ranges from completely unaffected to patients with virtual absence of development. Muscular hypo- and hypertonia, movement...... be considered in neonates with absence of voluntary movements, respiratory insufficiency and swallowing problems, especially if associated with 3-methylglutaconic aciduria, neutropenia and cataracts. Being an important differential diagnosis of hyperekplexia (exaggerated startle responses), we advise performing...

  10. Resistance to checkpoint blockade therapy through inactivation of antigen presentation.

    Science.gov (United States)

    Sade-Feldman, Moshe; Jiao, Yunxin J; Chen, Jonathan H; Rooney, Michael S; Barzily-Rokni, Michal; Eliane, Jean-Pierre; Bjorgaard, Stacey L; Hammond, Marc R; Vitzthum, Hans; Blackmon, Shauna M; Frederick, Dennie T; Hazar-Rethinam, Mehlika; Nadres, Brandon A; Van Seventer, Emily E; Shukla, Sachet A; Yizhak, Keren; Ray, John P; Rosebrock, Daniel; Livitz, Dimitri; Adalsteinsson, Viktor; Getz, Gad; Duncan, Lyn M; Li, Bo; Corcoran, Ryan B; Lawrence, Donald P; Stemmer-Rachamimov, Anat; Boland, Genevieve M; Landau, Dan A; Flaherty, Keith T; Sullivan, Ryan J; Hacohen, Nir

    2017-10-26

    Treatment with immune checkpoint blockade (CPB) therapies often leads to prolonged responses in patients with metastatic melanoma, but the common mechanisms of primary and acquired resistance to these agents remain incompletely characterized and have yet to be validated in large cohorts. By analyzing longitudinal tumor biopsies from 17 metastatic melanoma patients treated with CPB therapies, we observed point mutations, deletions or loss of heterozygosity (LOH) in beta-2-microglobulin (B2M), an essential component of MHC class I antigen presentation, in 29.4% of patients with progressing disease. In two independent cohorts of melanoma patients treated with anti-CTLA4 and anti-PD1, respectively, we find that B2M LOH is enriched threefold in non-responders (~30%) compared to responders (~10%) and associated with poorer overall survival. Loss of both copies of B2M is found only in non-responders. B2M loss is likely a common mechanism of resistance to therapies targeting CTLA4 or PD1.

  11. Efficient Capsid Antigen Presentation From Adeno-Associated Virus Empty Virions In Vivo.

    Science.gov (United States)

    Pei, Xiaolei; Earley, Lauriel Freya; He, Yi; Chen, Xiaojing; Hall, Nikita Elexa; Samulski, Richard Jude; Li, Chengwen

    2018-01-01

    Adeno-associated virus (AAV) vectors have been successfully applied in clinical trials for hemophilic patients. Although promising, the clinical results suggest that the capsid-specific CD8+T cell response has a negative effect on therapeutic success. In an in vitro analysis using an engineered AAV virus carrying immune-dominant SIINFEKL peptide in the capsid backbone, we have previously demonstrated that capsid antigen presentation from full (genome containing) AAV capsids requires endosome escape and is proteasome dependent and that no capsid antigen presentation is induced from empty virions. In the present study, we examined capsid antigen presentation from administration of empty virions in animal models. In wild-type mice, similar to AAV full particles, capsid antigen presentation from AAV empty virion infection was dose dependent, and the kinetics studies showed that antigen presentation was detected from 2 to 40 days after AAV empty virion administration. In the transporter associated with antigen processing 1 deficient (TAP-/-) mice, capsid antigen presentation was inhibited from both AAV full and empty virions, but higher inhibition was achieved from AAV full particle administration than that from empty virions. This indicates that the pathway of capsid antigen presentation from AAV transduction is dependent on proteasome-mediated degradation of AAV capsids (mainly for full particles) and that the endosomal pathway may also play a role in antigen presentation from empty particles but not full virions. The capsid antigen presentation efficiency from AAV preparations was positively correlated with the amount of empty virions contaminated with full particles. Collectively, the results indicate that contamination of AAV empty virions induces efficient antigen presentation in vivo and the mechanism of capsid antigen presentation from empty virions involves both endosomal and proteasomal pathways. The elucidation of capsid antigen presentation from AAV empty

  12. Antigen presentation by hapten-specific B lymphocytes. II. Specificity and properties of antigen-presenting B lymphocytes, and function of immunoglobulin receptors

    International Nuclear Information System (INIS)

    Abbas, A.K.; Haber, S.; Rock, K.L.

    1985-01-01

    Studies were designed to examine the ability of hapten-binding murine B lymphocytes to present hapten-protein conjugates to protein antigen-specific, Ia-restricted T cell hybridomas. BALB/c B cells specific for TNP or FITC presented hapten-modified proteins (TNP-G1 phi, TNP-OVA, or FITC-OVA) to the relevant T cell hybridomas at concentrations below 0.1 microgram/ml. Effective presentation of the same antigens by B lymphocyte-depleted splenocytes, and of unmodified proteins by either hapten-binding B cells or Ig spleen cells, required about 10(3)-to 10(4)-fold higher concentrations of antigen. The use of two different haptens and two carrier proteins showed that this extremely efficient presentation of antigen was highly specific, with hapten specificity being a property of the B cells and carrier specificity of the responding T cells. The presentation of hapten-proteins by hapten-binding B lymphocytes was radiosensitive and was not affected by the depletion of plastic-adherent cells, suggesting that conventional APCs (macrophages or dendritic cells) are not required in this phenomenon. Antigen-pulsing and antibody-blocking experiments showed that this hapten-specific antigen presentation required initial binding of antigen to surface Ig receptors. Moreover, linked recognition of hapten and carrier determinants was required, but these recognition events could be temporally separated. Finally, an antigen-processing step was found to be necessary, and this step was disrupted by ionizing radiation. These data suggest a role for B cell surface Ig in providing a specific high-affinity receptor to allow efficient uptake or focusing of antigen for its subsequent processing and presentation to T lymphocytes

  13. Prolonged Intrauterine Retention of Foetal Bones after Midtrimester ...

    African Journals Online (AJOL)

    Prolonged retention of foetal bones in the uterus is a rare complication of induced abortion. We present the case of a 37 year old nullipara with retained foetal bones following a second trimester induced abortion. Accurate diagnosis and removal of the bony fragments led to restoration of fertility and subsequent delivery of a ...

  14. Viral sequestration of antigen subverts cross presentation to CD8(+ T cells.

    Directory of Open Access Journals (Sweden)

    Eric F Tewalt

    2009-05-01

    Full Text Available Virus-specific CD8(+ T cells (T(CD8+ are initially triggered by peptide-MHC Class I complexes on the surface of professional antigen presenting cells (pAPC. Peptide-MHC complexes are produced by two spatially distinct pathways during virus infection. Endogenous antigens synthesized within virus-infected pAPC are presented via the direct-presentation pathway. Many viruses have developed strategies to subvert direct presentation. When direct presentation is blocked, the cross-presentation pathway, in which antigen is transferred from virus-infected cells to uninfected pAPC, is thought to compensate and allow the generation of effector T(CD8+. Direct presentation of vaccinia virus (VACV antigens driven by late promoters does not occur, as an abortive infection of pAPC prevents production of these late antigens. This lack of direct presentation results in a greatly diminished or ablated T(CD8+ response to late antigens. We demonstrate that late poxvirus antigens do not enter the cross-presentation pathway, even when identical antigens driven by early promoters access this pathway efficiently. The mechanism mediating this novel means of viral modulation of antigen presentation involves the sequestration of late antigens within virus factories. Early antigens and cellular antigens are cross-presented from virus-infected cells, as are late antigens that are targeted to compartments outside of the virus factories. This virus-mediated blockade specifically targets the cross-presentation pathway, since late antigen that is not cross-presented efficiently enters the MHC Class II presentation pathway. These data are the first to describe an evasion mechanism employed by pathogens to prevent entry into the cross-presentation pathway. In the absence of direct presentation, this evasion mechanism leads to a complete ablation of the T(CD8+ response and a potential replicative advantage for the virus. Such mechanisms of viral modulation of antigen presentation

  15. Antigen presentation by resting B cells. Radiosensitivity of the antigen-presentation function and two distinct pathways of T cell activation

    International Nuclear Information System (INIS)

    Ashwell, J.D.; DeFranco, A.L.; Paul, W.E.; Schwartz, R.H.

    1984-01-01

    In this report we have examined the ability of small resting B cells to act as antigen-presenting cells (APC) to antigen-specific MHC-restricted T cells as assessed by either T cell proliferation or T cell-dependent B cell stimulation. We found that 10 of 14 in vitro antigen-specific MHC-restricted T cell clones and lines and three of four T cell hybridomas could be induced to either proliferate or secrete IL-2 in the presence of lightly irradiated (1,000 rads) purified B cells and the appropriate foreign antigen. All T cell lines and hybridomas were stimulated to proliferate or make IL-2 by macrophage- and dendritic cell-enriched populations and all T cells tested except one hybridoma caused B cell activation when stimulated with B cells as APC. Furthermore, lightly irradiated, highly purified syngeneic B cells were as potent a source of APC for inducing B cell activation as were low density dendritic and macrophage-enriched cells. Lymph node T cells freshly taken from antigen-primed animals were also found to proliferate when cultured with purified B cells and the appropriate antigen. This APC function was easily measured when the cells were irradiated with 1,000 rads, but was greatly diminished or absent when they were irradiated with 3,300 rads. In addition, this radiosensitivity allowed us to easily distinguish B cell antigen presentation from presentation by the dendritic cell and macrophage, as the latter was resistant to 3,300 rads. Finally, one T cell clone that failed to proliferate when B cells were used as APC was able to recruit allogeneic B cells to proliferate in the presence of syngeneic B cells and the appropriate antigen. This result suggests that there are at least two distinct pathways of activation in T cells, one that leads to T cell proliferation and one that leads to the secretion of B cell recruitment factor(s)

  16. Evaluation of placenta in foetal demise and foetal growth restriction.

    Science.gov (United States)

    Ch, Ujwala; Guruvare, Shyamala; Bhat, Sudha S; Rai, Lavanya; Rao, Sugandhi

    2013-11-01

    The study objective was to evaluate the pathological changes of the placenta in foetal death and foetal growth restriction and to find correlation of the findings with clinical causes. Prospective study at a tertiary care hospital. Gross and histopathological examinations of the placentae were carried out in pregnancies with foetal demise (IUD) and Foetal Growth Restriction (FGR). SPSS, version 11.5. Placentae of twenty seven women with foetal demise and of equal number of women with foetal growth restriction were studied. Placental weight was less than 10(th) percentile in 61.5% women in IUD group and in 93% women in the FGR group. Gross examination of placentae showed abnormalities in 12 (44%) women of IUD group and in 16 (59%) women of FGR group. Histopathological abnormalities were observed in 74.1% women of the IUD group and in 66.7% women of FGR group. Placental histopathology correlated with clinical risk factors in 60% women of IUD group and in 40% women of FGR group. Among the women with no clinically explainable cause for IUD and FGR, 86% and 57% had placental histopathological abnormalities respectively. The histopathological abnormalities of the placenta can be used to document the clinical causes of foetal demise and growth restriction; it may explain the causes in cases of clinically unexplained foetal demise and foetal growth restriction.

  17. Chloroquine inhibits accessory cell presentation of soluble natural and synthetic protein antigens

    DEFF Research Database (Denmark)

    Buus, S; Werdelin, O

    1984-01-01

    We have studied the in vitro effect of the lysosomotrophic agent, chloroquine, on the presentation of soluble protein antigens by guinea pig accessory cells. Chloroquine inhibited the capacity of antigen-pulsed accessory cells to stimulate proliferation in appropriately primed T cells. The effect...... was time- and dose-dependent. A brief treatment solely of the accessory cells with the drug compromised their ability to stimulate primed T cells in a subsequent culture provided the accessory cells were treated with chloroquine before their exposure to the antigen. These results suggest that chloroquine...... acts on an early event in the antigen handling by accessory cells. Chloroquine is a well known inhibitor of lysosomal proteolysis, and it is likely that its effect on antigen presentation is caused by an inhibition of antigen degradation....

  18. MRI of the foetal brain

    International Nuclear Information System (INIS)

    Rich, P.; Jones, R.; Britton, J.; Foote, S.; Thilaganathan, B.

    2007-01-01

    Ultrasound examinations for foetal brain abnormalities have been a part of the routine antenatal screening programme in the UK for many years. In utero brain magnetic resonance imaging (MRI) is now being used increasingly successfully to clarify abnormal ultrasound findings, often resulting in a change of diagnosis or treatment plan. Interpretation requires an understanding of foetal brain development, malformations and acquired diseases. In this paper we will outline the technique of foetal MRI, relevant aspects of brain development and provide illustrated examples of foetal brain pathology

  19. Management of foetal asphyxia by intrauterine foetal resuscitation

    Science.gov (United States)

    Velayudhareddy, S.; Kirankumar, H

    2010-01-01

    Management of foetal distress is a subject of gynaecological interest, but an anaesthesiologist should know about resuscitation, because he should be able to treat the patient, whenever he is directly involved in managing the parturient patient during labour analgesia and before an emergency operative delivery. Progressive asphyxia is known as foetal distress; the foetus does not breathe directly from the atmosphere, but depends on maternal circulation for its oxygen requirement. The oxygen delivery to the foetus depends on the placental (maternal side), placental transfer and foetal circulation. Oxygen transport to the foetus is reduced physiologically during uterine contractions in labour. Significant impairment of oxygen transport to the foetus, either temporary or permanent may cause foetal distress, resulting in progressive hypoxia and acidosis. Intrauterine foetal resuscitation comprises of applying measures to a mother in active labour, with the intention of improving oxygen delivery to the distressed foetus to the base line, if the placenta is functioning normally. These measures include left lateral recumbent position, high flow oxygen administration, tocolysis to reduce uterine contractions, rapid intravenous fluid administration, vasopressors for correction of maternal hypotension and amnioinfusion for improving uterine blood flow. Intrauterine Foetal Resuscitation measures are easy to perform and do not require extensive resources, but the results are encouraging in improving the foetal well-being. The anaesthesiologist plays a major role in the application of intrauterine foetal resuscitation measures. PMID:21189876

  20. Management of foetal asphyxia by intrauterine foetal resuscitation

    Directory of Open Access Journals (Sweden)

    S Velayudhareddy

    2010-01-01

    Full Text Available Management of foetal distress is a subject of gynaecological interest, but an anaesthesiologist should know about resuscitation, because he should be able to treat the patient, whenever he is directly involved in managing the parturient patient during labour analgesia and before an emergency operative delivery. Progressive asphyxia is known as foetal distress; the foetus does not breathe directly from the atmosphere, but depends on maternal circulation for its oxygen requirement. The oxygen delivery to the foetus depends on the placental (maternal side, placental transfer and foetal circulation. Oxygen transport to the foetus is reduced physiologically during uterine contractions in labour. Significant impairment of oxygen transport to the foetus, either temporary or permanent may cause foetal distress, resulting in progressive hypoxia and acidosis. Intrauterine foetal resuscitation comprises of applying measures to a mother in active labour, with the intention of improving oxygen delivery to the distressed foetus to the base line, if the placenta is functioning normally. These measures include left lateral recumbent position, high flow oxygen administration, tocolysis to reduce uterine contractions, rapid intravenous fluid administration, vasopressors for correction of maternal hypotension and amnioinfusion for improving uterine blood flow. Intrauterine Foetal Resuscitation measures are easy to perform and do not require extensive resources, but the results are encouraging in improving the foetal well-being. The anaesthesiologist plays a major role in the application of intrauterine foetal resuscitation measures.

  1. CLINICAL AND ULTRASONOGRAPHIC PREDICTORS OF FOETAL MACROSOMIA

    Directory of Open Access Journals (Sweden)

    Suneetha Kalam

    2017-01-01

    and odds ratio was found out. For statistical evaluation, a two-tailed probability value less than 0.05 was considered significant. RESULTS 87% of the study population were less than 30 years. More than half were multigravida. Among them, 24.5% had macrosomic babies while among the primigravida only 14% had macrosomic babies. About 30% had gestational diabetes mellitus. Previous history of macrosomic foetus was present in 18.44%. Among 110 macrosomic babies, 74 mothers of those babies had BMI more than 25. In ultrasonography, 45 babies had BPD more than 96 mm (90th percentile, 40 had HC more than 354 mm (90th percentile, 92 had AC more than 346 mm (90th percentile and 85 had FL more than 74 mm (90th percentile. Estimated foetal weight was more than 4000 grams in 86 patients. CONCLUSION Foetal macrosomia is more common among multigravida. There is significant association between the incidence of macrosomia and gestational diabetes mellitus. Previous macrosomic birth and high body mass index have influence over macrosomia. Biparietal diameter and head circumference are poor predictors of macrosomia. Estimated foetal weight is the best individual ultrasound parameter in predicting macrosomia followed by abdominal circumference.

  2. The Effect of Superparamagnetic Iron Oxide Nanoparticle Surface Charge on Antigen Cross-Presentation

    Science.gov (United States)

    Mou, Yongbin; Xing, Yun; Ren, Hongyan; Cui, Zhihua; Zhang, Yu; Yu, Guangjie; Urba, Walter J.; Hu, Qingang; Hu, Hongming

    2017-01-01

    Magnetic nanoparticles (NPs) of superparamagnetic iron oxide (SPIO) have been explored for different kinds of applications in biomedicine, mechanics, and information. Here, we explored the synthetic SPIO NPs as an adjuvant on antigen cross-presentation ability by enhancing the intracellular delivery of antigens into antigen presenting cells (APCs). Particles with different chemical modifications and surface charges were used to study the mechanism of action of antigen delivery. Specifically, two types of magnetic NPs, γFe2O3/APTS (3-aminopropyltrimethoxysilane) NPs and γFe2O3/DMSA (meso-2, 3-Dimercaptosuccinic acid) NPs, with the same crystal structure, magnetic properties, and size distribution were prepared. Then, the promotion of T-cell activation via dendritic cells (DCs) was compared among different charged antigen coated NPs. Moreover, the activation of the autophagy, cytosolic delivery of the antigens, and antigen degradation mediated by the proteasome and lysosome were measured. Our results indicated that positive charged γFe2O3/APTS NPs, but not negative charged γFe2O3/DMSA NPs, enhanced the cross-presentation ability of DCs. Increased cross-presentation ability induced by γFe2O3/APTS NPs was associated with increased cytosolic antigen delivery. On the contrary, γFe2O3/DMSA NPs was associated with rapid autophagy. Overall, our results suggest that antigen delivered in cytoplasm induced by positive charged particles is beneficial for antigen cross-presentation and T-cell activation. NPs modified with different chemistries exhibit diverse biological properties and differ greatly in their adjuvant potentials. Thus, it should be carefully considered many different effects of NPs to design effective and safe adjuvants.

  3. Identification of a peptide binding protein that plays a role in antigen presentation

    International Nuclear Information System (INIS)

    Lakey, E.K.; Margoliash, E.; Pierce, S.K.

    1987-01-01

    The helper T-cell response to globular proteins appears, in general, to require intracellular processing of the antigen, such that a peptide fragment containing the T-cell antigenic determinant is released and transported to and held on the surface of an Ia-expressing, antigen-presenting cell. However, the molecular details underlying these phenomena are largely unknown. The means by which antigenic peptides are anchored on the antigen-presenting cell surface was investigated. A cell surface protein is identified that was isolated by it ability to bind to a 24-amino acid peptide fragment of pigeon cytochrome c, residues 81-104, containing the major antigenic determinant for B10.A mouse T cells. This peptide binding protein, purified from [ 35 S]methionine-labeled cells, appears as two discrete bands of ≅72 and 74 kDa after NaDodSO 4 /PAGE. The protein can be eluted from the peptide affinity column with equivalent concentrations of either the antigenic pigeon cytochrome c peptide or the corresponding nonantigenic peptide of mouse cytochrome c. However, it does not bind to the native cytochromes c, either of pigeon or mouse, and thus the protein appears to recognize some structure available only in the free peptides. This protein plays a role in antigen presentation. Its expression is not major histocompatibility complex-restricted in that the blocking activity of the antisera can be absorbed on spleen cells from mice of different haplotypes. This peptide binding protein can be isolated from a variety of cell types, including B cells, T cells, and fibroblasts. The anchoring of processed peptides on the cell surface by such a protein may play a role in antigen presentation

  4. The perivascular phagocyte of the mouse pineal gland: An antigen-presenting cell

    DEFF Research Database (Denmark)

    Møller, Morten; Rath, Martin F; Klein, David C

    2006-01-01

    The perivascular space of the rat pineal gland is known to contain phagocytic cells that are immunoreactive for leukocyte antigens, and thus they appear to belong to the macrophage/microglial cell line. These cells also contain MHC class II proteins. We investigated this cell type in the pineal g...... for MHC class II protein and for CD68, a marker of monocytes/phagocytes. This study verifies that perivascular phagocytes with antigen-presenting properties are present in the mouse pineal gland....

  5. Identifying a Small Molecule Blocking Antigen Presentation in Autoimmune Thyroiditis.

    Science.gov (United States)

    Li, Cheuk Wun; Menconi, Francesca; Osman, Roman; Mezei, Mihaly; Jacobson, Eric M; Concepcion, Erlinda; David, Chella S; Kastrinsky, David B; Ohlmeyer, Michael; Tomer, Yaron

    2016-02-19

    We previously showed that an HLA-DR variant containing arginine at position 74 of the DRβ1 chain (DRβ1-Arg74) is the specific HLA class II variant conferring risk for autoimmune thyroid diseases (AITD). We also identified 5 thyroglobulin (Tg) peptides that bound to DRβ1-Arg74. We hypothesized that blocking the binding of these peptides to DRβ1-Arg74 could block the continuous T-cell activation in thyroiditis needed to maintain the autoimmune response to the thyroid. The aim of the current study was to identify small molecules that can block T-cell activation by Tg peptides presented within DRβ1-Arg74 pockets. We screened a large and diverse library of compounds and identified one compound, cepharanthine that was able to block peptide binding to DRβ1-Arg74. We then showed that Tg.2098 is the dominant peptide when inducing experimental autoimmune thyroiditis (EAT) in NOD mice expressing human DRβ1-Arg74. Furthermore, cepharanthine blocked T-cell activation by thyroglobulin peptides, in particular Tg.2098 in mice that were induced with EAT. For the first time we identified a small molecule that can block Tg peptide binding and presentation to T-cells in autoimmune thyroiditis. If confirmed cepharanthine could potentially have a role in treating human AITD. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Current status of multiple antigen-presenting peptide vaccine systems: Application of organic and inorganic nanoparticles

    Directory of Open Access Journals (Sweden)

    Taguchi Hiroaki

    2011-08-01

    Full Text Available Abstract Many studies are currently investigating the development of safe and effective vaccines to prevent various infectious diseases. Multiple antigen-presenting peptide vaccine systems have been developed to avoid the adverse effects associated with conventional vaccines (i.e., live-attenuated, killed or inactivated pathogens, carrier proteins and cytotoxic adjuvants. Recently, two main approaches have been used to develop multiple antigen-presenting peptide vaccine systems: (1 the addition of functional components, e.g., T-cell epitopes, cell-penetrating peptides, and lipophilic moieties; and (2 synthetic approaches using size-defined nanomaterials, e.g., self-assembling peptides, non-peptidic dendrimers, and gold nanoparticles, as antigen-displaying platforms. This review summarizes the recent experimental studies directed to the development of multiple antigen-presenting peptide vaccine systems.

  7. Human Parvovirus B19 Induced Apoptotic Bodies Contain Altered Self-Antigens that are Phagocytosed by Antigen Presenting Cells

    Science.gov (United States)

    Thammasri, Kanoktip; Rauhamäki, Sanna; Wang, Liping; Filippou, Artemis; Kivovich, Violetta; Marjomäki, Varpu; Naides, Stanley J.; Gilbert, Leona

    2013-01-01

    Human parvovirus B19 (B19V) from the erythrovirus genus is known to be a pathogenic virus in humans. Prevalence of B19V infection has been reported worldwide in all seasons, with a high incidence in the spring. B19V is responsible for erythema infectiosum (fifth disease) commonly seen in children. Its other clinical presentations include arthralgia, arthritis, transient aplastic crisis, chronic anemia, congenital anemia, and hydrops fetalis. In addition, B19V infection has been reported to trigger autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. However, the mechanisms of B19V participation in autoimmunity are not fully understood. B19V induced chronic disease and persistent infection suggests B19V can serve as a model for viral host interactions and the role of viruses in the pathogenesis of autoimmune diseases. Here we investigate the involvement of B19V in the breakdown of immune tolerance. Previously, we demonstrated that the non-structural protein 1 (NS 1) of B19V induces apoptosis in non-permissive cells lines and that this protein can cleave host DNA as well as form NS1-DNA adducts. Here we provide evidence that through programmed cell death, apoptotic bodies (ApoBods) are generated by B19V NS1 expression in a non-permissive cell line. Characterization of purified ApoBods identified potential self-antigens within them. In particular, signature self-antigens such as Smith, ApoH, DNA, histone H4 and phosphatidylserine associated with autoimmunity were present in these ApoBods. In addition, when purified ApoBods were introduced to differentiated macrophages, recognition, engulfment and uptake occurred. This suggests that B19V can produce a source of self-antigens for immune cell processing. The results support our hypothesis that B19V NS1-DNA adducts, and nucleosomal and lysosomal antigens present in ApoBods created in non-permissive cell lines, are a source of self-antigens. PMID:23776709

  8. Effector CD4+ T cells recognize intravascular antigen presented by patrolling monocytes.

    Science.gov (United States)

    Westhorpe, Clare L V; Norman, M Ursula; Hall, Pam; Snelgrove, Sarah L; Finsterbusch, Michaela; Li, Anqi; Lo, Camden; Tan, Zhe Hao; Li, Songhui; Nilsson, Susan K; Kitching, A Richard; Hickey, Michael J

    2018-02-21

    Although effector CD4 + T cells readily respond to antigen outside the vasculature, how they respond to intravascular antigens is unknown. Here we show the process of intravascular antigen recognition using intravital multiphoton microscopy of glomeruli. CD4 + T cells undergo intravascular migration within uninflamed glomeruli. Similarly, while MHCII is not expressed by intrinsic glomerular cells, intravascular MHCII-expressing immune cells patrol glomerular capillaries, interacting with CD4 + T cells. Following intravascular deposition of antigen in glomeruli, effector CD4 + T-cell responses, including NFAT1 nuclear translocation and decreased migration, are consistent with antigen recognition. Of the MHCII + immune cells adherent in glomerular capillaries, only monocytes are retained for prolonged durations. These cells can also induce T-cell proliferation in vitro. Moreover, monocyte depletion reduces CD4 + T-cell-dependent glomerular inflammation. These findings indicate that MHCII + monocytes patrolling the glomerular microvasculature can present intravascular antigen to CD4 + T cells within glomerular capillaries, leading to antigen-dependent inflammation.

  9. Ubiquitinated Proteins Isolated From Tumor Cells Are Efficient Substrates for Antigen Cross-Presentation.

    Science.gov (United States)

    Yu, Guangjie; Moudgil, Tarsem; Cui, Zhihua; Mou, Yongbin; Wang, Lixin; Fox, Bernard A; Hu, Hong-Ming

    2017-06-01

    We have previously shown that inhibition of the proteasome causes defective ribosomal products to be shunted into autophagosomes and subsequently released from tumor cells as defective ribosomal products in Blebs (DRibbles). These DRibbles serve as an excellent source of antigens for cross-priming of tumor-specific T cells. Here, we examine the role of ubiquitinated proteins (Ub-proteins) in this pathway. Using purified Ub-proteins from tumor cells that express endogenous tumor-associated antigen or exogenous viral antigen, we tested the ability of these proteins to stimulate antigen-specific T-cell responses, by activation of monocyte-derived dendritic cells generated from human peripheral blood mononuclear cells. Compared with total cell lysates, we found that purified Ub-proteins from both a gp100-specific melanoma cell line and from a lung cancer cell line expressing cytomegalovirus pp65 antigen produced a significantly higher level of IFN-γ in gp100- or pp65-specific T cells, respectively. In addition, Ub-proteins from an allogeneic tumor cell line could be used to stimulate tumor-infiltrating lymphocytes isolated and expanded from non-small cell lung cancer patients. These results establish that Ub-proteins provide a relevant source of antigens for cross-priming of antitumor immune responses in a variety of settings, including endogenous melanoma and exogenous viral antigen presentation, as well as antigen-specific tumor-infiltrating lymphocytes. Thus, ubiquitin can be used as an affinity tag to enrich for unknown tumor-specific antigens from tumor cell lysates to stimulate tumor-specific T cells ex vivo or to be used as vaccines to target short-lived proteins.

  10. Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells

    DEFF Research Database (Denmark)

    Kirkin, Alexei F.; Dzhandzhugazyan, Karine N.; Guldberg, Per

    2018-01-01

    In cancer cells, cancer/testis (CT) antigens become epigenetically derepressed through DNA demethylation and constitute attractive targets for cancer immunotherapy. Here we report that activated CD4+ T helper cells treated with a DNA-demethylating agent express a broad repertoire of endogenous CT...... antigens and can be used as antigen-presenting cells to generate autologous cytotoxic T lymphocytes (CTLs) and natural killer cells. In vitro, activated CTLs induce HLA-restricted lysis of tumor cells of different histological types, as well as cells expressing single CT antigens. In a phase 1 trial of 25...... patients with recurrent glioblastoma multiforme, cytotoxic lymphocytes homed to the tumor, with tumor regression ongoing in three patients for 14, 22, and 27 months, respectively. No treatment-related adverse effects were observed. This proof-of-principle study shows that tumor-reactive effector cells can...

  11. The Hsc/Hsp70 co-chaperone network controls antigen aggregation and presentation during maturation of professional antigen presenting cells.

    Directory of Open Access Journals (Sweden)

    Nadja Kettern

    Full Text Available The maturation of mouse macrophages and dendritic cells involves the transient deposition of ubiquitylated proteins in the form of dendritic cell aggresome-like induced structures (DALIS. Transient DALIS formation was used here as a paradigm to study how mammalian cells influence the formation and disassembly of protein aggregates through alterations of their proteostasis machinery. Co-chaperones that modulate the interplay of Hsc70 and Hsp70 with the ubiquitin-proteasome system (UPS and the autophagosome-lysosome pathway emerged as key regulators of this process. The chaperone-associated ubiquitin ligase CHIP and the ubiquitin-domain protein BAG-1 are essential for DALIS formation in mouse macrophages and bone-marrow derived dendritic cells (BMDCs. CHIP also cooperates with BAG-3 and the autophagic ubiquitin adaptor p62 in the clearance of DALIS through chaperone-assisted selective autophagy (CASA. On the other hand, the co-chaperone HspBP1 inhibits the activity of CHIP and thereby attenuates antigen sequestration. Through a modulation of DALIS formation CHIP, BAG-1 and HspBP1 alter MHC class I mediated antigen presentation in mouse BMDCs. Our data show that the Hsc/Hsp70 co-chaperone network controls transient protein aggregation during maturation of professional antigen presenting cells and in this way regulates the immune response. Similar mechanisms may modulate the formation of aggresomes and aggresome-like induced structures (ALIS in other mammalian cell types.

  12. Facts on the fragmentation of antigens in presenting cells, on the association of antigen fragments with MHC molecules in cell-free systems, and speculation on the cell biology of antigen processing

    DEFF Research Database (Denmark)

    Werdelin, O; Mouritsen, S; Petersen, B L

    1988-01-01

    The processing of a protein antigen is a multi-step event taking place in antigen-presenting cells. Processing is a prerequisite for the recognition of most antigens by T lymphocytes. The antigen is ingested by endocytosis, transported to an acid cellular compartment and subjected to proteolytic...... fragmentation. Some of the antigen fragments bind to MHC class II molecules and are transported to the surface of the antigen-presenting cell where the actual presentation to T lymphocytes occurs. The nature of the processed antigen, how and where it is derived and subsequently becomes associated with MHC...... molecules are the questions discussed in this review. To us, the entire concept of processing has appeal not only because it explains some hitherto well-established, but poorly understood, phenomena such as the fact that T lymphocytes focus their attention entirely upon antigens on other cells. It has...

  13. Role of interleukin-1 in antigen presentation by normal articular chondrocytes

    International Nuclear Information System (INIS)

    Tiku, M.L.; Liu, S.; Tiku, K.

    1986-01-01

    Recently the authors have described that normal articular chondrocytes of rabbits present antigen to immune T cells. In the present study the authors investigated the role of interleukin-1 (IL-1) on antigen presentation by chondrocytes. For these experiments the antigen pulsed chondroyctes were either untreated or fixed with paraformaldehyde and then co-cultured with immune T cells. T cell proliferation was measured by 3 H-thymidine incorporation. Pulsed non-fixed chondrocytes presented antigen, as expected, but pulsed and fixed cells failed to present antigen to T cells. The 3 H-TdR incorporation was partially restored by addition of purified human IL-1. Next, IL-1 activity was measured in primary chondrocyte culture supernatants stimulated with or without lipopolysaccharide (LPS) in comitogen thymocyte assay. No activity was detected in chondrocyte supernatants. Propagated chondrocyte culture supernatants also lacked IL-1 activity when stimulated with LPS in the presence of increasing concentration of indomethacin. On the other hand the authors observed that chondrocyte culture supernatants in a dose dependent manner inhibited human IL-1 induced 3 H-TdR incorporation of murine thymocytes. This suggested that these cells may produce an inhibitor of IL-1 and IL-1 production by chondrocytes may be essential for T cell proliferation by these cells. Inability to detect IL-1 in chondrocyte supernatants may be due to the presence of an inhibitor to IL-1. These findings may help in elucidating the immunological mechanisms in situations where chondrocytes and T cell interact, such as in arthritis

  14. Antigen detection in vivo after immunization with different presentation forms of rabies virus antigen: Involvement of marginal metallophilic macrophages in the uptake of immune-stimulating complexes

    NARCIS (Netherlands)

    Claassen, I.J.T.M.; Osterhaus, A.D.M.E.; Claassen, E.

    1995-01-01

    Several mechanisms have been postulated to explain the relatively high immunogenicity of antigens presented in immune-stimulating complexes (iscom). Their potency can in part be explained by the specific targeting of these structures to cells presenting antigens to the immune system. However, until

  15. Antigen detection in vivo after immunization with different presentation forms of rabies virus antigen: involvement of marginal metallophilic macrophages in the uptake of immune-stimulating complexes.

    NARCIS (Netherlands)

    I.J.Th.M. Claassen (Ivo); A.D.M.E. Osterhaus (Albert); H.J.H.M. Claassen (Eric)

    1995-01-01

    textabstractSeveral mechanisms have been postulated to explain the relatively high immunogenicity of antigens presented in immune-stimulating complexes (iscom). Their potency can in part be explained by the specific targeting of these structures to cells presenting antigens to the immune system.

  16. Antigen presentation and MHC class II expression by human esophageal epithelial cells: role in eosinophilic esophagitis.

    Science.gov (United States)

    Mulder, Daniel J; Pooni, Aman; Mak, Nanette; Hurlbut, David J; Basta, Sameh; Justinich, Christopher J

    2011-02-01

    Professional antigen-presenting cells (APCs) play a crucial role in initiating immune responses. Under pathological conditions, epithelial cells at mucosal surfaces act as nonprofessional APCs, thereby regulating immune responses at the site of exposure. Epithelial cells in the esophagus may contribute to the pathogenesis of eosinophilic esophagitis (EoE) by presenting antigens on the major histocompatibility complex (MHC) class II. Our goal was to demonstrate the ability of esophageal epithelial cells to process and present antigens on the MHC class II system and to investigate the contribution of epithelial cell antigen presentation to EoE. Immunohistochemistry detected HLA-DR, CD80, and CD86 expression and enzyme-linked immunosorbent assay detected interferon-γ (IFNγ) in esophageal biopsies. Antigen presentation was studied using the human esophageal epithelial cell line HET-1A by reverse transcriptase-PCR, flow cytometry, and confocal microscopy. T helper cell lymphocyte proliferation was assessed by flow cytometry and IL-2 secretion. IFNγ and MHC class II were increased in mucosa of patients with EoE. IFNγ increased mRNA of HLA-DP, HLA-DQ, HLA-DR, and CIITA in HET-1A cells. HET-1A engulfed cell debris and processed ovalbumin. HET-1A cells expressed HLA-DR after IFNγ treatment. HET-1A stimulated T helper cell activation. In this study, we demonstrated the ability of esophageal epithelial cells to act as nonprofessional APCs in the presence of IFNγ. Esophageal epithelial cell antigen presentation may contribute to the pathophysiology of eosinophilic esophagitis. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. A Genome-wide multidimensional RNAi screen reveals pathways controlling MHC class II antigen presentation

    NARCIS (Netherlands)

    Paul, Petra; van den Hoorn, Tineke; Jongsma, Marlieke L. M.; Bakker, Mark J.; Hengeveld, Rutger; Janssen, Lennert; Cresswell, Peter; Egan, David A.; van Ham, Marieke; ten Brinke, Anja; Ovaa, Huib; Beijersbergen, Roderick L.; Kuijl, Coenraad; Neefjes, Jacques

    2011-01-01

    MHC class II molecules (MHC-II) present peptides to T helper cells to facilitate immune responses and are strongly linked to autoimmune diseases. To unravel processes controlling MHC-II antigen presentation, we performed a genome-wide flow cytometry-based RNAi screen detecting MHC-II expression and

  18. Pros and Cons of Antigen-Presenting Cell Targeted Tumor Vaccines

    Directory of Open Access Journals (Sweden)

    Cleo Goyvaerts

    2015-01-01

    Full Text Available In therapeutic antitumor vaccination, dendritic cells play the leading role since they decide if, how, when, and where a potent antitumor immune response will take place. Since the disentanglement of the complexity and merit of different antigen-presenting cell subtypes, antitumor immunotherapeutic research started to investigate the potential benefit of targeting these subtypes in situ. This review will discuss which antigen-presenting cell subtypes are at play and how they have been targeted and finally question the true meaning of targeting antitumor-based vaccines.

  19. Equine infectious anemia virus-infected dendritic cells retain antigen presentation capability

    International Nuclear Information System (INIS)

    Rivera, Julie A.; McGuire, Travis C.

    2005-01-01

    To determine if equine monocyte-derived dendritic cells (DC) were susceptible to equine infectious anemia virus (EIAV) infection, ex vivo-generated DC were infected with virus in vitro. EIAV antigen was detected by immunofluorescence 3 days post-infection with maximum antigen being detected on day 4, whereas there was no antigen detected in DC incubated with the same amount of heat-inactivated EIAV. No cytolytic activity was observed after EIAV WSU5 infection of DC. These monocyte-derived DC were more effective than macrophages and B cells in stimulating allogenic T lymphocytes. Both infected macrophages and DC stimulated similar levels of memory CTL responses in mixtures of CD8+ and CD4+ cells as detected with 51 Cr-release assays indicating that EIAV infection of DC did not alter antigen presentation. However, EIAV-infected DC were more effective than infected macrophages when used to stimulate memory CTL in isolated CD8+ cells. The maintenance of antigen processing and presenting function by EIAV-infected DC in vitro suggests that this function is maintained during in vivo infection

  20. Impact of aging on antigen presentation cell function of dendritic cells.

    Science.gov (United States)

    Wong, Christine; Goldstein, Daniel R

    2013-08-01

    Older people exhibit increased mortality to infections and cancer as compared to younger people, indicating that aging impairs immunity. Dendritic cells (DCs) are key for bridging the innate and adaptive arms of the immune system by priming antigen specific T cells. Discerning how aging impacts DC function to initiate adaptive immune responses is of great biomedical importance as this could lead to the development of novel therapeutics to enhance immunity with aging. This review details reports indicating that aging impairs the antigen presenting function of DCs but highlights other studies indicating preserved DC function with aging. How aging impacts antigen presentation by DCs is complex and without a clear unifying biological underpinning. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. The role and mechanics of dendritic cells in tumor antigen acquisition and presentation following laser immunotherapy

    Science.gov (United States)

    Laverty, Sean M.; Dawkins, Bryan A.; Chen, Wei R.

    2018-02-01

    We extend our model of the antitumor immune response initiated by laser-immunotherapy treatment to more closely examine key steps in the immune response 1) tumor antigen acquisition by antigen-presenting dendritic cells (DCs) and 2) cytotoxic T cell (CTL) priming by lymphatic DCs. Specifically we explore the formation of DC-CTL complexes that lead to CTL priming. We find that the bias in the dissociation rate of the complex influences the outcome of treatment. In particular, a bias towards priming favors a rapid activated CTL response and the clearance of tumors.

  2. Skewing to the LFA-3 adhesion pathway by influenza infection of antigen-presenting cells

    NARCIS (Netherlands)

    van Kemenade, F. J.; Kuijpers, K. C.; de Waal-Malefijt, R.; van Lier, R. A.; Miedema, F.

    1993-01-01

    The effect of influenza (FLU) infection on heterotypic conjugate formation between antigen-presenting cells and T lymphocytes has been studied with FLU-specific T cell clones and FLU-infected B-lymphoblastoid cells (B-LCL). Conjugate formation between FLU-infected B-LCL (FLU+ B-LCL) and T cells was

  3. ImmunoChip Study Implicates Antigen Presentation to T Cells in Narcolepsy

    DEFF Research Database (Denmark)

    Faraco, Juliette; Lin, Ling; Kornum, Birgitte Rahbek

    2013-01-01

    receptor alpha (TRA@), variants in two additional narcolepsy loci, Cathepsin H (CTSH) and Tumor necrosis factor (ligand) superfamily member 4 (TNFSF4, also called OX40L), attained genome-wide significance. These findings underline the importance of antigen presentation by HLA Class II to T cells...

  4. A large, benign prostatic cyst presented with an extremely high serum prostate-specific antigen level.

    Science.gov (United States)

    Chen, Han-Kuang; Pemberton, Richard

    2016-01-08

    We report a case of a patient who presented with an extremely high serum prostate specific antigen (PSA) level and underwent radical prostatectomy for presumed prostate cancer. Surprisingly, the whole mount prostatectomy specimen showed only small volume, organ-confined prostate adenocarcinoma and a large, benign intraprostatic cyst, which was thought to be responsible for the PSA elevation. 2016 BMJ Publishing Group Ltd.

  5. Presenting Influenza A M2e Antigen on Recombinant Spores of Bacillus subtilis.

    Directory of Open Access Journals (Sweden)

    Tomasz Łęga

    Full Text Available Effective vaccination against influenza virus infection is a serious problem mainly due to antigenic variability of the virus. Among many of investigated antigens, the extracellular domain of the M2 protein (M2e features high homology in all strains of influenza A viruses and antibodies against M2e and is protective in animal models; this makes it a potential candidate for generation of a universal influenza vaccine. However, due to the low immunogenicity of the M2e, formulation of a vaccine based on this antigen requires some modification to induce effective immune responses. In this work we evaluated the possible use of Bacillus subtilis spores as a carrier of the Influenza A M2e antigen in mucosal vaccination. A tandem repeat of 4 consensus sequences coding for human-avian-swine-human M2e (M2eH-A-S-H peptide was fused to spore coat proteins and stably exposed on the spore surface, as demonstrated by the immunostaining of intact, recombinant spores. Oral immunization of mice with recombinant endospores carrying M2eH-A-S-H elicited specific antibody production without the addition of adjuvants. Bacillus subtilis endospores can serve as influenza antigen carriers. Recombinant spores constructed in this work showed low immunogenicity although were able to induce antibody production. The System of influenza antigen administration presented in this work is attractive mainly due to the omitting time-consuming and cost-intensive immunogen production and purification. Therefore modification should be made to increase the immunogenicity of the presented system.

  6. A population dynamics analysis of the interaction between adaptive regulatory T cells and antigen presenting cells.

    Directory of Open Access Journals (Sweden)

    David Fouchet

    Full Text Available BACKGROUND: Regulatory T cells are central actors in the maintenance of tolerance of self-antigens or allergens and in the regulation of the intensity of the immune response during infections by pathogens. An understanding of the network of the interaction between regulatory T cells, antigen presenting cells and effector T cells is starting to emerge. Dynamical systems analysis can help to understand the dynamical properties of an interaction network and can shed light on the different tasks that can be accomplished by a network. METHODOLOGY AND PRINCIPAL FINDINGS: We used a mathematical model to describe a interaction network of adaptive regulatory T cells, in which mature precursor T cells may differentiate into either adaptive regulatory T cells or effector T cells, depending on the activation state of the cell by which the antigen was presented. Using an equilibrium analysis of the mathematical model we show that, for some parameters, the network has two stable equilibrium states: one in which effector T cells are strongly regulated by regulatory T cells and another in which effector T cells are not regulated because the regulatory T cell population is vanishingly small. We then simulate different types of perturbations, such as the introduction of an antigen into a virgin system, and look at the state into which the system falls. We find that whether or not the interaction network switches from the regulated (tolerant state to the unregulated state depends on the strength of the antigenic stimulus and the state from which the network has been perturbed. CONCLUSION/SIGNIFICANCE: Our findings suggest that the interaction network studied in this paper plays an essential part in generating and maintaining tolerance against allergens and self-antigens.

  7. Rational design of nanoparticles towards targeting antigen-presenting cells and improved T cell priming.

    Science.gov (United States)

    Zupančič, Eva; Curato, Caterina; Paisana, Maria; Rodrigues, Catarina; Porat, Ziv; Viana, Ana S; Afonso, Carlos A M; Pinto, João; Gaspar, Rogério; Moreira, João N; Satchi-Fainaro, Ronit; Jung, Steffen; Florindo, Helena F

    2017-07-28

    Vaccination is a promising strategy to trigger and boost immune responses against cancer or infectious disease. We have designed, synthesized and characterized aliphatic-polyester (poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to investigate how the nature of protein association (adsorbed versus entrapped) and polymer/surfactant concentrations impact on the generation and modulation of antigen-specific immune responses. The ability of the NP formulations to target dendritic cells (DC), be internalized and activate the T cells was characterized and optimized in vitro and in vivo using markers of DC activation and co-stimulatory molecules. Ovalbumin (OVA) was used as a model antigen in combination with the engraftment of CD4 + and CD8 + T cells, carrying a transgenic OVA-responding T cell receptor (TCR), to trace and characterize the activation of antigen-specific CD4 + and CD8 + lymph node T cells upon NP vaccination. Accordingly, the phenotype and frequency of immune cell stimulation induced by the NP loaded with OVA, isolated or in combination with synthetic unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotide (ODN) motifs, were characterized. DC-NP interactions increased with incubation time, presenting internalization values between 50 and 60% and 30-40%, in vitro and in vivo, respectively. Interestingly, animal immunization with antigen-adsorbed NP up-regulated major histocompatibility complex (MHC) class II (MHCII), while NP entrapping the antigen up-regulated MHCI, suggesting a more efficient cross-presentation. On the other hand, rather surprisingly, the surfactant used in the NP formulation had a major impact on the activation of antigen presenting cells (APC). In fact, DC collected from lymph nodes of animals immunized with NP prepared using poly(vinil alcohol) (PVA), as a surfactant, expressed significantly higher levels of CD86, MHCI and MHCII. In addition, those NP prepared with PVA and co-entrapping OVA and the toll

  8. Robust and Accurate Discrimination of Self/Non-Self Antigen Presentations by Regulatory T Cell Suppression.

    Directory of Open Access Journals (Sweden)

    Chikara Furusawa

    Full Text Available The immune response by T cells usually discriminates self and non-self antigens, even though the negative selection of self-reactive T cells is imperfect and a certain fraction of T cells can respond to self-antigens. In this study, we construct a simple mathematical model of T cell populations to analyze how such self/non-self discrimination is possible. The results demonstrate that the control of the immune response by regulatory T cells enables a robust and accurate discrimination of self and non-self antigens, even when there is a significant overlap between the affinity distribution of T cells to self and non-self antigens. Here, the number of regulatory T cells in the system acts as a global variable controlling the T cell population dynamics. The present study provides a basis for the development of a quantitative theory for self and non-self discrimination in the immune system and a possible strategy for its experimental verification.

  9. Robust and Accurate Discrimination of Self/Non-Self Antigen Presentations by Regulatory T Cell Suppression.

    Science.gov (United States)

    Furusawa, Chikara; Yamaguchi, Tomoyuki

    The immune response by T cells usually discriminates self and non-self antigens, even though the negative selection of self-reactive T cells is imperfect and a certain fraction of T cells can respond to self-antigens. In this study, we construct a simple mathematical model of T cell populations to analyze how such self/non-self discrimination is possible. The results demonstrate that the control of the immune response by regulatory T cells enables a robust and accurate discrimination of self and non-self antigens, even when there is a significant overlap between the affinity distribution of T cells to self and non-self antigens. Here, the number of regulatory T cells in the system acts as a global variable controlling the T cell population dynamics. The present study provides a basis for the development of a quantitative theory for self and non-self discrimination in the immune system and a possible strategy for its experimental verification.

  10. Foetal and neonatal thyroid disorders.

    Science.gov (United States)

    Radetti, G; Zavallone, A; Gentili, L; Beck-Peccoz, P; Bona, G

    2002-10-01

    Thyroid hormones have been shown to be absolutely necessary for early brain development. During pregnancy, both maternal and foetal thyroid hormones contribute to foetal brain development and maternal supply explains why most of the athyreotic newborns usually do not show any signs of hypothyroidism at birth. Foetal and/or neonatal hypothyroidism is a rare disorder. Its incidence, as indicated by neonatal screening, is about 1:4000. Abnormal thyroid development (i.e. agenesia, ectopic gland, hypoplasia) or inborn errors in thyroid hormone biosynthesis are the most common causes of permanent congenital hypothyroidism. Recent studies reported that mutations involving Thyroid Transcriptor Factors (TTF) such as TTF-1, TTF-2, PAX-8 play an important role in altered foetal thyroid development. Deficiency of transcriptor factor (Pit-1, Prop-1, LHX-3) both in mother and in the foetus represents another rare cause of foetal hypothyroidism. At birth clinical picture may be not always so obvious and typical signs appear only after several weeks but a delayed diagnosis could have severe consequences consisting of delayed physical and mental development. Even if substitutive therapy is promptly started some learning difficulties might still arise suggesting that intrauterine adequate levels of thyroid hormones are absolutely necessary for a normal neurological development. Placental transfer of maternal antithyroid antibodies inhibiting fetal thyroid function can cause transient hypothyroidism at birth. If the mother with thyroid autoimmune disease is also hypothyroid during pregnancy and she doesn't receive substitutive therapy, a worse neurological outcome may be expected for her foetus. Foetal and/or neonatal hyperthyroidism is a rare condition and its incidence has been estimated around 1:4000-40000, according to various authors. The most common causes are maternal thyroid autoimmune disorders, such as Graves' disease and Hashimoto's thyroiditis. Rarer non autoimmune causes

  11. Regulatory T cells, maternal-foetal immune tolerance and recurrent miscarriage: new therapeutic challenging opportunities.

    Science.gov (United States)

    Alijotas-Reig, Jaume; Melnychuk, Taisiia; Gris, Josep Maria

    2015-03-15

    Because maternal alloreactive lymphocytes are not depleted during pregnancy, local and/or systemic mechanisms have to play a key role in altering the maternal immune response. Peripheral T regulatory cells (pTregs) at the maternal-foetal interface are necessary in situ to prevent early abortion, but only those pTregs that have been previously exposed to paternal alloantigens. It has been showed that pregnancy selectively stimulates the accumulation of maternal Foxp3(+)CD4(+)CD25(+) (Foxp3Tregs) cells with foetal specificity. Interestingly, after delivery, foetal-specific pTregs persist at elevated levels, maintain tolerance to pre-existing foetal antigen, and rapidly re-accumulate during subsequent pregnancy. pTreg up-regulation could be hypothesized as a possible future therapeutic strategy in humans. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  12. Three-day dendritic cells for vaccine development: Antigen uptake, processing and presentation

    Directory of Open Access Journals (Sweden)

    Schendel Dolores J

    2010-09-01

    Full Text Available Abstract Background Antigen-loaded dendritic cells (DC are capable of priming naïve T cells and therefore represent an attractive adjuvant for vaccine development in anti-tumor immunotherapy. Numerous protocols have been described to date using different maturation cocktails and time periods for the induction of mature DC (mDC in vitro. For clinical application, the use of mDC that can be generated in only three days saves on the costs of cytokines needed for large scale vaccine cell production and provides a method to produce cells within a standard work-week schedule in a GMP facility. Methods In this study, we addressed the properties of antigen uptake, processing and presentation by monocyte-derived DC prepared in three days (3d mDC compared with conventional DC prepared in seven days (7d mDC, which represent the most common form of DC used for vaccines to date. Results Although they showed a reduced capacity for spontaneous antigen uptake, 3d mDC displayed higher capacity for stimulation of T cells after loading with an extended synthetic peptide that requires processing for MHC binding, indicating they were more efficient at antigen processing than 7d DC. We found, however, that 3d DC were less efficient at expressing protein after introduction of in vitro transcribed (ivtRNA by electroporation, based on published procedures. This deficit was overcome by altering electroporation parameters, which led to improved protein expression and capacity for T cell stimulation using low amounts of ivtRNA. Conclusions This new procedure allows 3d mDC to replace 7d mDC for use in DC-based vaccines that utilize long peptides, proteins or ivtRNA as sources of specific antigen.

  13. Isolation of a peptide binding protein and its role in antigen presentation

    International Nuclear Information System (INIS)

    Lakey, E.; Pierce, S.K.; Margoliash, E.

    1986-01-01

    A mouse T cell hybrid, TPc9.1, recognizes pigeon cytochrome c (Pc) as processed and presented by histocompatible antigen presenting cells (APC). When paraformaldehyde fixed APC are employed, only a peptide fragment of Pc, Pc 81-104, and not the native Pc, is capable of stimulating TPc9.1 cells. Pc 81-104 appears to associate tightly with the APC surface since paraformaldehyde fixed APC which have been incubated with Pc 81-104 remain stimulatory following extensive washing. When APC are surface labeled with 125 I, solubilized and affinity purified on Pc 81-104-Sepharose 4B columns, two predominant polypeptides of approximately 72 and 74 kd are isolated. Little or no immunoglobulin, Class I or Class II proteins are obtained under these conditions. Antisera from rabbits immunized with the affinity purified material, but not preimmune sera, block the activation of TPc 9.1 cells by Pc as well as Pc 81-104 when presented by live APC. Furthermore, these antisera are even more effective in blocking the activation of TPc9.1 cells by either APC which had been pulsed with Pc and then paraformaldehyde fixed, or by Pc 81-104 when added to paraformaldehyde fixed APC, suggesting that these antisera were not affecting antigen processing. Thus, these peptide binding proteins may play a role in antigen presentation, and they are being further characterized

  14. Modulation of Immune Responses by Exosomes Derived from Antigen-Presenting Cells

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    Botros B. Shenoda

    2016-01-01

    Full Text Available Exosome-mediated signaling is important in mediating the inflammatory response. To exert their biological or pathophysiological functions in the recipient cells, exosomes deliver a diverse array of biomacromolecules including long and short coding and non-coding RNAs, proteins, and lipids. Exosomes secreted by antigen-presenting cells can confer therapeutic benefits by attenuating or stimulating the immune response. Exosomes play a crucial role in carrying and presenting functional major histocompatibility peptide complexes to modulate antigen-specific T cell responses. Exosomes from Dendritic Cells (DCs can activate T and B cells and have been explored for their immunostimulatory properties in cancer therapy. The immunosuppressive properties of exosomes derived from macrophages and DCs can reduce inflammation in animal models for several inflammatory disorders. This review focuses on the protective role of exosomes in attenuating inflammation or augmenting immune response, emphasizing studies on exosomes derived from DCs and macrophages.

  15. Antigen uptake and expression of antigen presentation-related immune genes in flounder (Paralichthys olivaceus) after vaccination with an inactivated Edwardsiella tarda immersion vaccine, following hyperosmotic treatment.

    Science.gov (United States)

    Gao, Yingli; Tang, Xiaoqian; Sheng, Xiuzhen; Xing, Jing; Zhan, Wenbin

    2016-08-01

    Antigen uptake is a critical process for activation of the immune system, and therefore the ability to enhance antigen uptake is a primary consideration in the development of an immersion vaccination of fish. In the present work, flounders (Paralichthys olivaceus) were immersed in three hyperosmotic solutions with 40, 50 and 60‰ salinities, then transferred into seawater of normal salinity (i.e. 30‰) containing formalin-inactivated Edwardsiella tarda for 30 min. The antigen uptake in vaccinated flounder was determined using an absolute quantitative PCR (qPCR). The results showed significantly higher antigen uptake in the tissues of flounders immersed in solutions with 50‰ and 60‰ salinity compared to the control group directly immersed in vaccine (DI) (P immersed in the 50‰ salinity solution, whereas there was no significant difference in antigen uptake between the 40‰ salinity group and the DI group (P > 0.05). A rapid and significant increase in antigen uptake was detected in the mucosal-associated tissues including the gill, skin and intestine (P immersion, which was significantly higher than the levels of uptake measured in the other tissues (P immersion (hpi). The expression profiles of four antigen presentation-related immune genes (MHC Iα, MHC IIα, CD4-1 and CD8α) were investigated after immersion. These four genes showed a significantly stronger response in the immersed flounders exposed to 50‰ salinity compared with the DI group (P immersion, notably 50‰ salinity significantly enhanced antigen uptake and the expression of selected genes associated with antigen presentation, providing evidence for an enhanced immune activation of the fish's immune response by the hyperosmotic immersion treatment prior to vaccination. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Antigen-presenting cells transfected with Hsp65 messenger RNA fail to treat experimental tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, C.D.; Trombone, A.P.F.; Lorenzi, J.C.C.; Almeida, L.P.; Gembre, A.F.; Padilha, E. [Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Ramos, S.G. [Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Silva, C.L.; Coelho-Castelo, A.A.M. [Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2012-09-21

    In the last several years, the use of dendritic cells has been studied as a therapeutic strategy against tumors. Dendritic cells can be pulsed with peptides or full-length protein, or they can be transfected with DNA or RNA. However, comparative studies suggest that transfecting dendritic cells with messenger RNA (mRNA) is superior to other antigen-loading techniques in generating immunocompetent dendritic cells. In the present study, we evaluated a new therapeutic strategy to fight tuberculosis using dendritic cells and macrophages transfected with Hsp65 mRNA. First, we demonstrated that antigen-presenting cells transfected with Hsp65 mRNA exhibit a higher level of expression of co-stimulatory molecules, suggesting that Hsp65 mRNA has immunostimulatory properties. We also demonstrated that spleen cells obtained from animals immunized with mock and Hsp65 mRNA-transfected dendritic cells were able to generate a mixed Th1/Th2 response with production not only of IFN-γ but also of IL-5 and IL-10. In contrast, cells recovered from mice immunized with Hsp65 mRNA-transfected macrophages were able to produce only IL-5. When mice were infected with Mycobacterium tuberculosis and treated with antigen-presenting cells transfected with Hsp65 mRNA (therapeutic immunization), we did not detect any decrease in the lung bacterial load or any preservation of the lung parenchyma, indicating the inability of transfected cells to confer curative effects against tuberculosis. In spite of the lack of therapeutic efficacy, this study reports for the first time the use of antigen-presenting cells transfected with mRNA in experimental tuberculosis.

  17. The role of cathepsin E in the antigen processing and presentation pathway.

    OpenAIRE

    Free, P. F.

    2006-01-01

    Although much has been unravelled with regards to the mechanisms of proteolysis of exogenously derived antigen for presentation via histocompatibility class-II (MHC-II), key questions remain unresolved. The exact role of each proteolytic enzyme in this process is not understood. The aspartic proteinase cathepsin E is hypothesised to play an important role. The aim of this study is to examine this by the use of novel aspartic proteinase inhibitors based upon the aspartic proteinase inhibitor p...

  18. CD1a presentation of endogenous antigens by group 2 innate lymphoid cells.

    Science.gov (United States)

    Hardman, Clare S; Chen, Yi-Ling; Salimi, Maryam; Jarrett, Rachael; Johnson, David; Järvinen, Valtteri J; Owens, Raymond J; Repapi, Emmanouela; Cousins, David J; Barlow, Jillian L; McKenzie, Andrew N J; Ogg, Graham

    2017-12-22

    Group 2 innate lymphoid cells (ILC2) are effectors of barrier immunity, with roles in infection, wound healing, and allergy. A proportion of ILC2 express MHCII (major histocompatibility complex II) and are capable of presenting peptide antigens to T cells and amplifying the subsequent adaptive immune response. Recent studies have highlighted the importance of CD1a-reactive T cells in allergy and infection, activated by the presentation of endogenous neolipid antigens and bacterial components. Using a human skin challenge model, we unexpectedly show that human skin-derived ILC2 can express CD1a and are capable of presenting endogenous antigens to T cells. CD1a expression is up-regulated by TSLP (thymic stromal lymphopoietin) at levels observed in the skin of patients with atopic dermatitis, and the response is dependent on PLA2G4A. Furthermore, this pathway is used to sense Staphylococcus aureus by promoting Toll-like receptor-dependent CD1a-reactive T cell responses to endogenous ligands. These findings define a previously unrecognized role for ILC2 in lipid surveillance and identify shared pathways of CD1a- and PLA2G4A-dependent ILC2 inflammation amenable to therapeutic intervention. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  19. Temporary hindlimb paresis following dystocia due to foetal macrosomia in a Celebes crested macaque (Macaca nigra).

    Science.gov (United States)

    Debenham, John James; Bettembourg, Vanessa; Østevik, Liv; Modig, Michaela; Jâderlund, Karin Hultin; Lervik, Andreas

    2017-04-01

    A multiparous Celebes crested macaque presented with dystocia due to foetal macrosomia, causing foetal mortality and hindlimb paresis. After emergency caesarean section, recovery of motor function took 1 month before hindlimbs were weight bearing and 2 months before re-integration with the troop. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Communication Profile of Primary School-Aged Children with Foetal Growth Restriction

    Science.gov (United States)

    Partanen, Lea Aulikki; Olsén, Päivi; Mäkikallio, Kaarin; Korkalainen, Noora; Heikkinen, Hanna; Heikkinen, Minna; Yliherva, Anneli

    2017-01-01

    Foetal growth restriction is associated with problems in neurocognitive development. In the present study, prospectively collected cohorts of foetal growth restricted (FGR) and appropriate for gestational age grown (AGA) children were examined at early school-age by using the Children's Communication Checklist-2 (CCC-2) to test the hypothesis that…

  1. Dendritic cells take up and present antigens from viable and apoptotic polymorphonuclear leukocytes.

    Directory of Open Access Journals (Sweden)

    Carlos Alfaro

    Full Text Available Dendritic cells (DC are endowed with the ability to cross-present antigens from other cell types to cognate T cells. DC are poised to meet polymorphonuclear leukocytes (PMNs as a result of being co-attracted by interleukin-8 (IL-8, for instance as produced by tumor cells or infected tissue. Human monocyte-derived and mouse bone marrow-derived DC can readily internalize viable or UV-irradiated PMNs. Such internalization was abrogated at 4°C and partly inhibited by anti-CD18 mAb. In mice, DC which had internalized PMNs containing electroporated ovalbumin (OVA protein, were able to cross-present the antigen to CD8 (OT-1 and CD4 (OT-2 TCR-transgenic T cells. Moreover, in humans, tumor cell debris is internalized by PMNs and the tumor-cell material can be subsequently taken up from the immunomagnetically re-isolated PMNs by DC. Importantly, if human neutrophils had endocytosed bacteria, they were able to trigger the maturation program of the DC. Moreover, when mouse PMNs with E. coli in their interior are co-injected in the foot pad with DC, many DC loaded with fluorescent material from the PMNs reach draining lymph nodes. Using CT26 (H-2(d mouse tumor cells, it was observed that if tumor cells are intracellularly loaded with OVA protein and UV-irradiated, they become phagocytic prey of H-2(d PMNs. If such PMNs, that cannot present antigens to OT-1 T cells, are immunomagnetically re-isolated and phagocytosed by H-2(b DC, such DC productively cross-present OVA antigen determinants to OT-1 T cells. Cross-presentation to adoptively transferred OT-1 lymphocytes at draining lymph nodes also take place when OVA-loaded PMNs (H-2(d are coinjected in the footpad of mice with autologous DC (H-2(b. In summary, our results indicate that antigens phagocytosed by short-lived PMNs can be in turn internalized and productively cross-presented by DC.

  2. ImmunoChip study implicates antigen presentation to T cells in narcolepsy.

    Directory of Open Access Journals (Sweden)

    Juliette Faraco

    Full Text Available Recent advances in the identification of susceptibility genes and environmental exposures provide broad support for a post-infectious autoimmune basis for narcolepsy/hypocretin (orexin deficiency. We genotyped loci associated with other autoimmune and inflammatory diseases in 1,886 individuals with hypocretin-deficient narcolepsy and 10,421 controls, all of European ancestry, using a custom genotyping array (ImmunoChip. Three loci located outside the Human Leukocyte Antigen (HLA region on chromosome 6 were significantly associated with disease risk. In addition to a strong signal in the T cell receptor alpha (TRA@, variants in two additional narcolepsy loci, Cathepsin H (CTSH and Tumor necrosis factor (ligand superfamily member 4 (TNFSF4, also called OX40L, attained genome-wide significance. These findings underline the importance of antigen presentation by HLA Class II to T cells in the pathophysiology of this autoimmune disease.

  3. Activation of nickel-specific CD4+ T lymphocytes in the absence of professional antigen-presenting cells.

    Science.gov (United States)

    Nasorri, Francesca; Sebastiani, Silvia; Mariani, Valentina; De Pità, Ornella; Puddu, Pietro; Girolomoni, Giampiero; Cavani, Andrea

    2002-01-01

    Allergic contact dermatitis ensues from exaggerated T cell responses to haptens. Dendritic cells are required for the initiation of hapten sensitization, but they may not be necessary for disease expression. Here we investigated the antigen-presenting cell requirement of nickel-specific CD4+ lymphocytes isolated from the blood of six allergic individuals. A significant proportion (42 out of 121; 35%) of the T cell clones proliferated in vitro to nickel also in the absence of professional antigen-presenting cells, suggesting a direct T-T hapten presentation. Antigen-presenting-cell-independent T cells showed a predominant T helper 1 phenotype. Nickel recognition by these T cells was major histocompatibility complex class II restricted, not influenced by CD28 triggering, independent from their state of activation, and did not require processing. The capacity of this T cell subset to be directly stimulated by nickel was not due to unique antigen-presenting properties, as both antigen-presenting-cell-dependent and antigen-presenting-cell-independent clones displayed comparable levels of HLA-DR, CD80, and CD86, and were equally capable of presenting nickel to antigen-presenting-cell-independent clones. In contrast, neither T cell types activated antigen-presenting-cell-dependent T lymphocytes. T-T presentation induced T cell receptor downregulation, CD25, CD80, CD86, and HLA-DR upregulation, and interferon-gamma release, although to a lesser extent compared to those induced by dendritic cell-T presentation. Following T-T presentation, the clones did not undergo unresponsiveness and maintained the capacity to respond to dendritic cells pulsed with antigen. In aggregate, our data suggest that antigen-presenting-cell-independent T cell activation can effectively amplify hapten- specific immune responses.

  4. The activation of the adaptive immune system: cross-talk between antigen-presenting cells, T cells and B cells.

    Science.gov (United States)

    den Haan, Joke M M; Arens, Ramon; van Zelm, Menno C

    2014-12-01

    The adaptive immune system consists of T and B cells that express clonally distributed antigen receptors. To achieve functional adaptive immune responses, antigen-specific T cell populations are stimulated by professional antigen-presenting cells like dendritic cells (DCs), which provide crucial stimulatory signals for efficient expansion and development of effector functions. Antigen-specific B cells receive costimulatory signals from helper T cells to stimulate affinity maturation and isotype switching. Here we elaborate on the interactions between DCs, T cells and B cells, and on the important signals for efficient induction of adaptive immune responses. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Homozygous mutation in the NPHP3 gene causing foetal nephronophthisis

    DEFF Research Database (Denmark)

    Abdullah, Uzma; Farooq, Muhammad; Fatima, Ambrin

    2017-01-01

    We present a case of a foetal sonographic finding of hyper-echogenic kidneys, which led to a strategic series of genetic tests and identified a homozygous mutation (c.424C > T, p. R142*) in the NPHP3 gene. Our study provides a rare presentation of NPHP3-related ciliopathy and adds to the mutation...

  6. Effect of cold nerve allograft preservation on antigen presentation and rejection

    Science.gov (United States)

    Ray, Wilson Z.; Kale, Santosh S.; Kasukurthi, Rahul; Papp, Esther M.; Johnson, Philip J.; Santosa, Katherine B.; Yan, Ying; Hunter, Daniel A.; Mackinnon, Susan E.; Tung, Thomas H.

    2010-01-01

    Object Nerve allotransplantation provides a temporary scaffold for host nerve regeneration and allows for the reconstruction of significant segmental nerve injuries. The need for systemic the current clinical utilization of nerve allografts, although this need is reduced by the practice of cold nerve allograft preservation. Activation of T cells in response to alloantigen presentation occurs in the context of donor antigen presenting cells (direct pathway) or host antigen-presenting cells (indirect pathway). The relative role of each pathway in eliciting an alloimmune response and its potential for rejection of the nerve allograft model has not previously been investigated. The objective of this investigation was to study the effect of progressive periods of cold nerve allograft preservation on antigen presentation and the alloimmune response. Methods The authors used wild type C57Bl/6 (B6), BALB/c, and major histocompatibility Class II–deficient (MHC−/−) C57Bl/6 mice as both nerve allograft recipients and donors. A nonvascularized nerve allograft was used to reconstruct a 1-cm sciatic nerve gap. Progressive cold preservation of donor nerve allografts was used. Quantitative assessment was made after 3 weeks using nerve histomorphometry. Results The donor-recipient combination lacking a functional direct pathway (BALB/c host with MHC−/− graft) rejected nerve allografts as vigorously as wild-type animals. Without an intact indirect pathway (MHC−/− host with BALB/c graft), axonal regeneration was improved (p < 0.052). One week of cold allograft preservation did not improve regeneration to any significant degree in any of the donor-recipient preservation did improve regeneration significantly (p < 0.05) for all combinations compared with wild-type animals without pretreatment. However, only in the presence of an intact indirect pathway (no direct pathway) did 4 weeks of cold preservation improve regeneration significantly compared with 1 week and no

  7. A Lipid Based Antigen Delivery System Efficiently Facilitates MHC Class-I Antigen Presentation in Dendritic Cells to Stimulate CD8+ T Cells

    Science.gov (United States)

    Maji, Mithun; Mazumder, Saumyabrata; Bhattacharya, Souparno; Choudhury, Somsubhra Thakur; Sabur, Abdus; Shadab, Md.; Bhattacharya, Pradyot; Ali, Nahid

    2016-06-01

    The most effective strategy for protection against intracellular infections such as Leishmania is vaccination with live parasites. Use of recombinant proteins avoids the risks associated with live vaccines. However, due to low immunogenicity, they fail to trigger T cell responses particularly of CD8+ cells requisite for persistent immunity. Previously we showed the importance of protein entrapment in cationic liposomes and MPL as adjuvant for elicitation of CD4+ and CD8+ T cell responses for long-term protection. In this study we investigated the role of cationic liposomes on maturation and antigen presentation capacity of dendritic cells (DCs). We observed that cationic liposomes were taken up very efficiently by DCs and transported to different cellular sites. DCs activated with liposomal rgp63 led to efficient presentation of antigen to specific CD4+ and CD8+ T cells. Furthermore, lymphoid CD8+ T cells from liposomal rgp63 immunized mice demonstrated better proliferative ability when co-cultured ex vivo with stimulated DCs. Addition of MPL to vaccine enhanced the antigen presentation by DCs and induced more efficient antigen specific CD8+ T cell responses when compared to free and liposomal antigen. These liposomal formulations presented to CD8+ T cells through TAP-dependent MHC-I pathway offer new possibilities for a safe subunit vaccine.

  8. Intestinal Epithelial Cells Modulate Antigen-Presenting Cell Responses to Bacterial DNA

    Science.gov (United States)

    Campeau, J. L.; Salim, S. Y.; Albert, E. J.; Hotte, N.

