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  1. Methylated DNA-binding protein is present in various mammalian cell types

    Energy Technology Data Exchange (ETDEWEB)

    Supakar, P.C.; Weist, D.; Zhang, D.; Inamdar, N.; Zhang, Xianyang; Khan, R.; Ehrlich, M. (Tulane Medical School, New Orleans, LA (USA)); Ehrlich, K.C. (Department of Agriculture, New Orleans, LA (USA))

    1988-08-25

    A DNA-binding protein from human placenta, methylated DNA-binding protein (MDBP), binds to certain DNA sequences only when they contain 5-methylcytosine (m{sup 5}C) residues at specific positions. The authors found a very similar DNA-binding activity in nuclear extracts of rat tissues, calf thymus, human embryonal carcinoma cells, HeLa cells, and mouse LTK cells. Like human placental MDBP, the analogous DNA-binding proteins from the above mammalian cell lines formed a number of different low-electrophoretic-mobility complexes with a 14-bp MDBP-specific oligonucleotide duplex. All of these complexes exhibited the same DNA methylation specificity and DNA sequence specificity. Although MDBP activity was found in various mammalian cell types, it was not detected in extracts of cultured mosquito cells and so may be associated only with cells with vertebrate-type DNA methylation.

  2. Type I Interferons as Regulators of Human Antigen Presenting Cell Functions

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    Sandra Gessani

    2014-05-01

    Full Text Available Type I interferons (IFNs are pleiotropic cytokines, initially described for their antiviral activity. These cytokines exhibit a long record of clinical use in patients with some types of cancer, viral infections and chronic inflammatory diseases. It is now well established that IFN action mostly relies on their ability to modulate host innate and adaptive immune responses. Work in recent years has begun to elucidate the mechanisms by which type I IFNs modify the immune response, and this is now recognized to be due to effects on multiple cell types, including monocytes, dendritic cells (DCs, NK cells, T and B lymphocytes. An ensemble of results from both animal models and in vitro studies emphasized the key role of type I IFNs in the development and function of DCs, suggesting the existence of a natural alliance between these cytokines and DCs in linking innate to adaptive immunity. The identification of IFN signatures in DCs and their dysregulation under pathological conditions will therefore be pivotal to decipher the complexity of this DC-IFN interaction and to better exploit the therapeutic potential of these cells.

  3. A case of squamous cell carcinoma of lung presenting with paraneoplastic type of acanthosis nigricans

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    Subhasis Mukherjee

    2011-01-01

    Full Text Available A 70-years-old male presented with blackening of both hands and face for last six months which was progressive and attended dermatology outpatients department. Dermatologist opined the skin lesions as acanthosis nigricans. He was referred to our department to evaluate for any underlying internal malignancy as he was a smoker. His chest X-ray revealed right sided hilar prominence with a mid zone cavity with fluid level. Fibreoptic bronchoscopy was done, there was one ulcerative growth in right middle lobe bronchus. Biopsy from the ulcer revealed probable squamous cell carcinoma. CT scan of thorax was also done and CT guided FNAC of Rt lung lesion yielded non small cell carcinoma. His skin lesions were also biopsied and diagnosis of acanthosis nigricans was confirmed. Here we report a case of acanthosis nigricans associated with non-small cell cancer of lung.

  4. Innovative Approaches to Treating Type 1 Diabetes Addressed in Beta-Cell Replacement Presentations

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    ... Camp Fundraising Events Step Out Walk to Stop Diabetes Tour de Cure Father of the Year Stop Diabetes at School ... Forecast Stop Diabetes Step Out: Walk to Stop Diabetes Tour de Cure Living With Type 2 Diabetes Recipes for Healthy ...

  5. Homing of antigen-presenting cells (APCs in head kidney and spleen – salmon head kidney hosts diverse APC types

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    Dimitar Borisov Iliev

    2013-06-01

    Full Text Available Lymph nodes and spleen are major organs where mammalian APCs initiate and orchestrate Ag-specific immune responses. Unlike mammals, teleosts lack lymph nodes and an interesting question is whether alternative organs may serve as sites for antigen presentation in teleosts. In the current study, fluorescent ovalbumin (Ova and CpG oligonucleotides (ODNs injected intra-abdominally were detected in significant numbers of salmon head kidney (HK MHCII+ cells over a period of 2 weeks while in spleen the percentage of these was transient and declined from day 1 post injection. In vitro studies further shed light on the properties of the diverse MHCII+ cell types found in HK. The ultrastructure of a subpopulation of MHCII+ cells with a high capacity to endocytose and process Ova indicated that these were able to perform constitutive macropinocytosis. Upon stimulation with CpG ODNs these cells upregulated CD86 and gave very high levels of TNF mRNA indicating that these are professional APCs, related to macrophages and dendritic cells (DCs. A subpopulation of HK granulocytes expressed high levels of surface MHCII and upon CpG stimulation upregulated most of the tested APC marker genes. Although these granulocytes expressed TNF weakly, they had relatively high basal levels of IL-1β mRNA and the CpG stimulation upregulated IL-1β, along with its signaling and decoy receptors, to the highest levels as compared to other HK cell types. Interestingly, the high expression of IL-1β mRNA in the granulocytes correlated with a high autophagy flux as demonstrated by LC3-II conversion. Autophagy has recently been found to be implicated in IL-1β processing and secretion and the presented data suggests that granulocytes of salmon, and perhaps other teleost species, may serve as a valuable model to study the involvement of autophagy in regulation of the vertebrate immune response.

  6. Microsatellite alterations are also present in the less aggressive types of adult T-cell leukemia-lymphoma.

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    Marcelo Magalhães

    2015-01-01

    Full Text Available Adult T-cell leukemia/lymphoma (ATL is a mature T-cell neoplasia etiologically linked to HTLV-1. Manifestations of ATL are diverse and different clinical types with different tissue involvement and aggressiveness have been described. The mechanisms that lead to the development of ATL clinical types have not yet been clarified. Considering that in ATL patients HTLV-1 infection generally occurs in childhood, a multistep carcinogenesis model has been proposed. Microsatellite alterations are important genetic events in cancer development and these alterations have been reported in the aggressive types of ATL. Little is known about oncogenesis of the less aggressive types.In this study we investigated the role of the microsatellite alterations in the pathogenesis mediated by HTLV-1 in the different types of ATL. We examined the presence of microsatellite instability (MSI and loss of heterozigosity (LOH in matched pair samples (tumoral and normal of 24 patients with less aggressive types (smoldering and chronic and in aggressive types (acute and lymphoma of ATL. Four microsatellite markers D10S190, D10S191, D1391 and DCC were analyzed. MSI was found in four patients, three smoldering and one chronic, and LOH in four patients, three smoldering and one acute. None of the smoldering patients with microsatellite alterations progressed to aggressive ATL.To our knowledge, this is the first report describing the presence of MSI and LOH in the less aggressive types of ATL. These results indicate that microsatellite alterations may participate in the development of the less aggressive types of ATL.

  7. 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

  8. Types of Stem Cells

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    ... Stem Cell Glossary Search Toggle Nav Types of Stem Cells Stem cells are the foundation from which all ... Learn About Stem Cells > Types of Stem Cells Stem cells Stem cells are the foundation for every organ ...

  9. Diffuse large B cell lymphoma presenting as Horner's syndrome in a patient diagnosed with neurofibromatosis type 1: a case report and review of the literature

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    Lueangarun Saoraya

    2012-01-01

    Full Text Available Abstract Introduction Horner's syndrome has a variety of etiologies ranging from benign to serious life-threatening conditions and has been infrequently reported as a presenting symptom of patients with lymphoid neoplasms. Only one case of Burkitt's lymphoma presenting with toothache, paresthesia, and Horner's syndrome has been described and no case reports of diffuse large B-cell lymphoma as the etiology of Horner's syndrome currently exist in the literature. In addition, lymphoid neoplasms have rarely been reported to occur in patients with neurofibromatosis type 1 despite an increased risk of many types of cancer in such cases. Case presentation A 28-year-old Thai man presented with a progressively enlarged left supraclavicular mass together with a significant weight loss and night sweating for four months. He also noticed hoarseness and ptosis of his left eye associated with double vision for two months. Physical examination revealed large supraclavicular lymphadenopathy and Horner's syndrome (ptosis, miosis, and anhydrosis on the left side of his face. A large mediastinal mass was clearly detected by chest X-ray and computed tomography and subsequent lymph node biopsy provided a diagnosis of diffuse large B-cell lymphoma. Interestingly, the patient was also definitely diagnosed with neurofibromatosis type 1 from multiple café au lait macules, axillary freckles, three neurofibromas, multiple Lisch nodules, and a history of affected family members. He subsequently received chemotherapy with a good response. Twenty-seven cases of various types of lymphoid neoplasms previously reported to occur in neurofibromatosis type 1 patients were also extracted from the literature. All cases were non-Hodgkin lymphoma and the major subtype was T-cell. Only nine cases were B-cell lymphoma. The majority of cases were young with a median age at lymphoma diagnosis of 9.4 years (range 1.1 to 77 years. Two-thirds of the cases were boys or men. Other concomitant

  10. Chitosan as an Immunomodulating Adjuvant on T-Cells and Antigen-Presenting Cells in Herpes Simplex Virus Type 1 Infection

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    Bunsoon Choi

    2016-01-01

    Full Text Available Herpes disease caused by herpes simplex virus type 1 (HSV-1 is an intractable condition. It is a major concern in public health. Our purpose of this study was to verify the function of chitosan as an adjuvant for immune regulation specifically under herpes simplex virus type 1 (HSV-1 infection. Ahead of HSV infection, chitosan, heat inactivated green fluorescent protein expressing HSV (G-HSV, and a combination of chitosan and G-HSV were used to pretreat ICR mice followed by HSV-1 infection. Using flow cytometric analysis, the frequencies of T-cells, monocytes, dendritic cells (DCs, and natural killer (NK cells were analyzed by surface expression of CD4+, CD8+, CD14+, CD11c+, NK1.1+, and DX5+ cells. In HSV infected mice, chitosan treatment significantly increased the frequencies of CD4+ T-cells (33.6±5.78% compared to those in the control group (24.02±12.47%, p=0.05. The frequencies of DC and NK cells were also significantly different between chitosan treated mice and control mice. In addition, anti-HSV IgG antibody was downregulated in chitosan treated mice. These results suggest that chitosan is a potential modulator or immune stimulator as an adjuvant in HSV-1 infected mice.

  11. Chitosan as an Immunomodulating Adjuvant on T-Cells and Antigen-Presenting Cells in Herpes Simplex Virus Type 1 Infection

    Science.gov (United States)

    Jo, Do-Hyun; Anower, A. K. M. Mostafa; Islam, S. M. Shamsul

    2016-01-01

    Herpes disease caused by herpes simplex virus type 1 (HSV-1) is an intractable condition. It is a major concern in public health. Our purpose of this study was to verify the function of chitosan as an adjuvant for immune regulation specifically under herpes simplex virus type 1 (HSV-1) infection. Ahead of HSV infection, chitosan, heat inactivated green fluorescent protein expressing HSV (G-HSV), and a combination of chitosan and G-HSV were used to pretreat ICR mice followed by HSV-1 infection. Using flow cytometric analysis, the frequencies of T-cells, monocytes, dendritic cells (DCs), and natural killer (NK) cells were analyzed by surface expression of CD4+, CD8+, CD14+, CD11c+, NK1.1+, and DX5+ cells. In HSV infected mice, chitosan treatment significantly increased the frequencies of CD4+ T-cells (33.6 ± 5.78%) compared to those in the control group (24.02 ± 12.47%, p = 0.05). The frequencies of DC and NK cells were also significantly different between chitosan treated mice and control mice. In addition, anti-HSV IgG antibody was downregulated in chitosan treated mice. These results suggest that chitosan is a potential modulator or immune stimulator as an adjuvant in HSV-1 infected mice. PMID:28096567

  12. CLEC4F is an inducible C-type lectin in F4/80-positive cells and is involved in alpha-galactosylceramide presentation in liver.

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    Chih-Ya Yang

    Full Text Available CLEC4F, a member of C-type lectin, was first purified from rat liver extract with high binding affinity to fucose, galactose (Gal, N-acetylgalactosamine (GalNAc, and un-sialylated glucosphingolipids with GalNAc or Gal terminus. However, the biological functions of CLEC4F have not been elucidated. To address this question, we examined the expression and distribution of murine CLEC4F, determined its binding specificity by glycan array, and investigated its function using CLEC4F knockout (Clec4f-/- mice. We found that CLEC4F is a heavily glycosylated membrane protein co-expressed with F4/80 on Kupffer cells. In contrast to F4/80, CLEC4F is detectable in fetal livers at embryonic day 11.5 (E11.5 but not in yolk sac, suggesting the expression of CLEC4F is induced as cells migrate from yolk cells to the liver. Even though CLEC4F is not detectable in tissues outside liver, both residential Kupffer cells and infiltrating mononuclear cells surrounding liver abscesses are CLEC4F-positive upon Listeria monocytogenes (L. monocytogenes infection. While CLEC4F has strong binding to Gal and GalNAc, terminal fucosylation inhibits CLEC4F recognition to several glycans such as Fucosyl GM1, Globo H, Bb3∼4 and other fucosyl-glycans. Moreover, CLEC4F interacts with alpha-galactosylceramide (α-GalCer in a calcium-dependent manner and participates in the presentation of α-GalCer to natural killer T (NKT cells. This suggests that CLEC4F is a C-type lectin with diverse binding specificity expressed on residential Kupffer cells and infiltrating monocytes in the liver, and may play an important role to modulate glycolipids presentation on Kupffer cells.

  13. Type II lepra reaction: an unusual presentation.

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    Chauhan, S; D'Cruz, S; Mohan, H; Singh, R; Ram, J; Sachdev, A

    2006-01-27

    Ulcers with maculo-papular rash are an unusual presenting feature of leprosy. They occur as result of neuropathy, type-2 lepra reaction or Lucio's phenomenon. The hall mark of type-2 reaction is erythema nodosum. Very rarely it manifests as ulcerative skin lesions. We describe one such unusual case of a young male who presented with multiple ulcers and maculo-papular rash over the legs, chest and abdomen. In addition to this, he had fever, heart murmur, pulmonary infiltrates, neuropathy, and deranged liver function. A clinical differential diagnosis of infective endocarditis and systemic nectrozing vasculitis was made. Skin biopsy showed dense inflammation with lepra bacilli consistent with type-2 lepra reaction.

  14. The putative Notch ligand HyJagged is a transmembrane protein present in all cell types of adult Hydra and upregulated at the boundary between bud and parent.

    Science.gov (United States)

    Prexl, Andrea; Münder, Sandra; Loy, Bernhard; Kremmer, Elisabeth; Tischer, Susanne; Böttger, Angelika

    2011-09-07

    The Notch signalling pathway is conserved in pre-bilaterian animals. In the Cnidarian Hydra it is involved in interstitial stem cell differentiation and in boundary formation during budding. Experimental evidence suggests that in Hydra Notch is activated by presenilin through proteolytic cleavage at the S3 site as in all animals. However, the endogenous ligand for HvNotch has not been described yet. We have cloned a cDNA from Hydra, which encodes a bona-fide Notch ligand with a conserved domain structure similar to that of Jagged-like Notch ligands from other animals. Hyjagged mRNA is undetectable in adult Hydra by in situ hybridisation but is strongly upregulated and easily visible at the border between bud and parent shortly before bud detachment. In contrast, HyJagged protein is found in all cell types of an adult hydra, where it localises to membranes and endosomes. Co-localisation experiments showed that it is present in the same cells as HvNotch, however not always in the same membrane structures. The putative Notch ligand HyJagged is conserved in Cnidarians. Together with HvNotch it may be involved in the formation of the parent-bud boundary in Hydra. Moreover, protein distribution of both, HvNotch receptor and HyJagged indicate a more widespread function for these two transmembrane proteins in the adult hydra, which may be regulated by additional factors, possibly involving endocytic pathways.

  15. The putative Notch ligand HyJagged is a transmembrane protein present in all cell types of adult Hydra and upregulated at the boundary between bud and parent

    Directory of Open Access Journals (Sweden)

    Tischer Susanne

    2011-09-01

    Full Text Available Abstract Background The Notch signalling pathway is conserved in pre-bilaterian animals. In the Cnidarian Hydra it is involved in interstitial stem cell differentiation and in boundary formation during budding. Experimental evidence suggests that in Hydra Notch is activated by presenilin through proteolytic cleavage at the S3 site as in all animals. However, the endogenous ligand for HvNotch has not been described yet. Results We have cloned a cDNA from Hydra, which encodes a bona-fide Notch ligand with a conserved domain structure similar to that of Jagged-like Notch ligands from other animals. Hyjagged mRNA is undetectable in adult Hydra by in situ hybridisation but is strongly upregulated and easily visible at the border between bud and parent shortly before bud detachment. In contrast, HyJagged protein is found in all cell types of an adult hydra, where it localises to membranes and endosomes. Co-localisation experiments showed that it is present in the same cells as HvNotch, however not always in the same membrane structures. Conclusions The putative Notch ligand HyJagged is conserved in Cnidarians. Together with HvNotch it may be involved in the formation of the parent-bud boundary in Hydra. Moreover, protein distribution of both, HvNotch receptor and HyJagged indicate a more widespread function for these two transmembrane proteins in the adult hydra, which may be regulated by additional factors, possibly involving endocytic pathways.

  16. 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

    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...... & Discussion To examine the polarising effect of gut bacteria on APCs, surface markers and cytokines were measured. The co-stimulatory molecules CD40 and CD86 were induced to a different extent together with CD83. Interleukin-12 (a Th1 cytokine) was only induced by Lactobacillus acidophilus. Interleukin-10...

  17. Extranodal NK/T-cell lymphoma, nasal type (ENKTL-NT): An update on epidemiology, clinical presentation, and natural history in North American and European cases

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    Haverkos, Bradley M.; Pan, Zenggang; Gru, Alejandro A.; Freud, Aharon G.; Rabinovitch, Rachel; Xu-Welliver, Meng; Otto, Brad; Barrionuevo, Carlos; Baiocchi, Robert A.; Rochford, Rosemary; Porcu, Pierluigi

    2016-01-01

    Extranodal NK/T-cell lymphoma, nasal type (ENKTL-NT) is an aggressive extranodal non-Hodgkin lymphoma most commonly occurring in East Asia and Latin America but with increasing incidence in the U.S. Data on epidemiology, disease presentation, and outcome for European and North American (“Western”) cases are very limited. We review published landmark clinical studies on ENKTL-NT in the West and report in detail recent data, including our institutional experience. We highlight key observations in its epidemiology, natural history, and trends in clinical management. In the U.S., ENKTL-NT is more common among Asian Pacific Islanders (API) and Hispanics compared to non-Hispanic whites. Published studies indicate less heterogeneity in clinical presentation in Western ENKTL-NT compared to Asian patients. While there is variation in age at diagnosis, presence of antecedent lymphoproliferative disorders, and outcomes among racial/ethnic groups, the universal association of ENKTL-NT with EBV and the poor response of this neoplasm to anthracycline-based therapy are consistent across all geographic areas. PMID:27778143

  18. Mode of Tolerance Induction and Requirement for Aire Are Governed by the Cell Types That Express Self-Antigen and Those That Present Antigen.

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    Mouri, Yasuhiro; Ueda, Yoshihiro; Yamano, Tomoyoshi; Matsumoto, Minoru; Tsuneyama, Koichi; Kinashi, Tatsuo; Matsumoto, Mitsuru

    2017-12-15

    Aire controls the fate of autoreactive thymocytes (i.e., clonal deletion or development into regulatory T cells [Tregs]) through transcriptional control of the expression of tissue-restricted self-antigens (TRAs) from medullary thymic epithelial cells (mTECs) and bone marrow (BM)-derived cells. Although TRAs expressed by mTECs and BM-derived cells are suggested to complement each other to generate a full spectrum of TRAs, little is known about the relative contribution of TRAs from each component for establishment of self-tolerance. Furthermore, the precise role of Aire in specific types of Aire-expressing APCs remains elusive. We have approached these issues by generating two different types of transgenic mouse (Tg) model, which express a prefixed model self-antigen driven by the insulin promoter or the Aire promoter. In the insulin-promoter Tg model, mTECs alone were insufficient for clonal deletion, and BM-derived APCs were required for this action by utilizing Ag transferred from mTECs. In contrast, mTECs alone were able to induce Tregs, although at a much lower efficiency in the absence of BM-derived APCs. Importantly, lack of Aire in mTECs, but not in BM-derived APCs, impaired both clonal deletion and production of Tregs. In the Aire-promoter Tg model, both mTECs and BM-derived APCs could independently induce clonal deletion without Aire, and production of Tregs was impaired by the lack of Aire in mTECs, but not in BM-derived APCs. These results suggest that the fate of autoreactive thymocytes together with the requirement for Aire depend on the cell types that express self-antigens and the types of APCs involved in tolerance induction. Copyright © 2017 by The American Association of Immunologists, Inc.

  19. Enteroendocrine cell types revisited

    DEFF Research Database (Denmark)

    Engelstoft, Maja S; Egerod, Kristoffer Lihme; Lund, Mari L

    2013-01-01

    The GI-tract is profoundly involved in the control of metabolism through peptide hormones secreted from enteroendocrine cells scattered throughout the gut mucosa. A large number of recently generated transgenic reporter mice have allowed for direct characterization of biochemical and cell...... biological properties of these previously highly elusive enteroendocrine cells. In particular the surprisingly broad co-expression of six functionally related hormones in the intestinal enteroendocrine cells indicates that it should be possible to control not only the hormone secretion but also the type...... and number of enteroendocrine cells. However, this will require a more deep understanding of the factors controlling differentiation, gene expression and specification of the enteroendocrine cells during their weekly renewal from progenitor cells in the crypts of the mucosa....

  20. Red cell membrane: past, present, and future

    National Research Council Canada - National Science Library

    Mohandas, Narla; Gallagher, Patrick G

    2008-01-01

    .... The non-nucleated red cell is unique among human cell type in that the plasma membrane, its only structural component, accounts for all of its diverse antigenic, transport, and mechanical characteristics...

  1. Nanoscale artificial antigen presenting cells for T cell immunotherapy.

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    Perica, Karlo; De León Medero, Andrés; Durai, Malarvizhi; Chiu, Yen Ling; Bieler, Joan Glick; Sibener, Leah; Niemöller, Michaela; Assenmacher, Mario; Richter, Anne; Edidin, Michael; Oelke, Mathias; Schneck, Jonathan

    2014-01-01

    Artificial antigen presenting cells (aAPC), which deliver stimulatory signals to cytotoxic lymphocytes, are a powerful tool for both adoptive and active immunotherapy. Thus far, aAPC have been synthesized by coupling T cell activating proteins such as CD3 or MHC-peptide to micron-sized beads. Nanoscale platforms have different trafficking and biophysical interaction properties and may allow development of new immunotherapeutic strategies. We therefore manufactured aAPC based on two types of nanoscale particle platforms: biocompatible iron-dextran paramagnetic particles (50-100 nm in diameter) and avidin-coated quantum dot nanocrystals (~30 nm). Nanoscale aAPC induced antigen-specific T cell proliferation from mouse splenocytes and human peripheral blood T cells. When injected in vivo, both iron-dextran particles and quantum dot nanocrystals enhanced tumor rejection in a subcutaneous mouse melanoma model. This is the first description of nanoscale aAPC that induce antigen-specific T cell proliferation in vitro and lead to effective T cell stimulation and inhibition of tumor growth in vivo. Artifical antigen presenting cells could revolutionize the field of cancer-directed immunotherapy. This team of investigators have manufactured two types of nanoscale particle platform-based aAPCs and demonstrates that both iron-dextran particles and quantum dot nanocrystals enhance tumor rejection in a melanoma model, providing the first description of nanoscale aAPCs that lead to effective T cell stimulation and inhibition of tumor growth. © 2013.

  2. The Neck Region of the C-type Lectin DC-SIGN Regulates Its Surface Spatiotemporal Organization and Virus-binding Capacity on Antigen-presenting Cells*

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    Manzo, Carlo; Torreno-Pina, Juan A.; Joosten, Ben; Reinieren-Beeren, Inge; Gualda, Emilio J.; Loza-Alvarez, Pablo; Figdor, Carl G.; Garcia-Parajo, Maria F.; Cambi, Alessandra

    2012-01-01

    The C-type lectin DC-SIGN expressed on dendritic cells (DCs) facilitates capture and internalization of a plethora of different pathogens. Although it is known that DC-SIGN organizes in nanoclusters at the surface of DCs, the molecular mechanisms responsible for this well defined nanopatterning and role in viral binding remain enigmatic. By combining biochemical and advanced biophysical techniques, including optical superresolution and single particle tracking, we demonstrate that DC-SIGN intrinsic nanoclustering strictly depends on its molecular structure. DC-SIGN nanoclusters exhibited free, Brownian diffusion on the cell membrane. Truncation of the extracellular neck region, known to abrogate tetramerization, significantly reduced nanoclustering and concomitantly increased lateral diffusion. Importantly, DC-SIGN nanocluster dissolution exclusively compromised binding to nanoscale size pathogens. Monte Carlo simulations revealed that heterogeneity on nanocluster density and spatial distribution confers broader binding capabilities to DC-SIGN. As such, our results underscore a direct relationship between spatial nanopatterning, driven by intermolecular interactions between the neck regions, and receptor diffusion to provide DC-SIGN with the exquisite ability to dock pathogens at the virus length scale. Insight into how virus receptors are organized prior to virus binding and how they assemble into functional platforms for virus docking is helpful to develop novel strategies to prevent virus entry and infection. PMID:23019323

  3. Professional differences in antigen presentation to iNKT cells.

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    De Libero, Gennaro; Mori, Lucia

    2014-01-16

    Invariant natural killer T cells are preactivated lymphocytes that react upon recognition of CD1d-antigen complexes. Accordingly, any type of CD1d-positive cell could behave as antigen-presenting cell (APC). In this issue of Immunity, Arora et al. (2014), report that professional APCs still make the difference. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. 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

  5. Receptor-mediated phagocytosis elicits cross-presentation in nonprofessional antigen-presenting cells.

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    Giodini, Alessandra; Rahner, Christoph; Cresswell, Peter

    2009-03-03

    In cross-presentation by dendritic cells (DCs), internalized proteins are retrotranslocated into the cytosol, degraded by the proteasome, and the generated antigenic peptides bind to MHC class I molecules for presentation on the cell surface. Endoplasmic reticulum (ER) contribution to phagosomal membranes is thought to provide antigen access to the ER-associated degradation (ERAD) machinery, allowing cytosolic dislocation. Because the ERAD pathway is present in all cell types and exogenous antigens encounter an ER-containing compartment during phagocytosis, we postulated that forcing phagocytosis in cell types other than DCs would render them competent for cross-presentation. Indeed, FcRgammaIIA expression endowed 293T cells with the capacity for both phagocytosis and ERAD-mediated cross-presentation of an antigen provided as an immune complex. The acquisition of this ability by nonprofessional antigen-presenting cells suggests that a function potentially available in all cell types has been adapted by DCs for presentation of exogenous antigens by MHC class I molecules.

  6. Characterization of vibrissa germinative cells: transition of cell types.

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    Osada, A; Kobayashi, K

    2001-12-01

    Germinative cells, small cell masses attached to the stalks of dermal papillae that are able to differentiate into the hair shaft and inner root sheath, form follicular bulb-like structures when co-cultured with dermal papilla cells. We studied the growth characteristics of germinative cells to determine the cell types in the vibrissa germinative tissue. Germinative tissues, attaching to dermal papillae, were cultured on 3T3 feeder layers. The cultured keratinocytes were harvested and transferred, equally and for two passages, onto lined dermal papilla cells (LDPC) and/or 3T3 feeder layers. The resulting germinative cells were classified into three types in the present experimental condition. Type 1 cells grow very well on either feeder layer, whereas Type 3 cells scarcely grow on either feeder layer. Type 2 cells are very conspicuous and are reversible. They grow well on 3T3 but growth is suppressed on LDPC feeder layers. The Type 2 cells that grow well on 3T3 feeder layers, however, are suppressed when transferred onto LDPC and the Type 2 cells that are suppressed on LDPC begin to grow again on 3T3. The transition of one cell type to another in vitro and the cell types that these germinative cell types correspond to in vivo is discussed. It was concluded that stem cells or their close progenitors reside in the germinative tissues of the vibrissa bulb except at late anagen-early catagen.

  7. Clinical presentation and outcome of adult-type granulosa cell tumors: A retrospective study of 30 patients in a single institute

    Directory of Open Access Journals (Sweden)

    Ben-Shian Huang

    2014-01-01

    Conclusion: Physicians should be alert to the difference in the symptom presentation of GCTs between pre- and postmenopausal women, giving particular attention to the usefulness of the preoperative serum level of cancer antigen 125 in patients with GCTs. More evidence is needed to confirm this observation.

  8. Presentation of lipid antigens to T cells.

    Science.gov (United States)

    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.

  9. Type II lepra reaction--an unusual presentation.

    Science.gov (United States)

    Ray, Avas Chandra; Sen, Sumit; Banerjee, Sabyasachi; Mukhopadhyay, Jotideb

    2012-06-01

    Type II lepra reaction usually present with skin lesions. We report a 23 years old male patient presented with fever for two weeks with no visible skin lesion suggestive of leprosy and with no history of either completion or concurrent anti leprosy drug treatment was eventually turned out to be a case of Hansen's presenting with type II lepra reaction.

  10. Langerhans Cell Histiocytosis Presenting as Uncontrolled Asthma

    Directory of Open Access Journals (Sweden)

    Frederic A. Rawlins

    2013-01-01

    Full Text Available Langerhans cell histiocytosis (LCH is an uncommon disorder affecting primarily young adult smokers. It is characterized by abnormal proliferation of Langerhans cells, specialized monocyte-macrophage lineage antigen-presenting cells. LCH can affect the lungs in isolation or as part of a systemic disease. Most commonly, the disease presents in the third or fourth decade without gender predominance. Symptoms typically include dyspnea and cough. Commonly, physical examination is unremarkable but cor pulmonale may be observed in advanced disease. The chest radiograph is typically abnormal with nodular or interstitial infiltrates and cystic changes. High-resolution computed tomography of the chest with these findings in the middle and upper lobes of an adult smoker is virtually diagnostic of LCH. Pulmonary function assessment is variable. Asthma has rarely been reported in association with this disorder. There are only three reported cases of the diagnosis of concomitant asthma which have been made in association with the diagnosis of LCH. We present a case in which our patient presented with signs and symptoms of asthma to include confirmatory findings of airway hyperresponsiveness. The diagnosis of LCH was established after the patient failed to respond to conventional treatment for asthma, and further evaluation was completed.

  11. Livedo reticularis in type 2 lepra reaction: A rare presentation.

    Science.gov (United States)

    Naveen, Kikkeri Narayanasetty; Athanikar, Sharatchandra Bhimrao; Hegde, Spandana Prakash; Athanikar, Vidisha Sharatchandra

    2014-04-01

    Type 2 lepra reaction or erythema nodosum leprosum (ENL) is an immune complex syndrome that occurs mostly in lepromatous leprosy and sometimes in borderline lepromatous leprosy patients. We present an untreated case of lepromatous leprosy, who presented with type 2 lepra reaction and livedo reticularis. Livedo reticularis, though seen in lucio phenomenon, is not a part of type 2 lepra reaction. The case is being reported for its rarity.

  12. The Antigen Presenting Cells Instruct Plasma Cell Differentiation

    Directory of Open Access Journals (Sweden)

    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.

  13. Spinocerebellar ataxia type 2 presenting with cognitive regression in childhood.

    Science.gov (United States)

    Ramocki, Melissa B; Chapieski, Lynn; McDonald, Ryan O; Fernandez, Fabio; Malphrus, Amy D

    2008-09-01

    Spinocerebellar ataxia type 2 typically presents in adulthood with progressive ataxia, dysarthria, tremor, and slow saccadic eye movements. Childhood-onset spinocerebellar ataxia type 2 is rare, and only the infantile-onset form has been well characterized clinically. This article describes a girl who met all developmental milestones until age 3(1/2) years, when she experienced cognitive regression that preceded motor regression by 6 months. A diagnosis of spinocerebellar ataxia type 2 was delayed until she presented to the emergency department at age 7 years. This report documents the results of her neuropsychologic evaluation at both time points. This case broadens the spectrum of spinocerebellar ataxia type 2 presentation in childhood, highlights the importance of considering a spinocerebellar ataxia in a child who presents with cognitive regression only, and extends currently available clinical information to help clinicians discuss the prognosis in childhood spinocerebellar ataxia type 2.

  14. Merkel cell carcinoma: A rare presentation

    Directory of Open Access Journals (Sweden)

    Prosanta Kumar Bhattacharjee

    2014-01-01

    Full Text Available A 33-year-old man presented with a lump at the right side of chest wall of 4 months duration which started bleeding suddenly from an ulcer at its center. Examination revealed a globular ulcerated mass 2 cm in diameter, on the anterior axillary fold, with adherent clot at its center. No regional lymphadenopathy was noted. Wide local excision with 2 cm margin was done. Biopsy report revealed malignant small round-cell tumor. Immunohistochemistry showed it to be cytokeratin-20-positive and S100-negative, suggesting the diagnosis of Merkel cell carcinoma. The patient did not receive any other adjuvant therapy. He is being followed-up for the last 4 years and has shown no features of recurrence so far.

  15. Transient neonatal hyperparathyroidism: a presenting feature of sialidosis type II.

    Science.gov (United States)

    Eminoglu, Tuba Fatma; Ozkan, Mehpare; Igdoura, Suleiman; Dursun, Arzu; Zenciroğlu, Ayşegül

    2013-01-01

    Sialidosis is a lysosomal storage disease caused by deficiency of α-N-acetyl neuraminidase-1. Sialidosis is classified into two main clinical variants: type I, the milder form of the disease, and type II, which can in turn be subdivided into three forms: congenital, infantile, and juvenile. We report a female patient with sialidosis type II, presenting with the congenital form of the disease with thrombocytopenia, pulmonary interstitial thickening, and transient secondary neonatal hyperparathyroidism.

  16. Merkel cell carcinoma: A rare presentation

    OpenAIRE

    Prosanta Kumar Bhattacharjee; Shyamal Kumar Halder; Rajendra Prashad Ray

    2014-01-01

    A 33-year-old man presented with a lump at the right side of chest wall of 4 months duration which started bleeding suddenly from an ulcer at its center. Examination revealed a globular ulcerated mass 2 cm in diameter, on the anterior axillary fold, with adherent clot at its center. No regional lymphadenopathy was noted. Wide local excision with 2 cm margin was done. Biopsy report revealed malignant small round-cell tumor. Immunohistochemistry showed it to be cytokeratin-20-positive and S100-...

  17. Characteristics of children presenting with newly diagnosed type 1 ...

    African Journals Online (AJOL)

    Background. The clinical presentation of type 1 diabetes in children can be acute or insidious, and symptoms may be subtle and frequently misinterpreted. Presentation with diabetic keto-acidosis (DKA) may be associated with significant morbidity and mortality in the paediatric population. This study aims to determine the ...

  18. [Immunohistochemical presentation of fibromodulin during wound healing of periodontal cells].

    Science.gov (United States)

    Qian, Hong; Huang, Qun; Xiao, Yin

    2010-04-01

    To investigate immunohistochemical presentation of fibromodulin in vitro during wound healing of three types of periodontal cells and discuss the role of fibromodulin. Cultured periodontal cells were wounded and followed by observation up to 7 days. The immunohistochemical expression of fibromodulin in periodontal cells was observed. Immunohistochemical localization of fibromodulin during cellular wound healing showed that newly migrating periodontal cells toward the wound area were expressed strongly for fibromodulin at day 1 after wounding; thereafter, fibromodulin expression was noted stronger in newly migrating periodontal cells localized in the central part of the wound area than those around the wound area. These data suggest that fibromodulin may be involved in the early events of wound healing for periodontal cells.

  19. TypingSuite: Integrated Software for Presenting Stimuli, and Collecting and Analyzing Typing Data

    Science.gov (United States)

    Mazerolle, Erin L.; Marchand, Yannick

    2015-01-01

    Research into typing patterns has broad applications in both psycholinguistics and biometrics (i.e., improving security of computer access via each user's unique typing patterns). We present a new software package, TypingSuite, which can be used for presenting visual and auditory stimuli, collecting typing data, and summarizing and analyzing the…

  20. Diffraction pattern study for cell type identification.

    Science.gov (United States)

    Mihailescu, M; Costescu, J

    2012-01-16

    This paper presents our study regarding diffracted intensity distribution in Fresnel and Fraunhofer approximation from different cell types. Starting from experimental information obtained through digital holographic microscopy, we modeled the cell shapes as oblate spheroids and built their phase-only transmission functions. In Fresnel approximation, the experimental and numerical diffraction patterns from mature and immature red blood cells have complementary central intensity values at different distances. The Fraunhofer diffraction patterns of deformed red blood cells were processed in the reciprocal space where, the isoamplitude curves were formed independently for each degree of cell deformation present within every sample; the values on each separate isoamplitude curve are proportional with the percentage of the respective cell type within the sample.

  1. Type I lepra reaction presenting as immune reconstitution inflammatory syndrome.

    Science.gov (United States)

    Kharkar, Vidya; Bhor, Urmila H; Mahajan, Sunanda; Khopkar, Uday

    2007-01-01

    Immune reconstitution inflammatory syndrome (IRIS) is an unusual inflammatory reaction due to infectious and non-infectious causes occurring in human Immunodeficiency virus (HIV)-infected patients. IRIS occurs after the initiation of antiretroviral therapy. There are no reports of type I lepra reaction due to IRIS in published literature from India. We report two cases of HIV-infected males who presented with borderline tuberculoid leprosy in type 1 reaction after the initiation of highly active antiretroviral treatment (HAART). Case 1 presented with multiple, tender, erythematous and hypoesthetic plaques on the trunk and extremities after 3 months of antiretroviral therapy. In case 2, type I lepra reaction was observed 2 months after the initiation of HAART.

  2. Asymmetric Cell Division of T Cells Upon Antigen Presentation Utilizes Multiple Conserved Mechanisms

    Science.gov (United States)

    Oliaro, Jane; Van Ham, Vanessa; Sacirbegovic, Faruk; Pasam, Anupama; Bomzon, Ze’ev; Pham, Kim; Ludford-Menting, Mandy J.; Waterhouse, Nigel J.; Bots, Michael; Hawkins, Edwin D.; Watt, Sally V.; Cluse, Leonie A.; Clarke, Chris J.P.; Izon, David J.; Chang, John T.; Thompson, Natalie; Gu, Min; Johnstone, Ricky W.; Smyth, Mark J.; Humbert, Patrick O.; Reiner, Steven L.; Russell, Sarah M.

    2013-01-01

    Asymmetric cell division is a potential means by which cell fate choices during an immune response are orchestrated. Defining the molecular mechanisms that underlie asymmetric division of T cells is paramount for determining the role of this process in the generation of effector and memory T cell subsets. In other cell types, asymmetric cell division is regulated by conserved polarity protein complexes that control the localization of cell fate determinants and spindle orientation during division. We have developed a tractable, in vitro model of naïve CD8+ T cells undergoing initial division while attached to dendritic cells during antigen presentation to investigate whether similar mechanisms might regulate asymmetric division of T cells. Using this system, we show that direct interactions with antigen presenting cells provide the cue for polarization of T cells. Interestingly, the immunological synapse disseminates before division even though the T cells retain contact with the antigen presenting cell. The cue from the antigen presenting cell is translated into polarization of cell fate determinants via the polarity network of the Par3 and Scribble complexes and orientation of the mitotic spindle during division is orchestrated by the Pins/G protein complex. These findings suggest that T cells have selectively adapted a number of evolutionarily conserved mechanisms to generate diversity through asymmetric cell division. PMID:20530266

  3. Dendritic cells derived from bone marrow cells fail to acquire and present major histocompatibility complex antigens from other dendritic cells

    Science.gov (United States)

    Bedford, Penelope A; Burke, Fiona; Stagg, Andrew J; Knight, Stella C

    2008-01-01

    Dendritic cells stimulate primary T-cell responses and a major activation route is via presentation of antigens pre-processed by other dendritic cells. This presentation of pre-processed antigens most likely proceeds through transfer of functional major histocompatibility complex (MHC) antigens through exosomes, ‘live nibbling’ or apoptotic vesicles. We hypothesized that not all dendritic cell populations may both donate MHC antigen to dendritic cells and present antigens acquired from other dendritic cells. All populations tested, including those derived from bone marrow precursor cells stimulated primary, allogeneic T-cell responses and acted as accessory cells for mitogen stimulation. Populations of responder type, splenic dendritic cells promoted allogeneic responses indirectly but those derived from bone marrow cells blocked rather than promoted T-cell proliferation. To identify mechanisms underlying this difference we studied transfer of I-A antigens between cells. Active, two-way transfer of allogeneic I-A occurred between splenic primary antigen presenting cells including CD8α+ lymphoid dendritic cells, CD8α− myeloid dendritic cells and B220+ cells; all these cell types donated as well as acquired MHC molecules. By contrast, the bone marrow-derived dendritic cells donated I-A antigens but acquired negligible amounts. Thus, dendritic cells derived directly from bone marrow cells may stimulate primary T-cell responses through transferring functional MHC to other dendritic cells but may not be able to acquire and present antigens from other dendritic cells. The evidence suggests that T-cell activation may be blocked by the presence of dendritic cells that have not matured through lymphoid tissues which are unable to acquire and present antigens pre-processed by other dendritic cells. PMID:18266716

  4. Neurofibromatosis Type 2 Presenting with Oculomotor Ophthalmoplegia and Distal Myopathy

    Directory of Open Access Journals (Sweden)

    Jessica Mani Penny Tevaraj

    2016-01-01

    Full Text Available Neurofibromatosis type 2 usually presents with bilateral acoustic schwannomas. We highlight the rare presentation of neurofibromatosis initially involving third nerve. A 23-year-old Malay female presented with left eye drooping of the upper lid and limitation of upward movement for 8 years. It was associated with right-sided body weakness, change in voice, and hearing disturbance in the right ear for the past 2 years. On examination, there was mild ptosis and limitation of movement superiorly in the left eye. Both eyes had posterior subcapsular cataract. Fundoscopy showed generalised optic disc swelling in both eyes. She also had palsy of the right vocal cord, as well as the third and eighth nerve. There was wasting of the distal muscles of her right hand, with right-sided decreased muscle power. Pedunculated cutaneous lesions were noted over her body and scalp. MRI revealed bilateral acoustic and trigeminal schwannomas with multiple extra-axial lesions and intradural extramedullary nodules. Patient was diagnosed with neurofibromatosis type 2 and planned for craniotomy and tumour debulking, but she declined treatment. Neurofibromatosis type 2 may uncommonly present with isolated ophthalmoplegia, so a thorough physical examination and a high index of suspicion are required to avoid missing this condition.

  5. Melanoma-inhibiting activity (MIA) mRNA is not exclusively transcribed in melanoma cells: low levels of MIA mRNA are present in various cell types and in peripheral blood

    NARCIS (Netherlands)

    de Vries, T. J.; Fourkour, A.; Punt, C. J.; Diepstra, H.; Ruiter, D. J.; van Muijen, G. N.

    1999-01-01

    The detection of minimal amounts of melanoma cells by tyrosinase reverse transcription polymerase chain reaction (RT-PCR) is seriously hampered by false negative reports in blood of melanoma patients with disseminated melanoma. Therefore, additional assays which make use of multiple melanoma markers

  6. An unusual presentation of osteogenesis imperfecta type I

    Directory of Open Access Journals (Sweden)

    Rebelo M

    2011-04-01

    Full Text Available Marta Rebelo, Jandira Lima, José Diniz Vieira, José Nascimento CostaDepartment of Internal Medicine, University Hospital of Coimbra, Coimbra, PortugalAbstract: Osteogenesis imperfecta (OI is a rare inherited disorder with a broad spectrum of clinical and genetic variability. The genetic diversity involves, in the majority of the cases, mutations in one of the genes that encodes the type 1 collagen protein (COL1 A1 and COL1 A2, but it is not a requirement for the diagnosis. The most benign form is OI type I. The authors present a case report of a 25-year-old woman who had severe low back pain associated with incapacity to walk and breast-feed post-partum. Symptoms developed 2 weeks after delivery. The radiological examination revealed severe osteoporosis with no abnormalities in the laboratory findings. The clinical signs and a positive personal and family history of multiple fractures in childhood suggested OI type I, although other diagnosis, such as pregnancy-associated osteoporosis, was also considered. The atypical presentation of this rare disorder in adulthood calls attention to the need for early diagnosis for prompt treatment. Treatment of OI is never curative, but it improves the quality of the patient’s life.Keywords: osteogenesis imperfecta, collagen, pregnancy, osteoporosis

  7. Unusual presentation of T-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Pandya Mona

    1997-01-01

    Full Text Available A 56-year old woman developed multiple papules, plaques and erythema - multiforme (EM like lesions on palms, soles, abdomen, back, axillary and gluteal folds of one month duration. She also had erythematous plaques, painful necrotising ulcers and oro-genital ulcerations. Skin biopsy was suggestive of plaque stage of cutaneous T-cell lymphoma.