    2012-01-01

    Intestinal epithelial cells and antigen-presenting cells orchestrate mucosal innate immunity. This study investigated the role of bacterial DNA in modulating epithelial and bone marrow-derived antigen-presenting cells (BM-APCs) and subsequent T-lymphocyte responses. Murine MODE-K epithelial cells and BM-APCs were treated with DNA from either Bifidobacterium breve or Salmonella enterica serovar Dublin directly and under coculture conditions with CD4+ T cells. Apical stimulation of MODE-K cells with S. Dublin DNA enhanced secretion of cytokines from underlying BM-APCs and induced interleukin-17 (IL-17) and gamma interferon (IFN-γ) secretion from CD4+ T cells. Bacterial DNA isolated from either strain induced maturation and increased cytokine secretion from BM-APCs. Conditioned medium from S. Dublin-treated MODE-K cells elicited an increase in cytokine secretion similar to that seen for S. Dublin DNA. Treatment of conditioned medium from MODE-K cells with RNase and protease prevented the S. Dublin-induced increased cytokine secretion. Oral feeding of mice with B. breve DNA resulted in enhanced levels of colonic IL-10 and transforming growth factor β (TGFβ) compared with what was seen for mice treated with S. Dublin DNA. In contrast, feeding mice with S. Dublin DNA increased levels of colonic IL-17 and IL-12p70. T cells from S. Dublin DNA-treated mice secreted high levels of IL-12 and IFN-γ compared to controls and B. breve DNA-treated mice. These results demonstrate that intestinal epithelial cells are able to modulate subsequent antigen-presenting and T-cell responses to bacterial DNA with pathogenic but not commensal bacterial DNA inducing effector CD4+ T lymphocytes. PMID:22615241

  9. A sub-population of circulating porcine gammadelta T cells can act as professional antigen presenting cells.

    Science.gov (United States)

    Takamatsu, H-H; Denyer, M S; Wileman, T E

    2002-09-10

    A sub-population of circulating porcine gammadelta T cells express cell surface antigens associated with antigen presenting cells (APCs), and are able to take up soluble antigen very effectively. Functional antigen presentation by gammadelta T cells to memory helper T cells was studied by inbred pig lymphocytes immunised with ovalbumin (OVA). After removing all conventional APCs from the peripheral blood of immunised pigs, the remaining lymphocytes still proliferated when stimulated with OVA. When gammadelta T cells were further depleted, OVA specific proliferation was abolished, but reconstitution with gammadelta T cells restored proliferation. The proliferation was blocked by monoclonal antibodies (mAb) against MHC class II or CD4, and by pre-treatment of gammadelta T cells with chloroquine. These results indicate that a sub-population of circulating porcine gammadelta T cells act as APCs and present antigen via MHC class II.

  10. Foetal uptake of coplanar polychlorinated biphenyl (PCB) congeners in mice

    International Nuclear Information System (INIS)

    Darnerud, P.O.; Sinjari, T.; Joensson, C.J.

    1996-01-01

    Earlier studies have shown that the Ah-receptor binding polychlorinated biphenyl (PCB) congener 3,3',4,4'-tetrachlorobiphenyl (IUPAC number CB-77) accumulated as hydroxy and methylsulphone metabolites in late gestational mice foetuses. In the present paper the foetal accumulation potential in mice of other dioxin-like PCB congeners was studied: 3,3'4,4',4-pentachlorobiphenyl, 3,3'4,4'5,5'-hexachlorobiphenyl and 2,3,3',4,4'-pentachlorobiphenyl (IUPAC numbers CB-126, CB-169, CB-105, to some extent dioxin-like) were compared to results of CB-77 (all congeners 14 C-labelled and in equimolar doses (2.0 μmol/kg body wt.)). CB-77 resulted in the comparatively strongest foetal 14 C-accumulation, when measured in plasma or whole body homogenate four days after administration (day 17 of pregnancy); the plasma 14 C-values (calculated as pmol/g wet wt.) were 760, 130, 60 and 40 for CB-77, -126, 105 and -169, respectively, and the CB-77 derived radioactivity in the foetal compartment was 3.6% of administered dose (i.e. a considerable portion of the remaining maternal body radioactivity). Thin-layer chromatography (TLC) results, suggesting extensive CB-77 metabolism and foetal metabolite uptake, support earlier findings. The effects of CB-77 and CB-169 on foetal 7-ethoxyresorufin-O-deethylase (EROD) activities (day 17 of gestation; two days after 5 mg/kg body wt. dose (14.0-17.0 μmol/kg body wt.)) was about 20 times lower than of CB-126. In the dam, high radioactivity levels were observed int he liver and fat (highest concentrations found in CB-126 and CB-105, respectively). Strain comparison - foetal 14 C-uptake (four days after administration of CB-77) in C57BL mice was almost five times higher than in NMRI - may be correlated to earlier observed differences in EROD activities between these strains. The present results indicate that congener and strain differences exist regarding both foetal and maternal distribution patterns of coplanar PCB congeners and point out the

  11. Papaya ringspot virus coat protein gene for antigen presentation Escherichia coli

    Czech Academy of Sciences Publication Activity Database

    Chatchen, S.; Juříček, Miloslav; Rueda, P.; Kertbundit, Sunee

    2006-01-01

    Roč. 39, č. 1 (2006), s. 16-21 ISSN 1225-8687 Grant - others:Thai Research Fund(TH) BT-B-06-PG-14-4503 Institutional research plan: CEZ:AV0Z50380511 Source of funding: V - iné verejné zdroje Keywords : antigen presentation * canine parvo virus * epitope * papaya ringspot virus Subject RIV: EF - Botanics Impact factor: 1.465, year: 2006 http://www.jbmb.or.kr/view_article.php3?cont=jbmb&kid=174&mid=3&pid=3

  12. Generation of competent bone marrow-derived antigen presenting cells from the deer mouse (Peromyscus maniculatus

    Directory of Open Access Journals (Sweden)

    Farrell Regina M

    2004-09-01

    Full Text Available Abstract Background Human infections with Sin Nombre virus (SNV and related New World hantaviruses often lead to hantavirus cardiopulmonary syndrome (HCPS, a sometimes fatal illness. Lungs of patients who die from HCPS exhibit cytokine-producing mononuclear infiltrates and pronounced pulmonary inflammation. Deer mice (Peromyscus maniculatus are the principal natural hosts of SNV, in which the virus establishes life-long persistence without conspicuous pathology. Little is known about the mechanisms SNV employs to evade the immune response of deer mice, and experimental examination of this question has been difficult because of a lack of methodologies for examining such responses during infection. One such deficiency is our inability to characterize T cell responses because susceptible syngeneic deer mice are not available. Results To solve this problem, we have developed an in vitro method of expanding and generating competent antigen presenting cells (APC from deer mouse bone marrow using commercially-available house mouse (Mus musculus granulocyte-macrophage colony stimulating factor. These cells are capable of processing and presenting soluble protein to antigen-specific autologous helper T cells in vitro. Inclusion of antigen-specific deer mouse antibody augments T cell stimulation, presumably through Fc receptor-mediated endocytosis. Conclusions The use of these APC has allowed us to dramatically expand deer mouse helper T cells in culture and should permit extensive characterization of T cell epitopes. Considering the evolutionary divergence between deer mice and house mice, it is probable that this method will be useful to other investigators using unconventional models of rodent-borne diseases.

  13. Cationic liposomes promote antigen cross-presentation in dendritic cells by alkalizing the lysosomal pH and limiting the degradation of antigens

    Directory of Open Access Journals (Sweden)

    Gao J

    2017-02-01

    Full Text Available Jie Gao,1–3 Lukasz J Ochyl,1,3 Ellen Yang,4 James J Moon1,3,5 1Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA; 2Department of Pharmaceutical Sciences, School of Pharmacy, Second Military Medical University, Shanghai, People’s Republic of China; 3Biointerfaces Institute, 4Department of Chemistry, 5Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA Abstract: Cationic liposomes (CLs have been widely examined as vaccine delivery nanoparticles since they can form complexes with biomacromolecules, promote delivery of antigens and adjuvant molecules to antigen-presenting cells (APCs, and mediate cellular uptake of vaccine components. CLs are also known to trigger antigen cross-presentation – the process by which APCs internalize extracellular protein antigens, degrade them into minimal CD8+ T-cell epitopes, and present them in the context of major histocompatibility complex-I (MHC-I. However, the precise mechanisms behind CL-mediated induction of cross-presentation and cross-priming of CD8+ T-cells remain to be elucidated. In this study, we have developed two distinct CL systems and examined their impact on the lysosomal pH in dendritic cells (DCs, antigen degradation, and presentation of peptide:MHC-I complexes to antigen-specific CD8+ T-cells. To achieve this, we have used 3β-[N-(N',N'-dimethylaminoethane-carbamoyl] cholesterol (DC-Chol and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP as the prototypical components of CLs with tertiary amine groups and compared the effect of CLs and anionic liposomes on lysosomal pH, antigen degradation, and cross-presentation by DCs. Our results showed that CLs, but not anionic liposomes, elevated the lysosomal pH in DCs and reduced antigen degradation, thereby promoting cross-presentation and cross-priming of CD8+ T-cell responses. These studies shed new light on CL-mediated cross-presentation and suggest that intracellular fate of vaccine

  14. Orthodontics and foetal pathology: a personal view on craniofacial patterning

    DEFF Research Database (Denmark)

    Kjær, Inger

    2009-01-01

    This article summarizes the essentials of studies on the craniofacial skeleton performed over 17 years. It presents data from research into foetal pathology resulting in new views on craniofacial patterning and/or fields for further discussion. The fields described cover all areas seen on profile...

  15. Dynamic imaging of experimental Leishmania donovani-induced hepatic granulomas detects Kupffer cell-restricted antigen presentation to antigen-specific CD8 T cells.

    Directory of Open Access Journals (Sweden)

    Lynette Beattie

    2010-03-01

    Full Text Available Kupffer cells (KCs represent the major phagocytic population within the liver and provide an intracellular niche for the survival of a number of important human pathogens. Although KCs have been extensively studied in vitro, little is known of their in vivo response to infection and their capacity to directly interact with antigen-specific CD8(+ T cells. Here, using a combination of approaches including whole mount and thin section confocal microscopy, adoptive cell transfer and intra-vital 2-photon microscopy, we demonstrate that KCs represent the only detectable population of mononuclear phagocytes within granulomas induced by Leishmania donovani infection that are capable of presenting parasite-derived peptide to effector CD8(+ T cells. This restriction of antigen presentation to KCs within the Leishmania granuloma has important implications for the identification of new candidate vaccine antigens and for the design of novel immuno-therapeutic interventions.

  16. Antigen presenting cells costimulatory signaling during pre-implantation pregnancy 

    Directory of Open Access Journals (Sweden)

    Anna Sławek

    2012-09-01

    Full Text Available  Success of pregnancy depends on many factors. Three phenomena inducing immune tolerance against semi-allogeneic conceptus may play a crucial role in the pre-implantation period of pregnancy: influence of sex hormones in sex cycle, presence of oocyte or embryo and the presence of semen in the female reproductive tract. On the other hand dendritic cells are the most effective antigen-presenting cells in regulation of immune phenomena and also are considered as potent participants in inducing immune tolerance in the pregnancy. They communicate with T cells in cell contact-dependent manner or via cytokines. During cell-cell contacts, costimulatory molecules play a key role and their expression is often dependent on cytokines milieu. Both costimulatory molecules and cytokines influence generation of T regulatory cells. Interactions of these molecules are closely related. In this paper we would like to pay attention to the importance of antigen presenting cells costimulatory potency in immune regulation during a pre-implantation period of pregnancy.

  17. Activation of professional antigen presenting cells by acharan sulfate isolated from giant African snail, Achatina fulica.

    Science.gov (United States)

    Kim, Hyun-Sun; Lee, Young-Hee; Lee, Young-Ran; Im, Sun-A; Lee, Jae-Kwon; Kim, Yeong Shik; Sim, Joon-Soo; Choi, Hyung Seok; Lee, Chong-Kil

    2007-07-01

    Acharan sulfate isolated from the giant African snail, Achatina fulica, has been reported to have antitumor activity in vivo. In an effort to determine the mechanisms of its antitumor activity, we examined the effects of acharan sulfate on professional antigen presenting cells (APCs). Acharan sulfate increased the phagocytic activity, the production of cytokines such as TNF-alpha and IL-1beta, and the release of nitric oxide on a macrophage cell line, Raw 264.7 cells. In addition, acharan sulfate induced phenotypic and functional maturation of immature dendritic cells (DCs). Immature DCs cultured with acharan sulfate expressed higher levels of class II MHC molecules and major co-stimulatory molecules such as B7-1, B7-2, and CD40. Functional maturation of immature DCs cultured in the presence of acharan sulfate was confirmed by the increased allostimulatory capacity and IL-12 production. These results suggest that the antitumor activity of acharan sulfate is partly due to the activation of professional antigen presenting cells.

  18. CD1d-mediated presentation of endogenous lipid antigens by adipocytes requires microsomal triglyceride transfer protein (MTP)

    DEFF Research Database (Denmark)

    Rakhshandehroo, Maryam; Gijzel, Sanne M W; Siersbæk, Rasmus

    2014-01-01

    -dependent fashion, but little is known about the lipid antigen presentation machinery in adipocytes. Here we show that CD1d, as well as the lipid antigen loading machinery genes pro-saposin (Psap), Niemann Pick type C2 (Npc2), α-galactosidase (Gla), are upregulated in early adipogenesis, and are transcriptionally...... presenting cells (APCs), which may present an important aspect of adipocyte-immune cell communication in the regulation of whole body energy metabolism and immune homeostasis....

  19. Understanding the immunogenicity and antigenicity of nanomaterials: Past, present and future

    International Nuclear Information System (INIS)

    Ilinskaya, Anna N.; Dobrovolskaia, Marina A.

    2016-01-01

    Nanoparticle immunogenicity and antigenicity have been under investigation for many years. During the past decade, significant progress has been made in understanding what makes a nanoparticle immunogenic, how immune cells respond to nanoparticles, what consequences of nanoparticle-specific antibody formation exist and how they challenge the application of nanoparticles for drug delivery. Moreover, it has been recognized that accidental contamination of therapeutic protein formulations with nanosized particulate materials may contribute to the immunogenicity of this type of biotechnology products. While the immunological properties of engineered nanomaterials and their application as vaccine carriers and adjuvants have been given substantial consideration in the current literature, little attention has been paid to nanoparticle immuno- and antigenicity. To fill in this gap, we herein provide an overview of this subject to highlight the current state of the field, review past and present research, and discuss future research directions. - Highlights: • Most engineered nanomaterials are not immunogenic per se. • Generation of nanoparticle-specific antibody can be T-cell dependent or independent. • Antibodies can be generated to particle core, terminal groups or surface coatings. • Engineered and accidental nanomaterials have distinct contribution to immunogenicity. • Tunable physicochemical properties make each nanoparticle unique.

  20. Understanding the immunogenicity and antigenicity of nanomaterials: Past, present and future

    Energy Technology Data Exchange (ETDEWEB)

    Ilinskaya, Anna N.; Dobrovolskaia, Marina A., E-mail: marina@mail.nih.gov

    2016-05-15

    Nanoparticle immunogenicity and antigenicity have been under investigation for many years. During the past decade, significant progress has been made in understanding what makes a nanoparticle immunogenic, how immune cells respond to nanoparticles, what consequences of nanoparticle-specific antibody formation exist and how they challenge the application of nanoparticles for drug delivery. Moreover, it has been recognized that accidental contamination of therapeutic protein formulations with nanosized particulate materials may contribute to the immunogenicity of this type of biotechnology products. While the immunological properties of engineered nanomaterials and their application as vaccine carriers and adjuvants have been given substantial consideration in the current literature, little attention has been paid to nanoparticle immuno- and antigenicity. To fill in this gap, we herein provide an overview of this subject to highlight the current state of the field, review past and present research, and discuss future research directions. - Highlights: • Most engineered nanomaterials are not immunogenic per se. • Generation of nanoparticle-specific antibody can be T-cell dependent or independent. • Antibodies can be generated to particle core, terminal groups or surface coatings. • Engineered and accidental nanomaterials have distinct contribution to immunogenicity. • Tunable physicochemical properties make each nanoparticle unique.

  1. Engineering tolerance using biomaterials to target and control antigen presenting cells.

    Science.gov (United States)

    Tostanoski, Lisa H; Gosselin, Emily A; Jewell, Christopher M

    2016-05-01

    Autoimmune diseases occur when cells of the adaptive immune system incorrectly recognize and attack "self" tissues. Importantly, the proliferation and differentiation of these cells is triggered and controlled by interactions with antigen presenting cells (APCs), such as dendritic cells. Thus, modulating the signals transduced by APCs (e.g., cytokines, costimulatory surface proteins) has emerged as a promising strategy to promote tolerance for diseases such as multiple sclerosis, type 1 diabetes, and lupus. However, many approaches have been hindered by non-specific activity of immunosuppressive or immunoregulatory cues, following systemic administration of soluble factors via traditional injections routes (e.g., subcutaneous, intravenous). Biomaterials offer a unique opportunity to control the delivery of tolerogenic signals in vivo via properties such as controlled particle size, tunable release kinetics, and co-delivery of multiple classes of cargo. In this review, we highlight recent reports that exploit these properties of biomaterials to target APCs and promote tolerance via three strategies, i) passive or active targeting of particulate carriers to APCs, ii) biomaterial-mediated control over antigen localization and processing, and iii) targeted delivery of encapsulated or adsorbed immunomodulatory signals. These reports represent exciting advances toward the goal of more effective therapies for autoimmune diseases, without the broad suppressive effects associated with current clinically-approved therapies.

  2. Conventional CD4+ T cells present bacterial antigens to induce cytotoxic and memory CD8+ T cell responses.

    Science.gov (United States)

    Cruz-Adalia, Aránzazu; Ramirez-Santiago, Guillermo; Osuna-Pérez, Jesús; Torres-Torresano, Mónica; Zorita, Virgina; Martínez-Riaño, Ana; Boccasavia, Viola; Borroto, Aldo; Martínez Del Hoyo, Gloria; González-Granado, José María; Alarcón, Balbino; Sánchez-Madrid, Francisco; Veiga, Esteban

    2017-11-17

    Bacterial phagocytosis and antigen cross-presentation to activate CD8 + T cells are principal functions of professional antigen presenting cells. However, conventional CD4 + T cells also capture and kill bacteria from infected dendritic cells in a process termed transphagocytosis (also known as transinfection). Here, we show that transphagocytic T cells present bacterial antigens to naive CD8 + T cells, which proliferate and become cytotoxic in response. CD4 + T-cell-mediated antigen presentation also occurs in vivo in the course of infection, and induces the generation of central memory CD8 + T cells with low PD-1 expression. Moreover, transphagocytic CD4 + T cells induce protective anti-tumour immune responses by priming CD8 + T cells, highlighting the potential of CD4 + T cells as a tool for cancer immunotherapy.

  3. 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.

  4. The placenta and foetal membranes of the lesser yellow house bat ...

    African Journals Online (AJOL)

    A discoidal hemodichorial placenta is present in Scotophilus borbonicus. Evidence is presented which suggests that histotrophic nutrition, in addition to hemotrophic nutrition, occurs. The foetal trophospongium phagocytoses cell debris and glandular secretions derived from the maternal endometrium (decidua basalis).

  5. Interleukin production by neonatal spleen cells during and as a result of antigen presentation: The effect of ultraviolet light

    International Nuclear Information System (INIS)

    Levin, D.; Gershon, H.

    1989-01-01

    Antigen presentation by neonatal murine spleen cells and the production of lymphokines and interleukins involved in the stimulation of a T-helper-2 (TH2) cell line (D10-G4.1) were studied as were the effects of ultra violet (UV)-irradiation on this system. Neonatal spleen cells are less capable than adult cells of performing the initial steps of the immune response required for antigen dependent activation of TH2 cells. These steps include soluble antigen processing and presentation and as a result reduced production of IL-4 and IL-1-Inducer Factor (IL-1-IF) by the T-helper cells and reduced production of IL-1 and IL-2 by the antigen presenting cell population. Spontaneous membrane IL-1 activity is low in the neonate, however, when exposed to IL-1-IF they can express adult levels. Ultraviolet (UV) irradiation of the antigen presenting population has a damaging effect on all the above mentioned processes. Antigen processing and presentation, induction of D10 IL-4 production and proliferation, and IL-2 production demonstrate two different age related patterns of UV-irradiation induced damage: a dose dependent inhibition when adult cells are irradiated and an inverse effect in which low doses of irradiation were more inhibitory than higher doses when neonatal cells are irradiated. However, the secretion and membrane expression of IL-1 by both age groups are directly and totally inhibited by the range of UV-irradiation doses used and cannot be reinduced with a supplement of a crude IL-1-IF. While the capacity to produced IL-1 is totally destroyed by UV-irradiation, the ability to produce IL-2 remains intact and remains responsive to an IL-2-Inducer activity during proper antigen presentation. The low responses of neonatal antigen presenting spleen cell populations and the damaging effect of UV on both neonatal and adult responses are not due to the induction of suppressor factors

  6. Identification of immunogenic hot spots within plum pox potyvirus capsid protein for efficient antigen presentation.

    Science.gov (United States)

    Fernández-Fernández, M Rosario; Martínez-Torrecuadrada, Jorge L; Roncal, Fernando; Domínguez, Elvira; García, Juan Antonio

    2002-12-01

    PEPSCAN analysis has been used to characterize the immunogenic regions of the capsid protein (CP) in virions of plum pox potyvirus (PPV). In addition to the well-known highly immunogenic N- and C-terminal domains of CP, regions within the core domain of the protein have also shown high immunogenicity. Moreover, the N terminus of CP is not homogeneously immunogenic, alternatively showing regions frequently recognized by antibodies and others that are not recognized at all. These results have helped us to design efficient antigen presentation vectors based on PPV. As predicted by PEPSCAN analysis, a small displacement of the insertion site in a previously constructed vector, PPV-gamma, turned the derived chimeras into efficient immunogens. Vectors expressing foreign peptides at different positions within a highly immunogenic region (amino acids 43 to 52) in the N-terminal domain of CP were the most effective at inducing specific antibody responses against the foreign sequence.

  7. Enhancement of MHC-I antigen presentation via architectural control of pH-responsive, endosomolytic polymer nanoparticles.

    Science.gov (United States)

    Wilson, John T; Postma, Almar; Keller, Salka; Convertine, Anthony J; Moad, Graeme; Rizzardo, Ezio; Meagher, Laurence; Chiefari, John; Stayton, Patrick S

    2015-03-01

    Protein-based vaccines offer a number of important advantages over organism-based vaccines but generally elicit poor CD8(+) T cell responses. We have previously demonstrated that pH-responsive, endosomolytic polymers can enhance protein antigen delivery to major histocompatibility complex class I (MHC-I) antigen presentation pathways thereby augmenting CD8(+) T cell responses following immunization. Here, we describe a new family of nanocarriers for protein antigen delivery assembled using architecturally distinct pH-responsive polymers. Reversible addition-fragmentation chain transfer (RAFT) polymerization was used to synthesize linear, hyperbranched, and core-crosslinked copolymers of 2-(N,N-diethylamino)ethyl methacrylate (DEAEMA) and butyl methacrylate (BMA) that were subsequently chain extended with a hydrophilic N,N-dimethylacrylamide (DMA) segment copolymerized with thiol-reactive pyridyl disulfide (PDS) groups. In aqueous solution, polymer chains assembled into 25 nm micellar nanoparticles and enabled efficient and reducible conjugation of a thiolated protein antigen, ovalbumin. Polymers demonstrated pH-dependent membrane-destabilizing activity in an erythrocyte lysis assay, with the hyperbranched and cross-linked polymer architectures exhibiting significantly higher hemolysis at pH ≤ 7.0 than the linear diblock. Antigen delivery with the hyperbranched and cross-linked polymer architecture enhanced in vitro MHC-I antigen presentation relative to free antigen, whereas the linear construct did not have a discernible effect. The hyperbranched system elicited a four- to fivefold increase in MHC-I presentation relative to the cross-linked architecture, demonstrating the superior capacity of the hyperbranched architecture in enhancing MHC-I presentation. This work demonstrates that the architecture of pH-responsive, endosomolytic polymers can have dramatic effects on intracellular antigen delivery, and offers a promising strategy for enhancing CD8(+) T cell

  8. Interaction of Cowpea Mosaic Virus (CPMV) Nanoparticles with Antigen Presenting Cells In Vitro and In Vivo

    Science.gov (United States)

    Rae, Chris S.; Manchester, Marianne

    2009-01-01

    Background Plant viruses such as Cowpea mosaic virus (CPMV) are increasingly being developed for applications in nanobiotechnology including vaccine development because of their potential for producing large quantities of antigenic material in plant hosts. In order to improve efficacy of viral nanoparticles in these types of roles, an investigation of the individual cell types that interact with the particles is critical. In particular, it is important to understand the interactions of a potential vaccine with antigen presenting cells (APCs) of the immune system. CPMV was previously shown to interact with vimentin displayed on cell surfaces to mediate cell entry, but the expression of surface vimentin on APCs has not been characterized. Methodology The binding and internalization of CPMV by several populations of APCs was investigated both in vitro and in vivo by flow cytometry and fluorescence confocal microscopy. The association of the particles with mouse gastrointestinal epithelium and Peyer's patches was also examined by confocal microscopy. The expression of surface vimentin on APCs was also measured. Conclusions We found that CPMV is bound and internalized by subsets of several populations of APCs both in vitro and in vivo following intravenous, intraperitoneal, and oral administration, and also by cells isolated from the Peyer's patch following gastrointestinal delivery. Surface vimentin was also expressed on APC populations that could internalize CPMV. These experiments demonstrate that APCs capture CPMV particles in vivo, and that further tuning the interaction with surface vimentin may facilitate increased uptake by APCs and priming of antibody responses. These studies also indicate that CPMV particles likely access the systemic circulation following oral delivery via the Peyer's patch. PMID:19956734

  9. Engineered artificial antigen presenting cells facilitate direct and efficient expansion of tumor infiltrating lymphocytes

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    Coukos George

    2011-08-01

    Full Text Available Abstract Background Development of a standardized platform for the rapid expansion of tumor-infiltrating lymphocytes (TILs with anti-tumor function from patients with limited TIL numbers or tumor tissues challenges their clinical application. Methods To facilitate adoptive immunotherapy, we applied genetically-engineered K562 cell-based artificial antigen presenting cells (aAPCs for the direct and rapid expansion of TILs isolated from primary cancer specimens. Results TILs outgrown in IL-2 undergo rapid, CD28-independent expansion in response to aAPC stimulation that requires provision of exogenous IL-2 cytokine support. aAPCs induce numerical expansion of TILs that is statistically similar to an established rapid expansion method at a 100-fold lower feeder cell to TIL ratio, and greater than those achievable using anti-CD3/CD28 activation beads or extended IL-2 culture. aAPC-expanded TILs undergo numerical expansion of tumor antigen-specific cells, remain amenable to secondary aAPC-based expansion, and have low CD4/CD8 ratios and FOXP3+ CD4+ cell frequencies. TILs can also be expanded directly from fresh enzyme-digested tumor specimens when pulsed with aAPCs. These "young" TILs are tumor-reactive, positively skewed in CD8+ lymphocyte composition, CD28 and CD27 expression, and contain fewer FOXP3+ T cells compared to parallel IL-2 cultures. Conclusion Genetically-enhanced aAPCs represent a standardized, "off-the-shelf" platform for the direct ex vivo expansion of TILs of suitable number, phenotype and function for use in adoptive immunotherapy.

  10. A viral, transporter associated with antigen processing (TAP)-independent, high affinity ligand with alternative interactions endogenously presented by the nonclassical human leukocyte antigen E class I molecule.

    Science.gov (United States)

    Lorente, Elena; Infantes, Susana; Abia, David; Barnea, Eilon; Beer, Ilan; García, Ruth; Lasala, Fátima; Jiménez, Mercedes; Mir, Carmen; Morreale, Antonio; Admon, Arie; López, Daniel

    2012-10-12

    The transporter associated with antigen processing (TAP) enables the flow of viral peptides generated in the cytosol by the proteasome and other proteases to the endoplasmic reticulum, where they complex with nascent human leukocyte antigen (HLA) class I. Later, these peptide-HLA class I complexes can be recognized by CD8(+) lymphocytes. Cancerous cells and infected cells in which TAP is blocked, as well as individuals with unusable TAP complexes, are able to present peptides on HLA class I by generating them through TAP-independent processing pathways. Here, we identify a physiologically processed HLA-E ligand derived from the D8L protein in TAP-deficient vaccinia virus-infected cells. This natural high affinity HLA-E class I ligand uses alternative interactions to the anchor motifs previously described to be presented on nonclassical HLA class I molecules. This octameric peptide was also presented on HLA-Cw1 with similar binding affinity on both classical and nonclassical class I molecules. In addition, this viral peptide inhibits HLA-E-mediated cytolysis by natural killer cells. Comparison between the amino acid sequences of the presenting HLA-E and HLA-Cw1 alleles revealed a shared structural motif in both HLA class molecules, which could be related to their observed similar cross-reactivity affinities. This motif consists of several residues located on the floor of the peptide-binding site. These data expand the role of HLA-E as an antigen-presenting molecule.

  11. Foetal response to music and voice.

    Science.gov (United States)

    Al-Qahtani, Noura H

    2005-10-01

    To examine whether prenatal exposure to music and voice alters foetal behaviour and whether foetal response to music differs from human voice. A prospective observational study was conducted in 20 normal term pregnant mothers. Ten foetuses were exposed to music and voice for 15 s at different sound pressure levels to find out the optimal setting for the auditory stimulation. Music, voice and sham were played to another 10 foetuses via a headphone on the maternal abdomen. The sound pressure level was 105 db and 94 db for music and voice, respectively. Computerised assessment of foetal heart rate and activity were recorded. 90 actocardiograms were obtained for the whole group. One way anova followed by posthoc (Student-Newman-Keuls method) analysis was used to find if there is significant difference in foetal response to music and voice versus sham. Foetuses responded with heart rate acceleration and motor response to both music and voice. This was statistically significant compared to sham. There was no significant difference between the foetal heart rate acceleration to music and voice. Prenatal exposure to music and voice alters the foetal behaviour. No difference was detected in foetal response to music and voice.

  12. HIV p24 as scaffold for presenting conformational HIV Env antigens.

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    Maria Tagliamonte

    Full Text Available Heterologous protein scaffolds engrafted with structurally defined HIV Env epitopes recognized by broadly neutralizing monoclonal antibodies (MAbs represent a promising strategy to elicit broad neutralizing antibodies. In such regards, a protein scaffold based on the HIV p24 CA protein is a highly attractive approach, providing also Gag epitopes for eliciting HIV non-neutralizing protective antibodies and specific CD4(+ and CD8(+ T cell responses. In the present study, computational techniques were employed to verify the presence of acceptor sites for conformational HIV Env epitopes and, as proof of concept, the analysis of HIV p24 CA-based scaffolds using a complete V3 loop in a MAb-bound conformation is presented. The V3-p24 epitope-scaffold proteins show the formation of capsomers made of hexamers similarly to the p24 wild type protein. Moreover, the conformational V3 loop presented on p24 scaffold is recognized by a panel of anti-V3 MAbs. The results suggest that HIV p24 CA protein has suitable acceptor sites for engrafting foreign epitopes, without disrupting the formation of capsomer hexamer structures, and that the V3 epitope does retain its antibody-bound conformation. This strongly support the feasibility of developing a scaffolding strategy based on p24 CA proteins displaying conformational minimal structural, antigenic HIV Env epitopes.

  13. Antigen Expression on Blast Cells and Hematological Parameters at Presentation in Acute Lymphoblastic Leukemia Patients

    International Nuclear Information System (INIS)

    Naeem, S.; Bukhari, M. H.

    2015-01-01

    Objective: To analyze the expression of various antigens on the leukemic blasts and to determine the hematological parameters, in Acute Lymphoblastic Leukemia (ALL) patients at presentation. Study Design: Observational study. Place and Duration of Study: King Edward Medical University, Lahore and Hameed Latif Hospital, Lahore, from February 2013 to March 2014. Methodology: A total of 50 newly diagnosed and untreated patients of ALL were selected from Mayo Hospital and Hameed Latif Hospital. These patients included both genders and all age groups. Hemoglobin, total leukocyte count and platelet count were determined on hematology analyser-Sysmex-Kx-2I. Blast cell percentage was estimated on Giemsa stained blood smears. Immuno phenotyping was done on bone marrow samples by 5 colour flow cytometery on Beckman Counter Navious Flow cytometer. An acute leukemia panel of 23 antibodies was used. The data was entered and analyzed in SPSS version 22. Results: Of the 50 ALL patients, 36 (72 percentage) were B-ALL and 14 (28 percentage) T-ALL. There were 18 (36 percentage) children and 32 (64 percentage) adults. T-ALL included 22 percentage of the childhood and 31 percentage of the adult cases. Immuno phenotypic analysis showed that CD19, CD79a and CD20 were B-lineage specific markers whereas cCD3, CD3 and CD5 were T-lineage specific. CD10 was the most sensitive marker for B-ALL and CD7 was the most sensitive marker of T-ALL. TdT was expressed in 92 percentage B-ALL and 71 percentage T-ALL cases, CD34 in 58 percentage and 43 percentage cases and CD45 in 83 percentage and 100 percentage respectively. High leukocyte count (> 50 x 109/L) was present in 58 percentage cases. Hemoglobin was < 10 g/dl in 74 percentage patients and platelet count was below 20 x 109/Lin 12 percentage patients. Leukocyte count, hemoglobin, platelet count and blast cell percentage did not show a significant difference in the two ALL immuno types. Conclusion: The frequency of T-ALL is higher in childhood

  14. STUDY OF MORPHOMETRIC CHANGES OF FOETAL STOMACH

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    Mohammed Aneesur Rahman

    2017-07-01

    Full Text Available BACKGROUND Interest in human development is very widespread largely because of the curiosity about our beginnings and desire to improve the quality of life. Understanding of the processes involved in the formation of various organs and systems has unrevealed most cryptic secrets of the nature. Human development begins at fertilisation when a male gamete or sperm unites with a female gamete or oocyte to form a single cell, a zygote. With the formation of zygote (single-celled stage, foetal development begins. The aim of the study is to- 1 Study the morphometric parameters of foetal stomach at various gestational ages. 2 Compare these observations with the previous studies. MATERIALS AND METHODS Present work was the cross-sectional study carried out in the Department of Anatomy in collaboration with the Department of Obstetrics and Gynaecology at SRTRGMC and Hospital, Ambajogai Dist., Beed, Maharashtra. For this, approval of Institutional Ethical Committee was taken. 30 aborted human foetuses of different age groups ranging from 12 to 36 weeks of fertilisation were taken from the Department of OB-GYN. Foetuses were preserved by using 10% formalin. Age of foetuses were determined by crown-rump length and history given by mother. Foetuses were dissected after preservation for 15 days and morphometric studies were done on stomach. RESULTS Various quantitative parameters like weight of foetus, crown-rump length, total length of stomach, weight of stomach, length of greater curvature, lesser curvature, width of cardia and width of pylorus were used. For the purpose of study and comparison with other researchers, the foetuses were divided into 3 groups. Morphometric changes were observed in different groups and compared with previous studies. CONCLUSION With the increase in the body weight, crown-rump length and gestational age of the foetus, there is gradual increase on various parameters of stomach.

  15. Polymer nanoparticles for cross-presentation of exogenous antigens and enhanced cytotoxic T-lymphocyte immune response

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    Song C

    2016-08-01

    Full Text Available Chanyoung Song,* Young-Woock Noh,* Yong Taik Lim SKKU Advanced Institute of Nanotechnology (SAINT, School of Chemical Engineering, Sungkyunkwan University, Suwon, South Korea *These authors contributed equally to this work Abstract: Effective induction of an antigen-specific cytotoxic T lymphocyte (CTL immune response is one of the key goals of cancer immunotherapy. We report the design and fabrication of polyethylenimine (PEI-coated polymer nanoparticles (NPs as efficient antigen-delivery carriers that can induce antigen cross-presentation and a strong CTL response. After synthesis of poly(d,l-lactide-co-glycolide (PLGA NPs containing ovalbumin (OVA by the double-emulsion solvent-evaporation method, cationic-charged PLGA NPs were generated by coating them with PEI. In a methyl tetrazolium salt assay, no discernible cytotoxic effect of PEI-coated PLGA (OVA NPs was observed. The capacity and mechanism of PEI-coated PLGA (OVA NPs for antigen delivery and cross-presentation on dendritic cells (DCs were determined by fluorescence microscopy and flow cytometry. PEI-coated PLGA (OVA NPs were internalized efficiently via phagocytosis or macropinocytosis in DCs and induced efficient cross-presentation of the antigen on MHC class I molecules via both endosome escape and a lysosomal processing mechanism. The DCs treated with PEI-coated PLGA (OVA NPs induced a release of IL-2 cytokine from OVA-specific CD8-OVA1.3 T cells more efficiently than DCs treated with PLGA (OVA NPs. Therefore, the PEI-coated PLGA (OVA NPs can induce antigen cross-presentation and are expected to be used for induction of a strong CTL immune response and for efficient anticancer immunotherapy. Keywords: antigen delivery, dendritic cells, polymer NPs, vaccine, cross-presentation

  16. MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape

    Energy Technology Data Exchange (ETDEWEB)

    Menachery, Vineet D.; Schafer, Alexandra; Burnum-Johnson, Kristin E.; Mitchell, Hugh D.; Eisfeld-Fenney, Amie J.; Walters, Kevin B.; Nicora, Carrie D.; Purvine, Samuel O.; Casey, Cameron P.; Monroe, Matthew E.; Weitz, Karl K.; Stratton, Kelly G.; Webb-Robertson, Bobbie-Jo M.; Gralinski, Lisa; Metz, Thomas O.; Smith, Richard D.; Waters, Katrina M.; Sims, Amy C.; Kawaoka, Yoshihiro; Baric, Ralph

    2018-01-16

    Convergent evolution dictates that diverse groups of viruses will target both similar and distinct host pathways in order to manipulate the immune response and improve infection. In this study, we sought to leverage this uneven viral antagonism to identify critical host factors that govern disease outcome. Utilizing a systems based approach, we examined differential regulation of IFNγ dependent genes following infection with highly pathogenic viruses including influenza (H5N1-VN1203, H1N1-CA04) and coronaviruses (SARS-CoV, MERS-CoV). Categorizing by function, we observed down regulation of genes associated with antigen presentation following both H5N1-VN1203 and MERS-CoV infection. Further examination revealed global down regulation of antigen presentation genes and was confirmed by proteomics for both H5N1-VN1203 and MERS-CoV infection. Importantly, epigenetic analysis suggested that DNA methylation rather than histone modification plays a crucial role in MERS-CoV mediated antagonism of antigen presentation genes; in contrast, H5N1-VN1203 likely utilizes a combination of epigenetic mechanisms to target antigen presentation. Together, the results indicate a common approach utilized by H5N1-VN1203 and MERS-CoV to modulate antigen presentation and the host adaptive immune response.

  17. A novel approach for reliable detection of cathepsin S activities in mouse antigen presenting cells.

    Science.gov (United States)

    Steimle, Alex; Kalbacher, Hubert; Maurer, Andreas; Beifuss, Brigitte; Bender, Annika; Schäfer, Andrea; Müller, Ricarda; Autenrieth, Ingo B; Frick, Julia-Stefanie

    2016-05-01

    Cathepsin S (CTSS) is a eukaryotic protease mostly expressed in professional antigen presenting cells (APCs). Since CTSS activity regulation plays a role in the pathogenesis of various autoimmune diseases like multiple sclerosis, atherosclerosis, Sjögren's syndrome and psoriasis as well as in cancer progression, there is an ongoing interest in the reliable detection of cathepsin S activity. Various applications have been invented for specific detection of this enzyme. However, most of them have only been shown to be suitable for human samples, do not deliver quantitative results or the experimental procedure requires technical equipment that is not commonly available in a standard laboratory. We have tested a fluorogen substrate, Mca-GRWPPMGLPWE-Lys(Dnp)-DArg-NH2, that has been described to specifically detect CTSS activities in human APCs for its potential use for mouse samples. We have modified the protocol and thereby offer a cheap, easy, reproducible and quick activity assay to detect CTSS activities in mouse APCs. Since most of basic research on CTSS is performed in mice, this method closes a gap and offers a possibility for reliable and quantitative CTSS activity detection that can be performed in almost every laboratory. Copyright © 2016. Published by Elsevier B.V.

  18. A novel strategy to improve antigen presentation for active immunotherapy in cancer. Fusion of the human papillomavirus type 16 E7 antigen to a cell penetrating peptide

    International Nuclear Information System (INIS)

    Granadillo, Milaid; Torrens, Isis; Guerra, Maribel

    2012-01-01

    Facilitating the delivery of exogenous antigens to antigen-presenting cells, ensuing processing and presentation via the major histocompatibility complex class I and induction of an effective immune response are fundamental for an effective therapeutic cancer vaccine. In this regard, we propose the use of cell-penetrating peptides fused to a tumor antigen. To demonstrate this concept we designed a fusion protein comprising a novel cell-penetrating and immunostimulatory peptide corresponding to residues 32 to 51 of the Limulus anti-lipopolysaccharide factor protein (LALF 32-51 ) linked to human papillomavirus 16 E7 antigen (LALF 32-51 -E7). In this work, we demonstrated that the immunization with LALF 32-51 -E7 using the TC-1 mouse model induces a potent and long-lasting anti-tumor response supported on an effective E7-specific CD8 +T -cell response. The finding that therapeutic immunization with LALF 32-51 or E7 alone, or an admixture of LALF32-51 and E7, does not induce significant tumor reduction indicates that covalent linkage between LALF 32-51 and E7 is required for the anti-tumor effect. These results support the use of this novel cell-penetrating peptide as an efficient means for delivering therapeutic targets into cellular compartments with the induction of a cytotoxic CD8 +T lymphocyte immune response. This approach is promissory for the treatment of tumors associated with the human papillomavirus 16, which is responsible for the 50% of cervical cancer cases worldwide and other malignancies. Furthermore, protein-based vaccines can circumvent the major histocompatibility complex specificity limitation associated with peptide vaccines providing a greater extent in their application

  19. STUDY OF BIOCHEMICAL PARAMETERS IN AMNIOTIC FLUID FOR ASSESSMENT OF FOETAL MATURITY IN CASES OF NORMAL PREGNANCY

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    Leela

    2015-11-01

    Full Text Available Assessment of foetal maturity had been proven of value in evaluating the foetal condition. Accurate assessment of foetal maturity is essential for the proper timing of delivery in various risk pregnancies. Amniotic Fluid analysis for foetal maturity had been of proven value. In the present study, study of biochemical parameters in amniotic fluid in respect of Creatinine, Uric Acid, Urea, Total Proteins, and Electrolytes i.e. Sodium, Potassium and Chloride has been done, along with Serum Electrolytes. Standard methodologies were adopted. The observations in the present study correlated with the works of Chadick et al and Pitkin and Zwirek. The levels of Creatinine, Uric Acid and Urea in Amniotic Fluid showed elevation, while Total Proteins and Serum Sodium showed a decline, as gestation progressed. The Serum and Amniotic Fluid Potassium and Chloride levels remain almost constant throughout the pregnancy. Thus, it is observed that the use of multiple parameters is desirable for accurate assessment of foetal maturity.

  20. Crossreactive autoantibodies directed against cutaneous and joint antigens are present in psoriatic arthritis.

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    Marzia Dolcino

    Full Text Available Psoriatic arthritis (PsA is a chronic inflammatory disease of unknown origin, characterized by erosions and new bone formation. Diagnosis of PsA is mainly clinical and there are no biomarkers available. Moreover in PsA autoantibodies have not been described so far. Indeed an autoimmune origin has been suggested but never proven. Aim of the study was to investigate the possible presence of autoantibodies typically associated with PsA.We used pooled IgG immunoglobulins derived from 30 patients with PsA to screen a random peptide library in order to identify disease relevant autoantigen peptides.Among the selected peptides, one was recognised by nearly all the patients' sera. The identified peptide (PsA peptide: TNRRGRGSPGAL shows sequence similarities with skin autoantigens, such as fibrillin 3, a constituent of actin microfibrils, desmocollin 3, a constituent of the desmosomes and keratin 78, a component of epithelial cytoskeleton. Interestingly the PsA peptide shares homology with the nebulin-related anchoring protein (N-RAP, a protein localized in the enthesis (point of insertion of a tendon or ligament to the bone, which represents the first affected site during early PsA. Antibodies affinity purified against the PsA peptide recognize fibrillin, desmocollin, keratin and N-RAP. Moreover antibodies directed against the PsA peptide are detectable in 85% of PsA patients. Such antibodies are not present in healthy donors and are present in 13/100 patients with seroposive rheumatoid arthritis (RA. In seronegative RA these antibodies are detectable only in 3/100 patients.Our results indicate that PsA is characterized by the presence of serum autoantibodies crossreacting with an epitope shared by skin and joint antigens.

  1. The Role of Multiscale Protein Dynamics in Antigen Presentation and T Lymphocyte Recognition

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    R. Charlotte Eccleston

    2017-07-01

    Full Text Available T lymphocytes are stimulated when they recognize short peptides bound to class I proteins of the major histocompatibility complex (MHC protein, as peptide–MHC complexes. Due to the diversity in T-cell receptor (TCR molecules together with both the peptides and MHC proteins they bind to, it has been difficult to design vaccines and treatments based on these interactions. Machine learning has made some progress in trying to predict the immunogenicity of peptide sequences in the context of specific MHC class I alleles but, as such approaches cannot integrate temporal information and lack explanatory power, their scope will always be limited. Here, we advocate a mechanistic description of antigen presentation and TCR activation which is explanatory, predictive, and quantitative, drawing on modeling approaches that collectively span several length and time scales, being capable of furnishing reliable biological descriptions that are difficult for experimentalists to provide. It is a form of multiscale systems biology. We propose the use of chemical rate equations to describe the time evolution of the foreign and host proteins to explain how the original proteins end up being presented on the cell surface as peptide fragments, while we invoke molecular dynamics to describe the key binding processes on the molecular level, including those of peptide–MHC complexes with TCRs which lie at the heart of the immune response. On each level, complementary methods based on machine learning are available, and we discuss the relationship between these divergent approaches. The pursuit of predictive mechanistic modeling approaches requires experimentalists to adapt their work so as to acquire, store, and expose data that can be used to verify and validate such models.

  2. Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation.

    Science.gov (United States)

    Imai, Jun; Otani, Mayu; Sakai, Takahiro; Hatta, Shinichi

    2017-08-21

    Dendritic cells (DCs) are highly capable of processing and presenting internalized exogenous antigens upon major histocompatibility class (MHC) I molecules also known as cross-presentation (CP). CP plays an important role not only in the stimulation of naïve CD8 + T cells and memory CD8 + T cells for infectious and tumor immunity but also in the inactivation of self-acting naïve T cells by T cell anergy or T cell deletion. Although the critical molecular mechanism of CP remains to be elucidated, accumulating evidence indicates that exogenous antigens are processed through endoplasmic reticulum-associated degradation (ERAD) after export from non-classical endocytic compartments. Until recently, characterizations of these endocytic compartments were limited because there were no specific molecular markers other than exogenous antigens. The method described here is a new vesicle isolation protocol, which allows for the purification of these endocytic compartments. Using this purified microsome, we reconstituted the ERAD-like transport, ubiquitination, and processing of the exogenous antigen in vitro, suggesting that the ubiquitin-proteasome system processed the exogenous antigen after export from this cellular compartment. This protocol can be further applied to other cell types to clarify the molecular mechanism of CP.

  3. Despite disorganized synapse structure, Th2 cells maintain directional delivery of CD40L to antigen-presenting B cells.

    Science.gov (United States)

    Gardell, Jennifer L; Parker, David C

    2017-01-01

    Upon recognition of peptide displayed on MHC molecules, Th1 and Th2 cells form distinct immunological synapse structures. Th1 cells have a bull's eye synapse structure with TCR/ MHC-peptide interactions occurring central to a ring of adhesion molecules, while Th2 cells have a multifocal synapse with small clusters of TCR/MHC interactions throughout the area of T cell/antigen-presenting cell interaction. In this study, we investigated whether this structural difference in the immunological synapse affects delivery of T cell help. The immunological synapse is thought to ensure antigen-specific delivery of cytolytic granules and killing of target cells by NK cells and cytolytic T cells. In helper T cells, it has been proposed that the immunological synapse may direct delivery of other effector molecules including cytokines. CD40 ligand (CD40L) is a membrane-bound cytokine essential for antigen-specific T cell help for B cells in the antibody response. We incubated Th1 and Th2 cells overnight with a mixture of antigen-presenting and bystander B cells, and the delivery of CD40L to B cells and subsequent B cell responses were compared. Despite distinct immunological synapse structures, Th1 and Th2 cell do not differ in their ability to deliver CD40L and T cell help in an antigen-specific fashion, or in their susceptibility to inhibition of help by a blocking anti-CD40L antibody.

  4. Robust and Accurate Discrimination of Self/Non-Self Antigen Presentations by Regulatory T Cell Suppression

    OpenAIRE

    Furusawa, Chikara; Yamaguchi, Tomoyuki

    2016-01-01

    The immune response by T cells usually discriminates self and non-self antigens, even though the negative selection of self-reactive T cells is imperfect and a certain fraction of T cells can respond to self-antigens. In this study, we construct a simple mathematical model of T cell populations to analyze how such self/non-self discrimination is possible. The results demonstrate that the control of the immune response by regulatory T cells enables a robust and accurate discrimination of self ...

  5. Antigen presentation by small intestinal epithelial cells uniquely enhances IFN-γ secretion from CD4{sup +} intestinal intraepithelial lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hatano, Ryo; Yamada, Kiyoshi; Iwamoto, Taku; Maeda, Nana; Emoto, Tetsuro; Shimizu, Makoto; Totsuka, Mamoru, E-mail: atotuka@mail.ecc.u-tokyo.ac.jp

    2013-06-14

    Highlights: •Small intestinal epithelial cells (sIECs). •sIECs are able to induce antigen specific proliferation of CD4{sup +} IELs. •sIECs induce markedly enhanced IFN-γ secretion by CD4{sup +} IELs. •Induction of enhanced IFN-γ secretion by sIECs is uniquely observed in CD4{sup +} IELs. -- Abstract: Small intestinal epithelial cells (sIECs) express major histocompatibility complex class II molecules even in a normal condition, and are known to function as antigen presenting cells (APCs) at least in vitro. These findings raised the possibility that sIECs play an important role in inducing immune responses against luminal antigens, especially those of intestinal intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs). We herein showed that antigenic stimulation with sIECs induced markedly greater secretion of interferon-gamma (IFN-γ) by CD4{sup +} IELs, but not interleukin (IL)-4, IL-10 and IL-17 although the proliferative response was prominently lower than that with T cell-depleted splenic APCs. In contrast, no enhanced IFN-γ secretion by CD4{sup +} LPLs and primed splenic CD4{sup +} T cells was observed when stimulated with sIECs. Taken together, these results suggest that sIECs uniquely activate CD4{sup +} IELs and induce remarkable IFN-γ secretion upon antigenic stimulation in vivo.

  6. Antigen presentation by small intestinal epithelial cells uniquely enhances IFN-γ secretion from CD4+ intestinal intraepithelial lymphocytes

    International Nuclear Information System (INIS)

    Hatano, Ryo; Yamada, Kiyoshi; Iwamoto, Taku; Maeda, Nana; Emoto, Tetsuro; Shimizu, Makoto; Totsuka, Mamoru

    2013-01-01

    Highlights: •Small intestinal epithelial cells (sIECs). •sIECs are able to induce antigen specific proliferation of CD4 + IELs. •sIECs induce markedly enhanced IFN-γ secretion by CD4 + IELs. •Induction of enhanced IFN-γ secretion by sIECs is uniquely observed in CD4 + IELs. -- Abstract: Small intestinal epithelial cells (sIECs) express major histocompatibility complex class II molecules even in a normal condition, and are known to function as antigen presenting cells (APCs) at least in vitro. These findings raised the possibility that sIECs play an important role in inducing immune responses against luminal antigens, especially those of intestinal intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs). We herein showed that antigenic stimulation with sIECs induced markedly greater secretion of interferon-gamma (IFN-γ) by CD4 + IELs, but not interleukin (IL)-4, IL-10 and IL-17 although the proliferative response was prominently lower than that with T cell-depleted splenic APCs. In contrast, no enhanced IFN-γ secretion by CD4 + LPLs and primed splenic CD4 + T cells was observed when stimulated with sIECs. Taken together, these results suggest that sIECs uniquely activate CD4 + IELs and induce remarkable IFN-γ secretion upon antigenic stimulation in vivo

  7. A molecular basis for the presentation of phosphorylated peptides by HLA-B antigens

    NARCIS (Netherlands)

    Alpízar, Adán; Marino, Fabio; Ramos-Fernández, Antonio; Lombardía, Manuel; Jeko, Anita; Pazos, Florencio; Paradela, Alberto; Santiago, César; Heck, Albert J R; Marcilla, Miguel

    2017-01-01

    As aberrant protein phosphorylation is a hallmark of tumor cells, the display of tumor-specific phosphopeptides by Human Leukocyte Antigen (HLA) class I molecules can be exploited in the treatment of cancer by T-cell-based immunotherapy. Yet, the characterization and prediction of HLA-I

  8. Variation of prostate-specific antigen expression in different tumour growth patterns present in prostatectomy specimens

    NARCIS (Netherlands)

    M.P.W. Gallee; E. Visser-de Jong (E.); J.A.G.M. van der Korput (J. A G M); Th.H. van der Kwast (Theo); F.J.W. ten Kate (Fiebo); F.H. Schröder (Fritz); J. Trapman (Jan)

    1990-01-01

    textabstractA series of 55 randomly chosen radical prostatectomy specimens was analyzed for expression of prostate-specific antigen (PSA) by immunohistochemical techniques. Tissue sections were selected in such a manner that in addition to glandular benign prostatic hyperplasia (BPH), one or more

  9. Minimum information about tolerogenic antigen-presenting cells (MITAP) : a first step towards reproducibility and standardisation of cellular therapies

    NARCIS (Netherlands)

    Lord, Phillip; Aguillon, Juan C; Anderson, Amy E; Appel, Silke; Benitez-Ribas, Daniel; Ten Brinke, Anja; Broere, Femke; Cools, Nathalie; Cuturi, Maria Cristina; Diboll, Julie; Geissler, Edward K; Giannoukakis, Nick; Gregori, Silvia; van Ham, S Marieke; Lattimer, Staci; Marshall, Lindsay; Harry, Rachel A; Hutchinson, James A; Isaacs, John D; Joosten, Irma; van Kooten, Cees; Lopez Diaz de Cerio, Ascension; Nikolic, Tatjana; Oral, Haluk Barbaros; Sofronic-Milosavljevic, Ljiljana; Ritter, Thomas; Riquelme, Paloma; Thomson, Angus W; Trucco, Massimo; Vives-Pi, Marta; Martinez-Caceres, Eva M; Hilkens, Catharien M U

    2016-01-01

    Cellular therapies with tolerogenic antigen-presenting cells (tolAPC) show great promise for the treatment of autoimmune diseases and for the prevention of destructive immune responses after transplantation. The methodologies for generating tolAPC vary greatly between different laboratories, making

  10. Arginine (Di)methylated Human Leukocyte Antigen Class I Peptides Are Favorably Presented by HLA-B*07

    NARCIS (Netherlands)

    Marino, Fabio; Mommen, Geert P M; Jeko, Anita; Meiring, Hugo D; van Gaans-van den Brink, Jacqueline A M; Scheltema, Richard A; van Els, Cécile A C M; Heck, Albert J R

    Alterations in protein post-translational modification (PTM) are recognized hallmarks of diseases. These modifications potentially provide a unique source of disease-related human leukocyte antigen (HLA) class I-presented peptides that can elicit specific immune responses. While phosphorylated HLA

  11. [Foetal/neonatal alloimmune thrombocytopenia. A review and case report].

    Science.gov (United States)

    Rodríguez Wilhelmi, P; Aranguren, A; Muñiz, E; Aranburu, E; Ezpeleta, I; Ardanaz, M F; Ayape, M L

    2008-01-01

    Foetal/neonatal alloimmune thrombocytopenia is the most common cause of severe thrombocytopenia in the newborn. It is an acute disorder which implies that foetal platelets are destroyed during the pregnancy due to a maternal alloimmune IgG antibody. More than 80% of Caucasians are HPA-1a specific. Intracranial haemorrhage, which occurs in 30% of cases, is the most serious complication, with a 10% mortality rate or a 20% rate of irreversible neurological sequels. The high risk of a recurrence of serious bleeding in future pregnancies led us to consider prophylaxis or prenatal treatment. An early diagnosis of this process allows an effective therapy to be carried out based on the infusion of compatible phenotype HPA platelets or endovenous immunoglobulins. We present the case of a 27 year old pregnant woman, who in the 35th week of a second pregnancy was diagnosed using echography with a bilateral foetal hydrocephaly. After caesarean delivery in the 36th week, the newborn presented haematomas in the left shoulder and gluteus, macrocephalia with tension of the fontanellas and hemorrhagic cerebrospinal fluid after insertion of an external ventricular derivation catheter. The haemogram revealed a severe trombocytopenia (9 x 109/L). In the light of clinical suspicion of foetal/neonatal alloimmune thrombocytopenia, infusion was made of platelets from a non-phenotyped donor for the HPA-1a system, and an endovenous immunoglobulin treatment was followed, with a recovery of platelet counts, but with neurological sequels that are probably irreversible. The immunohaematologal study confirmed the negative HPA-1a maternal phenotype, the neonatal HPA-1a positive phenotype and the presence of anti-HPA-1a alloantibodies in the maternal serum. Nowadays, the prophylaxis and treatment continue to be a controversial issue that is open to discussion, as is the possibility of implementing antenatal screening.

  12. An ECG simulator for generating maternal-foetal activity mixtures on abdominal ECG recordings

    International Nuclear Information System (INIS)

    Behar, Joachim; Andreotti, Fernando; Li, Qiao; Oster, Julien; Clifford, Gari D; Zaunseder, Sebastian

    2014-01-01

    Accurate foetal electrocardiogram (FECG) morphology extraction from non-invasive sensors remains an open problem. This is partly due to the paucity of available public databases. Even when gold standard information (i.e derived from the scalp electrode) is present, the collection of FECG can be problematic, particularly during stressful or clinically important events. In order to address this problem we have introduced an FECG simulator based on earlier work on foetal and adult ECG modelling. The open source foetal ECG synthetic simulator, fecgsyn, is able to generate maternal-foetal ECG mixtures with realistic amplitudes, morphology, beat-to-beat variability, heart rate changes and noise. Positional (rotation and translation-related) movements in the foetal and maternal heart due to respiration, foetal activity and uterine contractions were also added to the simulator. The simulator was used to generate some of the signals that were part of the 2013 PhysioNet Computing in Cardiology Challenge dataset and has been posted on Physionet.org (together with scripts to generate realistic scenarios) under an open source license. The toolbox enables further research in the field and provides part of a standard for industry and regulatory testing of rare pathological scenarios. (paper)

  13. Foetal radiography for suspected skeletal dysplasia: technique, normal appearances, diagnostic approach

    Energy Technology Data Exchange (ETDEWEB)

    Calder, Alistair D. [Great Ormond Street Hospital for Children NHS Foundation Trust, Radiology Department, London (United Kingdom); Offiah, Amaka C. [Sheffield Children' s NHS Foundation Trust, Academic Unit of Child Health, Sheffield (United Kingdom)

    2015-04-01

    Despite advances in antenatal imaging and genetic techniques, post-delivery post-mortem foetal radiography remains the key investigation in accurate diagnosis of skeletal dysplasia manifesting in the foetus. Foetal radiography is best performed using pathology-specimen radiography equipment and is often carried out in the pathology department without involvement of the radiology unit. However, paediatric radiologists may be asked to interpret post-mortem foetal radiographs when an abnormality is suspected. Many foetal radiographs are carried out before 20 weeks' gestation, and the interpreting radiologist needs to be familiar with the range of normal post-mortem foetal appearances at different gestational ages, as well as the appearances of some of the more commonly presenting skeletal dysplasias, and will benefit from a systematic approach when assessing more challenging cases. In this pictorial essay, we illustrate various normal post-mortem foetal radiographic appearances, give examples of commonly occurring skeletal dysplasias, and describe an approach to establishing more difficult diagnoses. (orig.)

  14. Foetal radiography for suspected skeletal dysplasia: technique, normal appearances, diagnostic approach

    International Nuclear Information System (INIS)

    Calder, Alistair D.; Offiah, Amaka C.

    2015-01-01

    Despite advances in antenatal imaging and genetic techniques, post-delivery post-mortem foetal radiography remains the key investigation in accurate diagnosis of skeletal dysplasia manifesting in the foetus. Foetal radiography is best performed using pathology-specimen radiography equipment and is often carried out in the pathology department without involvement of the radiology unit. However, paediatric radiologists may be asked to interpret post-mortem foetal radiographs when an abnormality is suspected. Many foetal radiographs are carried out before 20 weeks' gestation, and the interpreting radiologist needs to be familiar with the range of normal post-mortem foetal appearances at different gestational ages, as well as the appearances of some of the more commonly presenting skeletal dysplasias, and will benefit from a systematic approach when assessing more challenging cases. In this pictorial essay, we illustrate various normal post-mortem foetal radiographic appearances, give examples of commonly occurring skeletal dysplasias, and describe an approach to establishing more difficult diagnoses. (orig.)

  15. Estimation of foetal brain dose from I-131 in the foetal thyroid

    International Nuclear Information System (INIS)

    O'Hare, N.J.; Murphy, D.; Malone, J.F.; Gilligan, P.

    1997-01-01

    The ingestion of I-131 by pregnant women can have consequences for the developing foetus, in particular brain function. As the foetal thyroid accumulates iodine from the twelfth week of gestation onwards, the determination of foetal brain dose resulting from such I-131 accumulation is essential. Normal dosimetric methods fail to treat the case of the foetus. Using an approximation method based on the MIRD approach, a foetal dose estimation scheme is developed to allow the determination of foetal brain dose from foetal thyroid irradiation. Dose values are obtained for the foetus based on the maternal intake of I-131. It was found that the choice of biokinetic model for the mother/foetus has a large impact on the determined dose estimate. (author)

  16. Isolation of human foetal myoblasts and its application for microencapsulation

    Science.gov (United States)

    Li, Anna Aihua; Bourgeois, Jacqueline; Potter, Murray; Chang, Patricia L

    2008-01-01

    Abstract Foetal cells secrete more growth factors, generate less immune response, grow and proliferate better than adult cells. These characteristics make them desirable for recombinant modification and use in microencapsulated cellular gene therapeutics. We have established a system in vitro to obtain a pure population of primary human foetal myoblasts under several rounds of selection with non-collagen coated plates and identified by desmin staining. These primary myoblasts presented good proliferation ability and better differentiation characteristics in monolayer and after microencapsulation compared to murine myoblast C2C12 cells based on creatine phosphokinase (CPK), major histocompatibility complex (MHC) and multi-nucleated myotubule determination. The lifespan of primary myoblasts was 70 population doublings before entering into senescent state, with a population time of 18–24 hrs. Hence, we have developed a protocol for isolating human foetal primary myoblasts with excellent differentiation potential and robust growth and longevity. They should be useful for cell-based therapy in human clinical applications with microencapsulation technology. PMID:18366454

  17. Proteasomal targeting and minigene repetition improve cell-surface presentation of a transfected, modified melanoma tumour antigen

    DEFF Research Database (Denmark)

    Rasmussen, A B; Zocca, M-B; Bonefeld, C M

    2004-01-01

    Melanoma antigen recognized by T cell 1 (MART-1) is regarded as a candidate peptide for vaccination against malignant melanoma, and it is of importance to develop strategies to improve the vaccine-elicited T-cell activation towards MART-1. T-cell activation is, among other determinants, dependent...... on the density of specific major histocompatibility complex-peptide complexes on the surface of the antigen-presenting cell. In this study, we explored the cell-surface presentation of a substituted MART-1 peptide encoded by transfected minigenes. We investigated the potential of proteasomal targeting compared...... to non-proteasomal targeting of the epitope to increase its cell-surface presentation. Furthermore, we explored the potential of incorporating multiple minigenes instead of one to increase cell-surface presentation. We show that both proteasomal targeting and repetition of the minigene increase cell...

  18. Bone marrow-derived thymic antigen-presenting cells determine self-recognition of Ia-restricted T lymphocytes

    International Nuclear Information System (INIS)

    Longo, D.L.; Kruisbeek, A.M.; Davis, M.L.; Matis, L.A.

    1985-01-01

    The authors previously have demonstrated that in radiation-induced bone marrow chimeras, T-cell self-Ia restriction specificity appeared to correlate with the phenotype of the bone marrow-derived antigen-presenting (or dendritic) cell in the thymus during T-cell development. However, these correlations were necessarily indirect because of the difficulty in assaying thymic function directly by adult thymus transplant, which has in the past been uniformly unsuccessful. They now report success in obtaining functional T cells from nude mice grafted with adult thymuses reduced in size by treatment of the thymus donor with anti-thymocyte globulin and cortisone. When (B10 Scn X B10.D2)F1 nude mice (I-Ab,d) are given parental B10.D2 (I-Ad) thymus grafts subcutaneously, their T cells are restricted to antigen recognition in association with I-Ad gene products but not I-Ab gene products. Furthermore, thymuses from (B10 X B10.D2)F1 (I-Ab,d)----B10 (I-Ab) chimeras transplanted 6 months or longer after radiation (a time at which antigen-presenting cell function is of donor bone marrow phenotype) into (B10 X B10.D2)F1 nude mice generate T cells restricted to antigen recognition in association with both I-Ad and I-Ab gene products. Thymuses from totally allogeneic bone marrow chimeras appear to generate T cells of bone marrow donor and thymic host restriction specificity. Thus, when thymus donors are radiation-induced bone marrow chimeras, the T-cell I-region restriction of the nude mice recipients is determined at least in part by the phenotype of the bone marrow-derived thymic antigen presenting cells or dendritic cells in the chimeric thymus

  19. Manufacture of clinical-grade CD19-specific T cells stably expressing chimeric antigen receptor using Sleeping Beauty system and artificial antigen presenting cells.

    Directory of Open Access Journals (Sweden)

    Harjeet Singh

    Full Text Available Adoptive transfer of T cells expressing a CD19-specific chimeric antigen receptor (CAR is being evaluated in multiple clinical trials. Our current approach to adoptive immunotherapy is based on a second generation CAR (designated CD19RCD28 that signals through a CD28 and CD3-ζ endodomain. T cells are electroporated with DNA plasmids from the Sleeping Beauty (SB transposon/transposase system to express this CAR. Stable integrants of genetically modified T cells can then be retrieved when co-cultured with designer artificial antigen presenting cells (aAPC in the presence of interleukin (IL-2 and 21. Here, we reveal how the platform technologies of SB-mediated transposition and CAR-dependent propagation on aAPC were adapted for human application. Indeed, we have initiated clinical trials in patients with high-risk B-lineage malignancies undergoing autologous and allogeneic hematopoietic stem-cell transplantation (HSCT. We describe the process to manufacture clinical grade CD19-specific T cells derived from healthy donors. Three validation runs were completed in compliance with current good manufacturing practice for Phase I/II trials demonstrating that by 28 days of co-culture on γ-irradiated aAPC ∼10(10 T cells were produced of which >95% expressed CAR. These genetically modified and propagated T cells met all quality control testing and release criteria in support of infusion.

  20. A Large Size Chimeric Highly Immunogenic Peptide Presents Multistage Plasmodium Antigens as a Vaccine Candidate System against Malaria.

    Science.gov (United States)

    Lozano, José Manuel; Varela, Yahson; Silva, Yolanda; Ardila, Karen; Forero, Martha; Guasca, Laura; Guerrero, Yuly; Bermudez, Adriana; Alba, Patricia; Vanegas, Magnolia; Patarroyo, Manuel Elkin

    2017-11-01

    Rational strategies for obtaining malaria vaccine candidates should include not only a proper selection of target antigens for antibody stimulation, but also a versatile molecular design based on ordering the right pieces from the complex pathogen molecular puzzle towards more active and functional immunogens. Classical Plasmodium falciparum antigens regarded as vaccine candidates have been selected as model targets in this study. Among all possibilities we have chosen epitopes of Pf CSP, STARP; MSA1 and Pf 155/RESA from pre- and erythrocyte stages respectively for designing a large 82-residue chimeric immunogen. A number of options aimed at diminishing steric hindrance for synthetic procedures were assessed based on standard Fmoc chemistry such as building block orthogonal ligation; pseudo-proline and microwave-assisted procedures, therefore the large-chimeric target was produced, characterized and immunologically tested. Antigenicity and functional in vivo efficacy tests of the large-chimera formulations administered alone or as antigen mixtures have proven the stimulation of high antibody titers, showing strong correlation with protection and parasite clearance of vaccinated BALB/c mice after being lethally challenged with both P. berghei -ANKA and P. yoelii 17XL malaria strains. Besides, 3D structure features shown by the large-chimera encouraged as to propose using these rational designed large synthetic molecules as reliable vaccine candidate-presenting systems.

  1. A Large Size Chimeric Highly Immunogenic Peptide Presents Multistage Plasmodium Antigens as a Vaccine Candidate System against Malaria

    Directory of Open Access Journals (Sweden)

    José Manuel Lozano

    2017-11-01

    Full Text Available Rational strategies for obtaining malaria vaccine candidates should include not only a proper selection of target antigens for antibody stimulation, but also a versatile molecular design based on ordering the right pieces from the complex pathogen molecular puzzle towards more active and functional immunogens. Classical Plasmodium falciparum antigens regarded as vaccine candidates have been selected as model targets in this study. Among all possibilities we have chosen epitopes of PfCSP, STARP; MSA1 and Pf155/RESA from pre- and erythrocyte stages respectively for designing a large 82-residue chimeric immunogen. A number of options aimed at diminishing steric hindrance for synthetic procedures were assessed based on standard Fmoc chemistry such as building block orthogonal ligation; pseudo-proline and microwave-assisted procedures, therefore the large-chimeric target was produced, characterized and immunologically tested. Antigenicity and functional in vivo efficacy tests of the large-chimera formulations administered alone or as antigen mixtures have proven the stimulation of high antibody titers, showing strong correlation with protection and parasite clearance of vaccinated BALB/c mice after being lethally challenged with both P. berghei-ANKA and P. yoelii 17XL malaria strains. Besides, 3D structure features shown by the large-chimera encouraged as to propose using these rational designed large synthetic molecules as reliable vaccine candidate-presenting systems.

  2. Foetal stem cell derivation & characterization for osteogenic lineage

    Directory of Open Access Journals (Sweden)

    A Mangala Gowri

    2013-01-01

    Full Text Available Background & objectives: Mesencymal stem cells (MSCs derived from foetal tissues present a multipotent progenitor cell source for application in tissue engineering and regenerative medicine. The present study was carried out to derive foetal mesenchymal stem cells from ovine source and analyze their differentiation to osteogenic linage to serve as an animal model to predict human applications. Methods: Isolation and culture of sheep foetal bone marrow cells were done and uniform clonally derived MSC population was collected. The cells were characterized using cytochemical, immunophenotyping, biochemical and molecular analyses. The cells with defined characteristics were differentiated into osteogenic lineages and analysis for differentiated cell types was done. The cells were analyzed for cell surface marker expression and the gene expression in undifferentiated and differentiated osteoblast was checked by reverse transcriptase PCR (RT PCR analysis and confirmed by sequencing using genetic analyzer. Results: Ovine foetal samples were processed to obtain mononuclear (MNC cells which on culture showed spindle morphology, a characteristic oval body with the flattened ends. MSC population CD45 - /CD14 - was cultured by limiting dilution to arrive at uniform spindle morphology cells and colony forming units. The cells were shown to be positive for surface markers such as CD44, CD54, integrinβ1, and intracellular collagen type I/III and fibronectin. The osteogenically induced MSCs were analyzed for alkaline phosphatase (ALP activity and mineral deposition. The undifferentiated MSCs expressed RAB3B, candidate marker for stemness in MSCs. The osteogenically induced and uninduced MSCs expressed collagen type I and MMP13 gene in osteogenic induced cells. Interpretation & conclusions: The protocol for isolation of ovine foetal bone marrow derived MSCs was simple to perform, and the cultural method of obtaining pure spindle morphology cells was established

  3. Comprehensive Analysis of the Activation and Proliferation Kinetics and Effector Functions of Human Lymphocytes, and Antigen Presentation Capacity of Antigen-Presenting Cells in Xenogeneic Graft-Versus-Host Disease.

    Science.gov (United States)

    Kawasaki, Yasufumi; Sato, Kazuya; Hayakawa, Hiroko; Takayama, Norihito; Nakano, Hirofumi; Ito, Ryoji; Mashima, Kiyomi; Oh, Iekuni; Minakata, Daisuke; Yamasaki, Ryoko; Morita, Kaoru; Ashizawa, Masahiro; Yamamoto, Chihiro; Hatano, Kaoru; Fujiwara, Shin-Ichiro; Ohmine, Ken; Muroi, Kazuo; Kanda, Yoshinobu

    2018-04-17

    Xenogeneic graft-versus-host disease (GVHD) models in highly immunodeficient mice are currently being used worldwide to investigate human immune responses against foreign antigens in vivo. However, the individual roles of CD4 + and CD8 + T cells, and donor/host hematopoietic and nonhematopoietic antigen-presenting cells (APCs) in the induction and development of GVHD have not been fully investigated. In the present study, we comprehensively investigated the immune responses of human T cells and the antigen presentation capacity of donor/host hematopoietic and nonhematopoietic APCs in xenogeneic GVHD models using nonobese diabetic/Shi-scid-IL2rg null mice. CD4 + T cells and, to a lesser extent, CD8 + T cells individually mediated potentially lethal GVHD. In addition to inflammatory cytokine production, CD4 + T cells also supported the activation and proliferation of CD8 + T cells. Using bone marrow chimeras, we demonstrated that host hematopoietic, but not nonhematopoietic, APCs play a critical role in the development of CD4 + T cell-mediated GVHD. During early GVHD, we detected 2 distinct populations in memory CD4 + T cells. One population was highly activated and proliferated in major histocompatibility complex antigen (MHC) +/+ mice but not in MHC -/- mice, indicating alloreactive T cells. The other population showed a less activated and slowly proliferative status regardless of host MHC expression, and was associated with higher susceptibility to apoptosis, indicating nonalloreactive T cells in homeostasis-driven proliferation. These observations are clinically relevant to donor T cell response after allogeneic hematopoietic stem cell transplantation. Our findings provide a better understanding of the immunobiology of humanized mice and support the development of novel options for the prevention and treatment for GVHD. Copyright © 2018. Published by Elsevier Inc.

  4. A novel system of artificial antigen-presenting cells efficiently stimulates Flu peptide-specific cytotoxic T cells in vitro

    International Nuclear Information System (INIS)

    Han, Hui; Peng, Ji-Run; Chen, Peng-Cheng; Gong, Lei; Qiao, Shi-Shi; Wang, Wen-Zhen; Cui, Zhu-Qingqing; Yu, Xin; Wei, Yu-Hua; Leng, Xi-Sheng

    2011-01-01

    Highlights: → Adoptive immunotherapy depends on relevant numbers of cytolytic T lymphocytes. → An ideal artificial APCs system was successfully prepared in vivo. → Controlled release of IL-2 leads to much more T-cell expansion. → This system is better than general cellular APCs on T-cell expansion. -- Abstract: Therapeutic numbers of antigen-specific cytotoxic T lymphocytes (CTLs) are key effectors in successful adoptive immunotherapy. However, efficient and reproducible methods to meet the qualification remain poor. To address this issue, we designed the artificial antigen-presenting cell (aAPC) system based on poly(lactic-co-glycolic acid) (PLGA). A modified emulsion method was used for the preparation of PLGA particles encapsulating interleukin-2 (IL-2). Biotinylated molecular ligands for recognition and co-stimulation of T cells were attached to the particle surface through the binding of avidin-biotin. These formed the aAPC system. The function of aAPCs in the proliferation of specific CTLs against human Flu antigen was detected by enzyme-linked immunospot assay (ELISPOT) and MTT staining methods. Finally, we successfully prepared this suitable aAPC system. The results show that IL-2 is released from aAPCs in a sustained manner over 30 days. This dramatically improves the stimulatory capacity of this system as compared to the effect of exogenous addition of cytokine. In addition, our aAPCs promote the proliferation of Flu antigen-specific CTLs more effectively than the autologous cellular APCs. Here, this aAPC platform is proved to be suitable for expansion of human antigen-specific T cells.

  5. A novel system of artificial antigen-presenting cells efficiently stimulates Flu peptide-specific cytotoxic T cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Han, Hui [Department of Hepatobiliary Surgery, Peking University People' s Hospital, Beijing 100044 (China); Peng, Ji-Run, E-mail: pengjr@medmail.com.cn [Department of Hepatobiliary Surgery, Peking University People' s Hospital, Beijing 100044 (China); Chen, Peng-Cheng; Gong, Lei [Department of Hepatobiliary Surgery, Peking University People' s Hospital, Beijing 100044 (China); Qiao, Shi-Shi [Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052 (China); Wang, Wen-Zhen; Cui, Zhu-Qingqing; Yu, Xin; Wei, Yu-Hua [Department of Hepatobiliary Surgery, Peking University People' s Hospital, Beijing 100044 (China); Leng, Xi-Sheng, E-mail: lengxs2003@yahoo.com.cn [Department of Hepatobiliary Surgery, Peking University People' s Hospital, Beijing 100044 (China)

    2011-08-05

    Highlights: {yields} Adoptive immunotherapy depends on relevant numbers of cytolytic T lymphocytes. {yields} An ideal artificial APCs system was successfully prepared in vivo. {yields} Controlled release of IL-2 leads to much more T-cell expansion. {yields} This system is better than general cellular APCs on T-cell expansion. -- Abstract: Therapeutic numbers of antigen-specific cytotoxic T lymphocytes (CTLs) are key effectors in successful adoptive immunotherapy. However, efficient and reproducible methods to meet the qualification remain poor. To address this issue, we designed the artificial antigen-presenting cell (aAPC) system based on poly(lactic-co-glycolic acid) (PLGA). A modified emulsion method was used for the preparation of PLGA particles encapsulating interleukin-2 (IL-2). Biotinylated molecular ligands for recognition and co-stimulation of T cells were attached to the particle surface through the binding of avidin-biotin. These formed the aAPC system. The function of aAPCs in the proliferation of specific CTLs against human Flu antigen was detected by enzyme-linked immunospot assay (ELISPOT) and MTT staining methods. Finally, we successfully prepared this suitable aAPC system. The results show that IL-2 is released from aAPCs in a sustained manner over 30 days. This dramatically improves the stimulatory capacity of this system as compared to the effect of exogenous addition of cytokine. In addition, our aAPCs promote the proliferation of Flu antigen-specific CTLs more effectively than the autologous cellular APCs. Here, this aAPC platform is proved to be suitable for expansion of human antigen-specific T cells.

  6. Comparing Proteolytic Fingerprints of Antigen-Presenting Cells during Allergen Processing.

    Science.gov (United States)

    Hofer, Heidi; Weidinger, Tamara; Briza, Peter; Asam, Claudia; Wolf, Martin; Twaroch, Teresa E; Stolz, Frank; Neubauer, Angela; Dall, Elfriede; Hammerl, Peter; Jacquet, Alain; Wallner, Michael

    2017-06-08

    Endolysosomal processing has a critical influence on immunogenicity as well as immune polarization of protein antigens. In industrialized countries, allergies affect around 25% of the population. For the rational design of protein-based allergy therapeutics for immunotherapy, a good knowledge of T cell-reactive regions on allergens is required. Thus, we sought to analyze endolysosomal degradation patterns of inhalant allergens. Four major allergens from ragweed, birch, as well as house dust mites were produced as recombinant proteins. Endolysosomal proteases were purified by differential centrifugation from dendritic cells, macrophages, and B cells, and combined with allergens for proteolytic processing. Thereafter, endolysosomal proteolysis was monitored by protein gel electrophoresis and mass spectrometry. We found that the overall proteolytic activity of specific endolysosomal fractions differed substantially, whereas the degradation patterns of the four model allergens obtained with the different proteases were extremely similar. Moreover, previously identified T cell epitopes were assigned to endolysosomal peptides and indeed showed a good overlap with known T cell epitopes for all four candidate allergens. Thus, we propose that the degradome assay can be used as a predictor to determine antigenic peptides as potential T cell epitopes, which will help in the rational design of protein-based allergy vaccine candidates.

  7. Comparison of microglia and infiltrating CD11c+ cells as antigen presenting cells for T cell proliferation and cytokine response

    DEFF Research Database (Denmark)

    Wlodarczyk, Agnieszka; Løbner, Morten; Cédile, Oriane

    2014-01-01

    BACKGROUND: Tissue-resident antigen-presenting cells (APC) exert a major influence on the local immune environment. Microglia are resident myeloid cells in the central nervous system (CNS), deriving from early post-embryonic precursors, distinct from adult hematopoietic lineages. Dendritic cells...... (DC) and macrophages infiltrate the CNS during experimental autoimmune encephalomyelitis (EAE). Microglia are not considered to be as effective APC as DC or macrophages. METHODS: In this work we compared the antigen presenting capacity of CD11c+ and CD11c- microglia subsets with infiltrating CD11c......+ APC, which include DC. The microglial subpopulations (CD11c- CD45dim CD11b+ and CD11c+ CD45dim CD11b+) as well as infiltrating CD11c+ CD45high cells were sorted from CNS of C57BL/6 mice with EAE. Sorted cells were characterised by flow cytometry for surface phenotype and by quantitative real-time PCR...

  8. Crystal structure of a TAPBPR–MHC I complex reveals the mechanism of peptide editing in antigen presentation

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Jiansheng; Natarajan, Kannan; Boyd, Lisa F.; Morozov, Giora I.; Mage, Michael G.; Margulies, David H. (NIH); (Hebrew)

    2017-10-12

    Central to CD8+ T cell–mediated immunity is the recognition of peptide–major histocompatibility complex class I (p–MHC I) proteins displayed by antigen-presenting cells. Chaperone-mediated loading of high-affinity peptides onto MHC I is a key step in the MHC I antigen presentation pathway. However, the structure of MHC I with a chaperone that facilitates peptide loading has not been determined. We report the crystal structure of MHC I in complex with the peptide editor TAPBPR (TAP-binding protein–related), a tapasin homolog. TAPBPR remodels the peptide-binding groove of MHC I, resulting in the release of low-affinity peptide. Changes include groove relaxation, modifications of key binding pockets, and domain adjustments. This structure captures a peptide-receptive state of MHC I and provides insights into the mechanism of peptide editing by TAPBPR and, by analogy, tapasin.

  9. Probiotic metabolites from Bacillus coagulans GanedenBC30TM support maturation of antigen-presenting cells in vitro

    Science.gov (United States)

    Benson, Kathleen F; Redman, Kimberlee A; Carter, Steve G; Keller, David; Farmer, Sean; Endres, John R; Jensen, Gitte S

    2012-01-01

    AIM: To study the effects of probiotic metabolites on maturation stage of antigen-presenting immune cells. METHODS: Ganeden Bacillus coagulans 30 (GBC30) bacterial cultures in log phase were used to isolate the secreted metabolite (MET) fraction. A second fraction was made to generate a crude cell-wall-enriched fraction, by centrifugation and lysis, followed by washing. A preparation of MET was subjected to size exclusion centrifugation, generating three fractions: < 3 kDa, 3-30 kDa, and 30-200 kDa and activities were tested in comparison to crude MET and cell wall in primary cultures of human peripheral blood mononuclear cell (PBMC) as a source of antigen-presenting mononuclear phagocytes. The maturation status of mononuclear phagocytes was evaluated by staining with monoclonal antibodies towards CD14, CD16, CD80 and CD86 and analyzed by flow cytometry. RESULTS: Treatment of PBMC with MET supported maturation of mononuclear phagocytes toward both macrophage and dendritic cell phenotypes. The biological activity unique to the metabolites included a reduction of CD14+ CD16+ pro-inflammatory cells, and this property was associated with the high molecular weight metabolite fraction. Changes were also seen for the dendritic cell maturation markers CD80 and CD86. On CD14dim cells, an increase in both CD80 and CD86 expression was seen, in contrast to a selective increase in CD86 expression on CD14bright cells. The co-expression of CD80 and CD86 indicates effective antigen presentation to T cells and support of T helper cell differentiation. The selective expression of CD86 in the absence of CD80 points to a role in generating T regulatory cells. CONCLUSION: The data show that a primary mechanism of action of GBC30 metabolites involves support of more mature phenotypes of antigen-presenting cells, important for immunological decision-making. PMID:22563167

  10. Complex antigen presentation pathway for an HLA-A*0201-restricted epitope from Chikungunya 6K protein.

    Science.gov (United States)

    Lorente, Elena; Barriga, Alejandro; García-Arriaza, Juan; Lemonnier, François A; Esteban, Mariano; López, Daniel

    2017-10-01

    The adaptive cytotoxic T lymphocyte (CTL)-mediated immune response is critical for clearance of many viral infections. These CTL recognize naturally processed short viral antigenic peptides bound to human leukocyte antigen (HLA) class I molecules on the surface of infected cells. This specific recognition allows the killing of virus-infected cells. The T cell immune T cell response to Chikungunya virus (CHIKV), a mosquito-borne Alphavirus of the Togaviridae family responsible for severe musculoskeletal disorders, has not been fully defined; nonetheless, the importance of HLA class I-restricted immune response in this virus has been hypothesized. By infection of HLA-A*0201-transgenic mice with a recombinant vaccinia virus that encodes the CHIKV structural polyprotein (rVACV-CHIKV), we identified the first human T cell epitopes from CHIKV. These three novel 6K transmembrane protein-derived epitopes are presented by the common HLA class I molecule, HLA-A*0201. One of these epitopes is processed and presented via a complex pathway that involves proteases from different subcellular locations. Specific chemical inhibitors blocked these events in rVACV-CHIKV-infected cells. Our data have implications not only for the identification of novel Alphavirus and Togaviridae antiviral CTL responses, but also for analyzing presentation of antigen from viruses of different families and orders that use host proteinases to generate their mature envelope proteins.

  11. Loss of Proliferation and Antigen Presentation Activity following Internalization of Polydispersed Carbon Nanotubes by Primary Lung Epithelial Cells

    Science.gov (United States)

    Kumari, Mandavi; Sachar, Sumedha; Saxena, Rajiv K.

    2012-01-01

    Interactions between poly-dispersed acid functionalized single walled carbon nanotubes (AF-SWCNTs) and primary lung epithelial (PLE) cells were studied. Peritoneal macrophages (PMs, known phagocytic cells) were used as positive controls in this study. Recovery of live cells from cultures of PLE cells and PMs was significantly reduced in the presence of AF-SWCNTs, in a time and dose dependent manner. Both PLE cells as well as PMs could take up fluorescence tagged AF-SWCNTs in a time dependent manner and this uptake was significantly blocked by cytochalasin D, an agent that blocks the activity of acto-myosin fibers and therefore the phagocytic activity of cells. Confocal microscopic studies confirmed that AF-SWCNTs were internalized by both PLE cells and PMs. Intra-trachially instilled AF-SWCNTs could also be taken up by lung epithelial cells as well as alveolar macrophages. Freshly isolated PLE cells had significant cell division activity and cell cycling studies indicated that treatment with AF-SWCNTs resulted in a marked reduction in S-phase of the cell cycle. In a previously standardized system to study BCG antigen presentation by PLE cells and PMs to sensitized T helper cells, AF-SWCNTs could significantly lower the antigen presentation ability of both cell types. These results show that mouse primary lung epithelial cells can efficiently internalize AF-SWCNTs and the uptake of nanotubes interfered with biological functions of PLE cells including their ability to present BCG antigens to sensitized T helper cells. PMID:22384094

  12. Deletion of Batf3-dependent antigen-presenting cells does not affect atherosclerotic lesion formation in mice.

    Directory of Open Access Journals (Sweden)

    Jesus Gil-Pulido

    Full Text Available Atherosclerosis is the main underlying cause for cardiovascular events such as myocardial infarction and stroke and its development might be influenced by immune cells. Dendritic cells (DCs bridge innate and adaptive immune responses by presenting antigens to T cells and releasing a variety of cytokines. Several subsets of DCs can be discriminated that engage specific transcriptional pathways for their development. Basic leucine zipper transcription factor ATF-like 3 (Batf3 is required for the development of classical CD8α+ and CD103+ DCs. By crossing mice deficient in Batf3 with atherosclerosis-prone low density lipoprotein receptor (Ldlr-/--deficient mice we here aimed to further address the contribution of Batf3-dependent CD8α+ and CD103+ antigen-presenting cells to atherosclerosis. We demonstrate that deficiency in Batf3 entailed mild effects on the immune response in the spleen but did not alter atherosclerotic lesion formation in the aorta or aortic root, nor affected plaque phenotype in low density lipoprotein receptor-deficient mice fed a high fat diet. We thus provide evidence that Batf3-dependent antigen-presenting cells do not have a prominent role in atherosclerosis.

  13. A foetal tile from an archaeological site: anthropological investigation of human remains recovered in a medieval cemetery in Northern Italy.

    Science.gov (United States)

    Licata, Marta; Rossetti, Chiara; Tosi, Adelaide; Badino, Paola

    2018-06-01

    The recovery of foetal remains is very sporadic in archaeology, especially due the scarce degree of bone mineralisation. This paper presents the singular archaeological discovery of a foetal tile preserving the bone remains, object of our anthropological examination. The foetal tile was discovered during an archaeological excavation in a medieval site (Northern Italy). The tile was analysed by CT scan and later, human remains were anthropologically examined. The archaeological investigation revealed a special ritual destined to foetuses while forensic anthropological analysis allowed estimating the gestational age near to 21-24 weeks.

  14. Detection and partial characterization of a midlamina lucida-hemidesmosome-associated antigen (19-DEJ-1) present within human skin

    DEFF Research Database (Denmark)

    Fine, J D; Horiguchi, Y; Jester, J

    1989-01-01

    , esophagus, cervix, and cornea, and BMs surrounding smooth muscle in medium-sized vessels, placenta, uterus, and esophagus. When 16 human fetal skins (aged 54-142 gestational days) were examined, the antigen was first detected at 81 days. Using immunoperoxidase and immunogold staining techniques, indirect......A murine anti-human monoclonal antibody (19-DEJ-1) has been produced that binds to basement membranes (BMs) of the dermoepidermal junction and arrector pili muscles but not to either dermal glandular or vascular BMs. 19-DEJ-1 also recognizes BMs underneath epithelia of buccal mucosa, tongue......-specific proteoglycan that is present within BMs along the epithelial-connective tissue interface and around smooth muscle in skin and other selected organs. Its unique ultrastructural localization suggests the possibility that 19-DEJ-1 may recognize an antigenic epitope of either anchoring filaments or alternatively...

  15. Effect of BSA Antigen Sensitization during the Acute Phase of Influenza A Viral Infection on CD11c+ Pulmonary Antigen Presenting Cells

    Directory of Open Access Journals (Sweden)

    Fumitaka Sato

    2009-01-01

    Conclusions: BSA antigen sensitization during the acute phase of influenza A viral infection enhanced IL-10 production from naive CD4+ T cell interaction with CD11c+ pulmonary APCs. The IL-10 secretion evoked Th2 responses in the lungs with downregulation of Th1 responses and was important for the eosinophil recruitment into the lungs after BSA antigen challenge.

  16. Protein-scaffold Directed Nanoscale Assembly of T Cell Ligands: Artificial Antigen Presentation with Defined Valency, Density and Ratio.

    Science.gov (United States)

    Smith, Mason R; Tolbert, Stephanie V; Wen, Fei

    2018-05-07

    Tuning antigen presentation to T cells is a critical step in investigating key aspects of T cell activation. However, existing technologies have limited ability to control the spatial and stoichiometric organization of T cell ligands on 3D surfaces. Here, we developed an artificial antigen presentation platform based on protein-scaffold directed assembly that allows fine control over the spatial and stoichiometric organization of T cell ligands on a 3D yeast-cell surface. Using this system, we observed that the T cell activation threshold on a 3D surface is independent of peptide-major histocompatibility complex (pMHC) valency, but instead determined by the overall pMHC surface density. When intercellular adhesion molecule 1 (ICAM-1) was co-assembled with pMHC, it enhanced antigen recognition sensitivity by 6-fold. Further, T cells responded with different magnitudes to varying ratios of pMHC and ICAM-1 and exhibited a maximum response at a ratio of 15% pMHC and 85% ICAM-1, introducing an additional parameter for tuning T cell activation. This protein-scaffold directed assembly technology is readily transferrable to acellular surfaces for translational research as well as large-scale T-cell manufacturing.

  17. Sonographic correlation of foetal neck circumference and area with gestational age among pregnant women in Port Harcourt, Nigeria.

    Science.gov (United States)

    Abonyi, Obinna Everistus; Eze, Charles Ugwoke; Onwuzu, Sobechukwu W I

    2017-11-01

    The purpose of this study was to create a reference range nomogram of foetal neck circumference (FNC) and foetal neck area (FNA) in a Nigerian population using polynomial regression models. This cross-sectional study involved 723 pregnant women between 14 and 40 weeks of gestation. Axial measurements of the FNC and FNA were obtained in three measurements and the mean taken as the final value and the 5th, 50th and 95th percentiles for each foetal gestational age (FGA) were calculated. FNC and FNA correlated strongly with FGA, biparietal diameter, abdominal circumference, head circumference, and femoral length. Cubic models fitted the FNC vs FGA, and FNA vs. FGA values, and the mathematical relationships are given as: [Formula: see text] [Formula: see text] [Formula: see text]. Nomograms of FNC and FNA are thus generated. Impact statement The foetal neck circumference (FNC) and foetal neck area (FNA) can serve as predictors of foetal gestational age (FGA) since they correlate strongly and positively with FGA and known biometric parameters. The measurements obtained vary with the population studied. This study provides a nomogram of the FNA and FNC for an African population. The values correlate with that of the Caucasian population up to 32 weeks FGA. Interestingly, FNA and FNC measurements demonstrate high correlation but poor agreement in measurements between sonographers. Even though FNA and FNC could be used as predictors of foetal gestational age, the measurements vary significantly between sonographers. This is attributable to the difficulty in obtaining a satisfactory axial view of foetal neck, which is dependent on foetal presentation.

  18. Interferon-β Suppresses Murine Th1 Cell Function in the Absence of Antigen-Presenting Cells

    Science.gov (United States)

    Boivin, Nicolas; Baillargeon, Joanie; Doss, Prenitha Mercy Ignatius Arokia; Roy, Andrée-Pascale; Rangachari, Manu

    2015-01-01

    Interferon (IFN)-β is a front-line therapy for the treatment of the relapsing-remitting form of multiple sclerosis. However, its immunosuppressive mechanism of function remains incompletely understood. While it has been proposed that IFN-β suppresses the function of inflammatory myelin antigen-reactive T cells by promoting the release of immunomodulatory cytokines such as IL-27 from antigen-presenting cells (APCs), its direct effects on inflammatory CD4+ Th1 cells are less clear. Here, we establish that IFN-β inhibits mouse IFN-γ+ Th1 cell function in the absence of APCs. CD4+ T cells express the type I interferon receptor, and IFN-β can suppress Th1 cell proliferation under APC-free stimulation conditions. IFN-β-treated myelin antigen-specific Th1 cells are impaired in their ability to induce severe experimental autoimmune encephalomyelitis (EAE) upon transfer to lymphocyte-deficient Rag1-/- mice. Polarized Th1 cells downregulate IFN-γ and IL-2, and upregulate the negative regulatory receptor Tim-3, when treated with IFN-β in the absence of APCs. Further, IFN-β treatment of Th1 cells upregulates phosphorylation of Stat1, and downregulates phosphorylation of Stat4. Our data indicate that IFN-γ-producing Th1 cells are directly responsive to IFN-β and point to a novel mechanism of IFN-β-mediated T cell suppression that is independent of APC-derived signals. PMID:25885435

  19. Bovine lactoferrin counteracts Toll-like receptor mediated activation signals in antigen presenting cells.

    Directory of Open Access Journals (Sweden)

    Patrizia Puddu

    Full Text Available Lactoferrin (LF, a key element in mammalian immune system, plays pivotal roles in host defence against infection and excessive inflammation. Its protective effects range from direct antimicrobial activities against a large panel of microbes, including bacteria, viruses, fungi and parasites, to antinflammatory and anticancer activities. In this study, we show that monocyte-derived dendritic cells (MD-DCs generated in the presence of bovine LF (bLF fail to undergo activation by up-modulating CD83, co-stimulatory and major histocompatibility complex molecules, and cytokine/chemokine secretion. Moreover, these cells are weak activators of T cell proliferation and retain antigen uptake activity. Consistent with an impaired maturation, bLF-MD-DC primed T lymphocytes exhibit a functional unresponsiveness characterized by reduced expression of CD154 and impaired expression of IFN-γ and IL-2. The observed imunosuppressive effects correlate with an increased expression of molecules with negative regulatory functions (i.e. immunoglobulin-like transcript 3 and programmed death ligand 1, indoleamine 2,3-dioxygenase, and suppressor of cytokine signaling-3. Interestingly, bLF-MD-DCs produce IL-6 and exhibit constitutive signal transducer and activator of transcription 3 activation. Conversely, bLF exposure of already differentiated MD-DCs completely fails to induce IL-6, and partially inhibits Toll-like receptor (TLR agonist-induced activation. Cell-specific differences in bLF internalization likely account for the distinct response elicited by bLF in monocytes versus immature DCs, providing a mechanistic base for its multiple effects. These results indicate that bLF exerts a potent anti-inflammatory activity by skewing monocyte differentiation into DCs with impaired capacity to undergo activation and to promote Th1 responses. Overall, these bLF-mediated effects may represent a strategy to block excessive DC activation upon TLR-induced inflammation, adding

  20. A Francisella tularensis live vaccine strain that improves stimulation of antigen-presenting cells does not enhance vaccine efficacy.

    Directory of Open Access Journals (Sweden)

    Deanna M Schmitt

    Full Text Available Vaccination is a proven strategy to mitigate morbidity and mortality of infectious diseases. The methodology of identifying and testing new vaccine candidates could be improved with rational design and in vitro testing prior to animal experimentation. The tularemia vaccine, Francisella tularensis live vaccine strain (LVS, does not elicit complete protection against lethal challenge with a virulent type A Francisella strain. One factor that may contribute to this poor performance is limited stimulation of antigen-presenting cells. In this study, we examined whether the interaction of genetically modified LVS strains with human antigen-presenting cells correlated with effectiveness as tularemia vaccine candidates. Human dendritic cells infected with wild-type LVS secrete low levels of proinflammatory cytokines, fail to upregulate costimulatory molecules, and activate human T cells poorly in vitro. One LVS mutant, strain 13B47, stimulated higher levels of proinflammatory cytokines from dendritic cells and macrophages and increased costimulatory molecule expression on dendritic cells compared to wild type. Additionally, 13B47-infected dendritic cells activated T cells more efficiently than LVS-infected cells. A deletion allele of the same gene in LVS displayed similar in vitro characteristics, but vaccination with this strain did not improve survival after challenge with a virulent Francisella strain. In vivo, this mutant was attenuated for growth and did not stimulate T cell responses in the lung comparable to wild type. Therefore, stimulation of antigen-presenting cells in vitro was improved by genetic modification of LVS, but did not correlate with efficacy against challenge in vivo within this model system.

  1. Relative Efficacy of Uptake and Presentation of Mycobacterium bovis BCG Antigens by Type I Mouse Lung Epithelial Cells and Peritoneal Macrophages ▿

    Science.gov (United States)

    Kumari, Mandavi; Saxena, Rajiv K.

    2011-01-01

    Flow cytometric studies indicated that both peritoneal macrophages (PMs) and primary lung epithelial (PLE) cells isolated from mouse lungs could take up fluorescence-tagged Mycobacterium bovis BCG. BCG uptake in both cases was significantly inhibited by cytochalasin D, indicating active internalization of BCG by these cells. Confocal microscopy data further confirmed that BCG was internalized by PLE cells. BCG sonicate antigen (sBCG) had marked toxicity toward PMs but was relatively nontoxic to PLE cells. Accordingly, BCG sonicate antigen induced a significantly higher apoptotic and necrotic response in PMs compared to that in PLE cells. Both PMs and PLE cells exposed to BCG antigens and fixed thereafter could efficiently present antigens to purified BCG-sensitized T helper cells, as assessed by the release of interleukin-2 (IL-2) and gamma interferon (IFN-γ). If, however, PLE cells were fixed before exposure to BCG, antigen presentation was abrogated, indicating that the PLE cells may in some way process the BCG antigen. A comparison of efficacies of BCG-pulsed PLE cells and PMs to present antigen at various antigen-presenting cell (APC)/T cell ratios indicated that PMs had only marginally greater APC function than that of PLE cells. Staining with specific monoclonal antibodies indicated that the cultured PLE cells used for antigen presentation essentially comprised type I epithelial cells. Our results suggest that type I lung epithelial cells may present BCG antigens to sensitized T helper cells and that their performance as APCs is comparable with that of PMs. PMID:21646448

  2. Concentration of perfluorinated compounds and cotinine in human foetal organs, placenta, and maternal plasma

    DEFF Research Database (Denmark)

    Mamsen, Linn Salto; Jönsson, Bo A.G.; Lindh, Christian H.

    2017-01-01

    levels. Foetal exposure has previously been estimated from umbilical cord plasma, but the actual concentration in foetal organs has never been measured. Objectives The concentrations of 5 PFASs and cotinine – the primary metabolite of nicotine – were measured in human foetuses, placentas, and maternal...... plasma to evaluate to what extent these compounds were transferred from mother to foetus and to determine if the PFAS concentrations were associated with maternal cigarette smoking. Methods Thirty-nine Danish women who underwent legal termination of pregnancy before gestational week 12 were included; 24...... ratio for all five PFASs and cotinine. Smokers presented 99 ng/g cotinine in plasma, 108 ng/g in placenta, and 61 ng/g in foetal organs. No correlation between the maternal cotinine concentrations and PFAS concentrations was found. Conclusions PFASs were transferred from mother to foetus, however...

  3. The hemochromatosis protein HFE 20 years later: An emerging role in antigen presentation and in the immune system.

    Science.gov (United States)

    Reuben, Alexandre; Chung, Jacqueline W; Lapointe, Réjean; Santos, Manuela M

    2017-09-01

    Since its discovery, the hemochromatosis protein HFE has been primarily defined by its role in iron metabolism and homeostasis, and its involvement in the genetic disease termed hereditary hemochromatosis (HH). While HH patients are typically afflicted by dysregulated iron levels, many are also affected by several immune defects and increased incidence of autoimmune diseases that have thereby implicated HFE in the immune response. Growing evidence has supported an immunological role for HFE with recent studies describing HFE specifically as it relates to MHC I antigen presentation. Here, we present a comprehensive overview of the relationship between iron metabolism, HFE, and the immune system to better understand the origin and cause of immune defects in HH patients. We further describe the role of HFE in MHC I antigen presentation and its potential to impair autoimmune responses in homeostatic conditions, a mechanism which may be exploited by tumors to evade immune surveillance. Overall, this increased understanding of the role of HFE in the immune response sets the stage for better treatment and management of HH and other iron-related diseases, as well as of the immune defects related to this condition. © 2017 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

  4. Membrane-bound heat shock proteins facilitate the uptake of dying cells and cross-presentation of cellular antigen.

    Science.gov (United States)

    Zhu, Haiyan; Fang, Xiaoyun; Zhang, Dongmei; Wu, Weicheng; Shao, Miaomiao; Wang, Lan; Gu, Jianxin

    2016-01-01

    Heat shock proteins (HSPs) were originally identified as stress-responsive proteins and serve as molecular chaperones in different intracellular compartments. Translocation of HSPs to the cell surface and release of HSPs into the extracellular space have been observed during the apoptotic process and in response to a variety of cellular stress. Here, we report that UV irradiation and cisplatin treatment rapidly induce the expression of membrane-bound Hsp60, Hsp70, and Hsp90 upstream the phosphatidylserine exposure. Membrane-bound Hsp60, Hsp70 and Hsp90 could promote the release of IL-6 and IL-1β as well as DC maturation by the evaluation of CD80 and CD86 expression. On the other hand, Hsp60, Hsp70 and Hsp90 on cells could facilitate the uptake of dying cells by bone marrow-derived dendritic cells. Lectin-like oxidized LDL receptor-1 (LOX-1), as a common receptor for Hsp60, Hsp70, and Hsp90, is response for their recognition and mediates the uptake of dying cells. Furthermore, membrane-bound Hsp60, Hsp70 and Hsp90 could promote the cross-presentation of OVA antigen from E.G7 cells and inhibition of the uptake of dying cells by LOX-1 decreases the cross-presentation of cellular antigen. Therefore, the rapid exposure of HSPs on dying cells at the early stage allows for the recognition by and confers an activation signal to the immune system.

  5. Corruption of dendritic cell antigen presentation during acute GVHD leads to regulatory T-cell failure and chronic GVHD.

    Science.gov (United States)

    Leveque-El Mouttie, Lucie; Koyama, Motoko; Le Texier, Laetitia; Markey, Kate A; Cheong, Melody; Kuns, Rachel D; Lineburg, Katie E; Teal, Bianca E; Alexander, Kylie A; Clouston, Andrew D; Blazar, Bruce R; Hill, Geoffrey R; MacDonald, Kelli P A

    2016-08-11

    Chronic graft-versus-host disease (cGVHD) is a major cause of late mortality following allogeneic bone marrow transplantation (BMT) and is characterized by tissue fibrosis manifesting as scleroderma and bronchiolitis obliterans. The development of acute GVHD (aGVHD) is a powerful clinical predictor of subsequent cGVHD, suggesting that aGVHD may invoke the immunologic pathways responsible for cGVHD. In preclinical models in which sclerodermatous cGVHD develops after a preceding period of mild aGVHD, we show that antigen presentation within major histocompatibility complex (MHC) class II of donor dendritic cells (DCs) is markedly impaired early after BMT. This is associated with a failure of regulatory T-cell (Treg) homeostasis and cGVHD. Donor DC-restricted deletion of MHC class II phenocopied this Treg deficiency and cGVHD. Moreover, specific depletion of donor Tregs after BMT also induced cGVHD, whereas adoptive transfer of Tregs ameliorated it. These data demonstrate that the defect in Treg homeostasis seen in cGVHD is a causative lesion and is downstream of defective antigen presentation within MHC class II that is induced by aGVHD. © 2016 by The American Society of Hematology.

  6. The placenta and foetal membranes of the lesser yellow house bat ...

    African Journals Online (AJOL)

    1988-06-05

    Jun 5, 1988 ... A discoidal hemodichorial placenta is present in $cotophilus borbonicus. Evidence is presented which suggests that histotrophic nutrition, in addition to hemotrophic nutrition, occurs. The foetal trophospongium phagocytoses cell debris and glandular secretions derived from the maternal endometrium ...

  7. B lymphocytes as natural antigen-presenting cells (APC) of their own Ig receptor determinants

    International Nuclear Information System (INIS)

    Yurin, V.L.; Rudensky, A.Yu.; Rabinovich, O.R.; Kulakova, O.G.; Bobreneva, R.A.

    1986-01-01

    The authors use Igk-lb allotype-specific rat T cell proliferation(Pr) in vitro as a model of natural Ig determinants B cell presentation in Ig-specific T-B cell interactions. As shown before Igk-lb-specific responsiveness of AUG(RT-l/sup c/, Igk-la) and WAG (RT-l, Igk-la) rats is controlled by dominant Ir gene, linked to RT-l/sup c/. Only IgG(Igk-lb)-pulsed splenic APC of AUG(responder) but not WAG(non-responder) origin induce specific F 1 (WAGxAUG) T cell Pr. The same restriction was observed if purified B cells from Igk-l congeneic AUG-lb and WAG-lb rats were used as APC. B cell presentation was found to be sensitive to high irradiation dose(2000 rad). Anti-RT-l monoclonal antibody inhibition studies suggested RT-lB(I-A) molecule as a main restricting element of Igk-lb T cell recognition. B cell and splenic APC presentation of Igk-lb allotype was not inhibited by poly- and monoclonal anti-Igk-lb antibodies. Allelic exclusion of Igk-lb presentation by B cells from heterozygous F 1 (WAG-lbx AUG) rats was demonstrated by panning with antiallotypic reagents. Important, that irradiated anti-Igk-lb T cells induce specific Pr of normal Igk-lb-positive B cells. The data demonstrate MHC-restricted B cell presentation of their own receptor determinants, distinct from serologically-defined epitopes. T cell recognition of these determinants induce specific Pr of Ig-recognizing T cells and Ig-presenting B lymphocytes

  8. MHC class II-derived peptides can bind to class II molecules, including self molecules, and prevent antigen presentation

    DEFF Research Database (Denmark)

    Rosloniec, E F; Vitez, L J; Buus, S

    1990-01-01

    the alpha k-3 peptide binds slightly less well. These combined data, suggesting that class II-derived peptides can bind to MHC class II molecules, including the autologous molecule from which they are derived, have important implications for the molecular basis of alloreactivity and autoreactivity. Further...... found in the first and third polymorphic regions (PMR) of the A alpha k chain (alpha k-1 and alpha k-3) were capable of inhibiting the presentation of three different HEL-derived peptide antigens to their appropriate T cells. In addition, the alpha k-1 peptide inhibited the presentation of the OVA(323......-339) immunodominant peptide to the I-Ad-restricted T cell hybridomas specific for it. Prepulsing experiments demonstrated that the PMR peptides were interacting with the APC and not with the T cell hybridomas. These observations were confirmed and extended by the demonstration that the alpha k-1 and alpha k-3...

  9. Expression of cathepsins B, L, S, and D by gastric epithelial cells implicates them as antigen presenting cells in local immune responses.

    Science.gov (United States)

    Barrera, C; Ye, G; Espejo, R; Gunasena, S; Almanza, R; Leary, J; Crowe, S; Ernst, P; Reyes, V E

    2001-10-01

    Helicobacter pylori infection is linked to chronic gastritis, peptic ulcer and gastric carcinoma. During H. pylori infection, class II MHC expression by the gastric epithelium increases, as does the number of local CD4(+) T cells, which appear to be important in the associated pathogenesis. These observations suggested that the epithelium might present antigens to T cells. Thus, we sought to determine whether gastric epithelial cells process antigens to establish their function as local antigen presenting cells (APC). We examined a panel of gastric epithelial cell lines for expression of the antigen processing cathepsins B (CB), L (CL), S (CS), and D (CD). The mRNA for these enzymes were detected by RT-PCR and the enzymes in the gastric epithelial cells were identified by various independent methods. We corroborated the expression of CB and CD on gastric epithelial cells from human biopsy samples. The functions of these proteases were confirmed by assessing their ability to digest ovalbumin, a conventional dietary antigen, and proteins from H. pylori. In summary, multiple lines of evidence suggest gastric epithelial cells process antigens for presentation to CD4(+) T cells. To our knowledge, these are the first studies to document the antigen processing capacity of human gastric epithelial cells.

  10. A Critical Analysis of the Role of SNARE Protein SEC22B in Antigen Cross-Presentation

    Directory of Open Access Journals (Sweden)

    S. Julia Wu

    2017-06-01

    Full Text Available Cross-presentation initiates immune responses against tumors and viral infections by presenting extracellular antigen on MHC I to activate CD8+ T cell-mediated cytotoxicity. In vitro studies in dendritic cells (DCs established SNARE protein SEC22B as a specific regulator of cross-presentation. However, the in vivo contribution of SEC22B to cross-presentation has not been tested. To address this, we generated DC-specific Sec22b knockout (CD11c-Cre Sec22bfl/fl mice. Contrary to the paradigm, SEC22B-deficient DCs efficiently cross-present both in vivo and in vitro. Although in vitro small hairpin RNA (shRNA-mediated Sec22b silencing in bone-marrow-derived dendritic cells (BMDCs reduced cross-presentation, treatment of SEC22B-deficient BMDCs with the same shRNA produced a similar defect, suggesting the Sec22b shRNA modulates cross-presentation through off-target effects. RNA sequencing of Sec22b shRNA-treated SEC22B-deficient BMDCs demonstrated several changes in the transcriptome. Our data demonstrate that contrary to the accepted model, SEC22B is not necessary for cross-presentation, cautioning against extrapolating phenotypes from knockdown studies alone.

  11. Repopulated antigen presenting cells induced an imbalanced differentiation of the helper T cells in whole body gamma irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hae Ran; Jo, Sung Kee [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of); Paik, Sang Kee [Chungnam National University, Taejon (Korea, Republic of)

    2004-07-01

    Therapeutic irradiation of cancer patients, although it may be protected by several antioxidant agents against free radicals, often induces chronic sequelae such as inflammation (allergic inflammation). This is a limiting factor for radiotherapy. Following radiotherapy, the inflammation or injury can occur in any organ with a high radiosensitivity such as the lung, bladder, kidney, liver, stomach and intestine. The mechanism by which ionizing radiation initiates inflammation is, however, poorly understood. In recent studies, it was suggested that a factor for irradiation-induced inflammation might be the over production of IL-4 that enhances fibroblast proliferation and collagen synthesis. During the early stages after irradiation, type 2 of the helper T cells might be the major source of IL-4, and later on there seems to be an activation of the other IL-4 producing cell types, e.q. macrophages or mast cells. This is interesting because inflammation is classically seen to be dominated by Th1 cells secreting IFN-{gamma}. In the previous study, we were interested in the enhancement of the IL-4 and the IgE production during the development of immune cells after {gamma}-irradiation. We were able to deduce that IL-4 production was increased because of the shifted differentiation of the naive Th cells by the repopulated antigen presenting cells after irradiation. The aim of the present study was to precisely define whether antigen-presenting cells (APCs) of whole body irradiation-treated mice could influence the shifted differentiation of the Th cells. This view can be demonstrated by confirming that the shifted functional status of the Th cells is induced by the altered function of the repopulated macrophages after whole body irradiation (WBI)

  12. An African Thought on the Ethics of Human Foetal Life | Ebeh ...

    African Journals Online (AJOL)

    This paper presents an African thought on the ethics of human foetal life and this can be discussed against the backdrop of the African concept of life, person and community. In the process, it examines the fact of humanity and personhood of the human foetus and the role of the community in the determinant of humanity and ...

  13. New design of MHC class II tetramers to accommodate fundamental principles of antigen presentation.

    Science.gov (United States)

    Landais, Elise; Romagnoli, Pablo A; Corper, Adam L; Shires, John; Altman, John D; Wilson, Ian A; Garcia, K Christopher; Teyton, Luc

    2009-12-15

    Direct identification and isolation of Ag-specific T cells became possible with the development of MHC tetramers, based on fluorescent avidins displaying biotinylated peptide-MHC complexes. This approach, extensively used for MHC class I-restricted T cells, has met very limited success with class II peptide-MHC complex tetramers (pMHCT-2) for the detection of CD4(+)-specific T cells. In addition, a very large number of these reagents, although capable of specifically activating T cells after being coated on solid support, is still unable to stain. To try to understand this puzzle and design usable tetramers, we examined each parameter critical for the production of pMHCT-2 using the I-A(d)-OVA system as a model. Through this process, the geometry of peptide-MHC display by avidin tetramers was examined, as well as the stability of rMHC molecules. However, we discovered that the most important factor limiting the reactivity of pMHCT-2 was the display of peptides. Indeed, long peptides, as presented by MHC class II molecules, can be bound to I-A/HLA-DQ molecules in more than one register, as suggested by structural studies. This mode of anchorless peptide binding allows the selection of a broader repertoire on single peptides and should favor anti-infectious immune responses. Thus, beyond the technical improvements that we propose, the redesign of pMHCT-2 will give us the tools to evaluate the real size of the CD4 T cell repertoire and help us in the production and testing of new vaccines.

  14. The translocon protein Sec61 mediates antigen transport from endosomes in the cytosol for cross-presentation to CD8(+) T cells.

    Science.gov (United States)

    Zehner, Matthias; Marschall, Andrea L; Bos, Erik; Schloetel, Jan-Gero; Kreer, Christoph; Fehrenschild, Dagmar; Limmer, Andreas; Ossendorp, Ferry; Lang, Thorsten; Koster, Abraham J; Dübel, Stefan; Burgdorf, Sven

    2015-05-19

    The molecular mechanisms regulating antigen translocation into the cytosol for cross-presentation are under controversial debate, mainly because direct data is lacking. Here, we have provided direct evidence that the activity of the endoplasmic reticulum (ER) translocon protein Sec61 is essential for endosome-to-cytosol translocation. We generated a Sec61-specific intrabody, a crucial tool that trapped Sec61 in the ER and prevented its recruitment into endosomes without influencing Sec61 activity and antigen presentation in the ER. Expression of this ER intrabody inhibited antigen translocation and cross-presentation, demonstrating that endosomal Sec61 indeed mediates antigen transport across endosomal membranes. Moreover, we showed that the recruitment of Sec61 toward endosomes, and hence antigen translocation and cross-presentation, is dependent on dendritic cell activation by Toll-like receptor (TLR) ligands. These data shed light on a long-lasting question regarding antigen cross-presentation and point out a role of the ER-associated degradation machinery in compartments distinct from the ER. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Gluconeogenesis in rat placenta during foetal development

    International Nuclear Information System (INIS)

    Bagewadikar, R.S.; Sharma, C.; Nadkarni, G.B.

    1977-01-01

    Variations in glycogen levels in rat placenta have been correlated with gluconeogenesis in this tissue. Placental homogenate could synthesize substantial amounts of glucose from L-alanine-U- 14 C in early pregnancy. This has been substantiated by the observed enhancement in the activities of glucose 6-phosphatase, fructose 1, 6-diphosphatase and phosphoenolpyruvate carboxykinase. Gluconeogenic activity in placenta could proceed till the foetal liver was able to take over this function. The increase or decrease in placental glycogen is concomitant with glycogen synthetase, but not phosphorylase, activity. The reversible catalytic properties of placental aldolase also show subtle functional changes during and late phases of gestation. (author)

  16. Gluconeogenesis in rat placenta during foetal development

    Energy Technology Data Exchange (ETDEWEB)

    Bagewadikar, R S; Sharma, C; Nadkarni, G B [Bhabha Atomic Research Centre, Bombay (India). Biochemistry and Food Technology Div.

    1977-01-01

    Variations in glycogen levels in rat placenta have been correlated with gluconeogenesis in this tissue. Placental homogenate could synthesize substantial amounts of glucose from L-alanine-U-/sup 14/C in early pregnancy. This has been substantiated by the observed enhancement in the activities of glucose 6-phosphatase, fructose 1, 6-diphosphatase and phosphoenolpyruvate carboxykinase. Gluconeogenic activity in placenta could proceed till the foetal liver was able to take over this function. The increase or decrease in placental glycogen is concomitant with glycogen synthetase, but not phosphorylase, activity. The reversible catalytic properties of placental aldolase also show subtle functional changes during and late phases of gestation.

  17. Speech development delay in a child with foetal alcohol syndrome

    Directory of Open Access Journals (Sweden)

    Jacek Wilczyński

    2016-09-01

    Full Text Available A female foetus in her mother’s womb was exposed to high concentrations of alcohol at each stage of pregnancy on a long-term basis, which resulted in a permanent disability. In addition to a number of deficiencies in the overall functioning of the body of the child, there are serious problems pertaining to verbal communication. This thesis aims to describe foetal alcohol syndrome (FAS disease and present the basic problems with communication functions in a child, caused by damage of brain structures responsible for speech development. The thesis includes a speech diagnosis and therapy program adapted to the presented case. In the Discussion Section we have presented characteristics of communication disorders in case of children with FAS and the description of developmental malformations, neurobehavioral disorders, and environmental factors affecting the development of the child’s speech.

  18. Mass Spectrometry Reveals Changes in MHC I Antigen Presentation After Lentivector Expression of a Gene Regulation System

    Directory of Open Access Journals (Sweden)

    Roland Vogel

    2013-01-01

    Full Text Available The rapamycin-inducible gene regulation system was designed to minimize immune reactions in man and may thus be suited for gene therapy. We assessed whether this system indeed induces no immune responses. The protein components of the regulation system were produced in the human cell lines HEK 293T, D407, and HER 911 following lentiviral transfer of the corresponding genes. Stable cell lines were established, and the peptides presented by major histocompatibility complex class I (MHC I molecules on transduced and wild-type (wt cells were compared by differential mass spectrometry. In all cell lines examined, expression of the transgenes resulted in prominent changes in the repertoire of MHC I-presented self-peptides. No MHC I ligands originating from the transgenic proteins were detected. In vitro analysis of immunogenicity revealed that transduced D407 cells displayed slightly higher capacity than wt controls to promote proliferation of cytotoxic T cells. These results indicate that therapeutic manipulations within the genome of target cells may affect pathways involved in the processing of peptide antigens and their presentation by MHC I. This makes the genomic modifications visible to the immune system which may recognize these events and respond. Ultimately, the findings call attention to a possible immune risk.

  19. Smoking, physical exercise, BMI and late foetal death

    DEFF Research Database (Denmark)

    Morales-Suárez-Varela, Maria; Nohr, Ellen A; Bech, Bodil H

    2016-01-01

    The aim of this paper was to estimate the effect of maternal and paternal smoking on foetal death (miscarriage and stillbirth) and to estimate potential interactions with physical exercise and pre-pregnancy body mass index. We selected 87,930 pregnancies from the population-based Danish National......) for predominantly late foetal death (miscarriage and stillbirth). An interaction contrast ratio was used to assess potential effect measure modification of smoking by physical exercise and body mass index. The adjusted hazard ratio of foetal death was 1.22 (95 % CI 1.02-1.46) for couples where both parents smoked...... with a slightly higher hazard ratio for foetal death if both parents smoked. This study suggests that smoking may increase the negative effect of a high BMI on foetal death, but results were not statistically significant for the interaction between smoking and physical exercise....

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

    Science.gov (United States)

    Hsu, Peter; Nanan, Ralph

    2014-10-01

    In addition to genetic factors, environmental cues play important roles in shaping the immune system. The first environment that the developing foetal immune system encounters is the uterus. Although physically the mother and the foetus are separated by the placental membranes, various factors such as hormones and cytokines may provide "environmental cues" to the foetal immune system. Additionally, increasing evidence suggests that prenatal maternal environmental factors, particularly microbial exposure, might significantly influence the foetal immune system, affecting long-term outcomes, a concept termed foetal immune programming. Here we discuss the potential mediators of foetal immune programming, focusing on the role of pregnancy-related hormones, cytokines and regulatory T cells, which play a critical role in immune tolerance. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Dynamics of antigen presentation to transgene product-specific CD4+ T cells and of Treg induction upon hepatic AAV gene transfer

    Directory of Open Access Journals (Sweden)

    George Q Perrin

    2016-01-01

    Full Text Available The tolerogenic hepatic microenvironment impedes clearance of viral infections but is an advantage in viral vector gene transfer, which often results in immune tolerance induction to transgene products. Although the underlying tolerance mechanism has been extensively studied, our understanding of antigen presentation to transgene product-specific CD4+ T cells remains limited. To address this, we administered hepatotropic adeno-associated virus (AAV8 vector expressing cytoplasmic ovalbumin (OVA into wt mice followed by adoptive transfer of transgenic OVA-specific T cells. We find that that the liver-draining lymph nodes (celiac and portal are the major sites of MHC II presentation of the virally encoded antigen, as judged by in vivo proliferation of DO11.10 CD4+ T cells (requiring professional antigen-presenting cells, e.g., macrophages and CD4+CD25+FoxP3+ Treg induction. Antigen presentation in the liver itself contributes to activation of CD4+ T cells egressing from the liver. Hepatic-induced Treg rapidly disseminate through the systemic circulation. By contrast, a secreted OVA transgene product is presented in multiple organs, and OVA-specific Treg emerge in both the thymus and periphery. In summary, liver draining lymph nodes play an integral role in hepatic antigen presentation and peripheral Treg induction, which results in systemic regulation of the response to viral gene products.

  2. Changes in antigen-presenting cell function in the spleen and lymph nodes of ultraviolet-irradiated mice

    International Nuclear Information System (INIS)

    Gurish, M.F.; Lynch, D.H.; Daynes, R.A.

    1982-01-01

    It has been previously reported that mice exposed to ultraviolet (UV) radiation exhibit a decrease in splenic antigen-presenting cell (APC) function. The results presented here confirm this observation and further demonstrate that animals exposed daily to UV for extended periods of time (5 weeks instead of 6 days) no longer exhibit this depressed capability. In spite of the depression in splenic APC activity found in 6-day UV-irradiated mice, lymph node APC function from these same animals was elevated compared with that found in the lymph nodes from normal animals. Lymph node APC activity in animals that were splenectomized prior to the UV irradiation, however, was not enhanced over controls. Treatment of animals with a chemical irritant (turpentine) also caused a depression in splenic APC function without modifying lymph node activity. Collectively, our findings suggest that the observed decrease in splenic APC activity, found after the first week of UV exposures, may be attributable to the migration of splenic APC to peripheral lymphoid tissue which drain the site of epidermal inflammation

  3. The basics and advances of immunomodulators and antigen presentation: a key to development of potent memory response against pathogens.

    Science.gov (United States)

    Garai, Preeti; Gogoi, Mayuri; Gopal, Ganesh; Radhakrishnan, Yashwanth; Nandakumar, Krishnadas Subhadramma; Chakravortty, Dipshikha

    2014-10-01

    Immunomodulators are agents, which can modulate the immune response to specific antigens, while causing least toxicity to the host system. Being part of the modern vaccine formulations, these compounds have contributed remarkably to the field of therapeutics. Despite the successful record maintained by these agents, the requirement of novel immunomodulators keeps increasing due to the increasing severity of diseases. Hence, research regarding the same holds great importance. In this review, we discuss the role of immunomodulators in improving performance of various vaccines used for counteracting most threatening infectious diseases, mechanisms behind their action and criteria for development of novel immunomodulators. Understanding the molecular mechanisms underlying immune response is a prerequisite for development of effective therapeutics as these are often exploited by pathogens for their own propagation. Keeping this in mind, the present research in the field of immunotherapy focuses on developing immunomodulators that would not only enhance the protection against pathogen, but also generate a long-term memory response. With the introduction of advanced formulations including combination of different kinds of immunomodulators, one can expect tremendous success in near future.

  4. The 2.5 Å Structure of CD1c in Complex with a Mycobacterial Lipid Reveals an Open Groove Ideally Suited for Diverse Antigen Presentation

    Energy Technology Data Exchange (ETDEWEB)

    Scharf, Louise; Li, Nan-Sheng; Hawk, Andrew J.; Garzón, Diana; Zhang, Tejia; Fox, Lisa M.; Kazen, Allison R.; Shah, Sneha; Haddadian, Esmael J.; Gumperz, Jenny E.; Saghatelian, Alan; Faraldo-Gómez, José D.; Meredith, Stephen C.; Piccirilli, Joseph A.; Adams, Erin J. (Harvard); (UC); (MXPL-G); (UW-MED)

    2011-08-24

    CD1 molecules function to present lipid-based antigens to T cells. Here we present the crystal structure of CD1c at 2.5 {angstrom} resolution, in complex with the pathogenic Mycobacterium tuberculosis antigen mannosyl-{beta}1-phosphomycoketide (MPM). CD1c accommodated MPM's methylated alkyl chain exclusively in the A pocket, aided by a unique exit portal underneath the {alpha}1 helix. Most striking was an open F pocket architecture lacking the closed cavity structure of other CD1 molecules, reminiscent of peptide binding grooves of classical major histocompatibility complex molecules. This feature, combined with tryptophan-fluorescence quenching during loading of a dodecameric lipopeptide antigen, provides a compelling model by which both the lipid and peptide moieties of the lipopeptide are involved in CD1c presentation of lipopeptides.

  5. Detection rate of prostate cancer using prostate specific antigen in patients presenting with lower urinary tract symptoms: A retrospective study

    Directory of Open Access Journals (Sweden)

    Chavan P

    2009-01-01

    Full Text Available Background: Need for undertaking prostate biopsies for detection of prostate cancer is often decided on the basis of serum levels of prostate specific antigen (PSA. Aim: To evaluate the case detection rate of prostate cancer among patients presenting with lower urinary tract symptoms (LUTS on the basis of PSA levels and to assess the scope of prostate biopsy in these patients. Setting and Design: A retrospective study from a tertiary care center. Materials and Methods: The clinical and histopathological data of 922 patients presenting with LUTS in the last five years was obtained from the medical record section. They had been screened for prostate cancer using PSA and /or digital rectal examination examination followed by confirmation with prostate biopsy. Statistical Analysis Used: Detection rate and receiver operating characteristic curve were performed using SPSS 16 and Medcalc softwares. Results: The detection rate of prostate cancer according to the PSA levels was 0.6%, 2.3%, 2.5%, 34.1% and 54.9% in the PSA range of 0-4, 4-10, 10-20, 20-50 and> 50 ng/ml, respectively. Maximum prostate cancer cases were detected beyond a PSA value of 20 ng/ml whereas no significant difference in the detection rate was observed in the PSA range of 0-4, 4-10 and 10-20 ng/ml. Conclusion: A low detection rate of prostate cancer observed in the PSA range of 4-20 ng/ml in LUTS patients indicates the need for use of higher cutoff values of PSA in such cases. Therefore we recommend a cutoff of 20 ng/ml of PSA for evaluation of detection rate of prostate cancer among patients presenting with LUTS.

  6. Phase I study utilizing a novel antigen-presenting cell-targeted vaccine with Toll-like receptor stimulation to induce immunity to self-antigens in cancer patients.

    Science.gov (United States)

    Morse, Michael A; Chapman, Robert; Powderly, John; Blackwell, Kimberly; Keler, Tibor; Green, Jennifer; Riggs, Renee; He, Li-Zhen; Ramakrishna, Venky; Vitale, Laura; Zhao, Biwei; Butler, Stephen A; Hobeika, Amy; Osada, Takuya; Davis, Thomas; Clay, Timothy; Lyerly, H Kim

    2011-07-15

    The use of tumor-derived proteins as cancer vaccines is complicated by tolerance to these self-antigens. Tolerance may be broken by immunization with activated, autologous, ex vivo generated and antigen-loaded, antigen-presenting cells (APC); however, targeting tumor antigen directly to APC in vivo would be a less complicated strategy. We wished to test whether targeted delivery of an otherwise poorly immunogenic, soluble antigen to APC through their mannose receptors (MR) would induce clinically relevant immunity. Two phase I studies were conducted with CDX-1307, a vaccine composed of human chorionic gonadotropin beta-chain (hCG-β) fused to an MR-specific monoclonal antibody, administered either locally (intradermally) or systemically (intravenously) in patients with advanced epithelial malignancies. An initial dose escalation of single-agent CDX-1307 was followed by additional cohorts of CDX-1307 combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) and the Toll-like receptor (TLR) 3 agonist polyinosinic-polycytidylic acid (poly-ICLC) and TLR7/8 agonist resiquimod to activate the APC. CDX-1307 induced consistent humoral and T-cell responses to hCG-β when coadministered with TLR agonists. Greater immune responses and clinical benefit, including the longest duration of stable disease, were observed with immunization combined with local TLR agonists. Immune responses were induced equally efficiently in patients with elevated and nonelevated levels of serum hCG-β. Antibodies within the serum of vaccinated participants had tumor suppressive function in vitro. Toxicity consisted chiefly of mild injection site reactions. APC targeting and activation induce adaptive immunity against poorly immunogenic self-antigens which has implications for enhancing the efficacy of cancer immunotherapy.

  7. Immunologic effects of whole body ultraviolet (uv) irradiation. II. Defect in splenic adherent cell antigen presentation for stimulation of T cell proliferation

    International Nuclear Information System (INIS)

    Letvin, N.L.; Fox, I.J.; Greene, M.I.; Benacerraf, B.; Germain, R.N.

    1980-01-01

    Ultraviolet (uv) irradiation has been shown to alter many parameters of the immunologic reactivity of mice. The altered responsiveness of uv-irradiated mice, as measured by delayed-type hypersensitivity (DTH) and primary in vitro plaque-forming cell (PFC) responses to T-dependent antigens, has recently been correlated with a functional defect in the splenic adherent cell population of these animals. The present studies describe a model of this altered responsiveness, which allows further clarification of the effects of external uv irradiation on the splenic antigen-presenting cell (APC) in its interactions with T cells

  8. Lung cancer-associated tumor antigens and the present status of immunotherapy against non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Yasumoto, Kosei; Hanagiri, Takeshi; Takenoyama, Mitsuhiro

    2009-01-01

    Despite recent advances in surgery, irradiation, and chemotherapy, the prognosis of patients with lung cancer is still poor. Therefore, the development and application of new therapeutic strategies are essential for improving the prognosis of this disease. Significant progress in our understanding of tumor immunology and molecular biology has allowed us to identify the tumor-associated antigens recognized by cytotoxic T lymphocytes. Immune responses and tumor-associated antigens against not only malignant melanoma but also lung cancer have been elucidated at the molecular level. In a theoretical sense, tumor eradication is considered possible through antigen-based immunotherapy against such diseases. However, many clinical trials of cancer vaccination with defined tumor antigens have resulted in objective clinical responses in only a small number of patients. Tumor escape mechanisms from host immune surveillance remain a major obstacle for cancer immunotherapy. A better understanding of the immune escape mechanisms employed by tumor cells is necessary before we can develop a more effective immunotherapeutic approach to lung cancer. We review recent studies regarding the identification of tumor antigens in lung cancer, tumor immune escape mechanisms, and clinical vaccine trials in lung cancer. (author)

  9. Human Invariant Natural Killer T Cells Respond to Antigen-Presenting Cells Exposed to Lipids from Olea europaea Pollen.

    Science.gov (United States)

    Abos Gracia, Beatriz; López Relaño, Juan; Revilla, Ana; Castro, Lourdes; Villalba, Mayte; Martín Adrados, Beatriz; Regueiro, Jose Ramon; Fernández-Malavé, Edgar; Martínez Naves, Eduardo; Gómez Del Moral, Manuel

    2017-01-01

    Allergic sensitization might be influenced by the lipids present in allergens, which can be recognized by natural killer T (NKT) cells on antigen-presenting cells (APCs). The aim of this study was to analyze the effect of olive pollen lipids in human APCs, including monocytes as well as monocyte-derived macrophages (Mϕ) and dendritic cells (DCs). Lipids were extracted from olive (Olea europaea) pollen grains. Invariant (i)NKT cells, monocytes, Mϕ, and DCs were obtained from buffy coats of healthy blood donors, and their cell phenotype was determined by flow cytometry. iNKT cytotoxicity was measured using a lactate dehydrogenase assay. Gene expression of CD1A and CD1D was performed by RT-PCR, and the production of IL-6, IL-10, IL-12, and TNF-α cytokines by monocytes, Mϕ, and DCs was measured by ELISA. Our results showed that monocytes and monocyte-derived Mϕ treated with olive pollen lipids strongly activate iNKT cells. We observed several phenotypic modifications in the APCs upon exposure to pollen-derived lipids. Both Mϕ and monocytes treated with olive pollen lipids showed an increase in CD1D gene expression, whereas upregulation of cell surface CD1d protein occurred only in Mϕ. Furthermore, DCs differentiated in the presence of human serum enhance their surface CD1d expression when exposed to olive pollen lipids. Finally, olive pollen lipids were able to stimulate the production of IL-6 but downregulated the production of lipopolysaccharide- induced IL-10 by Mϕ. Olive pollen lipids alter the phenotype of monocytes, Mϕ, and DCs, resulting in the activation of NKT cells, which have the potential to influence allergic immune responses. © 2017 S. Karger AG, Basel.

  10. Antenatal diagnosis and management of foetal intestinal volvulus.

    Science.gov (United States)

    Yip, K W; Cheng, Y K Y; Leung, T Y

    2017-04-01

    In-utero intestinal volvulus is a rare but potential life threatening foetal complications. It is a surgical emergency and delay in diagnosis or treatment can increase the morbidity and mortality to the foetus. We report a case of mild foetal bowel dilatation diagnosed at 21 weeks of gestation. She was closely follow up and at 31 weeks of gestation, in-utero intestinal volvulus was diagnosed with the characteristic 'whirlpool' sign on ultrasound examination. This case emphasises the importance of early recognition and quick decision to delivery when intestinal volvulus is diagnosed. This enabled early surgical intervention to prevent further foetal morbidity.

  11. ASSESSMENT OF FOETAL COMPROMISE BY DOPPLER ULTRASOUND INVESTIGATION OF THE FOETAL CIRCULATION

    Directory of Open Access Journals (Sweden)

    Bindu Philip

    2017-09-01

    Full Text Available BACKGROUND The condition in which the foetus does not reach its growth potential is called Intrauterine Growth Restricted (IUGR. The mothers who are generally healthy and well nourished, the incidence of IUGR is 3-5%. The incidence of IUGR is 15-20% or higher in a women population with hypertension or previous growth restricted foetus. The aim of the study is to assess foetal compromise by Doppler ultrasound investigation of the foetal circulation. MATERIALS AND METHODS This study is a prospective study conducted between November 2013 to November 2016 in the Department of Radiodiagnosis and imaging of Mount Zion Medical College, Kerala. A total of 50 singleton pregnancies with suspected IUGR pregnancy attending the outpatient ward of Obstetrics and Gynaecology. Inclusion Criteria- Pregnancies from 29 weeks to 42 weeks of gestation complicated by intrauterine growth restriction and who are ultrasound confirmed. In the first trimester, gestational age determination was estimated by history of menstruation or biometry of foetus. Exclusion Criteria- Patients who had multiple gestations, congenital anomalies and history of membranes rupture. All the patients in the study were subjected to clinical history in detail to assess the risk factors of IUGR pregnancy, biometry of ultrasound and amniotic fluid assessment followed by Doppler ultrasound evaluation of uterine arteries, umbilical artery, middle cerebral artery, descending foetal thoracic aorta, ductus venous and umbilical vein. RESULTS Majority of the patients were in the age group of 21-24 years. All the patients were in the age group of 19-30 years. 45% of antenatal mothers examined were between 28-31 weeks of gestational age, 35% were between 32-36 weeks of gestation, 20% were between 37-42 weeks of gestation age. 15 antenatal mothers had elevated uterine artery resistance index (30%, 12 antenatal mothers had persistent early diagnostic notch (24%, 11 antenatal mothers had elevated systolic

  12. CD4+ T cell-mediated rejection of MHC class II-positive tumor cells is dependent on antigen secretion and indirect presentation on host APCs.

    Science.gov (United States)

    Haabeth, Ole Audun Werner; Fauskanger, Marte; Manzke, Melanie; Lundin, Katrin U; Corthay, Alexandre; Bogen, Bjarne; Tveita, Anders Aune

    2018-05-11

    Tumor-specific CD4+ T cells have been shown to mediate efficient anti-tumor immune responses against cancer. Such responses can occur through direct binding to MHC class II (MHC II)-expressing tumor cells or indirectly via activation of professional antigen-presenting cells (APC) that take up and present the tumor antigen. We have previously shown that CD4+ T cells reactive against an epitope within the Ig light chain variable region of a murine B cell lymphoma can reject established tumors. Given the presence of MHC II molecules at the surface of lymphoma cells, we investigated whether MHC II-restricted antigen presentation on tumor cells alone was required for rejection. Variants of the A20 B lymphoma cell line that either secreted or intracellularly retained different versions of the tumor-specific antigen revealed that antigen secretion by the MHC II-expressing tumor cells was essential both for the priming and effector phase of CD4+ T cell-driven anti-tumor immune responses. Consistent with this, genetic ablation of MHC II in tumor cells, both in the case of B lymphoma and B16 melanoma, did not preclude rejection of tumors by tumor antigen-specific CD4+ T cells in vivo. These findings demonstrate that MHC class II expression on tumor cells themselves is not required for CD4+ T cell-mediated rejection, and that indirect display on host APC is sufficient for effective tumor elimination. These results support the importance of tumor-infiltrating APC as mediators of tumor cell killing by CD4+ T cells. Copyright ©2018, American Association for Cancer Research.

  13. Induction of protective immunity to Theileria annulata using two major merozoite surface antigens presented by different delivery systems

    NARCIS (Netherlands)

    C. D'Oliveira; A. Feenstra; H.W. Vos (Helma); A.D.M.E. Osterhaus (Albert); B.R. Shiels; A.W.C.A. Cornelissen; F. Jongejan

    1997-01-01

    textabstractAllelic forms (Tams1-1 and Tams1-2) of the major merozoite surface antigen gene of Theileria annulata have recently been expressed in Escherichia coli and in Salmonella typhimurium aroA vaccine strain SL3261. To test the potential of subunit vaccines against T. annulata infection, we

  14. Migration of human antigen-presenting cells in a human skin graft onto nude mice model after contact sensitization

    NARCIS (Netherlands)

    Hoefakker, S.; Balk, H.P.; Boersma, W.J.A.; Joost, T. van; Notten, W.R.F.; Claassen, E.

    1995-01-01

    Fluorescent contact chemical allergens provoke sensitization after application on both syngeneic and allogeneic skin grafts in mice. We attempted to determine whether the functional activity in a contact sensitization response of human skin graft was affected at the level of antigen uptake and

  15. THE OCCURRENCE OF FOETAL DWARFIST{ IN THE ANGORA ...

    African Journals Online (AJOL)

    Foetal dwarfism following heat stress during preg- nancy has been .... with a low heat tolerance coefficient. lt has also been surmised that ... system by abnormal levels of maternal hormones. Star- ... and hence growth suppressing actions.

  16. Analysis of detergent-free lipid rafts isolated from CD4+ T cell line: interaction with antigen presenting cells promotes coalescing of lipid rafts

    Directory of Open Access Journals (Sweden)

    Kennedy Colleen

    2011-12-01

    Full Text Available Abstract Background Lipid rafts present on the plasma membrane play an important role in spatiotemporal regulation of cell signaling. Physical and chemical characterization of lipid raft size and assessment of their composition before, and after cell stimulation will aid in developing a clear understanding of their regulatory role in cell signaling. We have used visual and biochemical methods and approaches for examining individual and lipid raft sub-populations isolated from a mouse CD4+ T cell line in the absence of detergents. Results Detergent-free rafts were analyzed before and after their interaction with antigen presenting cells. We provide evidence that the average diameter of lipid rafts isolated from un-stimulated T cells, in the absence of detergents, is less than 100 nm. Lipid rafts on CD4+ T cell membranes coalesce to form larger structures, after interacting with antigen presenting cells even in the absence of a foreign antigen. Conclusions Findings presented here indicate that lipid raft coalescence occurs during cellular interactions prior to sensing a foreign antigen.

  17. The role of ghrelin, leptin and insulin in foetal development

    Directory of Open Access Journals (Sweden)

    Magdalena Warchoł

    2014-06-01

    Full Text Available introduction and objective. The growing epidemic of childhood obesity has forced scientists to search for methods to prevent feeding disorders. Increasing interest in appetite regulating hormones has revealed their influence on energy homeostasis after birth or even in[i] utero[/i]. state of knowledge. The presence of ghrelin in the stomach of human foetuses and the distinctive production in the pancreas of neonates suggests the role of ghrelin in pre- and post-natal development. The neonatal period appears to be a critical time for the formation of adipose tissue-hypothalamus circuits, thus the amount of adipocytes in foetal life may be a major regulator of food intake. Insulin’s orexigenic effect in the arcuate nucleus of the hypothalamus can be a major modulator of foetal development. objective. This review, based on available literature, aims to analyses the role of appetite regulating hormones in foetal development. summary. Different concentrations of hormones, such as ghrelin, leptin and insulin during foetal life raises the question whether or not they can be modulated, thereby avoiding obesity before birth. Children with pancreas agenesis showed smaller body size at birth, which emphasises the probable role of insulin in foetal growth. Study of sheep foetuses with IUGR confirmed these finding. Appetite-regulating hormones show different roles in foetal development and seem to be essential in the perinatal period.