  8. [Cell therapy for type I diabete].

    Science.gov (United States)

    Sokolova, I B

    2009-01-01

    Cell therapy is a modern and promising approach to type I diabetes mellitus treatment. Nowadays a wide range of cells is used in laboratory experiments and clinical studies, including allogeneic and xenogeneic cells of Langergance islets, bone marrow cells, haematopoietic stem cells, mesenchymal stem cells, and cord blood stem cells. Any type of the cells named could correct the status of the patients to a certain extent. However, full recovery after cell therapy has not been achieved yet.

  9. Dye solar cell research: EU delegation presentation

    CSIR Research Space (South Africa)

    Cummings, F

    2009-11-09

    Full Text Available Franscious Cummings Energy and Processes Materials Science and Manufacturing Council for Scientific and Industrial Research P.O. Box 395 Pretoria 0001, South Africa 13 November 2009 © CSIR 2007 www.csir.co.za CONTENT head2right...Background head2rightCSIR Dye Solar Cell Research head2rightCollaborations and Links head2rightAcknowledgements © CSIR 2007 www.csir.co.za BACKGROUND head2rightSA is dry: Annual rainfall average of 450 mm compared with a world average...

  10. Giant cell arteritis presenting as facial swelling.

    Science.gov (United States)

    Ricketti, Anthony J; Cleri, Dennis J; Godyn, Janusz J; Shenk, Suzanne H; Vernaleo, John R

    2008-01-01

    Facial swelling is commonly ascribed to angioedema and a host of other causes. Temporal arteritis (TA), a disease most often diagnosed in patients over the age of 50 years, frequently presents with nonspecific and often ignored complaints (headache, symptoms of polymyalgia rheumatica, low-grade fever, fever of unknown origin, loss of appetite, depression, joint pains, weight loss, hair loss, and even respiratory symptoms). The diagnosis of TA is highly likely in the presence of new-onset headaches, polymyalgia rheumatica, and a tender, cord-like, or swollen temporal artery. Facial swelling must be appreciated as another presentation of TA, especially when accompanied by other nonspecific symptoms. High clinical suspicion, immediate treatment, and definitive diagnosis by temporal artery biopsy are necessary to prevent the most severe vascular complications of blindness and cerebrovascular accidents. Treatment with corticosteroids is most often successful. Because this treatment is fraught with all the risks of high-dose and prolonged steroid therapy, it should only be initiated in cases of significant clinical suspicion, followed by a timely temporal artery biopsy to confirm the diagnosis. Delay in therapy increases the risk of a vascular catastrophe. Delay in obtaining a temporal artery biopsy after therapy has been initiated decreases the diagnostic sensitivity of the test. Other modalities of immunosuppressive therapy remain either unsuccessful or unproven. Concomitant low-dose aspirin therapy appears to hold promise.

  11. Asymmetric cell division of T cells upon antigen presentation uses multiple conserved mechanisms.

    Science.gov (United States)

    Oliaro, Jane; Van Ham, Vanessa; Sacirbegovic, Faruk; Pasam, Anupama; Bomzon, Ze'ev; Pham, Kim; Ludford-Menting, Mandy J; Waterhouse, Nigel J; Bots, Michael; Hawkins, Edwin D; Watt, Sally V; Cluse, Leonie A; Clarke, Chris J P; Izon, David J; Chang, John T; Thompson, Natalie; Gu, Min; Johnstone, Ricky W; Smyth, Mark J; Humbert, Patrick O; Reiner, Steven L; Russell, Sarah M

    2010-07-01

    Asymmetric cell division is a potential means by which cell fate choices during an immune response are orchestrated. Defining the molecular mechanisms that underlie asymmetric division of T cells is paramount for determining the role of this process in the generation of effector and memory T cell subsets. In other cell types, asymmetric cell division is regulated by conserved polarity protein complexes that control the localization of cell fate determinants and spindle orientation during division. We have developed a tractable, in vitro model of naive CD8(+) T cells undergoing initial division while attached to dendritic cells during Ag presentation to investigate whether similar mechanisms might regulate asymmetric division of T cells. Using this system, we show that direct interactions with APCs provide the cue for polarization of T cells. Interestingly, the immunological synapse disseminates before division even though the T cells retain contact with the APC. The cue from the APC is translated into polarization of cell fate determinants via the polarity network of the Par3 and Scribble complexes, and orientation of the mitotic spindle during division is orchestrated by the partner of inscuteable/G protein complex. These findings suggest that T cells have selectively adapted a number of evolutionarily conserved mechanisms to generate diversity through asymmetric cell division.

  12. Large-cell Neuroendocrine Carcinoma of the Lung: Unusual Presentation

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Serra Valdés

    2014-11-01

    Full Text Available Lung cancer is the leading cause of death among malignant tumors. Pulmonary neuroendocrine tumors encompass a broad spectrum of tumors including the large-cell neuroendocrine carcinoma. The case of a 57-year-old white housewife with a history of smoking, diabetes, hypothyroidism and hypertension who sought medical attention because of headache, vomiting, weight loss, neuropsychiatric symptoms and metastatic inguinal lymphadenopathy is presented. The symptoms resulted from the extrapulmonary metastases found. Imaging studies, histology and immunohistochemistry confirmed the diagnosis of large-cell carcinoma of the lung with neuroendocrine pattern. This type of highly aggressive tumor is usually diagnosed when there are already multiple metastases, which affects the short-term prognosis. The aim of this paper is to inform the medical community of this case due to the scarce reports in the literature.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Neurofibromatosis Type I presenting with Spontaneous Pneumothorax: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Shin, So Youn; Lee, Young Kyung; Moon, Ah Lim; Sung, Dong Wook [Kyunghee University College of Medicine, East-West Neo Medical Center, Seoul (Korea, Republic of)

    2010-08-15

    Neurofibromatosis type I is an autosomal dominant disease with variable clinical manifestations related to dermatologic, neurologic, skeletal, and endocrine system. Lung parenchymal involvement such as lung fibrosis and massive bullous emphysema is infrequent. Here, we report on a 36-year-old man with symptoms of dyspnea, and who has a spontaneous pneumothorax, multiple bullae, and pathologically confirmed neurofibromatosis type I

  15. Dysphagia is present but mild in myotonic dystrophy type 2

    NARCIS (Netherlands)

    S. Knuijt; R. Ensink; J. van Vliet; A. Tieleman; Bert de Swart; Baziel van Engelen

    2009-01-01

    The phenotype of myotonic dystrophy type 2 (DM2) shows similarities as well as differences to that of myotonic dystrophy type 1 (DM1). Dysphagia, a predominant feature in DM1, has not yet been examined in DM2. In a recent nationwide questionnaire survey of gastrointestinal symptoms in DM2, 12 out of

  16. Autoimmune Polyglandular Syndrome Type 2: An Unusual Presentation

    Directory of Open Access Journals (Sweden)

    Hamdollah Karamifar

    2010-05-01

    Full Text Available "nAutoimmune polyglandular syndrome (APS type 2 is characterized by the presence of Addison's disease, in association with autoimmune thyroid disease and/or type 1 diabetes mellitus. APS type 2 occurs most often in middle aged females and is rare in children. Here an 11 year old boy is reported with Addison's disease who developed symptom's of diabetes mellitus, goiter, malabsorption, macrocytic anemia and keratitis. APS type 2 occurs most often in middle aged females and is quite rare in children but one should think to autoimmune poly glandular syndrome type II in patient at any age especially in patients with Addison's disease.

  17. Artificial antigen presenting cells for use in adoptive immunotherapy

    Science.gov (United States)

    Turtle, Cameron J.; Riddell, Stanley R.

    2010-01-01

    The observation that T cells can recognize and specifically eliminate cancer cells has spurred interest in the development of efficient methods to generate large numbers of T cells with specificity for tumor antigens that can be harnessed for use in cancer therapy. Recent studies have demonstrated that during encounter with tumor antigen, the signals delivered to T cells by professional antigen presenting cells can affect T cell programming and their subsequent therapeutic efficacy. This has stimulated efforts to develop artificial antigen presenting cells that allow optimal control over the signals provided to T cells. In this review, we will discuss the advantages and disadvantages of cellular and acellular artificial antigen presenting cell systems and their use in T cell adoptive immunotherapy for cancer. PMID:20693850

  18. Present and future cell therapies for pancreatic beta cell replenishment.

    Science.gov (United States)

    Domínguez-Bendala, Juan; Ricordi, Camillo

    2012-12-21

    If only at a small scale, islet transplantation has successfully addressed what ought to be the primary endpoint of any cell therapy: the functional replenishment of damaged tissue in patients. After years of less-than-optimal approaches to immunosuppression, recent advances consistently yield long-term graft survival rates comparable to those of whole pancreas transplantation. Limited organ availability is the main hurdle that stands in the way of the widespread clinical utilization of this pioneering intervention. Progress in stem cell research over the past decade, coupled with our decades-long experience with islet transplantation, is shaping the future of cell therapies for the treatment of diabetes. Here we review the most promising avenues of research aimed at generating an inexhaustible supply of insulin-producing cells for islet regeneration, including the differentiation of pluripotent and multipotent stem cells of embryonic and adult origin along the beta cell lineage and the direct reprogramming of non-endocrine tissues into insulin-producing cells.

  19. Fetal stem cell transplantation: Past, present, and future.

    Science.gov (United States)

    Ishii, Tetsuya; Eto, Koji

    2014-09-26

    Since 1928, human fetal tissues and stem cells have been used worldwide to treat various conditions. Although the transplantation of the fetal midbrain substantia nigra and dopaminergic neurons in patients suffering from Parkinson's disease is particularly noteworthy, the history of other types of grafts, such as those of the fetal liver, thymus, and pancreas, should be addressed as there are many lessons to be learnt for future stem cell transplantation. This report describes previous practices and complications that led to current clinical trials of isolated fetal stem cells and embryonic stem (ES) cells. Moreover, strategies for transplantation are considered, with a particular focus on donor cells, cell processing, and the therapeutic cell niche, in addition to ethical issues associated with fetal origin. With the advent of autologous induced pluripotent stem cells and ES cells, clinical dependence on fetal transplantation is expected to gradually decline due to lasting ethical controversies, despite landmark achievements.

  20. Identification and quantitation of morphological cell types in electrophoretically separated human embryonic kidney cell cultures

    Science.gov (United States)

    Williams, K. B.; Kunze, M. E.; Todd, P. W.

    1985-01-01

    Four major cell types were identified by phase microscopy in early passage human embryonic kidney cell cultures. They are small and large epithelioid, domed, and fenestrated cells. Fibroblasts are also present in some explants. The percent of each cell type changes with passage number as any given culture grows. As a general rule, the fraction of small epithelioid cells increases, while the fraction of fenestrated cells, always small, decreases further. When fibroblasts are present, they always increase in percentage of the total cell population. Electrophoretic separation of early passage cells showed that the domed cells have the highest electrophoretic mobility, fibroblasts have an intermediate high mobility, small epithelioid cells have a low mobility, broadly distributed, and fenestrated cells have the lowest mobility. All cell types were broadly distributed among electrophoretic subfractions, which were never pure but only enriched with respect to a given cell type.

  1. A Web-Server of Cell Type Discrimination System

    Directory of Open Access Journals (Sweden)

    Anyou Wang

    2014-01-01

    Full Text Available Discriminating cell types is a daily request for stem cell biologists. However, there is not a user-friendly system available to date for public users to discriminate the common cell types, embryonic stem cells (ESCs, induced pluripotent stem cells (iPSCs, and somatic cells (SCs. Here, we develop WCTDS, a web-server of cell type discrimination system, to discriminate the three cell types and their subtypes like fetal versus adult SCs. WCTDS is developed as a top layer application of our recent publication regarding cell type discriminations, which employs DNA-methylation as biomarkers and machine learning models to discriminate cell types. Implemented by Django, Python, R, and Linux shell programming, run under Linux-Apache web server, and communicated through MySQL, WCTDS provides a friendly framework to efficiently receive the user input and to run mathematical models for analyzing data and then to present results to users. This framework is flexible and easy to be expended for other applications. Therefore, WCTDS works as a user-friendly framework to discriminate cell types and subtypes and it can also be expended to detect other cell types like cancer cells.

  2. Activated Brain Endothelial Cells Cross-Present Malaria Antigen.

    Science.gov (United States)

    Howland, Shanshan W; Poh, Chek Meng; Rénia, Laurent

    2015-06-01

    In the murine model of cerebral malaria caused by P. berghei ANKA (PbA), parasite-specific CD8+ T cells directly induce pathology and have long been hypothesized to kill brain endothelial cells that have internalized PbA antigen. We previously reported that brain microvessel fragments from infected mice cross-present PbA epitopes, using reporter cells transduced with epitope-specific T cell receptors. Here, we confirm that endothelial cells are the population responsible for cross-presentation in vivo, not pericytes or microglia. PbA antigen cross-presentation by primary brain endothelial cells in vitro confers susceptibility to killing by CD8+ T cells from infected mice. IFNγ stimulation is required for brain endothelial cross-presentation in vivo and in vitro, which occurs by a proteasome- and TAP-dependent mechanism. Parasite strains that do not induce cerebral malaria were phagocytosed and cross-presented less efficiently than PbA in vitro. The main source of antigen appears to be free merozoites, which were avidly phagocytosed. A human brain endothelial cell line also phagocytosed P. falciparum merozoites. Besides being the first demonstration of cross-presentation by brain endothelial cells, our results suggest that interfering with merozoite phagocytosis or antigen processing may be effective strategies for cerebral malaria intervention.

  3. Activated Brain Endothelial Cells Cross-Present Malaria Antigen.

    Directory of Open Access Journals (Sweden)

    Shanshan W Howland

    2015-06-01

    Full Text Available In the murine model of cerebral malaria caused by P. berghei ANKA (PbA, parasite-specific CD8+ T cells directly induce pathology and have long been hypothesized to kill brain endothelial cells that have internalized PbA antigen. We previously reported that brain microvessel fragments from infected mice cross-present PbA epitopes, using reporter cells transduced with epitope-specific T cell receptors. Here, we confirm that endothelial cells are the population responsible for cross-presentation in vivo, not pericytes or microglia. PbA antigen cross-presentation by primary brain endothelial cells in vitro confers susceptibility to killing by CD8+ T cells from infected mice. IFNγ stimulation is required for brain endothelial cross-presentation in vivo and in vitro, which occurs by a proteasome- and TAP-dependent mechanism. Parasite strains that do not induce cerebral malaria were phagocytosed and cross-presented less efficiently than PbA in vitro. The main source of antigen appears to be free merozoites, which were avidly phagocytosed. A human brain endothelial cell line also phagocytosed P. falciparum merozoites. Besides being the first demonstration of cross-presentation by brain endothelial cells, our results suggest that interfering with merozoite phagocytosis or antigen processing may be effective strategies for cerebral malaria intervention.

  4. Activated Brain Endothelial Cells Cross-Present Malaria Antigen

    Science.gov (United States)

    Howland, Shanshan W.; Poh, Chek Meng; Rénia, Laurent

    2015-01-01

    In the murine model of cerebral malaria caused by P. berghei ANKA (PbA), parasite-specific CD8+ T cells directly induce pathology and have long been hypothesized to kill brain endothelial cells that have internalized PbA antigen. We previously reported that brain microvessel fragments from infected mice cross-present PbA epitopes, using reporter cells transduced with epitope-specific T cell receptors. Here, we confirm that endothelial cells are the population responsible for cross-presentation in vivo, not pericytes or microglia. PbA antigen cross-presentation by primary brain endothelial cells in vitro confers susceptibility to killing by CD8+ T cells from infected mice. IFNγ stimulation is required for brain endothelial cross-presentation in vivo and in vitro, which occurs by a proteasome- and TAP-dependent mechanism. Parasite strains that do not induce cerebral malaria were phagocytosed and cross-presented less efficiently than PbA in vitro. The main source of antigen appears to be free merozoites, which were avidly phagocytosed. A human brain endothelial cell line also phagocytosed P. falciparum merozoites. Besides being the first demonstration of cross-presentation by brain endothelial cells, our results suggest that interfering with merozoite phagocytosis or antigen processing may be effective strategies for cerebral malaria intervention. PMID:26046849

  5. Present and future of allogeneic natural killer cell therapy

    Directory of Open Access Journals (Sweden)

    Okjae eLim

    2015-06-01

    Full Text Available Natural killer (NK cells are innate lymphocytes that are capable of eliminating tumor cells and are therefore used for cancer therapy. Although many early investigators used autologous NK cells, including lymphokine-activated killer cells, the clinical efficacies were not satisfactory. Meanwhile, human leukocyte antigen (HLA-haploidentical hematopoietic stem cell transplantation revealed the anti-tumor effect of allogeneic NK cells, and HLA-haploidentical, killer cell immunoglobulin-like receptor (KIR ligand-mismatched allogeneic NK cells are currently used for many protocols requiring NK cells. Moreover, allogeneic NK cells from non-HLA-related healthy donors have been recently used in cancer therapy. The use of allogeneic NK cells from non-HLA-related healthy donors allows the selection of donor NK cells with higher flexibility and to prepare expanded, cryopreserved NK cells for instant administration without delay for ex vivo expansion. In cancer therapy with allogeneic NK cells, optimal matching of donors and recipients is important to maximize the efficacy of the therapy. In this review, we summarize the present state of allogeneic NK cell therapy and its future directions.

  6. A Particular Type of Present Perfect Tense in Shahnameh

    Directory of Open Access Journals (Sweden)

    Moharram Rezayati Kishekhaleh

    2012-04-01

    Full Text Available Abstract The Shahnameh, the precious and eternal epic poem of Ferdosi, in the ocean of Persian literature is a deep and immense sea. It is full of shining pearls of Iranian culture, that studying of them could be used by researchers of Persian language and literature for various dimensions of literary, historical, social, mythical, religious, and linguistics, etc. This subject allocates for little part of linguistic characteristics i.e. present perfect tense and its kinds. Initially the history of research was considered briefly then the patterns of structure of this verb were studying in the language of ancient Persian, middle Persian and Dari Persian. We eventually, according to samples from the Shahnameh, scattered notions of researchers and their adding up, describe a certain kind of present perfect tense which, its history of structure and application in addition to Soghdi, Khwarizmi and Pahlavi languages, could be recognized at some today Iranian dialects

  7. A Particular Type of Present Perfect Tense in Shahnameh

    Directory of Open Access Journals (Sweden)

    Moharram Rezayati Kishekhaleh

    2012-03-01

    Full Text Available Abstract The Shahnameh, the precious and eternal epic poem of Ferdosi, in the ocean of Persian literature is a deep and immense sea. It is full of shining pearls of Iranian culture, that studying of them could be used by researchers of Persian language and literature for various dimensions of literary, historical, social, mythical, religious, and linguistics, etc. This subject allocates for little part of linguistic characteristics i.e. present perfect tense and its kinds. Initially the history of research was considered briefly then the patterns of structure of this verb were studying in the language of ancient Persian, middle Persian and Dari Persian. We eventually, according to samples from the Shahnameh, scattered notions of researchers and their adding up, describe a certain kind of present perfect tense which, its history of structure and application in addition to Soghdi, Khwarizmi and Pahlavi languages, could be recognized at some today Iranian dialects

  8. Retroperitoneal Gastrointestinal Type Schwannoma Presenting as a Renal Mass

    Directory of Open Access Journals (Sweden)

    Susan J. Hall

    2015-11-01

    Full Text Available Retroperitoneal schwannomas are extremely rare, and unreported in Urology. Often thought to be malignant from imaging the diagnosis is often delayed until Histology. We report a case of retroperitoneal schwanoma thought to be a malignant renal mass. Seventy three year old lady presented with abdominal pain. Imaging showed a mass attached to the renal pelvis thus she underwent a radical nephrectomy. Histology reported retroperitoneal schwannoma. Malignant forms are rare however treatment for these is surgical excision. Awareness of the existence of these tumors may help in avoiding unnecessary radical surgeries by opting for biopsy preoperatively.

  9. Mild cognitive decline: Concept, types, presentation, and management

    Directory of Open Access Journals (Sweden)

    Alka A Subramanyam

    2016-01-01

    Full Text Available As advancements are being made in the medical field, the average life span is increasing and more complaints related to the elderly are coming into notice. Of these, mild cognitive decline (MCD or mild cognitive impairment (MCI is recently becoming an increasingly recognized entity that is often considered a precursor of dementia but is found to have other outcomes as well. It also has variations in presentations; it does not present only as memory complaint but also in the form of other cognitive or behavioral manifestations and has always been a point of controversy regarding the objectivity of the diagnosis. It is considered as the appropriate stage for intervention to prevent its progression to dementia and therefore, requires early identification for which various diagnostic modalities such as neuroimaging, neuropsychological tests, and biological markers are considered. Currently, there are no specific treatment guidelines for MCD. Drugs used in Alzheimer′s disease (AD, lifestyle modifications, and other nonpharmacological approaches have shown some benefit in MCI but the results are variable; hence, the need for further research is warranted for effective preventive therapy. In this article, we will be discussing MCD as a clinical construct, evaluation of a person suspected of having MCD, and management of the same.

  10. Squamous Carcinoma of the Lung Presenting as Migraine-Type Headache: A Case Report

    Directory of Open Access Journals (Sweden)

    Eswaran Waran

    2015-03-01

    Full Text Available Introduction: Orthostatic hypotension has long been recognised as a paraneoplastic effect of lung cancer. Lung cancer presenting with orthostatic hypotension and migraine-type headaches has not been previously described in the literature. Case Report: A 62-year-old Caucasian male presented with headaches, typical of his migraine, after a 30-year migraine-free period. An examination revealed a significant postural drop in BP with reflex tachycardia and no other features of dysautonomia. Investigations showed a metastatic squamous cell lung cancer. Pharmacological treatment of orthostatic hypotension resolved the migraine-type headaches. Discussion: Orthostatic hypotension is associated with lung cancer. Prompt pharmacological treatment in patients not responding to non-pharmacological therapy can provide relief from disabling symptoms of orthostatic hypotension. In this patient, this included symptoms consistent with migraine-type headaches.

  11. B-Cell Cross-Presentation of Autologous Antigen Precipitates Diabetes

    Science.gov (United States)

    Mariño, Eliana; Tan, Bernice; Binge, Lauren; Mackay, Charles R.; Grey, Shane T.

    2012-01-01

    For autoimmune conditions like type 1 diabetes to progress, self-reactive CD8+ T cells would need to interact with peptide–antigen cross-presented on the surface of antigen-presenting cells in a major histocompatibility complex (MHC) class I-restricted fashion. However, the mechanisms by which autoantigen is cross-presented remain to be identified. In this study, we show cross-presentation of islet-derived autoantigens by B cells. B cells engage self-reactive CD8+ T cells in the pancreatic lymph node, driving their proliferative expansion and differentiation into granzyme B+interferon-γ+lysosomal-associated membrane protein 1+ effector cells. B-cell cross-presentation of insulin required proteolytic cleavage and endosomal localization and was sensitive to inhibitors of protein trafficking. Absent B-cell MHC class I, or B-cell receptor restriction to an irrelevant specificity, blunted the expansion of self-reactive CD8+ T cells, suggesting B-cell antigen capture and presentation are critical in vivo events for CD8 activation. Indeed, the singular loss of B-cell MHC class I subverted the conversion to clinical diabetes in NOD mice, despite the presence of a pool of activated, and B cell–dependent, interleukin-21–expressing Vβ4+CD4+ T cells. Thus, B cells govern the transition from clinically silent insulitis to frank diabetes by cross-presenting autoantigen to self-reactive CD8+ T cells. PMID:22829452

  12. Pattern of presentations seen in sickle cell retinopathy patients at ...

    African Journals Online (AJOL)

    Objective: To describe the pattern of presentation of sickle cell retinopathy patients who presented at the Eye Foundation Hospital Lagos, Nigeria between January 2002 and March 2003. Materials and Methods: The medical records of 27 patients who presented at the Eye Foundation Hospital with retinal changes due to ...

  13. Adult Langerhans cell histiocytosis presenting as metachronous colonic polyps

    Directory of Open Access Journals (Sweden)

    Aloísio Felipe-Silva

    2013-03-01

    Full Text Available Langerhans cell histiocytosis (LCH is a rare disease characterized by proliferation of Langerhans-type cells that express CD1a, Langerin (CD207 and S100 protein. Birbeck granules are a hallmark by ultrastructural examination. LCH presents with a wide clinical spectrum, ranging from solitary lesions of a single site (usually bone or skin to multiple or disseminated multisystemic lesions, which can lead to severe organ dysfunction. Most cases occur in children. Gastrointestinal tract involvement is rare and has been associated with systemic illness and poor prognosis especially in children under the age of 2 years. Adult gastrointestinal LCH is very rare. We report a case of a previously healthy, nonsmoking 48-year-old male who was referred for routine screening colonoscopy. Two sessile, smooth, firm and yellowish LCH polyps measuring 0.2 cm and 0.3 cm were detected in the sigmoid colon. Fifteen months later a second colonoscopy found two histologically confirmed hyperplastic polyps at the sigmoid colon. No other LCH lesions were seen. A third colonoscopy after 28 months of follow-up found a submucosal 0.5 cm infiltrated and ulcerated LCH polyp in the cecum, close to the ostium of the appendix. The patient had been asymptomatic for all this period. Imaging investigation for systemic or multiorgan disease did not find any sign of extracolonic involvement. On histology all lesions showed typical LCH features and immunohistochemical analysis showed strong and diffuse staining for CD1a and CD207. This case illustrates two distinct clinicopathologic features not previously reported in this particular clinical setting: metachronous colonic involvement and positivity for CD207.

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

    Science.gov (United States)

    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.

  15. Two case presentations of profound labial edema as a presenting symptom of hypermobility-type Ehlers-Danlos syndrome.

    Science.gov (United States)

    Krapf, Jill M; Goldstein, Andrew T

    2013-09-01

    Hypermobility-type Ehlers-Danlos syndrome (EDS), an often-missed diagnosis with the potential for serious sequelae, may have a variety of uncommon presentations, some of which may be gynecologic. The aim of this case report is to present two cases of profound labial edema associated with intercourse as a presenting symptom of hypermobility-type EDS. A 25-year-old female presented with severe labia minora swelling and bladder pressure associated with intercourse, in addition to persistent genital arousal. History revealed easy bruising, joint pain, and family history of aneurysm. A 22-year-old female presented with intermittent profound labial swelling for 6 years, associated with sensitivity and pain with intercourse. The patient has a history of joint pain and easy bruising, as well a sister with joint hypermobility and unexplained lymphedema. The presenting symptom of profound labial edema led to the diagnosis of hypermobility-type EDS. Patients with hypermobility syndrome exhibit an increased ratio of type III collagen to type I collagen, causing tissue laxity and venous insufficiency. Abnormal collagen may lead to gynecologic manifestations, including unexplained profound labial edema, pelvic organ prolapse in the absence of risk factors, and possibly persistent genital arousal. This case report highlights the need for further research to determine incidence of labial edema in hypermobility-type EDS and to further elucidate a potential correlation between profound labial edema and collagen disorders. © 2013 International Society for Sexual Medicine.

  16. An Adult Case of Bartter Syndrome Type III Presenting with Proteinuria

    Directory of Open Access Journals (Sweden)

    Eun Jung Cha

    2016-03-01

    Full Text Available Bartter syndrome (BS I–IV is a rare autosomal recessive disorder affecting salt reabsorption in the thick ascending limb of the loop of Henle. This report highlights clinicopathological findings and genetic studies of classic BS in a 22-year-old female patient who presented with persistent mild proteinuria for 2 years. A renal biopsy demonstrated a mild to moderate increase in the mesangial cells and matrix of most glomeruli, along with marked juxtaglomerular cell hyperplasia. These findings suggested BS associated with mild IgA nephropathy. Focal tubular atrophy, interstitial fibrosis, and lymphocytic infiltration were also observed. A genetic study of the patient and her parents revealed a mutation of the CLCNKB genes. The patient was diagnosed with BS, type III. This case represents an atypical presentation of classic BS in an adult patient. Pathologic findings of renal biopsy combined with genetic analysis and clinicolaboratory findings are important in making an accurate diagnosis.

  17. Giant Cell Myocarditis: Not Always a Presentation of Cardiogenic Shock

    Directory of Open Access Journals (Sweden)

    Rose Tompkins

    2015-01-01

    Full Text Available Giant cell myocarditis is a rare and often fatal disease. The most obvious presentation often described in the literature is one of rapid hemodynamic deterioration due to cardiogenic shock necessitating urgent consideration of mechanical circulatory support and heart transplantation. We present the case of a 60-year-old man whose initial presentation was consistent with myopericarditis but who went on to develop a rapid decline in left ventricular systolic function without overt hemodynamic compromise or dramatic symptomatology. Giant cell myocarditis was confirmed via endomyocardial biopsy. Combined immunosuppression with corticosteroids and calcineurin inhibitor resulted in resolution of symptoms and sustained recovery of left ventricular function one year later. Our case highlights that giant cell myocarditis does not always present with cardiogenic shock and should be considered in the evaluation of new onset cardiomyopathy of uncertain etiology as a timely diagnosis has distinct clinical implications on management and prognosis.

  18. Cell therapy for type 1 diabetes

    National Research Council Canada - National Science Library

    Muir, K R; Lima, M J; Docherty, H M; Docherty, K

    2014-01-01

    Cell therapy in the form of human islet transplantation has been a successful form of treatment for patients with type 1 diabetes for over 10 years, but is significantly limited by lack of suitable donor material...

  19. T-Cell Lymphomas Presenting as Colon Ulcers and Eosinophilia

    Directory of Open Access Journals (Sweden)

    Ping-Hsiu Wu

    2015-07-01

    Full Text Available Primary gastrointestinal T-cell lymphoma is an uncommon entity and primary colon T-cell lymphoma is even rarer. The majority of enteropathy-associated T-cell lymphomas present predominantly as ulcers or strictures in the endoscopic examinations, while primary B-cell lymphomas commonly present as exophytic lesions. Ulcerative colon T-cell lymphoma may mimic Crohn's disease (CD, which is a chronic inflammatory disease of the intestines with ulcer and fistula formations difficult for clinicians to diagnose based on endoscopic observations alone. Like CD, T-cell lymphoma may be characterized by the presence of multiple skipped ulcers distributed from the terminal ileum to the descending colon. Furthermore, it is difficult to diagnose this unusual lymphoma by a single endoscopic biopsy. Typically, the histological composition of T-cell lymphoma is made of medium to large atypical cells located in the base of the ulcer with extension to the muscle layer and the adjacent mucosa. However, it is common that biopsy specimens show only mixed inflammatory changes where the lymphoma cells are hard to be identified. The differential diagnosis of malignant lymphoma must be considered when clinically diagnosed CD is refractory to the medical treatment or when its clinical behavior becomes aggressive. The current study presents a rare case of primary colon T-cell lymphoma in a 56-year-old male with marked recent weight loss, watery diarrhea and bilateral neck lymphadenopathy, who received a laboratory checkup and endoscopic workup for colon biopsy. The initial pathological report was consistent with mucosal inflammation and benign colon ulcers. Interestingly, the blood test showed a prominent eosinophilia. A biopsy of the enlarged neck lymph nodes done approximately 1 month after the colon biopsy unexpectedly showed T-cell lymphoma, which led to a review of the initial colonic biopsy specimens. Additional immunohistochemical stains were used accordingly, which

  20. Unusual presentation of ocular trauma in sickle cell trait.

    Science.gov (United States)

    Pandey, Nidhi

    2015-09-01

    Sickle cell trait is usually considered as a benign condition. However under certain adverse circumstances, it can give rise to vaso-occlusive features as in sickle cell disease. We present here two cases, both involving healthy young males, who developed retinal vaso-occlusive features following blunt ocular trauma. There was a rapid progression of the retinopathy with the development of proliferative changes in both patients and also vitreous hemorrhage in one patient, within 2 months of the trauma. The development of retinopathy was independent of raised intraocular pressure. Both patients were found to have sickle cell trait.

  1. Angiotropic large cell lymphoma presenting as fever of unknown origin.

    Science.gov (United States)

    Kuvliev, E; Glamour, T; Shekar, R; West, B C

    1999-04-01

    Fever has never before been described as the chief complaint and major finding in angiotropic large cell lymphoma (ALCL). ALCL is a rare and usually fatal intravascular tumor characterized by a widespread proliferation of malignant mononuclear cells within vessels of small caliber, causing their blockage. The majority present as high-grade, B-cell lymphomas with a predilection for the central nervous system and the skin. We report a 61-year-old woman who presented with a fever of unknown origin (FUO) that lasted 9 weeks from onset to death. To our knowledge, this is the first case of ALCL to present solely as a FUO, and the second case of ALCL to be diagnosed by muscle biopsy. We suggest that this rare malignancy (ALCL) be considered in the differential diagnosis of FUO.

  2. Industrial n-type solar cells with >20% cell efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Romijn, I.G.; Anker, J.; Burgers, A.R.; Gutjahr, A.; Koppes, M.; Kossen, E.J.; Lamers, M.W.P.E.; Heurtault, Benoit; Saynova-Oosterling, D.S.; Tool, C.J.J. [ECN Solar Energy, Petten (Netherlands)

    2013-03-15

    To realize high efficiencies at low costs, ECN has developed the n-Pasha solar cell concept. The n-Pasha cell concept is a bifacial solar cell concept on n-Cz base material, with which average efficiencies of above 20% have been demonstrated. In this paper recent developments at ECN to improve the cost of ownership (lower Euro/Wp) of the n-Pasha cell concept are discussed. Two main drivers for the manufacturing costs of n-type solar cells are addressed: the n-type Cz silicon material and the silver consumption. We show that a large resistivity range between 2 and 8 cm can be tolerated for high cell efficiency, and that the costs due to the silver metallization can be significantly reduced while increasing the solar cell efficiency. Combining the improved efficiency and cost reduction makes the n-Pasha cell concept a very cost effective solution to manufacture high efficient solar cells and modules.

  3. OCT4 pseudogenes present in human leukemia cells.

    Science.gov (United States)

    Guo, Xiaoping; Tang, Yongmin

    2012-12-01

    The transcription factor OCT4 is expressed in embryonic stem cells (ESCs) and has been considered as a main regulator in maintaining pluripotency of ESCs. Several studies have showed OCT4 expression in human solid tumor and adult stem or progenitor cells. However, whether OCT4 is expressed in normal hematopoietic system including the peripheral blood and bone marrow remains controversial. Furthermore, the functional expression of OCT4 in leukemia cells and its potential significance in leukemia studies have been poorly defined. The aim of this study was to examine and analyze the genuine expression of OCT4 in human leukemia cells by means of RT-PCR, flow cytometry, PCR product sequencing and alignment with NCBI BLAST and DNAMAN software. The full lengths of the putative OCT4 genes were amplified in 2/9 leukemia cell lines and 7/49 leukemia patients' samples. However, many base mutations in putative OCT4 positive samples were found. Sequence alignment analysis showed a higher similarity between the putative OCT4 PCR products and the pseudogenes in chromosomes 1 and 8. The positive rates of OCT4 protein detected with flow cytometry were low, and almost all of them were less than 10% of positivity. A very small fraction of leukemia stem cells with OCT4 protein expression was found. We conclude that OCT4 pseudogenes in chromosomes 1 and 8 present in the panel of leukemia cells tested and the OCT4 protein is rarely detected with flow cytometry in leukemia cells.

  4. Metastatic Renal Cell Carcinoma to Jejunum: An Unusual Case Presentation

    Directory of Open Access Journals (Sweden)

    Igor Medic

    2017-07-01

    Full Text Available The small intestine is a very uncommon and peculiar site for metastasis from renal cell carcinoma (RCC. We present a clinical presentation of insidious and unusual development of a jejunal metastasis while having stable disease in a remainder of metastatic sites, in a patient undergoing immunotherapy with nivolumab. Due to the extreme rarity of metastatic renal cell carcinoma to the lumen of the small bowel, it is easy to overlook and misdiagnose symptoms of this pathologic entity, particularly when the remainder of metastatic disease responds well to ongoing therapy.

  5. Type 2 diabetes genes – Present status and data from Norwegian studies

    Directory of Open Access Journals (Sweden)

    Jens K. Hertel Hertel

    2013-06-01

    Full Text Available The worldwide rise in prevalence of type 2 diabetes has led to an intense search for the genetic risk factors of this disease. In type 2 diabetes and other complex disorders, multiple genetic and environmental factors, as well as the interaction between these factors, determine the phenotype. In this review, we summarize present knowledge, generated by more than two decades of efforts to dissect the genetic architecture of type 2 diabetes. Initial studies were either based on a candidate gene approach or attempted to fine-map signals generated from linkage analysis. Despite the detection of multiple genomic regions proposed to be linked to type 2 diabetes, subsequent positional fine-mapping of candidates were mostly inconclusive. However, the introduction of genome-wide association studies (GWAS, applied on thousands of patients and controls, completely changed the field. To date, more than 50 susceptibility loci for type 2 diabetes have been detected through the establishment of large research consortia, the application of GWAS on intermediary diabetes phenotypes and the use of study samples of different ethnicities. Still, the common variants identified in the GWAS era only explain some of the heritability seen for type 2 diabetes. Thus, focus is now shifting towards searching also for rare variants using new high-throughput sequencing technologies. For genes involved in the genetic predisposition to type 2 diabetes the emerging picture is that there are hundreds of different gene variants working in a complex interplay influencing pancreatic beta cell function/mass and, only to a lesser extent, insulin action. Several Norwegian studies have contributed to the field, extending our understanding of genetic risk factors in type 2 diabetes and in diabetes-related phenotypes like obesity and cardiovascular disease.

  6. Turning tumour cells into antigen presenting cells: The next step to improve cancer immunotherapy?

    Science.gov (United States)

    de Charette, Marie; Marabelle, Aurélien; Houot, Roch

    2016-11-01

    Downregulation/loss of the antigen presentation is a major immune escape mechanism in cancer. It allows tumour cells to become 'invisible' and avoid immune attack by antitumour T cells. In tumour harbouring properties of professional antigen presenting cells (i.e. tumour B cells in lymphoma), downregulation/loss of the antigen presentation may also prevent direct priming of naïve T cells by tumour cells. Here, we review treatments that may induce/restore antigen presentation by the tumour cells. These treatments may increase the generation of antitumour T cells and/or their capacity to recognise and eliminate tumour cells. By forcing tumour cells to present their antigens, these treatments may sensitise patients to T cell-based immunotherapies, including checkpoint inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Chronic urticaria as a presenting sign of hairy cell leukemia.

    Science.gov (United States)

    Clore, L S; Stafford, C T

    1999-01-01

    Chronic urticaria is a common clinical disorder that is idiopathic in over 75% of cases. Less commonly, urticaria may be the presenting manifestation of an allergic or infectious disease, endocrinopathy, inherited syndrome, or autoimmune disorder. Rarely, urticaria may be a sign of underlying malignancy, including leukemia. C.C. is a 48-year-old white female who was referred for evaluation of recurrent urticaria for 3 years. The pruritic, erythematous wheals were pinpoint, and appeared to be precipitated by heat, stress, and effort. Prick tests were negative except to D. pteronyssinus. CBCs over the past 5 years revealed WBCs of 2,300-5,000 cells/mm3. Skin biopsy revealed interstitial edema with infiltration of eosinophils and mast cells consistent with urticaria. The impression was probable cholinergic urticaria, for which hydroxyzine was prescribed with fair symptomatic control. One year later, she presented with bright red blood per rectum. Repeat physical examination revealed lymphadenopathy and splenomegaly. Subsequent laboratory studies showed pancytopenia. Endoscopy was normal except for small, nonbleeding hemorrhoids. Bone marrow biopsy revealed histologic evidence of hair, cell leukemia that was treated with 2-chlorodeoxyadenosine. Upon initiation of chemotherapy her pruritus and urticaria subsided. Recent CBC revealed Hgb 9.2 g/dL, platelets 290,000 cells/mm3, and WBC 4,100 cells/mm3. Peripheral blood smear showed no hairy cells.

  8. The exonuclease domain of Lassa virus nucleoprotein is involved in antigen-presenting-cell-mediated NK cell responses.

    Science.gov (United States)

    Russier, Marion; Reynard, Stéphanie; Carnec, Xavier; Baize, Sylvain

    2014-12-01

    Lassa virus is an Old World Arenavirus which causes Lassa hemorrhagic fever in humans, mostly in West Africa. Lassa fever is an important public health problem, and a safe and effective vaccine is urgently needed. The infection causes immunosuppression, probably due to the absence of activation of antigen-presenting cells (dendritic cells and macrophages), low type I interferon (IFN) production, and deficient NK cell function. However, a recombinant Lassa virus carrying D389A and G392A substitutions in the nucleoprotein that abolish the exonuclease activity and IFN activation loses its inhibitory activity and induces strong type I IFN production by dendritic cells and macrophages. We show here that during infection by this mutant Lassa virus, antigen-presenting cells trigger efficient human NK cell responses in vitro, including production of IFN-γ and cytotoxicity. NK cell activation involves close contact with both antigen-presenting cells and soluble factors. We report that infected dendritic cells and macrophages express the NKG2D ligands major histocompatibility complex (MHC) class I-related chains A and B and that they may produce interleukin-12 (IL-12), IL-15, and IL-18, all involved in NK cell functions. NK cell degranulation is significantly increased in cocultures, suggesting that NK cells seem to kill infected dendritic cells and macrophages. This work confirms the inhibitory function of Lassa virus nucleoprotein. Importantly, we demonstrate for the first time that Lassa virus nucleoprotein is involved in the inhibition of antigen-presenting cell-mediated NK cell responses. The pathogenesis and immune responses induced by Lassa virus are poorly known. Recently, an exonuclease domain contained in the viral nucleoprotein has been shown to be able to inhibit the type I IFN response by avoiding the recognition of viral RNA by cell sensors. Here, we studied the responses of NK cells to dendritic cells and macrophages infected with a recombinant Lassa virus in

  9. [Atypical presentation of a clinical case of giant cell arteritis].

    Science.gov (United States)

    Rosselló Aubach, L L; Torres Cortada, G; Cabau Rúbies, J; Aragón Sanz, M A; Oncins Torres, R

    2006-06-01

    We present a very unusual clinical case of giant cell arteritis with uterus involvement, in a women of 66 years old, that began clinical features of pain and functional limitation of shoulders and hip 3 mouth before been operated of uterus prolapse with hysterectomy. Biopsy of uterus found affected arterial vesels with wall sclerosis and granulomatous inflamation with giant cells, without necrosis, involving media and perivascular portions suggesting giant cell arteritis. In a previous reports review, we only found ten similar clinical cases. In that cases, clinical features were no suggestif of the disease. Although the well known tendency of arteritis to involve some specific vascular areas, the case we present is an example of the systemic course of the disease and his difficulty to diagnose.

  10. Extramedullary Myeloid Cell Tumour Presenting As Leukaemia Cutis

    Directory of Open Access Journals (Sweden)

    Thappa Devinder Mohan

    2002-01-01

    Full Text Available We herewith report a case of extramedullary myeloid cell tumour presenting as leukaemia cutis for its rarity. It occurred in a 50 year old male patient who presented to us with a 40 days history of painless raised solid skin swellings over the trunk. Histopathological examination of the skin biopsy and bone marrow biopsy showed features suggestive of non-Hodgkin’s lymphoma. Immunophenotyping on skin biopsy specimens and bone marrow biopsy found tumour cells expressing CD43 and Tdt but were negative for CD3 and CD20. These features were consistent with extramedullary myeloid cell tumour involving skin and subcutis (cutaneous manifestation of acute myeloid leukaemia.

  11. Renal epithelioid angiomyolipoma presenting clinically as renal cell ...

    African Journals Online (AJOL)

    We describe a 22-year old female who presented with a 5-year history of a palpable, painless mass in the right flank. Computerized tomography demonstrated a solid renal mass measuring 18 cm × 13 cm with peripheral calcification, areas of vascularity and necrosis. The appearance suggested renal cell carcinoma or ...