  18. MATERNAL AND FOETAL OUTCOME OF VAGINAL BIRTH AFTER CAESAREAN SECTION

    Directory of Open Access Journals (Sweden)

    Thulasi

    2016-04-01

    Full Text Available OBJECTIVES OF THE STUDY 1. To identify maternal and foetal factors responsible for the success or the failure of VBAC. 2. To study maternal and perinatal outcome while giving a trial of scar. METHOD OF COLLECTION OF DATA Study was conducted at P K Das Institute of Medical Sciences hospital. 50 cases obtained during the period of January 2013 to December 2013 were studied. Inclusion Criteria 1. Multigravida with previous one lower segment caesarean section at term in early labour. 2. Singleton pregnancy. 3. Cephalic presentation. 4. Who are willing for VBAC. 5. Well-informed subjects. Exclusion Criteria 1. Known classical scar and 2 or >caesarean sections. 2. Unknown uterine scar. 3. Multiple gestation. 4. Malpresentations. 5. Cephalopelvic disproportion. 6. Subjects with medical complication/obstetric risk factors. Cases are monitored with a partogram and continuous foetal monitor. METHODOLOGY Informed consent is taken after explaining the risks, benefits and potential complications in patients’ own language while giving a trial of scar. After the exclusion criteria, patients selected for VBAC is given a trial of scar. 1. Maternal monitoring of blood pressure and pulse rate every 15 minutes is done. 2. Continuous foetal monitoring in the active phase of labour. 3. Contraction stress test will be done in the active phase of labour. Uterine contractions are monitored every 30 minutes. Partogram is used to ensure adequate progress with respect to descent of the head, cervical dilatation, moulding and caput. 4. Pelvic examination every one hour to assess the progress of labour. 5. If labour has to be induced, done with great care particularly with prostaglandins – PGE 2 gel. Progress of labour should be assessed by a senior obstetrician, particularly in an unfavourable cervix. 6. Cross-matched blood is kept ready and a good intravenous line is established. 7. Oxytocin may be used with caution, as in any labour, for induction or augmentation. 8

  19. Presentation of human minor histocompatibility antigens by HLA-B35 and HLA-B38 molecules

    International Nuclear Information System (INIS)

    Yamamoto, Junji; Kariyone, Ai; Kano, Kyoichi; Takiguchi, Masafumi; Akiyama, Nobuo

    1990-01-01

    Cytotoxic T lymphocyte (CTL) clones specific for human minor histocompatibility antigens (hmHAs) were produced from a patient who had been grafted with the kidneys from his mother and two HLA-identical sisters. Of eight CTL clones generated, four recognized an hmHA (hmHA-1) expressed on cells from the mother and sister 3 (second donor); two recognized another antigen (hmHA-2) on cells from the father, sister (third donor), and sister 3; and the remaining two clones recognized still another antigen (hmHA-3) on cells from the father and sister 3. Panel studies revealed that CTL recognition of hmHA-1 was restricted by HLA-B35 and that of hmHA-2 and hmHA-3 was restricted by HLA-B38. The HLA-B35 restriction of the hmHA-1 -specific CTL clones was substantiated by the fact that they killed HLA-A null/HLA-B null Hmy2CIR targets transfected with HLA-B35 but not HLA-B51, -Bw52, or -Bw53 transfected Hmy2CIR targets. These data demonstrated that the five amino acids substitutions on the α 1 domain between HLA-B35 and -Bw53, which are associated with Bw4/Bw6 epitopes, play a critical role in the relationship of hmHA-1 to HLA-B35 molecules. The fact that the hmHA-1-specific CTLs failed to kill Hmy2CIR cells expressing HLA-B35/51 chimeric molecules composed of the α 1 domain of HLA-B35 and other domains of HLA-B51 indicated that eight residues on the α 2 domain also affect the interaction of hmHA-1 and the HLA-B35 molecules

  20. The prevalence of the maxillo-septal syndrome in Anglo-Saxon and Romano-British skulls and foetal specimens.

    Science.gov (United States)

    Griffin, C J

    1978-04-01

    Seventy-three pre-medieval British skulls were examined and the maxillo-septal syndrome was found in 42. Ten foetal specimens of crown rump length greater than 40 mm were also examined and the syndrome was found in three specimens. Deflection of the nasal septum was present in 56 specimens.

  1. Autophagy-related protein Vps34 controls the homeostasis and function of antigen cross-presenting CD8α+ dendritic cells.

    Science.gov (United States)

    Parekh, Vrajesh V; Pabbisetty, Sudheer K; Wu, Lan; Sebzda, Eric; Martinez, Jennifer; Zhang, Jianhua; Van Kaer, Luc

    2017-08-01

    The class III PI3K Vacuolar protein sorting 34 (Vps34) plays a role in both canonical and noncanonical autophagy, key processes that control the presentation of antigens by dendritic cells (DCs) to naive T lymphocytes. We generated DC-specific Vps34 -deficient mice to assess the contribution of Vps34 to DC functions. We found that DCs from these animals have a partially activated phenotype, spontaneously produce cytokines, and exhibit enhanced activity of the classic MHC class I and class II antigen-presentation pathways. Surprisingly, these animals displayed a defect in the homeostatic maintenance of splenic CD8α + DCs and in the capacity of these cells to cross-present cell corpse-associated antigens to MHC class I-restricted T cells, a property that was associated with defective expression of the T-cell Ig mucin (TIM)-4 receptor. Importantly, mice deficient in the Vps34-associated protein Rubicon, which is critical for a noncanonical form of autophagy called "Light-chain 3 (LC3)-associated phagocytosis" (LAP), lacked such defects. Finally, consistent with their defect in the cross-presentation of apoptotic cells, DC-specific Vps34 -deficient animals developed increased metastases in response to challenge with B16 melanoma cells. Collectively, our studies have revealed a critical role of Vps34 in the regulation of CD8α + DC homeostasis and in the capacity of these cells to process and present antigens associated with apoptotic cells to MHC class I-restricted T cells. Our findings also have important implications for the development of small-molecule inhibitors of Vps34 for therapeutic purposes.

  2. TEENAGE PREGNANCY: DEMOGRAPHICS, MATERNAL AND FOETAL OUTCOME

    Directory of Open Access Journals (Sweden)

    Radhika Gollapudi

    2016-08-01

    Full Text Available BACKGROUND Pregnancy though is a physiological event in a woman’s life, it has its own associated complications. In teenage pregnancies, the physical and emotional state of stress coupled with biological immaturity leads to adverse effect both on the health of the mother and the foetus. METHODS This study is a clinical prospective study analysing the demographics, maternal health issues and the foetal outcome in teenage pregnancies. The study was conducted over a period of one year at a government tertiary care center. Pregnant women in the age group of 13-19 years who delivered during the study period were included in the study group. All pregnant women over 20 years of age who delivered during the same period were taken as control group. Women who had medical disorders complicating pregnancy were excluded from the study. Anaemia, pregnancy induced hypertension, antepartum haemorrhage and mode of delivery were the maternal outcomes that were noted. Intrauterine growth retardation, prematurity, low birth weight, APGAR score were analysed with respect to the foetus. RESULTS In this study, the total number of pregnant women who delivered during the study period were 4782, 536 were teenage mothers, constituting 11.2% of the total pregnancies. Of the 536 teenage mothers, 69.78% belonged to the rural areas and 71.64% were found to have inadequate antenatal visits to the hospital. The mean age of teenage pregnancy was 17.18 years. Incidence of anaemia was 44.2% in comparison, the control group had an incidence of 33.02%. In our study, incidence of Pregnancy induced hypertension was 18.64% in teenage mothers and 10.6% in non-teenage mothers. The incidence of Antepartum Haemorrhage in our study was 8.94% in teenage mothers. Incidence of lower segment caesarean section was 22.76% in the teenage group as compared to 14.57% in the non-teenage group. In our study, 13.05% of teenage mothers had preterm deliveries as compared to 6.40% of non-teenage mothers

  3. STUDY OF MATERNAL AND FOETAL OUTCOME IN TWIN PREGNANCY

    Directory of Open Access Journals (Sweden)

    Burri Sandhya Rani

    2018-01-01

    Full Text Available BACKGROUND In comparison to singleton pregnancies, twin pregnancies are considered a high risk pregnancies associated with perinatal mortalities and maternal morbidities due to unnecessary use of ovulation induced drugs. The aim of the study is to evaluate the maternal and foetal outcomes in twin gestations and to find the various factors that contribute to adverse perinatal outcome. MATERIALS AND METHODS This study was carried out in Laxmi Narasimha Hospital, Warangal, Hanamkonda, Telangana, an over a period of May 2015 to August 2016. RESULTS Most of the women were in their fertile age i.e. in between 20-30 years of age (86.6%. In both primigravida and multigravidas, the twins were equal. Preterm labour complications were seen in 88.8% of the patients and PIH was seen in 11.2% of the patients. Anaemia was the most common mal-presentation seen in the patients which constituted to 33.3%. Number of patients who underwent mode of delivery through spontaneous vaginal section were 60 which constituted 66.7%, caesarean section were 25 which constituted 27.7%, instrumental vaginal section were 5 which constituted 5.6%. The number of patients who had the foetal birth weight 2000 grams were 55 which constituted 30.6%. The number of male babies were 110 (61.1% and female babies were 70 (38.9%. Number of live births were 170 (94.4%, still births were 10 (5.6%. Number of patients admitted in ICU were 100 (55.6%, Neonatal morbidity was seen in 38 patients (21.1%, neonatal mortality was seen in 10 patients (5.6%. The most common cause of neonatal death was septicaemia followed by respiratory distress, pulmonary distress and DIC. CONCLUSION This study concluded that deaths were majorly due to extremely premature and very low birth weight babies. These babies had septicaemia or respiratory distress. By averting pre-term births, by taking good rest, cervical encerclage, when incompetence is suspected, short term tocolysis, prevention of anaemia and pre

  4. Replication-deficient mutant Herpes Simplex Virus-1 targets professional antigen presenting cells and induces efficient CD4+ T helper responses.

    OpenAIRE

    Fiorentini, Simona; Marconi, Peggy; Avolio, Manuela; Marini, Elena; Garrafa, Emirena; Caracciolo, Sonia; Rossi, Daniele; Bozac, Alexandra; Becker, Pablo D; Gentili, Francesca; Facchetti, Fabio; Guzman, Carlos A; Manservigi, Roberto; Caruso, Arnaldo

    2007-01-01

    Both neutralizing antibodies and cytotoxic T-cells are necessary to control a viral infection. However, vigorous T helper responses are essential for their elicitation and maintenance. Here we show that a recombinant replication-deficient Herpes Simplex Virus (HSV)-1 vector encoding the Human Immunodeficiency Virus (HIV)-1 matrix protein p17 (T0-p17) was capable of infecting professional antigen presenting cells (APCs) in vitro and in vivo. The injection of T0-p17 in the mouse dermis generate...

  5. Selection of restriction specificities of virus-specific cytotoxic T cells in the thymus: no evidence for a crucial role of antigen-presenting cells

    International Nuclear Information System (INIS)

    Zinkernagel, R.M.

    1982-01-01

    The proposal was tested that (P1 X P2) F1 leads to P1 irradiation bone marrow chimeras expressed predominantly P1-restricted T cells because donor derived stem cells were exposed to recipient derived antigen-presenting cells in the thymus. Because P1 recipient-derived antigen-presenting cells are replaced only slowly after 6-8 wk by (P1 X P2) donor-derived antigen-presenting cells in the thymus and because replenished pools of mature T cells may by then prevent substantial numbers of P2-restricted T cells to be generated, a large portion of thymus cells and mature T cells were eliminated using the following treatments of 12-20-wk-old (P1 X P2) F1 leads to P1 irradiation bone marrow chimeras: (a) cortisone plus antilymphocyte serum, (b) Cytoxan, (c) three doses of sublethal irradiation (300 rad) 2d apart, and (d) lethal irradiation (850 rad) and reconstitution with T cell-depleted (P1 X P2) F1 stem cells. 12-20 wk after this second treatment, (P1 X P2) leads to P1 chimeras were infected with vaccinia-virus. Virus-specific cytotoxic T cell reactivity was expressed by chimeric T cells of (P1 X P[2) F1 origin and was restricted predominantly to P1. Virus-specific cytotoxic T cells, therefore, do not seem to be selected to measurable extent by the immigrating donor-derived antigen-presenting cells in the thymus; their selection depends apparently from the recipient-derived radioresistant thymus cells

  6. Foetal distribution and metabolism of N-Nitrosodiethylamine in mice

    International Nuclear Information System (INIS)

    Brittebo, E.B.; Lindgren, A.; Tjaelve, A.

    1981-01-01

    In pregnant NMRI mice, low-temperature autoradiography was used to study the distribution of N- 14 C-nitrosodiethylamine in foetal tissues, and autoradiography with heated tape-sections was used to trace nonvolatile metabolites. Autoradiography with 14 C-acetate was used to distinquish the part of the radiography which upon the degradation of N- 14 C-nitrosodiethylamine may be incorporated in the normal metabolism of the tissues. The results indicated that the non-metabolized N-nitrosodiethylamine passed to the foetuses with an even distribution in most foetal tissues on all the studied days of gestation (day 12, 14, 16 and 18). The autoradiographic results further indicated a metabolism of the substance in the mucosa of the foetal bronchial tree and in the foetal liver on day 18 of gestation, but not in earlier stages of pregnancy. This was substantiated by studies in vitro, which showed a marked capacity of the 18 day old foetal lung and liver (in contrast to tissues from 16 day old foetuses) to form 14 CO 2 from the N- 14 C-nitrosodiethylamine. Since the lung and liver are target tissues for the transplacental carcinogenesis of N-nitrosodiethylamine in NMRI mice, a causal relationship between metabolic ability and carcinogenesis may exist in these tissues. (Author)

  7. Neonatal colonisation expands a specific intestinal antigen-presenting cell subset prior to CD4 T-cell expansion, without altering T-cell repertoire.

    Directory of Open Access Journals (Sweden)

    Charlotte F Inman

    Full Text Available Interactions between the early-life colonising intestinal microbiota and the developing immune system are critical in determining the nature of immune responses in later life. Studies in neonatal animals in which this interaction can be examined are central to understanding the mechanisms by which the microbiota impacts on immune development and to developing therapies based on manipulation of the microbiome. The inbred piglet model represents a system that is comparable to human neonates and allows for control of the impact of maternal factors. Here we show that colonisation with a defined microbiota produces expansion of mucosal plasma cells and of T-lymphocytes without altering the repertoire of alpha beta T-cells in the intestine. Importantly, this is preceded by microbially-induced expansion of a signal regulatory protein α-positive (SIRPα(+ antigen-presenting cell subset, whilst SIRPα(-CD11R1(+ antigen-presenting cells (APCs are unaffected by colonisation. The central role of intestinal APCs in the induction and maintenance of mucosal immunity implicates SIRPα(+ antigen-presenting cells as orchestrators of early-life mucosal immune development.

  8. Inhibition of antigen-presenting activity of dendritic cells resulting from UV irradiation of murine skin is restored by in vitro photorepair of cyclobutane pyrimidine dimers

    International Nuclear Information System (INIS)

    Vink, A.A.; Roza, L.; Moodycliffe, A.M.; Shreedhar, V.

    1997-01-01

    Exposing skin to UVB (280-320 nm) radiation suppresses contact hypersensitivity by a mechanism that involves an alteration in the activity of cutaneous antigen-presenting cells (APC). UV-induced DNA damage appears to be an important molecular trigger for this effect. The specific target cells in the skin that sustain DNA damage relevant to the immunosuppressive effect have yet to be identified. We tested the hypothesis that UV-induced DNA damage in the cutaneous APC was responsible for their impaired ability to present antigen after in vivo UV irradiation. Cutaneous APC were collected from the draining lymph nodes of UVB-irradiated, hapten-sensitized mice and incubated in vitro with liposomes containing a photolyase, which, upon absorption of photoreactivating light, splits UV-induced cyclobutane pyrimidine dimers. Photosome treatment followed by photoreactivating light reduced the number of dimer-containing APC, restored the in vivo antigen-presenting activity of the draining lymph node cells, and blocked the induction of suppressor T cells. Neither Photosomes nor photoreactivating light alone, nor photoreactivating light given before Photosomes, restored APC activity, and Photosomes treatment did not reverse the impairment of APC function when isopsoralen plus UVA (320-400 nm) radiation was used instead of UVB. These controls indicate that the restoration of APC function matched the requirements of Photosome-mediated DNA repair for dimers and post-treatment photoreactivating light. These results provide compelling evidence that it is UV-induced DNA damage in cutaneous APC that leads to reduced immune function

  9. Characterisation of Antigen B Protein Species Present in the Hydatid Cyst Fluid of Echinococcus canadensis G7 Genotype.

    Science.gov (United States)

    Folle, Ana Maite; Kitano, Eduardo S; Lima, Analía; Gil, Magdalena; Cucher, Marcela; Mourglia-Ettlin, Gustavo; Iwai, Leo K; Rosenzvit, Mara; Batthyány, Carlos; Ferreira, Ana María

    2017-01-01

    The larva of cestodes belonging to the Echinococcus granulosus sensu lato (s.l.) complex causes cystic echinococcosis (CE). It is a globally distributed zoonosis with significant economic and public health impact. The most immunogenic and specific Echinococcus-genus antigen for human CE diagnosis is antigen B (AgB), an abundant lipoprotein of the hydatid cyst fluid (HF). The AgB protein moiety (apolipoprotein) is encoded by five genes (AgB1-AgB5), which generate mature 8 kDa proteins (AgB8/1-AgB8/5). These genes seem to be differentially expressed among Echinococcus species. Since AgB immunogenicity lies on its protein moiety, differences in AgB expression within E. granulosus s.l. complex might have diagnostic and epidemiological relevance for discriminating the contribution of distinct species to human CE. Interestingly, AgB2 was proposed as a pseudogene in E. canadensis, which is the second most common cause of human CE, but proteomic studies for verifying it have not been performed yet. Herein, we analysed the protein and lipid composition of AgB obtained from fertile HF of swine origin (E. canadensis G7 genotype). AgB apolipoproteins were identified and quantified using mass spectrometry tools. Results showed that AgB8/1 was the major protein component, representing 71% of total AgB apolipoproteins, followed by AgB8/4 (15.5%), AgB8/3 (13.2%) and AgB8/5 (0.3%). AgB8/2 was not detected. As a methodological control, a parallel analysis detected all AgB apolipoproteins in bovine fertile HF (G1/3/5 genotypes). Overall, E. canadensis AgB comprised mostly AgB8/1 together with a heterogeneous mixture of lipids, and AgB8/2 was not detected despite using high sensitivity proteomic techniques. This endorses genomic data supporting that AgB2 behaves as a pseudogene in G7 genotype. Since recombinant AgB8/2 has been found to be diagnostically valuable for human CE, our findings indicate that its use as antigen in immunoassays could contribute to false negative results in

  10. Characterisation of Antigen B Protein Species Present in the Hydatid Cyst Fluid of Echinococcus canadensis G7 Genotype

    Science.gov (United States)

    Folle, Ana Maite; Kitano, Eduardo S.; Lima, Analía; Gil, Magdalena; Cucher, Marcela; Mourglia-Ettlin, Gustavo; Iwai, Leo K.; Rosenzvit, Mara; Batthyány, Carlos

    2017-01-01

    The larva of cestodes belonging to the Echinococcus granulosus sensu lato (s.l.) complex causes cystic echinococcosis (CE). It is a globally distributed zoonosis with significant economic and public health impact. The most immunogenic and specific Echinococcus-genus antigen for human CE diagnosis is antigen B (AgB), an abundant lipoprotein of the hydatid cyst fluid (HF). The AgB protein moiety (apolipoprotein) is encoded by five genes (AgB1-AgB5), which generate mature 8 kDa proteins (AgB8/1-AgB8/5). These genes seem to be differentially expressed among Echinococcus species. Since AgB immunogenicity lies on its protein moiety, differences in AgB expression within E. granulosus s.l. complex might have diagnostic and epidemiological relevance for discriminating the contribution of distinct species to human CE. Interestingly, AgB2 was proposed as a pseudogene in E. canadensis, which is the second most common cause of human CE, but proteomic studies for verifying it have not been performed yet. Herein, we analysed the protein and lipid composition of AgB obtained from fertile HF of swine origin (E. canadensis G7 genotype). AgB apolipoproteins were identified and quantified using mass spectrometry tools. Results showed that AgB8/1 was the major protein component, representing 71% of total AgB apolipoproteins, followed by AgB8/4 (15.5%), AgB8/3 (13.2%) and AgB8/5 (0.3%). AgB8/2 was not detected. As a methodological control, a parallel analysis detected all AgB apolipoproteins in bovine fertile HF (G1/3/5 genotypes). Overall, E. canadensis AgB comprised mostly AgB8/1 together with a heterogeneous mixture of lipids, and AgB8/2 was not detected despite using high sensitivity proteomic techniques. This endorses genomic data supporting that AgB2 behaves as a pseudogene in G7 genotype. Since recombinant AgB8/2 has been found to be diagnostically valuable for human CE, our findings indicate that its use as antigen in immunoassays could contribute to false negative results in

  11. Organic extract of diesel exhaust particles stimulates expression of Ia and costimulatory molecules associated with antigen presentation in rat peripheral blood monocytes but not in alveolar macrophages

    International Nuclear Information System (INIS)

    Koike, Eiko; Kobayashi, Takahiro

    2005-01-01

    We hypothesized that diesel exhaust particles (DEP) induce the activation of antigen-presenting cells (APC) in lung. The present study was designed to clarify the following about DEP: (1) whether it affects the expression of Ia and B7 molecules in alveolar macrophages (AM) as a mature cell or in peripheral blood monocytes (PBM) as an immature cell (2) if it affects the antigen-presenting (AP) activity of PBM (3) what component of DEP is responsible for the effects, and (4) whether the effect of DEP is related to oxidative stress. DEP was extracted with methylene chloride. Cells were exposed to whole DEP, organic extract, or residual particles for 24 h. Cell-surface molecules were measured by flow cytometry. AP activity was assessed by antigen-specific T cell proliferation. Whole DEP or organic extract significantly increased the expression of Ia and B7 molecules on PBM but not on AM. No significant effect of residual particles was observed. A low concentration of organic extract also increased the AP activity of PBM. When the induction of an antioxidative enzyme was assessed, heme oxygenase-1 protein was found to be significantly increased by exposure to whole DEP, and the organic extract was more effective than the residual particles. Furthermore, the organic extract-induced expression of Ia antigen on PBM was reduced by the addition of an antioxidative agent. These results suggest that DEP may act on immature APC and enhance their AP activity and that the action contributing to oxidative stress may be mediated by organic compounds of DEP

  12. Tolerance induction to cytoplasmic beta-galactosidase by hepatic AAV gene transfer: implications for antigen presentation and immunotoxicity.

    Directory of Open Access Journals (Sweden)

    Ashley T Martino

    2009-08-01

    Full Text Available Hepatic gene transfer, in particular using adeno-associated viral (AAV vectors, has been shown to induce immune tolerance to several protein antigens. This approach has been exploited in animal models of inherited protein deficiency for systemic delivery of therapeutic proteins. Adequate levels of transgene expression in hepatocytes induce a suppressive T cell response, thereby promoting immune tolerance. This study addresses the question of whether AAV gene transfer can induce tolerance to a cytoplasmic protein.AAV-2 vector-mediated hepatic gene transfer for expression of cytoplasmic beta-galactosidase (beta-gal was performed in immune competent mice, followed by a secondary beta-gal gene transfer with E1/E3-deleted adenoviral Ad-LacZ vector to provoke a severe immunotoxic response. Transgene expression from the AAV-2 vector in approximately 2% of hepatocytes almost completely protected from inflammatory T cell responses against beta-gal, eliminated antibody formation, and significantly reduced adenovirus-induced hepatotoxicity. Consequently, approximately 10% of hepatocytes continued to express beta-gal 45 days after secondary Ad-LacZ gene transfer, a time point when control mice had lost all Ad-LacZ derived expression. Suppression of inflammatory T cell infiltration in the liver and liver damage was linked to specific transgene expression and was not seen for secondary gene transfer with Ad-GFP. A combination of adoptive transfer studies and flow cytometric analyses demonstrated induction of Treg that actively suppressed CD8(+ T cell responses to beta-gal and that was amplified in liver and spleen upon secondary Ad-LacZ gene transfer.These data demonstrate that tolerance induction by hepatic AAV gene transfer does not require systemic delivery of the transgene product and that expression of a cytoplasmic neo-antigen in few hepatocytes can induce Treg and provide long-term suppression of inflammatory responses and immunotoxicity.

  13. Replication-deficient mutant Herpes Simplex Virus-1 targets professional antigen presenting cells and induces efficient CD4+ T helper responses.

    Science.gov (United States)

    Fiorentini, Simona; Marconi, Peggy; Avolio, Manuela; Marini, Elena; Garrafa, Emirena; Caracciolo, Sonia; Rossi, Daniele; Bozac, Alexandra; Becker, Pablo D; Gentili, Francesca; Facchetti, Fabio; Guzman, Carlos A; Manservigi, Roberto; Caruso, Arnaldo

    2007-07-01

    Both neutralizing antibodies and cytotoxic T-cells are necessary to control a viral infection. However, vigorous T helper responses are essential for their elicitation and maintenance. Here we show that a recombinant replication-deficient Herpes Simplex Virus (HSV)-1 vector encoding the Human Immunodeficiency Virus (HIV)-1 matrix protein p17 (T0-p17) was capable of infecting professional antigen presenting cells (APCs) in vitro and in vivo. The injection of T0-p17 in the mouse dermis generated a strong p17-specific CD4+ T helper response preceding both p17-specific humoral and effector T cell responses. Moreover, we show that T0-p17 infection did not interfere with the endogenous processing of the transgene encoded antigen, since infected APCs were able to evoke a strong recall response in vitro. Our results demonstrate that replication-deficient HSV vectors can be appealing candidates for the development of vaccines able to trigger T helper responses.

  14. Differential presentation of endogenous and exogenous hepatitis B surface antigens influences priming of CD8(+) T cells in an epitope-specific manner.

    Science.gov (United States)

    Riedl, Petra; Reiser, Michael; Stifter, Katja; Krieger, Jana; Schirmbeck, Reinhold

    2014-07-01

    Little is known about whether presentation of endogenous and exogenous hepatitis B virus (HBV) surface antigens on APCs targeted by vaccination and/or virus-harboring hepatocytes influences de novo priming of CD8(+) T cells. We showed that surface antigen-expressing transfectants exclusively display a K(b) /S190 epitope, whereas cells pulsed with recombinant surface particles (rSPs) exclusively present a K(b) /S208 epitope to CD8(+) T cells. The differential presentation of these epitopes largely reflects the selective, but not exclusive, priming of K(b) /S190- and K(b) /S208-specific T cells in C57BL/6 mice by endogenous/DNA- or exogenous/protein-based vaccines, respectively. Silencing the K(b) /S190 epitope (K(b) /S190V194F ) in antigen-expressing vectors rescued the presentation of the K(b) /S208 epitope in stable transfectants and significantly enhanced priming of K(b) /S208-specific T cells in C57BL/6 mice. A K(b) /S190-mediated immunodominance operating in surface antigen-expressing cells, but not in rSP-pulsed cells, led to an efficient suppression in the presentation of the K(b) /S208 epitope and a consequent decrease in the priming of K(b) /S208-specific T cells. This K(b) /S190-mediated immunodominance also operated in 1.4HBV-S(mut) transgenic (tg) hepatocytes selectively expressing endogenous surface antigens and allowed priming of K(b) /S208- but not K(b) /S190-specific T cells in 1.4HBV-S(mut) tg mice. However, IFN-γ(+) K(b) /S208-specific T cells could not inhibit HBV replication in the liver of 1.4HBV-S(mut) tg mice. These results have practical implications for the design of T-cell-stimulating therapeutic vaccines. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. The actin cytoskeleton modulates the activation of iNKT cells by segregating CD1d nanoclusters on antigen-presenting cells

    Science.gov (United States)

    Torreno-Pina, Juan A.; Manzo, Carlo; Salio, Mariolina; Aichinger, Michael C.; Oddone, Anna; Lakadamyali, Melike; Shepherd, Dawn; Besra, Gurdyal S.; Cerundolo, Vincenzo

    2016-01-01

    Invariant natural killer T (iNKT) cells recognize endogenous and exogenous lipid antigens presented in the context of CD1d molecules. The ability of iNKT cells to recognize endogenous antigens represents a distinct immune recognition strategy, which underscores the constitutive memory phenotype of iNKT cells and their activation during inflammatory conditions. However, the mechanisms regulating such “tonic” activation of iNKT cells remain unclear. Here, we show that the spatiotemporal distribution of CD1d molecules on the surface of antigen-presenting cells (APCs) modulates activation of iNKT cells. By using superresolution microscopy, we show that CD1d molecules form nanoclusters at the cell surface of APCs, and their size and density are constrained by the actin cytoskeleton. Dual-color single-particle tracking revealed that diffusing CD1d nanoclusters are actively arrested by the actin cytoskeleton, preventing their further coalescence. Formation of larger nanoclusters occurs in the absence of interactions between CD1d cytosolic tail and the actin cytoskeleton and correlates with enhanced iNKT cell activation. Importantly and consistently with iNKT cell activation during inflammatory conditions, exposure of APCs to the Toll-like receptor 7/8 agonist R848 increases nanocluster density and iNKT cell activation. Overall, these results define a previously unidentified mechanism that modulates iNKT cell autoreactivity based on the tight control by the APC cytoskeleton of the sizes and densities of endogenous antigen-loaded CD1d nanoclusters. PMID:26798067

  16. Native IgG2a(b) is barely antigenic to major histocompatibility complex class II-restricted T cells owing to inefficient internalization by professional antigen-presenting cells.

    Science.gov (United States)

    Bartnes, K; Hannestad, K

    2000-04-01

    Peptide epitopes derived from immunoglobulin variable regions represent tumour-specific antigens on B-cell neoplasms and can be recognized by syngeneic, major histocompatibility complex (MHC) class II-restricted T cells. Immunoglobulin peptide/MHC class II complexes may also be involved in autoimmunity and CD4+ T-cell-mediated B-cell regulation. Thus, the IgG2a(b) H-chain allopeptide gamma2a(b) 435-451 presented on I-Ad mimics the epitope implicated in herpes simplex virus-induced autoimmune stromal keratitis and is the target of T helper 1 (Th1) clones that suppress IgG2a(b) production in vivo. We here report that spleen and thymus cells constitutively present the autologous gamma2a(b) epitope to a gamma2a(b) 435-451/I-A(d) reactive T-cell hybridoma as a function of the animal housing conditions (specific pathogen-free or not) and the serum levels of IgG2a(b). Constitutive presentation in the spleen was predominantly performed by dendritic cells. Whereas spleen cells poorly presented native IgG2a(b) to a gamma2a(b) 435-451/I-A(d) reactive T-cell hybridoma, IgG2a(b) in the form of immune complexes were presented > 200-fold more efficiently owing to internalization via low-affinity FcgammaR on macrophages. The antigenicity could also be improved by homotypic aggregation and by targeting IgG2a(b) to complement receptors on the A20 B-cell lymphoma. Mice without detectable IgG2a(b)-containing immune complexes typically exhibited minimal constitutive presentation. Nevertheless, native IgG2a(b) can sensitize antigen-presenting cells in vivo, as mice that were devoid of immune complexes and carried an IgG2a(b)-producing tumour did present constitutively, even at physiological IgG2a(b) serum levels. Whereas the amounts of IgG released from most B-cell lymphomas may be too low to allow spontaneous priming of tumour-specific MHC class II-restricted T cells, administration of tumour immunoglobulin in aggregated form might improve the efficacy of idiotype vaccination.

  17. Neonatal cerebral oxygenation is not linked to foetal vasculitis and predicts intraventricular haemorrhage in preterm infants

    DEFF Research Database (Denmark)

    Sørensen, Line Carøe; Maroun, Lisa Leth; Borch, K.

    2008-01-01

    AIM: The aim of the study was to compare the cerebral tissue oxygenation index (c-TOI) measured by near infrared spectroscopy (NIRS) in infants with and without foetal vasculitis. METHODS: Twenty-four infants with placental signs of a foetal inflammatory response (FIR), foetal vasculitis, were.......002). CONCLUSION: Cerebral oxygenation was not affected in the first day of life in preterm infants born with foetal vasculitis, while cerebral oxygenation in infants that later developed intraventricular haemorrhage was impaired Udgivelsesdato: 2008/11...

  18. Neonatal cerebral oxygenation is not linked to foetal vasculitis and predicts intraventricular haemorrhage in preterm infants

    DEFF Research Database (Denmark)

    Sorensen, Line C; Maroun, Lisa L; Borch, Klaus

    2008-01-01

    Aim: The aim of the study was to compare the cerebral tissue oxygenation index (c-TOI) measured by near infrared spectroscopy (NIRS) in infants with and without foetal vasculitis. Methods: Twenty-four infants with placental signs of a foetal inflammatory response (FIR), foetal vasculitis, were.......002). Conclusion: Cerebral oxygenation was not affected in the first day of life in preterm infants born with foetal vasculitis, while cerebral oxygenation in infants that later developed intraventricular haemorrhage was impaired....

  19. Aetiology, maternal and foetal outcome in 60 cases of obstetrical acute renal failure

    International Nuclear Information System (INIS)

    Khalil, M.A.M.; Azhar, A.; Anwar, N.

    2009-01-01

    Acute renal failure is a serious complication in pregnancy. Not only does it result in significant maternal morbidity and mortality but also results in significant number of foetal loss. Although incidence of obstetrical acute renal failure has decreased in developed countries but still it is one of the major health problem of developing nations. The objective of this study was to study aetiology, maternal and foetal outcome in obstetrical acute renal failure. This study was conducted at Department of Nephrology, Khyber Teaching Hospital, Peshawar from August 2006 to December 2007. It was a descriptive, case series study. Female patients with pregnancy and acute renal failure, irrespective of age, were included in the study. Patients were thoroughly examined and baseline urea, creatinine, serum electrolytes, peripheral smear, prothrombin time, partial thromboplastin time, fibrinogen degradation products, renal and obstetrical ultrasound were performed on each patient and 24-hr urinary protein and bacterial culture sensitivity on blood, urine or vaginal swabs were done in selected patients. Foetal and maternal outcome were recorded. Data were analysed using SPSS. A total of 60 patients were included in the study. Mean age of the patients was 29 +- 5.4 years and duration of gestation was 33 +- 4.9 weeks. Mean gravidity was 4 +- 2.2. Sixteen patients (26.66%) were treated conservatively while 44 (73.33%) required dialysis. Postpartum haemorrhage was present in 14 (23.33%), postpartum haemorrhage and disseminated intravascular coagulation (DIC) in 11 (18.33%), eclampsia-preeclampsia in 8 (13.33%), antepartum haemorrhage in 8 (13.33%), antepartum haemorrhage with DIC in 6 (10%), DIC alone in 4 (6.66%), obstructed labour in 3 (5%), septic abortion in 3 (3.33%), HELLP (haemolysis elevated liver enzyme and low platelet) in 2 (3.33%), urinary tract infection with sepsis in 1 (1.66%) and puerperal sepsis in 1 (1.66%). Foetal loss was 40 (66.66%). Maternal mortality was 9 (15

  20. Spontaneous CD4+ and CD8+ T-cell responses directed against cancer testis antigens are present in the peripheral blood of testicular cancer patients.

    Science.gov (United States)

    Pearce, Hayden; Hutton, Paul; Chaudhri, Shalini; Porfiri, Emilio; Patel, Prashant; Viney, Richard; Moss, Paul

    2017-07-01

    Cancer/testis antigen (CTAg) expression is restricted to spermatogenic cells in an immune-privileged site within the testis. However, these proteins are expressed aberrantly by malignant cells and T-cell responses against CTAgs develop in many cancer patients. We investigated the prevalence, magnitude and phenotype of CTAg-specific T cells in the blood of patients with testicular germ cell tumors (TGCTs). CD8 + and CD4 + T-cell responses against MAGE-A family antigens were present in 44% (20/45) of patients' samples assayed by ex vivo IFN-γ ELISPOT. The presence of MAGE-specific CD8 + T cells was further determined following short-term in vitro expansion through the use of pMHC-I multimers containing known immunogenic peptides. Longitudinal analysis revealed that the frequency of MAGE-specific T cells decreased by 89% following orchidectomy suggesting that persistence of tumor antigen is required to sustain CTAg-specific T-cell immunity. Notably, this decrease correlated with a decline in the global effector/memory T-cell pool following treatment. Spontaneous T-cell immunity against CTAg proteins therefore develops in many patients with testicular cancer and may play an important role in the excellent clinical outcome of patients with this tumor subtype. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Spontaneous CD4+ and CD8+ T‐cell responses directed against cancer testis antigens are present in the peripheral blood of testicular cancer patients

    Science.gov (United States)

    Pearce, Hayden; Hutton, Paul; Chaudhri, Shalini; Porfiri, Emilio; Patel, Prashant; Viney, Richard

    2017-01-01

    Cancer/testis antigen (CTAg) expression is restricted to spermatogenic cells in an immune‐privileged site within the testis. However, these proteins are expressed aberrantly by malignant cells and T‐cell responses against CTAgs develop in many cancer patients. We investigated the prevalence, magnitude and phenotype of CTAg‐specific T cells in the blood of patients with testicular germ cell tumors (TGCTs). CD8+ and CD4+ T‐cell responses against MAGE‐A family antigens were present in 44% (20/45) of patients’ samples assayed by ex vivo IFN‐γ ELISPOT. The presence of MAGE‐specific CD8+ T cells was further determined following short‐term in vitro expansion through the use of pMHC‐I multimers containing known immunogenic peptides. Longitudinal analysis revealed that the frequency of MAGE‐specific T cells decreased by 89% following orchidectomy suggesting that persistence of tumor antigen is required to sustain CTAg‐specific T‐cell immunity. Notably, this decrease correlated with a decline in the global effector/memory T‐cell pool following treatment. Spontaneous T‐cell immunity against CTAg proteins therefore develops in many patients with testicular cancer and may play an important role in the excellent clinical outcome of patients with this tumor subtype. PMID:28555838

  2. Diversity of natural self-derived ligands presented by different HLA class I molecules in transporter antigen processing-deficient cells.

    Directory of Open Access Journals (Sweden)

    Elena Lorente

    Full Text Available The transporter associated with antigen processing (TAP translocates the cytosol-derived proteolytic peptides to the endoplasmic reticulum lumen where they complex with nascent human leukocyte antigen (HLA class I molecules. Non-functional TAP complexes and viral or tumoral blocking of these transporters leads to reduced HLA class I surface expression and a drastic change in the available peptide repertoire. Using mass spectrometry to analyze complex human leukocyte antigen HLA-bound peptide pools isolated from large numbers of TAP-deficient cells, we identified 334 TAP-independent ligands naturally presented by four different HLA-A, -B, and -C class I molecules with very different TAP dependency from the same cell line. The repertoire of TAP-independent peptides examined favored increased peptide lengths and a lack of strict binding motifs for all four HLA class I molecules studied. The TAP-independent peptidome arose from 182 parental proteins, the majority of which yielded one HLA ligand. In contrast, TAP-independent antigen processing of very few cellular proteins generated multiple HLA ligands. Comparison between TAP-independent peptidome and proteome of several subcellular locations suggests that the secretory vesicle-like organelles could be a relevant source of parental proteins for TAP-independent HLA ligands. Finally, a predominant endoproteolytic peptidase specificity for Arg/Lys or Leu/Phe residues in the P(1 position of the scissile bond was found for the TAP-independent ligands. These data draw a new and intricate picture of TAP-independent pathways.

  3. Improved Prediction of Bovine Leucocyte Antigens (BoLA) Presented Ligands by Use of Mass-Spectrometry-Determined Ligand and in Vitro Binding Data

    DEFF Research Database (Denmark)

    Nielsen, Morten; Connelley, Tim; Ternette, Nicola

    2018-01-01

    Peptide binding to MHC class I molecules is the single most selective step in antigen presentation and the strongest single correlate to peptide cellular immunogenicity. The cost of experimentally characterizing the rules of peptide presentation for a given MHC-I molecule is extensive, and predic...... available at http://www.cbs.dtu.dk/services/NetMHCpan/NetBoLApan . The approach has here been applied to the BoLA-I system, but the pipeline is readily applicable to MHC systems in other species....

  4. A molecular assembly system for presentation of antigens on the surface of HBc virus-like particles

    Energy Technology Data Exchange (ETDEWEB)

    Blokhina, Elena A.; Kuprianov, Victor V. [Centre ' Bioengineering' , Russian Academy of Sciences, 117312 Prosp. 60-letya Oktyabrya 7-1, Moscow (Russian Federation); Stepanova, Ludmila A.; Tsybalova, Ludmila M. [Research Institute of Influenza, Russian Federation Ministry of Health and Social Development, St. Petersburg (Russian Federation); Kiselev, Oleg I. [Research Institute of Influenza, Russian Federation Ministry of Health and Social Development, St. Petersburg (Russian Federation); GenNanotech Ltd, St. Petersburg (Russian Federation); Ravin, Nikolai V., E-mail: nravin@biengi.ac.ru [Centre ' Bioengineering' , Russian Academy of Sciences, 117312 Prosp. 60-letya Oktyabrya 7-1, Moscow (Russian Federation); GenNanotech Ltd, St. Petersburg (Russian Federation); Skryabin, Konstantin G. [Centre ' Bioengineering' , Russian Academy of Sciences, 117312 Prosp. 60-letya Oktyabrya 7-1, Moscow (Russian Federation); GenNanotech Ltd, St. Petersburg (Russian Federation)

    2013-01-20

    Hepatitis B virus-like particles, icosahedral structures formed by multiple core protein dimers, are promising immune-enhancing vaccine carriers for foreign antigens. Insertions into the surface-exposed immunodominant loop are especially immunogenic. However, the need to conserve the particulate structure to ensure high immunogenicity imposes restraints on the nature of the heterologous sequence that can be inserted. We propose a new approach to constructing HBc particles linked to the target epitopes that relies on non-covalent interactions between the epitope and pre-assembled unmodified HBc particles. Interaction was enabled by fusion of the epitope to the GSLLGRMKGA peptide, binding to the spike tips. This peptide may be used as a 'binding tag' allowing in vitro construction of HBc particles carrying the target peptide. Such virus-like particles carrying multiple copies of the extracellular domain of the M2 protein of different influenza strains appeared to be highly immunogenic and protected immunised mice against a lethal influenza challenge.

  5. A molecular assembly system for presentation of antigens on the surface of HBc virus-like particles

    International Nuclear Information System (INIS)

    Blokhina, Elena A.; Kuprianov, Victor V.; Stepanova, Ludmila A.; Tsybalova, Ludmila M.; Kiselev, Oleg I.; Ravin, Nikolai V.; Skryabin, Konstantin G.

    2013-01-01

    Hepatitis B virus-like particles, icosahedral structures formed by multiple core protein dimers, are promising immune-enhancing vaccine carriers for foreign antigens. Insertions into the surface-exposed immunodominant loop are especially immunogenic. However, the need to conserve the particulate structure to ensure high immunogenicity imposes restraints on the nature of the heterologous sequence that can be inserted. We propose a new approach to constructing HBc particles linked to the target epitopes that relies on non-covalent interactions between the epitope and pre-assembled unmodified HBc particles. Interaction was enabled by fusion of the epitope to the GSLLGRMKGA peptide, binding to the spike tips. This peptide may be used as a “binding tag” allowing in vitro construction of HBc particles carrying the target peptide. Such virus-like particles carrying multiple copies of the extracellular domain of the M2 protein of different influenza strains appeared to be highly immunogenic and protected immunised mice against a lethal influenza challenge.

  6. RIP2 Is a Critical Regulator for NLRs Signaling and MHC Antigen Presentation but Not for MAPK and PI3K/Akt Pathways.

    Science.gov (United States)

    Wu, Xiao Man; Chen, Wen Qin; Hu, Yi Wei; Cao, Lu; Nie, Pin; Chang, Ming Xian

    2018-01-01

    RIP2 is an adaptor protein which is essential for the activation of NF-κB and NOD1- and NOD2-dependent signaling. Although NOD-RIP2 axis conservatively existed in the teleost, the function of RIP2 was only reported in zebrafish, goldfish, and rainbow trout in vitro . Very little is known about the role and mechanisms of piscine NOD-RIP2 axis in vivo . Our previous study showed the protective role of zebrafish NOD1 in larval survival through CD44a-mediated activation of PI3K-Akt signaling. In this study, we examined whether RIP2 was required for larval survival with or without pathogen infection, and determined the signaling pathways modulated by RIP2. Based on our previous report and the present study, our data demonstrated that NOD1-RIP2 axis was important for larval survival in the early ontogenesis. Similar to NOD1, RIP2 deficiency significantly affected immune system processes. The significantly enriched pathways were mainly involved in immune system, such as "Antigen processing and presentation" and "NOD-like receptor signaling pathway" and so on. Furthermore, both transcriptome analysis and qRT-PCR revealed that RIP2 was a critical regulator for expression of NLRs (NOD-like receptors) and those genes involved in MHC antigen presentation. Different from NOD1, the present study showed that NOD1, but not RIP2 deficiency significantly impaired protein levels of MAPK pathways. Although RIP2 deficiency also significantly impaired the expression of CD44a, the downstream signaling of CD44a-Lck-PI3K-Akt pathway remained unchanged. Collectively, our works highlight the similarity and discrepancy of NOD1 and RIP2 in the regulation of immune signaling pathways in the zebrafish early ontogenesis, and confirm the crucial role of RIP2 in NLRs signaling and MHC antigen presentation, but not for MAPK and PI3K/Akt pathways.

  7. Effect of maternal hypoglycaemia during gestation on materno-foetal nutrient transfer and embryo-foetal development

    DEFF Research Database (Denmark)

    Jensen, Vivi F.H.; Mølck, Anne Marie; Lykkesfeldt, Jens

    2018-01-01

    of the chorio-allantoic placental circulation. Maternal hypoglycaemia is accompanied by foetal hypoglycaemia and maternal counter-regulatory measures including a priority to keep nutrients in the maternal circulation by restricting their transfer to the foetus. Concomitantly, the foetus initiates its own...... counter-regulatory attempt to secure nutrients for its development and survival. Despite these measures, there is a general decrease in nutrient transfer to the foetus, which may have severe consequences for foetal development such as malformations and delayed skeletal development....

  8. Cathepsin B in antigen-presenting cells controls mediators of the Th1 immune response during Leishmania major infection.

    Directory of Open Access Journals (Sweden)

    Iris J Gonzalez-Leal

    2014-09-01

    Full Text Available Resistance and susceptibility to Leishmania major infection in the murine model is determined by the capacity of the host to mount either a protective Th1 response or a Th2 response associated with disease progression. Previous reports involving the use of cysteine cathepsin inhibitors indicated that cathepsins B (Ctsb and L (Ctsl play important roles in Th1/Th2 polarization during L. major infection in both susceptible and resistant mouse strains. Although it was hypothesized that these effects are a consequence of differential patterns of antigen processing, the mechanisms underlying these differences were not further investigated. Given the pivotal roles that dendritic cells and macrophages play during Leishmania infection, we generated bone-marrow derived dendritic cells (BMDC and macrophages (BMM from Ctsb-/- and Ctsl-/- mice, and studied the effects of Ctsb and Ctsl deficiency on the survival of L. major in infected cells. Furthermore, the signals used by dendritic cells to instruct Th cell polarization were addressed: the expression of MHC class II and co-stimulatory molecules, and cytokine production. We found that Ctsb-/- BMDC express higher levels of MHC class II molecules than wild-type (WT and Ctsl-/- BMDC, while there were no significant differences in the expression of co-stimulatory molecules between cathepsin-deficient and WT cells. Moreover, both BMDC and BMM from Ctsb-/- mice significantly up-regulated the levels of interleukin 12 (IL-12 expression, a key Th1-inducing cytokine. These findings indicate that Ctsb-/- BMDC display more pro-Th1 properties than their WT and Ctsl-/- counterparts, and therefore suggest that Ctsb down-regulates the Th1 response to L. major. Moreover, they propose a novel role for Ctsb as a regulator of cytokine expression.

  9. Post-mortem magnetic resonance foetal imaging: a study of morphological correlation with conventional autopsy and histopathological findings.

    Science.gov (United States)

    Vullo, Annamaria; Panebianco, Valeria; Cannavale, Giuseppe; Aromatario, Mariarosaria; Cipolloni, Luigi; Frati, Paola; Santurro, Alessandro; Vullo, Francesco; Catalano, Carlo; Fineschi, Vittorio

    2016-11-01

    The aim of the present study is to offer our experience concerning post-mortem magnetic resonance (PMMR) in foetal death cases and an evaluation of the differences between the findings acquired by PMMR and by forensic autopsy. Fifteen foetuses were recruited from July 2014 to December 2015. These had suffered intrauterine death in women in the 21st to 38th week of gestation who were treated in the emergency department for non-perception of foetal movements. We performed a PMMR on foetuses, 3 ± 1 days on average from the time of death, and then a complete forensic autopsy was performed. All 15 foetuses were examined with a whole-body study protocol, starting from the skull, down to and including the lower limbs. The total time of examination ranged from 20 to 30 min in each case. The external evaluation and description of post-mortem phenomena (maceration), record of the weight and detection and the various measurements of foetal diameters were evaluated before performing autopsy. A complete histopathological study was performed in each case. Out of 15 cases examined, eight were negative for structural anatomical abnormalities and/or diseases, both in the preliminary radiological examination and the traditional autopsy. In the remaining seven cases, pathological findings were detected by PMMR with corresponding results at autopsy. PMMR can provide useful information on foetal medical conditions and result in improved diagnostic classification. It may enable the planning of a more suitable technique before proceeding to autopsy, including focusing on certain aspects of organ pathology otherwise not detectable. The association between PMMR, post-mortem examination and related histological study of the foetus-placenta unit could help reduce the percentage of cases in which the cause of foetal death remains unexplained. Lastly, it may allow a selective sampling of the organ in order to target histological investigations.

  10. Spirit(ed) away: preventing foetal alcohol syndrome with ...

    African Journals Online (AJOL)

    Foetal alcohol syndrome (FAS) is a growing concern in South Africa. In the Western Cape, prevalence rates for FAS are the highest in the world. Not surprisingly, the Western Cape also has some of the highest levels of alcohol consumption per capita. Although FAS is primarily caused by alcohol consumption during ...

  11. Foetal, neonatal and child vitamin D status and enamel hypomineralization

    NARCIS (Netherlands)

    J.T. van der Tas (Justin); M.E.C. Elfrink (Marlies); M.P. Heijboer (Rien); Rivadeneira, F. (Fernando); V.W.V. Jaddoe (Vincent); H.W. Tiemeier (Henning); J.D. Schoufour (Josje); H.A. Moll (Henriëtte); E.M. Ongkosuwito (Edwin); E.B. Wolvius (Eppo); R.G. Voortman (Trudy)

    2018-01-01

    textabstractObjectives: Recent literature suggested that higher vitamin D concentrations in childhood are associated with a lower prevalence of molar incisor hypomineralization (MIH). As tooth development already starts in utero, we aimed to study whether vitamin D status during foetal, postnatal

  12. Association of foetal haemoglobin with pancreatic enzymes in sickle ...

    African Journals Online (AJOL)

    Background/Aim: There are conflicting reports on the potential protective effects of foetal haemoglobin (HbF) in the elimination of symptoms of Sickle cell disease in the patients and reports which correlate the levels of HbF with pancreatic enzymes in SCD are scarce in the literature.This study correlates the levels of HbF on ...

  13. DNA Extraction from Chorionic Villi for Prenatal Diagnosis of Foetal ...

    African Journals Online (AJOL)

    BACKGROUND: Extraction of DNA from the chorionic villi is the first major step in the molecular determination of foetal haemoglobin genotype. There are few reports on DNA extraction from the chorionic villi. A desired method should be simple to conduct, reliable and cost effective. OBJECTIVE: The aim of the study was to ...

  14. umbilical cord parameters in ilorin: correlates and foetal outcome

    African Journals Online (AJOL)

    2014-08-08

    Aug 8, 2014 ... The foetal outcomes were assessed by APGAR scores, birth weight, admission to neonatal intensive ... between the umbilical cord parameters and perinatal events such as Apgar scores and birth weight. .... Suzuki S, Fuse Y. Length of the Umbilical Cord and. Perinatal Outcomes in Japanese Singleton ...

  15. Twin Delivery: Comparison of Incidence and Foetal Outcome in two ...

    African Journals Online (AJOL)

    Background: The incidence of twin delivery in Nigeria may have changed, in view of the worldwide increase in the rates of twinning attributed to increasing maternal age and use of fertility therapies. Objective: To determine the current incidence of twin delivery in Benin City and document the foetal outcome in twins.

  16. Upregulation of immunoproteasome subunits in myositis indicates active inflammation with involvement of antigen presenting cells, CD8 T-cells and IFNΓ.

    Directory of Open Access Journals (Sweden)

    Khetam Ghannam

    Full Text Available OBJECTIVE: In idiopathic inflammatory myopathies (IIM infiltration of immune cells into muscle and upregulation of MHC-I expression implies increased antigen presentation and involvement of the proteasome system. To decipher the role of immunoproteasomes in myositis, we investigated individual cell types and muscle tissues and focused on possible immune triggers. METHODS: Expression of constitutive (PSMB5, -6, -7 and corresponding immunoproteasomal subunits (PSMB8, -9, -10 was analyzed by real-time RT-PCR in muscle biopsies and sorted peripheral blood cells of patients with IIM, non-inflammatory myopathies (NIM and healthy donors (HD. Protein analysis in muscle biopsies was performed by western blot. Affymetrix HG-U133 platform derived transcriptome data from biopsies of different muscle diseases and from immune cell types as well as monocyte stimulation experiments were used for validation, coregulation and coexpression analyses. RESULTS: Real-time RT-PCR revealed significantly increased expression of immunoproteasomal subunits (PSMB8/-9/-10 in DC, monocytes and CD8+ T-cells in IIM. In muscle biopsies, the immunosubunits were elevated in IIM compared to NIM and exceeded levels of matched blood samples. Proteins of PSMB8 and -9 were found only in IIM but not NIM muscle biopsies. Reanalysis of 78 myositis and 20 healthy muscle transcriptomes confirmed these results and revealed involvement of the antigen processing and presentation pathway. Comparison with reference profiles of sorted immune cells and healthy muscle confirmed upregulation of PSMB8 and -9 in myositis biopsies beyond infiltration related changes. This upregulation correlated highest with STAT1, IRF1 and IFNγ expression. Elevation of T-cell specific transcripts in active IIM muscles was accompanied by increased expression of DC and monocyte marker genes and thus reflects the cell type specific involvement observed in peripheral blood. CONCLUSIONS: Immunoproteasomes seem to indicate

  17. Contribution of enhanced engagement of antigen presentation machinery to the clinical immunogenicity of a human interleukin (IL)-21 receptor-blocking therapeutic antibody.

    Science.gov (United States)

    Xue, L; Hickling, T; Song, R; Nowak, J; Rup, B

    2016-01-01

    Reliable risk assessment for biotherapeutics requires accurate evaluation of risk factors associated with immunogenicity. Immunogenicity risk assessment tools were developed and applied to investigate the immunogenicity of a fully human therapeutic monoclonal antibody, ATR-107 [anti-interleukin (IL)-21 receptor] that elicited anti-drug antibodies (ADA) in 76% of healthy subjects in a Phase 1 study. Because the ATR-107 target is expressed on dendritic cells (DCs), the immunogenicity risk related to engagement with DC and antigen presentation pathways was studied. Despite the presence of IL-21R on DCs, ATR-107 did not bind to the DCs more extensively than the control therapeutic antibody (PF-1) that had elicited low clinical ADA incidence. However, ATR-107, but not the control therapeutic antibody, was translocated to the DC late endosomes, co-localized with intracellular antigen-D related (HLA-DR) molecules and presented a dominant T cell epitope overlapping the complementarity determining region 2 (CDR2) of the light chain. ATR-107 induced increased DC activation exemplified by up-regulation of DC surface expression of CD86, CD274 (PD-L1) and CD40, increased expansion of activated DC populations expressing CD86(hi), CD40(hi), CD83(hi), programmed death ligand 1 (PD-L1)(hi), HLA-DR(hi) or CCR7(hi), as well as elevated secretion of tumour necrosis factor (TNF)-α by DCs. DCs exposed to ATR-107 stimulated an autologous T cell proliferative response in human donor cells, in concert with the detection of immunoglobulin (Ig)G-type anti-ATR-107 antibody response in clinical samples. Collectively, the enhanced engagement of antigen presentation machinery by ATR-107 was suggested. The approaches and findings described in this study may be relevant to identifying lower immunogenicity risk targets and therapeutic molecules. © 2015 British Society for Immunology.

  18. Upregulation of Immunoproteasome Subunits in Myositis Indicates Active Inflammation with Involvement of Antigen Presenting Cells, CD8 T-Cells and IFNγ

    Science.gov (United States)

    Ghannam, Khetam; Martinez-Gamboa, Lorena; Spengler, Lydia; Krause, Sabine; Smiljanovic, Biljana; Bonin, Marc; Bhattarai, Salyan; Grützkau, Andreas; Burmester, Gerd-R.

    2014-01-01

    Objective In idiopathic inflammatory myopathies (IIM) infiltration of immune cells into muscle and upregulation of MHC-I expression implies increased antigen presentation and involvement of the proteasome system. To decipher the role of immunoproteasomes in myositis, we investigated individual cell types and muscle tissues and focused on possible immune triggers. Methods Expression of constitutive (PSMB5, -6, -7) and corresponding immunoproteasomal subunits (PSMB8, -9, -10) was analyzed by real-time RT-PCR in muscle biopsies and sorted peripheral blood cells of patients with IIM, non-inflammatory myopathies (NIM) and healthy donors (HD). Protein analysis in muscle biopsies was performed by western blot. Affymetrix HG-U133 platform derived transcriptome data from biopsies of different muscle diseases and from immune cell types as well as monocyte stimulation experiments were used for validation, coregulation and coexpression analyses. Results Real-time RT-PCR revealed significantly increased expression of immunoproteasomal subunits (PSMB8/-9/-10) in DC, monocytes and CD8+ T-cells in IIM. In muscle biopsies, the immunosubunits were elevated in IIM compared to NIM and exceeded levels of matched blood samples. Proteins of PSMB8 and -9 were found only in IIM but not NIM muscle biopsies. Reanalysis of 78 myositis and 20 healthy muscle transcriptomes confirmed these results and revealed involvement of the antigen processing and presentation pathway. Comparison with reference profiles of sorted immune cells and healthy muscle confirmed upregulation of PSMB8 and -9 in myositis biopsies beyond infiltration related changes. This upregulation correlated highest with STAT1, IRF1 and IFNγ expression. Elevation of T-cell specific transcripts in active IIM muscles was accompanied by increased expression of DC and monocyte marker genes and thus reflects the cell type specific involvement observed in peripheral blood. Conclusions Immunoproteasomes seem to indicate IIM activity and

  19. Effects of low dose X-ray irradiation on antigen presentation and IL-12 secretion in human dendritic cells in vitro

    International Nuclear Information System (INIS)

    Yan Peng; Jiang Qisheng; Li Fengsheng; He Rui; Wang Cuilan; Li Xiao

    2012-01-01

    Objective: To explore the effects of low dose X-ray irradiation on the ability of antigen presentation and IL-12 secretion in human dendritic cells that had been cultured for different time in vitro. Methods: The human peripheral blood mononuclear cells (PBMC) were collected and differentiated to dendritic cells (DCs) by rhGM-CSF and rhIL-4 treatment in vitro. The DCs were divided into 3 groups, group A: DCs were cultured for 2 d and then irradiated with 0.05, 0.1, 0.2 and 0.5 Gy X-rays; group B: DCs were cultured for 6 d and then irradiated as above; group C:DCs were cultured without irradiation.At 8 d of cell culture, the DCs were applied to activate T cells and CCK-8 was used to detect MLR (mixed lymphocyte reaction), and the antigen presentation ability of DCs was evaluated. MTT assay was also used to test the cell-killing effect of the activated T-cells on A549 cells. IL-12 in the culture medium of DCs was detected by ELISA. Results: After irradiation with 0.2 and 0.5 Gy X-rays, the antigen presentation ability of DCs was decreased in group A (t=2.79 and 3.71, P<0.05), but significantly increased in group B (t=3.60 and 3.11, P<0.05). The ability of the T cell activation was detected and the proliferation of A549 cells was slightly inhibited by the DCs in group A (t=2.89 and 2.91, P<0.05), but was obviously inhibited by the DCs in group B (t=2.91 and 2.82, P<0.05). Meanwhile,the level of IL-12 was dramatically decreased in group A (t=4.44 and 6.93, P<0.05), but was increased in group B (t=3.51 and 4.12, P<0.05). Conclusions: The abilities of antigen presentation and proliferation inhibition of DCs could be down-regulated by low dose (<0.5 Gy) of X-ray irradiation at the early stage of DCs, but was up-regulated at the late stage of DCs culture. (authors)

  20. T cell ignorance is bliss: T cells are not tolerized by Langerhans cells presenting human papillomavirus antigens in the absence of costimulation

    Directory of Open Access Journals (Sweden)

    Andrew W. Woodham

    2016-12-01

    Full Text Available Human papillomavirus type 16 (HPV16 infections are intra-epithelial, and thus, HPV16 is known to interact with Langerhans cells (LCs, the resident epithelial antigen-presenting cells (APCs. The current paradigm for APC-mediated induction of T cell anergy is through delivery of T cell receptor signals via peptides on MHC molecules (signal 1, but without costimulation (signal 2. We previously demonstrated that LCs exposed to HPV16 in vitro present HPV antigens to T cells without costimulation, but it remained uncertain if such T cells would remain ignorant, become anergic, or in the case of CD4+ T cells, differentiate into Tregs. Here we demonstrate that Tregs were not induced by LCs presenting only signal 1, and through a series of in vitro immunizations show that CD8+ T cells receiving signal 1+2 from LCs weeks after consistently receiving signal 1 are capable of robust effector functions. Importantly, this indicates that T cells are not tolerized but instead remain ignorant to HPV, and are activated given the proper signals. Keywords: T cell anergy, T cell ignorance, Immune tolerance, Human papillomavirus, HPV16, Langerhans cells

  1. A Neospora caninum vaccine using recombinant proteins fails to prevent foetal infection in pregnant cattle after experimental intravenous challenge.

    Science.gov (United States)

    Hecker, Yanina P; Cóceres, Verónica; Wilkowsky, Silvina E; Jaramillo Ortiz, José M; Morrell, Eleonora L; Verna, Andrea E; Ganuza, Agustina; Cano, Dora B; Lischinsky, Lilian; Angel, Sergio O; Zamorano, Patricia; Odeón, Anselmo C; Leunda, María R; Campero, Carlos M; Morein, Bror; Moore, Dadín P

    2014-12-15

    The aim of the present study was to evaluate the immunogenicity and protective efficacy of rNcSAG1, rNcHSP20 and rNcGRA7 recombinant proteins formulated with immune stimulating complexes (ISCOMs) in pregnant heifers against vertical transmission of Neospora caninum. Twelve pregnant heifers were divided into 3 groups of 4 heifers each, receiving different formulations before mating. Immunogens were administered twice subcutaneously: group A animals were inoculated with three recombinant proteins (rNcSAG1, rNcHSP20, rNcGRA7) formulated with ISCOMs; group B animals received ISCOM-MATRIX (without antigen) and group C received sterile phosphate-buffered saline (PBS) only. The recombinant proteins were expressed in Escherichia coli and purified nickel resin. All groups were intravenously challenged with the NC-1 strain of N. caninum at Day 70 of gestation and dams slaughtered at week 17 of the experiment. Heifers from group A developed specific antibodies against rNcSAG1, rNcHSP20 and rNcGRA7 prior to the challenge. Following immunization, an statistically significant increase of antibodies against rNcSAG1 and rNcHSP20 in all animals of group A was detected compared to animals in groups B and C at weeks 5, 13 and 16 (P0.001). There were no differences in IFN-γ production among the experimental groups at any time point (P>0.05). Transplacental transmission was determined in all foetuses of groups A, B and C by Western blot, immunohistochemistry and nested PCR. This work showed that rNcSAG1, rNcHSP20 and rNcGRA7 proteins while immunogenic in cattle failed to prevent the foetal infection in pregnant cattle challenged at Day 70 of gestation. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. An Antigen-Presenting and Apoptosis-Inducing Polymer Microparticle Prolongs Alloskin Graft Survival by Selectively and Markedly Depleting Alloreactive CD8+ T Cells

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2017-06-01

    Full Text Available Selectively depleting the pathogenic T cells is a fundamental strategy for the treatment of allograft rejection and autoimmune disease since it retains the overall immune function of host. The concept of killer artificial antigen-presenting cells (KaAPCs has been developed by co-coupling peptide–major histocompatibility complex (pMHC multimer and anti-Fas monoclonal antibody (mAb onto the polymeric microparticles (MPs to induce the apoptosis of antigen-specific T cells. But little information is available about its in vivo therapeutic potential and mechanism. In this study, polyethylenimine (PEI-coated poly lactic-co-glycolic acid microparticle (PLGA MP was fabricated as a cell-sized scaffold to covalently co-couple H-2Kb-Ig dimer and anti-Fas mAb for the generation of alloantigen-presenting and apoptosis-inducing MPs. Intravenous infusions of the biodegradable KaAPCs prolonged the alloskin graft survival for 43 days in a single MHC-mismatched murine model, depleted the most of H-2Kb-alloreactive CD8+ T cells in peripheral blood, spleen, and alloskin graft in an antigen-specific manner and anti-Fas-dependent fashion. The cell-sized KaAPCs circulated throughout vasculature into liver, kidney, spleen, lymph nodes, lung, and heart, but few ones into local allograft at early stage, with a retention time up to 36 h in vivo. They colocalized with CD8+ T cells in secondary lymphoid organs while few ones contacted with CD4+ T cells, B cells, macrophage, and dendritic cells, or internalized by phagocytes. Importantly, the KaAPC treatment did not significantly impair the native T cell repertoire or non-pathogenic immune cells, did not obviously suppress the overall immune function of host, and did not lead to visible organ toxicity. Our results strongly document the high potential of PLGA MP-based KaAPCs as a novel antigen-specific immunotherapy for allograft rejection and autoimmune disorder. The in vivo mechanism of alloinhibition, tissue

  3. Cholera Toxin Promotes Th17 Cell Differentiation by Modulating Expression of Polarizing Cytokines and the Antigen-Presenting Potential of Dendritic Cells.

    Science.gov (United States)

    Kang, Jung-Ok; Lee, Jee-Boong; Chang, Jun

    2016-01-01

    Cholera toxin (CT), an exotoxin produced by Vibrio cholera, acts as a mucosal adjuvant. In a previous study, we showed that CT skews differentiation of CD4 T cells to IL-17-producing Th17 cells. Here, we found that intranasal administration of CT induced migration of migratory dendritic cell (DC) populations, CD103+ DCs and CD11bhi DCs, to the lung draining mediastinal lymph nodes (medLN). Among those DC subsets, CD11bhi DCs that were relatively immature had a major role in Th17 cell differentiation after administration of CT. CT-treated BMDCs showed reduced expression of MHC class II and CD86, similar to CD11bhi DCs in medLN, and these BMDCs promoted Th17 cell differentiation more potently than other BMDCs expressing higher levels of MHC class II and CD86. By analyzing the expression of activation markers such as CD25 and CD69, proliferation and IL-2 production, we determined that CT-treated BMDCs showed diminished antigen-presenting potential to CD4+ T cells compared with normal BMDCs. We also found that CT-stimulated BMDCs promote activin A expression as well as IL-6 and IL-1β, and activin A had a synergic role with TGF-β1 in CT-mediated Th17 cell differentiation. Taken together, our results suggest that CT-stimulated DCs promote Th17 cell differentiation by not only modulating antigen-presenting potential but also inducing Th polarizing cytokines.

  4. Antigen Presenting Cells and Stromal Cells Trigger Human Natural Killer Lymphocytes to Autoreactivity: Evidence for the Involvement of Natural Cytotoxicity Receptors (NCR and NKG2D

    Directory of Open Access Journals (Sweden)

    Alessandro Poggi

    2006-01-01

    Full Text Available Human natural killer (NK lymphocytes should not damage autologous cells due to the engagement of inhibitory receptor superfamily (IRS members by HLA-I. Nevertheless, NK cells kill self cells expressing low levels or lacking HLA-I, as it may occur during viral infections (missing-self hypothesis. Herein, we show that human NK cells can be activated upon binding with self antigen presenting cells or stromal cells despite the expression of HLA-I. Indeed, NK cells can kill and produce pro-inflammatory and regulating cytokines as IFN-γ, TNF-α and IL10 during interaction with autologous dendritic cells or bone marrow stromal cells or skin fibroblasts. The killing of antigen presenting and stromal cells is dependent on LFA1/ICAM1 interaction. Further, the natural cytotoxicity receptors (NCR NKp30 and NKp46 are responsible for the delivery of lethal hit to DC, whereas NKG2D activating receptor, the ligand of the MHC-related molecule MIC-A and the UL16 binding protein, is involved in stromal cell killing. These findings indicate that different activating receptors are involved in cell to self cell interaction. Finally, NK cells can revert the veto effect of stromal cells on mixed lymphocyte reaction further supporting the idea that NK cells may alter the interaction between T lymphocytes and microenvironment leading to autoreactivity.

  5. Nonspecific Presentation of a Multiloculated Prostatic Abscess After Transurethral Prostatic Biopsy for Elevated Prostate-specific Antigen Level

    OpenAIRE

    Gandhi, Nilay M.; Lin, Joseph; Schaeffer, Edward

    2014-01-01

    Prostate postbiopsy infectious complications typically present in the form of prostatitis and uncommonly urosepsis. Prostatic abscesses are generally found after multiple bouts of prostatitis and are associated with a clinically septic picture requiring intensive care unit admission and resuscitation. We report the case of a 65-year-old man who presented with prostatic abscess in the setting of nonspecific urinary symptoms after transrectal ultrasonography–guided prostate biopsy. At 4-month f...

  6. Magnitude of Alloresponses to MHC Class I/II Expressing Human Cardiac Myocytes is Limited by their Intrinsic Ability to Process and Present Antigenic Peptides

    Directory of Open Access Journals (Sweden)

    Aftab A. Ansari

    2003-01-01

    Full Text Available In this investigation we have explored the relationship between the weak allogenicity of cardiac myocytes and their capacity to present allo-antigens by examining the ability of a human cardiac myocyte cell line (W-1 to process and present nominal antigens. W-1 cells (HLA-A*0201 and HLA-DR β1*0301 pulsed with the influenza A matrix 1 (58-66 peptide (M1 were able to serve as targets for the HLA-A*0201 restricted CTL line PG, specific for M1-peptide. However, PG-CTLs were unable to lyse W-1 target cells infected with a recombinant vaccinia virus expressing the M1 protein (M1-VAC. Pretreatment of these M1-VAC targets with IFN-γ partially restored their ability to process and present the M1 peptide. However, parallel studies demonstrated that IFN-γ pretreated W-1's could not process tetanus toxin (TT or present the TT(830-843 peptide to HLA-DR3 restricted TT-primed T cells. Semi-quantitative RT-PCR measurements revealed significantly lower constitutive levels of expression for MHC class I, TAP-1/2, and LMP-2/7 genes in W-1s that could be elevated by pretreatment with IFN-γ to values equal to or greater than those expressed in EBV-PBLs. However, mRNA levels for the genes encoding MHC class II, Ii, CIITA, and DMA/B were markedly lower in both untreated and IFN-γ pretreated W-1s relative to EBV-PBLs. Furthermore, pulse-chase analysis of the corresponding genes revealed significantly lower protein levels and longer half-life expression in W-1s relative to EBV-PBLs. These results suggest that weak allogenicity of cardiac myocytes may be governed by their limited expression of MHC genes and gene products critical for antigen processing and presentation.

  7. Rainbow trout CK9, a CCL25-like ancient chemokine that attracts and regulates B cells and macrophages, the main antigen presenting cells in fish.

    Science.gov (United States)

    Aquilino, Carolina; Granja, Aitor G; Castro, Rosario; Wang, Tiehui; Abos, Beatriz; Parra, David; Secombes, Christopher J; Tafalla, Carolina

    2016-04-05

    CK9 is a rainbow trout (Oncorhynchus mykiss) CC chemokine phylogenetically related to mammalian CCL25. Although CK9 is known to be transcriptionally regulated in response to inflammation particularly in mucosal tissues, its functionality has never been revealed. In the current work, we have demonstrated that CK9 is chemoattractant for antigen presenting cells (APCs) expressing major histocompatibility complex class II (MHC II) on the cell surface. Among these APCs, CK9 has a strong chemotactic capacity for both B cells (IgM+ and IgT+) and macrophages. Along with its chemotactic capacities, CK9 modulated the MHC II turnover of B lymphocytes and up-regulated the phagocytic capacity of both IgM+ cells and macrophages. Although CK9 had no lymphoproliferative effects, it increased the survival of IgT+ lymphocytes. Furthermore, we have established that the chemoattractant capacity of CK9 is strongly increased after pre-incubation of leukocytes with a T-independent antigen, whereas B cell receptor (BCR) cross-linking strongly abrogated their capacity to migrate to CK9, indicating that CK9 preferentially attracts B cells at the steady state or under BCR-independent stimulation. These results point to CK9 being a key regulator of B lymphocyte trafficking in rainbow trout, able to modulate innate functions of teleost B lymphocytes and macrophages.

  8. The Ia.2 Epitope Defines a Subset of Lipid Raft Resident MHC Class II Molecules Crucial to Effective Antigen Presentation1

    Science.gov (United States)

    Busman-Sahay, Kathleen; Sargent, Elizabeth; Harton, Jonathan A.; Drake, James R.

    2016-01-01

    Previous work has established that binding of the 11-5.2 anti-I-Ak mAb, which recognizes the Ia.2 epitope on I-Ak class II molecules, elicits MHC class II signaling, whereas binding of two other anti-I-Ak mAb that recognize the Ia.17 epitope fail to elicit signaling. Using a biochemical approach, we establish that the Ia.2 epitope recognized by the widely used 11-5.2 mAb defines a subset of cell surface I-Ak molecules predominantly found within membrane lipid rafts. Functional studies demonstrate that the Ia.2 bearing subset of I-Ak class II molecules is critically necessary for effective B cell–T cell interactions especially at low antigen doses, a finding consistent with published studies on the role of raft-resident class II molecules in CD4 T cell activation. Interestingly, B cells expressing recombinant I-Ak class II molecules possessing a β chain-tethered HEL peptide lack the Ia.2 epitope and fail to partition into lipid rafts. Moreover, cells expressing Ia.2 negative tethered peptide-class II molecules are severely impaired in their ability to present both tethered peptide or peptide derived from exogenous antigen to CD4 T cells. These results establish the Ia.2 epitope as defining a lipid raft-resident MHC class II confomer vital to the initiation of MHC class II restricted B cell–T cell interactions. PMID:21543648

  9. B7.1 expression on tumor cells circumvents the need of professional antigen presentation for in vitro propagation of cytotoxic T cell lines.

    Science.gov (United States)

    Iezzi, G; Protti, M P; Rugarli, C; Bellone, M

    1996-01-01

    In vitro propagation of tumor-specific CTLs, to be used for identification of tumor antigens (Ag) and/or adoptive immunotherapy, is hampered by the need of large amounts of professional antigen-presenting cells (APC) used for periodical cycles of restimulation. We evaluated whether RMA T lymphoma cells, stably transfected with the cDNA encoding for the B7.1 costimulatory molecule, provided the activation signals to CD8+ T lymphocytes in the absence of professional APC and CD4+ helper cells. We demonstrate here that long-term CD8+ cell lines can be efficiently propagated in vitro by repeated cycles of stimulation with tumor cells stably expressing B7.1. Professional APC and CD4+ helper cells are not required as far as interleukin 2 is exogenously provided. Furthermore, CD8+ blasts needed both signal 1 (Ag in the contest of the MHC molecule) and signal 2 (interaction of costimulatory molecules) for restimulation. T cell blasts in the presence of signal 1 or 2 only still retained their effector potential but did not undergo clonal expansion. These results are very promising for further applications of specific immunotherapies in humans.

  10. Cutting edge: HLA-B27 acquires many N-terminal dibasic peptides: coupling cytosolic peptide stability to antigen presentation

    NARCIS (Netherlands)

    Herberts, Carla A.; Neijssen, Joost J.; de Haan, Jolanda; Janssen, Lennert; Drijfhout, Jan Wouter; Reits, Eric A.; Neefjes, Jacques J.

    2006-01-01

    Ag presentation by MHC class I is a highly inefficient process because cytosolic peptidases destroy most peptides after proteasomal generation. Various mechanisms shape the MHC class I peptidome. We define a new one: intracellular peptide stability. Peptides with two N-terminal basic amino acids are

  11. Airway eosinophils accumulate in the mediastinal lymph nodes but lack antigen-presenting potential for naive T cells

    NARCIS (Netherlands)

    van Rijt, Leonie S.; Vos, Nanda; Hijdra, Daniëlle; de Vries, Victor C.; Hoogsteden, Henk C.; Lambrecht, Bart N.

    2003-01-01

    Asthma is characterized by infiltration of the airway wall with eosinophils. Although eosinophils are considered to be effector cells, recent studies have reported their ability to activate primed Th2 cells. In this study, we investigated whether eosinophils are capable of presenting Ag to unprimed

  12. Effect of gamma radiation on resting B lymphocytes. II. Functional characterization of the antigen-presentation defect

    International Nuclear Information System (INIS)

    Ashwell, J.D.; Jenkins, M.K.; Schwartz, R.H.

    1988-01-01

    The effect of radiation on three discrete Ag-presentation functions in resting B cells was examined: 1) Ag uptake and processing, 2) expression of processed Ag in the context of functional class II molecules, and 3) provision of necessary co-stimulatory, or second, signals. Analysis of radiation's effect on B cell presentation of intact vs fragmented Ag or its effect on presentation by Ag-pulsed B cells indicated that damage to Ag uptake and processing could not account for the bulk of the radiation-induced Ag-presentation defect. Experiments with phosphatidylinositol hydrolysis as an indirect measure of TCR occupancy suggested that irradiation caused a fairly rapid (within 1 to 2 h) decrease in the ability of the B cell APC to display a stimulatory combination of Ag and class II molecule. Ag dose-response analyses demonstrated that when presenting a fragment of the Ag pigeon cytochrome c to a T cell clone, 3000 rad-treated B cell APC were able to stimulate approximately 50% as much phosphatidylinositol turnover as unirradiated B cells. It was also found that, in contrast to their inability to initiate T cell proliferation, and similarly to chemically cross-linked splenocytes, heavily irradiated resting B cells plus Ag induced a state of Ag hyporesponsiveness in T cell clones. This effect on T cells had the same Ag- and MHC-specificity as did receptor occupancy required for proliferation, indicating that heavily irradiated resting B cells bear functional class II molecules. Co-culture of T cells with allogeneic B cells and syngeneic heavily irradiated B cells or chemically cross-linked splenic APC plus Ag resulted in T cell proliferation and interfered with the induction of the hyporesponsive state. This co-stimulatory function was radiosensitive in resting allogeneic B cells

  13. A cross-cultural study on surrogate mother's empathy and maternal-foetal attachment.

    Science.gov (United States)

    Lorenceau, Ellen Schenkel; Mazzucca, Luis; Tisseron, Serge; Pizitz, Todd D

    2015-06-01

    Traditional and gestational surrogate mothers assist infertile couples by carrying their children. In 2005, a meta-analysis on surrogacy was conducted but no study had examined empathy and maternal-foetal attachment of surrogate mothers. Assessments of surrogate mothers show no sign of psychopathology, but one study showed differences on several MMPI-2 scales compared to a normative sample: surrogate mothers identified with stereotypically masculine traits such as assertiveness and competition. They had a higher self-esteem and lower levels of anxiety and depression. To determine if there is a difference in empathy and maternal-foetal attachment of surrogate mothers compared to a comparison group of mothers. Three groups of European traditional and gestational surrogate mothers (n=10), Anglo-Saxon traditional and gestational surrogate mothers (n=34) and a European normative sample of mothers (n=32) completed four published psychometric instruments: the Interpersonal Reactivity Index (empathy index), the Hospital Anxiety and Depressions Scale and the MC20, a social desirability scale. Pregnant surrogate mothers filled the Maternal Antenatal Attachment Scale (n=11). Statistical non-parametric analyses of variance were conducted. Depending on cultural background, surrogate mothers present differences in terms of empathy, anxiety and depression, social desirability and quality of attachment to the foetus compared to a normative sample. Environment plays a role for traditional and gestational surrogacy. Surrogate mothers of both groups are less anxious and depressed than normative samples. Maternal-foetal attachment is strong with a slightly lower quality of attachment. Surrogate mother's empathy indexes are similar to normative samples, sometimes higher. Copyright © 2014 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  14. Changes in foetal liver T2* measurements by MRI in response to maternal oxygen breathing: application to diagnosing foetal growth restriction

    International Nuclear Information System (INIS)

    Morris, David M; Semple, Scott IK; Gilbert, Fiona J; Redpath, Thomas W; Ross, John AS; McVicar, Alexandra; Haggarty, Paul; Abramovich, David R; Smith, Norman

    2010-01-01

    The motivation of the project was to investigate the use of oxygen-challenge magnetic resonance imaging (OC-MRI) as a method of diagnosing foetal growth restriction. Foetal growth restriction is associated with restricted foetal oxygen supply and is also associated with increased risks of perinatal mortality and morbidity, and a number of serious and chronic health problems. Measurements of T2* relaxation time, an MRI parameter which increases with blood oxygenation, were made in the right lobe of the foetal liver in 80 singleton pregnancies, before and after the mother breathed oxygen. The groups consisted of 41 foetuses with normal growth and 39 with apparent growth restriction. The mean ± SD gestational age at scanning was 35 ± 3 weeks. Changes in foetal liver T2* on maternal oxygen breathing showed no significant difference between the groups therefore the OC-MRI protocol used in this study has no value in the diagnosis of foetal growth restriction. A secondary finding was that a significant positive correlation of T2* change with gestational age was observed. Future studies on the use of oxygen-challenge MRI to investigate foetal growth restriction may therefore need to control for gestational age at the time of MR scanning in order to observe any underlying foetal growth-related effects

  15. Do Thyroid Disrupting Chemicals Influence Foetal Development during Pregnancy?

    Science.gov (United States)

    Hartoft-Nielsen, Marie-Louise; Boas, Malene; Bliddal, Sofie; Rasmussen, Åase Krogh; Main, Katharina; Feldt-Rasmussen, Ulla

    2011-01-01

    Maternal euthyroidism during pregnancy is crucial for normal development and, in particular, neurodevelopment of the foetus. Up to 3.5 percent of pregnant women suffer from hypothyroidism. Industrial use of various chemicals—endocrine disrupting chemicals (EDCs)—has been shown to cause almost constant exposure of humans with possible harmful influence on health and hormone regulation. EDCs may affect thyroid hormone homeostasis by different mechanisms, and though the effect of each chemical seems scarce, the added effects may cause inappropriate consequences on, for example, foetal neurodevelopment. This paper focuses on thyroid hormone influence on foetal development in relation to the chemicals suspected of thyroid disrupting properties with possible interactions with maternal thyroid homeostasis. Knowledge of the effects is expected to impact the general debate on the use of these chemicals. However, more studies are needed to elucidate the issue, since human studies are scarce. PMID:21918727

  16. The human placenta--an alternative for studying foetal exposure

    DEFF Research Database (Denmark)

    Myren, Maja; Mose, Tina; Mathiesen, Line

    2007-01-01

    Pregnant women are daily exposed to a wide selection of foreign substances. Sources are as different as lifestyle factors (smoking, daily care products, alcohol consumption, etc.), maternal medication or occupational/environmental exposures. The placenta provides the link between mother and foetus......, and though its main task is to act as a barrier and transport nutrients and oxygen to the foetus, many foreign compounds are transported across the placenta to some degree and may therefore influence the unborn child. Foetal exposures to environmental and medicinal products may have impact on the growth...... of the foetus (e.g. cigarette smoke) and development of the foetal organs (e.g. methylmercury and thalidomide). The scope of this review is to give insight to the placental anatomy, development and function. Furthermore, the compounds physical properties and the transfer mechanism across the placental barrier...

  17. Predicted MHC peptide binding promiscuity explains MHC class I 'hotspots' of antigen presentation defined by mass spectrometry eluted ligand data.

    Science.gov (United States)

    Jappe, Emma Christine; Kringelum, Jens; Trolle, Thomas; Nielsen, Morten

    2018-02-15

    Peptides that bind to and are presented by MHC class I and class II molecules collectively make up the immunopeptidome. In the context of vaccine development, an understanding of the immunopeptidome is essential, and much effort has been dedicated to its accurate and cost-effective identification. Current state-of-the-art methods mainly comprise in silico tools for predicting MHC binding, which is strongly correlated with peptide immunogenicity. However, only a small proportion of the peptides that bind to MHC molecules are, in fact, immunogenic, and substantial work has been dedicated to uncovering additional determinants of peptide immunogenicity. In this context, and in light of recent advancements in mass spectrometry (MS), the existence of immunological hotspots has been given new life, inciting the hypothesis that hotspots are associated with MHC class I peptide immunogenicity. We here introduce a precise terminology for defining these hotspots and carry out a systematic analysis of MS and in silico predicted hotspots. We find that hotspots defined from MS data are largely captured by peptide binding predictions, enabling their replication in silico. This leads us to conclude that hotspots, to a great degree, are simply a result of promiscuous HLA binding, which disproves the hypothesis that the identification of hotspots provides novel information in the context of immunogenic peptide prediction. Furthermore, our analyses demonstrate that the signal of ligand processing, although present in the MS data, has very low predictive power to discriminate between MS and in silico defined hotspots. © 2018 John Wiley & Sons Ltd.

  18. Men presenting with prostate-specific antigen (PSA) values of over 100 ng/mL.

    Science.gov (United States)

    Ang, Mann; Rajcic, Branimir; Foreman, Darren; Moretti, Kim; O'Callaghan, Michael E

    2016-04-01

    To investigate overall survival and prostate cancer-specific mortality in men with prostate cancer presenting with a PSA level PSA level extracted from the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC) database. Men included were diagnosed between January 1998 and August 2013. Patients were divided into groups according to diagnostic PSA level: 500 ng/mL. Outcomes measured include overall survival and prostate cancer-specific mortality. Clinical stage, Gleason score and the presence of bony metastasis was evaluated to determine if they were prognostic factors in patients with PSA over 100 at diagnosis. Cox proportional hazards and competing risks regression were used to model overall survival and prostate cancer-specific mortality outcomes respectively. Of this cohort, 241 patients (4.2%) had a diagnostic PSA level >100 ng/mL. Patients with PSA >100 ng/mL have a significant reduction in five (29.1% vs 62.5% vs 87%) and ten-year (18.2% vs 36.7% vs 70.7%) overall survival when compared to men with diagnostic PSA 20-100 and PSA level at diagnosis. Overall survival was associated with PSA level, Gleason score and age. There was a linear increase in risk (overall survival) as PSA increased until 200 and no association thereafter. Models of overall survival and prostate cancer-specific mortality incorporating a risk stratification developed by Izumi et al. predicted overall survival but not prostate cancer-specific mortality. The use of this stratification did not improve model accuracy. Only a small number of men (4.2%) with prostate cancer present with PSA >100 ng/mL at diagnosis. Overall survival at five and ten years was significantly poorer in patients with PSA >100 ng/mL. In this cohort of men presenting with PSA >100 at diagnosis, PSA level was not associated with prostate cancer-specific mortality. Gleason score and metastases are significant prognostic factors in this group of men. © 2016 The Authors BJU International © 2016

  19. An open-source framework for stress-testing non-invasive foetal ECG extraction algorithms.

    Science.gov (United States)

    Andreotti, Fernando; Behar, Joachim; Zaunseder, Sebastian; Oster, Julien; Clifford, Gari D

    2016-05-01

    Over the past decades, many studies have been published on the extraction of non-invasive foetal electrocardiogram (NI-FECG) from abdominal recordings. Most of these contributions claim to obtain excellent results in detecting foetal QRS (FQRS) complexes in terms of location. A small subset of authors have investigated the extraction of morphological features from the NI-FECG. However, due to the shortage of available public databases, the large variety of performance measures employed and the lack of open-source reference algorithms, most contributions cannot be meaningfully assessed. This article attempts to address these issues by presenting a standardised methodology for stress testing NI-FECG algorithms, including absolute data, as well as extraction and evaluation routines. To that end, a large database of realistic artificial signals was created, totaling 145.8 h of multichannel data and over one million FQRS complexes. An important characteristic of this dataset is the inclusion of several non-stationary events (e.g. foetal movements, uterine contractions and heart rate fluctuations) that are critical for evaluating extraction routines. To demonstrate our testing methodology, three classes of NI-FECG extraction algorithms were evaluated: blind source separation (BSS), template subtraction (TS) and adaptive methods (AM). Experiments were conducted to benchmark the performance of eight NI-FECG extraction algorithms on the artificial database focusing on: FQRS detection and morphological analysis (foetal QT and T/QRS ratio). The overall median FQRS detection accuracies (i.e. considering all non-stationary events) for the best performing methods in each group were 99.9% for BSS, 97.9% for AM and 96.0% for TS. Both FQRS detections and morphological parameters were shown to heavily depend on the extraction techniques and signal-to-noise ratio. Particularly, it is shown that their evaluation in the source domain, obtained after using a BSS technique, should be

  20. Foetal Alcohol Spectrum Disorders and Alterations in Brain and Behaviour

    OpenAIRE

    Guerri, Consuelo; Bazinet, Alissa; Riley, Edward P.

    2009-01-01

    The term ‘Foetal Alcohol Spectrum Disorders (FASD)’ refers to the range of disabilities that may result from prenatal alcohol exposure. This article reviews the effects of ethanol on the developing brain and its long-term structural and neurobehavioural consequences. Brain imaging, neurobehavioural and experimental studies demonstrate the devastating consequences of prenatal alcohol exposure on the developing central nervous system (CNS), identifying specific brain regions affected, the range...

  1. INFLUENCE OF AMNIOTIC FLUID INDEX ON FOETAL OUTCOME

    Directory of Open Access Journals (Sweden)

    Raja Lakshmi

    2015-03-01

    Full Text Available BACKGROUND AND OBJECTIVE: In these days of smaller families and the obstetrician having to share the onus of giving a healthy child capable of independent existence as well as to ensure that the population is limited for further progress of this developing country, the estimation o f foetal maturity assumes greatest practical importance. As means to achieving the end, estimates of foetal maturity have been done by various clinical and laboratory methods of which assessment of amniotic fluid index assumes importance. The objective is to study the correlation of amniotic fluid index on foetal outcome at term gestation . MATERIALS AND METHODS: The study was carried out on two hundred antenatal women who attended the institute of obstetrics and gynaecology at a Government Hospital for Wome n and Children in Visakhapatnam from Jan 2014 to Jan 2015. It is a comparative prospective study comparing 100 cases of Oligohydramnios (amniotic fluid index 5 cm as control group. RESU LTS : Perinatal outcome was inferred by noting the various parameters and Statistical Analysis was done by applying the chisquare (x2 test and the value of probability was taken . CONCLUSION: The goal of antepartum fetal surveillance is to identify the fetu s at increased risk. Amniotic fluid volume has been proved as an indirect measure of feto - placental function and hence the estimation of amniotic fluid volume assists the obstetrician in risk assessment

  2. Distinct Gut-Derived Bacteria Differentially Affect Three Types of Antigen-Presenting Cells and Impact on NK- and T-Cell Responses

    DEFF Research Database (Denmark)

    Fink, Lisbeth Nielsen; Hansen, Anne Marie Valentin; Frøkiær, Hanne

    Objectives Gut bacteria are assumed essential for development and maintenance of a balanced immune system. Specifically, stimulation of antigen-presenting cells (APCs) by gut bacteria is important for polarisation of the immune response. This experiment was designed to reveal similarities...... and differences between the reaction patterns of three types of human APCs when stimulated with intestinal bacteria. Furthermore, the effect of these APCs on NK-cells and T-cells was examined. Methodology The APCs used in this study were blood monocytes, blood dendritic cells, and dendritic cells differentiated...... from monocytes. Monocyte-derived dendritic cells constitute a commonly used model of dendritic cell function. The APCs were cultured for 18 h with four different gut bacteria: Lactobacillus acidophilus X37, Lactobacillus reuteri DSM 12246, E. coli Nissle 1917 or Bifidobacterium longum Q46. Results...

  3. Presentations

    International Nuclear Information System (INIS)

    2007-01-01

    The presented materials consist of presentations of international workshop which held in Warsaw from 4 to 5 October 2007. Main subject of the meeting was progress in manufacturing as well as research program development for neutron detector which is planned to be placed at GANIL laboratory and will be used in nuclear spectroscopy research

  4. [Risks factors associated with intra-partum foetal mortality in pre-term infants].

    Science.gov (United States)

    Zeballos Sarrato, Susana; Villar Castro, Sonia; Ramos Navarro, Cristina; Zeballos Sarrato, Gonzalo; Sánchez Luna, Manuel

    2017-03-01

    Pre-term delivery is one of the leading causes of foetal and perinatal mortality. However, perinatal risk factors associated with intra-partum foetal death in preterm deliveries have not been well studied. To analyse foetal mortality and perinatal risk factors associated with intra-partum foetal mortality in pregnancies of less than 32 weeks gestational age. The study included all preterm deliveries between 22 and 31 +1 weeks gestational age (WGA), born in a tertiary-referral hospital, over a period of 7 years (2008-2014). A logistic regression model was used to identify perinatal risk factors associated with intra-partum foetal mortality (foetal malformations and chromosomal abnormalities were excluded). During the study period, the overall foetal mortality was 63.1% (106/168) (≥22 weeks of gestation) occurred in pregnancies of less than 32 WGA. A total of 882 deliveries between 22 and 31+6 weeks of gestation were included for analysis. The rate of foetal mortality was 11.3% (100/882). The rate of intra-partum foetal death was 2.6% (23/882), with 78.2% (18/23) of these cases occurring in hospitalised pregnancies. It was found that Assisted Reproductive Techniques, abnormal foetal ultrasound, no administration of antenatal steroids, lower gestational age, and small for gestational age, were independent risk factors associated with intra-partum foetal mortality. This study showed that there is a significant percentage intra-partum foetal mortality in infants between 22 and 31+6 WGA. The analysis of intrapartum mortality and risk factors associated with this mortality is of clinical and epidemiological interest to optimise perinatal care and improve survival of preterm infants. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Microneedle arrays coated with charge reversal pH-sensitive copolymers improve antigen presenting cells-homing DNA vaccine delivery and immune responses.

    Science.gov (United States)

    Duong, Huu Thuy Trang; Kim, Nak Won; Thambi, Thavasyappan; Giang Phan, V H; Lee, Min Sang; Yin, Yue; Jeong, Ji Hoon; Lee, Doo Sung

    2018-01-10

    Successful delivery of a DNA vaccine to antigen-presenting cells and their subsequent stimulation of CD4 + and CD8 + T cell immunity remains an inefficient process. In general, the delivery of prophylactic vaccines is mainly mired by low transfection efficacy, poor immunogenicity, and safety issues from the materials employed. Currently, several strategies have been exploited to improve immunogenicity, but an effective strategy for safe and pain-free delivery of DNA vaccines is complicated. Herein, we report the rapid delivery of polyplex-based DNA vaccines using microneedle arrays coated with a polyelectrolyte multilayer assembly of charge reversal pH-responsive copolymer and heparin. The charge reversal pH-responsive copolymer, composed of oligo(sulfamethazine)-b-poly(ethylene glycol)-b-poly(amino urethane) (OSM-b-PEG-b-PAEU), was used as a triggering layer in the polyelectrolyte multilayer assembly on microneedles. Charge reversal characteristics of this copolymer, that is, the OSM-b-PEG-b-PAEU copolymer exhibit, positive charge at low pH (pH4.03) and becoming negative charge when exposed to physiological pH conditions (pH7.4), allowing the facile assembly and disassembly of polyelectrolyte multilayers. The electrostatic repulsion between heparin and OSM-b-PEG-b-PAEU charge reversal copolymer triggered the release of DNA vaccines. DNA vaccines laden on microneedles are effectively transfected into RAW 264.7 macrophage cells in vitro. Vaccination of BALB/c mice by DNA vaccine-loaded microneedle arrays coated with a polyelectrolyte multilayer generated antigen-specific robust immune responses. These findings provide potential strategy of charge reversal pH-responsive copolymers coated microneedles for DNA vaccine delivery. Copyright © 2017. Published by Elsevier B.V.

  6. Presentations

    International Nuclear Information System (INIS)

    2007-01-01

    The PARIS meeting held in Cracow, Poland from 14 to 15 May 2007. The main subjects discussed during this meeting were the status of international project dedicated to gamma spectroscopy research. The scientific research program includes investigations of giant dipole resonance, probe of hot nuclei induced in heavy reactions, Jacobi shape transitions, isospin mixing and nuclear multifragmentation. The mentioned programme needs Rand D development such as new scintillations materials as lanthanum chlorides and bromides as well as new photo detection sensors as avalanche photodiodes - such subjects are also subjects of discussion. Additionally results of computerized simulations of scintillation detectors properties by means of GEANT- 4 code are presented

  7. Presentation

    Directory of Open Access Journals (Sweden)

    Eduardo Vicente

    2013-06-01

    Full Text Available In the present edition of Significação – Scientific Journal for Audiovisual Culture and in the others to follow something new is brought: the presence of thematic dossiers which are to be organized by invited scholars. The appointed subject for the very first one of them was Radio and the invited scholar, Eduardo Vicente, professor at the Graduate Course in Audiovisual and at the Postgraduate Program in Audiovisual Media and Processes of the School of Communication and Arts of the University of São Paulo (ECA-USP. Entitled Radio Beyond Borders the dossier gathers six articles and the intention of reuniting works on the perspectives of usage of such media as much as on the new possibilities of aesthetical experimenting being build up for it, especially considering the new digital technologies and technological convergences. It also intends to present works with original theoretical approach and original reflections able to reset the way we look at what is today already a centennial media. Having broadened the meaning of “beyond borders”, four foreign authors were invited to join the dossier. This is the first time they are being published in this country and so, in all cases, the articles where either written or translated into Portuguese.The dossier begins with “Radio is dead…Long live to the sound”, which is the transcription of a thought provoking lecture given by Armand Balsebre (Autonomous University of Barcelona – one of the most influential authors in the world on the Radio study field. It addresses the challenges such media is to face so that it can become “a new sound media, in the context of a new soundscape or sound-sphere, for the new listeners”. Andrew Dubber (Birmingham City University regarding the challenges posed by a Digital Era argues for a theoretical approach in radio studies which can consider a Media Ecology. The author understands the form and discourse of radio as a negotiation of affordances and

  8. Diagnosis of foetal membrane ruptures: Placental alpha ...

    African Journals Online (AJOL)

    Context: Pre‑labour rupture of membranes (PROM) is a common obstetric complication which presents a diagnostic challenge, especially in equivocal ... problematic with the need to balance the risk of prematurity with that of prolonged ... array of rapid, minimally invasive tests based on biochemical markers in amniotic fluid ...

  9. Evaluation of the ability of N-terminal fragment of lethal factor of Bacillus anthracis for delivery of Mycobacterium T cell antigen ESAT-6 into cytosol of antigen presenting cells to elicit effective cytotoxic T lymphocyte response

    International Nuclear Information System (INIS)

    Chandra, Subhash; Kaur, Manpreet; Midha, Shuchi; Bhatnagar, Rakesh; Banerjee-Bhatnagar, Nirupama

    2006-01-01

    We report the ability of N-terminal fragment of lethal factor of Bacillus anthracis to deliver genetically fused ESAT-6 (early secretory antigen target), a potent T cell antigen of Mycobacterium tuberculosis, into cytosol to elicit Cytotoxic T lymphocyte (CTL) response. In vitro Th1 cytokines data and CTL assay proved that efficient delivery of LFn.ESAT-6 occurs in cytosol, in the presence of protective antigen (PA), and leads to generation of effective CTL response. Since CTL response is essential for protection against intracellular pathogens and, it is well known that only single T cell epitope or single antigenic protein is not sufficient to elicit protective CTL response due to variation or polymorphism in MHC-I alleles among the individuals, we suggest that as a fusion protein LFn can be used to deliver multiepitopes of T cells or multiproteins which can generate effective CTLs against intracellular pathogens like M. tuberculosis. It can be used to enhance the protective efficacy of BCG vaccine

  10. Testicular dysgenesis syndrome: foetal origin of adult reproductive problems

    DEFF Research Database (Denmark)

    Wohlfahrt-Veje, Christine; Main, Katharina M; Skakkebaek, Niels Erik

    2009-01-01

    , the risk of testis cancer is significantly increased in men with cryptorchidism and/or infertility. Several recent studies point towards early dysgenesis of the foetal testis as the biological link between these disorders. Dysgenesis has been demonstrated in biopsies of the contralateral testis of men...... with testis cancer and in infertile men. The histological evidence includes immature seminiferous tubules with undifferentiated Sertoli cells, microliths and Sertoli-cell only tubules. Dysgenetic testes often have an irregular ultrasound pattern, where microliths may also be visible. Our current hypothesis...

  11. Foetal proglucagon processing in relation to adult appetite control

    DEFF Research Database (Denmark)

    Jensen, P B; Larsen, P J; Karlsen, C

    2011-01-01

    with a foetal processing pattern of proglucagon to both glucagon and GLP-1 (7-36amide), and is due to taste aversion. The sudden onset is characterized by a dramatic increase in circulating levels of biologically active GLP-1 (7-36amide), suggesting eventual saturation of proteolytic inactivation of its N-terminus....... neuropeptide Y (NPY) mRNA levels in the nucleus arcuatus. We now show that circulating levels of bioactive glucagon-like peptide-1 (GLP-1) (7-36amide) start to increase above control levels exactly at the time of onset of anorexia. At this time-point, bioactive glucagon as well as total glucagon precursors...

  12. Do Thyroid Disrupting Chemicals Influence Foetal Development during Pregnancy?

    DEFF Research Database (Denmark)

    Hartoft-Nielsen, Marie-Louise; Boas, Malene; Bliddal, Sofie

    2011-01-01

    Maternal euthyroidism during pregnancy is crucial for normal development and, in particular, neurodevelopment of the foetus. Up to 3.5 percent of pregnant women suffer from hypothyroidism. Industrial use of various chemicals-endocrine disrupting chemicals (EDCs)-has been shown to cause almost...... constant exposure of humans with possible harmful influence on health and hormone regulation. EDCs may affect thyroid hormone homeostasis by different mechanisms, and though the effect of each chemical seems scarce, the added effects may cause inappropriate consequences on, for example, foetal...

  13. Development of an enhanced bovine viral diarrhea virus subunit vaccine based on E2 glycoprotein fused to a single chain antibody which targets to antigen-presenting cells

    Directory of Open Access Journals (Sweden)

    Andrea Pecora

    2015-03-01

    Full Text Available Bovine viral diarrhea virus (BVDV is an important cause of economic losses worldwide. E2 is an immunodominant protein and a promising candidate to develop subunit vaccines. To improve its immunogenicity, a truncated E2 (tE2 was fused to a single chain antibody named APCH, which targets to antigen-presenting cells. APCH-tE2 and tE2 proteins were expressed in the baculovirus system and their immunogenicity was firstly compared in guinea pigs. APCH-tE2 vaccine was the best one to evoke a humoral response, and for this reason, it was selected for a cattle vaccination experiment. All the bovines immunized with 1.5 µg of APCH-tE2 developed high levels of neutralizing antibodies against BVDV up to a year post-immunization, demonstrating its significant potential as a subunit vaccine. This novel vaccine is undergoing scale-up and was transferred to the private sector. Nowadays, it is being evaluated for registration as the first Argentinean subunit vaccine for cattle.

  14. Recipient dendritic cells, but not B cells, are required antigen-presenting cells for peripheral alloreactive CD8+ T-cell tolerance.

    Science.gov (United States)

    Mollov, J L; Lucas, C L; Haspot, F; Gaspar, J Kurtz C; Guzman, A; Sykes, M

    2010-03-01

    Induction of mixed allogeneic chimerism is a promising approach for achieving donor-specific tolerance, thereby obviating the need for life-long immunosuppression for solid organ allograft acceptance. In mice receiving a low dose (3Gy) of total body irradiation, allogeneic bone marrow transplantation combined with anti-CD154 tolerizes peripheral CD4 and CD8 T cells, allowing achievement of mixed chimerism with specific tolerance to donor. With this approach, peripheral CD8 T-cell tolerance requires recipient MHC class II, CD4 T cells, B cells and DCs. Recipient-type B cells from chimeras that were tolerant to donor still promoted CD8 T-cell tolerance, but their role could not be replaced by donor-type B cells. Using recipients whose B cells or DCs specifically lack MHC class I and/or class II or lack CD80 and CD86, we demonstrate that dendritic cells (DCs) must express CD80/86 and either MHC class I or class II to promote CD8 tolerance. In contrast, B cells, though required, did not need to express MHC class I or class II or CD80/86 to promote CD8 tolerance. Moreover, recipient IDO and IL-10 were not required. Thus, antigen presentation by recipient DCs and not by B cells is critical for peripheral alloreactive CD8 T cell tolerance.

  15. Development of an enhanced bovine viral diarrhea virus subunit vaccine based on E2 glycoprotein fused to a single chain antibody which targets to antigen-presenting cells.

    Science.gov (United States)

    Pecora, Andrea; Malacari, Darío A; Pérez Aguirreburualde, María S; Bellido, Demian; Escribano, José M; Dus Santos, María J; Wigdorovitz, Andrés

    2015-01-01

    Bovine viral diarrhea virus (BVDV) is an important cause of economic losses worldwide. E2 is an immunodominant protein and a promising candidate to develop subunit vaccines. To improve its immunogenicity, a truncated E2 (tE2) was fused to a single chain antibody named APCH, which targets to antigen-presenting cells. APCH-tE2 and tE2 proteins were expressed in the baculovirus system and their immunogenicity was firstly compared in guinea pigs. APCH-tE2 vaccine was the best one to evoke a humoral response, and for this reason, it was selected for a cattle vaccination experiment. All the bovines immunized with 1.5 μg of APCH-tE2 developed high levels of neutralizing antibodies against BVDV up to a year post-immunization, demonstrating its significant potential as a subunit vaccine. This novel vaccine is undergoing scale-up and was transferred to the private sector. Nowadays, it is being evaluated for registration as the first Argentinean subunit vaccine for cattle. Copyright © 2014 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. 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.

  17. Carcinoma in situ testis displays permissive chromatin modifications similar to immature foetal germ cells

    DEFF Research Database (Denmark)

    Almstrup, K; Nielsen, J E; Mlynarska, O

    2010-01-01

    The majority of testicular germ cell cancers develop through a pre-invasive carcinoma in situ (CIS) stage. The CIS cell is a neoplastic counterpart of foetal germ cells. During their development, foetal germ cells undergo extensive and essential epigenetic modifications, but little is known about...

  18. Is there a relationship between foetal position and both preferred lying posture after birth and pattern of subsequent postural deformity in non-ambulant people with cerebral palsy?

    Science.gov (United States)

    Porter, D; Michael, S; Kirkwood, C

    2010-09-01

    A pattern of postural deformity was observed in a previous study that included an association between direction of spinal curvature and direction of windsweeping with more windswept deformities occurring to the right and lateral spinal curvatures occurring convex to the left. The direction of this pattern was found to be associated with preferred lying posture in early life. The aim of this study was to test the association between foetal position and both the preferred lying posture after birth, and the direction of subsequent postural deformity in non-ambulant children with cerebral palsy (CP). A retrospective cohort study was carried out involving 60 participants at level five on the gross motor function classification for CP. Foetal position during the last month of pregnancy was taken from antenatal records and parents were interviewed to identify preferred lying posture in the first year of life. At the time of the physical assessment ages ranged from 1 year and 1 month to 19 years with a median age of 13 years and 1 month. Foetal presentation was found to be associated with the preferred lying posture with participants carried in a left occipito-anterior/lateral position more likely to adopt a supine head right lying posture, and vice versa. An association was also observed between the foetal position and asymmetrical postural deformity occurring later in life with participants carried in a left occipito-anterior/lateral presentation more likely to have a convex left spinal curve, a lower left pelvic obliquity, and a windswept hip pattern to the right. Clinicians should be aware of the association between foetal presentation, asymmetrical lying posture, and the direction of subsequent postural deformity for severely disabled children. A hypothesis is described that might help to explain these findings.

  19. STR typing of formalin-fixed paraffin embedded (FFPE) aborted foetal tissue in criminal paternity cases.

    Science.gov (United States)

    Reshef, Ayeleth; Barash, Mark; Voskoboinik, Lev; Brauner, Paul; Gafny, Roni

    2011-03-01

    Sexual assault or rape cases occasionally result in unwanted pregnancies. In almost all such cases the foetus is aborted. A forensic laboratory may receive the foetus, the placenta, or paraffin embedded abortion material for paternity testing. Obtaining a foetal profile DNA from a foetus or placenta may not be successful due to the age or condition of the tissue. Moreover, maternal contamination of placental material will invariably result in a mixed DNA profile. However, the use of properly screened abortion material from paraffin blocks will almost always result in obtaining a foetal DNA profile. Furthermore, foetal tissue fixed in paraffin blocks does not require special conditions for submission and storage as required to preserve fresh foetal or placental tissue. As hospitals routinely prepare foetal tissue in paraffin blocks, which should be readily obtainable by forensic laboratories, these samples would appear to be the preferred choice for paternity testing. 2010 Forensic Science Society. Published by Elsevier Ireland Ltd. All rights reserved.

  20. FATAL FOETAL ABNORMALITY, IRISH CONSTITUTIONAL LAW, AND MELLET v IRELAND.

    Science.gov (United States)

    de Londras, Fiona

    2016-12-27

    Under the Irish Constitution abortion is allowed only where the life of the pregnant woman is at risk. The provision in question, Article 40.3.3 (or the 8th Amendment) has long been criticised for failing to respect women's autonomy, and in Mellet v Ireland, the UN Human Rights Committee found that Amanda Jane Mellet, who travelled to Liverpool to access abortion following a finding that her foetus suffered a fatal abnormality, had suffered a violation of her rights under the International Covenant on Civil and Political Rights (ICCPR). In this commentary I demonstrate the value of Mellet when compared to the possible legal findings in such circumstances under both the Constitution and the European Convention on Human Rights, and argue that the findings are not restricted to cases of fatal foetal abnormality. Rather, the Committee's decision illustrates the suffering that all women in Ireland who travel to access abortion experience, arguably constituting a violation of their right to be free from cruel, inhuman, and degrading treatment. On that reading, Mellet signifies the need to implement a comprehensive rethink of Irish abortion law including, but going beyond, access to abortion in cases of fatal foetal abnormality. © The Author 2016. Published by Oxford University Press; all rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Acquired Protective Immunity in Atlantic Salmon Salmo salar against the Myxozoan Kudoa thyrsites Involves Induction of MHIIβ+ CD83+ Antigen-Presenting Cells.

    Science.gov (United States)

    Braden, Laura M; Rasmussen, Karina J; Purcell, Sara L; Ellis, Lauren; Mahony, Amelia; Cho, Steven; Whyte, Shona K; Jones, Simon R M; Fast, Mark D

    2018-01-01

    The histozoic myxozoan parasite Kudoa thyrsites causes postmortem myoliquefaction and is responsible for economic losses to salmon aquaculture in the Pacific Northwest. Despite its importance, little is known about the host-parasite relationship, including the host response to infection. The present work sought to characterize the immune response in Atlantic salmon during infection, recovery, and reexposure to K. thyrsites After exposure to infective seawater, infected and uninfected smolts were sampled three times over 4,275 degree-days. Histological analysis revealed infection severity decreased over time in exposed fish, while in controls there was no evidence of infection. Following a secondary exposure of all fish, severity of infection in the controls was similar to that measured in exposed fish at the first sampling time but was significantly reduced in reexposed fish, suggesting the acquisition of protective immunity. Using immunohistochemistry, we detected a population of MHIIβ + cells in infected muscle that followed a pattern of abundance concordant with parasite prevalence. Infiltration of these cells into infected myocytes preceded destruction of the plasmodium and dissemination of myxospores. Dual labeling indicated a majority of these cells were CD83 + /MHIIβ + Using reverse transcription-quantitative PCR, we detected significant induction of cellular effectors, including macrophage/dendritic cells ( mhii / cd83 / mcsf ), B cells ( igm / igt ), and cytotoxic T cells ( cd8 / nkl ), in the musculature of infected fish. These data support a role for cellular effectors such as antigen-presenting cells (monocyte/macrophage and dendritic cells) along with B and T cells in the acquired protective immune response of Atlantic salmon against K. thyrsites . Copyright © 2017 American Society for Microbiology.

  2. Molecular basis for the presence of glycosylated onco-foetal fibronectin in oral carcinomas

    DEFF Research Database (Denmark)

    Wandall, Hans H; Dabelsteen, Sally; Sørensen, Jens Ahm

    2007-01-01

    spliced IIICS region. Using cell culture experiments, immunohistochemical staining of primary tissue, and RT-PCR of tumour cells isolated by laser capture techniques we have examined the molecular basis for the production of GOF in oral carcinomas. Immuno-histochemical investigation confirmed the stromal......Glycosylated onco-foetal fibronectin (GOF) deposited in the stroma of oral squamous cell carcinomas correlates with survival. One of the two polypeptide GalNAc-transferases, GalNAc-T3 or GalNAc-T6, is required for the biosynthesis of GOF by the initiation of a unique O-glycan in the alternative...... deposition of GOF in oral carcinomas. However, neither GalNAc-T3 nor GalNAc-T6 could be detected in stromal fibroblasts. In contrast both transferases were present in the oral squamous carcinoma cells, suggesting that GOF is produced by the oral cancer cells and not only the stromal cells. RT-PCR analysis...

  3. Amelioration of renal ischaemia-reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells.

    Science.gov (United States)

    Rogers, N M; Stephenson, M D; Kitching, A R; Horowitz, J D; Coates, P T H

    2012-05-01

    Renal ischaemia-reperfusion (IR) injury is an inevitable consequence of renal transplantation, causing significant graft injury, increasing the risk of rejection and contributing to poor long-term graft outcome. Renal injury is mediated by cytokine and chemokine synthesis, inflammation and oxidative stress resulting from activation of the NF-κB pathway. We utilized liposomal incorporation of a potent inhibitor of the NF-κB pathway, curcumin, to target delivery to renal tubular epithelial and antigen-presenting cells. Liposomes containing curcumin were administered before bilateral renal ischaemia in C57/B6 mice, with subsequent reperfusion. Renal function was assessed from plasma levels of urea and creatinine, 4 and 24 h after reperfusion. Renal tissue was examined for NF-κB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT-PCR and Western blotting. Liposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll-like receptor-4, heat shock protein-70 and TNF-α mRNA expression. Liposomal curcumin also reduced neutrophil infiltration and diminished inflammatory chemokine expression. Curcumin liposomes reduced intracellular superoxide generation and increased superoxide dismutase levels, decreased inducible NOS mRNA expression and 3-nitrotyrosine staining consistent with limitations in nitrosative stress and inhibited renal tubular mRNA and protein expression of thioredoxin-interacting protein. These actions of curcumin were mediated by inhibition of NF-κB, MAPK and phospho-S6 ribosomal protein. Liposomal delivery of curcumin promoted effective, targeted delivery of this non-toxic compound that provided cytoprotection via anti-inflammatory and multiple antioxidant mechanisms following renal IR injury. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  4. EFFECT OF LIPOSOMAL CLODRONATE-DEPENDENT DEPLETION OF PROFESSIONAL ANTIGEN PRESENTING CELLS ON NUMBERS AND PHENOTYPE OF CANINE CD4+CD25+FOXP3+ REGULATORY T CELLS

    Science.gov (United States)

    Weaver, Kriston F.; Stokes, John V.; Gunnoe, Sagen A.; Follows, Joyce S.; Shafer, Lydia; Ammari, Mais G.; Archer, Todd M.; Thomason, John M.; Mackin, Andrew J.; Pinchuk, Lesya M.

    2015-01-01

    Regulatory T cells (Tregs) are known to control autoreactivity during and subsequent to the development of the peripheral immune system. Professional antigen presenting cells (APCs), dendritic cells (DCs) and monocytes, have an important role in inducing Tregs. For the first time, this study evaluated proportions and phenotypes of Tregs in canine peripheral blood depleted of professional APCs, utilizing liposomal clodronate (LC) and multicolor flow cytometry analysis. Our results demonstrate that LC exposure promoted short term decreases followed by significant increases in the proportions or absolute numbers of CD4+CD25+FOXP3+ Tregs in dogs. In general, the LC-dependent Treg fluctuations were similar to the changes in the levels of CD14+ monocytes in Walker hounds. However, the proportions of monocytes showed more dramatic changes compared to the proportions of Tregs that were visually unchanged after LC treatment over the study period. At the same time, absolute Treg numbers showed, similarly to the levels of CD14+ monocytes, significant compensatory gains as well as the recovery during the normalization period. We confirm the previous data that CD4+ T cells with the highest CD25 expression were highly enriched for FOXP3. Furthermore, for the first time, we report that CD4+CD25lowFOXP3+ is the major regulatory T cell subset affected by LC exposure. The increases within the lowest CD25 expressers of CD4+FOXP3+ cells together with compensatory gains in the proportion of CD14+ monocytes during compensatory and normalization periods suggest the possible direct or indirect roles of monocytes in active recruitment and generation of Tregs from naïve CD4+ T cells. PMID:25950023

  5. Increase in a distinct pulmonary macrophage subset possessing an antigen-presenting cell phenotype and in vitro APC activity following silica exposure

    International Nuclear Information System (INIS)

    Migliaccio, Christopher T.; Hamilton, Raymond F.; Holian, Andrij

    2005-01-01

    Silica inhalation results in chronic lung inflammation and fibrosis. While the role of the alveolar macrophage (AM) is considered key to the effects of silica on lung pathology, the etiology is not completely understood. Evidence suggests an increase in antigen presenting cell (APC) activity as a contributing factor to this process, as well as potential roles for both AM and interstitial macrophages (IM) in silicosis. In order to study the effects of crystalline silica on the APC activity of pulmonary macrophages, mice were exposed intranasally and changes in pulmonary macrophage populations were assessed using flow cytometry. Following intranasal instillation of silica, a significant increase in the APC activity of AM was observed, as well as a significant increase in a subset of IM expressing classic APC markers (MHC class II, CD11c). In addition, an in vitro system using bone marrow-derived macrophages (BMDM) was generated to assess the effects of silica on the APC activity of macrophages in vitro. Data using BMDM in the in vitro APC assay demonstrated a significant increase in APC activity following silica exposure, but not following exposure to saline or a control particle (TiO 2 ). Using a combination of in vivo and in vitro experiments, the current study describes a significant increase in an interstitial macrophage subset with an APC phenotype, as well as an increase in the APC activity of both AM and BMDM, as a direct result of exposure to crystalline silica. These studies suggest a specific mechanism, macrophage subset activation, by which crystalline silica exposure results in chronic pulmonary inflammation and, eventually, fibrosis

  6. Porcine foetal and neonatal CYP3A liver expression

    Directory of Open Access Journals (Sweden)

    Marie Louise Hiort Hermann

    2011-05-01

    Full Text Available Human cytochrome P450 3A7 (CYP3A7 and cytochrome P450 3A4 (CYP3A4 are hepatic metabolising enzymes which participates in the biotransformation of endo- and exogenous substances in foetuses and neonates respectively. These CYP3A enzymes display an inverse relationship: CYP3A7 is the dominant enzyme in the foetal liver, whereas the expression of CYP3A4 is low. After parturition there is a shift in the expression, thus CYP3A7 is down regulated, while the level of CYP3A4 gradually increases and becomes the dominant metabolising CYP3A enzyme in the adult. The minipig is increasingly being used as a model for humans in biomedical studies, because of its many similarities with the human physiology and anatomy. The aim of this study was to examine whether, as in humans, a shift is seen in the hepatic expression of a CYP3A7- like enzyme to cytochrome P450 3A29 (CYP3A29 (an orthologue to the human CYP3A4 in minipigs. This was elucidated by examining the hepatic mRNA expression of CYP3A7 and CYP3A29 in 39 foetuses and newborn Göttingen minipigs using quantitative real time polymerase chain reaction (qPCR. Furthermore the immunochemical level of CYP3A7-LE and CYP3A29 was measured in liver microsomes using western blotting. The expression of CYP3A29 was approximately 9- fold greater in neonates compared to foetuses, and a similar difference was reflected on the immunochemical level. It was not possible to detect a significant level of foetal CYP3A7 mRNA, but immunoblotting showed a visible difference depending on age. This study demonstrates an increase in the expression of CYP3A29, the CYP3A4 orthologue in perinatal minipigs as in humans, which suggests that the minipig could be a good model when testing for human foetal toxicity towards CYP3A4 substrates.

  7. Calcipotriol inhibits the proliferation of hyperproliferative CD29 positive keratinocytes in psoriatic epidermis in the absence of an effect on the function and number of antigen-presenting cells

    DEFF Research Database (Denmark)

    Jensen, A.M.; Llado, Minna Fyhn Lykke; Skov, L.

    1998-01-01

    The aim of this study was to elucidate some of the possible mechanisms of action of the vitamin D analogue calcipotriol in vivo. Calcipotriol is finding increasing use in the treatment of psoriasis, but the primary target cell in vivo has not yet been identified. We treated psoriatic patients...... psoriatic and normal skin, calcipotriol treatment did not alter the capacity of epidermal antigen-presenting cells to stimulate the proliferation of autologous T cells, either in the absence or in the presence of exogenous antigen. Epidermal cell suspensions were analysed further by staining...... for infiltrating leucocytes (CD45+) and Langerhans cells (CD1a+). Flow cytometric analysis showed that calcipotriol did not alter the number of CD45+ cells or Langerhans cells in psoriatic skin. These results indicate that calcipotriol does not alter either the number of the function of epidermal antigen...

  8. Laterality of foetal self-touch in relation to maternal stress.

    Science.gov (United States)

    Reissland, Nadja; Aydin, Ezra; Francis, Brian; Exley, Kendra

    2015-01-01

    This longitudinal observational study investigated whether foetuses change their hand preference with gestational age, and also examined the effects of maternal stress on lateralized foetal self-touch. Following ethical approval, fifteen healthy foetuses (eight girls and seven boys) were scanned four times from 24 to 36 weeks gestation. Self-touch behaviours which resulted in a touch of the foetal face/head were coded in 60 scans for 10 min and analysed in terms of frequency of the foetuses using left and right hands to touch their face. The joint effects of foetal age, stress and sex on laterality were assessed. We modelled the proportion of right self-touches for each foetal scan using a generalized linear mixed model, taking account of the repeated measures design. There was substantial variability in hand preference between foetuses. However, there was no significant increase in the proportion of right-handed touches with foetal age. No sex differences in handedness were identified. However, maternally reported stress level was significantly positively related to foetal left-handed self-touches (odds ratio 0.915; p < .0001). This longitudinal study provides important new insights into the effect of recent maternal stress on foetal predominant hand use during self-touch.

  9. Foetal Fentanyl Exposure and Ion Trapping after Intravenous and Transdermal Administration to the Ewe.

    Science.gov (United States)

    Heikkinen, Emma M; Kokki, Hannu; Heikkinen, Aki; Ranta, Veli-Pekka; Räsänen, Juha; Voipio, Hanna-Marja; Kokki, Merja

    2017-02-01

    Opioids given to pregnant and parturient women are relatively freely transferred across the placenta. Spinal, epidural and intravenous fentanyl has been studied in pregnant women and neonates, but foetal safety of fentanyl dosing with transdermal patch during pregnancy and labour is not sufficiently studied. Foetal pH is physiologically lower than maternal pH, and thus, opioids, which are weak bases, are ionized and may cumulate to foetus. Foetal asphyxia may further worsen acidosis, and ion trapping induced by low pH is assumed to increase the foetal exposure to opioids. Here, we show that no correlation between foetal acidosis and ion trapping of fentanyl could be found. In three experiments, 29 pregnant sheep were administered fentanyl with 2 μg/kg/h patch supplemented with IV boluses/infusion. Foetal exposure to fentanyl was extensive, median 0.34 ng/ml (quartiles 0.21, 0.42), yet drug accumulation to foetus was not observed, and median of foetal/maternal concentration (F/M) ratio was 0.63 (0.43, 0.75) during the first hours after the fentanyl administration. Low foetal pH and pH difference between ewe and the foetus did not correlate with fentanyl concentration in the foetus or F/M ratio. At steady-state during the second patch worn, foetal plasma fentanyl was low, 0.13 ng/ml, and the median of F/M ratio was 0.69. Our results demonstrate that drug accumulation to foetus caused by ion trapping seen with some weak base opioids may not be that significant with fentanyl. These results have a clinical relevance when fentanyl is dosed to pregnant woman and the foetus is acidemic. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  10. Approximate distribution of dose among foetal organs for radioiodine uptake via placenta transfer

    Science.gov (United States)

    Millard, R. K.; Saunders, M.; Palmer, A. M.; Preece, A. W.

    2001-11-01

    Absorbed radiation doses to internal foetal organs were calculated according to the medical internal radiation dose (MIRD) technique in this study. Anthropomorphic phantoms of the pregnant female as in MIRDOSE3 enabled estimation of absorbed dose to the whole foetus at two stages of gestation. Some foetal organ self-doses could have been estimated by invoking simple spherical models for thyroid, liver, etc, but we investigated the use of the MIRDOSE3 new-born phantom as a surrogate for the stage 3 foetus, scaled to be compatible with total foetal body mean absorbed dose/cumulated activity. We illustrate the method for obtaining approximate dose distribution in the foetus near term following intake of 1 MBq of 123I, 124I, 125I or 131I as sodium iodide by the mother using in vivo biodistribution data examples from a good model of placenta transfer. Doses to the foetal thyroid of up to 1.85 Gy MBq-1 were predicted from the 131I uptake data. Activity in the foetal thyroid was the largest contributor to absorbed dose in the foetal body, brain, heart and thymus. Average total doses to the whole foetus ranged from 0.16 to 1.2 mGy MBq-1 for stages 1 and 3 of pregnancy using the MIRDOSE3 program, and were considerably higher than those predicted from the maternal contributions alone. Doses to the foetal thymus and stomach were similar, around 2-3 mGy MBq-1. Some foetal organ doses from the radioiodides were ten times higher than to the corresponding organs of the mother, and up to 100 times higher to the thyroid. The fraction of activity uptakes in foetal organs were distributed similarly to the maternal ones.

  11. Approximate distribution of dose among foetal organs for radioiodine uptake via placenta transfer

    Energy Technology Data Exchange (ETDEWEB)

    Millard, R.K. [Medical Physics Research Centre, Bristol Oncology Centre, Bristol (United Kingdom)]. E-mail: rkmillard_69@yahoo.co.uk; Saunders, M.; Palmer, A.M.; Preece, A.W. [Medical Physics Research Centre, Bristol Oncology Centre, Bristol (United Kingdom)

    2001-11-01

    Absorbed radiation doses to internal foetal organs were calculated according to the medical internal radiation dose (MIRD) technique in this study. Anthropomorphic phantoms of the pregnant female as in MIRDOSE3 enabled estimation of absorbed dose to the whole foetus at two stages of gestation. Some foetal organ self-doses could have been estimated by invoking simple spherical models for thyroid, liver, etc, but we investigated the use of the MIRDOSE3 new-born phantom as a surrogate for the stage 3 foetus, scaled to be compatible with total foetal body mean absorbed dose/cumulated activity. We illustrate the method for obtaining approximate dose distribution in the foetus near term following intake of 1 MBq of {sup 123}I, {sup 124}I, {sup 125}I or {sup 131}I as sodium iodide by the mother using in vivo biodistribution data examples from a good model of placenta transfer. Doses to the foetal thyroid of up to 1.85 Gy MBq{sup -1} were predicted from the {sup 131}I uptake data. Activity in the foetal thyroid was the largest contributor to absorbed dose in the foetal body, brain, heart and thymus. Average total doses to the whole foetus ranged from 0.16 to 1.2 mGy MBq{sup -1} for stages 1 and 3 of pregnancy using the MIRDOSE3 program, and were considerably higher than those predicted from the maternal contributions alone. Doses to the foetal thymus and stomach were similar, around 2-3 mGy MBq{sup -1}. Some foetal organ doses from the radioiodides were ten times higher than to the corresponding organs of the mother, and up to 100 times higher to the thyroid. The fraction of activity uptakes in foetal organs were distributed similarly to the maternal ones. (author)

  12. Foetal exposure to food and environmental carcinogens in human beings.

    Science.gov (United States)

    Myöhänen, Kirsi; Vähäkangas, Kirsi

    2012-02-01

    Exposure to many different chemicals during pregnancy through maternal circulation is possible. Transplacental transfer of xenobiotics can be demonstrated using human placental perfusion. Also, placental perfusion can give information about the placental kinetics as well as metabolism and accumulation in the placenta because it retains the tissue structure and function. Although human placental perfusion has been used extensively to study the transplacental transfer of drugs, the information on food and environmental carcinogens is much more limited. This review deals with the foetal exposure to food and environmental carcinogens in human beings. In particular, human transplacental transfer of the food carcinogens such as acrylamide, glycidamide and nitrosodimethylamine are in focus. Because these carcinogens are genotoxic, the functional capacity of human placenta to induce DNA adduct formation or metabolize these above mentioned CYP2E1 substrates is of interest in this context. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

  13. Porcine foetal and neonatal CYP3A liver expression

    DEFF Research Database (Denmark)

    Hermann-Bank, Marie Louise; Skaanild, Mette Tingleff

    2011-01-01

    enzyme in the foetal liver, whereas the expression of CYP3A4 is low. After parturition there is a shift in the expression, thus CYP3A7 is down regulated, while the level of CYP3A4 gradually increases and becomes the dominant metabolising CYP3A enzyme in the adult. The minipig is increasingly being used......3A4) in minipigs. This was elucidated by examining the hepatic mRNA expression of CYP3A7 and CYP3A29 in 39 foetuses and newborn Göttingen minipigs using quantitative real time polymerase chain reaction (qPCR). Furthermore the immunochemical level of CYP3A7-LE and CYP3A29 was measured in liver...

  14. Partial foetal retention following aglepristone treatment in a bitch.

    Science.gov (United States)

    Rigau, T; Rodríguez-Gil, J-E; García, F; del Alamo, M M Rivera

    2011-08-01

    This short communication describes the case of partial foetal retention in an 18-month-old female French bulldog following induction of abortion owing to an undesired mating. Abortion was induced with aglepristone administered in two consecutive protocols of a dual injection 1 day apart. After failure of the first treatment to achieve abortion, 15 days later, a second treatment was administered. Delivering of aborted foetus occurred 2 days after the last administration. Five weeks after the abortion, the female showed a weak haemorrhagic vaginal discharge. On ultrasound examination, the presence of uterine wall distension as well as a puppy skull inside the uterus was observed. This clinical case makes clear that although aglepristone is a very reliable drug, follow-up of the female during treatment and in the immediate post-partum is necessary to ensure a good outcome. © 2010 Blackwell Verlag GmbH.

  15. Embryonic and foetal Islet-1 positive cells in human hearts are also positive to c-Kit

    Directory of Open Access Journals (Sweden)

    C. Serradifalco

    2011-12-01

    Full Text Available During embryogenesis, the mammalian heart develops from a primitive heart tube originating from two bilateral primary heart fields located in the lateral plate mesoderm. Cells belongings to the pre-cardiac mesoderm will differentiate into early cardiac progenitors, which express early transcription factors which are also common to the Isl-1 positive cardiac progenitor cells isolated from the developing pharyngeal mesoderm and the foetal and post-natal mice hearts. A second population of cardiac progenitor cells positive to c-Kit has been abundantly isolated from adult hearts. Until now, these two populations have been considered two different sets of progenitor cells present in the heart in different stages of an individual life. In the present study we collected embryonic, foetal and infant hearts, and we tested the hypotheses that c-Kit positive cells, usually isolated from the adult heart, are also present in the intra-uterine life and persist in the adult heart after birth, and that foetal Isl-1 positive cells are also positive to c-Kit. Using immunohistochemistry we studied the temporal distribution of Isl-1 positive and c-Kit/CD105 double positive cells, and by immunofluorescence and confocal analysis we studied the co-localization of c-Kit and Isl-1 positive cells. The results indicated that cardiomyocytes and interstitial cells were positive for c-Kit from the 9th to the 19th gestational week, that cells positive for both c-Kit and CD105 appeared in the interstitium at the 17th gestational week and persisted in the postnatal age, and that the Isl-1 positive cells were a subset of the c-Kit positive population.

  16. Characterization of Yellow Fever Virus Infection of Human and Non-human Primate Antigen Presenting Cells and Their Interaction with CD4+ T Cells.

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    Yu Cong

    2016-05-01

    Full Text Available Humans infected with yellow fever virus (YFV, a mosquito-borne flavivirus, can develop illness ranging from a mild febrile disease to hemorrhagic fever and death. The 17D vaccine strain of YFV was developed in the 1930s, has been used continuously since development and has proven very effective. Genetic differences between vaccine and wild-type viruses are few, yet viral or host mechanisms associated with protection or disease are not fully understood. Over the past 20 years, a number of cases of vaccine-associated disease have been identified following vaccination with 17D; these cases have been correlated with reduced immune status at the time of vaccination. Recently, several studies have evaluated T cell responses to vaccination in both humans and non-human primates, but none have evaluated the response to wild-type virus infection. In the studies described here, monocyte-derived macrophages (MDM and dendritic cells (MoDC from both humans and rhesus macaques were evaluated for their ability to support infection with either wild-type Asibi virus or the 17D vaccine strain and the host cytokine and chemokine response characterized. Human MoDC and MDM were also evaluated for their ability to stimulate CD4+ T cells. It was found that MoDC and MDM supported viral replication and that there were differential cytokine responses to infection with either wild-type or vaccine viruses. Additionally, MoDCs infected with live 17D virus were able to stimulate IFN-γ and IL-2 production in CD4+ T cells, while cells infected with Asibi virus were not. These data demonstrate that wild-type and vaccine YFV stimulate different responses in target antigen presenting cells and that wild-type YFV can inhibit MoDC activation of CD4+ T cells, a critical component in development of protective immunity. These data provide initial, but critical insight into regulatory capabilities of wild-type YFV in development of disease.

  17. A Neoglycoconjugate Containing the Human Milk Sugar LNFPIII Drives Anti-Inflammatory Activation of Antigen Presenting Cells in a CD14 Dependent Pathway.

    Directory of Open Access Journals (Sweden)

    Smanla Tundup

    Full Text Available The milk pentasaccharide LNFPIII has therapeutic action for metabolic and autoimmune diseases and prolongs transplant survival in mice when presented as a neoglycoconjugate. Within LNFPIII is the Lewisx trisaccharide, expressed by many helminth parasites. In humans, LNFPIII is found in human milk and also known as stage-specific embryonic antigen-1. LNFPIII-NGC drives alternative activation of macrophages and dendritic cells via NFκB activation in a TLR4 dependent mechanism. However, the connection between LNFPIII-NGC activation of APCs, TLR4 signaling and subsequent MAP kinase signaling leading to anti-inflammatory activation of APCs remains unknown. In this study we determined that the innate receptor CD14 was essential for LNFPIII-NGC induction of both ERK and NFkB activation in APCs. Induction of ERK activation by LNFPIII-NGC was completely dependent on CD14/TLR4-Ras-Raf1/TPL2-MEK axis in bone marrow derived dendritic cells (BMDCs. In addition, LNFPIII-NGC preferentially induced the production of Th2 "favoring" chemokines CCL22 and matrix metalloprotease protein-9 in a CD14 dependent manner in BMDCs. In contrast, LNFPIII-NGC induces significantly lower levels of Th1 "favoring" chemokines, MIP1α, MIP1β and MIP-2 compared to levels in LPS stimulated cells. Interestingly, NGC of the identical human milk sugar LNnT, minus the alpha 1-3 linked fucose, failed to activate APCs via TLR4/MD2/CD14 receptor complex, suggesting that the alpha 1-3 linked fucose in LNFPIII and not on LNnT, is required for this process. Using specific chemical inhibitors of the MAPK pathway, we found that LNFPIII-NGC induction of CCL22, MMP9 and IL-10 production was dependent on ERK activation. Over all, this study suggests that LNFPIII-NGC utilizes CD14/TLR4-MAPK (ERK axis in modulating APC activation to produce anti-inflammatory chemokines and cytokines in a manner distinct from that seen for the pro-inflammatory PAMP LPS. These pathways may explain the in vivo

  18. Foetal dosimetry--is the ICRP dosimetric system for humans now complete?

    Energy Technology Data Exchange (ETDEWEB)

    Jones, Steve [Westlakes Research Institute, Cumbria (United Kingdom)

    2002-03-01

    data for the foetus should be interpreted. Both Stather et al and ICRP-88 emphasise that the data on the radiosensitivity of the foetus, and the relative radiosensitivity of organs within the foetus, are very sparse. The new data permit the calculation of equivalent dose to the foetus and its internal organs for various exposure scenarios and for a number of stages during its development, but to convert equivalent doses into effective doses, values of tissue weighting factors are required. This is potentially a complex problem, as both the absolute and relative radiosensitivities of foetal tissues are likely to change during development; ICRP-88 pragmatically uses 'conventional' tissue weighting factors [6] whilst acknowledging the uncertainty involved. Questions also arise as to the timing of dose delivery; the dose coefficients presented in ICRP-88 are the committed doses to the foetus incurred both during development and after birth, so for long-lived nuclides (abstract truncated)

  19. Phthalate-Induced Pathology in the Foetal Testis Involves More Than Decreased Testosterone Production

    Science.gov (United States)

    Foetal exposure to phthalates is known to adversely impact male reproductive development and function. Developmental anomalies of reproductive tract have been attributed to impaired testosterone synthesis. However, species differences in the ability to produce testosterone have...

  20. Epigenetic features of testicular germ cell tumours in relation to epigenetic characteristics of foetal germ cells

    DEFF Research Database (Denmark)

    Kristensen, Dina Graae; Skakkebæk, Niels E; Rajpert-De Meyts, Ewa

    2013-01-01

    in humans. However, the common precursor of testicular cancers- the carcinoma in situ (CIS) cell- is thought to be an arrested foetal germ cell. Therefore studies of CIS cells may leverage information on human foetal germ cell development and, in particular, when neoplastic transformation is initiated....... In this review, we will focus on current knowledge of the epigenetics of CIS cells and relate it to the epigenetic changes occurring in early developing germ cells of mice during specification, migration and colonization. We will focus on DNA methylation and some of the best studied histone modifications like H3...... event in the initiation of testicular germ cell cancer. Even though only sparse information is available on epigenetic cues in human foetal germ cells, these indicate that the developmental patterns differ from the findings in mice and emphasize the need for further studies of foetal germ cell...

  1. NON-INVASIVE MONITORING OF FOETAL ANAEMIA IN KELL SENSITIZED PREGNANCY.

    Science.gov (United States)

    Memon, Zaibunnisa; Sheikh, Sana Sadiq

    2015-01-01

    We report a case of Kell sensitized pregnancy with good neonatal outcome. Anti-K antibodies were detected in maternal serum in early pregnancy as a part of routine antibody screening test. The middle cerebral artery doppler monitoring and serial titers were carried out to screen for foetal anaemia. Despite of rising antibody titers, serial middle cerebral artery doppler was normal and did not showed foetal anaemia. The pregnancy was carried out till term and patient delivered at 37 weeks of pregnancy with no evidence of foetal anaemia. This case underlines the need of general screening on rare antibodies in all pregnant women and that non-invasive monitoring of foetal anaemia can be done with anti-k titers and middle cerebral artery Doppler.

  2. CD80 and CD86 Costimulatory Molecules Differentially Regulate OT-II CD4+ T Lymphocyte Proliferation and Cytokine Response in Cocultures with Antigen-Presenting Cells Derived from Pregnant and Pseudopregnant Mice

    Directory of Open Access Journals (Sweden)

    Tomasz Maj

    2014-01-01

    Full Text Available Immune phenomena during the preimplantation period of pregnancy are poorly understood. The aim of our study was to assess the capacity for antigen presentation of splenic antigen-presenting cells (APCs derived from pregnant and pseudopregnant mice in in vitro conditions. Therefore, sorted CD11c+ dendritic cells and macrophages F4/80+ and CD11b+ presenting ovalbumin (OVA were cocultured with CD4+ T cells derived from OT-II mice’s (C57BL6/J-Tg(TcraTcrb1100Mjb/J spleen. After 132 hours of cell culture, proliferation of lymphocytes (ELISA-BrdU, activation of these cells (flow cytometry, cytokine profile (ELISA, and influence of costimulatory molecules blocking on these parameters were measured. We did not detect any differences in regulation of Th1/Th2 cytokine balance. CD86 seems to be the main costimulatory molecule involved in the proliferation response but CD80 is the main costimulatory molecule influencing cytokine secretion in pregnant mice. In conclusion, this study showed that CD80 and CD86 costimulatory molecules regulate OT-II CD4+ T lymphocyte proliferation and cytokine response in cocultures with antigen-presenting cells derived from pregnant and pseudopregnant mice. The implications of these changes still remain unclear.

  3. Effects of gestational and pregestational diabetes mellitus on the foetal heart: a cross-sectional study.

    Science.gov (United States)

    Dervisoglu, Pinar; Kosecik, Mustafa; Kumbasar, Serkan

    2018-04-01

    We examined the foetal cardiac structural and functional characteristics in diabetic pregnancies versus non-diabetic, healthy pregnancies. Between August 2015 and April 2016, 32 pregnant women with pregestational diabetes, 36 pregnant women with gestational diabetes, and 42 healthy pregnant women were scheduled to have foetal echocardiograms to assess cardiac structure and function. In the diabetic groups, the foetal interventricular septum (IVS) thickness was significantly greater than in non-diabetics (p 2 SD from normal. The peak velocity of tricuspid E, and the E/A ratio were significantly lower in the diabetic groups (p diabetic group than in the control group (p  .05). Interventricular septal hypertrophy is the most common structural abnormality in diabetic pregnancies. These changes do not pose a risk to the foetal unless they cause functional impairment. Thus, we believe that it is important for diabetic pregnant women to be monitored for foetal cardiac diastolic dysfunction. Impact statement What is already known on this subject? Pregestational insulin-dependent diabetes mellitus is a relatively common condition in pregnancy, affecting up to 0.5% of the pregnant population. Foetuses of diabetic mothers are at an increased risk of perinatal morbidity and death. Gestational diabetes mellitus is under-recognised and affects up to 4% of pregnancies. Although diabetes mellitus is known to increase the risk of cardiovascular defects and structural changes (myocardial hypertrophy and diastolic dysfunction) due to foetal hyperglycaemia and hyperinsulinism, similar data in women with gestational diabetes is scarce. Moreover, the effect of maternal hyperglycaemia on foetal cardiac structure and function is unclear because of discordant results from previous studies. What do the results of this study add? In this study, we have used foetal echocardiography, two-dimensional US, pulsed wave Doppler and TDI to characterise the foetal cardiac structure and

  4. Symptoms, medical course and procedures in foetal alcohol syndrome

    Directory of Open Access Journals (Sweden)

    Agata Horecka-Lewitowicz

    2013-08-01

    Full Text Available The effects of alcohol consumption by a pregnant woman are irreversible. Developing organs are damaged in children subject to prenatal alcohol exposure; the central nervous system is the most exposed to the toxic effects of alcohol. The type and extent of the damage in the foetus depends, among others, on the amount of consumed alcohol, the time span during which it is consumed, the stage of development of the foetus, as well as the state of health and the degree of nutrition of the pregnant woman. Characteristic symptoms, which are results of the teratogenic effects of alcohol in foetal life, can be observed in subsequent phases of the child’s development. Apart from the somatic changes (especially the characteristic facial appearance and short stature, one may observe disorders in functioning at school, among peers and in the family. Early diagnosis (until the age of 6, the environment in which the child develops, undertaking a therapy adjusted to the capabilities of the patient and the family, adjusting requirements at school and including the whole family in the therapy are significant factors which influence further functioning of the child.

  5. Hepatitis B virus induces IL-23 production in antigen presenting cells and causes liver damage via the IL-23/IL-17 axis.

    Directory of Open Access Journals (Sweden)

    Qinghong Wang

    Full Text Available IL-23 regulates myriad processes in the innate and adaptive immune systems, and is a critical mediator of the proinflammatory effects exerted by Th17 cells in many diseases. In this study, we investigated whether and how hepatitis B virus (HBV causes liver damage directly through the IL-23 signaling pathway. In biopsied liver tissues from HBV-infected patients, expression of both IL-23 and IL-23R was remarkably elevated. In vivo observations also indicated that the main sources of IL-23 were myeloid dendritic cells (mDCs and macrophages. Analysis of in vitro differentiated immature DCs and macrophages isolated from healthy donors revealed that the HBV surface antigen (HBsAg efficiently induces IL-23 secretion in a mannose receptor (MR-dependent manner. Culture with an endosomal acidification inhibitor and the dynamin inhibitor showed that, upon binding to the MR, the HBsAg is taken up by mDCs and macrophages through an endocytosis mechanism. In contrast, although the HBV core antigen (HBcAg can also stimulate IL-23 secretion from mDCs, the process was MR- and endocytosis-independent. In addition, IL-23 was shown to be indispensible for HBsAg-stimulated differentiation of naïve CD4(+ T cells into Th17 cells, which were determined to be the primary source of IL-17 in HBV-infected livers. The cognate receptor, IL-17R, was found to exist on the hepatic stellate cells and mDCs, both of which might represent the potential target cells of IL-17 in hepatitis B disease. These data provide novel insights into a yet unrecognized mechanism of HBV-induced hepatitis, by which increases in IL-23 expression, through an MR/endocytosis-dependent or -independent manner, produce liver damage through the IL-23/IL-17 axis.

  6. Immunochromatographic antigen testing alone is sufficient to identify asymptomatic refugees at risk of severe malaria presenting to a single health service in Victoria.