  12. Thymic B Cells Are Licensed to Present Self Antigens for Central T Cell Tolerance Induction

    NARCIS (Netherlands)

    Yamano, Tomoyoshi; Nedjic, Jelena; Hinterberger, Maria; Steinert, Madlen; Koser, Sandra; Pinto, Sheena; Gerdes, Norbert; Lutgens, Esther; Ishimaru, Naozumi; Busslinger, Meinrad; Brors, Benedikt; Kyewski, Bruno; Klein, Ludger

    2015-01-01

    Thymic antigen-presenting cells (APCs) such as dendritic cells and medullary thymic epithelial cells (mTECs) use distinct strategies of self-antigen expression and presentation to mediate central tolerance. The thymus also harbors B cells; whether they also display unique tolerogenic features and

  13.  An Uncommon Presentation of Giant Cell Tumor

    Directory of Open Access Journals (Sweden)

    Gopal Malhotra

    2011-09-01

    Full Text Available  Giant Cell Tumors commonly occur at the ends of long bones. However in rare cases, they can occur in the bones of the hands and feet. Tumors in these locations occur in younger patients; in addition, these tumors are more commonly multifocal and are associated with a higher risk for local recurrence than tumors at the ends of long bones. Since lesions in the small bones may be multifocal, a patient with a giant cell tumor of the small bones should undergo a skeletal survey to exclude similar lesions elsewhere. Primary surgical treatment ranges from curettage or excision with or without bone grafting to amputation. The success of surgical treatment depends on the completeness with which the tumor was removed. We are presenting a case report of a 34 year old female, who presented with a swelling in the right hand, following trauma. X-ray of the hand showed an osteolytic expansile lesion at the base of the 1st metacarpal bone. The lesion was initially curetted and then treated by local resection with bone grafting. Histological examination revealed a typical benign giant cell tumor composed of closely packed stromal cells with a variable admixture of giant cells. Follow up at the end of one year did not reveal any recurrence of the tumor.

  14. Dendritic cell maturation and cross-presentation: timing matters!

    Science.gov (United States)

    Alloatti, Andrés; Kotsias, Fiorella; Magalhaes, Joao Gamelas; Amigorena, Sebastian

    2016-07-01

    As a population, dendritic cells (DCs) appear to be the best cross-presenters of internalized antigens on major histocompatibility complex class I molecules in the mouse. To do this, DCs have developed a number of unique and dedicated means to control their endocytic and phagocytic pathways: among them, the capacity to limit acidification of their phagosomes, to prevent proteolytic degradation, to delay fusion of phagosomes to lysosomes, to recruit ER proteins to phagosomes, and to export phagocytosed antigens to the cytosol. The regulation of phagocytic functions, and thereby of antigen processing and presentation by innate signaling, represents a critical level of integration of adaptive and innate immune responses. Understanding how innate signals control antigen cross-presentation is critical to define effective vaccination strategies for CD8(+) T-cell responses. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Cell type discovery and representation in the era of high-content single cell phenotyping.

    Science.gov (United States)

    Bakken, Trygve; Cowell, Lindsay; Aevermann, Brian D; Novotny, Mark; Hodge, Rebecca; Miller, Jeremy A; Lee, Alexandra; Chang, Ivan; McCorrison, Jamison; Pulendran, Bali; Qian, Yu; Schork, Nicholas J; Lasken, Roger S; Lein, Ed S; Scheuermann, Richard H

    2017-12-21

    A fundamental characteristic of multicellular organisms is the specialization of functional cell types through the process of differentiation. These specialized cell types not only characterize the normal functioning of different organs and tissues, they can also be used as cellular biomarkers of a variety of different disease states and therapeutic/vaccine responses. In order to serve as a reference for cell type representation, the Cell Ontology has been developed to provide a standard nomenclature of defined cell types for comparative analysis and biomarker discovery. Historically, these cell types have been defined based on unique cellular shapes and structures, anatomic locations, and marker protein expression. However, we are now experiencing a revolution in cellular characterization resulting from the application of new high-throughput, high-content cytometry and sequencing technologies. The resulting explosion in the number of distinct cell types being identified is challenging the current paradigm for cell type definition in the Cell Ontology. In this paper, we provide examples of state-of-the-art cellular biomarker characterization using high-content cytometry and single cell RNA sequencing, and present strategies for standardized cell type representations based on the data outputs from these cutting-edge technologies, including "context annotations" in the form of standardized experiment metadata about the specimen source analyzed and marker genes that serve as the most useful features in machine learning-based cell type classification models. We also propose a statistical strategy for comparing new experiment data to these standardized cell type representations. The advent of high-throughput/high-content single cell technologies is leading to an explosion in the number of distinct cell types being identified. It will be critical for the bioinformatics community to develop and adopt data standard conventions that will be compatible with these new

  16. An unusual presentation of gastric mucosa-associated lymphoid tissue (MALT-type lymphoma

    Directory of Open Access Journals (Sweden)

    Bikram Shrestha

    2016-09-01

    Full Text Available Mucosa-associated lymphoid tissue (MALT-type lymphoma is a relatively rare disease; nevertheless, it is the third most common lymphoma type, accounting for 5–7% of all non-Hodgkin lymphomas. Case series and retrospective analysis published in the literature have suggested that extra gastrointestinal (GI MALT-type lymphoma can occur simultaneously with MALT-type lymphoma involving the GI tract. We report the case of a healthy, 64-year-old Caucasian male who presented with progressive fatigue, non-productive cough, and worsening exertional shortness of breath for 3 months who was subsequently diagnosed with gastric extra-nodal marginal zone B-cell lymphoma or MALToma with simultaneous metastasis to the lung (bronchi based on biopsy reports. Case presentation: A 64-year-old Caucasian male presented to the emergency room complaining of progressive fatigue for 3 months which had progressed to the point of hindering his usual activities of daily living (ADL. He had recently visited his primary care provider for evaluation of a non-productive cough and exertional shortness of breath. A chest radiography obtained at the time showed bilateral infiltrates. He was then treated for atypical pneumonia but his symptoms unfortunately did not improve. Initial investigations in the emergency room revealed severe anemia and a positive stool guaiac test. Imaging showed bilateral pulmonary infiltrates and an irregular gastric mass. Gastric and transbronchial biopsies were suggestive of extra-nodal marginal zone B-cell lymphoma with simultaneous metastasis to the bronchi. He was treated symptomatically with transfusion of packed red blood cells (PRBC and intravenous iron followed by radiotherapy. Helicobacter pylori infection was ruled out eliminating the possibility of treating him with eradication therapy. Conclusion: Although the stomach is the most common and most extensively studied site of involvement of MALT lymphomas, they can also emerge in many other

  17. 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...... gland of mice. Actively phagocytosing cells with a prominent lysosomal system were found in the pericapillary spaces of the mouse pineal gland following intravenous injection of horseradish peroxidase. The cells also exhibited strong acid phosphatase activity. Perivascular cells were immunopositive...... 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....

  18. Multicentric Giant Cell Tumor of Bone: Synchronous and Metachronous Presentation

    Directory of Open Access Journals (Sweden)

    Reiner Wirbel

    2013-01-01

    Full Text Available A 27-year-old man treated 2.5 years ago for synchronous multicentric giant cell tumor of bone located at the right proximal humerus and the right 5th finger presented now with complaints of pain in his right hip and wrist of two-month duration. Radiology and magnetic resonance revealed multicentric giant cell tumor lesions of the right proximal femur, the left ileum, the right distal radius, and the left distal tibia. The patient has an eighteen-year history of a healed osteosarcoma of the right tibia that was treated with chemotherapy, resection, and allograft reconstruction. A literature review establishes this as the first reported case of a patient with synchronous and metachronous multicentric giant cell tumor who also has a history of osteosarcoma.

  19. Dendritic Cells and Their Role in Allergy: Uptake, Proteolytic Processing and Presentation of Allergens

    Directory of Open Access Journals (Sweden)

    Piotr Humeniuk

    2017-07-01

    Full Text Available Dendritic cells (DCs are the most important antigen presenting cells to activate naïve T cells, which results in the case of Type 1 allergies in a Type 2 helper T cell (Th2-driven specific immune response towards allergens. So far, a number of different subsets of specialized DCs in different organs have been identified. In the recent past methods to study the interaction of DCs with allergenic proteins, their different uptake and processing mechanisms followed by the presentation to T cells were developed. The following review aims to summarize the most important characteristics of DC subsets in the context of allergic diseases, and highlights the recent findings. These detailed studies can contribute to a better understanding of the pathomechanisms of allergic diseases and contribute to the identification of key factors to be addressed for therapeutic interventions.

  20. CENTRAL GIANT CELL GRANULOMA OF THE MANDIBLE: A RARE PRESENTATION

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    Virendra SINGH

    2012-06-01

    Full Text Available Central giant cell granuloma (CGCG is an intra-osseous lesion consisting of cellular fibrosis tissue containing multiple foci of hemorrhage, multinucleated giant cells and trabecules of woven bone. This lesion accounts for less than 7% of all benign jaw tumours. Jaffe considered it as a locally reparative reaction of bone, which can be possibly due to either an inflammatory response, hemorrhage or local trauma. Females are affected more frequently than males. It occurs over a wide age range.It has been reported that this lesion is diagnosed during the first two decades of life in approximately 48% of cases, and 60% of cases are evident before the age of 30. It is considerably more common in the mandible than in the maxilla. Most lesions occur in the molar and premolar area, some of these extending up to the ascending ramus. The presence of giant cell granuloma in the mandibular body area, the entire ramus, condyle and coronoid represents a therapeutic challenge for the oral and maxillofacial surgeons. The aim of this report is to describe an unusual presentation of central giant cell granuloma involving the mandibular body, ramus, condylar and coronoid processes, and to discuss the differentiated diagnosis, the radiographic presentation and the management of this lesion.

  1. Stratification of Antigen-presenting Cells within the Normal Cornea

    Directory of Open Access Journals (Sweden)

    Jared E. Knickelbein

    2009-11-01

    Full Text Available The composition and location of professional antigen presenting cells (APC varies in different mucosal surfaces. The cornea, long considered an immune-privileged tissue devoid of APCs, is now known to host a heterogeneous network of bone marrow-derived cells. Here, we utilized transgenic mice that express enhanced green fluorescent protein (EGFP from the CD11c promoter (pCD11c in conjunction with immunohistochemical staining to demonstrate an interesting stratification of APCs within non-inflamed murine corneas. pCD11c+ dendritic cells (DCs reside in the basal epithelium, seemingly embedded in the basement membrane. Most DCs express MHC class II on at least some dendrites, which extend up to 50 µm in length and traverse up 20 µm tangentially towards the apical surface of the epithelium. The DC density diminishes from peripheral to central cornea. Beneath the DCs and adjacent to the stromal side of the basement membrane reside pCD11c-CD11b+ putative macrophages that express low levels of MHC class II. Finally, MHC class IIpCD11c-CD11b+ cells form a network throughout the remainder of the stroma. This highly reproducible stratification of bone marrow-derived cells is suggestive of a progression from an APC function at the exposed corneal surface to an innate immune barrier function deeper in the stroma.

  2. Impairments of Antigen-Presenting Cells in Pulmonary Tuberculosis

    Directory of Open Access Journals (Sweden)

    Ludmila V. Sakhno

    2015-01-01

    Full Text Available The phenotype and functional properties of antigen-presenting cells (APC, that is, circulating monocytes and generated in vitro macrophages and dendritic cells, were investigated in the patients with pulmonary tuberculosis (TB differing in lymphocyte reactivity to M. tuberculosis antigens (PPD-reactive versus PPD-anergic patients. We revealed the distinct impairments in patient APC functions. For example, the monocyte dysfunctions were displayed by low CD86 and HLA-DR expression, 2-fold increase in CD14+CD16+ expression, the high numbers of IL-10-producing cells, and enhanced IL-10 and IL-6 production upon LPS-stimulation. The macrophages which were in vitro generated from peripheral blood monocytes under GM-CSF were characterized by Th1/Th2-balance shifting (downproduction of IFN-γ coupled with upproduction of IL-10 and by reducing of allostimulatory activity in mixed lymphocyte culture. The dendritic cells (generated in vitro from peripheral blood monocytes upon GM-CSF + IFN-α were characterized by impaired maturation/activation, a lower level of IFN-γ production in conjunction with an enhanced capacity to produce IL-10 and IL-6, and a profound reduction of allostimulatory activity. The APC dysfunctions were found to be most prominent in PPD-anergic patients. The possible role of APC impairments in reducing the antigen-specific T-cell response to M. tuberculosis was discussed.

  3. A web-server of cell type discrimination system

    National Research Council Canada - National Science Library

    Wang, Anyou; Zhong, Yan; Wang, Yanhua; He, Qianchuan

    2014-01-01

    ...), induced pluripotent stem cells (iPSCs), and somatic cells (SCs). Here, we develop WCTDS, a web-server of cell type discrimination system, to discriminate the three cell types and their subtypes like fetal versus adult SCs...

  4. A Web-Server of Cell Type Discrimination System

    National Research Council Canada - National Science Library

    Wang, Anyou; Zhong, Yan; Wang, Yanhua; He, Qianchuan

    2014-01-01

    ...), induced pluripotent stem cells (iPSCs), and somatic cells (SCs). Here, we develop WCTDS, a web-server of cell type discrimination system, to discriminate the three cell types and their subtypes like fetal versus adult SCs...

  5. Choroidal dendritic cells require activation to present antigen and resident choroidal macrophages potentiate this response.

    Science.gov (United States)

    Forrester, J V; Lumsden, L; Duncan, L; Dick, A D

    2005-03-01

    The uveal compartment of the eye contains extensive networks of resident macrophages and dendritic cells. These cells are now recognised to have a role in many ocular pathologies. The aim of this study was to isolate, characterise, and compare the function of ciliary body/choroid dendritic cells and macrophages from the normal eye. Explants of rat and human ciliary body/choroid were cultured in vitro for various periods of time and cells harvested either from the supernatant fluid or from enzyme digested and washed explants. The cells were then phenotyped by microscopy and flow cytometry, examined by video time lapse photomicroscopy, and analysed functionally in a series of immunoassays. Two main types of dendritic cell were identified: large veil-like MHC class II(mid) motile but relatively non-translocatory cells and small MHC class II(hi) motile and rapidly translocating cells. Tissue macrophages mainly remained associated with the explants in culture but gradually lost their resident tissue marker (ED2) and detached from the explants as clusters of low density, large, CR3 (ED7)(+) cells, some of which underwent apoptosis. Video time lapse studies showed dendritic cells constantly interacting with large single cells and cell clusters by traversing the interstices of the cell clusters. In functional studies, freshly isolated dendritic cells were poor presenters of antigen and required activation by short term culture for acquisition of antigen presenting function. In contrast, dendritic cell depleted choroidal cell preparations containing macrophages and other cells failed to present antigen even after short term culture but augmented the antigen presenting function of dendritic cells when tested in co-culture. At least two types of dendritic cells are present in the normal ciliary body/choroid layer of the eye. It is likely that these cells have different functions based on their motility and potential to migrate to secondary lymphoid tissue either during normal

  6. Regulation of hematopoietic stem cell behavior by the nanostructured presentation of extracellular matrix components.

    Directory of Open Access Journals (Sweden)

    Christine Anna Muth

    Full Text Available Hematopoietic stem cells (HSCs are maintained in stem cell niches, which regulate stem cell fate. Extracellular matrix (ECM molecules, which are an essential part of these niches, can actively modulate cell functions. However, only little is known on the impact of ECM ligands on HSCs in a biomimetic environment defined on the nanometer-scale level. Here, we show that human hematopoietic stem and progenitor cell (HSPC adhesion depends on the type of ligand, i.e., the type of ECM molecule, and the lateral, nanometer-scaled distance between the ligands (while the ligand type influenced the dependency on the latter. For small fibronectin (FN-derived peptide ligands such as RGD and LDV the critical adhesive interligand distance for HSPCs was below 45 nm. FN-derived (FN type III 7-10 and osteopontin-derived protein domains also supported cell adhesion at greater distances. We found that the expression of the ECM protein thrombospondin-2 (THBS2 in HSPCs depends on the presence of the ligand type and its nanostructured presentation. Functionally, THBS2 proved to mediate adhesion of HSPCs. In conclusion, the present study shows that HSPCs are sensitive to the nanostructure of their microenvironment and that they are able to actively modulate their environment by secreting ECM factors.

  7. Blastic plasmacytoid dendritic cell neoplasm with absolute monocytosis at presentation

    Directory of Open Access Journals (Sweden)

    Jaworski JM

    2015-02-01

    Full Text Available Joseph M Jaworski,1,2 Vanlila K Swami,1 Rebecca C Heintzelman,1 Carrie A Cusack,3 Christina L Chung,3 Jeremy Peck,3 Matthew Fanelli,3 Micheal Styler,4 Sanaa Rizk,4 J Steve Hou1 1Department of Pathology and Laboratory Medicine, Hahnemann University Hospital/Drexel University College of Medicine, Philadelphia, PA, USA; 2Department of Pathology, Mercy Fitzgerald Hospital, Darby, PA, USA; 3Department of Dermatology, Hahnemann University Hospital/Drexel University College of Medicine, Philadelphia, PA, USA; 4Department of Hematology/Oncology, Hahnemann University Hospital/Drexel University College of Medicine, Philadelphia, PA, USA Abstract: Blastic plasmacytoid dendritic cell neoplasm is an uncommon malignancy derived from precursors of plasmacytoid dendritic cells. Nearly all patients present initially with cutaneous manifestations, with many having extracutaneous disease additionally. While response to chemotherapy initially is effective, relapse occurs in most, with a leukemic phase ultimately developing. The prognosis is dismal. While most of the clinical and pathologic features are well described, the association and possible prognostic significance between peripheral blood absolute monocytosis (>1.0 K/µL and blastic plasmacytoid dendritic cell neoplasm have not been reported. We report a case of a 68-year-old man who presented with a rash for 4–5 months. On physical examination, there were multiple, dull-pink, indurated plaques on the trunk and extremities. Complete blood count revealed thrombocytopenia, absolute monocytosis of 1.7 K/µL, and a negative flow cytometry study. Biopsy of an abdominal lesion revealed typical features of blastic plasmacytoid dendritic cell neoplasm. Patients having both hematologic and nonhematologic malignancies have an increased incidence of absolute monocytosis. Recent studies examining Hodgkin and non-Hodgkin lymphoma patients have suggested that this is a negative prognostic factor. The association between

  8. TAP-deficient human iPS cell-derived myeloid cell lines as unlimited cell source for dendritic cell-like antigen-presenting cells.

    Science.gov (United States)

    Haruta, M; Tomita, Y; Yuno, A; Matsumura, K; Ikeda, T; Takamatsu, K; Haga, E; Koba, C; Nishimura, Y; Senju, S

    2013-05-01

    We previously reported a method to generate dendritic cell (DC)-like antigen-presenting cells (APC) from human induced pluripotent stem (iPS) cells. However, the method is relatively complicated and laborious. In the current study, we attempted to establish a method through which we could obtain a large number of functional APC with a simple procedure. We transduced iPS cell-derived CD11b(+) myeloid cells with genes associated with proliferative or anti-senescence effects, enabling the cells to propagate for more than 4 months in a macrophage colony-stimulating factor (M-CSF)-dependent manner while retaining their capacity to differentiate into functional APC. We named these iPS cell-derived proliferating myeloid cells 'iPS-ML', and the iPS-ML-derived APC 'ML-DC'. In addition, we generated TAP2-deficient iPS cell clones by zinc finger nuclease-aided targeted gene disruption. TAP2-deficient iPS cells and iPS-ML avoided recognition by pre-activated allo-reactive CD8(+) T cells. TAP2-deficient ML-DC expressing exogenously introduced HLA-A2 genes stimulated HLA-A2-restricted MART-1-specific CD8(+) T cells obtained from HLA-A2-positive allogeneic donors, resulting in generation of MART-1-specific cytotoxic T lymphocyte (CTL) lines. TAP-deficient iPS-ML introduced with various HLA class I genes may serve as an unlimited source of APC for vaccination therapy. If administered into allogeneic patients, ML-DC with appropriate genetic modifications may survive long enough to stimulate antigen-specific CTL and, after that, be completely eliminated. Based on the present study, we propose an APC-producing system that is simple, safe and applicable to all patients irrespective of their HLA types.

  9. An atypical presentation and diagnostic dilemma of sickle cell disease

    Directory of Open Access Journals (Sweden)

    Mohammad Mizanur Rahman

    2017-06-01

    Full Text Available A 5½ year old male child of a consanguineous couple presented with moderately high fever, hepatosplenomegaly and severe pain in the left upper quadrant of the abdomen for four days. On examination, the child was found severely anemic, ill-looking and mildly icteric but the abdomen was soft and non-tender. Radiological investigations and ultrasonography of the whole abdomen revealed the diagnosis of space occupying lesions which may be either due to splenic abscess/cyst or leukemia/lymphoma. However, blood film revealed the features of hereditary hemolytic anemia and later on hemoglobin electrophoresis initially commented as HbS–beta thalassemia but subsequent family screening of the patient turned out to a case of homozygous sickle cell anemia or sickle cell disease. To resolve such diagnostic dilemma, it is very much essential to analyze critically the history including family history, clinical and physical findings as well as investigational findings.

  10. 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

  11. Enteroantigen-presenting B cells efficiently stimulate CD4(+) T cells in vitro

    DEFF Research Database (Denmark)

    Schmidt, Esben Gjerløff Wedebye; Kristensen, Nanna Ny; Claesson, Mogens Helweg

    2011-01-01

    Presentation of enterobacterial antigens by antigen-presenting cells and activation of enteroantigen-specific CD4(+) T cells are considered crucial steps in inflammatory bowel disease (IBD) pathology. The detrimental effects of such CD4(+) T cells have been thoroughly demonstrated in models...... of colitis. Also, we have previously established an in vitro assay where murine enteroantigen-specific colitogenic CD4(+) CD25(-) T cells are activated by splenocytes pulsed with an enterobacterial extract....

  12. Esophageal Squamous Cell Carcinoma Presenting with Streptococcus intermedius Cerebral Abscess

    Directory of Open Access Journals (Sweden)

    Rabih Nayfe

    2017-01-01

    Full Text Available Background. Cerebral abscess is caused by inoculation of an organism into the brain parenchyma from a site distant from the central nervous system. Streptococcus intermedius (S. intermedius is a commensal organism that is normally present in the aerodigestive tract and was reported to be the cause of brain abscesses after esophageal dilatation or upper endoscopy. Case Presentation. We report the case of a 53-year-old female who presented with hematemesis and melena followed by left-sided weakness. Initially, her hemiplegia was found to be secondary to a right thalamic brain abscess caused by S. intermedius. Investigations led to the diagnosis of a mid-esophageal squamous cell carcinoma. We hypothesize that the cause of the abscess with this bacterium that naturally resides in the digestive tract and oral cavity is secondary to hematogenous spread from breach in the mucosal integrity from ulceration due to the cancer. Conclusion. To our knowledge, our case is the first in the literature to describe a brain abscess caused by S. intermedius in association with a previously undiagnosed esophageal squamous cell carcinoma without any prior esophageal intervention.

  13. T Cells Compete for Access to Antigen-Bearing Antigen-Presenting Cells

    Science.gov (United States)

    Kedl, Ross M.; Rees, William A.; Hildeman, David A.; Schaefer, Brian; Mitchell, Tom; Kappler, John; Marrack, Philippa

    2000-01-01

    These studies tested whether antigenic competition between T cells occurs. We generated CD8+ T cell responses in H-2b mice against the dominant ovalbumin epitope SIINFEKL (ova8) and subdominant epitope KRVVFDKL, using either vaccinia virus expressing ovalbumin (VV-ova) or peptide-pulsed dendritic cells. CD8+ T cell responses were visualized by major histocompatibility complex class I–peptide tetrameric molecules. Transfer of transgenic T cells with high affinity for ova8 (OT1 T cells) completely inhibited the response of host antigen-specific T cells to either antigen, demonstrating that T cells can directly compete with each other for response to antigen. OT1 cells also inhibited CD8+ T cell responses to an unrelated peptide, SIYRYGGL, providing it was presented on the same dendritic cells as ova8. These inhibitions were not due to a more rapid clearance of virus or antigen-presenting cells (APCs) by the OT1 cells. Rather, the inhibition was caused by competition for antigen and antigen-bearing cells, since it could be overcome by the injection of large numbers of antigen-pulsed dendritic cells. These results imply that common properties of T cell responses, such as epitope dominance and secondary response affinity maturation, are the result of competitive interactions between antigen-bearing APC and T cell subsets. PMID:11034600

  14. Langerhans cell histiocytosis: An uncommon presentation, successfully treated by thalidomide

    Directory of Open Access Journals (Sweden)

    Mohammad Shahidi-Dadras

    2011-01-01

    Full Text Available Langerhans cell histiocytosis (LCH is a rare disease and generally affects children under 15 years of age. Adult onset form and cutaneous features at presentation are uncommon. There are some options for treatment of the skin lesions of LCH such as topical and intralesional corticosteroid, nitrogen mustard, etc., which are not completely curative. Herein, we report a case of perianal LCH in a 20-year-old man with one-year history of recalcitrant well-demarcated, erythematous, and ulcerated plaque surrounding the anal orifice, with pain and difficulty in defecation that was successfully treated with thalidomide.

  15. Optical cell stimulation for neuronal excitation (Conference Presentation)

    Science.gov (United States)

    Johannsmeier, Sonja; Heeger, Patrick; Terakawa, Mitsuhiro; Heisterkamp, Alexander; Ripken, Tammo; Heinemann, Dag

    2017-02-01

    Optical manipulation of cellular functions represents a growing field in biomedical sciences. The possibility to modulate specific targets with high spatial and temporal precision in a contactless manner allows a broad range of applications. Here, we present a study on stimulation of neuronal cells by optical means. As a long-term objective, we seek to improve the performance of current electric neurostimulation, especially in the context of cochlear implants. Firstly, we tested a gold nanoparticle mediated approach to modulate transmembrane conductivity by irradiation using a picosecond pulsed Nd:YAG laser at 532 nm for 40 ms in a neuroblastoma cell line (N2A) and primary murine neurons. The light absorption leads to a rapid temperature increase of the gold nanoparticles, which can induce an increased permeabilisation of the cellular membrane. Calcium transients were recorded as an indicator of neuronal activity. Although calcium signals were reliably detected upon laser irradiation, the temporal behavior did not resemble action potentials. The origin of these signals was investigated by an inhibitor study. These results indicate calcium induced calcium release (CICR) as the major source of the calcium transients. Consecutively, we tested alternative approaches for cell stimulation, such as glutamate release and optogenetics, and evaluated the potential of these methods for the application in a cochlear implant. Compared to the gold nanoparticle approach, both techniques induce less cellular stress and reliably produce action potentials.

  16. Phase imaging of mechanical properties of live cells (Conference Presentation)

    Science.gov (United States)

    Wax, Adam

    2017-02-01

    The mechanisms by which cells respond to mechanical stimuli are essential for cell function yet not well understood. Many rheological tools have been developed to characterize cellular viscoelastic properties but these typically require direct mechanical contact, limiting their throughput. We have developed a new approach for characterizing the organization of subcellular structures using a label free, noncontact, single-shot phase imaging method that correlates to measured cellular mechanical stiffness. The new analysis approach measures refractive index variance and relates it to disorder strength. These measurements are compared to cellular stiffness, measured using the same imaging tool to visualize nanoscale responses to flow shear stimulus. The utility of the technique is shown by comparing shear stiffness and phase disorder strength across five cellular populations with varying mechanical properties. An inverse relationship between disorder strength and shear stiffness is shown, suggesting that cell mechanical properties can be assessed in a format amenable to high throughput studies using this novel, non-contact technique. Further studies will be presented which include examination of mechanical stiffness in early carcinogenic events and investigation of the role of specific cellular structural proteins in mechanotransduction.

  17. Dependence of herpes simplex virus type 1-induced cell fusion on cell type

    Energy Technology Data Exchange (ETDEWEB)

    Bzik, D.J.; Person, S.

    1981-04-15

    Syncytial mutants of herpes simplex virus type 1 (HSV-1), such as syn20, cause extensive fusion of human embryonic lung (HEL) cells but only a small amount of fusion of human epidermoid carcinoma No. 2 (HEp-2) cells. In order to determine the cellular basis of this difference in fusion, sparse cultures of syn20-infected HEL or HEp-2 cells, previously labeled with (/sup 3/H)thymidine, were surrounded with uninfected, unlabeled HEL or HEp-2 cells. The fusion of radioactive with nonradioactive cells was determined at different times after infection using radioautography. The major difference in the fusion capacity of HEL and HEp-2 cells was not due to a difference in cell-surface receptors for a fusion factor in the two cell types. The process of infection of HEp-2 cells did not cause the plasma membranes of the cells to become refractory to fusion, because syn20-infected HEL cells fused equally well with either uninfected or infected HEp-2 cells. In a mixed infection with equal numbers of MP and its nonsyncytial parent, mP, extensive fusion was observed for infected HEL cells and significantly less fusion was observed for infected African green monkey (CV-1), baby hamster kidney (BHK-21), and HEp-2 cells.

  18. Antigen-presenting cells in human cutaneous leishmaniasis due to Leishmania major

    DEFF Research Database (Denmark)

    ElHassan, A M; Gaafar, A; Theander, T G

    1995-01-01

    In this study biopsies from skin lesions and draining lymph nodes of patients suffering from cutaneous leishmaniasis caused by Leishmania major were examined by immunohistochemistry, and by light and electron microscopy to identify the types of antigen-presenting cells (APC) and their location. APC...

  19. Connecting the dots: artificial antigen presenting cell-mediated modulation of natural killer T cells.

    Science.gov (United States)

    Sun, Wenji; Subrahmanyam, Priyanka B; East, James E; Webb, Tonya J

    2012-11-01

    Natural killer T (NKT) cells constitute an important subset of T cells that can both directly and indirectly mediate antitumor immunity. However, we and others have reported that cancer patients have a reduction in both NKT cell number and function. NKT cells can be stimulated and expanded with α-GalCer and cytokines and these expanded NKT cells retain their phenotype, remain responsive to antigenic stimulation, and display cytotoxic function against tumor cell lines. These data strongly favor the use of ex vivo expanded NKT cells in adoptive immunotherapy. NKT cell based-immunotherapy has been limited by the use of autologous antigen-presenting cells, which can vary substantially in their quantity and quality. A standardized system that relies on artificial antigen-presenting cells (aAPCs) could produce the stimulating effects of dendritic cell (DC) without the pitfalls of allo- or xenogeneic cells. In this review, we discuss the progress that has been made using CD1d-based aAPC and how this acellular antigen presenting system can be used in the future to enhance our understanding of NKT cell biology and to develop NKT cell-specific adoptive immunotherapeutic strategies.

  20. Dental pulp stem cell-derived chondrogenic cells demonstrate differential cell motility in type I and type II collagen hydrogels.

    Science.gov (United States)

    Yao, Li; Flynn, Nikol

    2018-02-13

    Advances in the development of biomaterials and stem cell therapy provide a promising approach to regenerating degenerated discs. The normal nucleus pulposus (NP) cells exhibit the similar phenotype as chondrocytes. Because dental pulp stem cells (DPSCs) can be differentiated into chondrogenic cells, the DPSCs and DPSCs-derived chondrogenic cells encapsulated in type I and type II collagen hydrogels can potentially be transplanted into degenerated nucleus pulposus (NP) to repair damaged tissue. The motility of transplanted cells is critical because the cells need to migrate away from the hydrogels containing the cells of high density and disperse into the NP tissue after implantation. The purpose of this study was to determine the motility of DPSC and DPSC-derived chondrogenic cells in type I and type II collagen hydrogels. The time lapse imaging that recorded cell migration was analyzed to quantify the cell migration velocity and distance. The cell viability of DPSCs in native or 4S-StarPEG - crosslinked type I and type II collagen hydrogels was determined using LIVE/DEAD ® cell viability assay and AlamarBlue® assay. DPSCs were differentiated into chondrogenic cells. The migration of DPSCs and DPSC-derived chondrogenic cells in these hydrogels was recorded using a time lapse imaging system. This study was funded by Regional Institute on Aging and Wichita Medical Research and Education Foundation and the authors declare no competing interest. DPSCs showed high cell viability in non-crosslinked and crosslinked collagen hydrogels. DPSCs migrated in collagen hydrogels, and the cell migration speed was not significantly different in either type I collagen or type II collagen hydrogels. The migration speed of DPSC-derived chondrogenic cells was higher in type I collagen hydrogel than in type II collagen hydrogel. Crosslinking of type I collagen with 4S-StarPEG significantly reduced the cell migration speed of DPSC-derived chondrogenic cells. After implantation of

  1. Cell type-specific bipolar cell input to ganglion cells in the mouse retina.

    Science.gov (United States)

    Neumann, S; Hüser, L; Ondreka, K; Auler, N; Haverkamp, S

    2016-03-01

    Many distinct ganglion cell types, which are the output elements of the retina, were found to encode for specific features of a visual scene such as contrast, color information or movement. The detailed composition of retinal circuits leading to this tuning of retinal ganglion cells, however, is apart from some prominent examples, largely unknown. Here we aimed to investigate if ganglion cell types in the mouse retina receive selective input from specific bipolar cell types or if they sample their synaptic input non-selectively from all bipolar cell types stratifying within their dendritic tree. To address this question we took an anatomical approach and immunolabeled retinae of two transgenic mouse lines (GFP-O and JAM-B) with markers for ribbon synapses and type 2 bipolar cells. We morphologically identified all green fluorescent protein (GFP)-expressing ganglion cell types, which co-stratified with type 2 bipolar cells and assessed the total number of bipolar input synapses and the proportion of synapses deriving from type 2 bipolar cells. Only JAM-B ganglion cells received synaptic input preferentially from bipolar cell types other than type 2 bipolar cells whereas the other analyzed ganglion cell types sampled their bipolar input most likely from all bipolar cell terminals within their dendritic arbor. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Primary Colonic Signet Ring Cell Carcinoma Presenting Carcinocythemia: An Autopsy Case

    Directory of Open Access Journals (Sweden)

    Ryosuke Misawa

    2008-09-01

    Full Text Available Primary colorectal signet ring cell carcinoma (SRCC is a rare but distinctive type of mucin-producing adenocarcinoma of the large intestine with still controversial clinicopathological features and prognosis. We encountered primary colonic SRCC in a 51-year-old Japanese man with extensive bone metastasis ultimately leading to carcinocythemia before the initiation of chemotherapy and surgical intervention. Three days before death, besides progressive disseminated intravascular coagulation that had been present on admission, hematological examination showed sudden leukocytosis with nonhematopoietic cells that subsequently turned out to be signet ring cells (SRCs. Carcinocythemia, the presence of circulating cancer cells in peripheral blood, is considered to be a rare but an ominous phenomenon occurring in the advanced stage of certain types of cancers, particularly mammary lobular carcinoma. It can be assumed that carcinoma cells lacking intercellular cohesiveness and polarized cell membrane organization, including SRCs as well as lobular carcinoma cells, can readily get access to the peripheral circulation; however, to our knowledge, this is the first report of primary colorectal SRCC that presented carcinocythemia. Extensive bone metastatic sites, in the present case, may have functioned as a reservoir of circulating SRCs.

  3. Type I collagen gel protects murine fibrosarcoma L929 cells from TNFα-induced cell death

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hong-Ju; He, Wen-Qi; Chen, Ling; Liu, Wei-Wei; Xu, Qian; Xia, Ming-Yu; Hayashi, Toshihiko [China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016 (China); Fujisaki, Hitomi; Hattori, Shunji [Nippi Research Institute of Biomatrix, Toride, Ibaraki 302-0017 (Japan); Tashiro, Shin-ichi [Institute for Clinical and Biomedical Sciences, Kyoto 603-8072 (Japan); Onodera, Satoshi [Department of Clinical and Pharmaceutical Sciences, Showa Pharmaceutical University, Tokyo 194-8543 (Japan); Ikejima, Takashi, E-mail: ikejimat@vip.sina.com [China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016 (China)

    2015-02-20

    Murine fibrosarcoma L929 cells have been used to test efficacy of proinflammatory cytokine TNFα. In the present study, we reported on protective effect of type I collagen gel used as L929 cell culture. L929 cell grew and proliferated well on collagen gel. However, the L929 cells exhibited cobblestone-like morphology which was much different from the spread fusiform shape when cultured on conventional cell dishes as well as the cells tended to aggregate. On conventional cell culture dishes, the cells treated with TNFα became round in shape and eventually died in a necroptotic manner. The cells cultured on collagen gel, however, were completely unaffected. TNFα treatment was reported to induce autophagy in L929 cells on the plastic dish, and therefore we investigated the effect of collagen gel on induction of autophagy. The results indicated that autophagy induced by TNFα treatment was much reduced when the cells were cultured on collagen gel. In conclusion, type I collagen gel protected L929 cell from TNFα-induced cell death. - Highlights: • Collagen gel culture changed the morphology of L929 cells. • L929 cell cultured on collagen gel were resistant to TNFα-induced cell death. • Collagen gel culture inhibited TNFα-induced autophagy in L929 cells.

  4. Stem Cell: Past, Present and Future- A Review Article | Avasthi ...

    African Journals Online (AJOL)

    having the potency to differentiate into wide range of adult cells. Self renewal and totipotency are characteristic of stem cells. Though totipotency is shown by very early embryonic stem cells, the adult stem cells possess multipotency and differential plasticity which can be exploited for future generation of therapeutic options.

  5. Morphological types of epithelial-mesenchymal cell contacts in odontogenesis.

    Science.gov (United States)

    Burgess, A M; Katchburian, E

    1982-01-01

    During early stages of odontogenesis, differentiating ameloblasts form cytoplasmic processes which penetrate deeply into developing uncalcified dentine. Some of these cytoplasmic protrusions form close approximations or contacts with odontoblast processes. The contacts are of a variety of morphological types, but their membranes never fuse or form any known type of cell junction. The present results, together with those derived from other studies, suggest that the approximations or contacts may play a role in inductive mechanisms of the cytodifferentiation of odontogenic cells. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7153175

  6. Artificial antigen presenting cell (aAPC) mediated activation and expansion of natural killer T cells.

    Science.gov (United States)

    East, James E; Sun, Wenji; Webb, Tonya J

    2012-12-29

    Natural killer T (NKT) cells are a unique subset of T cells that display markers characteristic of both natural killer (NK) cells and T cells(1). Unlike classical T cells, NKT cells recognize lipid antigen in the context of CD1 molecules(2). NKT cells express an invariant TCRα chain rearrangement: Vα14Jα18 in mice and Vα24Jα18 in humans, which is associated with Vβ chains of limited diversity(3-6), and are referred to as canonical or invariant NKT (iNKT) cells. Similar to conventional T cells, NKT cells develop from CD4-CD8- thymic precursor T cells following the appropriate signaling by CD1d (7). The potential to utilize NKT cells for therapeutic purposes has significantly increased with the ability to stimulate and expand human NKT cells with α-Galactosylceramide (α-GalCer) and a variety of cytokines(8). Importantly, these cells retained their original phenotype, secreted cytokines, and displayed cytotoxic function against tumor cell lines. Thus, ex vivo expanded NKT cells remain functional and can be used for adoptive immunotherapy. However, NKT cell based-immunotherapy has been limited by the use of autologous antigen presenting cells and the quantity and quality of these stimulator cells can vary substantially. Monocyte-derived DC from cancer patients have been reported to express reduced levels of costimulatory molecules and produce less inflammatory cytokines(9,10). In fact, murine DC rather than autologous APC have been used to test the function of NKT cells from CML patients(11). However, this system can only be used for in vitro testing since NKT cells cannot be expanded by murine DC and then used for adoptive immunotherapy. Thus, a standardized system that relies on artificial Antigen Presenting Cells (aAPC) could produce the stimulating effects of DC without the pitfalls of allo- or xenogeneic cells(12, 13). Herein, we describe a method for generating CD1d-based aAPC. Since the engagement of the T cell receptor (TCR) by CD1d-antigen complexes is

  7. Differential regulation of C-type lectin expression on tolerogenic dendritic cell subsets

    NARCIS (Netherlands)

    van Vliet, Sandra J.; van Liempt, Ellis; Geijtenbeek, Teunis B. H.; van Kooyk, Yvette

    2006-01-01

    Antigen presenting cells (APC) express high levels of C-type lectins, which play a major role in cellular interactions as well as pathogen recognition and antigen presentation. The C-type lectin macrophage galactose-type lectin (MGL), expressed by dendritic cells (DC) and macrophages, mediates

  8. Differential use of autophagy by primary dendritic cells specialized in cross-presentation

    Science.gov (United States)

    Mintern, Justine D; Macri, Christophe; Chin, Wei Jin; Panozza, Scott E; Segura, Elodie; Patterson, Natalie L; Zeller, Peter; Bourges, Dorothee; Bedoui, Sammy; McMillan, Paul J; Idris, Adi; Nowell, Cameron J; Brown, Andrew; Radford, Kristen J; Johnston, Angus PR; Villadangos, Jose A

    2015-01-01

    Antigen-presenting cells survey their environment and present captured antigens bound to major histocompatibility complex (MHC) molecules. Formation of MHC-antigen complexes occurs in specialized compartments where multiple protein trafficking routes, still incompletely understood, converge. Autophagy is a route that enables the presentation of cytosolic antigen by MHC class II molecules. Some reports also implicate autophagy in the presentation of extracellular, endocytosed antigen by MHC class I molecules, a pathway termed “cross-presentation.” The role of autophagy in cross-presentation is controversial. This may be due to studies using different types of antigen presenting cells for which the use of autophagy is not well defined. Here we report that active use of autophagy is evident only in DC subtypes specialized in cross-presentation. However, the contribution of autophagy to cross-presentation varied depending on the form of antigen: it was negligible in the case of cell-associated antigen or antigen delivered via receptor-mediated endocytosis, but more prominent when the antigen was a soluble protein. These findings highlight the differential use of autophagy and its machinery by primary cells equipped with specific immune function, and prompt careful reassessment of the participation of this endocytic pathway in antigen cross-presentation. PMID:25950899

  9. Human cell-based artificial antigen-presenting cells for cancer immunotherapy.

    Science.gov (United States)

    Butler, Marcus O; Hirano, Naoto

    2014-01-01

    Adoptive T-cell therapy, where anti-tumor T cells are first prepared in vitro, is attractive since it facilitates the delivery of essential signals to selected subsets of anti-tumor T cells without unfavorable immunoregulatory issues that exist in tumor-bearing hosts. Recent clinical trials have demonstrated that anti-tumor adoptive T-cell therapy, i.e. infusion of tumor-specific T cells, can induce clinically relevant and sustained responses in patients with advanced cancer. The goal of adoptive cell therapy is to establish anti-tumor immunologic memory, which can result in life-long rejection of tumor cells in patients. To achieve this goal, during the process of in vitro expansion, T-cell grafts used in adoptive T-cell therapy must be appropriately educated and equipped with the capacity to accomplish multiple, essential tasks. Adoptively transferred T cells must be endowed, prior to infusion, with the ability to efficiently engraft, expand, persist, and traffic to tumor in vivo. As a strategy to consistently generate T-cell grafts with these capabilities, artificial antigen-presenting cells have been developed to deliver the proper signals necessary to T cells to enable optimal adoptive cell therapy. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Langerhans cell histiocytosis: A case presentation and literature ...

    African Journals Online (AJOL)

    a complete blood count with differential counts, renal and liver function tests, measurement of .... Langerhans cells express characteristic cell surface proteins called the CD1a protein and langerin. These cells can ... Hepatic involvement is defined as hepatic enlargement, liver function test abnormalities and/or histological ...

  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. Human natural killer cells promote cross-presentation of tumor cell-derived antigens by dendritic cells.

    Science.gov (United States)

    Deauvieau, Florence; Ollion, Vincent; Doffin, Anne-Claire; Achard, Carole; Fonteneau, Jean-François; Verronese, Estelle; Durand, Isabelle; Ghittoni, Raffaella; Marvel, Jacqueline; Dezutter-Dambuyant, Colette; Walzer, Thierry; Vie, Henri; Perrot, Ivan; Goutagny, Nadège; Caux, Christophe; Valladeau-Guilemond, Jenny

    2015-03-01

    Dendritic cells (DCs) cross-present antigen (Ag) to initiate T-cell immunity against most infections and tumors. Natural killer (NK) cells are innate cytolytic lymphocytes that have emerged as key modulators of multiple DC functions. Here, we show that human NK cells promote cross-presentation of tumor cell-derived Ag by DC leading to Ag-specific CD8(+) T-cell activation. Surprisingly, cytotoxic function of NK cells was not required. Instead, we highlight a critical and nonredundant role for IFN-γ and TNF-α production by NK cells to enhance cross-presentation by DC using two different Ag models. Importantly, we observed that NK cells promote cell-associated Ag cross-presentation selectively by monocytes-derived DC (Mo-DC) and CD34-derived CD11b(neg) CD141(high) DC subsets but not by myeloid CD11b(+) DC. Moreover, we demonstrate that triggering NK cell activation by monoclonal antibodies (mAbs)-coated tumor cells leads to efficient DC cross-presentation, supporting the concept that NK cells can contribute to therapeutic mAbs efficiency by inducing downstream adaptive immunity. Taken together, our findings point toward a novel role of human NK cells bridging innate and adaptive immunity through selective induction of cell-associated Ag cross-presentation by CD141(high) DC, a process that could be exploited to better harness Ag-specific cellular immunity in immunotherapy. © 2014 UICC.