    Science.gov (United States)

    Fedele, Pasquale L; Wheeler, Michael; Lemoh, Christopher; Chunilal, Sanjeev

    2014-10-01

    Current screening guidelines for malaria in new refugees include a combination of thick and thin film examination and immunochromatographic antigen test (ICT). However, as the prevalence of malaria in our population has decreased due to changing refugee demographics, we sought to determine if an ICT alone can reliably exclude malaria in our asymptomatic refugee population.A retrospective analysis was conducted of all investigations for malaria performed from 1 August 2011 to 31 July 2013, including thick and thin blood film examination, BinaxNOW ICT, and external morphological and polymerase chain reaction (PCR) validation where applicable.Malaria was diagnosed in 45 of 1248 (3.6%) patients investigated, all of whom were symptomatic and the majority (71.1%) returned travellers. All 599 asymptomatic refugees screened were negative. Overall, 42 of 45 malaria cases were detected by the ICT; sensitivity 93.3% (95% CI 80.7-98.3%) and negative predictive value (NPV) 99.8% (99.2-99.9%). All 21 cases of Plasmodium falciparum and 20 of 22 cases of Plasmodium vivax were detected, giving a sensitivity of 100% (80.8-100%) and 90.9% (69.4-98.4%) respectively. Too few cases of Plasmodium malariae and no cases of Plasmodium ovale or Plasmodium knowlesi were diagnosed for adequate assessment to be carried out.These data suggest that full malaria screening in all asymptomatic refugees with the combination of thick and thin blood films and rapid antigen test may not be warranted. Alternative screening approaches should be considered, including the use of ICT alone, or limiting screening of asymptomatic refugees to only those originating from countries with high incidence of malaria.

  7. High resolution post-mortem MRI of non-fixed in situ foetal brain in the second trimester of gestation. Normal foetal brain development

    Energy Technology Data Exchange (ETDEWEB)

    Scola, Elisa; Palumbo, Giovanni; Avignone, Sabrina; Cinnante, Claudia Maria [Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Neuroradiology Unit, Milan (Italy); Conte, Giorgio [Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Neuroradiology Unit, Milan (Italy); Universita degli Studi di Milano, Postgraduation School in Radiodiagnostics, Milan (Italy); Boito, Simona; Persico, Nicola [Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Department of Obstetrics and Gynaecology ' L. Mangiagalli' , Milan (Italy); Rizzuti, Tommaso [Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Pathology Unit, Milan (Italy); Triulzi, Fabio [Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Neuroradiology Unit, Milan (Italy); Universita degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan (Italy)

    2018-01-15

    To describe normal foetal brain development with high resolution post-mortem MRI (PMMRI) of non-fixed foetal brains. We retrospectively collected PMMRIs of foetuses without intracranial abnormalities and chromosomal aberrations studied after a termination of pregnancy due to extracranial abnormalities or after a spontaneous intrauterine death. PMMRIs were performed on a 3-T scanner without any fixation and without removing the brain from the skull. All PMMRIs were evaluated in consensus by two neuroradiologists. Our analysis included ten PMMRIs (median gestational age (GA): 21 weeks; range: 17-28 weeks). At 19 and 20 weeks of GA, the corticospinal tracts are recognisable in the medulla oblongata, becoming less visible from 21 weeks. Prior to 20 weeks the posterior limb of the internal capsule (PLIC) is more hypointense than surrounding deep grey nuclei; starting from 21 weeks the PLIC becomes isointense, and is hyperintense at 28 weeks. From 19-22 weeks, the cerebral hemispheres show transient layers: marginal zone, cortical plate, subplate, and intermediate, subventricular and germinal zones. PMMRI of non-fixed in situ foetal brains preserves the natural tissue contrast and skull integrity. We assessed foetal brain development in a small cohort of foetuses, focusing on 19-22 weeks of gestation. (orig.)

  8. High resolution post-mortem MRI of non-fixed in situ foetal brain in the second trimester of gestation. Normal foetal brain development

    International Nuclear Information System (INIS)

    Scola, Elisa; Palumbo, Giovanni; Avignone, Sabrina; Cinnante, Claudia Maria; Conte, Giorgio; Boito, Simona; Persico, Nicola; Rizzuti, Tommaso; Triulzi, Fabio

    2018-01-01

    To describe normal foetal brain development with high resolution post-mortem MRI (PMMRI) of non-fixed foetal brains. We retrospectively collected PMMRIs of foetuses without intracranial abnormalities and chromosomal aberrations studied after a termination of pregnancy due to extracranial abnormalities or after a spontaneous intrauterine death. PMMRIs were performed on a 3-T scanner without any fixation and without removing the brain from the skull. All PMMRIs were evaluated in consensus by two neuroradiologists. Our analysis included ten PMMRIs (median gestational age (GA): 21 weeks; range: 17-28 weeks). At 19 and 20 weeks of GA, the corticospinal tracts are recognisable in the medulla oblongata, becoming less visible from 21 weeks. Prior to 20 weeks the posterior limb of the internal capsule (PLIC) is more hypointense than surrounding deep grey nuclei; starting from 21 weeks the PLIC becomes isointense, and is hyperintense at 28 weeks. From 19-22 weeks, the cerebral hemispheres show transient layers: marginal zone, cortical plate, subplate, and intermediate, subventricular and germinal zones. PMMRI of non-fixed in situ foetal brains preserves the natural tissue contrast and skull integrity. We assessed foetal brain development in a small cohort of foetuses, focusing on 19-22 weeks of gestation. (orig.)

  9. Foetal haemoglobin and disease severity in sickle cell anaemia patients in Kampala, Uganda

    Directory of Open Access Journals (Sweden)

    Mpalampa Lena

    2012-09-01

    Full Text Available Abstract Background Sickle cell anaemia (SCA is a major chronic health problem in Uganda. In patients with SCA, the level of foetal haemoglobin (HbF has been found to be important in influencing the clinical course of the disease. Thus populations with high levels of HbF like those in Saudi Arabia have been described as having a milder clinical course with fewer complications as compared to populations with lower levels. Disease modifying drugs can increase the Hb F levels and modify the presentation of SCA. Methods This was a cross sectional study in which we determined foetal haemoglobin levels and examined the relationship between HbF levels and disease severity in SCA patients in Mulago Hospital, Kampala, Uganda. We consecutively enrolled 216 children aged 1 year to 18 years with SCA attending the Sickle Cell Clinic at Mulago Hospital whose guardians had given consent. The history included age at onset of initial symptoms and diagnosis, number of hospitalisations and blood transfusions and other complications of SCA (cardiovascular accidents, avascular hip necrosis and priapism. A detailed physical examination was performed to assess the current state and help describe the disease severity for each patient. Blood samples were drawn for HbF levels. HbF levels ≥10% was defined as high. Results Of the 216 children, (80 37% had HbF levels ≥10%. Significant correlations were observed between HbF level and several clinical parameters independent of age including age at diagnosis (p value 0.013, number of hospitalisations (p value 0.024 and transfusions (p value 0.018 since birth. Conclusion A third of the children with SCA attending the Sickle cell clinic in Mulago Hospital have high HbF levels. Higher HbF level is associated with later onset of symptoms and presentation, and less severe disease characterised by fewer hospitalisations and blood transfusions. We suggest HbF levels should be determined at initial contact for patients with SCA to

  10. Interleukin-19: a constituent of the regulome that controls antigen presenting cells in the lungs and airway responses to microbial products.

    Directory of Open Access Journals (Sweden)

    Carol Hoffman

    Full Text Available Interleukin (IL-19 has been reported to enhance chronic inflammatory diseases such as asthma but the in vivo mechanism is incompletely understood. Because IL-19 is produced by and regulates cells of the monocyte lineage, our studies focused on in vivo responses of CD11c positive (CD11c+ alveolar macrophages and lung dendritic cells.IL-19-deficient (IL-19-/- mice were studied at baseline (naïve and following intranasal challenge with microbial products, or recombinant cytokines. Naïve IL-19-/- mixed background mice had a decreased percentage of CD11c+ cells in the bronchoalveolar-lavage (BAL due to the deficiency in IL-19 and a trait inherited from the 129-mouse strain. BAL CD11c+ cells from fully backcrossed IL-19-/- BALB/c or C57BL/6 mice expressed significantly less Major Histocompatibility Complex class II (MHCII in response to intranasal administration of lipopolysaccharide, Aspergillus antigen, or IL-13, a pro-allergic cytokine. Neurogenic-locus-notch-homolog-protein-2 (Notch2 expression by lung monocytes, the precursors of BAL CD11c+ cells, was dysregulated: extracellular Notch2 was significantly decreased, transmembrane/intracellular Notch2 was significantly increased in IL-19-/- mice relative to wild type. Instillation of recombinant IL-19 increased extracellular Notch2 expression and dendritic cells cultured from bone marrow cells in the presence of IL-19 showed upregulated extracellular Notch2. The CD205 positive subset among the CD11c+ cells was 3-5-fold decreased in the airways and lungs of naïve IL-19-/- mice relative to wild type. Airway inflammation and histological changes in the lungs were ameliorated in IL-19-/- mice challenged with Aspergillus antigen that induces T lymphocyte-dependent allergic inflammation but not in IL-19-/- mice challenged with lipopolysaccharide or IL-13.Because MHCII is the molecular platform that displays peptides to T lymphocytes and Notch2 determines cell fate decisions, our studies suggest that

  11. Incidental detection of prostate-specific antigen-negative metastatic prostate cancer initially presented with solitary pulmonary nodule on fluorodeoxyglucose positron emission tomography/computed tomography

    International Nuclear Information System (INIS)

    Erdogan, Ezgi Basak; Buyukpinarbasili, Nur; Ziyade, Sedat; Akman, Tolga; Turk, Haci Mehmet; Aydin, Mehmet

    2005-01-01

    A 71-year-old male patient with solitary pulmonary nodule underwent fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) showing slightly increased FDG uptake in this nodule. In addition, PET/CT detected hypermetabolic sclerotic bone lesions in the right second rib and 7 th thoracic vertebrae, which were interpreted as possible metastases, and mildly increased FDG uptake in the prostate gland highly suspicious of malignancy. The patient's prostate-specific antigen (PSA) level was within normal range (3.8 ng/dL). The histopathological examination of the lung nodule and right second rib lesion proved metastases from prostate cancer, then the prostate biopsy-confirmed prostate adenocarcinoma. The unique feature of this case is to emphasize the importance of performing PET/CT for solitary pulmonary nodule in detecting PSA-negative metastatic prostate cancer. This case indicated that it should be kept in mind that, even if the PSA is negative, a lung metastasis of prostate cancer may be an underlying cause in patients evaluated for solitary pulmonary nodule by FDG PET/CT

  12. Smoking, physical exercise, BMI and late foetal death: a study within the Danish National Birth Cohort.

    Science.gov (United States)

    Morales-Suárez-Varela, Maria; Nohr, Ellen A; Bech, Bodil H; Wu, Chunsen; Olsen, Jørn

    2016-10-01

    The aim of this paper was to estimate the effect of maternal and paternal smoking on foetal death (miscarriage and stillbirth) and to estimate potential interactions with physical exercise and pre-pregnancy body mass index. We selected 87,930 pregnancies from the population-based Danish National Birth Cohort. Information about lifestyle, occupational, medical and obstetric factors was obtained from a telephone interview and data on pregnancy outcomes came from the Danish population based registries. Cox regression was used to estimate the hazard ratios (adjusted for potential confounders) for predominantly late foetal death (miscarriage and stillbirth). An interaction contrast ratio was used to assess potential effect measure modification of smoking by physical exercise and body mass index. The adjusted hazard ratio of foetal death was 1.22 (95 % CI 1.02-1.46) for couples where both parents smoked compared to non-smoking parents (miscarriage: 1.18, 95 % CI 0.96-1.44; stillbirth: 1.32, 95 % CI 0.93-1.89). On the additive scale, we detected a small positive interaction for stillbirth between smoking and body mass index (overweight women). In conclusion, smoking during pregnancy was associated with a slightly higher hazard ratio for foetal death if both parents smoked. This study suggests that smoking may increase the negative effect of a high BMI on foetal death, but results were not statistically significant for the interaction between smoking and physical exercise.

  13. Early Effects of Lipopolysaccharide-Induced Inflammation on Foetal Brain Development in Rat

    Directory of Open Access Journals (Sweden)

    Cristina A Ghiani

    2011-10-01

    Full Text Available Studies in humans and animal models link maternal infection and imbalanced levels of inflammatory mediators in the foetal brain to the aetiology of neuropsychiatric disorders. In a number of animal models, it was shown that exposure to viral or bacterial agents during a period that corresponds to the second trimester in human gestation triggers brain and behavioural abnormalities in the offspring. However, little is known about the early cellular and molecular events elicited by inflammation in the foetal brain shortly after maternal infection has occurred. In this study, maternal infection was mimicked by two consecutive intraperitoneal injections of 200 μg of LPS (lipopolysaccharide/kg to timed-pregnant rats at GD15 (gestational day 15 and GD16. Increased thickness of the CP (cortical plate and hippocampus together with abnormal distribution of immature neuronal markers and decreased expression of markers for neural progenitors were observed in the LPS-exposed foetal forebrains at GD18. Such effects were accompanied by decreased levels of reelin and the radial glial marker GLAST (glial glutamate transporter, and elevated levels of pro-inflammatory cytokines in maternal serum and foetal forebrains. Foetal inflammation elicited by maternal injections of LPS has discrete detrimental effects on brain development. The early biochemical and morphological changes described in this work begin to explain the sequelae of early events that underlie the neurobehavioural deficits reported in humans and animals exposed to prenatal insults.

  14. Foetal trauma, body memory and early infant communication: a case illustration.

    Science.gov (United States)

    Merchant, John

    2015-11-01

    This paper presents the complex case of a male patient who started life as an unwanted pregnancy and adoptee in an era of socio-cultural shame and blame. When able to contact his birth mother later in life, he experienced a number of confronting synchronicities as well as visions which he felt were related to failed abortion attempts and to other pre- and post-natal events. The case material lends weight not only to Freud's, Ehrenwald's and FitzHerbert's assertions that the earliest form of mother-infant communications is telepathic in nature but that this mode of communication can be retained if emotional trauma inhibits normal developmental processes. Contemporary neuroscience research is presented supporting the hypothesis that emotional memory can become imbedded in the psyche/soma of the foetus. Such memory traces can later emerge into imagery and/or words if the traumatic impingement has been substantial enough and if other defensive strategies are in place. Clinical implications are then suggested regarding analysts' attention to the emotional conditions underpinning their patients' conceptions and foetal development; the connection to projective identification components of the countertransference as being aspects of the earliest telepathic mother/infant communication channel and the need for reductive analyses in analyst training programmes. © 2015, The Society of Analytical Psychology.

  15. Morphogenesis of the rhea (Rhea americana respiratory system in different embryonic and foetal stages

    Directory of Open Access Journals (Sweden)

    Renata P. Sousa

    Full Text Available ABSTRACT: The rhea (Rhea americana is an important wild species that has been highlighted in national and international livestock. This research aims to analyse embryo-foetal development in different phases of the respiratory system of rheas. Twenty-three embryos and foetuses were euthanized, fixed and dissected. Fragments of the respiratory system, including the nasal cavity, larynx, trachea, syrinx, bronchi and lungs, were collected and processed for studies using light and scanning electron microscopy. The nasal cavity presented cubic epithelium in the early stages of development. The larynx exhibited typical respiratory epithelium between 27 and 31 days. The trachea showed early formation of hyaline cartilage after 15 days. Syrinx in the mucous membrane of 18-day foetuses consisted of ciliated epithelium in the bronchial region. The main bronchi had ciliated epithelium with goblet cells in the syringeal region. In the lung, the parabronchial stage presented numerous parabronchi between 15 and 21 days. This study allowed the identification of normal events that occur during the development of the rhea respiratory system, an important model that has not previously been described. The information generated here will be useful for the diagnosis of pathologies that affect this organic system, aimed at improving captive production systems.

  16. Foetal death in utero: detection on 99Tc-labelled leucocytoscintigraphy

    International Nuclear Information System (INIS)

    MsGennisken, M.R.; Salehi, N.; Jenkins, B.; Better, N.

    1998-01-01

    Full text: We present the case of a 26-year-old female from Nauru who presented with recent intermittent fever and vague abdominal pain, which had persisted despite antibiotics. Past history included aplastic anaemia and neutropenia. Ultrasound was not helpful and a labelled white blood cell scan was then organised. The patient''s white blood cells were labelled with 99 mTc tin colloid by the standard in vitro technique and whole body imaging as well as SPECT imaging of the abdomen was performed at five hours on a Siemen''s triple-headed camera. The study demonstrated increased white cell concentration on the right side of the pelvis anteriorly. Subsequent computed tomographic correlation suggested the uterus and right ovary as a potential source of infection. A gynaecological opinion was sought, and dilatation and curettage performed. This revealed infected foetal products. Following the curette and intravenous antibiotics, the patient''s health improved. The patient had denied pregnancy prior to the study. In retrospect, she confirmed irregular menstrual blood loss and weight gain over several months

  17. Foetal death in utero: detection on {sup 99}Tc-labelled leucocytoscintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    MsGennisken, M.R.; Salehi, N.; Jenkins, B.; Better, N. [Royal Melbourne Hospital, Parkville, VIC, (Australia). Department of Nuclear Medicine

    1998-03-01

    Full text: We present the case of a 26-year-old female from Nauru who presented with recent intermittent fever and vague abdominal pain, which had persisted despite antibiotics. Past history included aplastic anaemia and neutropenia. Ultrasound was not helpful and a labelled white blood cell scan was then organised. The patient``s white blood cells were labelled with {sup 99}mTc tin colloid by the standard in vitro technique and whole body imaging as well as SPECT imaging of the abdomen was performed at five hours on a Siemen``s triple-headed camera. The study demonstrated increased white cell concentration on the right side of the pelvis anteriorly. Subsequent computed tomographic correlation suggested the uterus and right ovary as a potential source of infection. A gynaecological opinion was sought, and dilatation and curettage performed. This revealed infected foetal products. Following the curette and intravenous antibiotics, the patient``s health improved. The patient had denied pregnancy prior to the study. In retrospect, she confirmed irregular menstrual blood loss and weight gain over several months.

  18. Luteolin-7-O-Glucoside Present in Lettuce Extracts Inhibits Hepatitis B Surface Antigen Production and Viral Replication by Human Hepatoma Cells in Vitro

    Directory of Open Access Journals (Sweden)

    Xiao-Xian Cui

    2017-12-01

    Full Text Available Hepatitis B virus (HBV infection is endemic in Asia and chronic hepatitis B (CHB is a major public health issue worldwide. Current treatment strategies for CHB are not satisfactory as they induce a low rate of hepatitis B surface antigen (HBsAg loss. Extracts were prepared from lettuce hydroponically cultivated in solutions containing glycine or nitrate as nitrogen sources. The lettuce extracts exerted potent anti-HBV effects in HepG2 cell lines in vitro, including significant HBsAg inhibition, HBV replication and transcription inhibition, without exerting cytotoxic effects. When used in combination interferon-alpha 2b (IFNα-2b or lamivudine (3TC, the lettuce extracts synergistically inhibited HBsAg expression and HBV replication. By using differential metabolomics analysis, Luteolin-7-O-glucoside was identified and confirmed as a functional component of the lettuce extracts and exhibited similar anti-HBV activity as the lettuce extracts in vitro. The inhibition rate on HBsAg was up to 77.4%. Moreover, both the lettuce extracts and luteolin-7-O-glucoside functioned as organic antioxidants and, significantly attenuated HBV-induced intracellular reactive oxygen species (ROS accumulation. Luteolin-7-O-glucoside also normalized ROS-induced mitochondrial membrane potential damage, which suggests luteolin-7-O-glucoside inhibits HBsAg and HBV replication via a mechanism involving the mitochondria. Our findings suggest luteolin-7-O-glucoside may have potential value for clinical application in CHB and may enhance HBsAg and HBV clearance when used as a combination therapy.

  19. Contribution to the study of embryo-foetal risks due to radiodiagnosis

    International Nuclear Information System (INIS)

    Vibert, M.-R.

    1976-01-01

    During the last few years appreciable numbers of women have undergone pelvic irradiations for diagnostic reasons at the start of an unsuspected pregnancy. In such cases opinions on the danger of radiations are often extremely divergent: - for some authors no danger exists at the doses used for radiodiagnosis and the pregnancy need never be terminated; - for others on the contrary the risk of malformation is not negligible and should lead to systematic therapeutic abortion. These over-categorically opposed attitudes motivated the present work. The aim is to estimate the embryo-foetal risks, especially as a function of the radiation dose given by dosimetry, but also to warm radiologists of the harm they may cause to a foetus when they irradiate the pelvis of a women of child-bearing age without accounting for the date of her latest period, hence a possible pregnancy. The conclusions to emerge from this work should always be interpreted with two important facts in mind: - One concerns the evaluation of irradiation. Dosimetry is not an exact measurement but only an indication, often underestimated, of the dose actually received and since the existence of a threshold dose has not been proved this evaluation must be considered with caution. - The other concerns the effect of this irradiation on the unborn child, about which little is known [fr

  20. Detection and identification of the atypical bovine pestiviruses in commercial foetal bovine serum batches.

    Directory of Open Access Journals (Sweden)

    Hongyan Xia

    Full Text Available The recently emerging atypical bovine pestiviruses have been detected in commercial foetal bovine serum (FBS of mainly South American origin so far. It is unclear how widely the viruses are presented in commercial FBS of different geographic origins. To further investigate the possible pestivirus contamination of commercially available FBS batches, 33 batches of FBS were obtained from ten suppliers and analysed in this study for the presence of both the recognised and the atypical bovine pestiviruses. All 33 batches of FBS were positive by real-time RT-PCR assays for at least one species of bovine pestiviruses. According to the certificate of analysis that the suppliers claimed for each batch of FBS, BVDV-1 was detected in all 11 countries and BVDV-2 was detected exclusively in the America Continent. The atypical pestiviruses were detected in 13 batches claimed to originate from five countries. Analysis of partial 5'UTR sequences showed a high similarity among these atypical bovine pestiviruses. This study has demonstrated, for the first time that commercial FBS batches of different geographic origins are contaminated not only with the recognised species BVDV-1 and BVDV-2, but also with the emerging atypical bovine pestiviruses.

  1. Structure of neuro-endocrine and neuro-epithelial interactions in human foetal pancreas.

    Science.gov (United States)

    Krivova, Yuliya; Proshchina, Alexandra; Barabanov, Valeriy; Leonova, Olga; Saveliev, Sergey

    2016-12-01

    In the pancreas of many mammals including humans, endocrine islet cells can be integrated with the nervous system components into neuro-insular complexes. The mechanism of the formation of such complexes is not clearly understood. The present study evaluated the interactions between the nervous system components, epithelial cells and endocrine cells in the human pancreas. Foetal pancreas, gestational age 19-23 weeks (13 cases) and 30-34 weeks (7 cases), were studied using double immunohistochemical labeling with neural markers (S100 protein and beta III tubulin), epithelial marker (cytokeratin 19 (CK19)) and antibodies to insulin and glucagon. We first analyse the structure of neuro-insular complexes using confocal microscopy and provide immunohistochemical evidences of the presence of endocrine cells within the ganglia or inside the nerve bundles. We showed that the nervous system components contact with the epithelial cells located in ducts or in clusters outside the ductal epithelium and form complexes with separate epithelial cells. We observed CK19-positive cells inside the ganglia and nerve bundles which were located separately or were integrated with the islets. Therefore, we conclude that neuro-insular complexes may forms as a result of integration between epithelial cells and nervous system components at the initial stages of islets formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Metabolism of [14C] testosterone by human foetal and brain tissue

    International Nuclear Information System (INIS)

    Jenkins, J.S.; Hall, C.J.

    1977-01-01

    The metabolism of [ 14 C] testosterone in vitro by various areas of the human foetal brain has been studied and compared with that of an adult brain. The predominant metabolites were 5α-dihydrotestosterone and 5α-androstane-3α,17β-diol, and also androstenedione, and all areas of the foetal brain showed similar activity. In the foetal pituitary gland, the activity of 5α-reductase was less prominent than that of 17β-hydroxysteroid-dehydrogenase. Small quantities of oestradiol-17 β were produced from testosterone by the hypothalamus, temporal lobe and amygdala only, and no aromatization could be detected in the pituitary gland. 5α-Reductase activity was much lower in adult brain tissues and no oestradiol was identified in adult temporal lobe tissue. (author)

  3. Correlation among foetal number, corpora lutea and plasma progesterone in rockland-swiss mice. [Progesterone determination by radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Simon, N G; Bridges, R S; Gandelmann, R [Rutgers - the State Univ., New Brunswick. NJ (USA). Dept. of Psychology; Rutgers - the State Univ., Newark, NJ (USA). Inst. of Animal Behavior)

    1978-01-01

    The relationship among plasma progesterone, number of corpora lutea, and foetal number was assessed in Rockland-Swiss albino mice. While number of corpora lutea and foetal number were significantly correlated, neither was related to plasma progesterone level. This finding in the mouse is similar to results reported in the rabbit.

  4. Sex Differences in the Association between Foetal Growth and Child Attention at Age Four: Specific Vulnerability of Girls

    Science.gov (United States)

    Murray, Elizabeth; Matijasevich, Alicia; Santos, Iná S.; Barros, Aluísio J. D.; Anselmi, Luciana; Barros, Fernando C.; Stein, Alan

    2015-01-01

    Background: Recent evidence suggests that impaired foetal growth may provide an early indication of increased risk of child attention problems. However, despite both foetal growth and child attention problems differing by sex, few studies have examined sex differences in this association. Furthermore, no studies have been conducted in low- and…

  5. Are foetal ultrasonographic and maternal blood progesterone measurements near parturition reliable predictors of the time of birth in the domestic cat?

    Science.gov (United States)

    Keiser, R; Reichler, I M; Balogh, O

    2017-06-01

    In cats, accuracy of parturition day prediction by ultrasonographic measurement of foetal structures is decreasing towards the end of gestation. Foetal measurements during the last days of pregnancy are scarce. We determined foetal biparietal, abdominal and eye diameter (BPD, AD and ED, respectively) by ultrasonography as well as maternal blood progesterone (P4) within five days of delivery to predict parturition date and calculate accuracy of prediction. Foetal BPD at birth was compared with newborn kitten head diameter (HD). Kitten HD, crown-rump length (CRL) and body weight were compared by breed and gender. Ultrasonography measurements were carried out on the day of parturition in 14 queens, and on days 62-63 after the first mating and repeated 24-72 hr later in ten other cats. Accuracy of parturition day prediction using BPD and AD was determined based on the equations of Beccaglia et al. (2008) Veterinary Research Communications, 32(Suppl 1), S99 and Garcia Mitacek et al. (2015) Theriogenology, 84, 1131. Progesterone was measured at the time of presentation and repeated 24-72 hr later if parturition did not occur. Data were analysed with linear regression, t test, Mann-Whitney U test, one-way anova and Kruskal-Wallis test. There was a moderate relationship between BPD, days before birth (DBB) and litter size. AD and DBB had a low agreement, and ED was not associated with DBB. BPD at birth was significantly related to HD. The accuracy of parturition day prediction using BPD and AD was 27-53% and 17-35%, respectively. Kitten HD was associated with body weight, and both were inversely related to litter size. Newborn biometric measurements differed by breed but not by gender. Progesterone decreased towards parturition and reached 3.18 ± 1.68 ng/ml on the day of delivery. In conclusion, close to birth, the combination of foetal ultrasonography and maternal blood P4 rather than each as a sole predictor of parturition is recommended. © 2017 Blackwell Verlag

  6. Immunity to tumour antigens.

    Science.gov (United States)

    Li, Geng; Ali, Selman A; McArdle, Stephanie E B; Mian, Shahid; Ahmad, Murrium; Miles, Amanda; Rees, Robert C

    2005-01-01

    During the last decade, a large number of human tumour antigens have been identified. These antigens are classified as tumour-specific shared antigens, tissue-specific differentiation antigens, overexpressed antigens, tumour antigens resulting from mutations, viral antigens and fusion proteins. Antigens recognised by effectors of immune system are potential targets for antigen-specific cancer immunotherapy. However, most tumour antigens are self-proteins and are generally of low immunogenicity and the immune response elicited towards these tumour antigens is not always effective. Strategies to induce and enhance the tumour antigen-specific response are needed. This review will summarise the approaches to discovery of tumour antigens, the current status of tumour antigens, and their potential application to cancer treatment.

  7. [Face presentation: retrospective study of 32 cases at term].

    Science.gov (United States)

    Ducarme, G; Ceccaldi, P-F; Chesnoy, V; Robinet, G; Gabriel, R

    2006-05-01

    To determine the etiologic factors, circumstances of diagnosis, obstetrical management and complications of face presentation and to value the maternal and foetal prognosis of this presentation. Thirty-two cases of face presentation have been observed in the maternity wards of Reims and Troyes over the last 12 years. The incidence of face presentation was 0.7 per 1000 deliveries. Spontaneous vaginal delivery occurred with mento-anterior presentation 73% of the time and caesarean section was performed in 100% of mento-posterior presentation. There was no increasing rate of foetal or maternal mortality and morbidity with vaginal delivery. Face presentation is an unusual complication of pregnancy with obstetric factors that predispose the foetus to face presentation. The low foetal and maternal mortality and morbidity substantiate the effectiveness of conservative management in face presentation.

  8. Radioimmunoassays of hidden viral antigens

    International Nuclear Information System (INIS)

    Neurath, A.R.; Strick, N.; Baker, L.; Krugman, S.

    1982-01-01

    Antigens corresponding to infectious agents may be present in biological specimens only in a cryptic form bound to antibodies and, thus, may elude detection. We describe a solid-phase technique for separation of antigens from antibodies. Immune complexes are precipitated from serum by polyethylene glycol, dissociated with NaSCN, and adsorbed onto nitrocellulose or polystyrene supports. Antigens remain topographically separated from antibodies after removal of NaSCN and can be detected with radiolabeled antibodies. Genomes from viruses immobilized on nitrocellulose can be identified by nucleic acid hybridization. Nanogram quantities of sequestered hepatitis B surface and core antigens and picogram amounts of hepatitis B virus DNA were detected. Antibody-bound adenovirus, herpesvirus, and measles virus antigens were discerned by the procedure

  9. Materno-foetal outcome of labour in obese women in Yaounde ...

    African Journals Online (AJOL)

    The objectives of the study were to determine the socio-demographic characteristics of pregnant women with obesity and morbid obesity determine the mean birth weight, foetal length and Apgar score of the babies as well as associated maternal complications. This was a descriptive cross sectional prospective study ...

  10. Serum levels of antioxidant vitamins in foetal haemoglobin (HbF ...

    African Journals Online (AJOL)

    Background: sickle cell anaemia (SCA) is one of the commonest health problems of Nigerian children. Method: The serum levels of antioxidant vitamins A (retinol), C (ascorbic acid) and E (alpha-tocopherol) were determined in foetal haemogbobin persistent sickle cell anaemic (Hb SS + F), sickle cell anaemic (Hb SS) and ...

  11. Post-mortem MRI of the foetal spine and spinal cord

    International Nuclear Information System (INIS)

    Widjaja, E.; Whitby, E.H.; Cohen, M.; Paley, M.N.J.; Griffiths, P.D.

    2006-01-01

    Aims: To compare the findings of post-mortem magnetic resonance imaging (MRI) of the foetal spine with autopsy with a view to using post-mortem MRI as an alternative or adjunct to autopsy, particularly in foetal and neonatal cases. Materials and Methods: The brains and spines of 41 foetuses, with a gestational age range of 14-41 weeks, underwent post-mortem MRI before autopsy. Post-mortem MRI of the brain consisted of T2-weighted sequences in three orthogonal planes and MRI of the spine consisted of T2-weighted sequence in the sagittal and axial planes in all cases and coronal planes in selected cases. Results: Thirty of 41 (78%) foetal spines were found to be normal at autopsy and on post-mortem MRI. Eleven of 41 (22%) foetal spines were abnormal: eight foetuses had myelomeningocoeles and Chiari 2 deformities, one foetus had limited dorsal myeloschisis, one foetus had caudal regression syndrome, and one had diastematomyelia. The post-mortem MRI findings concurred with the autopsy findings in 10/11 of the abnormal cases, the disagreement being the case of diastematomyelia that was shown on post-mortem MRI but was not diagnosed at autopsy. Conclusions: In this series, post-mortem MRI findings agreed with the autopsy findings in 40/41(98%) cases and in one case the post-mortem MRI demonstrated an abnormality not demonstrated at autopsy

  12. The highly antigenic 53/25 kDa Taenia solium protein fraction with cathepsin-L like activity is present in the oncosphere/cysticercus and induces non-protective IgG antibodies in pigs

    Science.gov (United States)

    Zimic, Mirko; Pajuelo, Mónica; Gilman, Robert H.; Gutiérrez, Andrés H.; Rueda, Luis D.; Flores, Myra; Chile, Nancy; Verástegui, Manuela; Gonzalez, Armando; García, Héctor H.; Sheen, Patricia

    2011-01-01

    Cathepsin L-like proteases are secreted by several parasites including Taenia solium. The mechanism used by T. solium oncospheres to degrade and penetrate the intestine and infect the host is incompletely understood. It is assumed that intestinal degradation is driven by the proteolytic activity of enzymes secreted by the oncosphere. Blocking the proteolytic activity by an antibody response would prevent the oncosphere penetration and further infection. Serine and cysteine proteases including chymotrypsin, trypsin, elastase, and cathepsin L, are secreted by T. solium and Taenia saginata oncospheres when cultured in vitro, being potential vaccine candidates. However, the purification of a sufficient quantity of proteases secreted by oncospheres to conduct a vaccine trial is costly and lengthy. A 53/25 kDa cathepsin L-like fraction partially purified from T. solium cyst fluid was described previously as an important antigen for immunodiagnostics. In this study we found that this antigen is present in the T. solium oncosphere and is also secreted by the cysticercus. This protein fraction was tested for its ability to protect pigs against an oral challenge with T. solium oncospheres in a vaccine trial. IgG antibodies against the 53/25 kDa cathepsin L-like protein fraction were elicited in the vaccinated animals but did not confer protection. PMID:22119017

  13. Heat shock protein 90-mediated peptide-selective presentation of cytosolic tumor antigen for direct recognition of tumors by CD4(+) T cells.

    Science.gov (United States)

    Tsuji, Takemasa; Matsuzaki, Junko; Caballero, Otavia L; Jungbluth, Achim A; Ritter, Gerd; Odunsi, Kunle; Old, Lloyd J; Gnjatic, Sacha

    2012-04-15

    Tumor Ag-specific CD4(+) T cells play important functions in tumor immunosurveillance, and in certain cases they can directly recognize HLA class II-expressing tumor cells. However, the underlying mechanism of intracellular Ag presentation to CD4(+) T cells by tumor cells has not yet been well characterized. We analyzed two naturally occurring human CD4(+) T cell lines specific for different peptides from cytosolic tumor Ag NY-ESO-1. Whereas both lines had the same HLA restriction and a similar ability to recognize exogenous NY-ESO-1 protein, only one CD4(+) T cell line recognized NY-ESO-1(+) HLA class II-expressing melanoma cells. Modulation of Ag processing in melanoma cells using specific molecular inhibitors and small interfering RNA revealed a previously undescribed peptide-selective Ag-presentation pathway by HLA class II(+) melanoma cells. The presentation required both proteasome and endosomal protease-dependent processing mechanisms, as well as cytosolic heat shock protein 90-mediated chaperoning. Such tumor-specific pathway of endogenous HLA class II Ag presentation is expected to play an important role in immunosurveillance or immunosuppression mediated by various subsets of CD4(+) T cells at the tumor local site. Furthermore, targeted activation of tumor-recognizing CD4(+) T cells by vaccination or adoptive transfer could be a suitable strategy for enhancing the efficacy of tumor immunotherapy.

  14. Comparative potency of different UV sources in reducing the density and antigen-presenting capacity of Langerhans cells in C3H mice

    NARCIS (Netherlands)

    Pierik, F.H.

    1994-01-01

    Although broadband UV.B irradiation has been shown to induce selective immunosuppression in a variety of experimental systems, the wavelength dependence of the immunornodulation and the initial events in the skin remain unclear. In the present study three UV lamps werc used at suberythermal doses on

  15. Bcl-xL regulates CD1d-mediated antigen presentation to NKT cells by altering CD1d trafficking through the endocytic pathway.

    Science.gov (United States)

    Subrahmanyam, Priyanka B; Carey, Gregory B; Webb, Tonya J

    2014-09-01

    NKT cells are a unique subset of T cells that recognize glycolipid Ags presented in the context of CD1d molecules. NKT cells mount strong antitumor responses and are a major focus in developing effective cancer immunotherapy. It is known that CD1d molecules are constantly internalized from the cell surface, recycled through the endocytic compartments, and re-expressed on the cell surface. However, little is known about the regulation of CD1d-mediated Ag processing and presentation in B cell lymphoma. Prosurvival factors of the Bcl-2 family, such as Bcl-xL, are often upregulated in B cell lymphomas and are intimately linked to sphingolipid metabolism, as well as the endocytic compartments. We hypothesized that Bcl-xL can regulate CD1d-mediated Ag presentation to NKT cells. We found that overexpression or induction of Bcl-xL led to increased Ag presentation to NKT cells. Conversely, the inhibition or knockdown of Bcl-xL led to decreased NKT cell activation. Furthermore, knockdown of Bcl-xL resulted in the loss of CD1d trafficking to lysosome-associated membrane protein 1(+) compartments. Rab7, a late endosomal protein, was upregulated and CD1d molecules accumulated in the Rab7(+) late endosomal compartment. These results demonstrate that Bcl-xL regulates CD1d-mediated Ag processing and presentation to NKT cells by altering the late endosomal compartment and changing the intracellular localization of CD1d. Copyright © 2014 by The American Association of Immunologists, Inc.

  16. Developmental origins of adult health and disease: the role of periconceptional and foetal nutrition.

    Science.gov (United States)

    McMillen, I Caroline; MacLaughlin, Severence M; Muhlhausler, Beverly S; Gentili, Sheridan; Duffield, Jaime L; Morrison, Janna L

    2008-02-01

    The 'developmental origins of adult health and disease' hypothesis stated that environmental factors, particularly maternal undernutrition, act in early life to programme the risks for adverse health outcomes, such as cardiovascular disease, obesity and the metabolic syndrome in adult life. Early physiological tradeoffs, including activation of the foetal hypothalamo-pituitary-adrenal (HPA) axis, confer an early fitness advantage such as foetal survival, while incurring delayed health costs. We review the evidence that such tradeoffs are anticipated from conception and that the periconceptional nutritional environment can programme the developmental trajectory of the stress axis and the systems that maintain and regulate arterial blood pressure. There is also evidence that restriction of placental growth and function, results in an increased dependence of the maintenance of arterial blood pressure on the sequential recruitment of the sympathetic nervous system and HPA axis. While the 'early origins of adult disease' hypothesis has focussed on the impact of maternal undernutrition, an increase in maternal nutritional intake and in maternal body mass intake has become more prevalent in developed countries. Exposure to overnutrition in foetal life results in a series of central and peripheral neuroendocrine responses that in turn programme development of the fat cell and of the central appetite regulatory system. While the physiological responses to foetal undernutrition result in the physiological trade off between foetal survival and poor health outcomes that emerge after reproductive senescence, exposure to early overnutrition results in poor health outcomes that emerge in childhood and adolescence. Thus, the effects of early overnutrition can directly impact on reproductive fitness and on the health of the next generation. In this context, the physiological responses to relative overnutrition in early life may directly contribute to an intergenerational cycle of

  17. Parental decision-making after ultrasound diagnosis of a serious foetal abnormality.

    Science.gov (United States)

    Bijma, Hilmar H; Wildschut, Hajo I J; van der Heide, Agnes; Passchier, Jan; Wladimiroff, Juriy W; van der Maas, Paul J

    2005-01-01

    The purpose of this article is to provide clinicians who are involved in the field of foetal medicine with a comprehensive overview of theories that are relevant for the parental decision-making process after ultrasound diagnosis of a serious foetal abnormality. Since little data are available of parental decision-making after ultrasound diagnosis of foetal abnormality, we reviewed the literature on parental decision-making in genetic counselling of couples at increased genetic risk together with the literature on general decision-making theories. The findings were linked to the specific situation of parental decision-making after an ultrasound diagnosis of foetal abnormality. Based on genetic counselling studies, several cognitive mechanisms play a role in parental decision-making regarding future pregnancies. Parents often have a binary perception of risk. Probabilistic information is translated into two options: the child will or will not be affected. The graduality of chance seems to be of little importance in this process. Instead, the focus shifts to the possible consequences for future family life. General decision-making theories often focus on rationality and coherence of the decision-making process. However, studies of both the influence of framing and the influence of stress indicate that emotional mechanisms can have an important and beneficial function in the decision-making process. Cognitive mechanisms that are elicited by emotions and that are not necessarily rational can have an important and beneficial function in parental decision-making after ultrasound diagnosis of a foetal abnormality. Consequently, the process of parental decision-making should not solely be assessed on the basis of its rationality, but also on the basis of the parental emotional outcome. Copyright (c) 2005 S. Karger AG, Basel.

  18. Increased antigen presentation but impaired T cells priming after upregulation of interferon-beta induced by lipopolysaccharides is mediated by upregulation of B7H1 and GITRL.

    Directory of Open Access Journals (Sweden)

    Fang Wang

    Full Text Available Dendritic cells are able to present Ag-derived peptides on MHC class I and II molecules and induce T cells priming. Lipopolysaccharides (LPS, an activator of Toll-like 4 receptor (TLR4 signaling, has been demonstrated to facilitate Ag-presentation, up-regulate surface molecules expression but impair T cells priming. In this study, we investigated the effect of LPS on nicotine-enhanced DCs-dependent T cells priming and the mechanisms of LPS orchestrating the immunosuppressive program. We could demonstrate that the treatment with LPS resulted in increased surface molecules expression, enhanced Ag-presentation, up-regulated release of TGF-beta, TNF-alpha, IL-6, and IFN-beta. Concomititantly, the upregulation of IFN-beta in DCs induces the up-regulation of coinhibitory molecules B7H1 and GITRL, which cause an impaired activation of naïve Ag-specific T cells and the induction of T cell tolerance by enhancing B7H1-PD-1 interactions and promoting GITRL-GITL facilitated Treg generation, respectively. These data provide a mechanistic basis for the immunomodulatory action of IFN-beta which might open new possibilities in the development of therapeutic approaches aimed at the control of excessive immune response and persistent infection.

  19. Delivery of Large Heterologous Polypeptides across the Cytoplasmic Membrane of Antigen-Presenting Cells by the Bordetella RTX Hemolysin Moiety Lacking the Adenylyl Cyclase Domain

    Czech Academy of Sciences Publication Activity Database

    Holubová, Jana; Kamanová, Jana; Jelínek, J.; Tomala, Jakub; Mašín, Jiří; Kosová, Martina; Staněk, Ondřej; Bumba, Ladislav; Michálek, J.; Kovář, Marek; Šebo, Peter

    2012-01-01

    Roč. 80, č. 3 (2012), s. 1181-1192 ISSN 0019-9567 R&D Projects: GA AV ČR IAA500200914; GA ČR(CZ) GAP207/11/0717; GA ČR GAP301/11/0325; GA MŠk 1M0506; GA MŠk 2B06161 Institutional research plan: CEZ:AV0Z50200510 Keywords : MHC CLASS-I * ESCHERICHIA-COLI * PRESENTATION PATHWAY Subject RIV: EE - Microbiology, Virology Impact factor: 4.074, year: 2012

  20. Carcinoma-associated antigens

    International Nuclear Information System (INIS)

    Bartorelli, A.; Accinni, R.

    1981-01-01

    This invention relates to novel antigens associated with breast carcinoma, anti-sera specific to said antigens, 125 I-labeled forms of said antigens and methods of detecting said antigens in serum or plasma. The invention also relates to a diagnostic kit containing standardised antigens or antisera or marked forms thereof for the detection of said antigens in human blood, serum or plasma. (author)

  1. African-American (AA) men with local-regional prostate cancer (PC) present with higher prostate specific antigen (PSA) levels than whites: results of RTOG 94-12

    International Nuclear Information System (INIS)

    Vijayakumar, S.; Winter, K.; Sause, W.; Gallagher, M.J.; Perez, C.; Bondy, M.

    1996-01-01

    Purpose/Objective: To use pretreatment serum PSA levels as an 20), gleason score (2-5,6-7,7-10), race (whites and AAs), and two interactions viz (a) PSA by race (p=0.0012) and (b) PSA by total gleason score (p=0.0001). When race was replaced by educational status, or income, or both, the fits (0.8246,0.8197, and 0.7815, respectively) were not as good as the fit with race in the model. Conclusion: The findings of this nation-wide prospective registration study with a high percentage of AA patient participation confirms previous, smaller, geographically-limited studies (1,2,3) results that AA patients with non-metastatic PC present with a higher mean PSA values than whites. The multivariate findings imply that, for each level of total gleason score, there is a higher percentage of whites with PSA levels 20. Education and/or income as surrogates of sociological status could not completely explain the racial differences. Other reasons for health-care barriers among AAs need to be identified

  2. Human platelet antigens in Burmese, Karen and north-eastern Thais.

    Science.gov (United States)

    Phuangtham, R; Romphruk, A; Puapairoj, C; Leelayuwat, C; Romphruk, A V

    2017-02-01

    A comparative study of allele frequencies at HPA-1 to -6 and HPA-15 in Burmese and Karen populations as well as at HPA-15 in north-eastern Thais (NET) is presented. Human platelet antigens (HPAs) are clinically important in several immune platelet disorders, including foetal and neonatal alloimmune thrombocytopenia (FNAIT), post-transfusion purpura (PTP) and platelet transfusion refractoriness (PTR). The knowledge of antigen frequencies in a population is essential for the evaluation of patients suffering from immune-mediated platelet disorders. A total of 285 unrelated, healthy Burmese, 242 Karen and 300 NET were recruited to this study. Genotype and allele frequencies of HPA-1 to -6 and HPA-15 were defined using polymerase chain reaction sequence-specific primers (PCR-SSP) RESULTS: No individuals homozygous for HPA-1bb, -2bb, -4bb, -5bb and -6bb were detected. HPA-1a, -2a, -4a, -5a and -6a were present in all samples of Burmese and Karen origin. HPA-1b, -2b, -4b, -5b and -6b were rare in these populations. The frequencies of HPA-3a/-3b were 60·4/39·6% in Burmese and 55·8/44·2% in Karen, respectively. Frequencies of HPA-15a/-15b were 57·2/42·8% in Burmese, 52·5/47·5% in Karen and 49·8/50·2% in NET. The frequencies of HPA genotypes in our study indicates that HPA-1a, -2a, -4a, -5a and -6a are unlikely involved in FNAIT, PTP and PTR in Burmese and Karen populations. However, HPA-1b, -2b, -3a, -3b, -4b, -5b, -6b, -15a and -15b may likely stimulate alloantibodies in these populations. © 2016 British Blood Transfusion Society.

  3. The impact of delayed maternity on foetal growth in Spain: An assessment by population attributable fraction.

    Science.gov (United States)

    Varea, Carlos; Terán, José Manuel; Bernis, Cristina; Bogin, Barry

    2017-09-18

    Delayed childbearing is considered a risk factor for maternal-foetal health. As in other higher-income countries, in Spain age at maternity has steadily increased during the last two decades. To quantify the impact of the delay in the age at maternity on small for gestational age (SGA) categories of maternity and parity. Primipara 35-39 years old mothers have the highest PAF p in the three categories of SGA, with the maximum value for SGA maternity is a significant adjusted risk factor for SGA, contributing to the increase of its prevalence. However, results also suggest a limited clinical impact of delayed maternity on foetal growth. Positive changes in maternal profile associated with the shift in maternal age might contribute to explain the limited impact of mothers aged 35 years and older on negative birth outcome in Spain. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  4. A lymphoblastoid response of human foetal lymphocytes to ultraviolet-irradiated herpes simplex virus

    International Nuclear Information System (INIS)

    Westmoreland, D.

    1980-01-01

    Cultures of foetal lymphocytes were exposed to u.v.-irradiated herpes simplex virus (HSV). The cells responded with increased 6- 3 H-thymidine incorporation, the formation of clumps of enlarged lymphoblastoid cells and cell division. This response was first detected 3 to 4 days after exposure to virus material and was shown to be virus-dose dependent. The ability to stimulate foetal cells was considerably more u.v. resistant than infectivity. Two isolates of HSV type 2 (4663 and 37174), which had a high 'transforming' ability, produced large numbers of non-infectious particles (particle: infectivity ratios in excess of 10 4 ). The cells, which responded to u.v.-irradiated HSV with blastoid transformation, were associated with the non-E-rosetting (T-cell-depleted) subpopulation. (author)

  5. MODE OF DELIVERY AND FOETAL OUTCOME IN MECONIUM-STAINED LIQUOR: A RETROSPECTIVE STUDY

    Directory of Open Access Journals (Sweden)

    Anitha Narasimhaiah

    2016-08-01

    Full Text Available AIMS AND OBJECTIVES To study the incidence of MSL, mode of delivery and foetal outcome in women with MSL in labour. MATERIALS AND METHODS A retrospective study was conducted from January 2014 to December 2015 on patients admitted in labour room of Dr. B. R. Ambedkar Medical College and Hospital and assessed for MSL, mode of delivery and foetal outcome. RESULTS Out of the 1661 deliveries 195 (11.73 % were complicated with MSL. Chi square test was applied to analyse Grades of meconium and APGAR score at 95 % confidence and p value of < 0.05 was obtained which was statistically significant. CONCLUSION MSL alone is not an indication for Caesarean Section and is not associated with adverse neonatal outcome. Increase in the grades of MSL is associated with more adverse outcome.

  6. Biogenesis of corticosteroids in monolayer cultures of human foetal adrenal cells

    International Nuclear Information System (INIS)

    Goodyer, C.G.; Torday, J.S.; St George Hall, C.; Smith, B.T.; Giroud, C.J.P.

    1976-01-01

    Human foetal adrenal cells were grown in monolayer culture and their steroidogenic capacity observed for up to a month. The cells produced a complex array of steroids and some of their ester sulphates from endogenous as well as from [ 14 C] and[ 3 H] precursors. ACTH stimulated corticoidogenesis, particularly cortisol secretion, and markedly enhanced the incorporation of progesterone and pregnenolone into cortisol. Following incubation with the same precursors, large amounts of radioactivity remained water soluble. From the butanol extractable material of this fraction, dehydroepiandrosterone sulphate was characterized as the main metabolite of pregnenolone and corticosterone and 11-deoxycorticosterone sulphates as the main metabolites of progesterone. With time in culture there was a decrease in steroidogenesis as well as a steady decline in responsiveness to ACTH, mainly manifested by cortisol secretion. The medium from homologous foetal pituitary cultures stimulated cortisol production by the human adrenal cell monolayer. (author)

  7. A comparison of foetal SAR in three sets of pregnant female models

    International Nuclear Information System (INIS)

    Dimbylow, Peter J; Nagaoka, Tomoaki; Xu, X George

    2009-01-01

    This paper compares the foetal SAR in the HPA hybrid mathematical phantoms with the 26-week foetal model developed at the National Institute of Information and Communications Technology, Tokyo, and the set of 13-, 26- and 38-week boundary representation models produced at Rensselaer Polytechnic Institute. FDTD calculations are performed at a resolution of 2 mm for a plane wave with a vertically aligned electric field incident upon the body from the front, back and two sides from 20 MHz to 3 GHz under isolated conditions. The external electric field values required to produce the ICNIRP public exposure localized restriction of 2 W kg -1 when averaged over 10 g of the foetus are compared with the ICNIRP reference levels.

  8. Biopsychosocial effects of foetal alcohol syndrome among children from the Interventional Care Facility in Otwock

    Directory of Open Access Journals (Sweden)

    Aneta Sęk

    2017-06-01

    Full Text Available Objective: The aim of the study was to present the biopsychosocial effects of foetal alcohol syndrome among the children from the Interventional Care Facility in Otwock in the years 2012–2015. Material and methods: We analysed medical records from the years 2012 to 2015. Medical documentation consisted of the child’s stay record, psychological diagnosis, maternal interview, social interview, a round check report, medical assessment and consultation records, neurological examination reports and physiotherapist reports. The study included medical documentation of 18 girls (29% and 44 boys (71%. In total, 62 children aged between 3 days and 1 year were included in the study group. Results: Consumption of alcohol during pregnancy is still declared by many women (69%, including 44% of mothers consuming alcohol throughout the duration of pregnancy. All children in the Interventional Care Facility had at least 2 dysmorphic facial features. Sucking dysfunction, which caused difficulty when feeding, was observed in 59 children, and dysaesthesia – in 56 children. Children with foetal alcohol syndrome were very tearful, experienced tensions (58 children, hyperactivity (59 children as well as sleep disorders (60 children. They frequently experienced emotional disorders (60 children and problems with establishing contact with other people (44 children. Conclusions: It was found that alcohol has teratogenic effects on the developing foetus. Any amount of alcohol consumed by a pregnant woman can cause damage to the foetus. Foetal exposure to alcohol leads to multiple disorders that occur not only in the biological, but also in the psychological sphere. The study confirmed that children with foetal alcohol syndrome suffer from multiple health problems and have difficulty functioning in society due to their “otherness”.

  9. Identification and characterization of insulin receptors on foetal-mouse brain-cortical cells.

    OpenAIRE

    Van Schravendijk, C F; Hooghe-Peters, E L; De Meyts, P; Pipeleers, D G

    1984-01-01

    The occurrence of insulin receptors was investigated in freshly dissociated brain-cortical cells from mouse embryos. By analogy with classical insulin-binding cell types, binding of 125I-insulin to foetal brain-cortical cells was time- and pH-dependent, only partially reversible, and competed for by unlabelled insulin and closely related peptides. Desalanine-desasparagine-insulin, pig proinsulin, hagfish insulin and turkey insulin were respectively 2%, 4%, 2% and 200% as potent as bovine insu...

  10. Associations Between Maternal-Foetal Attachment and Infant Developmental Outcomes: A Systematic Review.

    Science.gov (United States)

    Branjerdporn, Grace; Meredith, Pamela; Strong, Jenny; Garcia, Jenniffer

    2017-03-01

    Objectives Infant developmental outcomes may be influenced by a range of prenatal maternal characteristics. While there is some evidence to suggest that maternal-foetal attachment may be associated with infant developmental outcomes, there is a need to systematically review this evidence to guide future research and clinical practice. Methods Five electronic databases were systematically scanned. Key journals and reference lists were hand-searched. Papers were included if: (1) pregnant women were assessed for maternal-foetal attachment; (2) the infants were later assessed, under 2 years old, for any developmental outcome (e.g., social-emotional, cognition, motor, language, adaptive behaviour); and (3) they were published in English. Two independent reviewers used the STROBE checklist to appraise the quality of each paper. Results Of the 968 papers identified, eight were included in the review, and four of these were of low quality (infant temperament (n = 5), adaptive behaviour (e.g., colic, sleep) (n = 2), and milestone attainment (n = 1). There is some evidence to suggest that lower maternal-foetal attachment is related to suboptimal developmental outcomes. However, these results should be interpreted with caution due to the limited and low quality studies available. Conclusions Although maternal-foetal attachment may be associated with infant developmental outcomes, future research is required which: (1) considers a range of developmental outcomes, (2) has increased scientific rigour, (3) assesses mother-infant dyads at different prenatal and postnatal time points, and (4) examines different target populations.

  11. Combining and benchmarking methods of foetal ECG extraction without maternal or scalp electrode data

    International Nuclear Information System (INIS)

    Behar, Joachim; Oster, Julien; Clifford, Gari D

    2014-01-01

    Despite significant advances in adult clinical electrocardiography (ECG) signal processing techniques and the power of digital processors, the analysis of non-invasive foetal ECG (NI-FECG) is still in its infancy. The Physionet/Computing in Cardiology Challenge 2013 addresses some of these limitations by making a set of FECG data publicly available to the scientific community for evaluation of signal processing techniques. The abdominal ECG signals were first preprocessed with a band-pass filter in order to remove higher frequencies and baseline wander. A notch filter to remove power interferences at 50 Hz or 60 Hz was applied if required. The signals were then normalized before applying various source separation techniques to cancel the maternal ECG. These techniques included: template subtraction, principal/independent component analysis, extended Kalman filter and a combination of a subset of these methods (FUSE method). Foetal QRS detection was performed on all residuals using a Pan and Tompkins QRS detector and the residual channel with the smoothest foetal heart rate time series was selected. The FUSE algorithm performed better than all the individual methods on the training data set. On the validation and test sets, the best Challenge scores obtained were E1 = 179.44, E2 = 20.79, E3 = 153.07, E4 = 29.62 and E5 = 4.67 for events 1–5 respectively using the FUSE method. These were the best Challenge scores for E1 and E2 and third and second best Challenge scores for E3, E4 and E5 out of the 53 international teams that entered the Challenge. The results demonstrated that existing standard approaches for foetal heart rate estimation can be improved by fusing estimators together. We provide open source code to enable benchmarking for each of the standard approaches described. (paper)

  12. Foetal dose conversion coefficients for ICRP-compliant pregnant models from idealised proton exposures

    International Nuclear Information System (INIS)

    Taranenko, V.; Xu, X. G.

    2009-01-01

    Protection of pregnant women and their foetus against external proton irradiations poses a unique challenge. Assessment of foetal dose due to external protons in galactic cosmic rays and as secondaries generated in aircraft walls is especially important during high-altitude flights. This paper reports a set of fluence to absorbed dose conversion coefficients for the foetus and its brain for external monoenergetic proton beams of six standard configurations (the antero-posterior, the postero-anterior, the right lateral, the left lateral, the rotational and the isotropic). The pregnant female anatomical definitions at each of the three gestational periods (3, 6 and 9 months) are based on newly developed RPI-P series of models whose organ masses were matched within 1% with the International Commission on Radiological Protection reference values. Proton interactions and the transport of secondary particles were carefully simulated using the Monte Carlo N-Particle extended code (MCNPX) and the phantoms consisting of several million voxels at 3 mm resolution. When choosing the physics models in the MCNPX, it was found that the advanced Cascade-Exciton intranuclear cascade model showed a maximum of 9% foetal dose increase compared with the default model combination at intermediate energies below 5 GeV. Foetal dose results from this study are tabulated and compared with previously published data that were based on simplified anatomy. The comparison showed a strong dependence upon the source geometry, energy and gestation period: The dose differences are typically less than 20% for all sources except ISO where systematically 40-80% of higher doses were observed. Below 200 MeV, a larger discrepancy in dose was found due to the Bragg peak shift caused by different anatomy. The tabulated foetal doses represent the latest and most detailed study to date offering a useful set of data to improve radiation protection dosimetry against external protons. (authors)

  13. Maternal and foetal outcome in hellp syndrome at tertiary care hospital

    International Nuclear Information System (INIS)

    Sadaf, N.; Haq, G.; Din, S.S.U.

    2013-01-01

    Objective: To determine maternal and foetal outcome in patients of Haemolysis, Elevated Liver enzyme and Low Platelet Cont syndrome. Methods: The descriptive case series was conducted at the Gynae Unit II of Civil Hospital, Karachi, over a period of 12 months in two episodes; first from December 28, 2006, to February 28, 2007, and then from September 1, 2007, to June 30, 2008. It comprised 40 consecutive women with pre-ecampsia and eclampsia along with altered platelet count who met the syndrome criteria. A pre-designed proforma was administered for data collection. Maternal and foetal outcomes were noted. SPSS 10 was used for statistical analysis. Result: Among the 40 mothers, cesarean section was the most common outcome (n=24; 60%). Pulmonary oedema was found in 2 (5%) cases, acute renal failure in 10 (25%), disseminated intravascular coagulation in 6 (15%), and abruptio placenta in 5 (12.5%). Intrauterine growth restriction as a foetal outcome was observed in 18 (45%) cases. Pre-term birth was the result in 20 (50%) cases, and perinatal mortality was high (n=23; 57.5%). Conclusion: Management and delivery of HELLP syndrome patients should be performed at tertiary care centres, where highly trained obstetrician, neonatal intensive care unit personnel and Multi-disciplinary facilities are available. Correct diagnosis and timely intervention can decrease the risk of maternal and perinatal mortality. (author)

  14. Controversies and considerations regarding the termination of pregnancy for foetal anomalies in Islam.

    Science.gov (United States)

    Al-Matary, Abdulrahman; Ali, Jaffar

    2014-02-05

    Approximately one-fourth of all the inhabitants on earth are Muslims. Due to unprecedented migration, physicians are often confronted with cultures other than their own that adhere to different paradigms. In Islam, and most religions, abortion is forbidden. Islam is considerably liberal concerning abortion, which is dependent on (i) the threat of harm to mothers, (ii) the status of the pregnancy before or after ensoulment (on the 120th day of gestation), and (iii) the presence of foetal anomalies that are incompatible with life. Considerable variation in religious edicts exists, but most Islamic scholars agree that the termination of a pregnancy for foetal anomalies is allowed before ensoulment, after which abortion becomes totally forbidden, even in the presence of foetal abnormalities; the exception being a risk to the mother's life or confirmed intrauterine death. The authors urge Muslim law makers to also consider abortion post ensoulment if it is certain that the malformed foetus will decease soon after birth or will be severely malformed and physically and mentally incapacitated after birth to avoid substantial hardship that may continue for years for mothers and family members. The authors recommend that an institutional committee governed and monitored by a national committee make decisions pertaining to abortion to ensure that ethics are preserved and mistakes are prevented. Anomalous foetuses must be detected at the earliest possible time to enable an appropriate medical intervention prior to the 120th day.

  15. Prenatal malnutrition and subsequent foetal loss risk: Evidence from the 1959-1961 Chinese famine

    Directory of Open Access Journals (Sweden)

    Shige Song

    2013-10-01

    Full Text Available Background: Scientists disagree on whether prenatal malnutrition has long-term influences on women's reproductive function, and empirical evidence of such long-term effects remains limited and inconsistent. Methods: Using the retrospective pregnancy history of 12,567 Chinese women collected in a nationally representative sample survey in 2001, this study conducted difference-in-differences analyses to investigate the relationship between prenatal exposure to the 1959-1961 Great Leap Forward Famine in China and the subsequent risk of involuntary foetal loss, including miscarriage and stillbirth, and how this relationship changes between the rural and urban populations. Results: Prenatal exposure to the Great Leap Forward Famine had no long-term effect on women's risk of miscarriage. Such an exposure increased the risk of stillbirth among urban women but not among rural women. Conclusions: The results support the foetal origins hypothesis. The significant urban-rural difference in the effect of prenatal famine exposure on stillbirth suggests the presence of a long-term negative foetal origins effect and a strong selection effect caused by famine-induced population attrition.

  16. Ontogeny of Sex-Related Differences in Foetal Developmental Features, Lipid Availability and Fatty Acid Composition

    Directory of Open Access Journals (Sweden)

    Consolacion Garcia-Contreras

    2017-05-01

    Full Text Available Sex-related differences in lipid availability and fatty acid composition during swine foetal development were investigated. Plasma cholesterol and triglyceride concentrations in the mother were strongly related to the adequacy or inadequacy of foetal development and concomitant activation of protective growth in some organs (brain, heart, liver and spleen. Cholesterol and triglyceride availability was similar in male and female offspring, but female foetuses showed evidence of higher placental transfer of essential fatty acids and synthesis of non-essential fatty acids in muscle and liver. These sex-related differences affected primarily the neutral lipid fraction (triglycerides, which may lead to sex-related postnatal differences in energy partitioning. These results illustrate the strong influence of the maternal lipid profile on foetal development and homeorhesis, and they confirm and extend previous reports that female offspring show better adaptive responses to maternal malnutrition than male offspring. These findings may help guide dietary interventions to ensure adequate fatty acid availability for postnatal development.

  17. Modulation of Th1/Th2 Immune Responses by Killed Propionibacterium acnes and Its Soluble Polysaccharide Fraction in a Type I Hypersensitivity Murine Model: Induction of Different Activation Status of Antigen-Presenting Cells

    Directory of Open Access Journals (Sweden)

    Carla Cristina Squaiella-Baptistão

    2015-01-01

    Full Text Available Propionibacterium acnes (P. acnes is a gram-positive anaerobic bacillus present in normal human skin microbiota, which exerts important immunomodulatory effects, when used as heat- or phenol-killed suspensions. We previously demonstrated that heat-killed P. acnes or its soluble polysaccharide (PS, extracted from the bacterium cell wall, suppressed or potentiated the Th2 response to ovalbumin (OVA in an immediate hypersensitivity model, depending on the treatment protocol. Herein, we investigated the mechanisms responsible for these effects, using the same model and focusing on the activation status of antigen-presenting cells (APCs. We verified that higher numbers of APCs expressing costimulatory molecules and higher expression levels of these molecules are probably related to potentiation of the Th2 response to OVA induced by P. acnes or PS, while higher expression of toll-like receptors (TLRs seems to be related to Th2 suppression. In vitro cytokines production in cocultures of dendritic cells and T lymphocytes indicated that P. acnes and PS seem to perform their effects by acting directly on APCs. Our data suggest that P. acnes and PS directly act on APCs, modulating the expression of costimulatory molecules and TLRs, and these differently activated APCs drive distinct T helper patterns to OVA in our model.

  18. Determination of first pregnancy and foetal measurements in Egyptian Baladi goats (Capra hircus

    Directory of Open Access Journals (Sweden)

    Hussein A. Amer

    2008-06-01

    Full Text Available This study was conducted using B-mode transrectal (TR and transabdominal (TA ultrasonography to determine early pregnancy and fetometry. A total of 110 does aged between 8 and 36 months were used. The detection of early pregnancy and foetal number was measured. The relationship between gestation age and crown-rump length (CRL and bi-parietal diameter (BPD was determined from days 40 to 109 of gestation. The accuracy of foetal sexing was determined by differentiation of genital tubercle (GT from days 40 to 109 of gestation and then followed up after birth. The examination revealed 95.5% of does were pregnant, with 100% accuracy in detecting pregnancy for positive cases. The foetal number was 45.7% and 54.3% for single and twins/triplets. The TR probe enabled more reliable and early recognition of foetal fluid (5 days and heart beats (4 days than the TA probe. The TR observation of heart beats is recommended as conclusive evidence of the presence of a live foetus. The TA convex probe was used from days 40-89 to measure CRL and from days 40-109 to measure BPD. The relation between gestational age and CRL or BPD were highly significant (p0.05 higher in single, compared to multiple pregnancies. In total, 83.3% and 70.2% of single and twins and triplets were sexed. After birth, one case was misdiagnosed by ultrasound, i.e. 83.3% (single and 68.4% (twins and triplets were sexed. However, identification of GT in male foetuses was possible from day 40 onwards. From a total 105 scanned does, 80 (76.2% were sexed and 75.2% of cases were sexed after birth. B-mode real-time ultrasonography is recommended as a reliable means that can be used in field conditions to provide early detection of gestation as early as 19-27 days after mating, for CRL or BPD measuring and foetal sexing from day 40 of gestation onwards.

  19. Determination of first pregnancy and foetal measurements in Egyptian Baladi goats (Capra hircus).

    Science.gov (United States)

    Amer, Hussein A

    2008-01-01

    This study was conducted using B-mode transrectal (TR) and transabdominal (TA) ultrasonography to determine early pregnancy and fetometry. A total of 110 does aged between 8 and 36 months were used. The detection of early pregnancy and foetal number was measured. The relationship between gestation age and crown-rump length (CRL) and bi-parietal diameter (BPD) was determined from days 40 to 109 of gestation. The accuracy of foetal sexing was determined by differentiation of genital tubercle (GT) from days 40 to 109 of gestation and then followed up after birth. The examination revealed 95.5% of does were pregnant, with 100% accuracy in detecting pregnancy for positive cases. The foetal number was 45.7% and 54.3% for single and twins/triplets. The TR probe enabled more reliable and early recognition of foetal fluid (5 days) and heart beats (4 days) than the TA probe. The TR observation of heart beats is recommended as conclusive evidence of the presence of a live foetus. The TA convex probe was used from days 40-89 to measure CRL and from days 40-109 to measure BPD. The relation between gestational age and CRL or BPD were highly significant (p0.05) higher in single, compared to multiple pregnancies. In total, 83.3% and 70.2% of single and twins and triplets were sexed. After birth, one case was misdiagnosed by ultrasound, i.e. 83.3% (single) and 68.4% (twins and triplets) were sexed. However, identification of GT in male foetuses was possible from day 40 onwards. From a total 105 scanned does, 80 (76.2%) were sexed and 75.2% of cases were sexed after birth. B-mode real-time ultrasonography is recommended as a reliable means that can be used in field conditions to provide early detection of gestation as early as 19-27 days after mating, for CRL or BPD measuring and foetal sexing from day 40 of gestation onwards.

  20. Assessment of growth dynamics of human cranium middle fossa in foetal period.

    Science.gov (United States)

    Skomra, Andrzej; Kędzia, Alicja; Dudek, Krzysztof; Bogacz, Wiesław

    2014-01-01

    Available literature analysis demonstrated smallness of studies of cranial base. The goal of the study was to analyse the medial fossa of the human cranium in the foetal period against other fossae. Survey material consisted of 110 human foetuses at a morphological age of 16-28 weeks of foetal life, CRL 98-220 mm. Anthropological, preparation method, reverse method and statistical analysis were utilized. The survey incorporated the following computer programmes: Renishaw, TraceSurf, AutoCAD, CATIA. The reverse method seems especially interesting (impression with polysiloxane (silicone elastomer of high adhesive power used in dentistry) with 18 D 4823 activator. Elicited impression accurately reflected complex shape of cranium base. On assessing the relative rate of cranium medial fossa, the rate was found to be stable (linear model) for the whole of the analysed period and is 0.19%/week, which stands for the gradual and steady growth of the middle fossa in relation to the whole of the cranium base. At the same time, from the 16th till 28th week of foetal life, relative volume of the cranium middle fossa increases more intensively than cranium anterior fossa, whereas the cranium middle fossa volume as compared with the cranium posterior fossa is definitely slower. In the analysed period, the growth rate of the cranium base middle fossa was bigger in the 4th and 5th weeks than in the 6th and 7th weeks of foetal life. The investigations revealed cranium base asymmetry of the left side. Furthermore, the anterior fossae volume on the left side is significantly bigger than the one of the fossae on the right side. Volume growth rate is more intensive in the 4th and 5th than in the 6th and 7th weeks of foetal life. In the examined period, the relative growth rate of cranium base middle fossa is 0.19%/week and it is stable - linear model. The study revealed correlations in the form of mathematical models, which enabled foetuses age assessment.

  1. Participation of L3T4 in T cell activation in the absence of class II major histocompatibility complex antigens. Inhibition by anti-L3T4 antibodies is a function both of epitope density and mode of presentation of anti-receptor antibody

    DEFF Research Database (Denmark)

    Owens, T; Fazekas de St Groth, B

    1987-01-01

    two monoclonal antibodies, KJ16-133.18 and F23.1, that recognize a determinant encoded by the T cell receptor V beta 8 gene family. These antibodies were used to select two clones of T cells with surface phenotype Thy-1.2+, L3T4+, Lyt-2-, KJ16-133.18+, F23.1+, IA-, IE-. One of these clones (E9.D4......The recognition of many class II major histocompatibility complex (MHC)-associated antigens by T cells requires the participation of the L3T4 molecule. It has been proposed that this molecule acts to stabilize low affinity binding to antigen in association with MHC and thereby increases the avidity...... of T cell/antigen interactions. By using antibodies against the T cell antigen receptor (TCR) to activate T cells, thereby circumventing the requirement for antigen presenting cells and MHC-associated antigen, we have been able to study the function of L3T4 in the absence of class II MHC. We have used...

  2. Modulation of interferon-γ synthesis by the effects of lignin-like enzymatically polymerized polyphenols on antigen-presenting cell activation and the subsequent cell-to-cell interactions.

    Science.gov (United States)

    Yamanaka, Daisuke; Motoi, Masuro; Ishibashi, Ken-ichi; Miura, Noriko N; Adachi, Yoshiyuki; Ohno, Naohito

    2013-12-15

    Lignin-like polymerized polyphenols strongly activate lymphocytes and induce cytokine synthesis. We aimed to characterise the mechanisms of action of polymerized polyphenols on immunomodulating functions. We compared the reactivity of leukocytes from various organs to that of polymerized polyphenols. Splenocytes and resident peritoneal cavity cells (PCCs) responded to polymerized polyphenols and released several cytokines, whereas thymocytes and bone-marrow cells showed no response. Next, we eliminated antigen-presenting cells (APCs) from splenocytes to study their involvement in cytokine synthesis. We found that APC-negative splenocytes showed significantly reduced cytokine production induced by polymerized polyphenols. Additionally, adequate interferon-γ (IFN-γ) induction by polymerized polyphenols was mediated by the coexistence of APCs and T cells because the addition of T cells to PCCs increased IFN-γ production. Furthermore, inhibition of the T cell-APC interaction using neutralising antibodies significantly decreased cytokine production. Thus, cytokine induction by polymerized polyphenols was mediated by the interaction between APCs and T cells. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Carcino-Embryonic Antigen

    International Nuclear Information System (INIS)

    Akute, O.

    1999-02-01

    Tumour marker analysis has increased our understanding of the presence of tumours in the body. Carcino-embryonic antigen, CEA, is one of the best studied tumour markers and has proved an ideal diagnostic adjuvant. It has helped in quantifying the amount of disease present in a patient and thence to make accurate prognosis on the various diagnosed ailments. At UCH, it is observed that there is an increase in cancer related ailments and therefore the need for early diagnosis is more compelling in our environment to mitigate future cost of managing advanced manifestation

  4. Sirenomelia: a rare case of foetal congenital anomaly.

    Science.gov (United States)

    Dharmraj, Meena; Gaur, Sumitra

    2012-10-01

    Sirenomelia, alternatively known as 'mermaid syndrome' is a very rare congenital deformity in which the legs are fused together, giving them the appearance of the tail of a mermaid'. Other birth defects are always associated with sirenomelia, most commonly abnormalities of the kidneys, large intestines, and genitalia. The present case is a one of sirenomelia associated with an absent right kidney, mild left hydronephrosis, single umbilical artery, and severe oligohydramnios. We discuss the findings, relative to the present literature and related etiopathogenesis.

  5. Study of foetal heart rate patterns in pregnancy with intra-uterine growth restriction during antepartum period

    International Nuclear Information System (INIS)

    Fardiazar, Z.; Abassalizade, F.

    2013-01-01

    Objectives: To evaluate foetal heart rate pattern during antepartum period in pregnancies suffering from intra-uterine growth restriction. Methods: The case control study was conducted at the Alzahra Hospital, Tabriz, Iran from April 2008 to April 2011. It comprised 100 pregnancies with intra-uterine growth restriction and 92 normal pregnancies. The foetal heart rate pattern including basal heart rate, beat-to-beat variation, non-stress test (NST) result and acceleration and deceleration patterns of the heart rate were determined in both groups during the antepartum period. Findings were compared between the two groups and their relation with pregnancy-foetal outcomes was specified in the case group. SPSS 15 was used for statistical analysis. Results: There was no statistically significant difference between the foetus mean basal heart rate in the two groups (p <0.960). Frequency of cases with non-reactive non-stress test in the Cases was significantly higher than Controls (p <0.005). The difference in heart rate acceleration was also not statistically significant (p <0.618). Frequency of cases with low birth weight and caesarian was non-significantly but borderline higher among the Cases (p <0.081 and 0.060, respectively). Conclusion: Abnormal foetal heart rate pattern is more common in pregnancies marked by intra-uterine growth restriction and is directly associated with worse pregnancy/foetal outcomes. (author)

  6. Binding of hydrophobic antigens to surfaces

    DEFF Research Database (Denmark)

    2017-01-01

    A first aspect of the present invention is a method of detecting antibodies comprising the steps of: i) providing a first group of beads comprising a surface modified with C1-C10 alkyl groups comprising amine, ammonium, ether and/or hydroxyl groups, ii) contacting said first group of beads......-antigen-antibody conjugates, and v) detecting said bead-antigen-antibody conjugates. Further aspects include an antibody detection kit, a bead-antigen conjugate and a composition comprising at least two different groups of bead-antigen-conjugates....

  7. Sirenomelia: A Rare Case of Foetal Congenital Anomaly

    OpenAIRE

    Dharmraj, Meena; Gaur, Sumitra

    2012-01-01

    Sirenomelia, alternatively known as ?mermaid syndrome? is a very rare congenital deformity in which the legs are fused together, giving them the appearance of the tail of a mermaid?. Other birth defects are always associated with sirenomelia, most commonly abnormalities of the kidneys, large intestines, and genitalia. The present case is a one of sirenomelia associated with an absent right kidney, mild left hydronephrosis, single umbilical artery, and severe oligohydramnios. We discuss the fi...

  8. Foetal and adult human CYP3A isoforms in the bioactivation of organophosphorothionate insecticides.

    Science.gov (United States)

    Buratti, Franca M; Leoni, Claudia; Testai, Emanuela

    2006-12-15

    In humans organophosphorothionate pesticides (OPT) prenatal exposure has been demonstrated. Since OPT-induced neurodevelopmental effects may be due to in situ bioactivation by foetal enzymes, the catalytic activity of the foetal CYP3A7 toward chlorpyrifos (CPF), parathion (PAR), malathion (MAL) and fenthion (FEN) has been assessed by using recombinant enzymes. A comparison with the adult isoforms CYP3A4 and CYP3A5 has been also carried out. CYP3A7 was able to produce significant levels of oxon or sulfoxide from the four OPTs in the range of tested concentrations (0.05-200 microM). When the efficiencies of CYP3A isoforms were compared, the ranking, expressed as CLi values, were: CPF=3A4>3A5>3A7; PAR=3A4>3A7>3A5; MAL=3A4>3A7>3A5; FEN (sulfoxide formation)=3A4>3A5>3A7. The CYP3A5 efficiency appeared to be more dependent on the single insecticide than its related isozyme CYP3A4. Our results indicate that the levels of toxic metabolite formed in situ by CYP3A7 from CPF, MAL and PAR but not from FEN have the chance to inhibit acetylcholinesterase, following prenatal exposure to OPTs. However, due to the smaller weight of foetal liver, the contribution to total OPT biotransformation is relatively low. On the other hand, our results clearly indicate that at low CPF concentrations, the formation of the non-toxic metabolites is highly favoured in the foetus.

  9. Sonographic biophysical profile in detection of foetal hypoxia in 100 cases of suspected high risk pregnancy

    International Nuclear Information System (INIS)

    Ullah, N.; Khan, A.R.; Usman, M.

    2010-01-01

    Background: The foetus has become increasingly accessible and visible as a patient over the last two decades. Ultrasound imaging has broadened the scope of foetal assessment. Dynamic real time B-Mode ultrasound is used to monitor cluster of biophysical variables, both dynamic and static collectively termed as biophysical profile. The purpose of this study was to determine the effect of sonographic biophysical profile score on perinatal outcome in terms of mortality and morbidity. Methods: This descriptive study was carried on 100 randomly select ed high risk pregnant patients in Radiology Department PGMI, Government Lady Reading Hospital, Peshawar from December 2007 to June 2008. Manning biophysical profile including non-stress was employed for foetal screening, using Toshiba ultrasound machine model Nemio SSA-550A and 7.5 MHZ probe. Results: Out of 100 cases 79 (79%) had a normal biophysical profile in the last scan of 10/10 and had a normal perinatal outcome with 5 minutes Apgar score >7/10. In 13 (13%) cases Apgar score at 5 minute was < 7/10 and babies were shifted to nursery. There were 2 (2%) false positive cases that showed abnormal biophysical profile scores of 6/10 but babies were born with an Apgar score of 8/10 at 5 minutes. There were 2 (2%) neonatal deaths in this study group. The sensitivity of biophysical profile was 79.1%, specificity 92.9%. Predictive value for a positive test was 98.55%; predictive value for a negative test was 41.93%. Conclusion: Biophysical profile is highly accurate and reliable test of diagnosing foetal hypoxia. (author)

  10. No histologic evidence of foetal cardiotoxicity following exposure to maternal hydroxychloroquine.

    Science.gov (United States)

    Friedman, Deborah; Lovig, Leif; Halushka, Marc; Clancy, Robert M; Izmirly, Peter M; Buyon, Jill P

    2017-01-01

    It is currently recommended that hydroxychloroquine (HCQ) be maintained during pregnancy in patients with systemic lupus erythematosus. Recent data suggest that this Toll-like receptor inhibitor may also reduce the recurrence rate of anti-SSA/Ro associated congenital heart block (CHB). This case report describes a unique situation in which a CHB-afflicted, HCQ-exposed pregnancy was electively terminated. The heart did not reveal any characteristic features of cardiotoxicity, providing further evidence supporting the safety of foetal exposure to HCQ.

  11. Paracetamol (acetaminophen), aspirin (acetylsalicylic acid) and indomethacin are anti-androgenic in the rat foetal testis

    DEFF Research Database (Denmark)

    Kristensen, David Møbjerg; Lesné, L.; Fol, V. Le

    2012-01-01

    on gestational day 14.5 rat testes, we herein show that testosterone production was inhibited by paracetamol, at doses of 0.1??m to 100??m. Similar results were obtained for aspirin (1?100??m) and indomethacin (10??m). The production of the other Leydig cell hormone, Insl3, was not disrupted by exposure...... inhibit testosterone production in rat foetal testes in vitro and that these compounds had no effect on gonocyte survival. Parallel determinations of prostaglandin D2 (PGD2) production indicated that the effects of paracetamol and aspirin on PGD2 and testosterone were not connected, whereas the effects...

  12. 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)

    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.

    2008-01-01

    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 β (TGF-β) 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. PMID:18645038

  13. Recombinant Nonstructural 3 Protein, rNS3, of Hepatitis C Virus Along With Recombinant GP96 Induce IL-12, TNFα and α5integrin Expression in Antigen Presenting Cells

    Science.gov (United States)

    Hajizadeh, Mohammad Reza; Mokarram, Pooneh; Kamali sarvestani, Eskandar; Bolhassani, Azam; Mostafavi Pour, Zohreh

    2013-01-01

    Background Hepatitis C virus (HCV) infection is the main cause of chronic liver disease and to date there has been no vaccine development to prevent this infection. Among non-structural HCV proteins, NS3 protein is an excellent goal for a therapeutic vaccine, due to its large size and less variation in conserved regions. The immunogenic properties of heat shock proteins (HSPs) for instance GP96 have prompted investigations into their function as strong adjuvant to improve innate and adaptive immunity. Objectives The aim of this study was to examine additive effects of recombinant GP96 (rGP96) fragments accompanied by rNS3 on expression levels of α5integrin and pro-inflammatory cytokines, IL-12 and TNFα, in Antigen Presenting Cells (APCs). Materials and Methods Recombinant viral proteins (rNS3 and rRGD-NS3), N-terminal and C-terminal fragments of GP96 were produced and purified from E. coli in order to treat the cells; mouse spleen Dendritic Cells (DCs) and THP-1 macrophages. Results Our results showed that rNT-GP96 alone significantly increases the expression level of IL-12, TNFα and α5integrin in THP-1 macrophages and DCs, while IL-12 and TNFα expression levels were unaffected by either rNS3 or rRGD-NS3. Interestingly, the co-addition of these recombinant proteins with rNT-GP96 increased IL-12, TNFα and α5integrin expression. Pearson Correlation showed a direct association between α5integrin with IL-12 and TNF-α expression. Conclusions we have highlighted the role of rNS3 plus rNT-GP96 mediated by α5integrin in producing IL-12 and TNFα. It can be suggested that rNT-GP96 could enhance immunity characteristic of rNS3 protein via production of pro-inflammatory cytokines. PMID:24032046

  14. Polymorphisms of transporter associated with antigen presentation, tumor necrosis factor-α and interleukin-10 and their implications for protection and susceptibility to severe forms of dengue fever in patients in Sri Lanka

    Directory of Open Access Journals (Sweden)

    Anira N Fernando

    2015-01-01

    Full Text Available Context: To date, a clear understanding of dengue disease pathogenesis remains elusive. Some infected individuals display no symptoms while others develop severe life-threatening forms of the disease. It is widely believed that host genetic factors influence dengue severity. Aims: This study evaluates the relationship between certain polymorphisms and dengue severity in Sri Lankan patients. Settings and Design: Polymorphism studies are carried out on genes for; transporter associated with antigen presentation (TAP, promoter of tumor necrosis factor-α (TNF-α, and promoter of interleukin-10 (IL-10. In other populations, TAP1 (333, TAP2 (379, TNF-α (−308, and IL-10 (−1082, −819, −592 have been associated with dengue and a number of different diseases. Data have not been collected previously for these polymorphisms for dengue patients in Sri Lanka. Materials and Methods: The polymorphisms were typed by amplification refractory mutation system polymerase chain reaction in 107 dengue hemorrhagic fever (DHF patients together with 62 healthy controls. Statistical Analysis Used: Pearson′s Chi-square contingency table analysis with Yates′ correction. Results: Neither the TAP nor the IL-10 polymorphisms considered individually can define dengue disease outcome with regard to severity. However, the genotype combination, IL-10 (−592/−819/−1082 CCA/ATA was significantly associated with development of severe dengue in these patients, suggesting a risk factor to developing DHF. Also, identified is the genotype combination IL-10 (−592/−819/−1082 ATA/ATG which suggested a possibility for protection from DHF. The TNF-α (−308 GG genotype was also significantly associated with severe dengue, suggesting a significant risk factor. Conclusions: The results reported here are specific to the Sri Lankan population. Comparisons with previous reports imply that data may vary from population to population.

  15. Potential combined effects of maternal smoking and coffee intake on foetal death within the Danish National Birth Cohort

    DEFF Research Database (Denmark)

    Morales-Suárez-Varela, Maria; Nohr, Ellen A; Olsen, Jørn

    2018-01-01

    on the risk of foetal (early and late) death. The study included 90 086 pregnant women, with information about their smoking habit and coffee intake in early pregnancy, and several potential confounding factors. Interaction was studied by calculating both the hazard ratio (HR) in Cox's regression (linear......Background: Several studies have linked coffee intake and smoking to foetal death, but a possible interaction between both exposures remains unknown. Methods: We studied, within the Danish National Birth Cohort, the potential interaction between smoking and coffee drinking while pregnant...... and smoothed restricted cubic spline) and the interaction contrast ratio (ICR). Results: Women who neither smoked nor drank coffee were used as the reference group. Drinking more than 3 cups/d of coffee was associated with the highest risk of foetal death, spontaneous abortion and stillbirth for all smoking...

  16. Chemoselective ligation and antigen vectorization.

    Science.gov (United States)

    Gras-Masse, H

    2001-01-01

    The interest in cocktail-lipopeptide vaccines has now been confirmed by phase I clinical trials: highly diversified B-, T-helper or cytotoxic T-cell epitopes can be combined with a lipophilic vector for the induction of B- and T-cell responses of predetermined specificity. With the goal of producing an improved vaccine that should ideally induce a multispecific response in non-selected populations, increasing the diversity of the immunizing mixture represents one of the most obvious strategies.The selective delivery of antigens to professional antigen-presenting cells represents another promising approach for the improvement of vaccine efficacy. In this context, the mannose-receptor represents an attractive entry point for the targeting to dendritic cells of antigens linked to clustered glycosides or glycomimetics. In all cases, highly complex but fully characterized molecules must be produced. To develop a modular and flexible strategy which could be generally applicable to a large set of peptide antigens, we elected to explore the potentialities of chemoselective ligation methods. The hydrazone bond was found particularly reliable and fully compatible with sulphide ligation. Hydrazone/thioether orthogonal ligation systems could be developed to account for the nature of the antigens and the solubility of the vector systems. Copyright 2001 The International Association for Biologicals.

  17. Virosomes for antigen and DNA delivery

    NARCIS (Netherlands)

    Daemen, T; de Mare, A; Bungener, L; de Jonge, J; Huckriede, A; Wilschut, J

    2005-01-01

    Specific targeting and delivery as well as the display of antigens on the surface of professional antigen-presenting cells (APCs) are key issues in the design and development of new-generation vaccines aimed at the induction of both humoral and cell-mediated immunity. Prophylactic vaccination

  18. A group-specific inhibitor of lysosomal cysteine proteinases selectively inhibits both proteolytic degradation and presentation of the antigen dinitrophenyl-poly-L-lysine by guinea pig accessory cells to T cells

    DEFF Research Database (Denmark)

    Buus, S; Werdelin, O

    1986-01-01

    of antigens by guinea pig accessory cells. The proteinase inhibitor benzyloxycarbonyl-phenylalanylalanine-diazomethyl-ketone, which selectively inhibits cysteine proteinases, was used to block this set of enzymes in cultured cells. We demonstrate that the selective inhibition of the cysteine proteinases...

  19. Is foetal hyperexposure to androgens a cause of PCOS?

    Science.gov (United States)

    Filippou, Panagiota; Homburg, Roy

    2017-07-01

    Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting reproductive-aged women. The pathophysiology of this syndrome is still not completely understood but recent evidence suggests that the intra-uterine environment may be a key factor in the pathogenesis of PCOS, in particular, hyperexposure of the foetus to androgens. High concentrations of maternal serum testosterone during pregnancy have been shown to influence behaviour during childhood, the prevalence of autism disorders and anti-Mullerian hormone (AMH) concentrations in adolescence. They are also thought to re-programme the female reproductive axis to induce the features of PCOS in later life: oligo/anovulation, polycystic ovaries, hyperandrogenism and insulin resistance (IR). Support for this developmental theory for the aetiology of PCOS is gathering momentum, following results from first animal studies and now human data, which lend credence to many aspects of this hypothesis. In this review the recent available evidence is presented to support the hypothesis that hyperandrogenic changes in the intra-uterine environment could play a major part in the aetiological basis of PCOS. An extensive PubMED and MEDline database search was conducted. Relevant studies were identified using a combination of search terms: 'polycystic ovary syndrome', 'PCOS', 'aetiology', 'anti-Mullerian hormone', 'AMH', 'pathogenesis', 'kisspeptin', 'hyperandrogenism', 'insulin resistance', 'metabolic factors', 'placenta', 'developmental hypothesis', 'genetic and epigenetic origins'. A total of 82 studies were finally included in this review. There is robust evidence that a hyperandrogenic intra-uterine environment 'programmes' the genes concerned with ovarian steroidogenesis, insulin metabolism, gonadotrophin secretion and ovarian follicle development resulting in the development of PCOS in adult life. Once the evidence supporting this hypothesis has been expanded by additional studies, the door would be open to

  20. Importance of zinc for foetal and post-natal development in swine

    International Nuclear Information System (INIS)

    Palludan, B.; Wegger, I.

    1976-01-01

    Maternal zinc deficiency during the third trimester led to redeced zinc concentration in foetal plasma, liver, pancreas and bone. Zinc deposition in foetuses was an exponential function of time, the relative rate being 5.8 and 3.0% daily in normal and deficient foetuses respectively. Distribution of orally administered 65 Zn between maternal and foetal organs was studied. The percentage of absorbed 65 Zn transferred to the foeto-placental unit tended to be highest in zinc-deficient gilts. The greater the liver zinc pool the more 65 Zn accumulated in liver and the less in most other organs in both gilts and foetuses. The gestation period was prolonged and parturition impaired in gilts depleted of zinc late in pregnancy. Persistent loss of umbilical blood was seen and viability of the offspring was poor. However, clinical symptoms and morphological malformations were few. Abnormal ossification occurred as a result of the zinc deficiency. The nature of the changes depended on the period of gestation during which the gilts were depleted of zinc. Absorption of 65 Zn in newborn pigs was unaffected by the zinc status, and the same pattern of distribution among organs as in foetuses was seen. Litter size and weight were not influenced by maternal zinc depletion, and growth of surviving piglets was normal. Zinc stores were low in the newborn, but even when zinc depletion of the mother was continued during lactation, clinical symptoms of zinc deficiency in the piglets were not seen until shortly before weaning. (author)

  1. An efficient protocol for the detection of chromosomal abnormalities in spontaneous miscarriages or foetal deaths.

    Science.gov (United States)

    Dória, Sofia; Carvalho, Filipa; Ramalho, Carla; Lima, Vera; Francisco, Tânia; Machado, Ana Paula; Brandão, Otília; Sousa, Mário; Matias, Alexandra; Barros, Alberto

    2009-12-01

    Characterization of chromosomal abnormalities in 232 spontaneous miscarriages or foetal deaths using both classical and molecular cytogenetics. Chromosomal abnormalities are responsible for 40-50% of all early pregnancy losses. Conventional cytogenetics is associated with 10-40% of culture failure. Comparative genomic hybridization (CGH) is a DNA-based technique that screens chromosome imbalances in the whole genome and may overcome this problem, although additional methods are required to distinguish between different ploidies, mosaicisms and maternal cell contamination. For a full characterization of chromosomal aberrations in 232 spontaneous miscarriages or foetal deaths we applied a sequential protocol that uses conventional cytogenetics, plus CGH and touch fluorescence in situ hybridization (Touch FISH). Successful karyotyping was obtained in 173/232 (74.6%) of the cases, 66/173 (38.2%) of which had an abnormal chromosomal complement. CGH and Touch FISH analyses revealed another 19 abnormal cases in the 63 failures of culture. Overall there were 85/233 (36.6%) cases with an abnormal chromosomal complement, with examples from all three trimesters. Comparing cases, with or without chromosomal abnormalities, no statistical differences were found between women with one or recurrent miscarriages. On the contrary, significant differences were found comparing mean maternal ages or mean gestational ages, in cases with or without chromosomes abnormalities. Adopting this sequential protocol, chromosomal complement information was available even in cases with culture failure.

  2. Foetal Radiation Dose and Risk from Diagnostic Radiology Procedures: A Multinational Study

    International Nuclear Information System (INIS)

    Osei, Ernest K.; Darko, Johnson

    2012-01-01

    In diagnostic radiology examinations there is a benefit that the patient derives from the resulting diagnosis. Given that so many examinations are performed each year, it is inevitable that there will be occasions when an examination(s) may be inadvertently performed on pregnant patients or occasionally it may become clinically necessary to perform an examination(s) on a pregnant patient. In all these circumstances it is necessary to request an estimation of the foetal dose and risk. We initiated a study to investigate fetal doses from different countries. Exposure techniques on 367 foetuses from 414 examinations were collected and investigated. The FetDoseV4 program was used for all dose and risk estimations. The radiation doses received by the 367 foetuses ranges: <0.001–21.9 mGy depending on examination and technique. The associated probability of induced hereditary effect ranges: <1 in 200000000 (5 × 10 −9 ) to 1 in 10000 (1 × 10 −4 ) and the risk of childhood cancer ranges <1 in 12500000 (8 × 10 −8 ) to 1 in 500 (2 × 10 −3 ). The data indicates that foetal doses from properly conducted diagnostic radiology examinations will not result in any deterministic effect and a negligible risk of causing radiation induced hereditary effect in the descendants of the unborn child

  3. Long-term effects of foetal undernutrition on intermediary metabolism in growing lambs

    DEFF Research Database (Denmark)

    Kiani, Ali; Nielsen, Mette Benedicte Olaf; Tauson, Anne-Helene

    2011-01-01

    The objective of this study was to investigate the effects of foetal undernutrition on the metabolism in growing lambs. Seven-month-old lambs whose nothers had been fed either restrictively (RN; n = 14) or adequately (AN; n = 6) in late gestation were fasted for three days. One hour before fasting......, IGF-I and leptin were not different between the two groups of lambs. Unexpectedly, at the end of the 3 d fasting, in spite of lower NEFA concentration (1.6 ± 0.03 vs. 1.9 ± 0.05 mM in Groups RN and AN, respectively), the BOHB concentration in RN lambs (0.94 ± 0.02 mM) was significantly higher than...... that in AN lambs (0.78 ± 0.04 mM). This higher rate of BOHB production might be interpreted as perturbations in etone body metabolism potentially induced by under-nutrition during foetal life. However, more investigations are necessary to clarify this interrelationship....

  4. Software for the estimation of foetal radiation dose to patients and staff in diagnostic radiology

    Energy Technology Data Exchange (ETDEWEB)

    Osei, E K [Department of Radiation Physics, Princess Margaret Hospital, 610 University Avenue, Toronto ON M5G 2M9 (Canada); Darko, J B [Department of Radiation Physics, Princess Margaret Hospital, 610 University Avenue, Toronto ON M5G 2M9 (Canada); Faulkner, K [Quality Assurance Centre, Newcastle General Hospital, Westgate Road, Newcastle Upon Tyne NE4 6BE (United Kingdom); Kotre, C J [Regional Medical Physics Department, Newcastle General Hospital, Westgate Road, Newcastle Upon Tyne NE4 6BE (United Kingdom)

    2003-06-01

    Occasionally, it is clinically necessary to perform a radiological examination(s) on a woman who is known to be pregnant or an examination is performed on a woman who subsequently discovers that she was pregnant at the time. In radiological examinations, especially of the lower abdomen and pelvis area, the foetus is directly irradiated. It is therefore important to be able to determine the absorbed dose to the foetus in diagnostic radiology for pregnant patients as well as the foetal dose from occupational exposure of the pregnant worker. The determination of the absorbed dose to the unborn child in diagnostic radiology is of interest as a basis for risk estimates from medical exposure of the pregnant patient and occupational exposure of the pregnant worker. In this paper we describe a simple computer program, FetDose, which calculates the dose to the foetus from both medical and occupational exposures of the pregnant woman. It also calculates the risks of in utero exposure, compares calculated doses with published data in the literature and provides information on the natural spontaneous risks. The program will be a useful tool for the medical and paramedical personnel who are involved with foetal dose (and hence risks) calculations and counselling of pregnant women who may be concerned about in utero exposure of their foetuses.

  5. Software for the estimation of foetal radiation dose to patients and staff in diagnostic radiology

    International Nuclear Information System (INIS)

    Osei, E K; Darko, J B; Faulkner, K; Kotre, C J

    2003-01-01

    Occasionally, it is clinically necessary to perform a radiological examination(s) on a woman who is known to be pregnant or an examination is performed on a woman who subsequently discovers that she was pregnant at the time. In radiological examinations, especially of the lower abdomen and pelvis area, the foetus is directly irradiated. It is therefore important to be able to determine the absorbed dose to the foetus in diagnostic radiology for pregnant patients as well as the foetal dose from occupational exposure of the pregnant worker. The determination of the absorbed dose to the unborn child in diagnostic radiology is of interest as a basis for risk estimates from medical exposure of the pregnant patient and occupational exposure of the pregnant worker. In this paper we describe a simple computer program, FetDose, which calculates the dose to the foetus from both medical and occupational exposures of the pregnant woman. It also calculates the risks of in utero exposure, compares calculated doses with published data in the literature and provides information on the natural spontaneous risks. The program will be a useful tool for the medical and paramedical personnel who are involved with foetal dose (and hence risks) calculations and counselling of pregnant women who may be concerned about in utero exposure of their foetuses

  6. Thymosin beta(4 and beta(10 levels in pre-term newborn oral cavity and foetal salivary glands evidence a switch of secretion during foetal development.

    Directory of Open Access Journals (Sweden)

    Sonia Nemolato

    Full Text Available BACKGROUND: Thymosin beta(4, its sulfoxide, and thymosin beta(10 were detected in whole saliva of human pre-term newborns by reversed-phase high performance chromatography coupled to electrospray ion-trap mass spectrometry. METHODOLOGY/PRINCIPAL FINDINGS: Despite high inter-individual variability, concentration of beta-thymosins increases with an inversely proportional trend to postmenstrual age (PMA: gestational age plus chronological age after birth reaching a value more than twenty times higher than in adult whole saliva at 190 days (27 weeks of PMA (thymosin beta(4 concentration: more than 2.0 micromol/L versus 0.1 micromol/L. On the other hand, the ratio between thymosin beta(4 and thymosin beta(10 exhibits a constant value of about 4 along all the range of PMA (190-550 days of PMA examined. In order to investigate thymosin beta(4 origin and to better establish the trend of its production as a function of gestational age (GA, immunohistochemical analysis of major and minor salivary glands of different pre-term fetuses were carried out, starting from 84 days (12 weeks of gestational age. Reactive granules were seen in all glands with a maximum of expression around 140-150 days of GA, even though with high inter- and intra-individual variability. In infants and adults reactive granules in acinar cells were not observed, but just a diffuse cytoplasmatic staining in ductal cells. SIGNIFICANCE: This study outlines for the first time that salivary glands during foetal life express and secrete peptides such as beta-thymosins probably involved in the development of the oral cavity and its annexes. The secretion increases from about 12 weeks till to about 21 weeks of GA, subsequently it decreases, almost disappearing in the period of expected date of delivery, when the gland switches towards the secretion of adult specific salivary peptides. The switch observed may be an example of further secretion switches involving other exocrine and endocrine

  7. The C Terminus of the Nucleoprotein of Influenza A Virus Delivers Antigens Transduced by Tat to the trans-Golgi Network and Promotes an Efficient Presentation through HLA Class I

    OpenAIRE

    Bettosini, Francesca; Fiorillo, Maria Teresa; Magnacca, Adriana; Leone, Laura; Torrisi, Maria Rosaria; Sorrentino, Rosa

    2005-01-01

    Cytotoxic T lymphocytes (CTLs) are the most powerful weapon of the immune system to eliminate cells infected by intracellular parasites or tumors. However, very often, escape mechanisms overcome CTL immune surveillance by impairing the classical HLA class I antigen-processing pathway. Here, we describe a strategy for CTL activation based on the ability of Tat to mediate transcellular delivery of viral proteins encompassing HLA class I-restricted epitopes. In this system, the recombinant prote...

  8. Children adopted from Poland display a high risk of foetal alcohol spectrum disorders and some may go undiagnosed

    NARCIS (Netherlands)

    Knuiman, S.; Rijk, C.H.A.M.; Hoksbergen, R.A.C.; van Baar, A.L.

    2015-01-01

    Aim: Children adopted from Central and Eastern Europe often have negative early experiences, including prenatal exposure to alcohol. We examined a group of Polish children, adopted by Dutch parents, to see how many were diagnosed with foetal alcohol spectrum disorders (FASD) and to what extent

  9. Loss-of-function mutations in SCN4A> cause severe foetal hypokinesia or 'classical' congenital myopathy

    DEFF Research Database (Denmark)

    Zaharieva, Irina T; Thor, Michael G; Oates, Emily C

    2016-01-01

    Congenital myopathies are a clinically and genetically heterogeneous group of muscle disorders characterized by congenital or early-onset hypotonia and muscle weakness, and specific pathological features on muscle biopsy. The phenotype ranges from foetal akinesia resulting in in utero or neonatal...

  10. Stem cells from foetal adnexa and fluid in domestic animals: an update on their features and clinical application.

    Science.gov (United States)

    Iacono, E; Rossi, B; Merlo, B

    2015-06-01

    Over the past decade, stem cell research has emerged as an area of major interest for its potential in regenerative medicine applications. This is in constant need of new cell sources to conceive regenerative medicine approaches for diseases that are still without therapy. Scientists drew the attention towards alternative sources such as foetal adnexa and fluid, as these sources possess many advantages: first of all, cells can be extracted from discarded foetal material and it is non-invasive and inexpensive for the patient; secondly, abundant stem cells can be obtained; and finally, these stem cell sources are free from ethical considerations. Cells derived from foetal adnexa and fluid preserve some of the characteristics of the primitive embryonic layers from which they originate. Many studies have demonstrated the differentiation potential in vitro and in vivo towards mesenchymal and non-mesenchymal cell types; in addition, the immune-modulatory properties make these cells a good candidate for allo- and xenotransplantation. Naturally occurring diseases in domestic animals can be more ideal as disease model of human genetic and acquired diseases and could help to define the potential therapeutic use efficiency and safety of stem cells therapies. This review offers an update on the state of the art of characterization of domestic animals' MSCs derived from foetal adnexa and fluid and on the latest findings in pre-clinical or clinical setting of the stem cell populations isolated from these sources. © 2015 Blackwell Verlag GmbH.

  11. Effect of Transient Maternal Hypotension on Apoptotic Cell Death in Foetal Rat Brain

    Directory of Open Access Journals (Sweden)

    Hamit Özyürek

    2014-03-01

    Full Text Available Background: Intrauterine perfusion insufficiency induced by transient maternal hypotension has been reported to be associated with foetal brain malformations. However, the effects of maternal hypotension on apoptotic processes in the foetal brain have not been investigated experimentally during the intrauterine period. Aims: The aim of this study was to investigate the effects of transient maternal hypotension on apoptotic cell death in the intrauterine foetal brain. Study Design: Animal experimentation. Methods: Three-month-old female Wistar albino rats were allocated into four groups (n=5 each. The impact of hypoxic/ischemic injury induced by transient maternal hypotension on the 15th day of pregnancy (late gestation in rats was investigated at 48 (H17 group or 96 hours (H19 group after the insult. Control groups underwent the same procedure except for induction of hypotension (C17 and H17 groups. Brain sections of one randomly selected foetus from each pregnant rat were histopathologically evaluated for hypoxic/ischemic injury in the metencephalon, diencephalon, and telencephalon by terminal transferase-mediated dUTP nick end labelling and active cysteine-dependent aspartate-directed protease-3 (caspase-3 positivity for cell death. Results: The number of terminal transferase-mediated dUTP nick end labelling (+ cells in all the areas examined was comparable in both hypotension and control groups. The H17 group had active caspase-3 (+ cells in the metencephalon and telencephalon, sparing diencephalon, whereas the C19 and H19 groups had active caspase-3 (+ cells in all three regions. The number of active caspase-3 (+ cells in the telencephalon in the H19 group was higher compared with the metencephalon and diencephalon and compared with H17 group (p<0.05. Conclusion: Our results suggest that prenatal hypoxic/ischemic injury triggers apoptotic mechanisms. Therefore, blockade of apoptotic pathways, considering the time pattern of the insult, may

  12. Antigenic determinants and functional domains in core antigen and e antigen from hepatitis B virus

    International Nuclear Information System (INIS)

    Salfeld, J.; Pfaff, E.; Noah, M.; Schaller, H.

    1989-01-01

    The precore/core gene of hepatitis B virus directs the synthesis of two polypeptides, the 21-kilodalton subunit (p21c) forming the viral nucleocapsid (serologically defined as core antigen [HBcAg]) and a secreted processed protein (p17e, serologically defined as HBe antigen [HBeAg]). Although most of their primary amino acid sequences are identical, HBcAg and HBeAg display different antigenic properties that are widely used in hepatitis B virus diagnosis. To locate and to characterize the corresponding determinants, segments of the core gene were expressed in Escherichia coli and probed with a panel of polyclonal or monoclonal antibodies in radioimmunoassays or enzyme-linked immunosorbent assays, Western blots, and competition assays. Three distinct major determinants were characterized. It is postulated that HBcAg and HBeAg share common basic three-dimensional structure exposing the common linear determinant HBe1 but that they differ in the presentation of two conformational determinants that are either introduced (HBc) or masked (HBe2) in the assembled core. The simultaneous presentation of HBe1 and HBc, two distinctly different antigenic determinants with overlapping amino acid sequences, is interpreted to indicate the presence of slightly differently folded, stable conformational states of p21c in the hepatitis virus nucleocapsid

  13. Understanding original antigenic sin in influenza with a dynamical system.

    Science.gov (United States)

    Pan, Keyao

    2011-01-01

    Original antigenic sin is the phenomenon in which prior exposure to an antigen leads to a subsequent suboptimal immune response to a related antigen. Immune memory normally allows for an improved and rapid response to antigens previously seen and is the mechanism by which vaccination works. I here develop a dynamical system model of the mechanism of original antigenic sin in influenza, clarifying and explaining the detailed spin-glass treatment of original antigenic sin. The dynamical system describes the viral load, the quantities of healthy and infected epithelial cells, the concentrations of naïve and memory antibodies, and the affinities of naïve and memory antibodies. I give explicit correspondences between the microscopic variables of the spin-glass model and those of the present dynamical system model. The dynamical system model reproduces the phenomenon of original antigenic sin and describes how a competition between different types of B cells compromises the overall effect of immune response. I illustrate the competition between the naïve and the memory antibodies as a function of the antigenic distance between the initial and subsequent antigens. The suboptimal immune response caused by original antigenic sin is observed when the host is exposed to an antigen which has intermediate antigenic distance to a second antigen previously recognized by the host's immune system.

  14. Evaluation of the foetal time to death in mice after application of direct and indirect euthanasia methods.

    Science.gov (United States)

    Muñoz-Mediavilla, C; Cámara, J A; Salazar, S; Segui, B; Sanguino, D; Mulero, F; de la Cueva, E; Blanco, I

    2016-04-01

    Directive 2010/63/EU on the protection of animals used for scientific purposes requires that the killing of mammal foetuses during the last third of their gestational period should be accomplished through effective and humane methods. The fact that murine foetuses are resistant to hypoxia-mediated euthanasia renders the current euthanasia methods ineffective or humane for the foetuses when these methods are applied to pregnant female mice. We have assessed the time to death of foetuses after performing either indirect (dam euthanasia) or direct (via intraplacental injection--a new approach to euthanasia) euthanasia methods in order to determine a euthanasia method that is appropriate, ethical and efficient for the killing of mouse foetuses. The respective times to death of foetuses after performing the three most commonly used euthanasia methods (namely cervical dislocation, CO2inhalation and intraperitoneal sodium pentobarbital administration) were recorded. Absence of foetal heartbeat was monitored via ultrasound. We consider that the most effective and humane method of foetal euthanasia was the one able to achieve foetal death within the shortest possible period of time. Among the indirect euthanasia methods assessed, the administration of a sodium pentobarbital overdose to pregnant female mice was found to be the fastest for foetuses, with an average post-treatment foetal death of approximately 29.8 min. As for the direct euthanasia method assessed, foetal time to death after intraplacental injection of sodium pentobarbital was approximately 14 min. Significant differences among the different mouse strains employed were found. Based on the results obtained in our study, we consider that the administration of a sodium pentobarbital overdose by intraplacental injection to be an effective euthanasia method for murine foetuses. © The Author(s) 2015.

  15. Dutch guideline for clinical foetal-neonatal and paediatric post-mortem radiology, including a review of literature.

    Science.gov (United States)

    Sonnemans, L J P; Vester, M E M; Kolsteren, E E M; Erwich, J J H M; Nikkels, P G J; Kint, P A M; van Rijn, R R; Klein, W M

    2018-06-01

    Clinical post-mortem radiology is a relatively new field of expertise and not common practice in most hospitals yet. With the declining numbers of autopsies and increasing demand for quality control of clinical care, post-mortem radiology can offer a solution, or at least be complementary. A working group consisting of radiologists, pathologists and other clinical medical specialists reviewed and evaluated the literature on the diagnostic value of post-mortem conventional radiography (CR), ultrasonography, computed tomography (PMCT), magnetic resonance imaging (PMMRI), and minimally invasive autopsy (MIA). Evidence tables were built and subsequently a Dutch national evidence-based guideline for post-mortem radiology was developed. We present this evaluation of the radiological modalities in a clinical post-mortem setting, including MIA, as well as the recently published Dutch guidelines for post-mortem radiology in foetuses, neonates, and children. In general, for post-mortem radiology modalities, PMMRI is the modality of choice in foetuses, neonates, and infants, whereas PMCT is advised in older children. There is a limited role for post-mortem CR and ultrasonography. In most cases, conventional autopsy will remain the diagnostic method of choice. Based on a literature review and clinical expertise, an evidence-based guideline was developed for post-mortem radiology of foetal, neonatal, and paediatric patients. What is Known: • Post-mortem investigations serve as a quality check for the provided health care and are important for reliable epidemiological registration. • Post-mortem radiology, sometimes combined with minimally invasive techniques, is considered as an adjunct or alternative to autopsy. What is New: • We present the Dutch guidelines for post-mortem radiology in foetuses, neonates and children. • Autopsy remains the reference standard, however minimal invasive autopsy with a skeletal survey, post-mortem computed tomography, or post

  16. The impact of the maternal-foetal environment on outcomes of surgery for congenital heart disease in neonates.

    Science.gov (United States)

    Gaynor, James William; Parry, Samuel; Moldenhauer, Julie S; Simmons, Rebecca A; Rychik, Jack; Ittenbach, Richard F; Russell, William W; Zullo, Erin; Ward, John Laurenson; Nicolson, Susan C; Spray, Thomas L; Johnson, Mark P

    2018-02-13

    Pregnancies with congenital heart disease in the foetus have an increased prevalence of pre-eclampsia, small for gestational age and preterm birth, which are evidence of an impaired maternal-foetal environment (MFE). The impact of an impaired MFE, defined as pre-eclampsia, small for gestational age or preterm birth, on outcomes after cardiac surgery was evaluated in neonates (n = 135) enrolled in a study evaluating exposure to environmental toxicants and neuro-developmental outcomes. The most common diagnoses were transposition of the great arteries (n = 47) and hypoplastic left heart syndrome (n = 43). Impaired MFE was present in 28 of 135 (21%) subjects, with small for gestational age present in 17 (61%) patients. The presence of an impaired MFE was similar for all diagnoses, except transposition of the great arteries (P MFE (14 vs 38 days, P MFE (11.7% vs 2.8%, P = 0.104). However, for the entire cohort, survival at 36 months was greater for those without an impaired MFE (96% vs 68%, P = 0.001). For patients with hypoplastic left heart syndrome, survival was also greater for those without an impaired MFE (90% vs 43%, P = 0.007). An impaired MFE is common in pregnancies in which the foetus has congenital heart disease. After cardiac surgery in neonates, the presence of an impaired MFE was associated with lower survival at 36 months of age for the entire cohort and for the subgroup with hypoplastic left heart syndrome. © The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  17. [Foetal therapy for Down syndrome: a pro-active ethical reflection].

    Science.gov (United States)

    de Wert, G M W R; Dondorp, W J

    2016-01-01

    Prenatal screening for Down syndrome has to date focused on facilitating the informed choice to continue or not with a pregnancy. The non-invasive prenatal test (NIPT) for Down syndrome does potentially offer the option to apply foetal neurocognitive therapy for Down syndrome (FTDS). Current research in animal models looks promising and therefore a proactive ethical reflection in relation to clinical trials is urgently needed. This discussion includes an exploration of the ethical aspects of FTDS. There seem to be no convincing a priori objections on the basis of the social model of disability. Arguments in terms of (respect for) autonomy, wellbeing and justice seem to in principle support such therapy. Still, both the conditions for sound clinical trials and the implications of possible effective therapy for current prenatal screening need further scrutiny.

  18. A Phosphorylcholine-Containing Glycolipid-like Antigen Present on the Surface of Infective Stage Larvae of Ascaris spp. Is a Major Antibody Target in Infected Pigs and Humans.

    Directory of Open Access Journals (Sweden)

    Johnny Vlaminck

    2016-12-01

    Full Text Available The pig parasite Ascaris suum plays and important role in veterinary medicine and represents a suitable model for A. lumbricoides, which infects over 800 million people. In pigs, continued exposure to Ascaris induces immunity at the level of the gut, protecting the host against migrating larvae. The objective of this study was to identify and characterize parasite antigens targeted by this local immune response that may be crucial for parasite invasion and establishment and to evaluate their protective and diagnostic potential.Pigs were immunized by trickle infection for 30 weeks, challenged with 2,000 eggs at week 32 and euthanized two weeks after challenge. At necropsy, there was a 100% reduction in worms recovered from the intestine and a 97.2% reduction in liver white spots in comparison with challenged non-immune control animals. Antibodies purified from the intestinal mucus or from the supernatant of cultured antibody secreting cells from mesenteric lymph nodes of immune pigs were used to probe L3 extracts to identify antibody targets. This resulted in the recognition of a 12kDa antigen (As12 that is actively shed from infective Ascaris L3. As12 was characterized as a phosphorylcholine-containing glycolipid-like antigen that is highly resistant to different enzymatic and chemical treatments. Vaccinating pigs with an As12 fraction did not induce protective immunity to challenge infection. However, serological analysis using sera or plasma from experimentally infected pigs or naturally infected humans demonstrated that the As12 ELISA was able to detect long-term exposure to Ascaris with a high diagnostic sensitivity (98.4% and 92%, respectively and specificity (95.5% and 90.0% in pigs and humans, respectively.These findings show the presence of a highly stage specific, glycolipid-like component (As12 that is actively secreted by infectious Ascaris larvae and which acts as a major antibody target in infected humans and pigs.

  19. Foetal loss and enhanced fertility observed in mice treated with Zidovudine or Nevirapine.

    Science.gov (United States)

    Onwuamah, Chika K; Ezechi, Oliver C; Herbertson, Ebiere C; Audu, Rosemary A; Ujah, Innocent A O; Odeigah, Peter G C

    2014-01-01

    Health concerns for HIV-infected persons on antiretroviral therapy (ART) have moved from morbidity to the challenges of long-term ART. We investigated the effect of Zidovudine or Nevirapine on reproductive capacity across two mouse generations. A prospective mouse study with drugs administered through one spermatogenic cycle. Mouse groups (16 males and 10 females) were given Zidovudine or Nevirapine for 56 days. Males were mated to untreated virgin females to determine dominant lethal effects. Twenty females (10 treated and 10 untreated) mated with the treated males per dose and gave birth to the F1 generation. Parental mice were withdrawn from drugs for one spermatogenic cycle and mated to the same dams to ascertain if effects are reversible. The F1 generation were exposed for another 56 days and mated to produce the F2 generation. Foetal loss was indicated in the dominant lethal assay as early as four weeks into drug administration to the males. At the first mating of the parental generation to produce the F1 generation, births from 10 dams/dose when the 'father-only' was exposed to Zidovudine (10, 100 and 250 mg/kg) was 3, 2 and 1 while it was 7, 1 and 4 respectively when 'both-parents' were exposed. Similarly births from the parental generation first mating when the 'father-only' was exposed to Nevirapine (5, 50 and 150 mg/kg) was 2, 2 and 0 while it was 6, 5 and 9 respectively when 'both-parents' were exposed. However, fertility was not significantly different neither by dose nor by the parental exposure. The F1 mice mated to produce the F2 generation recorded only one birth. The dominant lethal analysis showed foetal loss occurred when the "fathers-only" were treated while fertility was enhanced when "both-parents" were on therapy at the time of mating.

  20. Influence of Maternal Obesity and Gestational Weight Gain on Maternal and Foetal Lipid Profile.

    Science.gov (United States)

    Cinelli, Giulia; Fabrizi, Marta; Ravà, Lucilla; Ciofi Degli Atti, Marta; Vernocchi, Pamela; Vallone, Cristina; Pietrantoni, Emanuela; Lanciotti, Rosalba; Signore, Fabrizio; Manco, Melania

    2016-06-15

    Fatty acids (FAs) are fundamental for a foetus's growth, serving as an energy source, structural constituents of cellular membranes and precursors of bioactive molecules, as well as being essential for cell signalling. Long-chain polyunsaturated FAs (LC-PUFAs) are pivotal in brain and visual development. It is of interest to investigate whether and how specific pregnancy conditions, which alter fatty acid metabolism (excessive pre-pregnancy body mass index (BMI) or gestational weight gain (GWG)), affect lipid supply to the foetus. For this purpose, we evaluated the erythrocyte FAs of mothers and offspring (cord-blood) at birth, in relation to pre-pregnancy BMI and GWG. A total of 435 mothers and their offspring (237 males, 51%) were included in the study. Distribution of linoleic acid (LA) and α-linolenic acid (ALA), and their metabolites, arachidonic acid, dihomogamma linoleic (DGLA) and ecosapentanoic acid, was significantly different in maternal and foetal erythrocytes. Pre-pregnancy BMI was significantly associated with maternal percentage of MUFAs (Coeff: -0.112; p = 0.021), LA (Coeff: -0.033; p = 0.044) and DHA (Coeff. = 0.055; p = 0.0016); inadequate GWG with DPA (Coeff: 0.637; p = 0.001); excessive GWG with docosaexahenoic acid (DHA) (Coeff. = -0.714; p = 0.004). Moreover, pre-pregnancy BMI was associated with foetus percentage of PUFAs (Coeff: -0.172; p = 0.009), omega 6 (Coeff: -0.098; p = 0.015) and DHA (Coeff: -0.0285; p = 0.036), even after adjusting for maternal lipids. Our findings show that maternal GWG affects maternal but not foetal lipid profile, differently from pre-pregnancy BMI, which influences both.

  1. Foetal loss and enhanced fertility observed in mice treated with Zidovudine or Nevirapine.

    Directory of Open Access Journals (Sweden)

    Chika K Onwuamah

    Full Text Available Health concerns for HIV-infected persons on antiretroviral therapy (ART have moved from morbidity to the challenges of long-term ART. We investigated the effect of Zidovudine or Nevirapine on reproductive capacity across two mouse generations.A prospective mouse study with drugs administered through one spermatogenic cycle. Mouse groups (16 males and 10 females were given Zidovudine or Nevirapine for 56 days. Males were mated to untreated virgin females to determine dominant lethal effects. Twenty females (10 treated and 10 untreated mated with the treated males per dose and gave birth to the F1 generation. Parental mice were withdrawn from drugs for one spermatogenic cycle and mated to the same dams to ascertain if effects are reversible. The F1 generation were exposed for another 56 days and mated to produce the F2 generation.Foetal loss was indicated in the dominant lethal assay as early as four weeks into drug administration to the males. At the first mating of the parental generation to produce the F1 generation, births from 10 dams/dose when the 'father-only' was exposed to Zidovudine (10, 100 and 250 mg/kg was 3, 2 and 1 while it was 7, 1 and 4 respectively when 'both-parents' were exposed. Similarly births from the parental generation first mating when the 'father-only' was exposed to Nevirapine (5, 50 and 150 mg/kg was 2, 2 and 0 while it was 6, 5 and 9 respectively when 'both-parents' were exposed. However, fertility was not significantly different neither by dose nor by the parental exposure. The F1 mice mated to produce the F2 generation recorded only one birth.The dominant lethal analysis showed foetal loss occurred when the "fathers-only" were treated while fertility was enhanced when "both-parents" were on therapy at the time of mating.

  2. Psychiatric disease in late adolescence and young adulthood. Foetal programming by maternal hypothyroidism?

    Science.gov (United States)

    Andersen, Stine Linding; Olsen, Jørn; Wu, Chun Sen; Laurberg, Peter

    2014-07-01

    Lack of maternal thyroid hormones during foetal brain development may lead to structural abnormalities in the brain. We hypothesized that maternal hypothyroidism during the pregnancy could programme the foetus to development of psychiatric disease later in life. Danish nationwide register study. Singletons live-born 1980-1990. Cox proportional hazards model was used to estimate adjusted hazard ratio (aHR) with 95% confidence interval for offspring redemption of ≥2 prescriptions of a psychiatric drug from age 15 to 31 years. Among 542 100 adolescents and young adults included, altogether 3979 (0·7%) were born to mothers with hypothyroidism registered before 1996. In crude analyses, the use of a psychiatric drug was more frequent in late adolescence and young adulthood when the mother had hypothyroidism (P hypothyroidism often also had a psychiatric registration (38·5% vs 27·7%, P hypothyroidism was associated with an increased risk of having redeemed prescriptions of anxiolytics [aHR 1·23 (1·03-1·48)] and antipsychotics [aHR 1·22 (1·03-1·44)] in late adolescence and young adulthood. For antidepressants, aHR was 1·07 (0·98-1·17). The association between maternal hypothyroidism and the use of a psychiatric drug in late adolescence and young adulthood was partly confounded by maternal psychiatric history, but foetal programming by maternal hypothyroidism may be part of the mechanisms leading to the use of anxiolytics and antipsychotics. © 2014 John Wiley & Sons Ltd.

  3. Carcinoembryonic antigen (CEA)

    International Nuclear Information System (INIS)

    Ephraim, K.H.; Cox, P.H.; Hamer, C.J.A. v.d.; Berends, W.; Delhez, H.

    1977-01-01

    The carcinoembryonic antigen (CEA) is a complex of antigen determinants and also the carrier of these determinants. Chemically it is a glycoprotein. Its occurrence in blood serum or urine is correlated with malignant disease. Several radioimmunoassays (RIA) have been developed, one by Hoffmann-Laroche and one by the Rotterdam Radiotherapeutic Institute. Both methods and the Hoffmann assay kit are tested. Specifications are given for isolation of the antigen, preparation of the antiserum, and the execution of the RIA. Biochemical and clinical aspects are discussed

  4. Antigen injection (image)

    Science.gov (United States)

    Leprosy is caused by the organism Mycobacterium leprae . The leprosy test involves injection of an antigen just under ... if your body has a current or recent leprosy infection. The injection site is labeled and examined ...

  5. Preliminary evaluation of foetal liver volume by three-dimensional ultrasound in women with gestational diabetes mellitus.

    Science.gov (United States)

    İlhan, Gülşah; Gültekin, Hüseyin; Kubat, Ayça; Gokmen Karasu, Ayse Filiz; Güngör, Emre Sinan; Zebitay, Galip Ali; Verit Atmaca, Fatma Ferda

    2018-03-19

    The aim of the study was to assess the standard foetal biometric measurements and foetal liver volume (FLV) in pregnancies complicated by gestational diabetes mellitus (GDM) at the time of GDM screening and to compare the results with foetuses in normal pregnancies. Ninety-seven pregnant women with normal singleton uncomplicated pregnancies between 24 and 28 weeks of gestation were allocated into GDM (+) (n: 33) and GDM (-) (n: 64) groups based on their 75 g oral glucose tolerance test results. Foetal biometric measurements and FLV measurements of the groups were compared. Although there were no significant differences in the standard biometric measurements between the two groups, FLV was significantly higher in the women with GDM (p liver length and foetal liver volume (FLV) have been evaluated as ultrasound parameters of glycaemic control. While the evaluation of foetal liver dimensions has a role in identifying foetal growth acceleration, previous studies addressed patients with insulin-dependent diabetes mellitus rather than gestational diabetes mellitus, utilised two-dimensional ultrasound and did not argue the diagnostic value of these findings. What do the results of this study add? In our study, besides the standard biometric measurements, the FLV measurements were evaluated by a three-dimensional ultrasound. Although there were no significant differences in the standard biometric measurements between the GDM (+) and GDM (-) groups, the FLV was significantly higher in women with GDM. The FLV was found to be a potential predictive factor for GDM. The ROC analysis implied that as a cut-off value of FLV of 32.72 cm 3 for GDM prediction, the sensitivity was 78.8% and the specificity was 56.3%. What are the implications of these findings for clinical practise and/or further research? Screening for GDM with oral glucose tolerance test within the limited weeks of gestation may not always be feasible. On the other hand, the mid-trimester ultrasound scanning

  6. Leukemia-associated antigens in man.

    Science.gov (United States)

    Brown, G; Capellaro, D; Greaves, M

    1975-12-01

    Rabbit antisera raised against acute lymphoblastic leukemia (ALL) cells were used to distinguish ALL from other leukemias, to identify rare leukemia cells in the bone marrow of patients in remission, and to define human leukemia-associated antigens. Antibody binding was studied with the use of immunofluorescence reagents and the analytic capacity of the Fluorescence Activated Cell Sorter-1 (FACS-1). The results indicated that most non-T-cell ALL have three leukemia-associated antigens on their surface which are absent from normal lymphoid cells: 1) an antigen shared with myelocytes, myeloblastic leukemia cells, and fetal liver (hematopoietic) cells; 2) an antigen shared with a subset of intermediate normoblasts in normal bone marrow and fetal liver; and 3) an antigen found thus far only on non-T-cell ALL and in some acute undifferentiated leukemias, which we therefore regard as a strong candidate for a leukemia-specific antigen. These antigens are absent from a subgroup of ALL patients in which the lymphoblasta express T-cell surface markers. Preliminary studies on the bone marrow samples of patients in remission indicated that rare leukemia cells were present in some samples. The implications of these findings with respect to the heterogeneity and cell origin(s) of ALL, its diagnosis, and its potential monitoring during treatment were discussed.

  7. Rapid spread and association of Schmallenberg virus with ruminant abortions and foetal death in Austria in 2012/2013.

    Science.gov (United States)

    Steinrigl, Adolf; Schiefer, Peter; Schleicher, Corina; Peinhopf, Walter; Wodak, Eveline; Bagó, Zoltán; Schmoll, Friedrich

    2014-10-15

    Schmallenberg virus (SBV) has emerged in summer-autumn 2011 in north-western Europe. Since then, SBV has been continuously spreading over Europe, including Austria, where antibodies to SBV, as well as SBV genome, were first detected in autumn 2012. This study was performed to demonstrate the dynamics of SBV spread within Austria, after its probable first introduction in summer 2012. True seroprevalence estimates for cattle and small ruminates were calculated to demonstrate temporal and regional differences of infection. Furthermore, the probability of SBV genome detection in foetal tissues of aborted or stillborn cattle and small ruminants as well as in allantoic fluid samples from cows with early foetal losses was retrospectively assessed. SBV first reached Austria most likely in July-August 2012, as indicated by retrospective detection of SBV antibodies and SBV genome in archived samples. From August to October 2012, a rapid increase in seroprevalence to over 98% in cattle and a contemporaneous peak in the detection of SBV genome in foetal tissues and allantoic fluid samples was noted, indicating widespread acute infections. Notably, foetal malformations were absent in RT-qPCR positive foetuses at this time of the epidemic. SBV spread within Austrian cattle reached a plateau phase as early as October 2012, without significant regional differences in SBV seroprevalence (98.4-100%). Estimated true seroprevalences among small ruminates were comparatively lower than in cattle and regionally different (58.3-95.6% in October 2012), potentially indicating an eastward spread of the infection, as well as different infection dynamics between cattle and small ruminants. Additionally, the probability of SBV genome detection over time differed significantly between small ruminant and cattle samples subjected to RT-qPCR testing. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Review of Mycobacteriumavium subsp. paratuberculosis antigen candidates with diagnostic potential

    DEFF Research Database (Denmark)

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

    2011-01-01

    antigens, heat shock antigens and hypothetical antigens. Strategies for evaluation of novel antigen candidates are discussed critically. Relatively few of the described antigens were evaluated for their use in CMI based diagnostic assays and so far, no obvious candidate has been identified...... to development of antibodies and shedding of detectable amounts of MAP. At present, available diagnostic assays are limited by the lack of MAP specific antigens included in these assays resulting in poor specificity. The objective of this review is to provide a systematic overview of diagnostic MAP antigen...... faeces; however, these diagnostic tools are often not applicable until years after infection. Detection of MAP specific cell-mediated immune (CMI) responses can serve as an alternative and be implemented in a diagnostic tool. CMI responses can be measured at an early stage of infection, prior...

  9. Are 3D ultrasound and office hysteroscopy useful for the assessment of uterine cavity after late foetal loss?

    Science.gov (United States)

    Thellier, E; Levaillant, J-M; Pourcelot, A-G; Houllier, M; Fernandez, H; Capmas, P

    2018-05-01

    To assess the efficacy of office hysteroscopy and 3D ultrasound for the diagnostic of uterine anomalies after late foetal loss. This retrospective observational study took place in the gynaecologic unit of a teaching hospital from 2009 to 2014. Women with late foetal loss (<22 weeks of gestation) had an office hysteroscopy and 3D ultrasound within three months after delivery. The results of the ultrasound and hysteroscopy were recorded and compared. Eighty women were included with a mean age of 29.8 years (28.2-31.4). Forty-seven women had both hysteroscopy and 3D ultrasound, and a uterine cavity's anomaly (bicornuate uterus, T-Shape uterus and septate uterus) was found in ten women (21%) at 3D sonography and in 13 women (28%) at office hysteroscopy. Concordance between the two exams was very good with a kappa at 0.83. In three cases, a uterine cavity's anomaly was found at hysteroscopy whereas sonography was normal. Anomalies at ultrasound (uterine cavity's anomaly, myometrium anomaly or ovarian anomaly) were found in 27.6% of cases. Both 3D ultrasound and office hysteroscopy are useful for assessment of the uterine cavity after late foetal loss. The application of these two exams is important, as hysteroscopy is generally used for assessment of the uterine cavity and endometrium, while 3D ultrasound is generally used to identify the precise type of uterine malformation and for the examination of the myometrium and annexes. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  10. “New” Antigenic Targets and Methodological Approaches for Refining Laboratory Diagnosis of Antiphospholipid Syndrome

    Science.gov (United States)

    Misasi, Roberta; Capozzi, Antonella; Longo, Agostina; Recalchi, Serena; Lococo, Emanuela; Alessandri, Cristiano; Conti, Fabrizio; Valesini, Guido

    2015-01-01

    Antiphospholipid antibodies (aPLs) are a heterogeneous group of antibodies directed against phospholipids or protein/phospholipid complexes. Currently, aPLs are assessed using either “solid-phase” assays that identify anticardiolipin antibodies and anti-β2-glycoprotein I antibodies or “liquid-phase” assay that identifies lupus anticoagulant. However, in the last few years, “new” antigenic targets and methodological approaches have been employed for refining laboratory diagnosis of antiphospholipid syndrome (APS). In this review the potential diagnostic value of antibodies to domains of β2-GPI, prothrombin/phosphatidylserine, vimentin/cardiolipin, protein S, protein C, annexin A2, annexin A5, and phospholipid antigens is discussed. Moreover, new technical approaches, including chemiluminescence, multiline dot assay, and thin layer chromatography (TLC) immunostaining, which utilize different supports for detection of aPL, have been developed. A special focus has been dedicated on “seronegative” APS, that is, those patients with a clinical profile suggestive of APS (thromboses, recurrent miscarriages, or foetal loss), who are persistently negative for the routinely used aPL. Recent findings suggest that, in sera from patients with SN-APS, antibodies may be detected using “new” antigenic targets (mainly vimentin/cardiolipin) or methodological approaches different from traditional techniques (TLC immunostaining). Thus, APS represents a mosaic, in which antibodies against different antigenic targets may be detected thanks to the continuously evolving new technologies. PMID:25874238

  11. [Massive increase of foetal abdominal circumference due to hereditary polycystic kidney disease].

    Science.gov (United States)

    Dukic, L; Schaffelder, R; Schaible, T; Sütterlin, M; Siemer, J

    2010-06-01

    Autosomal recessive polycystic kidney disease (ARPKD) is a rare condition with a poor prognosis. We report on a 30-year-old primagravid woman in the 34th) week of gestation who was admitted to our hospital. ARPKD of the foetus had been sonographically suspected since the 26th week of gestation. Ultrasound examination showed big polycystic kidneys on both sides. The non-consanguineous parents wanted a maximum therapy for the infant. Foetal digitalisation because of heart insufficiency and prophylactic lung maturation was started. In the further course, Doppler sonographic values worsened and a Caesarean section was performed in the 34th week of gestation at the demand of the parents and due to the expected problems in case of a vaginal delivery. The weight of the newborn was 3,780 g and the abdominal circumference was 50 cm. The newborn was intubated immediately after birth and artificial ventilation was performed. Extracorporeal membrane oxygenation was not possible due to the bad cardial condition. The boy died 16 h after delivery. The parents refused genetic examination and autopsy of the newborn. ARPKD is a severe disease that may have obstetric relevance, due to the massively increased abdominal circumference. Therefore, termination of pregnancy or preterm induction of labor should be considered in order to avoid Caesarean section. Additionally, early prenatal diagnosis with genetic analysis of PRKD1 in cases of suspected ARPKD can be helpful. Georg Thieme Verlag KG Stuttgart, New York.

  12. Offspring Hormones Reflect the Maternal Prenatal Social Environment: Potential for Foetal Programming?

    Science.gov (United States)

    Meise, Kristine; von Engelhardt, Nikolaus; Forcada, Jaume; Hoffman, Joseph Ivan

    2016-01-01

    Females of many species adaptively program their offspring to predictable environmental conditions, a process that is often mediated by hormones. Laboratory studies have shown, for instance, that social density affects levels of maternal cortisol and testosterone, leading to fitness-relevant changes in offspring physiology and behaviour. However, the effects of social density remain poorly understood in natural populations due to the difficulty of disentangling confounding influences such as climatic variation and food availability. Colonially breeding marine mammals offer a unique opportunity to study maternal effects in response to variable colony densities under similar ecological conditions. We therefore quantified maternal and offspring hormone levels in 84 Antarctic fur seals (Arctocephalus gazella) from two closely neighbouring colonies of contrasting density. Hair samples were used as they integrate hormone levels over several weeks or months and therefore represent in utero conditions during foetal development. We found significantly higher levels of cortisol and testosterone (both P hormonally mediated maternal effects may depend more strongly on the maternal regulation of androgen rather than cortisol levels. PMID:26761814

  13. Perinatal grief following a termination of pregnancy for foetal abnormality: the impact of coping strategies.

    Science.gov (United States)

    Lafarge, Caroline; Mitchell, Kathryn; Fox, Pauline

    2013-12-01

    Pregnancy termination for foetal abnormality (TFA) can have significant psychological repercussions, but little is known about the coping strategies involved in dealing with TFA. This study examined the relationships between women's coping strategies and perinatal grief. A total of 166 women completed a survey online. Coping and perinatal grief were measured using the Brief COPE and Short Perinatal Grief Scales. Data were analysed through multiple regression analyses. Despite using mostly adaptive coping strategies, women's levels of grief were high and varied according to obstetric and termination variables. Grief was predicted by behavioural disengagement, venting, planning, religion, self-blame, being recently bereaved, being childless at the time of TFA, not having had children/being pregnant since TFA and uncertainty about the decision to terminate the pregnancy. Acceptance and positive reframing negatively predicted grief. Identifying women vulnerable to poor psychological adjustment and promoting coping strategies associated with lower levels of grief may be beneficial. This could be addressed through information provision and interventions such as Cognitive Behavioural Therapy or Acceptance and Commitment Therapy. © 2013 John Wiley & Sons, Ltd.

  14. Do intrauterine or genetic influences explain the foetal origins of chronic disease? A novel experimental method for disentangling effects

    Directory of Open Access Journals (Sweden)

    Hay Dale

    2007-06-01

    Full Text Available Abstract Background There is much evidence to suggest that risk for common clinical disorders begins in foetal life. Exposure to environmental risk factors however is often not random. Many commonly used indices of prenatal adversity (e.g. maternal gestational stress, gestational diabetes, smoking in pregnancy are influenced by maternal genes and genetically influenced maternal behaviour. As mother provides the baby with both genes and prenatal environment, associations between prenatal risk factors and offspring disease maybe attributable to true prenatal risk effects or to the "confounding" effects of genetic liability that are shared by mother and offspring. Cross-fostering designs, including those that involve embryo transfer have proved useful in animal studies. However disentangling these effects in humans poses significant problems for traditional genetic epidemiological research designs. Methods We present a novel research strategy aimed at disentangling maternally provided pre-natal environmental and inherited genetic effects. Families of children aged 5 to 9 years born by assisted reproductive technologies, specifically homologous IVF, sperm donation, egg donation, embryo donation and gestational surrogacy were contacted through fertility clinics and mailed a package of questionnaires on health and mental health related risk factors and outcomes. Further data were obtained from antenatal records. Results To date 741 families from 18 fertility clinics have participated. The degree of association between maternally provided prenatal risk factor and child outcome in the group of families where the woman undergoing pregnancy and offspring are genetically related (homologous IVF, sperm donation is compared to association in the group where offspring are genetically unrelated to the woman who undergoes the pregnancy (egg donation, embryo donation, surrogacy. These comparisons can be then examined to infer the extent to which prenatal effects

  15. Evaluation of Antigen-Conjugated Fluorescent Beads to Identify Antigen-Specific B Cells.

    Science.gov (United States)

    Correa, Isabel; Ilieva, Kristina M; Crescioli, Silvia; Lombardi, Sara; Figini, Mariangela; Cheung, Anthony; Spicer, James F; Tutt, Andrew N J; Nestle, Frank O; Karagiannis, Panagiotis; Lacy, Katie E; Karagiannis, Sophia N

    2018-01-01

    Selection of single antigen-specific B cells to identify their expressed antibodies is of considerable interest for evaluating human immune responses. Here, we present a method to identify single antibody-expressing cells using antigen-conjugated fluorescent beads. To establish this, we selected Folate Receptor alpha (FRα) as a model antigen and a mouse B cell line, expressing both the soluble and the membrane-bound forms of a human/mouse chimeric antibody (MOv18 IgG1) specific for FRα, as test antibody-expressing cells. Beads were conjugated to FRα using streptavidin/avidin-biotin bridges and used to select single cells expressing the membrane-bound form of anti-FRα. Bead-bound cells were single cell-sorted and processed for single cell RNA retrotranscription and PCR to isolate antibody heavy and light chain variable regions. Variable regions were then cloned and expressed as human IgG1/k antibodies. Like the original clone, engineered antibodies from single cells recognized native FRα. To evaluate whether antigen-coated beads could identify specific antibody-expressing cells in mixed immune cell populations, human peripheral blood mononuclear cells (PBMCs) were spiked with test antibody-expressing cells. Antigen-specific cells could comprise up to 75% of cells selected with antigen-conjugated beads when the frequency of the antigen-positive cells was 1:100 or higher. In PBMC pools, beads conjugated to recombinant antigens FRα and HER2 bound antigen-specific anti-FRα MOv18 and anti-HER2 Trastuzumab antibody-expressing cells, respectively. From melanoma patient-derived B cells selected with melanoma cell line-derived protein-coated fluorescent beads, we generated a monoclonal antibody that recognized melanoma antigen-coated beads. This approach may be further developed to facilitate analysis of B cells and their antibody profiles at the single cell level and to help unravel humoral immune repertoires.

  16. Evaluation of Antigen-Conjugated Fluorescent Beads to Identify Antigen-Specific B Cells

    Directory of Open Access Journals (Sweden)

    Isabel Correa

    2018-03-01

    Full Text Available Selection of single antigen-specific B cells to identify their expressed antibodies is of considerable interest for evaluating human immune responses. Here, we present a method to identify single antibody-expressing cells using antigen-conjugated fluorescent beads. To establish this, we selected Folate Receptor alpha (FRα as a model antigen and a mouse B cell line, expressing both the soluble and the membrane-bound forms of a human/mouse chimeric antibody (MOv18 IgG1 specific for FRα, as test antibody-expressing cells. Beads were conjugated to FRα using streptavidin/avidin-biotin bridges and used to select single cells expressing the membrane-bound form of anti-FRα. Bead-bound cells were single cell-sorted and processed for single cell RNA retrotranscription and PCR to isolate antibody heavy and light chain variable regions. Variable regions were then cloned and expressed as human IgG1/k antibodies. Like the original clone, engineered antibodies from single cells recognized native FRα. To evaluate whether antigen-coated beads could identify specific antibody-expressing cells in mixed immune cell populations, human peripheral blood mononuclear cells (PBMCs were spiked with test antibody-expressing cells. Antigen-specific cells could comprise up to 75% of cells selected with antigen-conjugated beads when the frequency of the antigen-positive cells was 1:100 or higher. In PBMC pools, beads conjugated to recombinant antigens FRα and HER2 bound antigen-specific anti-FRα MOv18 and anti-HER2 Trastuzumab antibody-expressing cells, respectively. From melanoma patient-derived B cells selected with melanoma cell line-derived protein-coated fluorescent beads, we generated a monoclonal antibody that recognized melanoma antigen-coated beads. This approach may be further developed to facilitate analysis of B cells and their antibody profiles at the single cell level and to help unravel humoral immune repertoires.

  17. Evaluation of Antigen-Conjugated Fluorescent Beads to Identify Antigen-Specific B Cells

    Science.gov (United States)

    Correa, Isabel; Ilieva, Kristina M.; Crescioli, Silvia; Lombardi, Sara; Figini, Mariangela; Cheung, Anthony; Spicer, James F.; Tutt, Andrew N. J.; Nestle, Frank O.; Karagiannis, Panagiotis; Lacy, Katie E.; Karagiannis, Sophia N.