  13. Diabetic lipemia presenting as eruptive xanthomas in a child with autoimmune polyglandular syndrome type IIIa.

    Science.gov (United States)

    Batra, Prerna; Singhal, Rashi; Shah, Dheeraj

    2014-05-01

    Diabetic lipemia, although common in type 2 diabetes, is rare in type 1 diabetes mellitus. It may manifest as lipemia retinalis, eruptive xanthomas, fatty liver, and pancreatitis. We describe a 6-year-old girl diagnosed with autoimmune poly-glandular syndrome type IIIa, who presented with diabetic lipemia manifesting as eruptive xanthomas. Probable metabolic derangements causing such severe lipid abnormalities and its treatment are discussed.

  14. Type 1 (reversal) lepra reaction in borderline leprosy with unusual clinical presentation--a case report.

    Science.gov (United States)

    Kar, H K; Saxena, A K; Jain, R K; Sharma, A K

    1987-01-01

    A male 26 years old patient with BB type of leprosy was encountered with a typical clinical presentations of up-grading (reversal) Type 1 Lepra Reaction. These included sudden appearance of tender, erythematous nodular eruptions mimicking ENL, severe constitutional symptoms like high grade fever, malaise, vomiting, epistaxis, joint pain and tenosynovitis simulating Type 2 Lepra Reaction. To the best of our knowledge, this may be the first such case in our hand.

  15. Imaging the Interactions Between B Cells and Antigen-Presenting Cells.

    Science.gov (United States)

    Wang, Jia C; Bolger-Munro, Madison; Gold, Michael R

    2018-01-01

    In vivo, B cells are often activated by antigens that are displayed on the surface of antigen-presenting cells (APCs). Binding of membrane-associated antigens to the B cell receptor (BCR) causes rapid cytoskeleton-dependent changes in the spatial organization of the BCR and other B cell membrane proteins, leading to the formation of an immune synapse. This process has been modeled using antigens attached to artificial planar lipid bilayers or to plasma membrane sheets. As a more physiological system for studying B cell-APC interactions, we have expressed model antigens in easily transfected adherent cell lines such as Cos-7 cells. The model antigens that we have used are a transmembrane form of a single-chain anti-Igκ antibody and a transmembrane form of hen egg lysozyme that is fused to a fluorescent protein. This has allowed us to study multiple aspects of B cell immune synapse formation including cytoskeletal reorganization, BCR microcluster coalescence, BCR-mediated antigen gathering, and BCR signaling. Here, we provide protocols for expressing these model antigens on the surface of Cos-7 cells, transfecting B cells with siRNAs or with plasmids encoding fluorescent proteins, using fixed cell and live cell fluorescence microscopy to image B cell-APC interactions, and quantifying APC-induced changes in BCR spatial organization and signaling.

  16. Engineered T Regulatory Type 1 Cells for Clinical Application

    Directory of Open Access Journals (Sweden)

    Silvia Gregori

    2018-02-01

    Full Text Available T regulatory cells, a specialized subset of T cells, are key players in modulating antigen (Ag-specific immune responses in vivo. Inducible T regulatory type 1 (Tr1 cells are characterized by the co-expression of CD49b and lymphocyte-activation gene 3 (LAG-3 and the ability to secrete IL-10, TGF-β, and granzyme (Gz B, in the absence of IL-4 and IL-17. The chief mechanisms by which Tr1 cells control immune responses are secretion of IL-10 and TGF-β and killing of myeloid cells via GzB. Tr1 cells, first described in peripheral blood of patients who developed tolerance after HLA-mismatched fetal liver hematopoietic stem cell transplantation, have been proven to modulate inflammatory and effector T cell responses in several immune-mediated diseases. The possibility to generate and expand Tr1 cells in vitro in an Ag-specific manner has led to their clinical use as cell therapy in patients. Clinical grade protocols to generate or to enrich and expand Tr1 cell medicinal products have been established. Proof-of-concept clinical trials with Tr1 cell products have demonstrated the safety and the feasibility of this approach and indicated some clinical benefit. In the present review, we provide an overview on protocols established to induce/expand Tr1 cells in vitro for clinical application and on results obtained in Tr1 cell-based clinical trials. Moreover, we will discuss a recently developed protocol to efficient convert human CD4+ T cells into a homogeneous population of Tr1-like cells by lentiviral vector-mediated IL-10 gene transfer.

  17. Janus particles as artificial antigen-presenting cells for T cell activation.

    Science.gov (United States)

    Chen, Bo; Jia, Yilong; Gao, Yuan; Sanchez, Lucero; Anthony, Stephen M; Yu, Yan

    2014-01-01

    Here we show that the multifunctionality of Janus particles can be exploited for in vitro T cell activation. We engineer bifunctional Janus particles on which the spatial distribution of two ligands, anti-CD3 and fibronectin, mimics the "bull's eye" protein pattern formed in the membrane junction between a T cell and an antigen-presenting cell. Different levels of T cell activation can be achieved by simply switching the spatial distribution of the two ligands on the surfaces of the "bull's eye" particles. We find that the ligand pattern also affects clustering of intracellular proteins. This study demonstrates that anisotropic particles, such as Janus particles, can be developed as artificial antigen-presenting cells for modulating T cell activation.

  18. [TNF-α, diabetes type 1 and regulatory T cells].

    Science.gov (United States)

    Ryba, Monika; Myśliwska, Jolanta

    2010-01-01

    Recent studies on animal models of diabetes as well as human regulatory T cells have shown that α impairs the ability of these cells to prevent the disease. NOD mice treated with α had decreased frequency of regulatory T cells, whereas anti-TNF administration induced the increase in the number of these cells and disease prevention. The action of α also influenced the suppressive potential of Tregs. Increased susceptibility of Tregs to the modulatory effects of α involves signaling through TNFR2 that is expressed on the surface of this cell population. It seems that α neutralization may rescue regulatory T cells and restore their function in several autoimmune and inflammatory diseases. This review describes recent data concerning regulatory T cells in the context of inflammation that is present during diabetes type 1. It describes how TNF contributes to the pathogenesis of type 1 diabetes, what is the impact of this cytokine on regulatory T cell population and therapeutic effects that result from its neutralization in several inflammatory and autoimmune diseases.

  19. Types and distribution of mucous cells of the abalone Haliotis ...

    African Journals Online (AJOL)

    The types and distribution of mucous cells of Haliotis diversicolorwere observed and analyzed using the alcian blue and periodic acid schiffs (AB-PAS) reaction and histological procedures. According to the color of the mucous cells, they were divided into four types: Type I, pure red; type II, pure blue; type III, purple reddish; ...

  20. Mobile Applications in Cell Biology Present New Approaches for Cell Modelling

    Science.gov (United States)

    de Oliveira, Mayara Lustosa; Galembeck, Eduardo

    2016-01-01

    Cell biology apps were surveyed in order to identify whether there are new approaches for modelling cells allowed by the new technologies implemented in tablets and smartphones. A total of 97 apps were identified in 3 stores surveyed (Apple, Google Play and Amazon), they are presented as: education 48.4%, games 26.8% and medicine 15.4%. The apps…

  1. Cell fine structure and function - Past and present

    Science.gov (United States)

    Fernandez-Moran, H.

    1970-01-01

    Electron microscopic studies of nerve membrane fine structure, discussing cell membrane multienzyme and macromolecular energy and information transduction, protein synthesis and nucleic acids interrelations

  2. Cardiac Glycoside Glucoevatromonoside Induces Cancer Type-Specific Cell Death

    Directory of Open Access Journals (Sweden)

    Naira F. Z. Schneider

    2018-03-01

    Full Text Available Cardiac glycosides (CGs are natural compounds used traditionally to treat congestive heart diseases. Recent investigations repositioned CGs as potential anticancer agents. To discover novel cytotoxic CG scaffolds, we selected the cardenolide glucoevatromonoside (GEV out of 46 CGs for its low nanomolar anti-lung cancer activity. GEV presented reduced toxicity toward non-cancerous cell types (lung MRC-5 and PBMC and high-affinity binding to the Na+/K+-ATPase α subunit, assessed by computational docking. GEV-induced cell death was caspase-independent, as investigated by a multiparametric approach, and culminates in severe morphological alterations in A549 cells, monitored by transmission electron microscopy, live cell imaging and flow cytometry. This non-canonical cell death was not preceded or accompanied by exacerbation of autophagy. In the presence of GEV, markers of autophagic flux (e.g. LC3I-II conversion were impacted, even in presence of bafilomycin A1. Cell death induction remained unaffected by calpain, cathepsin, parthanatos, or necroptosis inhibitors. Interestingly, GEV triggered caspase-dependent apoptosis in U937 acute myeloid leukemia cells, witnessing cancer-type specific cell death induction. Differential cell cycle modulation by this CG led to a G2/M arrest, cyclin B1 and p53 downregulation in A549, but not in U937 cells. We further extended the anti-cancer potential of GEV to 3D cell culture using clonogenic and spheroid formation assays and validated our findings in vivo by zebrafish xenografts. Altogether, GEV shows an interesting anticancer profile with the ability to exert cytotoxic effects via induction of different cell death modalities.

  3. Surface-Engineering of Red Blood Cells as Artificial Antigen Presenting Cells Promising for Cancer Immunotherapy.

    Science.gov (United States)

    Sun, Xiaoqi; Han, Xiao; Xu, Ligeng; Gao, Min; Xu, Jun; Yang, Rong; Liu, Zhuang

    2017-10-01

    The development of artificial antigen presenting cells (aAPCs) to mimic the functions of APCs such as dendritic cells (DCs) to stimulate T cells and induce antitumor immune responses has attracted substantial interests in cancer immunotherapy. In this work, a unique red blood cell (RBC)-based aAPC system is designed by engineering antigen peptide-loaded major histocompatibility complex-I and CD28 activation antibody on RBC surface, which are further tethered with interleukin-2 (IL2) as a proliferation and differentiation signal. Such RBC-based aAPC-IL2 (R-aAPC-IL2) can not only provide a flexible cell surface with appropriate biophysical parameters, but also mimic the cytokine paracrine delivery. Similar to the functions of matured DCs, the R-aAPC-IL2 cells can facilitate the proliferation of antigen-specific CD8+ T cells and increase the secretion of inflammatory cytokines. As a proof-of-concept, we treated splenocytes from C57 mice with R-aAPC-IL2 and discovered those splenocytes induced significant cancer-cell-specific lysis, implying that the R-aAPC-IL2 were able to re-educate T cells and induce adoptive immune response. This work thus presents a novel RBC-based aAPC system which can mimic the functions of antigen presenting DCs to activate T cells, promising for applications in adoptive T cell transfer or even in direct activation of circulating T cells for cancer immunotherapy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. FUEL CELL PROTON EXCHANGE MEMBRANE - PRESENT AND PERSPECTIVES

    Directory of Open Access Journals (Sweden)

    Victor CIUPINA

    2012-05-01

    Full Text Available The fuel cells could contribute to the reduction of the pollution emission and the fossil fuels due to the conversion efficiency which is higher than the other energy conversion systems. There are many possibilities to improve the efficiency and to reduce the weight of the fuel cells by the integration of new nanostructured materials.

  5. Renal epithelioid angiomyolipoma presenting clinically as renal cell ...

    African Journals Online (AJOL)

    M.S. Johnson

    (AML) and its potentially malignant variant epithelioid angiomy- olipoma (EAML). PEComas are associated with the tuberous sclerosis complex and characterized by the World Health Organi- zation as a “proliferation of perivascular epithelioid cells (PECs)”. [1]. EAML is often confused with renal cell carcinoma (RCC) given.

  6. Renal Cell Carcinoma Presenting with Cutaneous Metastasis: A Case Report

    Directory of Open Access Journals (Sweden)

    Nilufer Onak Kandemir

    2010-01-01

    Full Text Available Renal cell carcinoma is the most common kidney tumor in adults. Cutaneous metastasis is a rare first symptom of the disease. This paper describes the diagnosis of a renal cell carcinoma that was indicated by cutaneous metastasis in the head and neck region, and considers the etiopathogenesis of such cases. A careful skin examination is important to detect cutaneous metastasis associated with renal cell carcinomas. Metastatic skin lesions in the head and neck region must be taken into consideration during a differential diagnosis.

  7. Renal Cell Carcinoma Presenting with Cutaneous Metastasis: A Case Report

    Science.gov (United States)

    Onak Kandemir, Nilufer; Barut, Figen; Yılmaz, Kıvanç; Tokgoz, Husnu; Hosnuter, Mubin; Ozdamar, Sukru Oguz

    2010-01-01

    Renal cell carcinoma is the most common kidney tumor in adults. Cutaneous metastasis is a rare first symptom of the disease. This paper describes the diagnosis of a renal cell carcinoma that was indicated by cutaneous metastasis in the head and neck region, and considers the etiopathogenesis of such cases. A careful skin examination is important to detect cutaneous metastasis associated with renal cell carcinomas. Metastatic skin lesions in the head and neck region must be taken into consideration during a differential diagnosis. PMID:20811607

  8. Type II Odontoid Fracture with Atlantoaxial Dislocation Presenting as Symptomatic Seizures: A Case Report.

    Science.gov (United States)

    Bu, Guoyun; Shuang, Feng; Liu, Gang; Wu, Ye; Hou, Shuxun; Ren, Dongfeng

    2016-12-01

    To report symptomatic seizures of a patient with an old type II odontoid fracture with atlantoaxial dislocation. The type II odontoid fracture is a dangerous disease and presents as neurological deficits. Because of the compression of upper cervical cord, without timely diagnosis and treatment, a type II odontoid fracture may result in sudden death. Although it has been shown that epileptic seizures may lead to type II odontoid fracture, there is no report of symptomatic seizures in patients with odontoid fracture. A 16-year-old adolescent boy with neurological deficits, especially grand mal seizures for duration of 5 years, was diagnosed as an old type II odontoid fracture with atlantoaxial dislocation and treated in our hospital. A 1-year follow-up was performed. Systematic analyses of the clinical history, manifestations, physical examination, and radiologic results of the patient revealed an old type II odontoid fracture. Magnetic resonance imaging showed spinal cord compression and degeneration. The patient received posterior atlantoaxial fixation and fusion procedure following successful closed reduction. The frequency of seizures was reduced to once a month and there was a thorough recovery in other neurological functions 1 year after the operation. Old type II odontoid fracture might present as symptomatic seizures in addition to other neurological deficits. Posterior atlantoaxial screw-plate fixation and fusion is an effective treatment for old type II odontoid fracture. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Spectrum of clinical presentations in familial hemophagocytic lymphohistiocytosis type 5 patients with mutations in STXBP2

    DEFF Research Database (Denmark)

    Meeths, Marie; Entesarian, Miriam; Al-Herz, Waleed

    2010-01-01

    in patients with mutations in STXBP2 encoding Munc18-2, recently associated with familial HLH type 5. The disease severity among 11 persons studied here was highly variable and, accordingly, age at diagnosis ranged from 2 months to 17 years. Remarkably, in addition to typical manifestations of familial HLH...... (FHL), the clinical findings included colitis, bleeding disorders, and hypogammaglobulinemia in approximately one-third of the patients. Laboratory analysis revealed impairment of NK-cell degranulation and cytotoxic capacity. Interleukin-2 stimulation of lymphocytes in vitro rescued the NK cell...

  10. Mast cells regulate CD4+ T cell differentiation in absence of antigen presentation.

    Science.gov (United States)

    Rodriguez Cetina Biefer, Hector; Heinbokel, Timm; Uehara, Hirofumi; Camacho, Virginia; Minami, Koichiro; Nian, Yeqi; Koduru, Suresh; El Fatimy, Rachid; Ghiran, Ionita; Trachtenberg, Alexander J; de la Fuente, Miguel A; Azuma, Haruhito; Akbari, Omid; Tullius, Stefan G; Vasudevan, Anju; Elkhal, Abdallah

    2018-02-19

    Given their unique capacity for antigen uptake, processing, and presentation, antigen presenting cells (APCs) are critical for initiating and regulating innate and adaptive immune responses. We have previously shown the role of nicotinamide adenine dinucleotide (NAD + ) in T cell differentiation independently of the cytokine milieu, while the precise mechanisms remained unknown. The objective of this study is to further dissect the mechanism of actions of NAD + , and to determine the impact of APCs on NAD + -mediated T cell activation. Isolated dendritic cells and bone marrow-derived mast cells were used to characterize the mechanisms of action of NAD + on CD4 + T cell fate in vitro. Furthermore, NAD + -mediated CD4 + T cell differentiation was investigated in vivo using WT C57BL/6, Mast cell -/- , MHC class ll -/- , WASP -/- , 5C.C7 Rag2 -/- and CD11b-DTR transgenic mice. Finally, we tested the physiological impact of NAD + on the systemic immune response in the context of Listeria monocytogenes infection. Our in vivo and in vitro findings indicate that following NAD + administration MCs, exclusively, promote CD4 + T cell differentiation, both in absence of antigen and independently of major APCs. Moreover, we found that MCs mediated CD4 + T cell differentiation independently of MHC-II and TCR signaling machinery. More importantly, although treatment with NAD + resulted in a decreased MHC-II expression on CD11c + cells, MC-mediated CD4 + T cell differentiation rendered mice resistant to the administration of lethal doses of Listeria monocytogenes. Collectively, our study unravels a novel cellular and molecular pathway that regulates innate and adaptive immunity via MCs, exclusively, and underscores the therapeutic potential of NAD + in the context of primary immunodeficiencies and antimicrobial resistance. Copyright © 2018. Published by Elsevier Inc.

  11. Antigen cross-presentation by dendritic cell subsets: one general or all sergeants?

    Science.gov (United States)

    Nierkens, Stefan; Tel, Jurjen; Janssen, Edith; Adema, Gosse J.

    2015-01-01

    Antigen cross-presentation describes the process through which dendritic cells (DCs) acquire exogenous antigens for presentation on MHC class I molecules. The ability to cross-present has been thought of as a feature of specialized DC subsets. Emerging data, however, suggest that the cross-presenting ability of each DC subset is tuned by and dependent on several factors, such as DC location and activation status, and the type of antigen and inflammatory signals. Thus, we argue that capacity of cross-presentation is not an exclusive trait of one or several distinct DC subtypes, but rather a common feature of the DC family in both mice and humans. Understanding DC subset activation and antigen-presentation pathways might yield improved tools and targets to exploit the unique cross-presenting capacity of DCs in immunotherapy. PMID:23540650

  12. Activation of Type II Cells into Regenerative Stem Cell Antigen-1+ Cells during Alveolar Repair

    Science.gov (United States)

    Kumar, Varsha Suresh; Zhang, Wei; Rehman, Jalees; Malik, Asrar B.

    2015-01-01

    The alveolar epithelium is composed of two cell types: type I cells comprise 95% of the gas exchange surface area, whereas type II cells secrete surfactant, while retaining the ability to convert into type I cells to induce alveolar repair. Using lineage-tracing analyses in the mouse model of Pseudomonas aeruginosa–induced lung injury, we identified a population of stem cell antigen (Sca)-1–expressing type II cells with progenitor cell properties that mediate alveolar repair. These cells were shown to be distinct from previously reported Sca-1–expressing bronchioalveolar stem cells. Microarray and Wnt reporter studies showed that surfactant protein (Sp)-C+Sca-1+ cells expressed Wnt signaling pathway genes, and inhibiting Wnt/β-catenin signaling prevented the regenerative function of Sp-C+Sca-1+ cells in vitro. Thus, P. aeruginosa–mediated lung injury induces the generation of a Sca-1+ subset of type II cells. The progenitor phenotype of the Sp-C+Sca-1+ cells that mediates alveolar epithelial repair might involve Wnt signaling. PMID:25474582

  13. Preimplantation HLA typing for stem cell transplantation treatment of hemoglobinopathies

    Directory of Open Access Journals (Sweden)

    Anver Kuliev

    2014-09-01

    Full Text Available Preimplantation genetic diagnosis (PGD for HLA typing is steadily becoming an option for at risk couples with thalassemic children, requiring HLA matched bone marrow transplantation treatment. The paper presents the world’s largest PGD experience of 475 cases for over 2 dozens thalassemia mutations, resulting in birth of 132 unaffected children. A total of 146 cases were performed together with preimplantation HLA typing, resulting in detection and transfer of HLA matched unaffected embryos in 83 of them, yielding the birth of 16 HLA matched children, potential donors for their affected siblings. The presented experience of HLA matched stem cell transplantation for thalassemia, following PGD demonstrated a successful hematopoietic reconstitution both for younger and older patients. The data show that PGD is an efficient approach for HLA matched stem cell transplantation treatment for thalassemia.

  14. Human thymic epithelial cells present superantigens to T-cell lines and thymocytes

    DEFF Research Database (Denmark)

    Jlrgensen, A; Nielsen, M; Svejgaard, A

    1996-01-01

    It is generally accepted that thymic epithelial cells (TEC) act as accessory cells in positive selection of pre-T cells. However, our knowledge of the antigen presentation and accessory cell function to human TEC is limited. Here we present results obtained by the use of serum-free cultured human...... TEC, showing that IFN-gamma-treated TEC are able to support T-cell-mediated responses to the bacterial superantigens (Sag) SEA and SEB, even at very low Sag concentrations. T-cell responses to TEC-presented Sags were dependent on the presence of the adhesion molecules ICAM-1, ICAM-2, LFA-1, and LFA-3......, but not on CD4 and CD8 molecules. There is a low but significant expression of B7 molecules on human TEC, and treatment of TEC with anti-B7.1 and anti-B7.2 antibodies before Sag pulsing leads to decreased Sag responses, indicating a significant importance of B7 molecules on TEC. Both CD4+ T-cell lines and CD4...

  15. Identification of intermediate cell types by keratin expression in the developing human prostate

    NARCIS (Netherlands)

    Xue, Y; Smedts, F; Debruyne, FMJ; de la Rosette, JJMCH; Schalken, JA

    1998-01-01

    BACKGROUND. The secretory acini of the adult human prostate contain basal, luminal, and intermediate types of exocrine cells. Intermediate cells are thought to play an important role in normal growth and neoplastic transformation. In this study we investigated whether this cell type is present in

  16. HIV-1 Trans Infection of CD4+ T Cells by Professional Antigen Presenting Cells

    Science.gov (United States)

    Rinaldo, Charles R.

    2013-01-01

    Since the 1990s we have known of the fascinating ability of a complex set of professional antigen presenting cells (APCs; dendritic cells, monocytes/macrophages, and B lymphocytes) to mediate HIV-1 trans infection of CD4+ T cells. This results in a burst of virus replication in the T cells that is much greater than that resulting from direct, cis infection of either APC or T cells, or trans infection between T cells. Such APC-to-T cell trans infection first involves a complex set of virus subtype, attachment, entry, and replication patterns that have many similarities among APC, as well as distinct differences related to virus receptors, intracellular trafficking, and productive and nonproductive replication pathways. The end result is that HIV-1 can sequester within the APC for several days and be transmitted via membrane extensions intracellularly and extracellularly to T cells across the virologic synapse. Virus replication requires activated T cells that can develop concurrently with the events of virus transmission. Further research is essential to fill the many gaps in our understanding of these trans infection processes and their role in natural HIV-1 infection. PMID:24278768

  17. DNA of Erythroid Origin Is Present in Human Plasma and Informs the Types of Anemia.

    Science.gov (United States)

    Lam, W K Jacky; Gai, Wanxia; Sun, Kun; Wong, Raymond S M; Chan, Rebecca W Y; Jiang, Peiyong; Chan, Natalie P H; Hui, Winnie W I; Chan, Anthony W H; Szeto, Cheuk-Chun; Ng, Siew C; Law, Man-Fai; Chan, K C Allen; Chiu, Rossa W K; Lo, Y M Dennis

    2017-10-01

    There is much interest in the tissue of origin of circulating DNA in plasma. Data generated using DNA methylation markers have suggested that hematopoietic cells of white cell lineages are important contributors to the circulating DNA pool. However, it is not known whether cells of the erythroid lineage would also release DNA into the plasma. Using high-resolution methylation profiles of erythroblasts and other tissue types, 3 genomic loci were found to be hypomethylated in erythroblasts but hypermethylated in other cell types. We developed digital PCR assays for measuring erythroid DNA using the differentially methylated region for each locus. Based on the methylation marker in the ferrochelatase gene, erythroid DNA represented a median of 30.1% of the plasma DNA of healthy subjects. In subjects with anemia of different etiologies, quantitative analysis of circulating erythroid DNA could reflect the erythropoietic activity in the bone marrow. For patients with reduced erythropoietic activity, as exemplified by aplastic anemia, the percentage of circulating erythroid DNA was decreased. For patients with increased but ineffective erythropoiesis, as exemplified by β-thalassemia major, the percentage was increased. In addition, the plasma concentration of erythroid DNA was found to correlate with treatment response in aplastic anemia and iron deficiency anemia. Plasma DNA analysis using digital PCR assays targeting the other 2 differentially methylated regions showed similar findings. Erythroid DNA is a hitherto unrecognized major component of the circulating DNA pool and is a noninvasive biomarker for differential diagnosis and monitoring of anemia. © 2017 American Association for Clinical Chemistry.

  18. The Effect of Socio-Economic Status on Severity of Periocular Basal Cell Carcinoma at Presentation.

    Science.gov (United States)

    Lim, Lik Thai; Agarwal, Pankaj K; Young, David; Ah-Kee, Elliott Yann; Diaper, Charles J M

    2015-01-01

    To evaluate the influence of socio-economic factors on size of periocular basal cell carcinoma at presentation. All periocular basal cell carcinoma cases receiving treatment from the oculoplastics team in South Glasgow Hospitals NHS Trust, Glasgow, between 1999 and 2009, were identified retrospectively. Information collected included demographic details of patients, side and site of lesions, type of lesions, and size of lesions. The size of lesion was defined as small for any dimension not exceeding 5 mm, medium for dimensions between 6 mm and 10 mm, and large for dimensions exceeding 11 mm. Home address was used to determine the Scottish Index of Multiple Deprivation rank. The demographics, size of lesion, and Scottish Index of Multiple Deprivation rank were investigated using the general linear regression modelling. Of the 67 cases, 24 were men and 43 were women. The mean age was 71.5 years. There were a total of 67 identified cases, of which 38 presented with small-size lesions, 24 with medium-size lesions, and 5 with large-size lesions. Scottish Index of Multiple Deprivation is related to the presenting incidence of basal cell carcinoma, with the lower ranks presenting more frequently. Socio-economic deprivation is associated with larger and more frequent presentation of periocular basal cell carcinoma. This highlights the importance of raising awareness among populations of the more deprived areas of the significance of lumps and bumps within the periocular regions.

  19. The Basics of Artificial Antigen Presenting Cells in T Cell-Based Cancer Immunotherapies.

    Science.gov (United States)

    Neal, Lillian R; Bailey, Stefanie R; Wyatt, Megan M; Bowers, Jacob S; Majchrzak, Kinga; Nelson, Michelle H; Haupt, Carl; Paulos, Chrystal M; Varela, Juan C

    2017-01-01

    Adoptive T cell transfer (ACT) can mediate objective responses in patients with advanced malignancies. There have been major advances in this field, including the optimization of the ex vivo generation of tumor-reactive lymphocytes to ample numbers for effective ACT therapy via the use of natural and artificial antigen presenting cells (APCs). Herein we review the basic properties of APCs and how they have been manufactured through the years to augment vaccine and T cell-based cancer therapies. We then discuss how these novel APCs impact the function and memory properties of T cells. Finally, we propose new ways to synthesize aAPCs to augment the therapeutic effectiveness of antitumor T cells for ACT therapy.

  20. Genomic Analysis of Immune Cell Infiltrates Across 11 Tumor Types.

    Science.gov (United States)

    Iglesia, Michael D; Parker, Joel S; Hoadley, Katherine A; Serody, Jonathan S; Perou, Charles M; Vincent, Benjamin G

    2016-11-01

    Immune infiltration of the tumor microenvironment has been associated with improved survival for some patients with solid tumors. The precise makeup and prognostic relevance of immune infiltrates across a broad spectrum of tumors remain unclear. Using mRNA sequencing data from The Cancer Genome Atlas (TCGA) from 11 tumor types representing 3485 tumors, we evaluated lymphocyte and macrophage gene expression by tissue type and by genomic subtypes defined within and across tumor tissue of origin (Cox proportional hazards, Pearson correlation). We investigated clonal diversity of B-cell infiltrates through calculating B-cell receptor (BCR) repertoire sequence diversity. All statistical tests were two-sided. High expression of T-cell and B-cell signatures predicted improved overall survival across many tumor types including breast, lung, and melanoma (breast CD8_T_Cells hazard ratio [HR] = 0.36, 95% confidence interval [CI] = 0.16 to 0.81, P = .01; lung adenocarcinoma B_Cell_60gene HR = 0.71, 95% CI = 0.58 to 0.87, P = 7.80E-04; melanoma LCK HR = 0.86, 95% CI = 0.79 to 0.94, P = 6.75E-04). Macrophage signatures predicted worse survival in GBM, as did B-cell signatures in renal tumors (Glioblastoma Multiforme [GBM]: macrophages HR = 1.62, 95% CI = 1.17 to 2.26, P = .004; renal: B_Cell_60gene HR = 1.17, 95% CI = 1.04 to 1.32, P = .009). BCR diversity was associated with survival beyond gene segment expression in melanoma (HR = 2.67, 95% CI = 1.32 to 5.40, P = .02) and renal cell carcinoma (HR = 0.36, 95% CI = 0.15 to 0.87, P = .006). These data support existing studies suggesting that in diverse tissue types, heterogeneous immune infiltrates are present and typically portend an improved prognosis. In some tumor types, BCR diversity was also associated with survival. Quantitative genomic signatures of immune cells warrant further testing as prognostic markers and potential biomarkers of response to cancer immunotherapy.

  1. Squamous cell carcinoma presenting as cutaneous horn in diabetic ...

    African Journals Online (AJOL)

    ... not the horn itself, which is just dead keratin, but rather the nature of the underlying disease, although the horns are usually benign and that's why the case is reported. Keywords: Cutaneous horn; Cornu cutaneum; Squamous Cell Carcinoma; Diabetes Mellitus. Sudanese Journal of Dermatology Vol. 4 (2) 2006: pp. 86-91 ...

  2. Towards efficient cancer immunotherapy: advances in developing artificial antigen-presenting cells

    Science.gov (United States)

    Eggermont, Loek J.; Paulis, Leonie E.; Tel, Jurjen; Figdor, Carl G.

    2014-01-01

    Active anti-cancer immune responses depend on efficient presentation of tumor antigens and co-stimulatory signals by antigen-presenting cells (APCs). Therapy with autologous natural APCs is costly and time-consuming and results in variable outcomes in clinical trials. Therefore, development of artificial APCs (aAPCs) has attracted significant interest as an alternative. We discuss the characteristics of various types of acellular aAPCs, and their clinical potential in cancer immunotherapy. The size, shape, and ligand mobility of aAPCs and their presentation of different immunological signals can all have significant effects on cytotoxic T cell activation. Novel optimized aAPCs, combining carefully tuned properties, may lead to efficient immunomodulation and improved clinical responses in cancer immunotherapy. PMID:24998519

  3. Vγ9Vδ2-T cells as antigen presenting cells for iNKT cell based cancer immunotherapy

    Science.gov (United States)

    Werter, Inge M.; Schneiders, Famke L.; Scotet, Emmanuel; Verheul, Henk M.W.; de Gruijl, Tanja D.; van der Vliet, Hans J.

    2014-01-01

    CD1d-restricted invariant natural killer T cells (iNKT) constitute an important immunoregulatory T-cell subset involved in the induction of antitumor immune responses. Here, we provide a view on the recent observation that Vγ9Vδ2-T cells, through trogocytosis of CD1d-containing membrane fragments, have the capacity to act as antigen presenting cells for iNKT. PMID:25941612

  4. Summary: present and future challenges for stem cell research.

    Science.gov (United States)

    Hogan, B L M

    2008-01-01

    Stem cell research is being driven forward at an intense pace by creative interactions among scientists working in different fields. These include developmental and reproductive biology, regeneration, genomics, live cell imaging, RNA biology, and cancer biology, to name a few. Numerous model systems and techniques are being exploited, and lab scientists are teaming up with bioengineers and clinicians. The ferment of ideas that makes the field so exciting was in full evidence throughout the Symposium. However, many challenges still need to be overcome to translate basic discoveries into therapeutic outcomes that will save lives and fulfill the promises that have been made. This chapter summarizes some of the highlights of the Symposium and indicates future directions that are being taken by leaders in the field.

  5. Gastrointestinal Stromal Cell Tumor (GIST) Presenting as an ...

    African Journals Online (AJOL)

    Background: Gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors that may mimic ovarian tumor on presurgical testing. These tumors are usually asymptomatic, often discovered accidentally during endoscopic or radiologic examinations,. Case Presentations: In first case a 50 years old woman presented ...

  6. Langerhans cell histiocytosis: A case presentation and literature ...

    African Journals Online (AJOL)

    Once the diagnosis has been confirmed, all cases should be referred to a paediatric oncologist for risk stratification and further management. We present a case of a toddler with LCH with skeletal involvement, who primarily presented to an orthopaedic surgeon. Relevant knowledge about this condition is reviewed.

  7. Bartter syndrome Type III and congenital anomalies of the kidney and urinary tract: an antenatal presentation

    NARCIS (Netherlands)

    Westland, R.; Hack, W.W.; van der Horst, H.J.; Uittenbogaard, L.B.; van Hagen, J.M.; van der Valk, P.; Kamsteeg, E.J.; Heuvel, L.P.W.J. van den; van Wijk, J.A.

    2012-01-01

    Bartter syndrome encompasses a variety of inheritable renal tubular transport disorders characterized by hypokalemia and hypochloremic metabolic alkalosis. Bartter syndrome Type III is caused by genetic alterations in the chloride channel kidney B (CLCNKB) gene and often presents in the first 2

  8. Choline Deficiency Causes Colonic Type II Natural Killer T (NKT) Cell Loss and Alleviates Murine Colitis under Type I NKT Cell Deficiency

    Science.gov (United States)

    Sagami, Shintaro; Ueno, Yoshitaka; Tanaka, Shinji; Fujita, Akira; Niitsu, Hiroaki; Hayashi, Ryohei; Hyogo, Hideyuki; Hinoi, Takao; Kitadai, Yasuhiko; Chayama, Kazuaki

    2017-01-01

    Serum levels of choline and its derivatives are lower in patients with inflammatory bowel disease (IBD) than in healthy individuals. However, the effect of choline deficiency on the severity of colitis has not been investigated. In the present study, we investigated the role of choline deficiency in dextran sulfate sodium (DSS)-induced colitis in mice. Methionine-choline-deficient (MCD) diet lowered the levels of type II natural killer T (NKT) cells in the colonic lamina propria, peritoneal cavity, and mesenteric lymph nodes, and increased the levels of type II NKT cells in the livers of wild-type B6 mice compared with that in mice fed a control (CTR) diet. The gene expression pattern of the chemokine receptor CXCR6, which promotes NKT cell accumulation, varied between colon and liver in a manner dependent on the changes in the type II NKT cell levels. To examine the role of type II NKT cells in colitis under choline-deficient conditions, we assessed the severity of DSS-induced colitis in type I NKT cell-deficient (Jα18-/-) or type I and type II NKT cell-deficient (CD1d-/-) mice fed the MCD or CTR diets. The MCD diet led to amelioration of inflammation, decreases in interferon (IFN)-γ and interleukin (IL)-4 secretion, and a decrease in the number of IFN-γ and IL-4-producing NKT cells in Jα18-/- mice but not in CD1d-/- mice. Finally, adaptive transfer of lymphocytes with type II NKT cells exacerbated DSS-induced colitis in Jα18-/- mice with MCD diet. These results suggest that choline deficiency causes proinflammatory type II NKT cell loss and alleviates DSS-induced colitis. Thus, inflammation in DSS-induced colitis under choline deficiency is caused by type II NKT cell-dependent mechanisms, including decreased type II NKT cell and proinflammatory cytokine levels. PMID:28095507

  9. Regulation of T Helper Cell Responses During Antigen Presentation by Norepinephrine-exposed Endothelial Cells.

    Science.gov (United States)

    Xu, Linghui; Ding, Wanhong; Stohl, Lori L; Zhou, Xi K; Azizi, Shayan; Chuang, Ethan; Lam, Jimmy; Wagner, John A; Granstein, Richard D

    2017-11-21

    Dermal blood vessels and regional lymph nodes are innervated by sympathetic nerves and, under stress, sympathetic nerves release norepinephrine (NE). Exposure of primary murine dermal microvascular endothelial cells (pDMECs) to NE followed by co-culture with Langerhans cells (LCs), responsive CD4+ T cells and antigen resulted in modulation of CD4+ T cell responses. NE-treatment of pDMECs induced increased production of interleukin (IL)-6 and IL-17A while downregulating interferon (IFN)-γ and IL-22 release. This effect did not require contact between pDMECs and LCs or T cells and depended on pDMEC production of IL-6. The presence of NE-treated pDMECs increased the proportion of CD4+ T cells expressing intracellular IL-17A and increased IL-17A mRNA while decreasing the proportion of IFN-γ- or IL-22-expressing CD4+ T cells and mRNA levels for those cytokines. Retinoic acid receptor-related orphan receptor gamma (RORγt) mRNA was significantly increased in CD4+ T cells while T-box transcription factor (T-bet) mRNA was decreased. Intradermal administration of NE prior to hapten immunization at the injection site produced a similar bias in draining lymph node CD4+ T cells toward IL-17A and away from IFN-γ and IL-22 production. Under stress, release of NE may have significant regulatory effects on the outcome of antigen presentation through actions on ECs as well as enhancement of inflammatory skin disorders involving IL-17/Th17 cells. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Human macrophages and dendritic cells can equally present MART-1 antigen to CD8(+ T cells after phagocytosis of gamma-irradiated melanoma cells.

    Directory of Open Access Journals (Sweden)

    María Marcela Barrio

    Full Text Available Dendritic cells (DC can achieve cross-presentation of naturally-occurring tumor-associated antigens after phagocytosis and processing of dying tumor cells. They have been used in different clinical settings to vaccinate cancer patients. We have previously used gamma-irradiated MART-1 expressing melanoma cells as a source of antigens to vaccinate melanoma patients by injecting irradiated cells with BCG and GM-CSF or to load immature DC and use them as a vaccine. Other clinical trials have used IFN-gamma activated macrophage killer cells (MAK to treat cancer patients. However, the clinical use of MAK has been based on their direct tumoricidal activity rather than on their ability to act as antigen-presenting cells to stimulate an adaptive antitumor response. Thus, in the present work, we compared the fate of MART-1 after phagocytosis of gamma-irradiated cells by clinical grade DC or MAK as well as the ability of these cells to cross present MART-1 to CD8(+ T cells. Using a high affinity antibody against MART-1, 2A9, which specifically stains melanoma tumors, melanoma cell lines and normal melanocytes, the expression level of MART-1 in melanoma cell lines could be related to their ability to stimulate IFN-gamma production by a MART-1 specific HLA-A*0201-restricted CD8(+ T cell clone. Confocal microscopy with Alexa Fluor®(647-labelled 2A9 also showed that MART-1 could be detected in tumor cells attached and/or fused to phagocytes and even inside these cells as early as 1 h and up to 24 h or 48 h after initiation of co-cultures between gamma-irradiated melanoma cells and MAK or DC, respectively. Interestingly, MART-1 was cross-presented to MART-1 specific T cells by both MAK and DC co-cultured with melanoma gamma-irradiated cells for different time-points. Thus, naturally occurring MART-1 melanoma antigen can be taken-up from dying melanoma cells into DC or MAK and both cell types can induce specific CD8(+ T cell cross-presentation thereafter.

  11. Internal fixation in compound type III fractures presenting after golden period

    Directory of Open Access Journals (Sweden)

    Azam Quamar

    2007-01-01

    Full Text Available Objective: Patients often reach the hospital late after passage of golden hours (initial 6 hours after sustaining high-velocity injuries. The decision of internal fixation in Gustilo′s Type IIIA and IIIB fractures becomes a formidable challenge in patients reaching late. The purpose of the present study was to find out if internal fixation could be safely undertaken in these patients. Materials and Methods: Sixty-three patients, having 70 compound fractures (46 Type IIIA and 24 IIIB, which were internally fixed after 6h but within 24h after injury, were included in the present analysis. Follow-up ranged from 18 to 48 months with mean of 28 months. Result: Overall infection rate noted was (n = 11 15.71% (8.7% in IIIA, and 29.16% in IIIB. The difference in deep infection rate between Type IIIA and Type IIIB was found to be statistically significant ( P value < 0.01. Nonunion was seen in five fractures. Functional evaluation using Katenjian′s criteria, showed 62.85% (44 fractures of 70 good to excellent results. Conclusion: Satisfactory results may be obtained in Gustilo′s Type IIIA and IIIB fractures even if fixed after the golden period, provided strict protocol such as aggressive debridement, prophylactic antibiotic coverage, early soft tissue reconstruction and timely bone grafting is followed. The primary coverage of the wound is discouraged.

  12. Degradation mechanism of planar perovskite solar cells (Presentation Recording)

    Science.gov (United States)

    Qin, Chuanjiang; Matsushima, Toshinori; Adachi, Chihaya

    2015-10-01

    Organic-inorganic hybrid halide perovskites are an interesting class of materials that have excellent semiconductor properties, and demonstrated promising applications on many fields, such as solar cells, water photolysis, light emitting diodes, and amplified spontaneous emission. So far, the device lifetime is still short, and this is an important key issue faced for all researchers in this field.[1] The deep understanding of their durability and degradation mechanism is critical and necessary toward future applications. Towards development of efficient and long-term stable perovskite solar cells (PSCs), we firstly studied the relationship between crystallization, morphology, device architecture, efficiency and durability of encapsulated PSCs. Furthermore, the degradation mechanism of the devices was elucidated by different experimental methods. The well crystallized and fully covered perovskite layer improves not only power conversion efficiency but also long-time durability. Compared to a widely used silver counter electrode, lithium fluoride/aluminum and gold electrode-based PSCs demonstrated better durability owing to less chemical degradation and interface changing. We also confirmed that the amount of accumulated charge carriers induces the degradation of the PSCs, which was proved by a thermally stimulated current technique. Finally, we realized a planar PSC with excellent durability by improving device encapsulation and optimizing device structures. Reference: 1. M. Grätzel, Nature Materials 2014, 13, 838-842.

  13. Rare Atypical Presentations in Type 2 Lepra Reaction: A Case Series

    Science.gov (United States)

    Mitra, Debdeep

    2017-01-01

    Abstract Background Leprosy or Hansen’s disease is a chronic mycobacterial infection caused by mycobacterium leprae. Reactions in Leprosy represent an acute inflammataory response during the natural chronic course of infection. Type 2 lepra reaction is a Th2-mediated type III hypersensitivity reaction in leprosy, with a characteristic cutaneous manifestation in the form of erythema nodosum leprosum (ENL). This presentation describes unusual presentations of Type 2 lepra reaction in five patients. Methods Patient data and dermatological findings were analyzed in three men and two women diagnosed with Hansen’s disease (Leprosy). Results Findings included multiple tender, polycyclic, necrotic lesions distributed over the face in one patient, and painful, fluid-filled lesions on both arms and lower limbs in another. The third patient showed erythematous, tender nodules, bullae, and necrotic ulcers over the back and upper and lower limbs. The fourth showed erythematous tender nodules over the face, neck, back, and extremities, predominantly in sun-exposed areas. The fifth revealed multiple erythematous, severely tender nodules and urticarial plaques mimicking those of Sweet’s syndrome. Diagnosis of borderline or lepromatous leprosy with atypical Type 2 reaction were made in all cases. Conclusion Type 2 lepra reactions are antigen antibody-mediated immune complex reactions that present with constitutional symptoms and ENL characterized by tender, erythematous, evanescent nodules mainly on the face, arms, and legs. Over 50% of lepromatous leprosy patients and 25% of borderline lepromatous leprosy patients experienced type 2 lepra reactions prior to the advent of multi-drug therapy. Thalidomide is the drug of choice for severe atypical lepra reactions because of its anti-tumor necrosis factor-α action. Awareness of these atypical variants and prompt diagnosis and treatment are essential to prevent mortality and morbidity in potentially treatable patients

  14. Fatal Case of Type A Aortic Dissection Presenting As Acute Renal Failure

    Directory of Open Access Journals (Sweden)

    Fuat Ozkan

    2014-08-01

    Full Text Available Aortic dissection is a life-threatening illness requiring early diagnosis and treatment. Uncommon early presentations mimicking various illnesses can delay diagnosis. Acute renal failure (ARF is an uncommon complication of type A aortic dissection (AAD. Presentation with ARF is associated with an increased risk of in-hospital death and persistence of renal dysfunction at midterm follow-up in type B aortic dissection, but not AAD. We report a case of a type A aortic dissection complicated by ARF, with a fatal outcome. A 56-year-old male was transferred to the emergency service with anuria and rapid deterioration of renal function. Computed tomography showed type A aortic dissection with near-complete collapse of the true lumen at the level of the renal arteries and complicated with left renal infarct. Because of deterioration of his general condition during hemodialysis, he was treated with supportive measures including ventilatory support. He died two days after admission. Aortic dissection initially mimicking ARF is rare. Accurate early diagnosis of aortic dissection with indeterminate presentation is crucial. [Arch Clin Exp Surg 2014; 3(4.000: 254-256

  15. Targeted regulation of self-peptide presentation prevents type I diabetes in mice without disrupting general immunocompetence.

    Science.gov (United States)

    Yi, Woelsung; Seth, Nilufer P; Martillotti, Tom; Wucherpfennig, Kai W; Sant'Angelo, Derek B; Denzin, Lisa K

    2010-04-01

    Peptide loading of MHC class II (MHCII) molecules is directly catalyzed by the MHCII-like molecule HLA-DM (DM). Another MHCII-like molecule, HLA-DO (DO), associates with DM, thereby modulating DM function. The biological role of DO-mediated regulation of DM activity in vivo remains unknown; however, it has been postulated that DO expression dampens presentation of self antigens, thereby preventing inappropriate T cell activation that ultimately leads to autoimmunity. To test the idea that DO modulation of the MHCII self-peptide repertoire mediates self tolerance, we generated NOD mice that constitutively overexpressed DO in DCs (referred to herein as NOD.DO mice). NOD mice are a mouse model for type 1 diabetes, an autoimmune disease mediated by the destruction of insulin-secreting pancreatic beta cells. Our studies showed that diabetes development was completely blocked in NOD.DO mice. Similar to NOD mice, NOD.DO animals selected a diabetogenic T cell repertoire, and the numbers and function of Tregs were normal. Indeed, immune system function in NOD.DO mice was equivalent to that in NOD mice. NOD.DO DCs, however, presented an altered MHCII-bound self-peptide repertoire, thereby preventing the activation of diabetogenic T cells and subsequent diabetes development. These studies show that DO expression can shape the overall MHCII self-peptide repertoire to promote T cell tolerance.

  16. Presenting Different Selves to Different People: Self-Presentation as a Function of Relationship Type and Contingent Self-Esteem.

    Science.gov (United States)

    Øverup, Camilla S; Brunson, Julie A; Acitelli, Linda K

    2015-01-01

    Past work has established a connection between self-esteem and self-presentation; however, research has not explored how self-esteem that is contingent on one's relationship may influence self-presentational tactics in that relationship. Across two studies, undergraduate students reported on the extent to which their self-esteem depended on their friendship and romantic relationship, as well as the extent to which they engaged in self-presentation behaviors in those relationships. The results suggest that relationship-specific contingent self-esteem predicts relationship-specific self-presentation; however, friendship-contingent self-esteem predicted self-presentation in both friendships and romantic relationships. These results suggest that individuals are keenly and differentially attuned to qualitatively different relationships, and when perceiving potential problems, they attempt to remedy those through their self-presentations. Furthermore, results indicate the possibility that self-esteem tied to a particular relationship may not be as important as self-esteem based more generally on one's relationships.

  17. MHC class II antigen presentation by B cells in health and disease

    NARCIS (Netherlands)

    Souwer, Yuri

    2009-01-01

    MHC class II antigen presentation by B cells is important to activate CD4+ T cells that stimulate the B cell to produce antibodies. Besides this, disruption of MHC class II antigen presentation could play a role in immune escape by tumor cells. This thesis describes MHC class II antigen presentation

  18. Orbital mantle cell lymphoma presenting as myasthenia gravis.

    Science.gov (United States)

    Karlin, Justin; Peck, Travis; Prenshaw, Karyn; Portell, Craig A; Kirzhner, Maria

    2017-08-18

    A 69-year-old man, previously treated with pyridostigmine for myasthenia gravis (manifesting as ptosis and diplopia) was evaluated for several concomitant bilateral anterior orbital masses. Imaging revealed 3 discrete, solid masses within and around the orbits. An incisional biopsy demonstrated atypical lymphocytes positive for CD20 and Cyclin-D1, consistent with mantle cell lymphoma. The patient received induction chemotherapy with a rituximab-based regimen. He experienced resolution of his diplopia and ptosis after one cycle of chemotherapy and achieved complete remission of the orbital masses and myasthenia symptoms after 6 cycles. Myasthenia gravis is most commonly associated with thymoma, but may also be observed with other malignancies. Recognition that orbital lymphoma may coexist with myasthenia gravis will help in expediting the diagnosis of future cases and in guiding treatment decisions.

  19. Cell Death and Ageing – A Question of Cell Type

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    Pidder Jansen-Dürr

    2002-01-01

    Full Text Available Replicative senescence of human cells in primary culture is a widely accepted model for studying the molecular mechanisms of human ageing. The standard model used for studying human ageing consists of fibroblasts explanted from the skin and grown into in vitro senescence. From this model, we have learned much about molecular mechanisms underlying the human ageing process; however, the model presents clear limitations. In particular, a long-standing dogma holds that replicative senescence involves resistance to apoptosis, a belief that has led to considerable confusion concerning the role of apoptosis during human ageing. While there are data suggesting that apoptotic cell death plays a key role for ageing in vitro and in the pathogenesis of various age-associated diseases, this is not reflected in the current literature on in vitro senescence. In this article, I summarize key findings concerning the relationship between apoptosis and ageing in vivo and also review the literature concerning the role of apoptosis during in vitro senescence. Recent experimental findings, summarized in this article, suggest that apoptotic cell death (and probably other forms of cell death are important features of the ageing process that can also be recapitulated in tissue culture systems to some extent. Another important lesson to learn from these studies is that mechanisms of in vivo senescence differ considerably between various histotypes.

  20. A DEFICIENCY OF ANTIGEN-PRESENTING CELLS IN PATIENTS WITH PULMONARY TUBERCULOSIS

    Directory of Open Access Journals (Sweden)

    L. V. Sakhno

    2009-01-01

    Full Text Available Abstract. The phenotype and functional properties of antigen-presenting cells (APCs: blood monocytes and in vitro generated macrophages/dendritic cells were investigated in patients with pulmonary tuberculosis (TB, n = 192 with different levels of proliferative response to M. tuberculosis antigens (PPD-responsive vs PPD - anergic patients, n = 118 and 74, respectively. A functional deficiency of all 3 types of APCs was revealed in patients with TB. I.e., a monocyte disfunction was displayed by low CD86 and HLA-DR expression, 2-fold increase of CD14+CD16+ subset, high level of FasL+ and IL-10+ cells, and enhanced IL-10 and IL-6 production upon LPS-stimulation. The in vitro generated macrophages from blood monocytes challenged with GM-CSF, were characterized by shifted Th1/Th2 balance (down-regulated production of IFNγ and IL-18 combined with up-regulation of IL-6 and IL-10, and reduced allostimulatory activity in mixed lymphocyte culture. The dendritic cells were characterized by decrease of mature, activated CD25+ cells, low level of IFNγ production in conjunction with enhanced capacity to produce IL - 10 and IL-6, and profound reduction of functional (allostimulatory activity. The APC disfunction of were most prominent in PPD-anergic patients. A possible role of APC disfunctions in disturbed antigen-specific T-cell response to M. tuberculosis is discussed.

  1. Development of Primer Pairs from Molecular Typing of Rabies Virus Variants Present in Mexico

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    Fernando Bastida-González

    2016-01-01

    Full Text Available Nucleoprotein (N gene from rabies virus (RABV is a useful sequence target for variant studies. Several specific RABV variants have been characterized in different mammalian hosts such as skunk, dog, and bats by using anti-nucleocapsid monoclonal antibodies (MAbs via indirect fluorescent antibody (IFA test, a technique not available in many laboratories in Mexico. In the present study, a total of 158 sequences of N gene from RABV were used to design eight pairs of primers (four external and four internal primers, for typing four different RABV variants (dog, skunk, vampire bat, and nonhematophagous bat which are most common in Mexico. The results indicate that the primer and the typing variant from the brain samples, submitted to nested and/or real-time PCR, are in agreement in all four singleplex reactions, and the designed primer pairs are an alternative for use in specific variant RABV typing.

  2. Comparison of Types of Cell Death: Apoptosis and Necrosis.

    Science.gov (United States)

    Manning, Francis; Zuzel, Katherine

    2003-01-01

    Cell death is an essential factor in many biological processes including development. Discusses two types of cell death: (1) necrosis (induced by sodium azide); and (2) apoptosis (induced by sodium chromate). Illustrates key features that differ between these two types of cells death including loss of membrane integrity and internucleosomal DNA…

  3. Exploiting absorption-induced self-heating in solar cells (Conference Presentation)

    Science.gov (United States)

    Ullbrich, Sascha; Fischer, Axel; Erdenebileg, Enkhtur; Koerner, Christian; Reineke, Sebastian; Leo, Karl; Vandewal, Koen

    2017-04-01

    Absorption of light inevitably leads to a self-heating of each type of solar cell, either due to the excess energy of absorbed photons or non-radiative recombination of charge carriers. Although the effect of temperature on solar cell parameters such as the open-circuit voltage are well known, it is often ignored in Suns-Voc measurements [1]. This measurement technique enables direct access to the diode ideality factor without an influence by series resistance. A frequently seen decrease of the ideality factor or a saturation of the open-circuit voltage at high illumination intensities is often attributed solely to surface recombination [2], the shape of the density of states (DOS) [3], or the quality of the back contact in inorganic solar cells [4]. In this work, we present an analytical model for taking into account absorption induced self-heating in Suns-Voc measurements and validate it for various solar cell technologies such as small molecule organic solar cells, perovskite solar cells, and inorganic solar cells. Furthermore, with an adapted Suns-Voc technique, we are able to not only correctly determine the ideality factor, but also the relevant energy gap of the solar cell, which is especially of interest in the field of novel solar cell technologies. [1] R.A. Sinton and A. Cuevas, EU PVSEC, 1152-1155 (2000) [2] K. Tvingstedt and C. Deibel, Adv. Energy Mater. 6, 1502230 (2016) [3] T. Kirchartz and J. Nelson, Phys. Rev. B 86, 165201 (2012) [4] S. Glunz, J. Nekarda, H. Maeckel et al., EU PVSEC, 849-853 (2007)

  4. Rare atypical presentations in Type 2 lepra reaction: a case series.

    Science.gov (United States)

    Vijendran, Pragasam; Verma, Rajesh; Vasudevan, Biju; Mitra, Debdeep; Badad, Ambresh; Neema, Shekhar

    2014-03-01

    Type 2 lepra reaction is a Th2-mediated type III hypersensitivity reaction in leprosy, with a characteristic cutaneous manifestation in the form of erythema nodosum leprosum (ENL). We describe unusual presentations of Type 2 lepra reaction in five patients. Patient data and dermatological findings were analyzed in three men and two women diagnosed with Hansen's disease. Findings included multiple tender, polycyclic, necrotic lesions distributed over the face in one patient, and painful, fluid-filled lesions on both arms and lower limbs in another. The third patient showed erythematous, tender nodules, bullae, and necrotic ulcers over the back and upper and lower limbs. The fourth showed erythematous tender nodules over the face, neck, back, and extremities, predominantly in sun-exposed areas. The fifth revealed multiple erythematous, severely tender nodules and urticarial plaques mimicking those of Sweet's syndrome. Diagnosis of borderline or lepromatous leprosy with atypical Type 2 reaction were made in all cases. Type 2 lepra reactions are antigen antibody-mediated immune complex reactions that present with constitutional symptoms and ENL characterized by tender, erythematous, evanescent nodules mainly on the face, arms, and legs. Over 50% of lepromatous leprosy patients and 25% of borderline lepromatous leprosy patients experienced type 2 lepra reactions prior to the advent of multi-drug therapy. Thalidomide is the drug of choice for severe atypical lepra reactions because of its anti-tumor necrosis factor-α action. Awareness of these atypical variants and prompt diagnosis and treatment are essential to prevent mortality and morbidity in potentially treatable patients. © 2013 The International Society of Dermatology.

  5. Eutirucallin, a RIP-2 Type Lectin from the Latex of Euphorbia tirucalli L. Presents Proinflammatory Properties

    Science.gov (United States)

    Santana, Sanzio Silva; Gennari-Cardoso, Margareth Leitão; Carvalho, Fernanda Caroline; Roque-Barreira, Maria Cristina; Santiago, André da Silva; Alvim, Fátima Cerqueira; Pirovani, Carlos Priminho

    2014-01-01

    Lectins are carbohydrate-binding proteins that recognize and modulate physiological activities and have been used as a toll for detection and identification of biomolecules, and therapy of diseases. In this study we have isolated a lectin present in the latex of Euphorbia tirucalli, and named it Eutirucallin. The latex protein extract was subjected to ion exchange chromatography and showed two peaks with haemagglutinating activity. Polypeptides of 32 kDa protein extract strongly interacted with immobilized galactose (α-lactose > D-N-acetylgalactosamine). The Eutirucallin was obtained with a yield of 5.6% using the α-lactose column. The lectin domain has 32 kDa subunits and at least two of which are joined by disulfide bridges. The agglutinating capacity for human erythrocytes A+, B+ and O+ is inhibited by D-galactose. The haemagglutinating activity of Eutirucallin was independent of Ca2+ and maintained until the temperature of 55°C. Eutirucallin presented biological activities such as neutrophils recruitment and cytokine prodution by macrophages. The analysis of the trypsin-digested Eutirucallin by ms/ms in ESI-Q-TOFF resulted in nine peptides similar to type 2 ribosome-inactivating protein (type-2 RIP). It's partial sequence showed a similarity of 67.4 – 83.1% for the lectin domain of type-2 RIP [Ricin and Abrin (83.1%), Viscumin, Ebulin, Pulchellin, Cinnamomin, Volkensin and type-2 RIP Iris hollandica]. Our data suggest that Eutirucallin is a new member of type 2 ribosome-inactivating protein and presents biotechnological potential. PMID:24558388

  6. Biodegradable nanoellipsoidal artificial antigen presenting cells for antigen specific T-cell activation.

    Science.gov (United States)

    Meyer, Randall A; Sunshine, Joel C; Perica, Karlo; Kosmides, Alyssa K; Aje, Kent; Schneck, Jonathan P; Green, Jordan J

    2015-04-01

    Non-spherical nanodimensional artificial antigen presenting cells (naAPCs) offer the potential to systemically induce an effective antigen-specific immune response. In this report it is shown biodegradable ellipsoidal naAPCs mimic the T-Cell/APC interaction better than equivalent spherical naAPCs. In addition, it is demonstrated ellipsoidal naAPCs offer reduced non-specific cellular uptake and a superior pharmacokinetic profile compared to spherical naAPCs. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. The ability of B cells and dendritic cells to present antigen increases during ontogeny.

    Science.gov (United States)

    Muthukkumar, S; Goldstein, J; Stein, K E

    2000-11-01

    The immune response to polysaccharide (PS) Ags in mice is delayed during ontogeny even when administered in a thymus-dependent (TD) form. In this study, Neisseria meningitidis group C PS-tetanus toxoid conjugate (MCPS-TT) vaccine was used to examine whether the delay in the development of Ab responses to TD PS conjugate vaccines in neonatal mice is due to defective Ag presentation. The results show that B cells and dendritic cells (DC) from 3- and 7-day-old mice were severely defective in presenting TT and MCPS-TT to Ag-specific T cell clones. The ability of these cells to present Ag reaches adult levels by 4 wk. The development of anti-MCPS and anti-TT Abs in neonatal mice parallels the functional ability of their APC to present Ag. DC from neonatal mice expressed very low levels of MHC class II, costimulatory molecules B7.1, B7.2, and CD11c but high levels of monocyte-specific markers F4/80 and CD11b and granulocyte marker, Ly6G. Significant changes in the expression of these markers were observed as the age of the mice increased. MHC class II, B7.1 and B7.2, and CD11c all increased with age, reaching adult levels between 3 and 4 wk, concurrent with the function of APC. These results demonstrate that one reason neonates fail to produce high titers of anti-PS Abs even when immunized in a TD form is that their B cells and DC are not fully functional.

  8. [6]-Gingerol, from Zingiber officinale, potentiates GLP-1 mediated glucose-stimulated insulin secretion pathway in pancreatic β-cells and increases RAB8/RAB10-regulated membrane presentation of GLUT4 transporters in skeletal muscle to improve hyperglycemia in Leprdb/db type 2 diabetic mice.

    Science.gov (United States)

    Samad, Mehdi Bin; Mohsin, Md Nurul Absar Bin; Razu, Bodiul Alam; Hossain, Mohammad Tashnim; Mahzabeen, Sinayat; Unnoor, Naziat; Muna, Ishrat Aklima; Akhter, Farjana; Kabir, Ashraf Ul; Hannan, J M A

    2017-08-09

    GTPases that are responsible for GLUT4 vesicle fusion to the membrane. Collectively, our study reports that GLP-1 mediates the insulinotropic activity of [6]-Gingerol, and [6]-Gingerol treatment facilitates glucose disposal in skeletal muscles through increased activity of glycogen synthase 1 and enhanced cell surface presentation of GLUT4 transporters.

  9. Differences in symptom presentation and hospital mortality according to type of acute myocardial infarction.

    Science.gov (United States)

    Canto, Andrew J; Kiefe, Catarina I; Goldberg, Robert J; Rogers, William J; Peterson, Eric D; Wenger, Nanette K; Vaccarino, Viola; Frederick, Paul D; Sopko, George; Zheng, Zhi-Jie; Canto, John G

    2012-04-01

    Chest pain/discomfort (CP) is the hallmark symptom of acute myocardial infarction (MI), but some patients with MI present without CP. We hypothesized that MI type (ST-segment elevation MI [STEMI] or non-STEMI [NSTEMI]) may be associated with the presence or absence of CP. We investigated the association between CP at presentation and MI type, hospital care, and mortality among 1,143,513 patients with MI in the National Registry of Myocardial Infarction (NRMI) from 1994 to 2006. Overall, 43.6% of patients with NSTEMI and 27.1% of patients with STEMI presented without CP. For both MI type, patients without CP were older, were more frequently female, had more diabetes or history of heart failure, were more likely to delay hospital arrival, and were less likely to receive evidence-based medical therapies and invasive cardiac procedures. Multivariable analysis indicated that NSTEMI (vs STEMI) was the strongest predictor of atypical symptoms (adjusted odds ratio [95% CI], 1.93 [1.91-1.95]). Within the 4 CP/MI type categories, hospital mortality was highest for no CP/STEMI (27.8%), followed by no CP/NSTEMI (15.3%) and CP/STEMI (9.6%), and was lowest for CP/NSTEMI (5.4%). The adjusted odds ratio of mortality was 1.38 (1.35-1.41) for no CP (vs CP) in the STEMI group and 1.31 (1.28-1.34) in the NSTEMI group. Hospitalized patients with NSTEMI were nearly 2-fold more likely to present without CP than patients with STEMI. Patients with MI without CP were less quickly diagnosed and treated and had higher adjusted odds of hospital mortality, regardless of whether they had ST-segment elevation. Copyright © 2012 Mosby, Inc. All rights reserved.

  10. Interaction of colloidal nanoparticles with cells (Conference Presentation)

    Science.gov (United States)

    Parak, Wolfgang J.

    2017-02-01

    What happens to inorganic nanoparticles (NPs), such as plasmonic gold or silver, superparamagnetic iron oxide, or fluorescent quantum dot NPs, after they have been administrated to an animal or a human being? The review discusses the integrity, biodistribution, and fate of NPs after in vivo administration. First the hybrid nature of the NPs is described, by conceptually dividing them into the inorganic NP core, an engineered surface coating around the core which comprises the ligand shell and optionally also bioconjugation, and into the corona of adsorbed biological molecules. It is shown that in vivo all of these three compounds may degrade individually and that each of them can drastically modify the life-cycle and biodistribution of the whole hetero-structure. The NPs thus may be disintegrated into different parts, of which biodistribution and fate would need to be analyzed individually. Multiple labelling and quantification strategies for such purpose will be discussed. All reviewed data indicate that in vivo NPs no longer should be considered as homogeneous entity, but should be seen as inorganic/organic/biological nano-hybrids with complex and intricately linked degradation pathways. References: M. Chanana, P. Rivera Gil, M. A. Correa-Duarte, L. M. Liz-Marzán. W. J. Parak, "Physicochemical Properties of Protein-Coated Gold Nanoparticles in Biological Fluids and Cells before and after Proteolytic Digestion", Angewandte Chemie International Edition 52, 4179-4183 (2013). W. G. Kreyling, A. M. Abdelmonem, Z. Ali, F. Alves, M. Geiser, N. Haberl, R. Hartmann, S. Hirn, K. Kantner, D. Jimenez de Aberasturi, G. Khadem-Saba, J.-M. Montenegro, J. Rejman, T. Rojo, I. Ruiz de Larramendi, R. Ufartes, A. Wenk, W. J. Parak, "In vivo integrity of polymer-coated gold nanoparticles", Nature Nanotechnology 10, 619-623 (2015).J. Clerk Maxwell, A Treatise on Electricity and Magnetism, 3rd ed., vol. 2. Oxford: Clarendon, 1892, pp.68-73.

  11. A Rare Form of Chronic Granulomatous Disease (Type Iva Presenting as Inflammatory Bowel Disease

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    Francisco A Sylvester

    1996-01-01

    Full Text Available Neutrophil dysfunction syndromes can sometimes mimic the clinical and pathological features of inflammatory bowel disease. The case of a 3.5-year-old boy with chronic diarrhea, abdominal pain, poor growth since infancy and microcytic, hypochromic anemia is presented. After an extensive diagnostic evaluation, he was found to have a rare variant (type IVA of chronic granulomatous disease. His gastrointestinal symptoms markedly improved during therapy with gamma-interferon. Chronic granulomatous disease can present initially with a clinical picture suggestive of chronic intestinal inflammation. Therefore it should be considered in the differential diagnosis of atypical inflammatory bowel disease, both in children and young adults.

  12. Atypical clinical presentation of mucopolysaccharidosis type II (Hunter syndrome: a case report

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    Sharma Subodh

    2010-05-01

    Full Text Available Abstract Introduction We present a very rare case of mucopolysaccharidosis with atypical presentation such as mild mental retardation, an acrocephalic head and no corneal clouding. The purpose of presenting this case is to highlight the distinctive manifestation of mucopolysaccharidosis type II (Hunter syndrome. Case presentation A 10-year-old East Asian boy presented with abdominal distension of five years' duration and complained of shortness of breath on and off for the same period. On examination his head was large and his head circumference was 54.5 cm. His neck was short, he had coarse facial features, a depressed nasal bridge and small stubby fingers with flexion of distal interphalangeal joints, and a low arched palate was observed. There was mild mental retardation. Conclusion Based on clinical findings and radiological features it is possible to diagnose a case of mucopolysaccharidosis. Careful and systemic approach is needed to accurately diagnose the exact type as enzymatic studies are not available in most centers.

  13. Basal Cell Carcinoma in Type 2 Segmental Darier's Disease

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    Lynne Robertson

    2012-01-01

    Full Text Available Background. Darier's disease (DD, also known as Keratosis Follicularis or Darier-White disease, is a rare disorder of keratinization. DD can present as a generalized autosomal dominant condition as well as a localized or segmental postzygotic condition (Vázquez et al., 2002. Clinical features of DD include greasy, warty papules and plaques on seborrheic areas, dystrophic nails, palmo-plantar pits, and papules on the dorsum of the hands and feet. Objective. We report a case of basal cell carcinoma developing in a patient with type 2 segmental DD. Conclusion. According to the current literature, Type 2 segmental disease is a rare presentation of Darier's disease with only 8 previous cases reported to date. In addition, nonmelanoma skin cancer (NMSC arising from DD is rarely reported; however, there may be an association between DD and risk of carcinogenesis.

  14. Beta-cell failure in type 2 diabetes mellitus.

    Science.gov (United States)

    Lencioni, Cristina; Lupi, Roberto; Del Prato, Stefano

    2008-06-01

    Diabetes mellitus has been defined as a "group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both" and encompasses a wide range of heterogeneous conditions. Common type 2 diabetes mellitus (T2DM) results from a combination of genetic and acquired factors. However, lifestyle factors, particularly overeating and physical inactivity, are the major clinical determinants of T2DM. Insulin resistance is a common feature of T2DM, but it is unlikely to cause T2DM unless progressive loss of beta-cell function develops. Significant reduction in beta-cell function is already present at the time of T2DM diagnosis, and it continuously declines irrespective of treatment. As such, the progressive loss of beta-cell function dictates the rate of worsened glycemic control. Development of progressive deterioration accelerates via gluco- and lipotoxicity, loss of beta-cell function, and shrinkage of beta-cell mass. Understanding the causes for beta-cell failure is therefore of capital importance to develop new and more effective therapeutic strategies.

  15. Type-specific cell line models for type-specific ovarian cancer research.

    Directory of Open Access Journals (Sweden)

    Michael S Anglesio

    Full Text Available BACKGROUND: OVARIAN CARCINOMAS CONSIST OF AT LEAST FIVE DISTINCT DISEASES: high-grade serous, low-grade serous, clear cell, endometrioid, and mucinous. Biomarker and molecular characterization may represent a more biologically relevant basis for grouping and treating this family of tumors, rather than site of origin. Molecular characteristics have become the new standard for clinical pathology, however development of tailored type-specific therapies is hampered by a failure of basic research to recognize that model systems used to study these diseases must also be stratified. Unrelated model systems do offer value for study of biochemical processes but specific cellular context needs to be applied to assess relevant therapeutic strategies. METHODS: We have focused on the identification of clear cell carcinoma cell line models. A panel of 32 "ovarian cancer" cell lines has been classified into histotypes using a combination of mutation profiles, IHC mutation-surrogates, and a validated immunohistochemical model. All cell lines were identity verified using STR analysis. RESULTS: Many described ovarian clear cell lines have characteristic mutations (including ARID1A and PIK3CA and an overall molecular/immuno-profile typical of primary tumors. Mutations in TP53 were present in the majority of high-grade serous cell lines. Advanced genomic analysis of bona-fide clear cell carcinoma cell lines also support copy number changes in typical biomarkers such at MET and HNF1B and a lack of any recurrent expressed re-arrangements. CONCLUSIONS: As with primary ovarian tumors, mutation status of cancer genes like ARID1A and TP53 and a general immuno-profile serve well for establishing histotype of ovarian cancer cell We describe specific biomarkers and molecular features to re-classify generic "ovarian carcinoma" cell lines into type specific categories. Our data supports the use of prototype clear cell lines, such as TOV21G and JHOC-5, and questions the use of

  16. Facial Nerve Palsy: An Unusual Presenting Feature of Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Ozcan Yildiz

    2011-01-01

    Full Text Available Lung cancer is the second most common type of cancer in the world and is the most common cause of cancer-related death in men and women; it is responsible for 1.3 million deaths annually worldwide. It can metastasize to any organ. The most common site of metastasis in the head and neck region is the brain; however, it can also metastasize to the oral cavity, gingiva, tongue, parotid gland and lymph nodes. This article reports a case of small cell lung cancer presenting with metastasis to the facial nerve.

  17. Building the right centriole for each cell type.

    Science.gov (United States)

    Loncarek, Jadranka; Bettencourt-Dias, Mónica

    2017-12-28

    The centriole is a multifunctional structure that organizes centrosomes and cilia and is important for cell signaling, cell cycle progression, polarity, and motility. Defects in centriole number and structure are associated with human diseases including cancer and ciliopathies. Discovery of the centriole dates back to the 19th century. However, recent advances in genetic and biochemical tools, development of high-resolution microscopy, and identification of centriole components have accelerated our understanding of its assembly, function, evolution, and its role in human disease. The centriole is an evolutionarily conserved structure built from highly conserved proteins and is present in all branches of the eukaryotic tree of life. However, centriole number, size, and organization varies among different organisms and even cell types within a single organism, reflecting its cell type-specialized functions. In this review, we provide an overview of our current understanding of centriole biogenesis and how variations around the same theme generate alternatives for centriole formation and function. © 2018 Loncarek and Bettencourt Dias.

  18. Alveolar epithelial type II cells induce T cell tolerance to specific antigen

    DEFF Research Database (Denmark)

    Lo, Bernice; Hansen, Søren; Evans, Kathy

    2008-01-01

    II) constitutively express the class II MHC led us to hypothesize that Type II cells play a role in the adaptive immune response. Because Type II cells do not express detectable levels of the costimulatory molecules CD80 and CD86, we propose that Type II cells suppress activation of naive T cells...

  19. Survival and signaling changes in antigen presenting cell subsets after radiation

    Science.gov (United States)

    Parker, Jennifer Janell

    Radiation therapy is a widely used cancer treatment that has the potential to influence anti-tumor immune responses. Both myeloablative and non-myeloablative radiation are often used as part of preparatory regimens for hematopoetic stem cell transplantation, in combination with other chemotherapy or immuno-modulatory (e.g. Anti-thymocyte globulin (ATG)) therapies for both cytotoxic and immune modulatory purposes. However, the mechanisms responsible for the effect of radiation on antigen presenting cell (APC) responsiveness and radioresistance are poorly understood. The first studies described in this thesis were designed to identify and characterize early radiation-induced signaling changes in antigen presenting cells and to determine the effects of these signaling changes on APC receptor expression and function. The NFkappaB pathway in antigen presenting cells was chosen for study because it is activated by radiation in a wide range of other cell types and plays a vital role in the maintenance and regulation of the immune system. The effects of therapeutically relevant doses radiation (2 and 20 Gy) were compared at various timepoints in the human monocytic cell line (U937) using phospho-flow cytometry staining methods and cytometric analysis. These studies demonstrated that radiation-induced changes in the phosphorylation state of NFkappaB family members that were p53 independent. However, these changes were dependent upon activation of ATM in response to single or double-stranded breaks in DNA, as shown in experiments using an inhibitor of ATM and ATM siRNA knockdown U937 cells. In addition, studies examining the effect of radiation on co-stimulatory receptors with and without inhibition of the NFkappaB pathway via phospho-flow cytometry revealed that radiation-induced phosphorylation of NEMO promoted the activation and functional maturation of U937 cells. Furthermore, functional studies using both phospho-flow cytometry and/or mixed lymphocyte reactions to

  20. Cell type-specific and common characteristics of exosomes derived from mouse cell lines: Yield, physicochemical properties, and pharmacokinetics.

    Science.gov (United States)

    Charoenviriyakul, Chonlada; Takahashi, Yuki; Morishita, Masaki; Matsumoto, Akihiro; Nishikawa, Makiya; Takakura, Yoshinobu

    2017-01-01

    Exosomes are small membrane vesicles secreted from cells and are expected to be used as drug delivery systems. Important characteristics of exosomes, such as yield, physicochemical properties, and pharmacokinetics, may be different among different cell types. However, there is limited information about the effect of cell type on these characteristics. In the present study, we evaluated these characteristics of exosomes derived from five different types of mouse cell lines: B16BL6 murine melanoma cells, C2C12 murine myoblast cells, NIH3T3 murine fibroblasts cells, MAEC murine aortic endothelial cells, and RAW264.7 murine macrophage-like cells. Exosomes were collected using a differential ultracentrifugation method. The exosomes collected from all the cell types were negatively charged globular vesicles with a diameter of approximately 100nm. C2C12 and RAW264.7 cells produced more exosomes than the other types of cells. The exosomes were labeled with a fusion protein of Gaussia luciferase and lactadherin to evaluate their pharmacokinetics. After intravenous injection into mice, all the exosomes rapidly disappeared from the systemic circulation and mainly distributed to the liver. In conclusion, the exosome yield was significantly different among the cell types, and all the exosomes evaluated in this study showed comparable physicochemical and pharmacokinetic properties. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Human antigen-presenting cells respond differently to gut-derived probiotic bacteria but mediate similar strain-dependent NK and T cell activation

    DEFF Research Database (Denmark)

    Fink, Lisbeth Nielsen; Zeuthen, Louise Hjerrild; Ferlazzo, Guido

    2007-01-01

    , in vitro assessment of the immunomodulatory effects of distinct strains may depend strongly on the cell type used as a model. To select the most appropriate model for screening of beneficial bacteria in human cells, the response to strains of intestinal bacteria of three types of antigen-presenting cells...... (APC) was compared; blood myeloid dendritic cells (DC), monocyte-derived DC and monocytes, and the effector response of natural killer cells and naïve T cells was characterized. Maturation induced by gut-derived bacteria differed between APC, with blood DC and monocytes responding with the production...... of IL-6 and tumour necrosis factor-alpha to bacteria, which elicited mainly IL-10 in monocyte-derived DC. In contrast, comparable IFN-gamma production patterns were found in both natural killer cells and T cells induced by all bacteria-matured APC. An inhibitory effect of certain strains on this IFN...

  2. Cell type-specific glycoconjugates of collecting duct cells during maturation of the rat kidney.

    Science.gov (United States)

    Holthöfer, H

    1988-08-01

    The ontogeny of lectin-positive epithelial cell types and the maturation of polarized expression of the glycocalyx of the collecting ducts (CD) of the rat kidney were studied from samples of 18th-day fetal and neonatal kidneys of various ages. Lectins from Dolichos biflorus (DBA) and Vicia villosa (VVA), with preferential affinity to principal cells, stained virtually all CD cells of the fetal kidneys. However, within two days postnatally, the number of cells positive for DBA and VVA decreased to amounts found in the adult kidneys. Moreover, a characteristic change occurred rapidly after birth in the intracellular polarization of the reactive glycoconjugates, from a uniform plasmalemmal to a preferentially apical staining. In contrast, lectins from Arachis hypogaea (PNA), Maclura pomifera (MPA) and Lotus tetragonolobus (LTA), reacting indiscriminatively with principal and intercalated cells of adult kidneys, stained most CD cells in the fetal kidneys, and failed to show any postnatal change in the amount of positive cells or in the intracellular polarization. The immunocytochemical tests for (Na + K)-ATPase and carbonic anhydrase (CA II) revealed the characteristic postnatal decrease in the amount of principal cells and simultaneous increase in the amount of CA II rich intercalated cells. DBA and VVA reactive cells also decreased postnatally, paralleling the changes observed in the (Na + K)-ATPase positive principal cells. The present results suggest that the expression of the cell type-specific glycocalyx of principal and intercalated cells is developmentally regulated, undergoes profound changes during maturation, and is most likely associated with electrolyte transport phenomena.

  3. Selective transport of internalized antigens to the cytosol for MHC class I presentation in dendritic cells

    NARCIS (Netherlands)

    Rodriguez, A; Regnault, A; Kleijmeer, M; Ricciardi-Castagnoli, P; Amigorena, S

    1999-01-01

    In order for cytotoxic T cells to initiate immune responses, peptides derived from internalized antigens must be presented to the cytotoxic T cells on major histocompatibility complex (MHC) class I molecules. Here we show that dendritic cells, the only antigen-presenting cells that initiate immune

  4. Both conventional and interferon killer dendritic cells have antigen-presenting capacity during influenza virus infection

    NARCIS (Netherlands)

    C.H. Geurts van Kessel (Corine); I.M. Bergen (Ingrid); F. Muskens (Femke); L. Boon (Louis); H.C. Hoogsteden (Henk); A.D.M.E. Osterhaus (Albert); G.F. Rimmelzwaan (Guus); B.N.M. Lambrecht (Bart)

    2009-01-01

    textabstractNatural killer cells are innate effector cells known for their potential to produce interferon-γ and kill tumour and virus-infected cells. Recently, B220+CD11cintNK1.1+ NK cells were found to also have antigen-presenting capacity like dendritic cells (DC), hence their name

  5. 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...

  6. Presentation, pathology and prognosis of renal disease in type 2 diabetes.

    Science.gov (United States)

    Tan, Jasmine; Zwi, L Jonathan; Collins, John F; Marshall, Mark R; Cundy, Tim

    2017-01-01

    Non-diabetic renal disease (NDRD) is common in patients with type 2 diabetes (T2D), but the relationship between its presentation and prognosis is unknown. In a retrospective cohort study, we compared renal and patient survival among 263 patients with T2D who had native renal biopsies between 2002 and 2008 from three Auckland hospitals in New Zealand. The presence of diabetic nephropathy (DN), NDRD or mixed (DN and NDRD) was determined from biopsy. We examined clinical associations according to NDRD etiologies and mode of presentation-acute (defined by acute kidney injury (AKI)) or non-acute. Patients were followed until end-stage renal disease, death or December 2015. Survival was compared using Log-rank test. 94 (36%) patients had DN, 72 (27%) had NDRD, and 97 (37%) had mixed pathologies. Obesity-related focal segmental glomerulosclerosis was the most common NDRD (46%) in patients with non-acute presentations, whereas interstitial nephritis or immune-complex glomerulonephritides were the most prevalent in those with acute presentations (60%). DN was commonly associated with AKI (pRenal survival was best in the NDRD group (prenal prognosis was worse in those with more advanced DN lesions and those with an acute presentation (pRenal disease in patients with T2D is heterogeneous. The renal prognosis differs markedly according to histopathological diagnosis and mode of presentation.

  7. DC-SIGN, a C-type lectin on dendritic cells that unveils many aspects of dendritic cell biology

    NARCIS (Netherlands)

    Geijtenbeek, Teunis B. H.; Engering, Anneke; van Kooyk, Yvette

    2002-01-01

    Dendritic cells (DC) are present in essentially every tissue where they operate at the interface of innate and acquired immunity by recognizing pathogens and presenting pathogen-derived peptides to T cells. It is becoming clear that not all C-type lectins on DC serve as antigen receptors recognizing

  8. Does Parkinson's disease and type-2 diabetes mellitus present common pathophysiological mechanisms and treatments?

    Science.gov (United States)

    Lima, Marcelo M S; Targa, Adriano D S; Noseda, Ana C D; Rodrigues, Lais S; Delattre, Ana Marcia; dos Santos, Fabiola V; Fortes, Mariana H; Maturana, Maira J; Ferraz, Anete C

    2014-04-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease afflicting about 1% of people over 65 years old and 4-5% of people over 85 years. It is proposed that a cascade of deleterious factors is set in motion within that neuron made not of one, but rather of multiple factors such as free radicals, excitotoxicity, neuroinflammation, and apoptosis to cite only some of the most salient. In this scenario, chronic systemic inflammation, as well as impaired mitochondrial metabolism, have also been suspected of playing a role in the development of type-2 diabetes, and the possibility of a shared pathophysiology of PD and type-2 diabetes has been proposed. The discussion about the interactions between PD and type-2 diabetes mellitus began in the 1960's and there is still controversy. Insulin and dopamine may exert reciprocal regulation hence; hypoinsulinemia induced by streptozotocin decreased the amounts of dopamine transporter and tyrosine hydroxylase transcripts in the substantia nigra pars compacta. Accordingly, dopamine depletion in the striatum is able to decreases insulin signaling in basal ganglia, indicating that, perhaps, PD may be considered as a risk factor for the development of type-2 diabetes mellitus. In this sense, it is described that peroxisome proliferator-activated receptor-γ, ATP-sensitive K(+) channels, AMP-activated protein kinase, glucagon-like peptide-1 and dipeptidyl peptidase-4 are important therapeutic targets for PD and reinforces the association with diabetes. Therefore, the objective of the present review is to contextualize the mutual pathophysiological interactions between PD and type-2 diabetes mellitus, as well as the potential common treatments.

  9. 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.

  10. FasL Mediates T-Cell Eradication of Tumor Cells Presenting Low Levels of Antigens | Center for Cancer Research

    Science.gov (United States)

    One approach to cancer immunotherapy, as opposed to therapeutic vaccination, is the transfusion of large numbers of tumor-specific killer T cells (cytotoxic T cells or CTLs) into patients. The body’s own defense killer T cells are a subgroup of T lymphocytes (a type of white blood cells) that are capable of inducing death in tumor cells. CTLs can cause the death of target cells either by releasing granules containing toxic molecules including perforin, or by producing a membrane protein called Fas ligand (FasL) which on interaction with the tumor cell results in cell death.

  11. Long QTc Syndrome Type 2 Presenting in a Postpartum Patient on Medroxyprogesterone

    Directory of Open Access Journals (Sweden)

    John Kern

    2014-01-01

    Full Text Available Introduction. Congenital long QT syndrome type 2 (LQTS2 is a rare inherited cardiac abnormality resulting in increased risk of polymorphic ventricular tachycardia (PVT. Case Description. A 21-year-old postpartum female presented with syncopal episode after phone alarm. She was noted to have PVT on telemetry monitoring in the emergency department. EKG revealed QTc of 530. The patient’s only medication was medroxyprogesterone. She ultimately received a dual chamber pacemaker with ICD. Discussion. LQTS2 is associated with alarm sounds as a precipitating factor. Postpartum hormonal shifts as well as medroxyprogesterone have significant effect on native QTc duration.

  12. Neurofibromatosis Type 1 Presenting with Plexiform Neurofibromas in Two Patients: MRI Features

    Directory of Open Access Journals (Sweden)

    Ahmet Mesrur Halefoglu

    2012-01-01

    Full Text Available Neurofibromatosis type 1 (NF1, also known as peripheral neurofibromatosis or von Recklinghausen’s disease, is one of the most common genetic disorders. It is inherited in an autosomal dominant pattern. Multiple cutaneous neurofibromas are hallmark lesions of NF1. Localized and plexiform neurofibromas of the paraspinal and sacral region are the most common abdominal neoplasms in NF1. Herein, we report two patients with a known history of NF1 presenting with multiple, extensive localized and plexiform neurofibromas. We describe the important distinguishing features of these tumors as seen on magnetic resonance imaging (MRI, including very bright signal intensity and target sign on T2 weighted images.

  13. Differences between T cell-type and natural killer cell-type chronic active Epstein-Barr virus infection.

    Science.gov (United States)

    Kimura, Hiroshi; Hoshino, Yo; Hara, Shinya; Sugaya, Naomi; Kawada, Jun-Ichi; Shibata, Yukiko; Kojima, Seiji; Nagasaka, Tetsuro; Kuzushima, Kiyotaka; Morishima, Tsuneo

    2005-02-15

    Infections of T cells and natural killer (NK) cells play a central role in the pathogenesis of chronic active Epstein-Barr virus (CAEBV) infection. To characterize the virologic and cytokine profiles of T cell-type and NK cell-type infection, 39 patients with CAEBV infection were analyzed. Patients with T cell-type infection had higher titers of immunoglobulin G against early and late EBV antigens, suggesting lytic cycle infection. However, the pattern of EBV gene expression was latency type II; BZLF1, which is a hallmark of lytic cycle infection, could not be detected in any patients, regardless of infection type. Patients with CAEBV infection had high concentrations of proinflammatory, T helper cell type 1, and anti-inflammatory cytokines. The cytokine profile in patients with NK cell-type infection was similar to that in patients with T cell-type infection, but the concentration of IL-13 was high in patients with NK cell-type infection. These findings should help to clarify the pathogenesis of CAEBV infection and facilitate the development of more-effective treatments.

  14. Loss of proliferation and antigen presentation activity following internalization of polydispersed carbon nanotubes by primary lung epithelial cells.

    Directory of Open Access Journals (Sweden)

    Mandavi Kumari

    Full Text Available 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.

  15. Rabbit heart cell culture, strain RHF-1. II. Behavior of adenovirus types 1 to 4.

    Science.gov (United States)

    ANKUDAS, M M; KHOOBYARIAN, N

    1962-12-01

    Ankudas, Milda M. (University of Illinois, Chicago) and Newton Khoobyarian. Rabbit heart cell cultures, strain RHF-1. II. Behavior of adenovirus types 1 to 4. J. Bacteriol. 84:1287-1291. 1962.-In general, the findings indicate that adsorption to RHF-1 cells of adenovirus types 1, 2, and 4, but not type 3, precedes the events leading toward virus multiplication. Adenovirus type 3 attained maximal adsorption (90%) in 2 hr, with no evidence of virus multiplication. Under optimal conditions in the present experiments, the type 1 virus appeared to be released from the infected cells at a much slower rate than types 2 and 4. No correlation seemed to exist between the extent of cytopathic changes produced by type 1 in RHF-1 cells and the rise in virus infectivity during the logarithmic phase. On the other hand, the progression of cytopathic effect of type 2- and type 4-infected cells appeared to be a direct result of virus propagation. Further-more, the relative yield of virus per host cell, though small in quantity, was more or less similar for all three types. Histopathologically, no marked difference among the cells infected with types 1, 2, and 4 was clearly evident. Upon serial subculturing of these viruses in RHF-1 cells, a concomitant decrease in infectious virus, as well as complement-fixing antigen titers at each passage level, was also noted.