    2018-01-01

    Selection of single antigen-specific B cells to identify their expressed antibodies is of considerable interest for evaluating human immune responses. Here, we present a method to identify single antibody-expressing cells using antigen-conjugated fluorescent beads. To establish this, we selected Folate Receptor alpha (FRα) as a model antigen and a mouse B cell line, expressing both the soluble and the membrane-bound forms of a human/mouse chimeric antibody (MOv18 IgG1) specific for FRα, as test antibody-expressing cells. Beads were conjugated to FRα using streptavidin/avidin-biotin bridges and used to select single cells expressing the membrane-bound form of anti-FRα. Bead-bound cells were single cell-sorted and processed for single cell RNA retrotranscription and PCR to isolate antibody heavy and light chain variable regions. Variable regions were then cloned and expressed as human IgG1/k antibodies. Like the original clone, engineered antibodies from single cells recognized native FRα. To evaluate whether antigen-coated beads could identify specific antibody-expressing cells in mixed immune cell populations, human peripheral blood mononuclear cells (PBMCs) were spiked with test antibody-expressing cells. Antigen-specific cells could comprise up to 75% of cells selected with antigen-conjugated beads when the frequency of the antigen-positive cells was 1:100 or higher. In PBMC pools, beads conjugated to recombinant antigens FRα and HER2 bound antigen-specific anti-FRα MOv18 and anti-HER2 Trastuzumab antibody-expressing cells, respectively. From melanoma patient-derived B cells selected with melanoma cell line-derived protein-coated fluorescent beads, we generated a monoclonal antibody that recognized melanoma antigen-coated beads. This approach may be further developed to facilitate analysis of B cells and their antibody profiles at the single cell level and to help unravel humoral immune repertoires. PMID:29628923

  18. Inhibition of PIM1 kinase attenuates inflammation-induced pro-labour mediators in human foetal membranes in vitro.

    Science.gov (United States)

    Lim, Ratana; Barker, Gillian; Lappas, Martha

    2017-06-01

    Does proviral integration site for Moloney murine leukaemic virus (PIM)1 kinase play a role in regulating the inflammatory processes of human labour and delivery? PIM1 kinase plays a critical role in foetal membranes in regulating pro-inflammatory and pro-labour mediators. Infection and inflammation have strong causal links to preterm delivery by stimulating pro-inflammatory cytokines and collagen degrading enzymes, which can lead to rupture of membranes. PIM1 has been shown to have a role in immune regulation and inflammation in non-gestational tissues; however, its role has not been explored in the field of human labour. PIM1 expression was analysed in myometrium and/or foetal membranes obtained at term and preterm (n = 8-9 patients per group). Foetal membranes, freshly isolated amnion cells and primary myometrial cells were used to investigate the effect of PIM1 inhibition on pro-labour mediators (n = 5 patients per treatment group). Foetal membranes, from term and preterm, were obtained from non-labouring and labouring women, and from preterm pre-labour rupture of membranes (PPROM) (n = 9 per group). Amnion was collected from women with and without preterm chorioamnionitis (n = 8 per group). Expression of PIM1 kinase was determined by qRT-PCR and western blotting. To determine the effect of PIM1 kinase inhibition on the expression of pro-inflammatory and pro-labour mediators induced by bacterial products lipopolysaccharide (LPS) (10 μg/ml) and flagellin (1 μg/ml) and pro-inflammatory cytokine tumour necrosis factor (TNF) (10 ng/ml), chemical inhibitors SMI-4a (20 μM) and AZD1208 (50 μM) were used in foetal membrane explants and siRNA against PIM1 was used in primary amnion cells. Statistical significance was set at P membranes after spontaneous term labour compared to no labour at term and in amnion with preterm chorioamnionitis compared to preterm with no chorioamnionitis. There was no change in PIM1 expression with preterm labour or PPROM

  19. Allosensibilisation to erythrocyte antigens (literature review

    Directory of Open Access Journals (Sweden)

    N. V. Mineeva

    2015-01-01

    Full Text Available In this article literature review of the causes of allosensibilisation to erythrocyte antigens are presented. It is shown that the ability to produce antierythrocyte antibodies is affected by many factors, principal of whom it is difficult to identify. For the allosensibilisation development requires genetically determined differences in erythrocyte antigens phenotypes of donor and recipient, mother and fetus, which can lead to immune response and antibodies production. The biochemical nature of erythrocyte antigens, antigen dose (the amount of transfused doses, the number of antigens determinants on donor and fetus erythrocytes, the number of pregnancies are important. Individual patient characteristics: age, gender, diseases, the use of immunosuppressive therapy and the presence of inflammatory processes, are also relevant. Note that antibody to one erythrocyte antigens have clinical value, and to the other – have no. The actual data about frequency of clinically significant antibodies contribute to the development of post-transfusion hemolytic complications prophylaxis as well as the improvement of laboratory diagnosis of hemolytic disease of the newborn in the presence of maternal antierythrocyte antibodies.

  20. The Change of Perinatal Mortality Over Three Decades in a Reference Centre in the Aegean Region: Neonatal Mortality has decreased but Foetal Mortality Remains Unchanged

    Directory of Open Access Journals (Sweden)

    Nilgün Kültürsay

    2017-12-01

    Full Text Available Background: Perinatal, foetal and neonatal mortality statistics are important to show the development of a health care system in a country. However, in our country there are very few national and regional data about the changing pattern of perinatal neonatal mortality along with the development of new technologies in this area. Aims: Evaluation of the changes in mortality rates and the causes of perinatal and neonatal deaths within years in a perinatal reference centre which serves a high-risk population. Study Design: Cross-sectional retrospective study. Methods: The perinatal, neonatal and foetal mortality rates in the years 1979-1980 (1st time point and 1988-1989 (2nd time point were compared with the year 2008 (3rd time point. The causes of mortality were assessed by Wigglesworth classification and death reports. The neonatal mortality in the neonatal intensive care unit was also calculated. Results: Foetal mortality rates were 44/1000, 31.4/1000 and 41.75/1000 births, perinatal mortality rates were 35.6/1000, 18.8/1000 and 9/1000 births, and neonatal mortality rates were 35.6/1000, 18.8/1000 and 9/1000 live births for the three study time points, respectively. The mortality rate in neonatal intensive care unit decreased consistently from 33%, to 22.6% and 10%, respectively, together with decreasing neonatal mortality rates. The causes of perinatal deaths were foetal death 85%, immaturity 4%, and lethal congenital malformations 8% according to Wigglesworth classification in 2008, showing the high impact of foetal deaths on this high perinatal mortality rate. Infectious causes of neonatal deaths decreased but congenital anomalies increased in the last decades. Conclusion: Although neonatal mortality rate decreased significantly; foetal mortality rate has stayed unchanged since the late eighties. In order to decrease foetal and perinatal mortality rates more efficiently, reducing consanguineous marriages and providing better antenatal care for

  1. Antigen smuggling in tuberculosis.

    Science.gov (United States)

    Hudrisier, Denis; Neyrolles, Olivier

    2014-06-11

    The importance of CD4 T lymphocytes in immunity to M. tuberculosis is well established; however, how dendritic cells activate T cells in vivo remains obscure. In this issue of Cell Host & Microbe, Srivastava and Ernst (2014) report a mechanism of antigen transfer for efficient activation of antimycobacterial T cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Antigen detection systems

    Science.gov (United States)

    Infectious agents or their constituent parts (antigens or nucleic acids) can be detected in fresh, frozen, or fixed tissues or other specimens, using a variety of direct or indirect assays. The assays can be modified to yield the greatest sensitivity and specificity but in most cases a particular m...

  3. Isocyanate test antigens

    International Nuclear Information System (INIS)

    Karol, M.H.; Alarie, Y.C.

    1980-01-01

    A test antigen for detecting antibodies to a diisocyanate comprises the reaction product of a protein and a monoisocyanate derived from the same radical as the diisocyanate. The diisocyanates most usually encountered and therefore calling for antibody detection are those of toluene, hexamethylene, methylene, isophorone and naphthylene. The preferred protein is human serum albumin. (author)

  4. β-endorphin antigen

    International Nuclear Information System (INIS)

    1981-01-01

    This invention relates to the production of antigens comprising β-endorphin, βsub(h)-endorphin, or βsub(c)-endorphin, in covalent conjugation with human gammaglobulin as immunogenic carrier material, and an antibody having the property of specifically binding β-endorphin or fragments thereof, containing the (6-15) residue sequence. (U.K.)

  5. Sex-related differences in the anteroposterior diameter of the foetal cisterna magna

    Energy Technology Data Exchange (ETDEWEB)

    Tao, G. [Department of Ultrasound, Qilu hospital of Shandong University, Jinan (China); Yew, D.T. [Department of Anatomy, Chinese University of Hong Kong (Hong Kong); Gu, T.; Liu, S.; Ma, Z.; Zhan, X.; Cheng, L. [Department of Ultrasound, Qilu hospital of Shandong University, Jinan (China); Li, C. [Department of Ultrasound, Qilu hospital of Shandong University, Jinan (China)], E-mail: chuanfuli2006@hotmail.com

    2008-09-15

    Aim: To measure the anteroposterior diameter of the foetal cisterna magna and observe whether there are differences according to sex. Materials and methods: Three hundred and thirty-seven Chinese women with low-risk pregnancies and a singleton foetus between 22 and 38 weeks' gestational age were included in this retrospective study. Informed consent of the volunteer subjects and hospital authority approval were first obtained. Double-blinded for gender, the anteroposterior diameter of the cisterna magna of the foetuses was measured by transabdominal sonography. Magnetic resonance imaging (MRI) was used for those foetuses with mega cisterna magna. All of the foetuses were healthy by prenatal and postnatal examination, including physical and imaging examination. Results: The mean anteroposterior diameter of the cisterna magna of all foetuses was 8.01 {+-} 1.79 mm. The anteroposterior diameter of the cisterna magna had no obvious correlation with the gestational age. The mean anteroposterior diameter of the cisterna magna of 179 male foetuses was 8.63 {+-} 2.16 mm, and the mean anteroposterior diameter of the cisterna magna of 158 female foetuses was 7.87 {+-} 1.74 mm. The size difference was statistically significant (p < 0.001). In the 33 foetuses with mega cisterna magna, the number of male foetuses was greater than female foetuses, and the proportion of the foetuses with mega cisterna magna in the male group was significantly higher than the foetuses in the female group (p < 0.05). Conclusion: Male foetuses had slightly larger anteroposterior diameters of the cisterna magna than female foetuses. The study would be useful for creating normal range values for the cisterna magna of male and female foetuses.

  6. Maternal and foetal outcome after epidural labour analgesia in high-risk pregnancies

    Directory of Open Access Journals (Sweden)

    Sukhen Samanta

    2016-01-01

    Full Text Available Background and Aims: Low concentration local anaesthetic improves uteroplacental blood flow in antenatal period and during labour in preeclampsia. We compared neonatal outcome after epidural ropivacaine plus fentanyl with intramuscular tramadol analgesia during labour in high-risk parturients with intrauterine growth restriction of mixed aetiology. Methods: Forty-eight parturients with sonographic evidence of foetal weight <1.5 kg were enrolled in this non-randomized, double-blinded prospective study. The epidural (E group received 0.15% ropivacaine 10 ml with 30 μg fentanyl incremental bolus followed by 7–15 ml 0.1% ropivacaine with 2 μg/ml fentanyl in continuous infusion titrated until visual analogue scale was three. Tramadol (T group received intramuscular tramadol 1 mg/kg as bolus as well as maintenance 4–6 hourly. Neonatal outcomes were measured with cord blood base deficit, pH, ionised calcium, sugar and Apgar score after delivery. Maternal satisfaction was also assessed by four point subjective score. Results: Baseline maternal demographics and neonatal birth weight were comparable. Neonatal cord blood pH, base deficit, sugar, and ionised calcium levels were significantly improved in the epidural group in comparison to the tramadol group. Maternal satisfaction (P = 0.0001 regarding labour analgesia in epidural group was expressed as excellent by 48%, good by 52% whereas it was fair in 75% and poor in 25% in the tramadol group. Better haemodynamic and pain scores were reported in the epidural group. Conclusion: Epidural labour analgesia with low concentration local anaesthetic is associated with less neonatal cord blood acidaemia, better sugar and ionised calcium levels. The analgesic efficacy and maternal satisfaction are also better with epidural labour analgesia.

  7. Cyclic hydrostatic pressure stimulates enhanced bone development in the foetal chick femur in vitro.

    Science.gov (United States)

    Henstock, J R; Rotherham, M; Rose, J B; El Haj, A J

    2013-04-01

    Mechanical loading of bone and cartilage in vivo results in the generation of cyclic hydrostatic forces as bone compression is transduced to fluid pressure in the canalicular network and the joint synovium. It has therefore been suggested that hydrostatic pressure is an important stimulus by which osteochondral cells and their progenitors sense and respond to mechanical loading in vivo. In this study, hydrostatic pressure regimes of 0-279kPa at 0.005-2Hz were applied to organotypically cultured ex vivo chick foetal femurs (e11) for 1hour per day in a custom designed bioreactor for 14days and bone formation assessed by X-ray microtomography and qualified by histology. We found that the mineralised portion of the developing femur cultured under any cyclic hydrostatic pressure regime was significantly larger and/or denser than unstimulated controls but that constant (non-cycling) hydrostatic pressure had no effect on bone growth. Further experiments showed that the increase in bone formation was directly proportional to stimulation frequency (R(2)=0.917), but independent of the magnitude of the pressure applied, whilst even very low frequencies of stimulation (0.005Hz) had significant effects on bone growth. Expression of Type-II collagen in both epiphyses and diaphysis was significantly upregulated (1.48-fold and 1.95-fold respectively), together with osteogenic genes (osteonectin and osteopontin) and the osteocyte maturation marker CD44. This work demonstrates that cyclic hydrostatic pressure promotes bone growth and mineralisation in a developmental model and supports the hypothesis that hydrostatic forces play an important role in regulating bone growth and remodelling in vivo. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Ultraviolet-C irradiation for inactivation of viruses in foetal bovine serum.

    Science.gov (United States)

    Vaidya, Vivek; Dhere, Rajeev; Agnihotri, Snehal; Muley, Ravindra; Patil, Sanjay; Pawar, Amit

    2018-07-05

    Foetal Bovine Serum (FBS) and porcine trypsin are one of the essential raw materials used in the manufacturing of cell culture based viral vaccines. Being from animal origin, these raw materials can potentially contaminate the final product by known or unknown adventitious agents. The issue is more serious in case of live attenuated viral vaccines, where there is no inactivation step which can take care of such adventitious agents. It is essential to design production processes which can offer maximum viral clearance potential for animal origin products. Ultraviolet-C irradiation is known to inactivate various adventitious viral agents; however there are limited studies on ultraviolet inactivation of viruses in liquid media. We obtained a recently developed UVivatec ultraviolet-C (UV-C) irradiation based viral clearance system for evaluating its efficacy to inactivate selected model viruses. This system has a unique design with spiral path of liquid allowing maximum exposure to UV-C light of a short wavelength of 254 nm. Five live attenuated vaccine viruses and four other model viruses were spiked in tissue culture media and exposed to UV-C irradiation. The pre and post UV-C irradiation samples were analyzed for virus content to find out the extent of inactivation of various viruses. These experiments showed substantial log reduction for the majority of the viruses with few exceptions based on the characteristics of these viruses. Having known the effect of UV irradiation on protein structure, we also evaluated the post irradiation samples of culture media for growth promoting properties using one of the most fastidious human diploid cells (MRC-5). UV-C exposure did not show any notable impact on the nutritional properties of culture media. The use of an UV-C irradiation based system is considered to be promising approach to mitigate the risk of adventitious agents in cell culture media arising through animal derived products. Copyright © 2018 Elsevier Ltd. All

  9. Transmission of electric and magnetic foetal cardiac signals in a case of ectopia cordis: the dominant role of the vernix caseosa

    International Nuclear Information System (INIS)

    Wakai, R.T.; Lengle, J.M.; Leuthold, A.C.

    2000-01-01

    Foetal electrocardiograms (fECGs) and foetal magnetocardiograms (fMCGs) were recorded in the 26th, 29th and 31st weeks of gestation from a foetus with ectopia cordis - a rare condition in which the heart lies outside the chest wall. This provided an opportunity to study foetal cardiograms uninfluenced by the insulating effects of the foetal skin and vernix caseosa. The fECG of the ectopia cordis foetus was striking. Unlike recordings from age-matched normal foetuses, recordings from this subject had very high signal-to-noise ratio and showed no anomalous signal transmission properties. In contrast, fMCGs recorded from the ectopia cordis foetus and normal foetuses were largely similar. Both showed high signal-to-noise ratio and signal transmission properties consistent with volume conduction. The findings corroborate the hypothesis that high foetal skin resistance due primarily to the vernix caseosa is responsible for the low amplitude and anomalous transmission properties of the normal fECG, and demonstrate that the fMCG is relatively insensitive to conductivity inhomogeneities. (author)

  10. Overview of Plant-Made Vaccine Antigens against Malaria

    Directory of Open Access Journals (Sweden)

    Marina Clemente

    2012-01-01

    Full Text Available This paper is an overview of vaccine antigens against malaria produced in plants. Plant-based expression systems represent an interesting production platform due to their reduced manufacturing costs and high scalability. At present, different Plasmodium antigens and expression strategies have been optimized in plants. Furthermore, malaria antigens are one of the few examples of eukaryotic proteins with vaccine value expressed in plants, making plant-derived malaria antigens an interesting model to analyze. Up to now, malaria antigen expression in plants has allowed the complete synthesis of these vaccine antigens, which have been able to induce an active immune response in mice. Therefore, plant production platforms offer wonderful prospects for improving the access to malaria vaccines.

  11. 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...

  12. Radioimmunoassay for the detection of Australia-SH antigen

    Energy Technology Data Exchange (ETDEWEB)

    Gerhardt, H [Giessen Univ. (Germany, F.R.). Zentrum fuer Innere Medizin

    1974-06-01

    Among infectious diseases, hepatitis presents a great problem in all countries with a high medical standard. The number of Australia antigen-positive cases rises from year to year, due to the increase in drug-fixer hepatitis and blood transfusions. Highly sensitive and at the same time practicable methods are therefore required for the identification of Australia antigen carriers and their elimination as blood donors. The most sensitive of all currently used tests for the detection of Australia antigen is the 'solid phase' radioimmunoassay since it permits an objective and quantitative measurement of the antigen.

  13. Where does distance matter? Distance to the closest maternity unit and risk of foetal and neonatal mortality in France.

    Science.gov (United States)

    Pilkington, Hugo; Blondel, Béatrice; Drewniak, Nicolas; Zeitlin, Jennifer

    2014-12-01

    The number of maternity units has declined in France, raising concerns about the possible impact of increasing travel distances on perinatal health outcomes. We investigated impact of distance to closest maternity unit on perinatal mortality. Data from the French National Vital Statistics Registry were used to construct foetal and neonatal mortality rates over 2001-08 by distance from mother's municipality of residence and the closest municipality with a maternity unit. Data from French neonatal mortality certificates were used to compute neonatal death rates after out-of-hospital birth. Relative risks by distance were estimated, adjusting for individual and municipal-level characteristics. Seven percent of births occurred to women residing at ≥30 km from a maternity unit and 1% at ≥45 km. Foetal and neonatal mortality rates were highest for women living at maternity unit. For foetal mortality, rates increased at ≥45 km compared with 5-45 km. In adjusted models, long distance to a maternity unit had no impact on overall mortality but women living closer to a maternity unit had a higher risk of neonatal mortality. Neonatal deaths associated with out-of-hospital birth were rare but more frequent at longer distances. At the municipal-level, higher percentages of unemployment and foreign-born residents were associated with increased mortality. Overall mortality was not associated with living far from a maternity unit. Mortality was elevated in municipalities with social risk factors and located closest to a maternity unit, reflecting the location of maternity units in deprived areas with risk factors for poor outcome. © The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association.

  14. Classification of caesarean section and normal vaginal deliveries using foetal heart rate signals and advanced machine learning algorithms.

    Science.gov (United States)

    Fergus, Paul; Hussain, Abir; Al-Jumeily, Dhiya; Huang, De-Shuang; Bouguila, Nizar

    2017-07-06

    Visual inspection of cardiotocography traces by obstetricians and midwives is the gold standard for monitoring the wellbeing of the foetus during antenatal care. However, inter- and intra-observer variability is high with only a 30% positive predictive value for the classification of pathological outcomes. This has a significant negative impact on the perinatal foetus and often results in cardio-pulmonary arrest, brain and vital organ damage, cerebral palsy, hearing, visual and cognitive defects and in severe cases, death. This paper shows that using machine learning and foetal heart rate signals provides direct information about the foetal state and helps to filter the subjective opinions of medical practitioners when used as a decision support tool. The primary aim is to provide a proof-of-concept that demonstrates how machine learning can be used to objectively determine when medical intervention, such as caesarean section, is required and help avoid preventable perinatal deaths. This is evidenced using an open dataset that comprises 506 controls (normal virginal deliveries) and 46 cases (caesarean due to pH ≤ 7.20-acidosis, n = 18; pH > 7.20 and pH machine-learning algorithms are trained, and validated, using binary classifier performance measures. The findings show that deep learning classification achieves sensitivity = 94%, specificity = 91%, Area under the curve = 99%, F-score = 100%, and mean square error = 1%. The results demonstrate that machine learning significantly improves the efficiency for the detection of caesarean section and normal vaginal deliveries using foetal heart rate signals compared with obstetrician and midwife predictions and systems reported in previous studies.

  15. Immobilization of Electroporated Cells for Fabrication of Cellular Biosensors: Physiological Effects of the Shape of Calcium Alginate Matrices and Foetal Calf Serum

    Directory of Open Access Journals (Sweden)

    Nikos Katsanakis

    2009-01-01

    Full Text Available In order to investigate the physiological effect of transfected cell immobilization in calcium alginate gels, we immobilized electroporated Vero cells in gels shaped either as spherical beads or as thin membrane layers. In addition, we investigated whether serum addition had a positive effect on cell proliferation and viability in either gel configuration. The gels were stored for four weeks in a medium supplemented or not with 20% (v/v foetal calf serum. Throughout a culture period of four weeks, cell proliferation and cell viability were assayed by optical microscopy after provision of Trypan Blue. Non-elaborate culture conditions (room temperature, non-CO2 enriched culture atmosphere were applied throughout the experimental period in order to evaluate cell viability under less than optimal storage conditions. Immobilization of electroporated cells was associated with an initially reduced cell viability, which was gradually increased. Immobilization was associated with maintenance of cell growth for the duration of the experimental period, whereas electroporated cells essentially died after a week in suspension culture. Considerable proliferation of immobilized cells was observed in spherical alginate beads. In both gel configurations, addition of serum was associated with increased cell proliferation. The results of the present study could contribute to an improvement of the storability of biosensors based on electroporated, genetically or membrane-engineered cells.

  16. Challenges in nourishing the intrauterine growth-restricted foetus - Lessons learned from studies in the intrauterine growth-restricted foetal sheep.

    Science.gov (United States)

    Hay, William W; Brown, Laura D; Rozance, Paul J; Wesolowski, Stephanie R; Limesand, Sean W

    2016-08-01

    Previous attempts to improve growth and development of the intrauterine growth-restricted (IUGR) foetus during pregnancy have not worked or caused harm. Our research identifies tissue-specific mechanisms underlying foetal growth restriction and then tests strategies to improve growth and ameliorate many of the metabolic problems before the infant is born. The goal of our studies is to reduce the impact of foetal growth restriction at critical stages of development on the lifelong complications of IUGR offspring. Defining specific mechanisms that cause growth restriction in the foetus might identify specific nutrients and hormones that could be given to the mother to improve foetal growth and reduce metabolic complications, using strategies first tested in our IUGR animal model. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  17. Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity

    NARCIS (Netherlands)

    Kreutz, M.; Giquel, B.; Hu, Q.; Abuknesha, R.; Uematsu, S.; Akira, S.; Nestle, F.O.; Diebold, S.S.

    2012-01-01

    Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC) by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is

  18. Deteksi Antigen pada Kriptokokosis

    Directory of Open Access Journals (Sweden)

    Robiatul Adawiyah

    2014-12-01

    Full Text Available AbstrakKriptokokosis merupakan infeksi sistemik yang disebabkan Cryptococcus sp. Predileksi jamur tersebut adalah susunan saraf pusat dan selaput otak. Terdapat 5 spesies Cryptococcus sp. yang menyebabkan penyakit pada manusia; yang paling banyak adalah Cr. neoformans dan Cr. gattii. Diagnosis kriptokokosis ditegakkan berdasarkan gejala klinis, pemeriksaan laboratoris serta radiologis. Pemeriksaan laboratoris dilakukan dengan identifikasi morfologi, serologi danPCR. Pemeriksaan secara morfologi dengan tinta India positif  bila jumlah sel jamur 10  sel/ml spesimen. Kultur dilakukan di media sabouraud dextrose agar (SDA dan niger sheed agar (NSA, jamur tumbuh setelah 5-7 hari. Deteksi antigen dan antibodi dilakukan pada cairan tubuh dan tidak membutuhkan waktu lama. Deteksi antibodi Cr.neoformans memiliki kelemahan yaitu tidak menunjukkan hasil positif pada infeksi akut, IgA masih positif setelah 1-2 tahun fase penyembuhan, IgG dapat persisten, pada individu imunokompromis menunjukkan hasil yang sangat kompleks dan dalam menentukan diagnosis sering tidak konsisten. Polisakarida adalah komponen paling berperan dalam virulensi Cr. neoformans. Komponen polisakarida terutama glucuronoxylomannan merupakan petanda penting dalam diagnosis kriptokokosis secara serologis. Deteksi antigen Cr. neoformans memiliki kelebihan yaitu menunjukkan hasil positif pada infeksi akut/kronis, sensitivitas dan spesifisitas tinggi, dapat mendeteksi polisakarida hingga 10 ng/ml sehingga dengan kadarantigen yang minimal tetap dapat mendiagnosis kriptokokosis.Kata kunci: Cr. neoformans, glucuronoxylomannan, antigenAbstractCryptococcosis is systemic infection that caused by Cryptococcus sp. Predilection of this fungi is the central nervous system and brain membrane. There are 5 species of Cryptococcus sp. that cause cryptococcosis in human; but the majority are caused by Cr. neoformans and Cr. gattii. The diagnosis of cryptococcosis is made based on clinical symptoms

  19. Carcinoembryonic Antigen Level in Liver Disease

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Kyoo Ok; Kim, Ki Whang; Park, Chang Yun [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1978-09-15

    Carcinoembryonic antigen was initially known as tumor specific antigen and had a potential diagnostic value in the detection of digestive tract malignancies. However, subsequent studies showed CEA and CEA-like antigen present in benign disease, particularly in liver. We had collected sera from 58 patients who had liver scan and later were diagnosed clinically and histologically as liver disease. We estimated CEA values and correlations were made with liver function tests in liver cirrhosis cases. The results: 1) The raised plasma carcinoembryonic antigen level were found in 13 (68.4%) of 19 patients cirrhosis, 5 (27.8%) of 18 patients in hepatoma, 5 (71%) of 7 patients in chronic active hepatitis, all 3 patients in liver abscesses, 2 (66.7%) of 3 patients in liver abscesses, 2 (66.7%) of 3 patients in obstructive biliary disease and none in each one patient of traumatic liver hematoma, subphrenic abscess and clonorchiasis. 2) There is no linear correlation between carcinoembryonic antigen level and liver function tests including serum bilirubin, alkaline phosphatase, SGOT and prothrombin time in liver patients.

  20. Carcinoembryonic Antigen Level in Liver Disease

    International Nuclear Information System (INIS)

    Choi, Kyoo Ok; Kim, Ki Whang; Park, Chang Yun

    1978-01-01

    Carcinoembryonic antigen was initially known as tumor specific antigen and had a potential diagnostic value in the detection of digestive tract malignancies. However, subsequent studies showed CEA and CEA-like antigen present in benign disease, particularly in liver. We had collected sera from 58 patients who had liver scan and later were diagnosed clinically and histologically as liver disease. We estimated CEA values and correlations were made with liver function tests in liver cirrhosis cases. The results: 1) The raised plasma carcinoembryonic antigen level were found in 13 (68.4%) of 19 patients cirrhosis, 5 (27.8%) of 18 patients in hepatoma, 5 (71%) of 7 patients in chronic active hepatitis, all 3 patients in liver abscesses, 2 (66.7%) of 3 patients in liver abscesses, 2 (66.7%) of 3 patients in obstructive biliary disease and none in each one patient of traumatic liver hematoma, subphrenic abscess and clonorchiasis. 2) There is no linear correlation between carcinoembryonic antigen level and liver function tests including serum bilirubin, alkaline phosphatase, SGOT and prothrombin time in liver patients.

  1. Characterization of antigen association with accessory cells: specific removal of processed antigens from the cell surface by phospholipases

    International Nuclear Information System (INIS)

    Falo, L.D. Jr.; Haber, S.I.; Herrmann, S.; Benacerraf, B.; Rock, K.L.

    1987-01-01

    To characterize the basis for the cell surface association of processed antigen with the antigen-presenting cell (APC) the authors analyzed its sensitivity to enzymatic digestion. Antigen-exposed APC that are treated with phospholipase and then immediately fixed lose their ability to stimulate antigen-plus-Ia-specific T-T hybridomas. This effect is seen with highly purified phospholipase A 2 and phospholipase C. In addition it is observed with three distinct antigens - ovalbumin, bovine insulin, and poly(LGlu 56 LLys 35 LPhe 9 )[(GluLysPhe)/sub n/]. The effect of phospholipases is highly specific. Identically treated APC are equivalent to control in their ability to stimulate alloreactive hybridomas specific for precisely the same Ia molecule that is corecognized by antigen-plus-Ia-specific hybrids. Furthermore, the antigen-presenting function of enzyme-treated, fixed APC can be reconstituted by the addition of exogenous in vitro processed or processing independent antigens. In parallel studies 125 I-labeled avidin was shown to specifically bind to APC that were previously exposed and allowed to process biotin-insulin. Biotin-insulin-exposed APC that are pretreated with phospholipase bind significantly less 125 I-labeled avidin than do untreated, exposed APC. Identical enzyme treatment does not reduce the binding of avidin to a biotinylated antibody already bound to class II major histocompatibility complex molecules of APC. These studies demonstrate that phospholipase effectively removes processed cell surface antigen

  2. Model-based comparison of maternal and foetal organ doses from 99mTc pertechnetate, DMSA, DTPA, HDP, MAA and MAG3 diagnostic intakes during pregnancy

    International Nuclear Information System (INIS)

    Saunders, Margaret; Palmer, Maria; Preece, Alan; Millard, Roger

    2002-01-01

    Organ residence times were calculated for diagnostic intakes of 99m Tc pertechnetate, 2,3-dimercaptosuccinic acid (DMSA), diethylene triamine penta-acetic acid (DTPA), hydroxymethylene diphosphonate (HDP), macroaggregated albumin (MAA) and mercapto-acetyltriglycine (MAG 3 ) during the 1st and 3rd stages of pregnancy and used with the MIRDOSE3 pregnant female phantoms for generation of dose estimates. At stage 3 individual foetal organ doses were estimated via a surrogate phantom based on that for the new-born but with mean dose/cumulated activity (S) values scaled for compatibility with foetal whole body S. Stage 1 or 3 whole foetus doses ranged from 5.2 to 0.77 μGy MBq -1 respectively, analogous to current ICRP estimates for these agents using similar in vivo biodistribution model databases. Most stage 3 maternal and foetal organ doses were similar within a factor of 3, being higher in the foetus than the mother with pertechnetate, DTPA and MAG 3 , and lower with DMSA, HDP and MAA. Doses were more uniformly distributed among foetal organs than in the mother. Placental transfer was greatest with pertechnetate, where dose to the stage 3 foetal thyroid was 60-140 μGy MBq -1 . With each agent there was more placental transfer in stage 3 than in stage 1, but doses to stage 1 whole foetus were always higher, with the contribution from the mother dominant. For DMSA, HDP and MAG 3 the maternal contribution to total foetal body dose exceeded 93% for both stages. (orig.)

  3. Antigenic analysis of some Nigerian street rabies virus using ...

    African Journals Online (AJOL)

    The authors studied 12 street rabies virus isolates from 3 states of Nigeria using both the anti-nucleocapsid and anti-glycoprotein monoclonal antibodies and cross-protection tests. It was observed that all the viruses were rabies having divergent antigenic presentation. Also noticed was an antigenic shift when the viruses ...

  4. Maternal and foetal outcome of 206 high risk pregnancy cases in border guard hospital, dhaka.

    Science.gov (United States)

    Shapla, N R; Islam, M A; Shahida, S M; Parveen, Z; Lipe, Y S

    2015-04-01

    This observational study was carried out to identify the various types of high risk pregnancy and to determine the maternal and foetal outcome. The study was carried out on 206 pregnant high risk women in the Gynecology and Obstetrics department of Border Guard Hospital, Dhaka from January 2012 to December 2012. During mentioned period among 598 pregnant women 206 high risk pregnancy cases were randomly selected. Pregnant women (gestational age from 34 weeks upto 40 weeks) having medical condition and pregnancy related high risk factors were included and uncomplicated pregnancy, pregnancy before 37 weeks, post dated pregnancy were excluded from this study. Data was collected from semi structured history sheet and data analysis done by percentage. High risk pregnant women were grouped into three. Group A and Group B includes pregnant women having medical condition before and during pregnancy respectively. Group C consists of pregnant women had pregnancy related high risk issues. Among 206 high risk pregnancy cases majority 47.57% women had medical condition during pregnancy, 31.55% patient had medical condition before pregnancy. Among them majority 30.58% of the patient suffered from pregnancy induced hypertension, 15.04% patients suffered from gestational Diabetes Mellitus and premature rupture of membranes were 12.13%. In this study majority 43.68% of high risk pregnant patients were in age group of 30-35 years, 19.90% pregnant women were in age group of >35 years and 19.40% were in age group of upto 20 years. Among study groups maximum 65.04% of the patients were multiparous. Among 206 study population 60.19% high risk pregnant women were at term at the time of delivery and 39.8% women delivered their babies preterm. Caesarean section was done in 69.41% of high risk pregnant women. After delivery majority 77.66% women had no complication, only 10.19%, 8.25%, 2.91% and 0.97% high risk pregnant women suffered from fever, UTI, abdominal wound infection and post

  5. Presence of tau pathology within foetal neural allografts in patients with Huntington's and Parkinson's disease.

    Science.gov (United States)

    Cisbani, Giulia; Maxan, Alexander; Kordower, Jeffrey H; Planel, Emmanuel; Freeman, Thomas B; Cicchetti, Francesca

    2017-11-01

    Cell replacement has been explored as a therapeutic strategy to repair the brain in patients with Huntington's and Parkinson's disease. Post-mortem evaluations of healthy grafted tissue in such cases have revealed the development of Huntington- or Parkinson-like pathology including mutant huntingtin aggregates and Lewy bodies. An outstanding question remains if tau pathology can also be seen in patients with Huntington's and Parkinson's disease who had received foetal neural allografts. This was addressed by immunohistochemical/immunofluorescent stainings performed on grafted tissue of two Huntington's disease patients, who came to autopsy 9 and 12 years post-transplantation, and two patients with Parkinson's disease who came to autopsy 18 months and 16 years post-transplantation. We show that grafts also contain tau pathology in both types of transplanted patients. In two patients with Huntington's disease, the grafted tissue showed the presence of hyperphosphorylated tau [both AT8 (phospho-tau Ser202 and Thr205) and CP13 (pSer202) immunohistochemical stainings] pathological inclusions, neurofibrillary tangles and neuropil threads. In patients with Parkinson's disease, the grafted tissue was characterized by hyperphosphorylated tau (AT8; immunofluorescent staining) pathological inclusions, neurofibrillary tangles and neuropil threads but only in the patient who came to autopsy 16 years post-transplantation. Abundant tau-related pathology was observed in the cortex and striatum of all cases studied. While the striatum of the grafted Huntington's disease patient revealed an equal amount of 3-repeat and 4-repeat isoforms of tau, the grafted tissue showed elevated 4-repeat isoforms by western blot. This suggests that transplants may have acquired tau pathology from the host brain, although another possibility is that this was due to acceleration of ageing. This finding not only adds to the recent reports that tau pathology is a feature of these neurodegenerative

  6. Bayesian nonparametric clustering in phylogenetics: modeling antigenic evolution in influenza.

    Science.gov (United States)

    Cybis, Gabriela B; Sinsheimer, Janet S; Bedford, Trevor; Rambaut, Andrew; Lemey, Philippe; Suchard, Marc A

    2018-01-30

    Influenza is responsible for up to 500,000 deaths every year, and antigenic variability represents much of its epidemiological burden. To visualize antigenic differences across many viral strains, antigenic cartography methods use multidimensional scaling on binding assay data to map influenza antigenicity onto a low-dimensional space. Analysis of such assay data ideally leads to natural clustering of influenza strains of similar antigenicity that correlate with sequence evolution. To understand the dynamics of these antigenic groups, we present a framework that jointly models genetic and antigenic evolution by combining multidimensional scaling of binding assay data, Bayesian phylogenetic machinery and nonparametric clustering methods. We propose a phylogenetic Chinese restaurant process that extends the current process to incorporate the phylogenetic dependency structure between strains in the modeling of antigenic clusters. With this method, we are able to use the genetic information to better understand the evolution of antigenicity throughout epidemics, as shown in applications of this model to H1N1 influenza. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  7. The potential for induction of autoimmune disease by a randomly-mutated self-antigen

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm

    2007-01-01

    -antigens can be immunogenic and lead to autoimmunity against wildtype self-antigens. In theory, modified self-antigens can arise by random errors and mutations during protein synthesis and would be recognized as foreign antigens by naïve B and T lymphocytes. Here, it is postulated that the initial auto......, a relation to an infectious disease is described, and it is thought that microbes can play a direct role in induction of autoimmunity, for instance by molecular mimicry or bystander activation of autoreactive T cells. In contrast, less attention has been given to the possibility that modified self......-antigen is not a germline self-antigen, but rather a mutated self-antigen. This mutated self-antigen might interfere with peripheral tolerance if presented to the immune system during an infection. The infection lead to bystander activation of naïve T and B cells with specificity for mutated self-antigen and this can lead...

  8. The utilization of health care services by children with Foetal Alcohol Syndrome in the Western Cape, South Africa.

    Science.gov (United States)

    Credé, Sarah; Sinanovic, Edina; Adnams, Colleen; London, Leslie

    2011-06-01

    The rates of Foetal Alcohol Syndrome (FAS) and Partial Foetal Alcohol Spectrum (PFAS) in South Africa are the highest reported worldwide. There is a paucity of research examining the health care costs of caring for children with FAS or PFAS in this country. A cross-sectional analytical study was conducted using an interviewer-administered questionnaire amongst caregivers of children (0-12 years) with FAS/PFAS in the Western Cape to estimate the utilization of health care services; the annual direct and indirect health care costs per child as well as the total cost to society for providing health care services to children with FAS/PFAS. It was found that the median number of annual visits to public health care facilities per child was 8 (IQR 4 to 14). The total average annual cost per child was $1039.38 (95% CI: $808.68; $1270.07) and the total annual societal cost for the Western Cape was $70,960,053.68 (95% CI: $5,528,895.48; $86,709,971.13). Caregivers in receipt of a social support grant reported spending significantly less on health care for a child with FAS/PFAS (Fisher's exact p=0.004). These study results confirm the significant burden of FAS/PFAS on the Western Cape economy and the health care system which has significant implications for FAS prevention. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  9. PREDICTIVE ACCURACY OF TRANSCEREBELLAR DIAMETER IN COMPARISON WITH OTHER FOETAL BIOMETRIC PARAMETERS FOR GESTATIONAL AGE ESTIMATION AMONG PREGNANT NIGERIAN WOMEN.

    Science.gov (United States)

    Adeyekun, A A; Orji, M O

    2014-04-01

    To compare the predictive accuracy of foetal trans-cerebellar diameter (TCD) with those of other biometric parameters in the estimation of gestational age (GA). A cross-sectional study. The University of Benin Teaching Hospital, Nigeria. Four hundred and fifty healthy singleton pregnant women, between 14-42 weeks gestation. Trans-cerebellar diameter (TCD), biparietal diameter (BPD), femur length (FL), abdominal circumference (AC) values across the gestational age range studied. Correlation and predictive values of TCD compared to those of other biometric parameters. The range of values for TCD was 11.9 - 59.7mm (mean = 34.2 ± 14.1mm). TCD correlated more significantly with menstrual age compared with other biometric parameters (r = 0.984, p = 0.000). TCD had a higher predictive accuracy of 96.9% ± 12 days), BPD (93.8% ± 14.1 days). AC (92.7% ± 15.3 days). TCD has a stronger predictive accuracy for gestational age compared to other routinely used foetal biometric parameters among Nigerian Africans.

  10. Pre-gestational stress reduces the ratio of 5-HIAA to 5-HT and the expression of 5-HT1A receptor and serotonin transporter in the brain of foetal rat

    Directory of Open Access Journals (Sweden)

    Huang Yuejun

    2012-02-01

    Full Text Available Abstract Background Many studies have found that stress before or during pregnancy is linked to an increased incidence of behavioural disorders in offspring. However, few studies have investigated hypothalamic-pituitary-adrenal (HPA axis activity and the serotonergic system as a consequence of pregestational stress. In the present study, we investigated the effect of pre-gestational stress on HPA axis activity in maternal rats and their foetuses and examined whether changes in HPA axis activity of maternal rats produced functional changes in the serotonergic system in the brain of foetuses. Results We used the behavioural tests to assess the model of chronic unpredictable stress (CUS in maternal rats. We found the activity in the open field and sucrose consumption was lower for rats with CUS than for the controls. Body weight but not brain weight was higher for control foetuses than those from the CUS group. Serum corticosterone and corticotrophin-releasing hormone levels were significantly higher for mothers with CUS before pregnancy and their foetuses than for the controls. Levels of 5-hydroxytryptamine (5-HT were higher in the hippocampus and hypothalamus of foetuses in the CUS group than in the controls, and 5-hydroxyindoleacetic acid (5-HIAA levels were lower in the hippocampus in foetuses in the CUS group than in the control group. Levels of 5-HIAA in the hypothalamus did not differ between foetuses in the CUS group and in the control group. The ratio of 5-HIAA to 5-HT was significantly lower for foetuses in the CUS group than in the control group. Levels of 5-HT1A receptor were significantly lower in the foetal hippocampus in the CUS group than in the control group, with no significant difference in the hypothalamus. The levels of serotonin transporter (SERT were lower in both the foetal hippocampus and foetal hypothalamus in the CUS group than in the control group. Conclusions Our data demonstrate that pre-gestational stress alters HPA

  11. Establishing the accuracy and acceptability of abdominal ultrasound to define the foetal head position in the second stage of labour: a validation study.

    LENUS (Irish Health Repository)

    Ramphul, Meenakshi

    2012-09-01

    To compare the diagnosis of the foetal head position in the second stage of labour by ultrasound scan performed by a novice sonographer and by clinical assessment, to that of an expert sonographer (gold standard); and to evaluate the acceptability of ultrasound in the second stage of labour to women and clinicians.

  12. Fluence to absorbed foetal dose conversion coefficients for photons in 50 keV-10 GeV calculated using RPI-P models

    International Nuclear Information System (INIS)

    Taranenko, V.; Xu, X.G.

    2008-01-01

    Radiation protection of pregnant females and the foetus against ionising radiation is of particular importance to radiation protection due to high foetal radiosensitivity. The only available set of foetal conversion coefficients for photons is based on stylised models of simplified anatomy. Using the RPI-P series of pregnant female and foetus models representing 3-, 6- and 9-month gestation, a set of new fluence to absorbed foetal dose conversion coefficients has been calculated. The RPI-P anatomical models were developed using novel 3D geometry modelling techniques. Organ masses were adjusted to agree within 1% with the ICRP reference data for a pregnant female. Monte Carlo dose calculations were carried out using the MCNPX and Penelope codes for external 50 keV-10 GeV photon beams of six standard configurations. The models were voxelised at 3-mm voxel resolution. Conversion coefficients were tabulated for the three gestational periods for the whole foetus and brain. Comparison with previously published data showed deviations up to 120% for the foetal doses at 50 keV. The discrepancy can be primarily ascribed to anatomical differences. Comparison with published data for five major mother organs is also provided for the 3-month model. Since the RPI-P models exhibit a high degree of anatomical realism, the reported dataset is recommended as a reference for radiation protection of the foetus against external photon exposure. (authors)

  13. Reduction-sensitive dextran nanogels aimed for intracellular delivery of antigens

    NARCIS (Netherlands)

    Li, Dandan; Kordalivand, Neda; Fransen, Marieke F.; Ossendorp, Ferry; Raemdonck, Koen; Vermonden, Tina; Hennink, Wim E.; Van Nostrum, Cornelus F.

    2015-01-01

    Targeting of antigens to dendritic cells (DCs) to induce strong cellular immune response can be established by loading in a nano-sized carrier and keeping the antigen associated with the particles until they are internalized by DCs. In the present study, a model antigen (ovalbumin, OVA) is

  14. Antigen antibody interactions

    CERN Document Server

    DeLisi, Charles

    1976-01-01

    1. 1 Organization of the Immune System One of the most important survival mechanisms of vertebrates is their ability to recognize and respond to the onslaught of pathogenic microbes to which they are conti- ously exposed. The collection of host cells and molecules involved in this recognition­ 12 response function constitutes its immune system. In man, it comprises about 10 cells 20 (lymphocytes) and 10 molecules (immunoglobulins). Its ontogenic development is c- strained by the requirement that it be capable of responding to an almost limitless variety of molecular configurations on foreign substances, while simultaneously remaining inert to those on self components. It has thus evolved to discriminate, with exquisite precision, between molecular patterns. The foreign substances which induce a response, called antigens, are typically large molecules such as proteins and polysaccharides. The portions of these with which immunoglobulins interact are called epitopes or determinants. A typical protein epitope m...

  15. Stevens Johnson Syndrome and Toxic Epidermal Necrolysis: Maternal and Foetal Outcomes in Twenty-Two Consecutive Pregnant HIV Infected Women.

    Directory of Open Access Journals (Sweden)

    Lauren Knight

    Full Text Available Stevens-Johnson syndrome (SJS and toxic epidermal necrolysis (TEN form a spectrum of a rare and life-threatening cutaneous drug reaction. SJS/TEN in pregnancy poses largely unknown risk factors and outcomes for both the mother and foetus compared to the general population.We conducted a study of consecutive pregnant women admitted to single tertiary referral centre in South Africa with SJS/TEN over a 3 year period. They were all managed by the same medical team using the same protocols. We evaluated their underlying illnesses, offending drugs and the course of pregnancy and outcomes to determine factors influencing maternal and foetal outcomes.We identified twenty-two women who developed SJS/TEN while pregnant, all of them HIV-infected. Their median age was 29 years. The majority 16/22 (73% had SJS, the milder variant of the disease affecting < 10% body surface area. Nevirapine was the offending drug in 21/22 (95% cases. All 22 of the mothers survived with 3/22 (14% developing postpartum sepsis. Pregnancy outcomes were known in 18/22 women and 9/18 (50% babies were delivered by caesarean section. There were 2 foetal deaths at 21 and 31 weeks respectively and both were associated with post-partum sepsis. Postnatal complications occurred in 5 cases, 3 involving the respiratory system and the other two being low birth weight deliveries. Eight placentae and one foetus were sent for histology and none showed macroscopic or microscopic features of SJS/TEN. On follow-up, only 12/20 children were tested for HIV at 6 weeks post-delivery and none of them were HIV-infected. All had received prophylactic ARVs including nevirapine.TEN, the severe form of the disease, was associated with poorer foetal outcomes. SJS/TEN-associated mortality is not increased in HIV-infected pregnant women. Maternal SJS/TEN does not seem to commonly manifest in the foetus.

  16. Antigen Loss Variants: Catching Hold of Escaping Foes.

    Science.gov (United States)

    Vyas, Maulik; Müller, Rolf; Pogge von Strandmann, Elke

    2017-01-01

    Since mid-1990s, the field of cancer immunotherapy has seen steady growth and selected immunotherapies are now a routine and preferred therapeutic option of certain malignancies. Both active and passive cancer immunotherapies exploit the fact that tumor cells express specific antigens on the cell surface, thereby mounting an immune response specifically against malignant cells. It is well established that cancer cells typically lose surface antigens following natural or therapy-induced selective pressure and these antigen-loss variants are often the population that causes therapy-resistant relapse. CD19 and CD20 antigen loss in acute lymphocytic leukemia and chronic lymphocytic leukemia, respectively, and lineage switching in leukemia associated with mixed lineage leukemia (MLL) gene rearrangements are well-documented evidences in this regard. Although increasing number of novel immunotherapies are being developed, majority of these do not address the control of antigen loss variants. Here, we review the occurrence of antigen loss variants in leukemia and discuss the therapeutic strategies to tackle the same. We also present an approach of dual-targeting immunoligand effectively retargeting NK cells against antigen loss variants in MLL-associated leukemia. Novel immunotherapies simultaneously targeting more than one tumor antigen certainly hold promise to completely eradicate tumor and prevent therapy-resistant relapses.

  17. Single cell biochemistry to visualize antigen presentation and drug resistance

    NARCIS (Netherlands)

    Griekspoor, Alexander Christiaan

    2006-01-01

    Many cellular processes are studied by biochemical techniques. Usually, this involves experiments where large number of cells are lysed, protein content is subsequently isolated and studied using antibodies to detect changes in protein levels, post-translational modifications, pairing with partner

  18. Development of Artificial Antigen Presenting Cells for Prostate Cancer Immunotherapy

    National Research Council Canada - National Science Library

    Schneck, Jonathan P; Oelke, Mathias

    2007-01-01

    While adoptive immunotherapy holds promise as a treatment for cancer, development of adoptive immunotherapy has been impeded by the lack of a reproducible and economically viable method for generating...

  19. Optimal foetal growth in the reduction of learning and behaviour disorder and prevention of sudden infant death (SIDS) after the first month.

    Science.gov (United States)

    Saugstad, L F

    1997-09-01

    A theory is presented that a diet low in polyunsaturated fatty acids (PUFA) in the third trimester of pregnancy may delay myelination and brain maturation. This may underpin learning and behaviour disorders and sudden infant death (SIDS) after the first month, conditions that are associated with lower than average birthweight. Epidemiological evidence is reviewed showing an inverse relation between the proportion of heavy newborns (> 3500 g) and infant mortality rate. Some countries with a lower proportion of heavy newborns despite equally high standards of living and medical care have higher post-neonatal death rates. The higher rates are solely due to SIDS which has a peak mortality within 80-100 days. It is hypothesised that as this is a time when myelination peaks, SIDS may be due to maturational delay. Evidence of subtle CNS changes in brainstem structures and in the neuromuscular system supports an instability in brainstem control systems. Moderate iatrogenic dietary restriction predominates today, but a rising number of women favour a low-caloric low-fat diet especially in the third trimester when the foetus is most susceptible. This may lead to a depressed birthweight, delayed somatic growth and neuronal maturation, such as is observed in SIDS victims. The majority exposed to suboptimal conditions survive, but a few suffer SIDS; confirming post-neonatal susceptibility. Many, especially males, present minor CNS signs and learning/behaviour disorders that could be the sequelae of repeated hypoxic episodes, such as recorded in more than 80% of SIDS victims. To reduce learning/behaviour disorders and prevent death from SIDS after the first month, it is necessary to ensure optimal development by promoting foetal growth. It is advised to avoid unnecessary dieting and to favour a diet high in PUFAs, thus prolonging pregnancy and so increasing birthweight.

  20. Targeting tumor antigens to secreted membrane vesicles in vivo induces efficient antitumor immune responses.

    Science.gov (United States)

    Zeelenberg, Ingrid S; Ostrowski, Matias; Krumeich, Sophie; Bobrie, Angélique; Jancic, Carolina; Boissonnas, Alexandre; Delcayre, Alain; Le Pecq, Jean-Bernard; Combadière, Béhazine; Amigorena, Sebastian; Théry, Clotilde

    2008-02-15

    Expression of non-self antigens by tumors can induce activation of T cells in vivo, although this activation can lead to either immunity or tolerance. CD8+ T-cell activation can be direct (if the tumor expresses MHC class I molecules) or indirect (after the capture and cross-presentation of tumor antigens by dendritic cells). The modes of tumor antigen capture by dendritic cells in vivo remain unclear. Here we examine the immunogenicity of the same model antigen secreted by live tumors either in association with membrane vesicles (exosomes) or as a soluble protein. We have artificially addressed the antigen to secreted vesicles by coupling it to the factor VIII-like C1C2 domain of milk fat globule epidermal growth factor-factor VIII (MFG-E8)/lactadherin. We show that murine fibrosarcoma tumor cells that secrete vesicle-bound antigen grow slower than tumors that secrete soluble antigen in immunocompetent, but not in immunodeficient, host mice. This growth difference is due to the induction of a more potent antigen-specific antitumor immune response in vivo by the vesicle-bound than by the soluble antigen. Finally, in vivo secretion of the vesicle-bound antigen either by tumors or by vaccination with naked DNA protects against soluble antigen-secreting tumors. We conclude that the mode of secretion can determine the immunogenicity of tumor antigens and that manipulation of the mode of antigen secretion may be used to optimize antitumor vaccination protocols.

  1. Goodbye warts, hello vitiligo: Candida antigen-induced depigmentation.

    Science.gov (United States)

    Wilmer, Erin N; Burkhart, Craig N; Morrell, Dean S

    2013-01-01

    Depigmentation after the use of topical immune modulators is a rare but reported event. Herein we present what is to our knowledge the first case of vitiligo at a site of Candida antigen injection. © 2012 Wiley Periodicals, Inc.

  2. Regulation of Msx-1, Msx-2, Bmp-2 and Bmp-4 during foetal and postnatal mammary gland development.

    Science.gov (United States)

    Phippard, D J; Weber-Hall, S J; Sharpe, P T; Naylor, M S; Jayatalake, H; Maas, R; Woo, I; Roberts-Clark, D; Francis-West, P H; Liu, Y H; Maxson, R; Hill, R E; Dale, T C

    1996-09-01

    Expression of the Msx-1 and Msx-2 homeobox genes have been shown to be coordinately regulated with the Bmp-2 and Bmp-4 ligands in a variety of developing tissues. Here we report that transcripts from all four genes are developmentally regulated during both foetal and postnatal mammary gland development. The location and time-course of the Bmp and Msx expression point to a role for Msx and Bmp gene products in the control of epithelial-mesenchymal interactions. Expression of Msx-2, but not Msx-1, Bmp-2 or Bmp-4 was decreased following ovariectomy, while expression of the human Msx-2 homologue was regulated by 17beta-oestradiol in the MCF-7 breast cancer cell line. The regulation of Msx-2 expression by oestrogen raises the possibility that hormonal regulation of mammary development is mediated through the control of epithelial-mesenchymal interactions.

  3. Foetal exposure to maternal stressful events increases the risk of having asthma and atopic diseases in childhood.

    Science.gov (United States)

    de Marco, Roberto; Pesce, Giancarlo; Girardi, Paolo; Marchetti, Pierpaolo; Rava, Marta; Ricci, Paolo; Marcon, Alessandro

    2012-12-01

    The natural history of asthma and atopic diseases begins in utero. Studies investigating the influence of foetal exposure to maternal stressful life events during pregnancy (SLEP) on asthma and atopic diseases are lacking. To test whether the children of mothers who had experienced SLEP are at an increased risk for asthma, atopic eczema and allergic rhinitis. The association between maternal SLEP (at least one among: divorce, mourning or loss of the job) and the occurrence of asthma and atopic diseases in childhood was studied in a population (n = 3854) of children, aged 3-14 yrs, living in Northern Italy. The parents filled in a standardized questionnaire about the children's health and the events occurred to their mothers during pregnancy. Three hundred and thirty-three (9%) of the mothers experienced SLEP. Their children had a statistically significantly higher lifetime prevalence of wheezing (31.6% vs. 23.1%), asthma (8.9% vs. 5.6%), allergic rhinitis (10.9% vs. 7.3%) and atopic eczema (29.7% vs. 21.1%) than those of mothers without SLEP. After adjusting for potential confounders, the foetal exposure to SLEP was positively associated with wheezing (OR: 1.41, 95% CI: 1.03-1.94), asthma (OR: 1.71, 95% CI: 1.02-2.89), allergic rhinitis (OR: 1.75, 95% CI: 1.08-2.84) and atopic eczema (OR: 1.53, 95% CI: 1.11-2.10). The children of mothers who had experienced SLEP were at a moderately increased risk of having wheezing, asthma, eczema and allergic rhinitis during their childhood. Maternal stress during pregnancy might enhance the expression of asthma and atopic phenotypes in children. © 2012 John Wiley & Sons A/S.

  4. Maternal-foetal attachment independently predicts the quality of maternal-infant bonding and post-partum psychopathology.

    Science.gov (United States)

    Petri, Eleonora; Palagini, Laura; Bacci, Olivia; Borri, Chiara; Teristi, Valentina; Corezzi, Camilla; Faraoni, Sara; Antonelli, Paolo; Cargioli, Claudio; Banti, Susanna; Perugi, Giulio; Mauri, Mauro

    2017-08-21

    The aim of this study was to evaluate the association of maternal antenatal attachment and post-partum psychopathology, maternal-infant bonding, while checking for antenatal psychopathology, for lifetime psychiatric diagnosis and for the known risk factors for peripartum depression. One hundred and six women recruited at the first month of pregnancy (T0) were evaluated with the structured interview for DSM-IV TR (SCID-I) to assess the presence of lifetime psychiatric diagnosis and with the Perinatal Depression Predictor Inventory-Revised (PDPI-R), the Edinburgh Postnatal Depression Scale (EPDS), and the State-Trait Anxiety Inventory (STAI). At the sixth month of pregnancy (T1) and at the first month post-partum (T2), all patients were evaluated with the PDPI-R, the EPDS, the STAI, at T1, with the Maternal Antenatal Attachment Scale (MAAS), and at T2 with the Maternal Postnatal Attachment Scale (MPAS). Multivariate regression analyses showed that maternal-foetal attachment was the variable most significantly associated with postnatal symptoms of depression and anxiety and with quality of maternal-infant attachment. The logistic regression analyses showed that antenatal attachment may predict postnatal depressive and anxiety symptoms (respectively, OR: 0.83 - IC [0.74 - 0.95], p = .005, OR: 0.88 - IC [0.79 - 0.98], p = .02), and the quality of maternal postnatal attachment (OR: 1.17 - IC [1.08 - 1.27], p depression, the sociodemographic variables and lifetime psychiatric diagnosis. The quality of maternal-foetal bonding may independently predict the quality of maternal-infant attachment and post-partum depressive and anxiety symptoms. A comprehensive assessment of maternal risk factors for perinatal psychopathology during pregnancy should include the evaluation of antenatal attachment that could be modifiable by specific interventions promoting the quality of maternal bonding.

  5. Cardiac re-entry dynamics and self-termination in DT-MRI based model of Human Foetal Heart

    Science.gov (United States)

    Biktasheva, Irina V.; Anderson, Richard A.; Holden, Arun V.; Pervolaraki, Eleftheria; Wen, Fen Cai

    2018-02-01

    The effect of human foetal heart geometry and anisotropy on anatomy induced drift and self-termination of cardiac re-entry is studied here in MRI based 2D slice and 3D whole heart computer simulations. Isotropic and anisotropic models of 20 weeks of gestational age human foetal heart obtained from 100μm voxel diffusion tensor MRI data sets were used in the computer simulations. The fiber orientation angles of the heart were obtained from the orientation of the DT-MRI primary eigenvectors. In a spatially homogeneous electrophysiological monodomain model with the DT-MRI based heart geometries, cardiac re-entry was initiated at a prescribed location in a 2D slice, and in the 3D whole heart anatomy models. Excitation was described by simplified FitzHugh-Nagumo kinetics. In a slice of the heart, with propagation velocity twice as fast along the fibres than across the fibers, DT-MRI based fiber anisotropy changes the re-entry dynamics from pinned to an anatomical re-entry. In the 3D whole heart models, the fiber anisotropy changes cardiac re-entry dynamics from a persistent re-entry to the re-entry self-termination. The self-termination time depends on the re-entry’s initial position. In all the simulations with the DT-MRI based cardiac geometry, the anisotropy of the myocardial tissue shortens the time to re-entry self-termination several folds. The numerical simulations depend on the validity of the DT-MRI data set used. The ventricular wall showed the characteristic transmural rotation of the helix angle of the developed mammalian heart, while the fiber orientation in the atria was irregular.

  6. 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.

  7. Increasing vaccine potency through exosome antigen targeting.

    Science.gov (United States)

    Hartman, Zachary C; Wei, Junping; Glass, Oliver K; Guo, Hongtao; Lei, Gangjun; Yang, Xiao-Yi; Osada, Takuya; Hobeika, Amy; Delcayre, Alain; Le Pecq, Jean-Bernard; Morse, Michael A; Clay, Timothy M; Lyerly, Herbert K

    2011-11-21

    While many tumor associated antigens (TAAs) have been identified in human cancers, efforts to develop efficient TAA "cancer vaccines" using classical vaccine approaches have been largely ineffective. Recently, a process to specifically target proteins to exosomes has been established which takes advantage of the ability of the factor V like C1C2 domain of lactadherin to specifically address proteins to exosomes. Using this approach, we hypothesized that TAAs could be targeted to exosomes to potentially increase their immunogenicity, as exosomes have been demonstrated to traffic to antigen presenting cells (APC). To investigate this possibility, we created adenoviral vectors expressing the extracellular domain (ECD) of two non-mutated TAAs often found in tumors of cancer patients, carcinoembryonic antigen (CEA) and HER2, and coupled them to the C1C2 domain of lactadherin. We found that these C1C2 fusion proteins had enhanced expression in exosomes in vitro. We saw significant improvement in antigen specific immune responses to each of these antigens in naïve and tolerant transgenic animal models and could further demonstrate significantly enhanced therapeutic anti-tumor effects in a human HER2+ transgenic animal model. These findings demonstrate that the mode of secretion and trafficking can influence the immunogenicity of different human TAAs, and may explain the lack of immunogenicity of non-mutated TAAs found in cancer patients. They suggest that exosomal targeting could enhance future anti-tumor vaccination protocols. This targeting exosome process could also be adapted for the development of more potent vaccines in some viral and parasitic diseases where the classical vaccine approach has demonstrated limitations. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Safety and efficacy of a new octavalent combined Erysipelas, Parvo and Leptospira vaccine in gilts against Leptospira interrogans serovar Pomona associated disease and foetal death.

    Science.gov (United States)

    Jacobs, A A C; Harks, F; Hoeijmakers, M; Collell, M; Segers, R P A M

    2015-07-31

    designed as an observational-longitudinal field study. At the start of the study, all breeding sows and replacement gilts on the farm were vaccinated twice with Porcilis(®) Ery+Parvo+Lepto at an interval of 4 weeks. Starting six months after the primary vaccination schedule, the animals were re-vaccinated during the second week of every subsequent lactation. New replacement gilts were vaccinated using the same schedule. After vaccination, the abortion rate reduced rapidly from 12.6% in winter months of 2012 (December 2011 to March 2012) to 0.5% in winter months of 2013, a statistical significant decrease of 96%. The total number of abortions on the farm decreased from 55 in 2012 to 6 in 2013. Thereafter, the abortion rate remained stable and in the period December 2013 to April 2014 was still low (0.6%). In conclusion, the present studies demonstrate that the octavalent Porcilis(®) Ery+Parvo+Lepto vaccine can be safely used in gilts and sows and induces significant protection, for the duration of at least one year, against serovar Pomona induced clinical signs, leptospiraemia and foetal death. Protection against Pomona associated reproductive failure was confirmed under field conditions where a significant reduction in abortion rate was observed. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Humoral immunity provides resident intestinal eosinophils access to luminal antigen via eosinophil-expressed low affinity Fc gamma receptors

    Science.gov (United States)

    Smith, Kalmia M.; Rahman, Raiann S.; Spencer, Lisa A.

    2016-01-01

    Eosinophils are native to the healthy gastrointestinal tract, and are associated with inflammatory diseases likely triggered by exposure to food allergens (e.g. food allergies and eosinophilic gastrointestinal disorders). In models of allergic respiratory diseases and in vitro studies, direct antigen engagement elicits eosinophil effector functions including degranulation and antigen presentation. However, it was not known whether intestinal tissue eosinophils that are separated from luminal food antigens by a columnar epithelium might similarly engage food antigens. Using an intestinal ligated loop model in mice, here we determined that resident intestinal eosinophils acquire antigen from the lumen of antigen-sensitized but not naïve mice in vivo. Antigen acquisition was immunoglobulin-dependent; intestinal eosinophils were unable to acquire antigen in sensitized immunoglobulin-deficient mice, and passive immunization with immune serum or antigen-specific IgG was sufficient to enable intestinal eosinophils in otherwise naïve mice to acquire antigen in vivo. Intestinal eosinophils expressed low affinity IgG receptors, and the activating receptor FcγRIII was necessary for immunoglobulin-mediated acquisition of antigens by isolated intestinal eosinophils in vitro. Our combined data suggest that intestinal eosinophils acquire lumen-derived food antigens in sensitized mice via FcγRIII antigen focusing, and may therefore participate in antigen-driven secondary immune responses to oral antigens. PMID:27683752

  10. 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...

  11. Natural selection promotes antigenic evolvability.

    Science.gov (United States)

    Graves, Christopher J; Ros, Vera I D; Stevenson, Brian; Sniegowski, Paul D; Brisson, Dustin

    2013-01-01

    The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed 'cassettes' that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios) and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish chronic infections.

  12. Natural selection promotes antigenic evolvability.

    Directory of Open Access Journals (Sweden)

    Christopher J Graves

    Full Text Available The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed 'cassettes' that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish

  13. Elucidating the mechanisms of protein antigen adsorption to the CAF/NAF liposomal vaccine adjuvant systems

    DEFF Research Database (Denmark)

    Hamborg, Mette; Rose, Fabrice; Jorgensen, Lene

    2014-01-01

    is generally known about how antigens and adjuvants interact at the molecular level. The aim of this study was to elucidate the mechanisms of interactions between the equally sized, but oppositely charged model protein antigens α-lactalbumin and lysozyme, and i) the clinically tested cationic liposomal...... antigens are presented to antigen-presenting cells, and may play an important role for the efficacy of the vaccine-induced immune response. These studies thus exemplify the importance of characterizing the molecular interactions between the vaccine antigen and adjuvant along with immunogenicity......The reverse vaccinology approach has recently resulted in the identification of promising protein antigens, which in combination with appropriate adjuvants can stimulate customized, protective immune responses. Although antigen adsorption to adjuvants influences vaccine efficacy and safety, little...

  14. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Molecular mimics of the tumour antigen MUC1.

    Directory of Open Access Journals (Sweden)

    Tharappel C James

    Full Text Available A key requirement for the development of cancer immunotherapy is the identification of tumour-associated antigens that are differentially or exclusively expressed on the tumour and recognized by the host immune system. However, immune responses to such antigens are often muted or lacking due to the antigens being recognized as "self", and further complicated by the tumour environment and regulation of immune cells within. In an effort to circumvent the lack of immune responses to tumour antigens, we have devised a strategy to develop potential synthetic immunogens. The strategy, termed mirror image phage display, is based on the concept of molecular mimicry as demonstrated by the idiotype/anti-idiotype paradigm in the immune system. Here as 'proof of principle' we have selected molecular mimics of the well-characterised tumour associated antigen, the human mucin1 protein (MUC1 from two different peptide phage display libraries. The putative mimics were compared in structure and function to that of the native antigen. Our results demonstrate that several of the mimic peptides display T-cell stimulation activity in vitro when presented by matured dendritic cells. The mimic peptides and the native MUC1 antigenic epitopes can cross-stimulate T-cells. The data also indicate that sequence homology and/or chemical properties to the original epitope are not the sole determining factors for the observed immunostimulatory activity of the mimic peptides.

  16. Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity.

    Directory of Open Access Journals (Sweden)

    Martin Kreutz

    Full Text Available Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is paramount. However, co-administration of unlinked adjuvant cannot ensure that all cells targeted by the antibody conjugates are appropriately activated. Furthermore, antigen-presenting cells (APC that do not present the desired antigen are equally strongly activated and could prime undesired responses against self-antigens. We, therefore, were interested in exploring targeted co-delivery of antigen and adjuvant in cis in form of antibody-antigen-adjuvant conjugates for the induction of anti-tumour immunity. In this study, we report on the assembly and characterization of conjugates consisting of DEC205-specific antibody, the model antigen ovalbumin (OVA and CpG oligodeoxynucleotides (ODN. We show that such conjugates are more potent at inducing cytotoxic T lymphocyte (CTL responses than control conjugates mixed with soluble CpG. However, our study also reveals that the nucleic acid moiety of such antibody-antigen-adjuvant conjugates alters their binding and uptake and allows delivery of the antigen and the adjuvant to cells partially independently of DEC205. Nevertheless, antibody-antigen-adjuvant conjugates are superior to antibody-free antigen-adjuvant conjugates in priming CTL responses and efficiently induce anti-tumour immunity in the murine B16 pseudo-metastasis model. A better understanding of the role of the antibody moiety is required to inform future conjugate vaccination strategies for efficient induction of anti-tumour responses.

  17. HLA antigens in juvenile onset diabetes.

    Science.gov (United States)

    Kikuchi, T; Toyota, T; Ouchi, E

    1980-11-01

    To study association between juvenile onset diabetes (JOD) and major histocompatibility gene complex, 40 patients with childhood onset diabetes and 120 healthy subjects were typed for HLA. Bw54 was present in 33 percent of the patients with JOD, while it appeared in 8 percent of the controls. Expressed as a relative risk, the antigen Bw54 confers a susceptibility to the development of JOD which is 5.3 times that in the controls. JOD shows a little high degree of association with A9 (78%). However, the A9-antigen is common in the Japanese and appears in 58 percent. Though less striking, the decreased frequency of B12 was 3 percent of JOD, less than 15 percent of the controls (p less than 0.05). There was no association between Bw54 and JOD with family history of diabetes.

  18. The relationship between maternal body composition in early pregnancy and foetal mid-thigh soft-tissue thickness in the third trimester in a high-risk obstetric population.

    Science.gov (United States)

    Anglim, Breffini; Farah, Nadine; O'Connor, Clare; Daly, Niamh; Kennelly, Mairead M; Turner, Michael J

    2017-07-01

    Maternal obesity is an emerging challenge in contemporary obstetrics. To date there has been no study analysing the relationship between specific maternal body composition measurements and foetal soft-tissue measurements. The aim of this study was to determine whether measurement of maternal body composition at booking predicts foetal soft-tissue trajectories in the third trimester. We analysed the relationship between foetal thigh in the third trimester and both maternal BMI and body composition using the Tanita digital scales in the first trimester. Foetal subcutaneous thigh tissue measurements were obtained at intervals of 28, 32 and 36 weeks of gestation. A total of 160 women were identified. There was a direct correlation between MTST at 36 weeks and BMI (p = .002). There was a positive correlation between MTST at 36 weeks and leg fat mass (p = .13) and leg fat free mass (p = .013). There was a positive correlation between arm fat free mass and MTST at 36 weeks. We showed there is an association between maternal fat distribution and foetal subcutaneous thigh tissue measurements. MTST may be more useful in determining if a child is at risk of macrosomia. Impact statement Previous studies have suggested that maternal obesity programmes intrauterine foetal adiposity and growth. The aim of this study was to examine the relationship in a high-risk obstetric population between measurements of maternal body composition in early pregnancy and the assessment of foetal adiposity in the third trimester using serial ultrasound measurements of mid-thigh soft-tissue thickness. BMI is only a surrogate measurement of fat and does not measure fat distribution. Our study shows the distribution of both maternal fat and fat-free mass in early pregnancy may be positively associated with foetal soft-tissue measurements in the third trimester. Maternal arthropometric measurements other than BMI may help predict babies at risk of macrosomia and neonatal adiposity.

  19. Anvendelse af prostataspecifikt antigen. En oversigt

    DEFF Research Database (Denmark)

    Brasso, K; Skaarup, P; Roosen, Jens Ulrik

    1998-01-01

    Since it was first introduced, measurement of prostate specific antigen has gained increasing interest, and prostate specific antigen is regarded as being the best tumour marker available. The antigen lacks cancer specificity, limiting the usefulness in early diagnosis, The use of prostate specific...... antigen in early diagnosis, staging, and in monitoring patients with prostate cancer is reviewed....

  20. Optimisation and evaluation of the foetal dose during a radiotherapy of the right parotid; Optimisation et evaluation de la dose foetale pendant une radiotherapie de la parotide droite

    Energy Technology Data Exchange (ETDEWEB)

    Marchesi, V.; Noel, A. [Centre Alexis-Vautrin, Unite de Radiophysique Medicale, 54 - Vandoeuvre-les-Nancy (France); Graff, P.; Beckendorf, V.; Peiffert, D. [Centre Alexis-Vautrin, Dept. de Radiotherapie, 54 - Vandoeuvre-les-Nancy (France); Noel, A. [Institut National Polytechnique de Lorraine, CRAN, CNRS UMR-7039, 54 - Vandoeuvre-les-Nancy (France)

    2008-09-15

    Purpose was to optimize and to estimate the dose delivered to the foetus during a postoperative irradiation of a 5-month twin pregnant woman presenting with adenocarcinoma of the right parotid. The treatment protocol aimed to deliver 66 Gy conformal radiation therapy on the tumour bed associated to a prophylactic irradiation of 50 Gy on the upper cervical nodes. A series of measurements allowed to estimate the delivered dose in the abdomen by the means of an ion chamber inserted in a water phantom placed side by side of an anthropomorphic Alderson Rando phantom simulating the body of the patient from the head to the pelvis. An appropriate optimisation of the number and orientation of beams were performed in order to minimize the peripheral dose, which is mostly dependent