  16. Efficient Presentation of Multiple Endogenous Epitopes to Both CD4+ and CD8+ Diabetogenic T Cells for Tolerance

    Directory of Open Access Journals (Sweden)

    Shamael R. Dastagir

    2017-03-01

    Full Text Available Antigen-specific immunotherapy of type 1 diabetes, typically via delivery of a single native β cell antigen, has had little clinical benefit to date. With increasing evidence that diabetogenic T cells react against multiple β cell antigens, including previously unappreciated neo-antigens that can be emulated by mimotopes, a shift from protein- to epitope-based therapy is warranted. To this end, we aimed to achieve efficient co-presentation of multiple major epitopes targeting both CD4+ and CD8+ diabetogenic T cells. We have compared native epitopes versus mimotopes as well as various targeting signals in an effort to optimize recognition by both types of T cells in vitro. Optimal engagement of all T cells was achieved with segregation of CD8 and CD4 epitopes, the latter containing mimotopes and driven by endosome-targeting signals, after delivery into either dendritic or stromal cells. The CD4+ T cell responses elicited by the endogenously delivered epitopes were comparable with high concentrations of soluble peptide and included functional regulatory T cells. This work has important implications for the improvement of antigen-specific therapies using an epitope-based approach to restore tolerance in type 1 diabetes and in a variety of other diseases requiring concomitant targeting of CD4+ and CD8+ T cells.

  17. Efficient Presentation of Multiple Endogenous Epitopes to Both CD4(+) and CD8(+) Diabetogenic T Cells for Tolerance.

    Science.gov (United States)

    Dastagir, Shamael R; Postigo-Fernandez, Jorge; Xu, Chunliang; Stoeckle, James H; Firdessa-Fite, Rebuma; Creusot, Rémi J

    2017-03-17

    Antigen-specific immunotherapy of type 1 diabetes, typically via delivery of a single native β cell antigen, has had little clinical benefit to date. With increasing evidence that diabetogenic T cells react against multiple β cell antigens, including previously unappreciated neo-antigens that can be emulated by mimotopes, a shift from protein- to epitope-based therapy is warranted. To this end, we aimed to achieve efficient co-presentation of multiple major epitopes targeting both CD4(+) and CD8(+) diabetogenic T cells. We have compared native epitopes versus mimotopes as well as various targeting signals in an effort to optimize recognition by both types of T cells in vitro. Optimal engagement of all T cells was achieved with segregation of CD8 and CD4 epitopes, the latter containing mimotopes and driven by endosome-targeting signals, after delivery into either dendritic or stromal cells. The CD4(+) T cell responses elicited by the endogenously delivered epitopes were comparable with high concentrations of soluble peptide and included functional regulatory T cells. This work has important implications for the improvement of antigen-specific therapies using an epitope-based approach to restore tolerance in type 1 diabetes and in a variety of other diseases requiring concomitant targeting of CD4(+) and CD8(+) T cells.

  18. Homologous Type of Malignant Mixed Mullerian Tumor of the Uterus Presenting as a Cervical Mass

    Directory of Open Access Journals (Sweden)

    Umur Kuyumcuoğlu

    2009-10-01

    Full Text Available Malignant mixed Mullerian tumors are composed of a mixture of sarcoma and carcinoma. The carcinomatous element is usually glandular, whereas the sarcomatous element may resemble normal endometrial stroma (homologous or so-called carcinosarcoma. Here, we present a homologous type of malignant mixed Mullerian tumor of the uterus that presented as a cervical mass. We describe a 55-year-old patient who had a cervical mass arising from the uterus. We performed total abdominal hysterectomy and bilateral salpingo-oophorectomy and surgical staging (including (peritoneal washings, suspicious areas or peritoneal surfaces sampled, infracolic omental sampling, pelvic and paraaortic lymph node sampling, and appendectomy. Carcinosarcomas of the uterine cervix are extremely rare, and when a post-menopausal woman with a cervical mass is admitted to the gynecology clinic, the physician should keep in mind that the mass might be a carcinosarcoma. [J Chin Med Assoc 2009;72(10:533–535

  19. Type 1 and type 2 diabetes in celiac disease: prevalence and effect on clinical and histological presentation.

    Science.gov (United States)

    Kylökäs, Antti; Kaukinen, Katri; Huhtala, Heini; Collin, Pekka; Mäki, Markku; Kurppa, Kalle

    2016-07-25

    Association between celiac disease and type 1 diabetes in adults is still somewhat unclear, and that between celiac disease and type 2 diabetes even less known. We studied these issues in a large cohort of adult celiac disease patients. The prevalence of type 1 and type 2 diabetes in 1358 celiac patients was compared with the population-based values. Furthermore, patients with celiac disease and concomitant type 1 or type 2 diabetes and those with celiac disease only underwent comparisons of clinical and histological features and adherence to gluten-free diet. The prevalence of type 1 diabetes (men/women) was 8.0 % /1.8 % in celiac patients and 0.7 % /0.3 % in the population, and that of type 2 diabetes 4.3 % /2.5 % and 4.4 % /3.0 %, respectively. Celiac patients with concomitant type 1 diabetes were younger (45 years vs 65 years and 52 years, P celiac patients with concomitant type 2 diabetes and patients with celiac disease only. Patients with concomitant type 2 diabetes had more hypercholesterolemia than the other groups (8 % vs 6 % and 4 %, P = 0.024), and both diabetes groups more hypertension (47 % and 31 % vs 15 %, P celiac disease only. Type 1 diabetes was markedly overrepresented in celiac disease, especially in men, whereas the prevalence of type 2 diabetes was comparable with the population. Concomitant type 1 or type 2 diabetes predisposes celiac patients to severe co-morbidities and type 1 diabetes also to poor dietary adherence.

  20. Collagen type I and type V are present in the same fibril in the avian corneal stroma

    OpenAIRE

    1988-01-01

    The distribution, supramolecular form, and arrangement of collagen types I and V in the chicken embryo corneal stroma were studied using electron microscopy, collagen type-specific monoclonal antibodies, and a preembedding immunogold method. Double-label immunoelectron microscopy with colloidal gold-tagged monoclonal antibodies was used to simultaneously localize collagen type I and type V within the chick corneal stroma. The results definitively demonstrate, for the first time, that both col...

  1. Collagen type I and type V are present in the same fibril in the avian corneal stroma.

    Science.gov (United States)

    Birk, D E; Fitch, J M; Babiarz, J P; Linsenmayer, T F

    1988-03-01

    The distribution, supramolecular form, and arrangement of collagen types I and V in the chicken embryo corneal stroma were studied using electron microscopy, collagen type-specific monoclonal antibodies, and a preembedding immunogold method. Double-label immunoelectron microscopy with colloidal gold-tagged monoclonal antibodies was used to simultaneously localize collagen type I and type V within the chick corneal stroma. The results definitively demonstrate, for the first time, that both collagens are codistributed within the same fibril. Type I collagen was localized to striated fibrils throughout the corneal stroma homogeneously. Type V collagen could be localized only after pretreatment of the tissue to partially disrupt collagen fibril structure. After such pretreatments the type V collagen was found in regions where fibrils were partially dissociated and not in regions where fibril structure was intact. When pretreated tissues were double labeled with antibodies against types I and V collagen coupled to different size gold particles, the two collagens colocalized in areas where fibril structure was partially disrupted. Antibodies against type IV collagen were used as a control and were nonreactive with fibrils. These results indicate that collagen types I and V are assembled together within single fibrils in the corneal stroma such that the interaction of these collagen types within heterotypic fibrils masks the epitopes on the type V collagen molecule. One consequence of the formation of such heterotypic fibrils may be the regulation of corneal fibril diameter, a condition essential for corneal transparency.

  2. Characterization of cloned cells from an immortalized fetal pulmonary type II cell line

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, R.F.; Waide, J.J.; Lechner, J.F.

    1995-12-01

    A cultured cell line that maintained expression of pulmonary type II cell markers of differentiation would be advantageous to generate a large number of homogenous cells in which to study the biochemical functions of type II cells. Type II epithelial cells are the source of pulmonary surfactant and a cell of origin for pulmonary adenomas. Last year our laboratory reported the induction of expression of two phenotypic markers of pulmonary type II cells (alkaline phosphatase activity and surfactant lipid synthesis) in cultured fetal rat lung epithelial (FRLE) cells, a spontaneously immortalized cell line of fetal rat lung type II cell origin. Subsequently, the induction of the ability to synthesize surfactant lipid became difficult to repeat. We hypothesized that the cell line was heterogenuous and some cells were more like type II cells than others. The purpose of this study was to test this hypothesis and to obtain a cultured cell line with type II cell phenotypic markers by cloning several FRLE cells and characterizing them for phenotypic markers of type II cells (alkaline phosphatase activity and presence of surfactant lipids). Thirty cloned cell lines were analyzed for induced alkaline phosphatase activity (on x-axis) and for percent of phospholipids that were disaturated (i.e., surfactant).

  3. 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.

  4. Development of the Nanobody display technology to target lentiviral vectors to antigen-presenting cells.

    Science.gov (United States)

    Goyvaerts, C; De Groeve, K; Dingemans, J; Van Lint, S; Robays, L; Heirman, C; Reiser, J; Zhang, X-Y; Thielemans, K; De Baetselier, P; Raes, G; Breckpot, K

    2012-12-01

    Lentiviral vectors (LVs) provide unique opportunities for the development of immunotherapeutic strategies, as they transduce a variety of cells in situ, including antigen-presenting cells (APCs). Engineering LVs to specifically transduce APCs is required to promote their translation towards the clinic. We report on the Nanobody (Nb) display technology to target LVs to dendritic cells (DCs) and macrophages. This innovative approach exploits the budding mechanism of LVs to incorporate an APC-specific Nb and a binding-defective, fusion-competent form of VSV.G in the viral envelope. In addition to production of high titer LVs, we demonstrated selective, Nb-dependent transduction of mouse DCs and macrophages both in vitro and in situ. Moreover, this strategy was translated to a human model in which selective transduction of in vitro generated or lymph node (LN)-derived DCs and macrophages, was demonstrated. In conclusion, the Nb display technology is an attractive approach to generate LVs targeted to specific cell types.

  5. Improved transfection of spleen-derived antigen-presenting cells in culture using TATp-liposomes.

    Science.gov (United States)

    Pappalardo, Juan Sebastián; Quattrocchi, Valeria; Langellotti, Cecilia; Di Giacomo, Sebastián; Gnazzo, Victoria; Olivera, Valeria; Calamante, Gabriela; Zamorano, Patricia I; Levchenko, Tatyana S; Torchilin, Vladimir P

    2009-02-20

    Antigen presenting cells (APC) are among the most important cells of the immune system since they link the innate and the adaptative immune responses, directing the type of immune response to be elicited. To modulate the immune response in immune preventing or treating therapies, gene delivery into immunocompetent cells could be used. However, APC are very resistant to transfection. To increase the efficiency of APC transfection, we have used liposome-based lipoplexes additionally modified with cell-penetrating TAT peptide (TATp) for better intracellular delivery of a model plasmid encoding for the enhanced-green fluorescent protein (pEGFP). pEGFP-bearing lipoplexes made of a mixture of PC:Chol:DOTAP (60:30:10 molar ratio) with the addition of 2% mol of polyethylene glycol-phosphatidylethanolamine (PEG-PE) conjugate (plain-L) or TATp-PEG-PE (TATp-L) were shown to effectively protect the incorporated DNA from degradation. Uptake assays of rhodamine-labeled lipoplexes and transfections with the EGFP reporter gene were performed with APC derived from the mouse spleen. TATp-L-based lipoplexes allowed for significantly enhanced both, the uptake and transfection in APC. Such a tool could be used for the APC transfection as a first step in immune therapy.

  6. Particle shape dependence of CD8+ T cell activation by artificial antigen presenting cells.

    Science.gov (United States)

    Sunshine, Joel C; Perica, Karlo; Schneck, Jonathan P; Green, Jordan J

    2014-01-01

    Previous work developing particle-based acellular, artificial antigen presenting cells (aAPCs) has focused exclusively on spherical platforms. To explore the role of shape, we generated ellipsoidal PLGA microparticles with varying aspect ratios (ARs) and synthesized aAPCs from them. The ellipsoidal biomimetic aAPCs with high-AR showed significantly enhanced in vitro and in vivo activity above spherical aAPCs with particle volume and antigen content held constant. Confocal imaging indicates that CD8+ T cells preferentially migrate to and are activated by interaction with the long axis of the aAPC. Importantly, enhanced activity of high-AR aAPCs was seen in a mouse melanoma model, with high-AR aAPCs improving melanoma survival compared to non-cognate aAPCs (p = 0.004) and cognate spherical aAPCs (p = 0.05). These findings indicate that particle geometry is a critical design criterion in the generation of aAPCs, and may offer insight into the essential role of geometry in the interaction between CD8+ T cells and biological APCs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Uptake and presentation of myelin basic protein by normal human b cells

    DEFF Research Database (Denmark)

    Brimnes, Marie Klinge; Hansen, Bjarke Endel; Nielsen, Leif Kofoed

    2014-01-01

    B cells may play both pathogenic and protective roles in T-cell mediated autoimmune diseases such as multiple sclerosis (MS). These functions relate to the ability of B cells to bind and present antigens. Under serum-free conditions we observed that 3-4% of circulating B cells from healthy donors...... were capable of binding the MS-associated self-antigen myelin basic protein (MBP) and of presenting the immunodominant peptide MBP85-99, as determined by staining with the mAb MK16 recognising the peptide presented by HLA-DR15-positive cells. In the presence of serum, however, the majority of B cells....... The mechanisms described here refute the general assumption that B-cell presentation of self-antigens requires uptake via specific B-cell receptors, and may be important for maintenance of tolerance as well as for driving T-cell responses in autoimmune diseases....

  8. 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

  9. Low numbers of FOXP3 positive regulatory T cells are present in all developmental stages of human atherosclerotic lesions.

    Directory of Open Access Journals (Sweden)

    Onno J de Boer

    Full Text Available BACKGROUND: T cell mediated inflammation contributes to atherogenesis and the onset of acute cardiovascular disease. Effector T cell functions are under a tight control of a specialized T cell subset, regulatory T cells (Treg. At present, nothing is known about the in situ presence of Treg in human atherosclerotic tissue. In the present study we investigated the frequency of naturally occurring Treg cells in all developmental stages of human atherosclerotic lesions including complicated thrombosed plaques. METHODOLOGY: Normal arteries, early lesions (American Heart Association classification types I, II, and III, fibrosclerotic plaques (types Vb and Vc and 'high risk' plaques (types IV, Va and VI were obtained at surgery and autopsy. Serial sections were immunostained for markers specific for regulatory T cells (FOXP3 and GITR and the frequency of these cells was expressed as a percentage of the total numbers of CD3+ T cells. Results were compared with Treg counts in biopsies of normal and inflammatory skin lesions (psoriasis, spongiotic dermatitis and lichen planus. PRINCIPLE FINDINGS: In normal vessel fragments T cells were virtually absent. Treg were present in the intima during all stages of plaque development (0.5-5%. Also in the adventitia of atherosclerotic vessels Treg were encountered, in similar low amounts. High risk lesions contained significantly increased numbers of Treg compared to early lesions (mean: 3.9 and 1.2%, respectively. The frequency of FOXP3+ cells in high risk lesions was also higher compared to stable lesions (1.7%, but this difference was not significant. The mean numbers of intimal FOXP3 positive cells in atherosclerotic lesions (2.4% was much lower than those in normal (24.3% or inflammatory skin lesions (28%. CONCLUSION: Low frequencies of Treg in all developmental stages of human plaque formation could explain the smoldering chronic inflammatory process that takes place throughout the longstanding course of

  10. Artificial human antigen-presenting cells are superior to dendritic cells at inducing cytotoxic T-cell responses.

    Science.gov (United States)

    Li, Hua; Shao, Shengwen; Cai, Jianshu; Burner, Danielle; Lu, Lingeng; Chen, Qiuqiang; Minev, Boris; Ma, Wenxue

    2017-11-01

    Peptide recognition through the MHC class I molecule by cytotoxic T lymphocytes (CTLs) leads to the killing of cancer cells. A potential challenge for T-cell immunotherapy is that dendritic cells (DCs) are exposed to the MHC class I-peptide complex for an insufficient amount of time. To improve tumour antigen presentation to T cells and thereby initiate a more effective T-cell response, we generated artificial antigen-presenting cells (aAPCs) by incubating human immature DCs (imDCs) with poly(lactic-co-glycolic) acid nanoparticles (PLGA-NPs) encapsulating tumour antigenic peptides, followed by maturation with lipopolysaccharide. Tumour antigen-specific CTLs were then induced using either peptide-loaded mature DCs (mDCs) or aAPCs, and their activities were analysed using both ELISpot and cytotoxicity assays. We found that the aAPCs induced significantly stronger tumour antigen-specific CTL responses than the controls, which included both mDCs and aAPCs loaded with empty nanoparticles. Moreover, frozen CTLs that were generated by exposure to aAPCs retained the capability to eradicate HLA-A2-positive tumour antigen-bearing cancer cells. These results indicated that aAPCs are superior to DCs when inducing the CTL response because the former are capable of continuously presenting tumour antigens to T cells in a sustained manner. The development of aAPCs with PLGA-NPs encapsulating tumour antigenic peptides is a promising approach for the generation of effective CTL responses in vitro and warrants further assessments in clinical trials. © 2017 John Wiley & Sons Ltd.

  11. Target cell cyclophilins facilitate human papillomavirus type 16 infection.

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    Malgorzata Bienkowska-Haba

    2009-07-01

    Full Text Available Following attachment to primary receptor heparan sulfate proteoglycans (HSPG, human papillomavirus type 16 (HPV16 particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV-induced diseases.

  12. Chronic lymphocytic lymphoma and concomitant renal cell carcinoma (Clear Cell Type: Review of the literature

    Directory of Open Access Journals (Sweden)

    Burak Uz

    2016-01-01

    Full Text Available In the present report, a 73 years-old male patient who developed clear cell type renal cell carcinoma (RCC 5 years after the diagnosis of chronic lymphocytic lymphoma (CLL and plausible explanations for this association were discussed by the authors. The incidence of CLL and RCC occurring in the same patient is higher than that expected in the general population. Various explicative hypotheses of this concurrence include treatment-related development of a second malignancy, immunomodulatory mechanisms, viral aetiology, cytokine (interleukin 6 release from a tumor, and common genetic mutations. Further investigations are warranted.

  13. Genome-Derived Cytosolic DNA Mediates Type I Interferon-Dependent Rejection of B Cell Lymphoma Cells

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    Yu J. Shen

    2015-04-01

    Full Text Available The DNA damage response (DDR induces the expression of type I interferons (IFNs, but the underlying mechanisms are poorly understood. Here, we show the presence of cytosolic DNA in different mouse and human tumor cells. Treatment of cells with genotoxic agents increased the levels of cytosolic DNA in a DDR-dependent manner. Cloning of cytosolic DNA molecules from mouse lymphoma cells suggests that cytosolic DNA is derived from unique genomic loci and has the potential to form non-B DNA structures, including R-loops. Overexpression of Rnaseh1, which resolves R-loops, reduced the levels of cytosolic DNA, type I Ifn transcripts, and type I IFN-dependent rejection of lymphoma cells. Live-cell imaging showed a dynamic contact of cytosolic DNA with mitochondria, an important organelle for innate immune recognition of cytosolic nucleotides. In summary, we found that cytosolic DNA is present in many tumor cells and contributes to the immunogenicity of tumor cells.

  14. Lupus erythematosus, thyroiditis, alopecia areata and vitiligo – A multiple autoimmune syndrome type 3 case presentation

    Directory of Open Access Journals (Sweden)

    Alin Laurentiu Tatu

    2017-04-01

    Full Text Available The combination of at least three autoimmune diseases in the same patient has defined as multiple autoimmune syndrome (MAS. Abnormalities of T cell-mediated immunity and humoral immunity have been described previously in the literature. Aims of work were to investigate the 22 years old patient with lupus erythematosus for three years and autoimune thyroiditis for one year, regardind other possible autoimmune conditions and to establish a treatment to control the diseases. The clinical exam revealed some circular hairless patches on the beard appeared about three months ago and white depigmented disseminated areas started one month ago and the laboratory investigations were performed. The modified laboratory findings were total IgE 530 UI/mL, Anti-SSA (anti-RO antibodies> 200 IU/mL, SSB negative, Antinuclear antibodies (ANA positive and fine speckled, Lupus anticoagulant testing positive, Anti-thyroid peroxidase antibodies 951 UI/ml, TSH 4,7 µUI/mL. The diagnosis of multiple autoimmune syndrome(MAS type 3 including Lupus erythematosus, autoimune Thyroiditis, Alopecia Areata and Vitiligo was established. Endocrine autoimmunities are associated with autoantibodies that react to specific antigens, whereas patients with collagen diseases synthesize immunoglobulins that recognize nonorgan-specific cellular targets, such as nucleoproteins and nucleic acids. Cellular autoimmunity is important in the pathogenesis MAS. The existence of one autoimmune disorder helps lead to the discovery of other autoimmune conditions.

  15. Epidemiology and clinical presentation of the four human parainfluenza virus types

    Directory of Open Access Journals (Sweden)

    Liu Wen-Kuan

    2013-01-01

    Full Text Available Abstract Background Human parainfluenza viruses (HPIVs are important causes of upper respiratory tract illness (URTI and lower respiratory tract illness (LRTI. To analyse epidemiologic and clinical characteristics of the four types of human parainfluenza viruses (HPIVs, patients with acute respiratory tract illness (ARTI were studied in Guangzhou, southern China. Methods Throat swabs (n=4755 were collected and tested from children and adults with ARTI over a 26-month period, and 4447 of 4755 (93.5% patients’ clinical presentations were recorded for further analysis. Results Of 4755 patients tested, 178 (3.7% were positive for HPIV. Ninety-nine (2.1% samples were positive for HPIV-3, 58 (1.2% for HPIV-1, 19 (0.4% for HPIV-2 and 8 (0.2% for HPIV-4. 160/178 (88.9% HPIV-positive samples were from paediatric patients younger than 5 years old, but no infant under one month of age was HPIV positive. Seasonal peaks of HPIV-3 and HPIV-1 occurred as autumn turned to winter and summer turned to autumn. HPIV-2 and HPIV-4 were detected less frequently, and their frequency of isolation increased when the frequency of HPIV-3 and HPIV-1 declined. HPIV infection led to a wide spectrum of symptoms, and more “hoarseness” (p=0.015, “abnormal pulmonary breathing sound” (p Conclusions HPIV infection led to a wide spectrum of symptoms, and similar clinical manifestations were found in the patients with four different types of HPIVs. The study suggested pathogenic activity of HPIV in gastrointestinal illness. The clinical presentation of HPIV infection may differ by patient age.

  16. In Vitro-Generated Tc17 Cells Present a Memory Phenotype and Serve As a Reservoir of Tc1 Cells In Vivo

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    Felipe Flores-Santibáñez

    2018-02-01

    Full Text Available Memory CD8+ T cells are ideal candidates for cancer immunotherapy because they can mediate long-term protection against tumors. However, the therapeutic potential of different in vitro-generated CD8+ T cell effector subsets to persist and become memory cells has not been fully characterized. Type 1 CD8+ T (Tc1 cells produce interferon-γ and are endowed with high cytotoxic capacity, whereas IL-17-producing CD8+ T (Tc17 cells are less cytotoxic but display enhanced self-renewal capacity. We sought to evaluate the functional properties of in vitro-generated Tc17 cells and elucidate their potential to become long lasting memory cells. Our results show that in vitro-generated Tc17 cells display a greater in vivo persistence and expansion in response to secondary antigen stimulation compared to Tc1 cells. When transferred into recipient mice, Tc17 cells persist in secondary lymphoid organs, present a recirculation behavior consistent with central memory T cells, and can shift to a Tc1 phenotype. Accordingly, Tc17 cells are endowed with a higher mitochondrial spare respiratory capacity than Tc1 cells and express higher levels of memory-related molecules than Tc1 cells. Together, these results demonstrate that in vitro-generated Tc17 cells acquire a central memory program and provide a lasting reservoir of Tc1 cells in vivo, thus supporting the use of Tc17 lymphocytes in the design of novel and more effective therapies.

  17. Uptake and presentation of myelin basic protein by normal human B cells.

    Directory of Open Access Journals (Sweden)

    Marie Klinge Brimnes

    Full Text Available B cells may play both pathogenic and protective roles in T-cell mediated autoimmune diseases such as multiple sclerosis (MS. These functions relate to the ability of B cells to bind and present antigens. Under serum-free conditions we observed that 3-4% of circulating B cells from healthy donors were capable of binding the MS-associated self-antigen myelin basic protein (MBP and of presenting the immunodominant peptide MBP85-99, as determined by staining with the mAb MK16 recognising the peptide presented by HLA-DR15-positive cells. In the presence of serum, however, the majority of B cells bound MBP in a complement-dependent manner, and almost half of the B cells became engaged in presentation of MBP85-99. Even though complement receptor 1 (CR1, CD35 and CR2 (CD21 both contributed to binding of MBP to B cells, only CR2 was important for the subsequent presentation of MBP85-99. A high proportion of MBP85-99 presenting B cells expressed CD27, and showed increased expression of CD86 compared to non-presenting B cells. MBP-pulsed B cells induced a low frequency of IL-10-producing CD4+ T cells in 3 out of 6 donors, indicating an immunoregulatory role of B cells presenting MBP-derived peptides. The mechanisms described here refute the general assumption that B-cell presentation of self-antigens requires uptake via specific B-cell receptors, and may be important for maintenance of tolerance as well as for driving T-cell responses in autoimmune diseases.

  18. Microbleeds in atypical presentations of Alzheimer's disease: a comparison to dementia of the Alzheimer's type.

    Science.gov (United States)

    Whitwell, Jennifer L; Kantarci, Kejal; Weigand, Stephen D; Lundt, Emily S; Gunter, Jeffrey L; Duffy, Joseph R; Strand, Edythe A; Machulda, Mary M; Spychalla, Anthony J; Drubach, Daniel A; Petersen, Ronald C; Lowe, Val J; Jack, Clifford R; Josephs, Keith A

    2015-01-01

    Microbleeds in the brain have been shown to occur in Alzheimer's disease (AD), affecting approximately a third of subjects that present with typical dementia of the Alzheimer's type (DAT). However, little is known about the frequency or distribution of microbleeds in subjects with AD that present with atypical clinical presentations. To determine whether the frequency and regional distribution of microbleeds in atypical AD differs from that observed in subjects with DAT, and to determine whether microbleeds in atypical AD are associated with age, demographics, or cognitive impairment. Fifty-five subjects with amyloid-β deposition on Pittsburgh compound B (PiB) PET who presented with predominant language (n = 37) or visuospatial/perceptual (n = 18) deficits underwent T2*weighted MRI. These subjects were compared to 41 PiB-positive subjects with DAT. Microbleeds were identified and assigned a lobar location. The proportion of subjects with microbleeds did not differ between atypical AD (42%) and DAT (32%). However, atypical AD had larger numbers of microbleeds than DAT. In addition, the topographic distribution of microbleeds differed between atypical AD and DAT, with atypical AD showing the highest density of microbleeds in the frontal lobes. Among atypical AD, number of microbleeds was associated with age, but not gender or cognition. Microbleeds were more common in subjects with language (51%) versus visuospatial/perceptual deficits (22%). Microbleeds are relatively common in both DAT and atypical AD, although atypical AD subjects appear to be at particular risk for developing large numbers of microbleeds and for developing microbleeds in the frontal lobe.

  19. The Concerted Action of Type 2 and Type 3 Deiodinases Regulates the Cell Cycle and Survival of Basal Cell Carcinoma Cells.

    Science.gov (United States)

    Miro, Caterina; Ambrosio, Raffaele; De Stefano, Maria Angela; Di Girolamo, Daniela; Di Cicco, Emery; Cicatiello, Annunziata Gaetana; Mancino, Giuseppina; Porcelli, Tommaso; Raia, Maddalena; Del Vecchio, Luigi; Salvatore, Domenico; Dentice, Monica

    2017-04-01

    Thyroid hormones (THs) mediate pleiotropic cellular processes involved in metabolism, cellular proliferation, and differentiation. The intracellular hormonal environment can be tailored by the type 1 and 2 deiodinase enzymes D2 and D3, which catalyze TH activation and inactivation respectively. In many cellular systems, THs exert well-documented stimulatory or inhibitory effects on cell proliferation; however, the molecular mechanisms by which they control rates of cell cycle progression have not yet been entirely clarified. We previously showed that D3 depletion or TH treatment influences the proliferation and survival of basal cell carcinoma (BCC) cells. Surprisingly, we also found that BCC cells express not only sustained levels of D3 but also robust levels of D2. The aim of the present study was to dissect the contribution of D2 to TH metabolism in the BCC context, and to identify the molecular changes associated with cell proliferation and survival induced by TH and mediated by D2 and D3. We used the CRISPR/Cas9 technology to genetically deplete D2 and D3 in BCC cells and studied the consequences of depletion on cell cycle progression and on cell death. Cell cycle progression was analyzed by fluorescence activated cell sorting analysis of synchronized cells, and the apoptosis rate by annexin V incorporation. Mechanistic investigations revealed that D2 inactivation accelerates cell cycle progression thereby enhancing the proportion of S-phase cells and cyclin D1 expression. Conversely, D3 mutagenesis drastically suppressed cell proliferation and enhanced apoptosis of BCC cells. Furthermore, the basal apoptotic rate was oppositely regulated in D2- and D3-depleted cells. Our results indicate that BCC cells constitute an example in which the TH signal is finely tuned by the concerted expression of opposite-acting deiodinases. The dual regulation of D2 and D3 expression plays a critical role in cell cycle progression and cell death by influencing cyclin D1-mediated

  20. Efficient electroluminescent cooling with a light-emitting diode coupled to a photovoltaic cell (Conference Presentation)

    Science.gov (United States)

    Xiao, Tianyao P.; Chen, Kaifeng; Santhanam, Parthiban; Fan, Shanhui; Yablonovitch, Eli

    2017-02-01

    The new breakthrough in photovoltaics, exemplified by the slogan "A great solar cell has to be a great light-emitting diode (LED)", has led to all the major new solar cell records, while also leading to extraordinary LED efficiency. As an LED becomes very efficient in converting its electrical input into light, the device cools as it operates because the photons carry away entropy as well as energy. If these photons are absorbed in a photovoltaic (PV) cell, the generated electricity can be used to provide part of the electrical input that drives the LED. Indeed, the LED/PV cell combination forms a new type of heat engine with light as the working fluid. The electroluminescent refrigerator requires only a small amount of external electricity to provide cooling, leading to a high coefficient of performance. We present the theoretical performance of such a refrigerator, in which the cool side (LED) is radiatively coupled to the hot side (PV) across a vacuum gap. The coefficient of performance is maximized by using a highly luminescent material, such as GaAs, together with device structures that optimize extraction of the luminescence. We consider both a macroscopic vacuum gap and a sub-wavelength gap; the latter allows for evanescent coupling of photons between the devices, potentially providing a further enhancement to the efficiency of light extraction. Using device assumptions based on the current record-efficiency solar cells, we show that electroluminescent cooling can, in certain regimes of cooling power, achieve a higher coefficient of performance than thermoelectric cooling.

  1. Patients With Type A Acute Aortic Dissection Presenting With an Abnormal Electrocardiogram.

    Science.gov (United States)

    Costin, Nathaniel I; Korach, Amit; Loor, Gabriel; Peterson, Mark D; Desai, Nimesh D; Trimarchi, Santi; de Vincentiis, Carlo; Ota, Takeyoshi; Reece, T Brett; Sundt, Thoralf M; Patel, Himanshu J; Chen, Edward P; Montgomery, Dan G; Nienaber, Christoph A; Isselbacher, Eric M; Eagle, Kim A; Gleason, Thomas G

    2018-01-01

    The electrocardiogram (ECG) is often used in the diagnosis of patients presenting with chest pain to emergency departments. Because chest pain is a common manifestation of type A acute aortic dissection (TAAAD), ECGs are obtained in much of this population. We evaluated the effect of particular ECG patterns on the diagnosis and treatment of TAAAD. TAAAD patients (N = 2,765) enrolled in the International Registry of Acute Aortic Dissection were stratified based on normal (n = 1,094 [39.6%]) and abnormal (n = 1,671 [60.4%]) findings on presenting ECGs and further subdivided according to specific ECG findings. Time data are presented in hours as medians (quartile 1 to quartile 3). Patients with ECGs with abnormal findings presented to the hospital sooner after symptom onset than those with ECGs with normal findings (1.4 [0.8 to 3.3] vs 2.0 [1.0 to 3.3]; p = 0.005). Specifically, this was seen in patients with infarction with new Q waves or ST elevation (1.3 [0.6 to 2.7] vs 1.5 [0.8 to 3.3]; p = 0.049). Interestingly, the time between symptom onset and diagnosis was longer with infarction with old Q waves (6.7 [3.2 to 18.4] vs 5.0 [2.9 to 11.8]; p = 0.034) and nonspecific ST-T changes (5.8 [3.0 to 13.8] vs 4.5 [2.8 to 10.5]; p = 0.002). Surgical mortality was higher in patients with abnormal ECG findings (20.6% vs 11.9%, p < 0.001), especially in those with ischemia by ECG (25.7% vs 16.8%, p < 0.001) and infarction with new Q waves or ST elevation (30.1% vs 17.1%, p < 0.001). TAAAD patients presenting with abnormal ECG results are sicker, have more in-hospital complications, and are more likely to die. The frequency of nonspecific ST-T abnormalities and its association with delay in diagnosis and treatment presents an opportunity for practice improvement. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  2. Type VI collagen increases cell survival and prevents anti-beta 1 integrin-mediated apoptosis.

    Science.gov (United States)

    Howell, S J; Doane, K J

    1998-05-25

    Cell-matrix interactions are important in the development of the avian cornea. Type VI collagen is present within the periocular mesenchyme prior to the migration of cells into the corneal stroma and is abundant in the mature stroma. Whether the interaction of cells with type VI collagen is essential for cellular survival in the cornea is not known. In the present study, we examined the interaction of corneal cells with type VI collagen in vitro to determine if it can increase cell proliferation and decrease apoptosis. In vivo analysis demonstrated that apoptosis occurs in the periocular region during early stages of avian corneal development, but in fully mature corneas apoptosis only occurs in the corneal epithelium and not in the stroma. In vitro analysis examined the importance of beta 1 integrin interactions with type VI collagen in mature corneal fibroblasts and the precursor cells. Using an anti-beta 1 integrin blocking antibody, CSAT, integrin/matrix interactions were disrupted. Results indicated that viability of both corneal fibroblasts and periocular mesenchyme cells was greater on type VI collagen than on type I collagen or BSA-blocked glass. In addition, less apoptosis was observed for both cell types on type VI collagen when beta 1 integrin--matrix interactions were disrupted. These data indicated that these cells require intact beta 1 interactions with type I collagen and with BSA-coated glass controls to remain viable. Thus, type VI collagen may play a role in the rescue of corneal cells from anti-beta 1 integrin-induced apoptosis by increasing cell survival, probably via a non-beta 1 integrin-dependent mechanism.

  3. Static balance in patients presenting diabetes mellitus type 2 with and without diabetic polyneuropathy.

    Science.gov (United States)

    Palma, Felipe H; Antigual, Diego U; Martínez, Sergio F; Monrroy, Manuel A; Gajardo, Rubén E

    2013-12-01

    To contrast the static balance in patients presenting diabetes mellitus type 2 (DM2) with and without polyneuropathy (DPN); and to correlate the rates from the scale Diabetic Neuropathy Examination (DNE) with the mean ratio of the center of pressure (CoP). Twenty patients, aged between 40 and 54, presenting DM2 and classified, according to DNE scale, in groups with (n = 10) and without (n = 10) DPN, were compared. Static balance was evaluated by means of the CoP mean ratio on a Wii Balance Board® under the conditions of open and closed eyes. After normality verification (Shapiro-Wilk), balance between both groups was compared by means of the Student t test and Mann-Whitney U test, as applicable. DNE rating was correlated with the mean ratio of CoP in the group with DPN, considering a significance level p static balance than patients without DPN in the closed eyes condition. Furthermore, the higher the rating in DNE, the stronger the displacement of CoP, which may be associated with higher risk of falls.

  4. Fibulin-2 is present in murine vascular lesions and is important for smooth muscle cell migration

    DEFF Research Database (Denmark)

    Ström, A.; Olin, A. I.; Aspberg, A.

    2006-01-01

    Objective: The vascular extracellular matrix (ECM) can affect smooth muscle cell (SMC) adhesion, migration and proliferation-events that are important during the atherosclerotic process. Fibulin-2 is a member of the ECM protein family of fibulins and has been found to cross-link versican/hyaluron......Objective: The vascular extracellular matrix (ECM) can affect smooth muscle cell (SMC) adhesion, migration and proliferation-events that are important during the atherosclerotic process. Fibulin-2 is a member of the ECM protein family of fibulins and has been found to cross-link versican...... migration was studied in the presence of two inhibiting peptides (FN III 3-5 and aggrecan C-type lectin-like domain). Results: Fibulin-2 is expressed in SMC rich regions of atherosclerotic lesions where it colocalises with versican and hyaluronan. It is also present in injury-induced vascular lesions...... and is upregulated during SMC phenotypic modulation in cell culture. Moreover, treatments with peptides that block the interaction between versican and fibulin-2 inhibit SMC migration in vitro. Conclusions: Fibulin-2 can be produced by SMC as a response to injury and may participate in the ECM organisation...

  5. T-cell dysfunction in HIV infection: anergy due to defective antigen-presenting cell function?

    NARCIS (Netherlands)

    Meyaard, L.; Schuitemaker, H.; Miedema, F.

    1993-01-01

    Before CD4+ T cells are depleted, T cells in asymptomatic HIV-infected individuals are functionally abnormal. These T cells are programmed for death, are non-responsive and fail to produce interleukin-2 after antigenic stimulation. Our view is that these different T-cell abnormalities are explained

  6. 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.

  7. Performance of mid infrared spectroscopy in skin cancer cell type identification

    Science.gov (United States)

    Kastl, Lena; Kemper, Björn; Lloyd, Gavin R.; Nallala, Jayakrupakar; Stone, Nick; Naranjo, Valery; Penaranda, Francisco; Schnekenburger, Jürgen

    2017-02-01

    Marker free optical spectroscopy is a powerful tool for the rapid inspection of pathologically suspicious skin lesions and the non-invasive detection of early skin tumors. This goal can be reached by the combination of signal localization and the spectroscopical detection of chemical cell signatures. We here present the development and application of mid infrared spectroscopy (midIR) for the analysis of skin tumor cell types and three dimensional tissue phantoms towards the application of midIR spectroscopy for fast and reliable skin diagnostics. We developed standardized in vitro skin systems with increasing complexity, from single skin cell types as fibroblasts, keratinocytes and melanoma cells, to mixtures of these and finally three dimensional skin cancer phantoms. The cell systems were characterized with different systems in the midIR range up to 12 μm. The analysis of the spectra by novel data processing algorithms demonstrated the clear separation of all cell types, especially melanoma cells. Special attention and algorithm training was required for closely related mesenchymal cell types as dedifferentiated melanoma cells and fibroblasts. Proof of concept experiments with mixtures of in vivo fluorescence labelled skin cell types allowed the test of the new algorithms performance for the identification of specific cell types. The intense training of the software systems with various samples resulted in a increased sensitivity and specificity of the combined midIR and software system. These data highlight the potential of midIR spectroscopy as sensitive and specific future optical biopsy technology.

  8. Defect internalization and tyrosine kinase activation in Aire deficient antigen presenting cells exposed to Candida albicans antigens.

    Science.gov (United States)

    Brännström, Johan; Hässler, Signe; Peltonen, Leena; Herrmann, Björn; Winqvist, Ola

    2006-12-01

    Patients with Autoimmune polyendocrine syndrome type I (APS I) present with multiple endocrine failures due to organ-specific autoimmune disease, thought to be T-cell-mediated. Paradoxically, APS I patients suffer from chronic mucocutaneous candidiasis. The mutated gene has been identified as the Autoimmune regulator (AIRE). Aire is expressed in medullary epithelial cells of the thymus and in antigen presenting cells in the periphery. T cells from Aire deficient mice and men displayed an enhanced proliferative response against Candida antigen in vitro, suggesting that Aire deficient T cells are competent in recognizing Candida albicans. In contrast, monocytes from APS I patients displayed a decreased and delayed internalization of zymosan. Furthermore, Candida antigen activated monocytes from APS I patients show decreased and altered phoshotyrosine kinase activation. In conclusion, Aire deficient APCs have a defect receptor mediated internalization of Candida which affects kinase activation, likely altering the innate Candida immune response.

  9. Adult type granulosa cell tumor - morphological features

    OpenAIRE

    Ioana Buda; Raluca Balan; Crauciuc Eduard; Ovidiu Toma

    2008-01-01

    Adult granulosa cell tumors (AGCT) account for approximately 1-2% of all ovarian tumors and 95% of all GCT. They occur more often in postmenopausal women, with a peak incidence between 50 and 55 years. Nine cases of AGCT were diagnosed in the Clinical Hospital of Obstetrics and Gynecology Iasi, in a 10 years period. The age of the patients ranged between 35 and 67 years, 4 of them (44.44%) being postmenopausal. The macroscopical appearance showed that all were unilateral tumors – ...

  10. Two types of galactosylated fucose motifs are present on N-glycans of Haemonchus contortus.

    Science.gov (United States)

    Paschinger, Katharina; Wilson, Iain B H

    2015-06-01

    N-Glycans from the nematode Haemonchus contortus (barber pole worm), a parasite of sheep and cattle, were the first to be described to possess up to three fucose residues associated with the N,N'-diacetylchitobiosyl core, two being on the reducing-terminal proximal GlcNAc and one on the distal core GlcNAc residue. The assumption was that truncated glycans from this organism with three hexose residues have the composition Man3GlcNAc2Fuc1-3. In this study, we have performed HPLC and MALDI-TOF MS/MS in combination with selected digestions of N-glycans from Haemonchus. A dominant trifucosylated Hex3HexNAc2Fuc3 glycan was modified not only with α1,6-fucose but also with a proximal core α1,3-fucose and a galactosylated distal α1,3-fucose; thereby, only two of the hexose residues were mannose. Other N-glycans displayed galactosylation of the core α1,6-fucose, antennal fucosylation or modification with phosphorylcholine. Thus, the N-glycans of Haemonchus contain a number of potentially immunogenic glycan epitopes also found in other parasites and our proposed structures are in line with the previously defined specificity of nematode glycosyltransferases as we show that distal fucosylation and the presence of an α1,6-mannose are apparently mutually exclusive. These data are thereby of importance for engineering cell lines capable of mimicking Haemonchus-type N-glycans in the preparation of recombinant proteins as vaccine candidates. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Femtosecond laser writing of new type of waveguides in silver containing glasses (Conference Presentation)

    Science.gov (United States)

    Abou Khalil, Alain; Bérubé, Jean-Philippe; Danto, Sylvain; Desmoulin, Jean-Charles; Cardinal, Thierry; Petit, Yannick G.; Canioni, Lionel; Vallée, Réal

    2017-03-01

    Femtosecond laser writing in glasses is a growing field of research and development in photonics, since it provides a versatile, robust and efficient approach to directly address 3D material structuring. Laser-glass interaction process has been studied for many years, especially the local changes of the refractive index that have been classified by three distinct types (types I, II and III, respectively). These refractive index modifications are widely used for the creation of photonics devices such as waveguides [1], couplers, photonic crystals to fabricate integrated optical functions in glasses for photonic applications as optical circuits or integrated sensors. Femtosecond laser writing in a home-developed silver containing zinc phosphate glasses induces the creation of fluorescent silver clusters distributed around the laser-glass interaction voxel [2]. In this paper, we introduce a new type of refractive index modification in glasses. It is based on the creation of these photo-induced silver clusters allowing a local change in the refractive index Δn = 5×10-3, which is sufficient for the creation of waveguides and photonics devices. The wave guiding process in our glasses along these structures with original geometry is demonstrated for wavelengths from visible to NIR [3], giving a promising access to integrated optical circuits in these silver containing glasses. Moreover, the characterization of the waveguides is presented, including their original geometry, the refractive index change, the mode profile, the estimation of propagation losses and a comparison with simulation results. 1. K. M. Davis, K. Miura, N. Sugimoto, and K. Hirao, Opt. Lett. 21, 1729-1731 (1996). 2. M. Bellec, A. Royon, K. Bourhis, J. Choi, B. Bousquet, M. Treguer, T. Cardinal, J.-J. Videau, M. Richardson, and L. Canioni, The Journal of Physical Chemistry C 114, 15584-15588 (2010). 3. S. Danto, F. Désévédavy, Y. Petit, J.-C. Desmoulin, A. Abou Khalil, C. Strutynski, M. Dussauze, F

  12. TYPE IC CHOLEDOCHAL CYST PRESENTING AN EXTRAHEPATAL CHOLESTASIS IN A 3 YEAR OLD BOY

    Directory of Open Access Journals (Sweden)

    Muhammad Reza

    2015-10-01

    Full Text Available Choledochal cyst is a rare congenital dilatation of the bile ducts, mostly diagnosed in childhood. Whenappropriate resection is not performed, cholangiocarcinoma may occur in a high incidence within thesecond decade of life. This report aims to present a rare case in experience of diagnosis and managementtype IC choledochal cyst in children. We present case of a 3-year-old boy who came with jaundice anditchy skin, abdominal pain, brownish urine, pales colored of stool. Abdominal ultrasonography andcomputed tomography scan revealed type IC choledochal cyst. Patient underwent complete cyst removalsurgery and bilioenteric anastomosis through Roux-en-y hepaticojejunostomy. Excision biopsy confirmedthe diagnosis of type IC choledochal cyst. Post surgical follow up shown good physical and laboratorycondition  and  there was no  recurrence  of  symptoms. Early  surgical  procedure  through Roux-en-yhepatojejunostomy, has been performed. Long  term  follow up also  facilities good prognostic  to  thepatient. [MEDICINA 2015;46:56-60].Kista  koledokus  adalah merupakan  penyakit  saluran  empedu  bawaan  yang  jarang  dijumpai  danbanyak terdiagnosis pada saat usia anak-anak. Tindakan berupa reseksi kista adalah yang terpentingdilakukan,  jika  tidak  segera  dilakukan  maka  dapat  meningkatkan  resiko  terjadinyacholangiocarcinoma dalam usia dekade kedua penderita dalam kehidupan. Tujuan kasus ini dilaporkanuntuk menggambarkan pengalaman dalam mendiagnosis dan tata  laksana kista koledokal tipe ICyang jarang pada anak-anak. Laporan kasus ini pada anak laki-laki berumur 3 tahun dengan keluhankulit tampak kuning dan gatal, nyeri perut, urin berwarna kecoklatan, tinja yang pucat. Ultrasonografidan CT  scan abdomen memperlihatkan adanya kista koledokus. Tindakan bedah  eksisi kista dananastomosis bilioenterik dengan menggunakan tehnik hepatojejunostomi Roux-en-y. Diagnosa kistakoledokus  tipe  IC  terkonfirmasi  saat

  13. Cell type-dependent localization of MLO proteins.

    Science.gov (United States)

    Jones, Daniel S; Kessler, Sharon A

    2017-11-02

    Mildew resistance locus O (MLO) proteins are transmembrane proteins that mediate cell-cell communication in plants. We recently demonstrated the importance of subcellular localization to MLO function during pollen tube reception. NORTIA (NTA), the MLO protein involved in this process, localizes to the Golgi of the synergid cell before interaction with the pollen tube. MLO proteins that can substitute for NTA's function in this pathway all partially localize with the same Golgi marker in the synergid cell. In this study, we report that MLO subcellular localization is cell type-dependent, with different distributions of some MLOs observed when ectopically expressed in the epidermal cells of tobacco and Arabidopsis compared to synergids. This dependency may be due to co-factors that influence MLO function within a given cell type, providing an intriguing new target for understanding MLO distribution and subsequent function in their respective processes.

  14. Germinal center B cells regulate their capability to present antigen by modulation of HLA-DO.

    Science.gov (United States)

    Glazier, Kim S; Hake, Sandra B; Tobin, Helen M; Chadburn, Amy; Schattner, Elaine J; Denzin, Lisa K

    2002-04-15

    Peptide acquisition by MHC class II molecules is catalyzed by HLA-DM (DM). In B cells, HLA-DO (DO) inhibits or modifies the peptide exchange activity of DM. We show here that DO protein levels are modulated during B cell differentiation. Remarkably, germinal center (GC) B cells, which have low levels of DO relative to naive and memory B cells, are shown to have enhanced antigen presentation capabilities. DM protein levels also were somewhat reduced in GC B cells; however, the ratio of DM to DO in GC B cells was substantially increased, resulting in more free DM in GC B cells. We conclude that modulation of DM and DO in distinct stages of B cell differentiation represents a mechanism by which B cells regulate their capacity to function as antigen-presenting cells. Efficient antigen presentation in GC B cells would promote GC B cell-T cell interactions that are essential for B cells to survive positive selection in the GC.

  15. Influence of Musculoskeletal Manifestations as the Only Presenting Symptom in B-Cell Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Kang, Seungcheol; Im, Ho Joon; Bae, Kunhyung; Park, Soo-Sung

    2017-03-01

    To evaluate the clinical and prognostic impact of musculoskeletal manifestations as the only initial presenting symptom in childhood acute lymphoblastic leukemia (ALL). We retrospectively reviewed 158 children with precursor B-cell type ALL who were followed up for >2 years. The patients were assigned to the groups musculoskeletal manifestations (n = 24) or nonmusculoskeletal manifestations (n = 134) based on initial presenting symptom. The symptom duration (regarding any initial presenting symptom) and the leukemic symptom duration (regarding symptoms of systemic manifestation, such as fever, bleeding, or pallor) were assessed, along with other clinical characteristics. The musculoskeletal manifestations group exhibited a longer symptom duration than the nonmusculoskeletal manifestations group (43 days vs 22 days, P = .006), but overall survival did not significantly differ between the groups. Multivariate analysis indicated that a longer symptom duration did not affect prognosis but that a longer leukemic symptom duration was associated with a poorer prognosis (hazard ratio, 7.720; P = .048). Musculoskeletal manifestations are associated significantly with diagnostic delay, but this delay does not affect the prognosis. Diagnostic delay after the onset of leukemic symptoms, however, does appear to affect the prognosis. Intensive evaluations for hematologic malignancies may be unnecessary in children who complain of limb pain without any definite cause, unless they also present with accompanying leukemic symptoms. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Defects in Antigen-Presenting Cells in the BB-DP Rat Model of Diabetes

    NARCIS (Netherlands)

    V. Sommandas (Vinod)

    2008-01-01

    textabstractType-1 diabetes is the result of a T cell mediated immune response against the insulin-producing β cells in the islet of Langerhans. In humans, until now, the disease is only clearly detectable at the onset of the disease. Therefore studies to identify initial factors involved in

  17. Type and Context of Alcohol-Related Injury among Patients Presenting to Emergency Departments in a Caribbean Country

    National Research Council Canada - National Science Library

    Sandra D Reid; Jannel Gentius

    2017-01-01

    .... Data on drinking patterns, injury type, drinking context prior to injury, and demographics were collected from patients presenting with injuries to the Emergency Departments (ED) of four hospitals...

  18. The pancreatic beta cells in human type 2 diabetes.

    Science.gov (United States)

    Marchetti, Piero; Bugliani, Marco; Boggi, Ugo; Masini, Matilde; Marselli, Lorella

    2012-01-01

    Bell-cell (beta-cell) impairment is central to the development and progression of human diabetes, as a result of the combined effects of genetic and acquired factors. Reduced islet number and/or reduced beta cells amount in the pancreas of individuals with Type 2 diabetes have been consistently reported. This is mainly due to increased beta cell death, not adequately compensated for by regeneration. In addition, several quantitative and/or qualitative defects of insulin secretion have been observed in Type 2 diabetes, both in vivo and ex vivo with isolated islets. All this is associated with modifications of islet cell gene and protein expression. With the identification of several susceptible Type 2 diabetes loci, the role of genotype in affecting beta-cell function and survival has been addressed in a few studies and the relationships between genotype and beta-cell phenotype investigated. Among acquired factors, the importance of metabolic insults (in particular glucotoxicity and lipotoxicity) in the natural history of beta-cell damage has been widely underlined. Continuous improvements in our knowledge of the beta cells in human Type 2 diabetes will lead to more targeted and effective strategies for the prevention and treatment of the disease.

  19. Ovarian Small Cell Carcinoma Hypercalcemic Type: A Case Report

    LENUS (Irish Health Repository)

    Rahma, M B.

    2016-09-01

    A 31-year-old female was diagnosed with small cell carcinoma of the ovary hypercalcaemic type (OSCCHT) post left oophorectomy. This is a rare aggressive ovarian tumour of which less than 300 cases were reported.

  20. Mid-infrared spectroscopy in skin cancer cell type identification

    Science.gov (United States)

    Kastl, Lena; Kemper, Björn; Lloyd, Gavin R.; Nallala, Jayakrupakar; Stone, Nick; Naranjo, Valery; Penaranda, Francisco; Schnekenburger, Jürgen

    2017-07-01

    Mid infrared spectroscopy samples were developed for the analysis of skin tumor cell types and three dimensional tissue phantoms towards the application of midIR spectroscopy for fast and reliable skin cancer diagnostics.

  1. Partial characterization of cell-type X collagen interactions.

    Science.gov (United States)

    Luckman, Steven P; Rees, Elaine; Kwan, Alvin P L

    2003-06-01

    Type X collagen is a short-chain non-fibrillar collagen that is deposited exclusively at sites of new bone formation. Although this collagen has been implicated in chondrocyte hypertrophy and endochondral ossification, its precise function remains unclear. One possible function could be to regulate the processes of chondrocyte hypertrophy through direct cell-type X collagen interactions. Adhesions of embryonic chick chondrocytes, and cell lines with known expression of collagen-binding integrins (MG63 and HOS), were assayed on chick type X collagen substrates, including the native, heat-denatured and pepsin-digested collagen, and the isolated C-terminal non-collagenous (NC1) domain. Type X collagen supported the greatest level of adhesion for all cell types tested. The involvement of the alpha2beta1 integrin in type X collagen-cell interaction was demonstrated by adhesion studies in the presence of Mg(2+) and Ca(2+) ions and integrin-function-blocking antibodies. Cells expressing alpha2beta1 integrin (chick chondrocytes and MG63 cells) also adhered to heat-denatured type X collagen and the isolated NC1 domain; however, removal of the non-collagenous domains by limited pepsinization of type X collagen resulted in very low levels of adhesion. Both focal contacts and actin stress-fibre formation were apparent in cells plated on type X collagen. The presence of alpha2 and beta1 integrin subunits in isolated chondrocytes and epiphyseal cartilage was also confirmed by immunolocalization. Our results demonstrate, for the first time, that type X collagen is capable of interacting directly with chondrocytes and other cells, primarily via alpha2beta1 integrin. These findings are atypical from the fibrillar collagen-cell interactions via collagen binding integrins in that: (1) the triple-helical conformation is not strictly required for cell adhesion; (2) the NC1 domain is also involved in the adhesion of alpha2beta1-expressing cells. These data form the basis for further

  2. Media presentation and public understanding of stem cells and stem cell research in Hungary

    OpenAIRE

    Vicsek, Lilla; Gergely, Júlia

    2011-01-01

    This paper reports on a research project which examined media coverage and audience perceptions of stem cells and stem cell research in Hungary, using focus groups and a media analysis. A background study was also conducted on the Hungarian legal, social and political situation linked to stem cell research, treatment and storage. Our data shows how stem cell research/treatments were framed by the focus group members in terms of medical results/cures and human interest stories – mirroring the ...

  3. Functionally diverse human T cells recognize non-microbial antigens presented by MR1.

    Science.gov (United States)

    Lepore, Marco; Kalinichenko, Artem; Calogero, Salvatore; Kumar, Pavanish; Paleja, Bhairav; Schmaler, Mathias; Narang, Vipin; Zolezzi, Francesca; Poidinger, Michael; Mori, Lucia; De Libero, Gennaro

    2017-05-18

    MHC class I-related molecule MR1 presents riboflavin- and folate-related metabolites to mucosal-associated invariant T cells, but it is unknown whether MR1 can present alternative antigens to other T cell lineages. In healthy individuals we identified MR1-restricted T cells (named MR1T cells) displaying diverse TCRs and reacting to MR1-expressing cells in the absence of microbial ligands. Analysis of MR1T cell clones revealed specificity for distinct cell-derived antigens and alternative transcriptional strategies for metabolic programming, cell cycle control and functional polarization following antigen stimulation. Phenotypic and functional characterization of MR1T cell clones showed multiple chemokine receptor expression profiles and secretion of diverse effector molecules, suggesting functional heterogeneity. Accordingly, MR1T cells exhibited distinct T helper-like capacities upon MR1-dependent recognition of target cells expressing physiological levels of surface MR1. These data extend the role of MR1 beyond microbial antigen presentation and indicate MR1T cells are a normal part of the human T cell repertoire.

  4. Intrinsic Variability Present in Wharton’s Jelly Mesenchymal Stem Cells and T Cell Responses May Impact Cell Therapy

    Directory of Open Access Journals (Sweden)

    Fernanda Vieira Paladino

    2017-01-01

    Full Text Available Wharton’s jelly mesenchymal stem cells (WJ-MSC exhibit immunomodulatory effects on T cell response. WJ-MSC are easy to collect, process, and proliferate rapidly in culture, but information on the variability of individual cell samples impacting upon in vitro expansion, immunomodulatory potential, and aging processes is still lacking. We propose to evaluate the immunomodulatory cytokine profile and capacity to inhibit T cell proliferation of WJ-MSC progressing to replicative senescence in order to analyze if expected responses are affected. Our results show that the gene expression of immunomodulatory molecules varied among samples with no specific pattern present. In coculture, all WJ-MSC were capable of inhibiting mitogen-activated CD3+ T cell proliferation, although to different degrees, and each PBMC responded with a different level of inhibition. Thus, we suggest that each WJ-MSC displays unique behavior, differing in patterns of cytokine mRNA expression and immunomodulatory capacity. We believe that variability between samples may play a role in the effectiveness of WJ-MSC employed therapeutically.

  5. The Effects of Psychological Type and Information Presentation on Decision Making

    Science.gov (United States)

    1989-12-01

    Sample, revealed that all cells were represented with the exception of the ENFP cell. Thirteen of the sixteen cells had five or fewer a1 Table 4... ENFP ENTP F= 1 F =0 F =2 F =1 M= 2 M =0 M =0 M= 2 Total = 3 Total = 0 Total = 2 Total = 3 (n = 37) observations; the remaining three cells had at...Total = 1 Total =6 NF = 11 NT = 40 ESTJ ESFJ ENFP ENTP F= 3 F 1 F 2 F 2 M= 12 M= 1 M =2 M= 5 Total = 15 Total = 2 Total = 4 Total = 7 (n = 127) Sub

  6. [Clinical types of FTLD: progressive nonfluent aphasia; comparative discussions on the associated clinical presentations].

    Science.gov (United States)

    Fukui, Toshiya

    2009-11-01

    Progressive nonfluent aphasia (PNFA) is one of the 3 clinical presentations of frontotemporal lobar degeneration (FTLD), the other 2 being frontotemporal dementia and semantic dementia (SD). PNFA and SD, both representing relentlessly progressive language impairment in the realm of FTLD, may share a large part with primary progressive aphasia (PPA). A salient distinction between PPA and PNFA or SD is that PPA includes another clinical type, namely, logopenic/phonemic aphasia (LPA), which is not represented in FTLD. This is primarily because LPA is usually caused by Alzheimer's disease (AD) and the brunt of the lesion is localized at the left temporo-parietal region of the brain. Further, PNFA/SD should be limited to the clinical consequencies of FTLD while PPA is more generous with regard to its causal pathology. By definition, PNFA is an expressive language impairment which is characterized by effortful speech, phonemic errors, grammatical impairment, and word-finding difficulties. Reading and writing may be comparatively impaired. Comprehension of single word meaning is normal, while comprehension of sentencies may sometimes be impaired. PNFA should be differentiated from SD, LPA, and pure progressive apraxia of speech (AOS or alternatively referred to as aphemia or anarthria). SD may be distinguished from PNFA by virtue of its fluency, characteristic loss of word meaning and absence of agrammatism. LPA is similar to PNFA, yet differs in that there is preservation of grammatical skills and speech motor function that is devoid of AOS and/or dysarthria. AOS is an impairment at the level of speech motor programming without language impairment. Thus, there may be a double dissociation between AOS and PNFA i. e., PNFA may or may not accompany AOS and vice versa. PNFA is associated with a localized lesion in the left frontotemporal area of the brain. Immunohistochemical investigations have revealed that ubiquitin/TAR DNA binding protein-43 (TDA-43) positive and tau

  7. Addison's disease in type 1 diabetes presenting with recurrent hypoglycaemia

    OpenAIRE

    McAulay, V.; Frier, B

    2000-01-01

    Primary adrenal insufficiency (Addison's disease) often develops insidiously. Although a rare disorder, it is more common in type 1 diabetes mellitus. A 19 year old male with type 1 diabetes and autoimmune hypothyroidism experienced recurrent severe hypoglycaemia over several months, despite a reduction in insulin dose, culminating in an adrenal crisis. Recurrent severe hypoglycaemia resolved after identification and treatment of the adrenocortical insufficiency. In type 1 diabetes, undiagnos...

  8. Functional and cytometric examination of different human lung epithelial cell types as drug transport barriers.

    Science.gov (United States)

    Min, Kyoung Ah; Rosania, Gus R; Kim, Chong-Kook; Shin, Meong Cheol

    2016-03-01

    To develop inhaled medications, various cell culture models have been used to examine the transcellular transport or cellular uptake properties of small molecules. For the reproducible high throughput screening of the inhaled drug candidates, a further verification of cell architectures as drug transport barriers can contribute to establishing appropriate in vitro cell models. In the present study, side-by-side experiments were performed to compare the structure and transport function of three lung epithelial cells (Calu-3, normal human bronchial primary cells (NHBE), and NL-20). The cells were cultured on the nucleopore membranes in the air-liquid interface (ALI) culture conditions, with cell culture medium in the basolateral side only, starting from day 1. In transport assays, paracellular transport across all three types of cells appeared to be markedly different with the NHBE or Calu-3 cells, showing low paracellular permeability and high TEER values, while the NL-20 cells showed high paracellular permeability and low TEER. Quantitative image analysis of the confocal microscope sections further confirmed that the Calu-3 cells formed intact cell monolayers in contrast to the NHBE and NL-20 cells with multilayers. Among three lung epithelial cell types, the Calu-3 cell cultures under the ALI condition showed optimal cytometric features for mimicking the biophysical characteristics of in vivo airway epithelium. Therefore, the Calu-3 cell monolayers could be used as functional cell barriers for the lung-targeted drug transport studies.

  9. Nanomaterial cytotoxicity is composition, size, and cell type dependent.

    Science.gov (United States)

    Sohaebuddin, Syed K; Thevenot, Paul T; Baker, David; Eaton, John W; Tang, Liping

    2010-08-21

    Despite intensive research efforts, reports of cellular responses to nanomaterials are often inconsistent and even contradictory. Additionally, relationships between the responding cell type and nanomaterial properties are not well understood. Using three model cell lines representing different physiological compartments and nanomaterials of different compositions and sizes, we have systematically investigated the influence of nanomaterial properties on the degrees and pathways of cytotoxicity. In this study, we selected nanomaterials of different compositions (TiO2 and SiO2 nanoparticles, and multi-wall carbon nanotubes [MWCNTs]) with differing size (MWCNTs of different diameters 50 nm; but same length 0.5-2 microm) to analyze the effects of composition and size on toxicity to 3T3 fibroblasts, RAW 264.7 macrophages, and telomerase-immortalized (hT) bronchiolar epithelial cells. Following characterization of nanomaterial properties in PBS and serum containing solutions, cells were exposed to nanomaterials of differing compositions and sizes, with cytotoxicity monitored through reduction in mitochondrial activity. In addition to cytotoxicity, the cellular response to nanomaterials was characterized by quantifying generation of reactive oxygen species, lysosomal membrane destabilization and mitochondrial permeability. The effect of these responses on cellular fate - apoptosis or necrosis - was then analyzed. Nanomaterial toxicity was variable based on exposed cell type and dependent on nanomaterial composition and size. In addition, nanomaterial exposure led to cell type dependent intracellular responses resulting in unique breakdown of cellular functions for each nanomaterial: cell combination. Nanomaterials induce cell specific responses resulting in variable toxicity and subsequent cell fate based on the type of exposed cell. Our results indicate that the composition and size of nanomaterials as well as the target cell type are critical determinants of

  10. Heterogeneity and Developmental Connections between Cell Types Inhabiting Teeth

    Directory of Open Access Journals (Sweden)

    Jan Krivanek

    2017-06-01

    Full Text Available Every tissue is composed of multiple cell types that are developmentally, evolutionary and functionally integrated into the unit we call an organ. Teeth, our organs for biting and mastication, are complex and made of many different cell types connected or disconnected in terms of their ontogeny. In general, epithelial and mesenchymal compartments represent the major framework of tooth formation. Thus, they give rise to the two most important matrix–producing populations: ameloblasts generating enamel and odontoblasts producing dentin. However, the real picture is far from this quite simplified view. Diverse pulp cells, the immune system, the vascular system, the innervation and cells organizing the dental follicle all interact, and jointly participate in transforming lifeless matrix into a functional organ that can sense and protect itself. Here we outline the heterogeneity of cell types that inhabit the tooth, and also provide a life history of the major populations. The mouse model system has been indispensable not only for the studies of cell lineages and heterogeneity, but also for the investigation of dental stem cells and tooth patterning during development. Finally, we briefly discuss the evolutionary aspects of cell type diversity and dental tissue integration.

  11. Heterogeneity and Developmental Connections between Cell Types Inhabiting Teeth.

    Science.gov (United States)

    Krivanek, Jan; Adameyko, Igor; Fried, Kaj

    2017-01-01

    Every tissue is composed of multiple cell types that are developmentally, evolutionary and functionally integrated into the unit we call an organ. Teeth, our organs for biting and mastication, are complex and made of many different cell types connected or disconnected in terms of their ontogeny. In general, epithelial and mesenchymal compartments represent the major framework of tooth formation. Thus, they give rise to the two most important matrix-producing populations: ameloblasts generating enamel and odontoblasts producing dentin. However, the real picture is far from this quite simplified view. Diverse pulp cells, the immune system, the vascular system, the innervation and cells organizing the dental follicle all interact, and jointly participate in transforming lifeless matrix into a functional organ that can sense and protect itself. Here we outline the heterogeneity of cell types that inhabit the tooth, and also provide a life history of the major populations. The mouse model system has been indispensable not only for the studies of cell lineages and heterogeneity, but also for the investigation of dental stem cells and tooth patterning during development. Finally, we briefly discuss the evolutionary aspects of cell type diversity and dental tissue integration.

  12. β-Cell Replacement in Mice Using Human Type 1 Diabetes Nuclear Transfer Embryonic Stem Cells.

    Science.gov (United States)

    Sui, Lina; Danzl, Nichole; Campbell, Sean R; Viola, Ryan; Williams, Damian; Xing, Yuan; Wang, Yong; Phillips, Neil; Poffenberger, Greg; Johannesson, Bjarki; Oberholzer, Jose; Powers, Alvin C; Leibel, Rudolph L; Chen, Xiaojuan; Sykes, Megan; Egli, Dieter

    2018-01-01

    β-Cells derived from stem cells hold great promise for cell replacement therapy for diabetes. Here we examine the ability of nuclear transfer embryonic stem cells (NT-ESs) derived from a patient with type 1 diabetes to differentiate into β-cells and provide a source of autologous islets for cell replacement. NT-ESs differentiate in vitro with an average efficiency of 55% into C-peptide-positive cells, expressing markers of mature β-cells, including MAFA and NKX6.1. Upon transplantation in immunodeficient mice, grafted cells form vascularized islet-like structures containing MAFA/C-peptide-positive cells. These β-cells adapt insulin secretion to ambient metabolite status and show normal insulin processing. Importantly, NT-ES-β-cells maintain normal blood glucose levels after ablation of the mouse endogenous β-cells. Cystic structures, but no teratomas, were observed in NT-ES-β-cell grafts. Isogenic induced pluripotent stem cell lines showed greater variability in β-cell differentiation. Even though different methods of somatic cell reprogramming result in stem cell lines that are molecularly indistinguishable, full differentiation competence is more common in ES cell lines than in induced pluripotent stem cell lines. These results demonstrate the suitability of NT-ES-β-cells for cell replacement for type 1 diabetes and provide proof of principle for therapeutic cloning combined with cell therapy. © 2017 by the American Diabetes Association.

  13. Towards Optimal Diagnosis of Type II Germ Cell Tumors

    NARCIS (Netherlands)

    J.A. Stoop (Hans)

    2011-01-01

    textabstractThe aim of the work described in this thesis is to improve the understanding of the pathobiology of testicular cancer (type II Germ Cell Tumors) to create possibilities for optimalization of diagnosis for this type of malignancy in routine pathology laboratories. The different studies

  14. Peroxynitrite modified DNA presents better epitopes for anti-DNA autoantibodies in diabetes type 1 patients.

    Science.gov (United States)

    Tripathi, Prashant; Moinuddin; Dixit, Kiran; Mir, Abdul Rouf; Habib, Safia; Alam, Khursheed; Ali, Asif

    2014-07-01

    Peroxynitrite (ONOO(-)), formed by the reaction between nitric oxide (NO) and superoxide (O2(-)), has been implicated in the etiology of numerous disease processes. Peroxynitrite interacts with DNA via direct oxidative reactions or via indirect radical-mediated mechanism. It can inflict both oxidative and nitrosative damages on DNA bases, generating abasic sites, resulting in the single strand breaks. Plasmid pUC 18 isolated from Escherichiacoli was modified with peroxynitrite, generated by quenched flow process. Modifications incurred in plasmid DNA were characterized by ultraviolet and fluorescence spectroscopy, circular dichroism, HPLC and melting temperature studies. Binding characteristics and specificity of antibodies from diabetes patients were analyzed by direct binding and inhibition ELISA. Peroxynitrite modification of pUC 18 plasmid resulted in the formation of strand breaks and base modification. The major compound formed when peroxynitrite reacted with DNA was 8-nitroguanine, a specific marker for peroxynitrite induced DNA damage in inflamed tissues. The concentration of 8-nitroguanine was found to be 3.8 μM. Sera from diabetes type 1 patients from different age groups were studied for their binding to native and peroxynitrite modified plasmid. Direct binding and competitive-inhibition ELISA results showed higher recognition of peroxynitrite modified plasmid, as compared to the native form, by auto-antibodies present in diabetes patients. The preferential recognition of modified plasmid by diabetes autoantibodies was further reiterated by gel shift assay. Experimentally induced anti-peroxynitrite-modified plasmid IgG was used as a probe to detect nitrosative lesions in the DNA isolated from diabetes patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Variable clinical presentation of an MUC1 mutation causing medullary cystic kidney disease type 1.

    Science.gov (United States)

    Bleyer, Anthony J; Kmoch, Stanislav; Antignac, Corinne; Robins, Vicki; Kidd, Kendrah; Kelsoe, John R; Hladik, Gerald; Klemmer, Philip; Knohl, Stephen J; Scheinman, Steven J; Vo, Nam; Santi, Ann; Harris, Alese; Canaday, Omar; Weller, Nelson; Hulick, Peter J; Vogel, Kristen; Rahbari-Oskoui, Frederick F; Tuazon, Jennifer; Deltas, Constantinos; Somers, Douglas; Megarbane, Andre; Kimmel, Paul L; Sperati, C John; Orr-Urtreger, Avi; Ben-Shachar, Shay; Waugh, David A; McGinn, Stella; Bleyer, Anthony J; Hodanová, Katerina; Vylet'al, Petr; Živná, Martina; Hart, Thomas C; Hart, P Suzanne

    2014-03-01

    The genetic cause of medullary cystic kidney disease type 1 was recently identified as a cytosine insertion in the variable number of tandem repeat region of MUC1 encoding mucoprotein-1 (MUC1), a protein that is present in skin, breast, and lung tissue, the gastrointestinal tract, and the distal tubules of the kidney. The purpose of this investigation was to analyze the clinical characteristics of families and individuals with this mutation. Families with autosomal dominant interstitial kidney disease were referred for genetic analysis over a 14-year period. Families without UMOD or REN mutations prospectively underwent genotyping for the presence of the MUC1 mutation. Clinical characteristics were retrospectively evaluated in individuals with the MUC1 mutation and historically affected individuals (persons who were both related to genetically affected individuals in such a way that ensured that they could be genetically affected and had a history of CKD stage IV or kidney failure resulting in death, dialysis, or transplantation). Twenty-four families were identified with the MUC1 mutation. Of 186 family members undergoing MUC1 mutational analysis, the mutation was identified in 95 individuals, 91 individuals did not have the mutation, and111 individuals were identified as historically affected. Individuals with the MUC1 mutation suffered from chronic kidney failure with a widely variable age of onset of end stage kidney disease ranging from 16 to >80 years. Urinalyses revealed minimal protein and no blood. Ultrasounds of 35 individuals showed no medullary cysts. There were no clinical manifestations of the MUC1 mutation detected in the breasts, skin, respiratory system, or gastrointestinal tract. MUC1 mutation results in progressive chronic kidney failure with a bland urinary sediment. The age of onset of end stage kidney disease is highly variable, suggesting that gene-gene or gene-environment interactions contribute to phenotypic variability.

  16. PREVALENCE OF MEIBOMIAN GLAND DISEASE IN TYPE II DIABETIC PATIENTS & ITS CLINICAL PRESENTATIONS

    Directory of Open Access Journals (Sweden)

    Reshma Pathan

    2015-01-01

    Full Text Available AIMS : To study the prevalence of the meibomian gland disease in typ e 2 diabetic patients and its clinical presentations. SETTING AND DESIGN : A hospital based cross sectional descriptive study of 100 type 2 diabetic patients attending a medical college was conducted. METHODS : Detailed diabetic history was recorded. Assessment of ocular surface i.e. the lid margins , conjunctiva , corneal surface was done via slit lamp biomicroscopy. Meibomian gland disease (MGD severity was assessed by the quality and expressibility of the meibomian secretion. Dry eye tests like schir mer’s test and tear film breakup time were done. STATISTICAL ANALYSIS USED : SPSS statistical software version 17 was used. RESULTS : 56% of the patients out of 100 diabetic patients had MGD. The most common symptom was burning (46.9% , followed by dryness ( 23.5% , 5.6% had conjunctival injection , 7.14% had corneal erosions , 25% had mucus debris , 53.65% had dry eye which was statistically significant (p=0.001 , 56.25% males and 72.2% females had the disease which was not statistically significant. CONCLUSION : The prevalence of Meibomian gland disease in the diabetic population was 56% which is more than the general population prevalence. Apart from other disorders diabetics are also more prone for ocular surface diseases like Meibomian gland disease. MGD is an important pre disposer for severe diseases like Dry eye in this subgroup of patients which can lead to complications like conjunctival keratinisations , corneal erosions and perforations. Careful examination of these patients for ocular surface disease and prompt treatment is required.

  17. Pattern of dyslipidaemia among the Bangladeshi type 2 diabetic patients presented with acute coronary syndrome.

    Science.gov (United States)

    Hoque, M H; Mahmood, M; Haque, M A; Salim, M A

    2014-10-01

    Increasing prevalence of diabetes and its complications in the developing communities would pose a threat in respect to their existing health care service. An increased incidence of atherosclerosis in insulin-dependent diabetic patients has long been recognized. Hyperlipidaemia, a common finding in these patients, may be one of the contributing factors. The objective of our study is to find out the patterns of dyslipidaemia among the Bangladeshi patients with type-2 diabetes mellitus presented with acute coronary syndrome. This study was conducted in the department of cardiology of BIRDEM and Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh during the period of January 2009 to December 2009. A total of 100 patients were included in this study, according to the inclusion and exclusion criteria. Diabetes Mellitus and Acute Coronary Syndrome was diagnosed according to the guideline of American Diabetic Association and American College of Cardiology respectively. Among the respondents Mean±SD of fasting blood sugar and 2 hours ABF were 9.23±3.6mmol/L and 12.61±8.52mmol/L respectively. Mean±SD of HbA1C of the respondents was 7.23±2.12. Total cholesterol level 200mg/dl were 27.0%, 42.0% and 31.0% respectively. HDL cholesterol 40mg/dl were 76.0% and 24.0% respectively. LDL cholesterol 150mg/dl were 43.0% and 57.0% respectively. TG within 40 to 160mg/dl and >160mg/dl were 73.0% and 27.0% respectively, Mean±SD of Total Cholesterol, HDL Cholesterol, LDL Cholesterol and Triglyceride were 162.43±38.62, 37.41±8.59, 137.43±22.73 and 156.43±41.92mg/dl respectively.

  18. Macropinocytosis in phagocytes: regulation of MHC class-II-restricted antigen presentation in dendritic cells

    OpenAIRE

    Liu, Zhenzhen; Roche, Paul A.

    2015-01-01

    AbstractDendritic cells (DCs) are outstanding antigen presenting cells (APCs) due to their robust ability to internalize extracellular antigens using endocytic processes such as receptor-mediated endocytosis, phagocytosis, and macropinocytosis. Macropinocytosis mediates the non-specific uptake of soluble antigens and occurs in DCs constitutively. Macropinocytosis plays a key role in DC-mediated antigen presentation to T cells against pathogens and the efficiency of macropinocytosis in antigen...

  19. Identification of XMRV infection-associated microRNAs in four cell types in culture.

    Science.gov (United States)

    Mohan, Ketha V K; Devadas, Krishnakumar; Sainath Rao, Shilpakala; Hewlett, Indira; Atreya, Chintamani

    2012-01-01

    XMRV is a gammaretrovirus that was thought to be associated with prostate cancer (PC) and chronic fatigue syndrome (CFS) in humans until recently. The virus is culturable in various cells of human origin like the lymphocytes, NK cells, neuronal cells, and prostate cell lines. MicroRNAs (miRNA), which regulate gene expression, were so far not identified in cells infected with XMRV in culture. Two prostate cell lines (LNCaP and DU145) and two primary cells, Peripheral Blood Lymphocytes [PBL] and Monocyte-derived Macrophages [MDM] were infected with XMRV. Total mRNA was extracted from mock- and virus-infected cells at 6, 24 and 48 hours post infection and evaluated for microRNA profile in a microarray. MicroRNA expression profiles of XMRV-infected continuous prostate cancer cell lines differ from that of virus-infected primary cells (PBL and MDMs). miR-193a-3p and miRPlus-E1245 observed to be specific to XMRV infection in all 4 cell types. While miR-193a-3p levels were down regulated miRPlus-E1245 on the other hand exhibited varied expression profile between the 4 cell types. The present study clearly demonstrates that cellular microRNAs are expressed during XMRV infection of human cells and this is the first report demonstrating the regulation of miR193a-3p and miRPlus-E1245 during XMRV infection in four different human cell types.

  20. Tumor Budding Cells, Cancer Stem Cells and Epithelial-Mesenchymal Transition-type Cells in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Eva eKaramitopoulou

    2013-01-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is one of the most lethal cancers with a 5-year survival rate of less than 5%. Moreover, PDAC escapes early detection and resists treatment. Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4 and dysregulation of PTEN/PI3K/AKT signaling. Through their interaction with WNT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial-mesenchymal transition (EMT. Emerging evidence has demonstrated that cancer stem cells (CSCs, small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion and metastasis in pancreatic cancer. EMT may be histologically represented by the presence of tumor budding which is described as the occurrence of single tumor cells or small clusters (<5 of dedifferentiated cells at the invasive front of gastrointestinal (including colorectal, oesophageal, gastric and ampullary carcinomas and is linked to poor prognosis. Tumor budding has recently been shown to occur frequently in PDAC and to be associated with adverse clinicopathological features and decreased disease-free and overall survival. The aim of this review is to present a short overview on the morphological and molecular aspects that underline the relationship between tumor budding cells, CSCs and EMT-type cells in PDAC.

  1. Biologically Inspired Design of Nanoparticle Artificial Antigen-Presenting Cells for Immunomodulation.

    Science.gov (United States)

    Hickey, John W; Vicente, Fernando P; Howard, Gregory P; Mao, Hai-Quan; Schneck, Jonathan P

    2017-10-10

    Particles engineered to engage and interact with cell surface ligands and to modulate cells can be harnessed to explore basic biological questions as well as to devise cellular therapies. Biology has inspired the design of these particles, such as artificial antigen-presenting cells (aAPCs) for use in immunotherapy. While much has been learned about mimicking antigen presenting cell biology, as we decrease the size of aAPCs to the nanometer scale, we need to extend biomimetic design to include considerations of T cell biology-including T-cell receptor (TCR) organization. Here we describe the first quantitative analysis of particle size effect on aAPCs with both Signals 1 and 2 based on T cell biology. We show that aAPCs, larger than 300 nm, activate T cells more efficiently than smaller aAPCs, 50 nm. The 50 nm aAPCs require saturating doses or require artificial magnetic clustering to activate T cells. Increasing ligand density alone on the 50 nm aAPCs did not increase their ability to stimulate CD8+ T cells, confirming the size-dependent phenomenon. These data support the need for multireceptor ligation and activation of T-cell receptor (TCR) nanoclusters of similar sizes to 300 nm aAPCs. Quantitative analysis and modeling of a nanoparticle system provides insight into engineering constraints of aAPCs for T cell immunotherapy applications and offers a case study for other cell-modulating particles.

  2. Presentation of an immunodominant immediate-early CD8+ T cell epitope resists human cytomegalovirus immunoevasion.

    Directory of Open Access Journals (Sweden)

    Stefanie Ameres

    Full Text Available Control of human cytomegalovirus (HCMV depends on CD8+ T cell responses that are shaped by an individual's repertoire of MHC molecules. MHC class I presentation is modulated by a set of HCMV-encoded proteins. Here we show that HCMV immunoevasins differentially impair T cell recognition of epitopes from the same viral antigen, immediate-early 1 (IE-1, that are presented by different MHC class I allotypes. In the presence of immunoevasins, HLA-A- and HLA-B-restricted T cell clones were ineffective, but HLA-C*0702-restricted T cell clones recognized and killed infected cells. Resistance of HLA-C*0702 to viral immunoevasins US2 and US11 was mediated by the alpha3 domain and C-terminal region of the HLA heavy chain. In healthy donors, HLA-C*0702-restricted T cells dominated the T cell response to IE-1. The same HLA-C allotype specifically protected infected cells from attack by NK cells that expressed a corresponding HLA-C-specific KIR. Thus, allotype-specific viral immunoevasion allows HCMV to escape control by NK cells and HLA-A- and HLA-B-restricted T cells, while the virus becomes selectively vulnerable to an immunodominant population of HLA-C-restricted T cells. Our work identifies a T cell population that may be of particular efficiency in HCMV-specific immunotherapy.

  3. Presentation of antigen to T lymphocytes by non-immune B-cell hybridoma clones: evidence for specific and non-specific presentation

    Science.gov (United States)

    Cohly, H. H.; Morrison, D. R.; Zouhair Atassi, M. Z.

    1989-01-01

    Non-immune SJL (H-2s) spleen cells were fused with non-secreting, non-antigen presenting (H-2d) Balb/c 653-myeloma cells and the hybridomas were cloned by two limiting dilutions. The resulting hybrid B-cell clones were tested for their antigen presentation capability to SJL T-cell lines that were specific for either lysozyme or myoglobin. In proliferative assays, 53% of the antigen presenting B-cell clones presented both myoglobin and lysozyme (general presenters) while the other 47% presented specifically either myoglobin or lysozyme (specific presenters). The ability to selectively present either myoglobin or lysozyme indicates that antigen presentation at the clonal level can be specific or non-specific depending on the particular B-cell clone.

  4. Downregulation of integrin β4 decreases the ability of airway epithelial cells to present antigens.

    Directory of Open Access Journals (Sweden)

    Chi Liu

    Full Text Available Airway epithelial cells have been demonstrated to be accessory antigen presentation cells (APC capable of activating T cells and may play an important role in the development of allergic airway inflammation of asthma. In asthmatic airways, loss of expression of the adhesion molecule integrin β4 (ITGB4 and an increase in Th2 inflammation bias has been observed in our previous study. Given that ITGB4 is engaged in multiple signaling pathways, we studied whether disruption of ITGB4-mediated cell adhesion may contribute to the adaptive immune response of epithelial cells, including their ability to present antigens, induce the activate and differentiate of T cells. We silenced ITGB4 expression in bronchial epithelial cells with an effective siRNA vector and studied the effects of ITGB4 silencing on the antigen presentation ability of airway epithelial cells. T cell proliferation and cytokine production was investigated after co-culturing with ITGB4-silenced epithelial cells. Surface expression of B7 homologs and the major histocompatibility complex (MHC class II was also detected after ITGB4 was silenced. Our results demonstrated that silencing of ITGB4 resulted in impaired antigen presentation processes and suppressed T cell proliferation. Meanwhile, decrease in Th1 cytokine production and increase in Th17 cytokine production was induced after co-culturing with ITGB4-silenced epithelial cells. Moreover, HLA-DR was decreased and the B7 homologs expression was different after ITGB4 silencing. Overall, this study suggested that downregulation of ITGB4 expression in airway epithelial cells could impair the antigen presentation ability of these cells, which further regulate airway inflammation reaction in allergic asthma.

  5. C-type lectin receptors in the control of T helper cell differentiation

    NARCIS (Netherlands)

    Geijtenbeek, Teunis B. H.; Gringhuis, Sonja I.

    2016-01-01

    Pathogen recognition by C-type lectin receptors (CLRs) expressed by dendritic cells is important not only for antigen presentation, but also for the induction of appropriate adaptive immune responses via T helper (TH) cell differentiation. CLRs act either by themselves or in cooperation with other

  6. Prenatal induced chronic dietary hypothyroidism delays but does not block adult-type Leydig cell development

    NARCIS (Netherlands)

    Rijntjes, E.; Teerds, K.J.; Swarts, H.J.

    2009-01-01

    Transient hypothyroidism induced by propyl-2-thiouracyl blocks postpartum Leydig cell development. In the present study, the effects of chronic hypothyroidism on the formation of this adult-type Leydig cell population were investigated, using a more physiological approach. Before mating, dams were

  7. Live birth potential of good morphology and vitrified blastocysts presenting abnormal cell divisions.

    Science.gov (United States)

    Azzarello, Antonino; Hoest, Thomas; Hay-Schmidt, Anders; Mikkelsen, Anne Lis

    2017-06-01

    This study included 238 good morphology blastocysts, which were transferred after vitrification-warming to 152 women by single blastocyst transfer in Holbæk Fertility Clinic, Denmark. Time-lapse recordings of transferred good morphology blastocysts were reassessed to recognize every abnormal cell division (ACD) from the 1st to the 4th cell cycle. ACDs were distinguished as failed cell divisions and multi-cell divisions. ACDs were recognized in 37.0% (no. 88/238) of good morphology blastocysts that were vitrified-warmed and transferred in our clinic. Good morphology blastocysts with ACDs showed a lower live birth rate (17.0%) than blastocyst with solely regular cell divisions (29.3%). ACDs could occur at more than one cell division in the same good morphology blastocyst. Reported as independent events, we observed ACDs occurring more frequently at the later cell cycles (1st: 1.3%; 2nd: 8.0%; 3rd: 18.5%; 4th: 18.1%). More blastocysts presented failed cell divisions (no. 95) than multi-cell divisions (no. 14). Live births were achieved from blastocysts showing multi-cell divisions at any cell cycle and failed cell divisions from the 2nd cell cycle. Analyses of the subgroup of first blastocyst transferred to each patient showed similar to results. In conclusion, good morphology blastocysts presenting ACDs can result in live birth although lower compared to blastocysts with solely regular cell division. Pre-implantation embryos in vitro may undergo self-selection or correcting processes. This supports the transfer of blastocysts instead of cleavage stage embryos, giving first priority to blastocyst showing solely regular cell divisions, and giving second priority to blastocysts presenting ACDs at any cell cycle. Copyright © 2017 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  8. Modelling epigenetic regulation of gene expression in 12 human cell types reveals combinatorial patterns of cell-type-specific genes.

    Science.gov (United States)

    Lu, Yiming; Qu, Wubin; Min, Bo; Liu, Zheyan; Chen, Changsheng; Zhang, Chenggang

    2014-06-01

    The maintenance of the diverse cell types in a multicellular organism is one of the fundamental mysteries of biology. Modelling the dynamic regulatory relationships between the histone modifications and the gene expression across the diverse cell types is essential for the authors to understand the mechanisms of the epigenetic regulation. Here, the authors thoroughly assessed the histone modification enrichment profiles at the promoters and constructed quantitative models between the histone modification abundances and the gene expression in 12 human cell types. The author's results showed that the histone modifications at the promoters exhibited remarkably cell-type-dependent variability in the cell-type-specific (CTS) genes. They demonstrated that the variable profiles of the modifications are highly predictive for the dynamic changes of the gene expression across all the cell types. Their findings revealed the close relationship between the combinatorial patterns of the histone modifications and the CTS gene expression. They anticipate that the findings and the methods they used in this study could provide useful information for the future studies of the regulatory roles of the histone modifications in the CTS genes.

  9. BMP signalling differentially regulates distinct haematopoietic stem cell types.

    Science.gov (United States)

    Crisan, Mihaela; Kartalaei, Parham Solaimani; Vink, Chris S; Vink, Chris; Yamada-Inagawa, Tomoko; Bollerot, Karine; van IJcken, Wilfred; van der Linden, Reinier; de Sousa Lopes, Susana M Chuva; Monteiro, Rui; Mummery, Christine; Dzierzak, Elaine

    2015-08-18

    Adult haematopoiesis is the outcome of distinct haematopoietic stem cell (HSC) subtypes with self-renewable repopulating ability, but with different haematopoietic cell lineage outputs. The molecular basis for this heterogeneity is largely unknown. BMP signalling regulates HSCs as they are first generated in the aorta-gonad-mesonephros region, but at later developmental stages, its role in HSCs is controversial. Here we show that HSCs in murine fetal liver and the bone marrow are of two types that can be prospectively isolated--BMP activated and non-BMP activated. Clonal transplantation demonstrates that they have distinct haematopoietic lineage outputs. Moreover, the two HSC types differ in intrinsic genetic programs, thus supporting a role for the BMP signalling axis in the regulation of HSC heterogeneity and lineage output. Our findings provide insight into the molecular control mechanisms that define HSC types and have important implications for reprogramming cells to HSC fate and treatments targeting distinct HSC types.

  10. p-Type MWT. Integrated cell and module technology

    Energy Technology Data Exchange (ETDEWEB)

    Tool, C.J.J.; Kossen, E.J.; Bennett, I.J.

    2013-10-15

    A major issue of concern in MWT solar cells is the increased leakage current at reversed bias voltage through the vias compared. At ECN we have been working on reducing this leakage current to levels comparable to H-pattern cells. In this study we present the results of this work. We further show the benefit of a combined cell and module design for MWT solar cells. At the cell level, MWT production costs per wafer are comparable with H-pattern while the cell output increases. At the module level this design results in a further increase of the power output.

  11. 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...... 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....... 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...

  12. The brain microvascular endothelium supports T cell proliferation and has potential for alloantigen presentation.

    Directory of Open Access Journals (Sweden)

    Julie Wheway

    Full Text Available Endothelial cells (EC form the inner lining of blood vessels and are positioned between circulating lymphocytes and tissues. Hypotheses have formed that EC may act as antigen presenting cells based on the intimate interactions with T cells, which are seen in diseases like multiple sclerosis, cerebral malaria (CM and viral neuropathologies. Here, we investigated how human brain microvascular EC (HBEC interact with and support the proliferation of T cells. We found HBEC to express MHC II, CD40 and ICOSL, key molecules for antigen presentation and co-stimulation and to take up fluorescently labeled antigens via macropinocytosis. In co-cultures, we showed that HBEC support and promote the proliferation of CD4(+ and CD8(+ T cells, which both are key in CM pathogenesis, particularly following T cell receptor activation and co-stimulation. Our findings provide novel evidence that HBEC can trigger T cell activation, thereby providing a novel mechanism for neuroimmunological complications of infectious diseases.

  13. The development and plasticity of alveolar type 1 cells

    Science.gov (United States)

    Yang, Jun; Hernandez, Belinda J.; Martinez Alanis, Denise; Narvaez del Pilar, Odemaris; Vila-Ellis, Lisandra; Akiyama, Haruhiko; Evans, Scott E.; Ostrin, Edwin J.; Chen, Jichao

    2016-01-01

    Alveolar type 1 (AT1) cells cover >95% of the gas exchange surface and are extremely thin to facilitate passive gas diffusion. The development of these highly specialized cells and its coordination with the formation of the honeycomb-like alveolar structure are poorly understood. Using new marker-based stereology and single-cell imaging methods, we show that AT1 cells in the mouse lung form expansive thin cellular extensions via a non-proliferative two-step process while retaining cellular plasticity. In the flattening step, AT1 cells undergo molecular specification and remodel cell junctions while remaining connected to their epithelial neighbors. In the folding step, AT1 cells increase in size by more than 10-fold and undergo cellular morphogenesis that matches capillary and secondary septa formation, resulting in a single AT1 cell spanning multiple alveoli. Furthermore, AT1 cells are an unexpected source of VEGFA and their normal development is required for alveolar angiogenesis. Notably, a majority of AT1 cells proliferate upon ectopic SOX2 expression and undergo stage-dependent cell fate reprogramming. These results provide evidence that AT1 cells have both structural and signaling roles in alveolar maturation and can exit their terminally differentiated non-proliferative state. Our findings suggest that AT1 cells might be a new target in the pathogenesis and treatment of lung diseases associated with premature birth. PMID:26586225

  14. Type I hair cell degeneration in the utricular macula of the waltzing guinea pig

    DEFF Research Database (Denmark)

    Severinsen, Stig A; Raarup, Merete Krog; Ulfendahl, Mats

    2008-01-01

    Waltzing guinea pigs are an inbred guinea pig strain with a congenital and progressive balance and hearing disorder. A unique rod-shaped structure is found in the type I vestibular hair cells, that traverses the cell in an axial direction, extending towards the basement membrane. The present study...... estimates the total number of utricular hair cells and supporting cells in waltzing guinea pigs and age-matched control animals using the optical fractionator method. Animals were divided into four age groups (1, 7, 49 and 343 day-old). The number of type I hair cells decreased by 20% in the 343 day......-old waltzing guinea pigs compared to age-matched controls and younger animals. Two-photon confocal laser scanning microscopy using antibodies against fimbrin and betaIII-tubulin showed that the rods were exclusive to type I hair cells. There was no significant change in the length of the filament rods with age...

  15. Type III collagen can be present on banded collagen fibrils regardless of fibril diameter

    OpenAIRE

    1987-01-01

    Monoclonal antibodies that recognize an epitope within the triple helix of type III collagen have been used to examine the distribution of that collagen type in human skin, cornea, amnion, aorta, and tendon. Ultrastructural examination of those tissues indicates antibody binding to collagen fibrils in skin, amnion, aorta, and tendon regardless of the diameter of the fibril. The antibody distribution is unchanged with donor age, site of biopsy, or region of tissue examined. In contrast, antibo...

  16. Oligopeptide antigens of the angiotensin lineage compete for presentation by paraformaldehyde-treated accessory cells to T cells

    DEFF Research Database (Denmark)

    Buus, S; Werdelin, O

    1986-01-01

    The heptapeptide antigen angiotensin III can be presented to guinea pig T cells by paraformaldehyde-treated antigen-presenting cells, which are incapable of processing antigens and presumably cannot even ingest them. We demonstrate here that the decapeptide angiotensin I can outcompete angiotensi...... of competition between antigens for presentation; but since they presumably are active also in untreated cells, they may play a physiologic role in the normal immune response.......The heptapeptide antigen angiotensin III can be presented to guinea pig T cells by paraformaldehyde-treated antigen-presenting cells, which are incapable of processing antigens and presumably cannot even ingest them. We demonstrate here that the decapeptide angiotensin I can outcompete angiotensin...

  17. Type 1 interferons contribute to the clearance of senescent cell.

    Science.gov (United States)

    Katlinskaya, Yuliya V; Carbone, Christopher J; Yu, Qiujing; Fuchs, Serge Y

    2015-01-01

    The major known function of cytokines that belong to type I interferons (IFN, including IFNα and IFNβ) is to mount the defense against viruses. This function also protects the genetic information of host cells from alterations in the genome elicited by some of these viruses. Furthermore, recent studies demonstrated that IFN also restrict proliferation of damaged cells by inducing cell senescence. Here we investigated the subsequent role of IFN in elimination of the senescent cells. Our studies demonstrate that endogenous IFN produced by already senescent cells contribute to increased expression of the natural killer (NK) receptor ligands, including MIC-A and ULBP2. Furthermore, neutralization of endogenous IFN or genetic ablation of its receptor chain IFNAR1 compromises the recognition of senescent cells and their clearance in vitro and in vivo. We discuss the role of IFN in protecting the multi-cellular host from accumulation of damaged senescent cells and potential significance of this mechanism in human cancers.

  18. Regulatory B cells present in lymph nodes draining a murine tumor

    Directory of Open Access Journals (Sweden)

    Andrea Maglioco

    2014-06-01

    Full Text Available In cancer, B cells have been classically associated with antibody secretion, antigen presentation and T cell activation. However, a possible role for B lymphocytes in impairing antitumor response and collaborating with tumor growth has been brought into focus. Recent reports have described the capacity of B cells to negatively affect immune responses in autoimmune diseases. The highly immunogenic mouse tumor MCC loses its immunogenicity and induces systemic immune suppression and tolerance as it grows. We have previously demonstrated that MCC growth induces a distinct and progressive increase in B cell number and proportion in the tumor draining lymph nodes (TDLN, as well as a less prominent increase in T regulatory cells. The aim of this research was to study B cell characteristics and function in the lymph node draining MCC tumor and to analyze whether these cells may be playing a role in suppressing antitumor response and favoring tumor progression. Results indicate that B cells from TDLN expressed increased CD86 and MHCII co-stimulatory molecules indicating activated phenotype, as well as intracellular IL-10, FASL and Granzyme B, molecules with regulatory immunosuppressive properties. Additionally, B cells showed high inhibitory upon T cell proliferation ex vivo, and a mild capacity to secrete antibodies. Our conclusion is that even when evidence of B cell-mediated activity of the immune response is present, B cells from TDLN exhibit regulatory phenotype and inhibitory activity, probably contributing to the state of immunological tolerance characteristic of the advanced tumor condition.

  19. Type VI secretion delivers bacteriolytic effectors to target cells.

    Science.gov (United States)

    Russell, Alistair B; Hood, Rachel D; Bui, Nhat Khai; LeRoux, Michele; Vollmer, Waldemar; Mougous, Joseph D

    2011-07-20

    Peptidoglycan is the major structural constituent of the bacterial cell wall, forming a meshwork outside the cytoplasmic membrane that maintains cell shape and prevents lysis. In Gram-negative bacteria, peptidoglycan is located in the periplasm, where it is protected from exogenous lytic enzymes by the outer membrane. Here we show that the type VI secretion system of Pseudomonas aeruginosa breaches this barrier to deliver two effector proteins, Tse1 and Tse3, to the periplasm of recipient cells. In this compartment, the effectors hydrolyse peptidoglycan, thereby providing a fitness advantage for P. aeruginosa cells in competition with other bacteria. To protect itself from lysis by Tse1 and Tse3, P. aeruginosa uses specific periplasmically localized immunity proteins. The requirement for these immunity proteins depends on intercellular self-intoxication through an active type VI secretion system, indicating a mechanism for export whereby effectors do not access donor cell periplasm in transit.

  20. Deconstructing autofluorescence: non-invasive detection and monitoring of biochemistry in cells and tissues (Conference Presentation)

    Science.gov (United States)

    Goldys, Ewa M.; Gosnell, Martin E.; Anwer, Ayad G.; Cassano, Juan C.; Sue, Carolyn M.; Mahbub, Saabah B.; Pernichery, Sandeep M.; Inglis, David W.; Adhikary, Partho P.; Jazayeri, Jalal A.; Cahill, Michael A.; Saad, Sonia; Pollock, Carol; Sutton-Mcdowall, Melanie L.; Thompson, Jeremy G.

    2016-03-01

    Automated and unbiased methods of non-invasive cell monitoring able to deal with complex biological heterogeneity are fundamentally important for biology and medicine. Label-free cell imaging provides information about endogenous fluorescent metabolites, enzymes and cofactors in cells. However extracting high content information from imaging of native fluorescence has been hitherto impossible. Here, we quantitatively characterise cell populations in different tissue types, live or fixed, by using novel image processing and a simple multispectral upgrade of a wide-field fluorescence microscope. Multispectral intrinsic fluorescence imaging was applied to patient olfactory neurosphere-derived cells, cell model of a human metabolic disease MELAS (mitochondrial myopathy, encephalomyopathy, lactic acidosis, stroke-like syndrome). By using an endogenous source of contrast, subtle metabolic variations have been detected between living cells in their full morphological context which made it possible to distinguish healthy from diseased cells before and after therapy. Cellular maps of native fluorophores, flavins, bound and free NADH and retinoids unveiled subtle metabolic signatures and helped uncover significant cell subpopulations, in particular a subpopulation with compromised mitochondrial function. The versatility of our method is further illustrated by detecting genetic mutations in cancer, non-invasive monitoring of CD90 expression, label-free tracking of stem cell differentiation, identifying stem cell subpopulations with varying functional characteristics, tissue diagnostics in diabetes, and assessing the condition of preimplantation embryos. Our optimal discrimination approach enables statistical hypothesis testing and intuitive visualisations where previously undetectable differences become clearly apparent.

  1. Subacute herpes simplex virus type 1 encephalitis as an initial presentation of chronic lymphocytic leukemia and multiple sclerosis: a case report

    Directory of Open Access Journals (Sweden)

    Corman Lourdes C

    2011-02-01

    Full Text Available Abstract Introduction Herpes simplex virus type 1 encephalitis presents acutely in patients who are immunocompetent. We report what we believe to be the first published case of a subacute course of herpes simplex virus type 1 encephalitis in a patient with asymptomatic chronic lymphocytic leukemia who subsequently developed multiple sclerosis. Case presentation A 49-year-old Caucasian woman with a history of fever blisters presented to the emergency department with a history of left temporal headache for four weeks, and numbness of the left face and leg for two weeks. A complete blood count revealed white blood cell count of 11,820 cells/mL, with an absolute lymphocyte count of 7304 cells/mL. The cerebrospinal fluid contained 6 white blood cells/μL, 63 red blood cells/μL, 54 mg glucose/dL, and 49 mg total protein/dL. Magnetic resonance imaging of the brain revealed meningoencephalitis and bilateral ventriculitis. Cerebrospinal fluid polymerase chain reaction for herpes simplex virus type 1 was positive, and the patient's symptoms resolved after ten days of treatment with parenteral aciclovir. Incidental findings on peripheral blood smear and flow cytometry testing confirmed chronic lymphocytic leukemia. One month later, she developed bilateral numbness of the hands and feet; a repeat cerebrospinal fluid polymerase chain reaction for herpes simplex virus type 1 at this time was negative. A repeat magnetic resonance imaging scan showed an expansion of the peri-ventricular lesions, and the cerebrospinal fluid contained elevated oligoclonal bands and myelin basic protein. A brain biopsy revealed gliosis consistent with multiple sclerosis, and the patient responded to treatment with high-dose parenteral steroids. Conclusion Herpes simplex virus type 1 encephalitis is a rare presentation of chronic lymphocytic leukemia. Our patient had an atypical, subacute course, presumably due to immunosuppression from chronic lymphocytic leukemia. This unusual

  2. Alveolar epithelial type II cell: defender of the alveolus revisited

    Directory of Open Access Journals (Sweden)

    Fehrenbach Heinz

    2001-01-01

    Full Text Available Abstract In 1977, Mason and Williams developed the concept of the alveolar epithelial type II (AE2 cell as a defender of the alveolus. It is well known that AE2 cells synthesise, secrete, and recycle all components of the surfactant that regulates alveolar surface tension in mammalian lungs. AE2 cells influence extracellular surfactant transformation by regulating, for example, pH and [Ca2+] of the hypophase. AE2 cells play various roles in alveolar fluid balance, coagulation/fibrinolysis, and host defence. AE2 cells proliferate, differentiate into AE1 cells, and remove apoptotic AE2 cells by phagocytosis, thus contributing to epithelial repair. AE2 cells may act as immunoregulatory cells. AE2 cells interact with resident and mobile cells, either directly by membrane contact or indirectly via cytokines/growth factors and their receptors, thus representing an integrative unit within the alveolus. Although most data support the concept, the controversy about the character of hyperplastic AE2 cells, reported to synthesise profibrotic factors, proscribes drawing a definite conclusion today.

  3. Pathogenic T helper type 17 cells contribute to type 1 diabetes independently of interleukin-22.

    Science.gov (United States)

    Bellemore, S M; Nikoopour, E; Krougly, O; Lee-Chan, E; Fouser, L A; Singh, B

    2016-03-01

    We have shown that pathogenic T helper type 17 (Th17) cells differentiated from naive CD4(+) T cells of BDC2·5 T cell receptor transgenic non-obese diabetic (NOD) mice by interleukin (IL)-23 plus IL-6 produce IL-17, IL-22 and induce type 1 diabetes (T1D). Neutralizing interferon (IFN)-γ during the polarization process leads to a significant increase in IL-22 production by these Th17 cells. We also isolated IL-22-producing Th17 cells from the pancreas of wild-type diabetic NOD mice. IL-27 also blocked IL-22 production from diabetogenic Th17 cells. To determine the functional role of IL-22 produced by pathogenic Th17 cells in T1D we neutralized IL-22 in vivo by using anti-IL-22 monoclonal antibody. We found that blocking IL-22 did not alter significantly adoptive transfer of disease by pathogenic Th17 cells. Therefore, IL-22 is not required for T1D pathogenesis. The IL-22Rα receptor for IL-22 however, increased in the pancreas of NOD mice during disease progression and based upon our and other studies we suggest that IL-22 may have a regenerative and protective role in the pancreatic islets. © 2015 British Society for Immunology.

  4. Antigen presentation by non-immune B-cell hybridoma clones: presentation of synthetic antigenic sites reveals clones that exhibit no specificity and clones that present only one epitope

    Science.gov (United States)

    Cohly, H. H.; Morrison, D. R.; Atassi, M. Z.

    1989-01-01

    Recently, we reported the preparation and antigen-presenting properties of hybridoma B-cell clones obtained after fusing non-secreting, non-antigen presenting Balb/c 653-myeloma cells with non-immune SJL spleen cells. It was found that antigen presentation at the clonal level can be specific or non-specific, depending on the particular B-cell clone. In the present work, one specific and one general presenter B-cell clones were tested for their epitope presentation ability to SJL T-cells that were specific to lysozyme or myoglobin. B-cell clone A1G12, a general presenter which presented both lysozyme and myoglobin to their respective T-cell lines, was found to present all five myoglobin epitopes while clone A1L16, a lysozyme specific presenter presented only one of the three epitopes of lysozyme. The latter reveals a hitherto unknown submolecular specificity (to a given epitope within a protein) for antigen presenting cells at the clonal level. Therefore, the specificity of T-cell recognition does not only derive from the T-cell but may also be dependent on the epitope specificity of the antigen-presenting B-cell.

  5. Lexicographical structuring: the number and types of fields, data distribution, searching and data presentation

    DEFF Research Database (Denmark)

    Bergenholtz, Henning; Pedersen, Heidi Agerbo

    2015-01-01

    in an existing dictionary. This part of the lexicographical work is what we call structuring, which encompasses a number of various lexicographical decisions. One of these is choosing the fields that a database should contain. Typically, for some of these field types, it will be easy to distribute data......, but for other fields it will require long considerations as there are several distribution options with different outcomes of varying usefulness. A second type of lexicographical decision to be made by the lexicographer is the predefined searching, which involves in what order searches are to be made...... dictionaries. However, only by producing monofunctional dictionaries is it possible to avoid the type of information overload, which makes polyfunctional dictionaries close to useless on electronic devices such as tablets and smartphones. In the case of monofunctional dictionaries, lexicographical structuring...

  6. Effects of Age of Transgressor, Damage, and Type of Presentation on Kindergarten Children's Moral Judgments

    Science.gov (United States)

    Rybash, John M.; And Others

    1975-01-01

    This study used both verbal and videotape presentation techniques to assess the role of cognitive conflict in children's moral judgments. The results indicated that the children presented problems via videotape based their moral judgments on intentions, while verbal presentation increased the number of moral judgments based on damage. (JMB)

  7. Unraveling the pathogenesis of type 1 diabetes with proteomics: present and future directions

    DEFF Research Database (Denmark)

    Sparre, Thomas; Larsen, Martin Røssel; Heding, Peter E

    2005-01-01

    of differentiating beta-cells, cytokine exposed islets, dietary manipulated islets, and in transplanted islets. Although that the studies have revealed a complex and detailed picture of the protein expression profiles many functional implications remain to be answered. In conclusion, a rather detailed picture...

  8. Constructing an in vitro cornea from cultures of the three specific corneal cell types.

    Science.gov (United States)

    Schneider, A I; Maier-Reif, K; Graeve, T

    1999-10-01

    This paper presents a reliable method for establishing pure cultures of the three types of corneal cells. This is believed to be the first time, corneal cells have been cultured from fetal pig corneas. Cell growth studies were performed in different media. Subcultures of the three corneal cell types were passaged until the 30th generation without their showing signs of senescence. For engineering an in vitro cornea, corneal epithelial cells were cultured over corneal stromal cells in an artificial biomatrix of collagen with an underlying layer of corneal endothelial cells. The morphology, histology, and differentiation of the in vitro cornea were investigated to determine the degree of comparability to the cornea in vivo. The in vitro construct displayed signs of transition to an organotypic phenotype of which the most prominent was the formation of two basement membranes.

  9. Raman spectroscopy for discrimination of neural progenitor cells and their lineages (Conference Presentation)

    Science.gov (United States)

    Chen, Keren; Ong, William; Chew, Sing Yian; Liu, Quan

    2017-02-01

    Neurological diseases are one of the leading causes of adult disability and they are estimated to cause more deaths than cancer in the elderly population by 2040. Stem cell therapy has shown great potential in treating neurological diseases. However, before cell therapy can be widely adopted in the long term, a number of challenges need to be addressed, including the fundamental research about cellular development of neural progenitor cells. To facilitate the fundamental research of neural progenitor cells, many methods have been developed to identify neural progenitor cells. Although great progress has been made, there is still lack of an effective method to achieve fast, label-free and noninvasive differentiation of neural progenitor cells and their lineages. As a fast, label-free and noninvasive technique, spontaneous Raman spectroscopy has been conducted to characterize many types of stem cells including neural stem cells. However, to our best knowledge, it has not been studied for the discrimination of neural progenitor cells from specific lineages. Here we report the differentiation of neural progenitor cell from their lineages including astrocytes, oligodendrocytes and neurons using spontaneous Raman spectroscopy. Moreover, we also evaluate the influence of system parameters during spectral acquisition on the quality of measured Raman spectra and the accuracy of classification using the spectra, which yield a set of optimal system parameters facilitating future studies.

  10. B lymphocytes as direct antigen-presenting cells for anti-tumor DNA vaccines

    Science.gov (United States)

    Colluru, Viswa Teja; McNeel, Douglas G.

    2016-01-01

    In spite of remarkable preclinical efficacy, DNA vaccination has demonstrated low immunogenicity in humans. While efforts have focused on increasing cross-presentation of DNA-encoded antigens, efforts to increase DNA vaccine immunogenicity by targeting direct presentation have remained mostly unexplored. In these studies, we compared the ability of different APCs to present antigen to T cells after simple co-culture with plasmid DNA. We found that human primary peripheral B lymphocytes, and not monocytes or in vitro derived dendritic cells (DCs), were able to efficiently encode antigen mRNA and expand cognate tumor antigen-specific CD8 T cells ex vivo. Similarly, murine B lymphocytes co-cultured with plasmid DNA, and not DCs, were able to prime antigen-specific T cells in vivo. Moreover, B lymphocyte-mediated presentation of plasmid antigen led to greater Th1-biased immunity and was sufficient to elicit an anti-tumor effect in vivo. Surprisingly, increasing plasmid presentation by B cells, and not cross presentation of peptides by DCs, further augmented traditional plasmid vaccination. Together, these data suggest that targeting plasmid DNA to B lymphocytes, for example through transfer of ex vivo plasmidloaded B cells, may be novel means to achieve greater T cell immunity from DNA vaccines. PMID:27661128

  11. X-linked hereditary motor sensory neuropathy (type 1) presenting with a stroke-like episode

    NARCIS (Netherlands)

    Anand, Geetha; Maheshwari, Nitin; Roberts, David; Padeniya, Anuruddha; Hamilton-Ayers, Michele; van der Knaap, Marjo; Fratter, Carl; Jayawant, Sandeep

    2010-01-01

    X-linked hereditary motor sensory neuropathy type 1 (CMTX 1) is caused by mutation in the GJB1 gene that codes for the connexin 32 protein. Central nervous system involvement with or without white matter changes on magnetic resonance imaging (MRI) has rarely been reported in this condition. We

  12. The Effects of Presenting Different Types of Vocabulary Clusters on Very Young Learners' Foreign Language Learning

    Science.gov (United States)

    Karabulut, Aslihan; Kesli Dollar, Yesim

    2016-01-01

    The main aim of this study was to find out which type of vocabulary cluster--semantic, thematic and unrelated--very young learners benefit from the most while learning foreign language vocabulary. The study also aimed at shedding light on the effects of these three vocabulary clusters on the immediate and delayed recall of foreign language…

  13. Extranodal interdigitating dendritic cell sarcoma presenting in the pleura: a case report.

    Science.gov (United States)

    Han, Hye-Suk; Lee, Ok-Jun; Lim, Sung-nam; An, Jin Young; Lee, Ki Man; Choe, Kang Hyeon; Lee, Ki Hyeong; Kim, Seung Taik

    2011-02-01

    Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare neoplasm arising from the antigen-presenting cells of the immune system. This disease usually involves the lymph nodes, and rarely, extranodal sites may be affected. The authors report a case of extranodal IDCS presenting in the pleura. A 32-yr-old man presented with progressive chest pain. Imaging studies showed diffuse pleural thickening with pleural effusion. Morphological and immunohistochemical analysis of an incisional biopsy of the pleura were consistent with a diagnosis of IDCS; tumor cells were positive for S100 and CD45, but negative for CD1a, CD21, CD35, B cell and T cell markers. The patient was administered chemotherapy, but died of progressive disease. Although its incidence is extremely rare, this case suggests that extranodal IDCS should be considered in the differential diagnosis of undifferentiated neoplasms and that immunohistochemical staining be performed using appropriate markers.

  14. 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.

  15. Cell-type specific four-component hydrogel.

    Directory of Open Access Journals (Sweden)

    Timo Aberle

    Full Text Available In the field of regenerative medicine we aim to develop implant matrices for specific tissue needs. By combining two per se, cell-permissive gel systems with enzymatic crosslinkers (gelatin/transglutaminase and fibrinogen/thrombin to generate a blend (technical term: quattroGel, an unexpected cell-selectivity evolved. QuattroGels were porous and formed cavities in the cell diameter range, possessed gelation kinetics in the minute range, viscoelastic properties and a mechanical strength appropriate for general cell adhesion, and restricted diffusion. Cell proliferation of endothelial cells, chondrocytes and fibroblasts was essentially unaffected. In contrast, on quattroGels neither endothelial cells formed vascular tubes nor did primary neurons extend neurites in significant amounts. Only chondrocytes differentiated properly as judged by collagen isoform expression. The biophysical quattroGel characteristics appeared to leave distinct cell processes such as mitosis unaffected and favored differentiation of sessile cells, but hampered differentiation of migratory cells. This cell-type selectivity is of interest e.g. during articular cartilage or invertebral disc repair, where pathological innervation and angiogenesis represent adverse events in tissue engineering.

  16. Selective culture of different types of human parotid gland cells.

    Science.gov (United States)

    Chan, Yen-Hui; Huang, Tsung-Wei; Young, Tai-Horng; Lou, Pei-Jen

    2011-03-01

    Advances in salivary gland tissue engineering can benefit patients diagnosed with xerostomia. Complexity of the gland explains the urgent demand for a reliable protocol to isolate and expand various gland cells that can be used for further study. Three cells with different morphologies were isolated from the same human parotid glands using different culture medium systems and then were identified by the expressions from mRNA to the protein level. Among the 34 specimens, parotid gland acinar cells, myoepithelial cells, and fibroblasts expressing specific markers that belonged to individual cell types, were successfully isolated and expanded from 30 specimens without a complex mechanical process and expensive flow technique. The proposed protocol is simple with a high success rate to culture various gland cells, making it highly promising for use in future tissue engineering studies. Copyright © 2010 Wiley Periodicals, Inc.

  17. Type-2 innate lymphoid cells in asthma and allergy.

    Science.gov (United States)

    McKenzie, Andrew N J

    2014-12-01

    Type-2 innate lymphoid cells (ILC2) belong to an expanding family of innate lymphocytes that provide a potent source of immune effector cytokines at the initiation of immune responses. ILC2 arise, under the control of the transcription factors RORα and GATA3, from lymphoid progenitors in the bone marrow, to secrete type-2 cytokines including IL-5 and IL-13. Using experimental models, ILC2 have been implicated in allergic diseases, such as asthma and atopic dermatitis, but also in metabolic homeostasis. Furthermore, recent reports have indicated that ILC2 not only play roles at the initiation of type-2 immunity but can also contribute to chronic pathology, such as fibrosis, and can impact on the priming of the adaptive T-cell response. The identification of ILC2 in patients with allergic dermatitis and allergic rhinitis indicates that these cells may represent new therapeutic targets.

  18. Role of Type 2 Innate Lymphoid Cells in Allergic Diseases.

    Science.gov (United States)

    Cosmi, Lorenzo; Liotta, Francesco; Maggi, Laura; Annunziato, Francesco

    2017-09-11

    The adaptive immune response orchestrated by type 2 T helper (Th2) lymphocytes, strictly cooperates with the innate response of group 2 innate lymphoid cells (ILC2), in the protection from helminths infection, as well as in the pathogenesis of allergic disease. The aim of this review is to explore the pathogenic role of ILC2 in different type 2-mediated disorders. Recent studies have shown that epithelial cell-derived cytokines and their responding cells, ILC2, play a pathogenic role in bronchial asthma, chronic rhinosinusitis, and atopic dermatitis. The growing evidences of the contribution of ILC2 in the induction and maintenance of allergic inflammation in such disease suggest the possibility to target them in therapy. Biological therapies blocking ILC2 activation or neutralizing their effector cytokines are currently under evaluation to be used in patients with type 2-dominated diseases.

  19. Overt attention and context factors: the impact of repeated presentations, image type, and individual motivation

    National Research Council Canada - National Science Library

    Kaspar, Kai; König, Peter

    2011-01-01

    The present study investigated the dynamic of the attention focus during observation of different categories of complex scenes and simultaneous consideration of individuals' memory and motivational state...

  20. Killer artificial antigen-presenting cells: the synthetic embodiment of a ‘guided missile’

    Science.gov (United States)

    Schütz, Christian; Oelke, Mathias; Schneck, Jonathan P; Mackensen, Andreas; Fleck, Martin

    2010-01-01

    At present, the treatment of T-cell-dependent autoimmune diseases relies exclusively on strategies leading to nonspecific suppression of the immune systems causing a substantial reduced ability to control concomitant infections or malignancies. Furthermore, long-term treatment with most drugs is accompanied by several serious adverse effects and does not consequently result in cure of the primary immunological malfunction. By contrast, antigen-specific immunotherapy offers the potential to achieve the highest therapeutic efficiency in accordance with minimal adverse effects. Therefore, several studies have been performed utilizing antigen-presenting cells specifically engineered to deplete allo- or antigen-specific T cells (‘guided missiles’). Many of these strategies take advantage of the Fas/Fas ligand signaling pathway to efficiently induce antigen-presenting cell-mediated apoptosis in targeted T cells. In this article, we discuss the advantages and shortcomings of a novel non-cell-based ‘killer artificial antigen-presenting cell’ strategy, developed to overcome obstacles related to current cell-based approaches for the treatment of T-cell-mediated autoimmunity. PMID:20636007

  1. Analysis Results for ARRA Projects: Enabling Fuel Cell Market Transformation (Presentation)

    Energy Technology Data Exchange (ETDEWEB)

    Kurtz, J.; Wipke, K.; Sprik, S.; Ramsden, T.; Ainscough, C.; Saur, G.

    2012-06-01

    This presentation discusses analysis results for American Recovery and Reinvestment Act early market fuel cell deployments and describes the objective of the project and its relevance to the Department of Energy Hydrogen and Fuel Cells Program; NREL's analysis approach; technical accomplishments including publication of a fourth set of composite data products; and collaborations and future work.

  2. Lymph node tuberculosis after allogeneic haematopoietic stem cell transplantation: an atypical presentation of an uncommon complication.

    Science.gov (United States)

    Martín-Sánchez, Guillermo; Drake-Pérez, Marta; Rodriguez, José Luis; Yañez, Lucrecia; Insunza, Andrés; Richard, Carlos

    2015-01-01

    Mycobacterium tuberculosis infections are uncommon complications in the haematopoietic stem cell post-transplant period. Most cases are reactivations of latent infections affecting the lung. We present an atypical case of isolated lymph node tuberculosis after an allogeneic haematopoietic stem cell transplantation, which highlights the importance of having a high suspicion index, even in non-endemic countries.

  3. Phosphoantigen Presentation to TCR γδ Cells, a Conundrum Getting Less Gray Zones.

    Science.gov (United States)

    De Libero, Gennaro; Lau, Sze-Yi; Mori, Lucia

    2014-01-01

    The mechanistic requirements of antigen recognition by T cells expressing a γδ TCR has revealed important differences with those of αβ TCR cells and, despite impressive new data generated in the very recent years, they remain poorly understood. Based on the structure of the TCR chains and the tissue distribution, γδ cells are represented in a variety of populations. The major subset of human peripheral blood γδ cells express Vγ9Vδ2 TCR heterodimers and are all stimulated by phosphorylated metabolites (commonly called phosphoantigens). Phosphoantigens are molecules with a very small mass and only stimulate Vγ9Vδ2 cells in the presence of antigen-presenting cells, suggesting a strict requirement for dedicated antigen-presenting molecules. Recent studies have identified butyrophilin (BTN) 3A1 as the molecule necessary to stimulate Vγ9Vδ2 cells. BTN3A1 extracellular, transmembrane, and cytoplasmic domains have different functions, including cognate interaction with the Vγ9Vδ2 TCR, binding of the phosphoantigens, and interaction with cytoplasmic proteins. This review mainly discusses the known molecular mechanisms of BTN3A1-mediated antigen presentation to γδ cells and proposes a model of phosphoantigen presentation, which integrates past and recent studies.

  4. Measuring dynamic membrane fluctuations in cell membrane using quantitative phase imaging (Conference Presentation)

    Science.gov (United States)

    Lee, SangYun; Kim, Kyoohyun; Park, YongKeun

    2017-02-01

    There is a strong correlation between the dynamic membrane fluctuations and the biomechanical properties of living cells. The dynamic membrane fluctuation consists of submicron displacements, and can be altered by changing the cells' pathophysiological conditions. These results have significant relevance to the understanding of RBC biophysics and pathology, as follows. RBCs must withstand large mechanical deformations during repeated passages through the microvasculature and the fenestrated walls of the splenic sinusoids. This essential ability is diminished with senescence, resulting in physiological destruction of the aging RBCs. Pathological destruction of the red cells, however, occurs in cells affected by a host of diseases such as spherocytosis, malaria, and Sickle cell disease, as RBCs depart from their normal discoid shape and lose their deformability. Therefore, quantifying the RBC deformability insight into a variety of problems regarding the interplay of cell structure, dynamics, and function. Furthermore, the ability to monitor mechanical properties of RBCs is of vital interest in monitoring disease progression or response to treatment as molecular and pharmaceutical approaches for treatment of chronic diseases. Here, we present the measurements of dynamic membrane fluctuations in live cells using quantitative phase imaging techniques. Measuring both the 3-D refractive index maps and the dynamic phase images of live cells are simultaneously measured, from which dynamic membrane fluctuation and deformability of cells are precisely calculated. We also present its applications to various diseases ranging from sickle cell diseases, babesiosis, and to diabetes.

  5. A case of acute autoimmune hepatitis presenting after incomplete-type CREST syndrome and chronic thyroiditis.

    Science.gov (United States)

    Himoto, Takashi; Nomura, Takako; Tani, Joji; Miyoshi, Hisaaki; Morishita, Asahiro; Yoneyama, Hirohito; Kurokohchi, Kazutaka; Kushida, Yoshio; Watanabe, Seishiro; Masaki, Tsutomu

    2014-09-01

    A 55-year-old woman was admitted to our hospital with acute hepatitis of unknown origin. She had a history of incomplete-type CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome and chronic thyroiditis approximately 10 years earlier. Although she achieved spontaneous remission without treatment, she was re-admitted 18 months later due to recurrent liver dysfunction. Liver biopsy was performed as we strongly suspected autoimmune hepatitis despite her normal serum immunoglobulin G level. Liver biopsy findings were histologically compatible with autoimmune hepatitis, and administering prednisolone (30 mg/day) led to a prompt recovery of her liver dysfunction. No relapse occurred during the tapering of prednisolone to a maintenance dose of 5 mg/day. Here we report a rare case of autoimmune hepatitis in a patient with a history of incomplete-type CREST syndrome and chronic thyroiditis.

  6. A Type-II First Branchial Cleft Anomaly Presenting as a Post ...

    African Journals Online (AJOL)

    hanumantp

    First branchial cleft anomalies are rare accounting for <8% of all branchial anomalies.[1] The average age of presentation is 19 years with an average delay of 3.5 years between initial presentation and adequate treatment due to diagnostic dilemma.[2] The spectrum of first branchial cleft anomalies includes cysts, sinuses ...

  7. Stem cell therapies for age-related macular degeneration: the past, present, and future

    Directory of Open Access Journals (Sweden)

    Dang Y

    2015-01-01

    Full Text Available Yalong Dang,1–3 Chun Zhang,1,2 Yu Zhu31Department of Ophthalmology, Peking University Third Hospital, Beijing, People’s Republic of China; 2Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing, People’s Republic of China; 3Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaAbstract: In the developed world, age-related macular degeneration (AMD is one of the major causes of irreversible blindness in the elderly. Although management of neovascular AMD (wet AMD has dramatically progressed, there is still no effective treatment for nonneovascular AMD (dry AMD, which is characterized by retinal pigment epithelial (RPE cell death (or dysfunction and microenvironmental disruption in the retina. Therefore, RPE replacement and microenvironmental regulation represent viable treatments for dry AMD. Recent advances in cell biology have demonstrated that RPE cells can be easily generated from several cell types (pluripotent stem cells, multipotent stem cells, or even somatic cells by spontaneous differentiation, coculturing, defined factors or cell reprogramming, respectively. Additionally, in vivo studies also showed that the restoration of visual function could be obtained by transplanting functional RPE cells into the subretinal space of recipient. More importantly, clinical trials approved by the US government have shown promising prospects in RPE transplantation. However, key issues such as implantation techniques, immune rejection, and xeno-free techniques are still needed to be further investigated. This review will summarize recent advances in cell transplantation for dry AMD. The obstacles and prospects in this field will also be discussed.Keywords: stem cell, age-related macular degeneration, retinal pigment epithelium, cell reprogramming, clinical trial

  8. A Self-Directed Method for Cell-Type Identification and Separation of Gene Expression Microarrays

    Science.gov (United States)

    Zuckerman, Neta S.; Noam, Yair; Goldsmith, Andrea J.; Lee, Peter P.

    2013-01-01

    Gene expression analysis is generally performed on heterogeneous tissue samples consisting of multiple cell types. Current methods developed to separate heterogeneous gene expression rely on prior knowledge of the cell-type composition and/or signatures - these are not available in most public datasets. We present a novel method to identify the cell-type composition, signatures and proportions per sample without need for a-priori information. The method was successfully tested on controlled and semi-controlled datasets and performed as accurately as current methods that do require additional information. As such, this method enables the analysis of cell-type specific gene expression using existing large pools of publically available microarray datasets. PMID:23990767

  9. Expanded human blood-derived γδT cells display potent antigen-presentation functions

    Directory of Open Access Journals (Sweden)

    Mohd Wajid Ali Khan

    2014-07-01

    Full Text Available Cell-based immunotherapy strategies target tumors directly (via cytolytic effector cells or aim at mobilizing endogenous anti-tumor immunity. The latter approach includes dendritic cells (DC, most frequently in the form of in vitro cultured peripheral blood monocytes-derived DC. Human blood γδT cells are selective for a single class of non-peptide agonists (phosphoantigens and develop into potent antigen-presenting cells (APC, termed γδT-APC, within 1-3 days of in vitro culture. Availability of large numbers of γδT-APC would be advantageous for use as a novel cellular vaccine. We here report optimal γδT cell expansion (>107 cells/ml blood when peripheral blood mononuclear cells (PBMC from healthy individuals and melanoma patients were stimulated with zoledronate and then cultured for 14 days in the presence of IL-2 and IL-15, yielding γδT cell cultures of variable purity (77±21% and 56±26%, respectively. They resembled effector-memory αβT (TEM cells and retained full functionality as assessed by in vitro tumor cell killing as well as secretion of proinflammatory cytokines (IFNγ, TNFα and cell proliferation in response to stimulation with phosphoantigens. Importantly, day 14 γδT cells expressed numerous APC-related cell surface markers and, in agreement, displayed potent in vitro APC functions. Day 14 γδT cells from PBMC of patients with cancer were equally effective as their counterparts derived from blood of healthy individuals and triggered potent CD8+ αβT cell responses following processing and cross-presentation of simple (influenza M1 and complex (tuberculin purified protein derivative protein antigens. Of note, and in clear contrast to peripheral blood γδT cells, the ability of day 14 γδT cells to trigger antigen-specific αβT cell responses did not depend on re-stimulation. We conclude that day 14 γδT cell cultures provide a convenient source of autologous APC for use in immunotherapy of

  10. PREVALENCE AND TYPES OF SPORTS INJURIES PRESENTING TO EMERGENCY DEPARTMENT SUEZ CANAL UNIVERSITY HOSPITAL

    Directory of Open Access Journals (Sweden)

    Adel Hamed Elbaih

    2016-10-01

    Full Text Available Inroduction: regular physical activity is essential for the prevention of various diseases and reduces the risk of premature mortality in general and coronary heart disease, hypertension, colon cancer, obesity and diabetes mellitus in particular. Aim of this study was to assess the most common sports causing injuries and to assess the types and mechanisms of these injuries. Patients and methods: The researcher examined 250 patients attending emergency departmentl. Results: The study showed that the most common type of sports involved in injury was football .The ankle was the most common affected part in the whole body . Chest contusion and back contusion were the most common types of sports injuries in head, neck and trunk. Fracture scaphoid and fissure radius were the most common sport injuries. Ankle sprain was the most common injury. The study showed that (62.7% of the studied patients who were playing football had injuries in the lower limbs. Ankle sprain was the most common sport injury that was associated with wearing football shoes . Conclusion: Ankle sprain was the most common sport injury associated with artificial grass court . Wrist sprain was the common sport injury in the upper limbs associated with artificial grass court .

  11. Diffuse-type giant cell tumor of the subcutaneous thigh

    Energy Technology Data Exchange (ETDEWEB)

    Sanghvi, D.A. [KEM Hospital, Department of Radiology, Parel, Mumbai (India); Purandare, N.C. [Tata Memorial Hospital, Bio Imaging Unit, Parel, Mumbai (India); Jambhekar, N.A.; Agarwal, A. [Tata Memorial Hospital, Department of Pathology, Parel, Mumbai (India); Agarwal, M.G. [Tata Memorial Hospital, Bone and Soft Tissue Unit, Parel, Mumbai (India)

    2007-04-15

    Diffuse-type giant cell tumor is an extra-articular form of pigmented villonodular synovitis. The localized form of this lesion (tenosynovial giant cell tumor) is frequent, representing the most common subset arising from the synovium of a joint, bursa or tendon sheath, with 85% of cases occurring in the fingers. The less frequent diffuse-type giant cell tumors are commonly located in the periarticular soft tissues, but on rare occasions these lesions can be purely intramuscular or subcutaneous We report the case of a 26-year-old female with diffuse-type giant cell tumor of the subcutaneous thigh, remote from a joint, bursa or tendon sheath. A review of the literature did not reveal any similar description of a diffuse-type giant cell tumor completely within the subcutaneous thigh, remote from a joint, bursa or tendon sheath. These lesions were initially regarded as inflammatory or reactive processes, but since the identification of clonal abnormalities in these patients, and in view of their capacity for autonomous growth, they are now widely considered to represent benign neoplasms. (orig.)

  12. Role of T Cells in Type 2 Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Chia-Chao Wu

    2011-01-01

    Full Text Available Type 2 diabetic nephropathy (DN is the most common cause of end-stage renal disease and is increasingly considered as an inflammatory disease characterized by leukocyte infiltration at every stage of renal involvement. Inflammation and activation of the immune system are closely involved in the pathogenesis of diabetes and its microvascular complications. Macrophage has been well recognized to play an important role in type 2 DN, leukocyte infiltration, and participated in process of DN, as was proposed recently. Th1, Th2, Th17, T reg, and cytotoxic T cells are involved in the development and progression of DN. The purpose of this review is to assemble current information concerning the role of T cells in the development and progression of type 2 DN. Specific emphasis is placed on the potential interaction and contribution of the T cells to renal damage. The therapeutic strategies involving T cells in the treatment of type 2 DN are also reviewed. Improving knowledge of the recognition of T cells as significant pathogenic mediators in DN reinforces the possibility of new potential therapeutic targets translated into future clinical treatments.

  13. Cell type-specific responses to salinity - the epidermal bladder cell transcriptome of Mesembryanthemum crystallinum.

    Science.gov (United States)

    Oh, Dong-Ha; Barkla, Bronwyn J; Vera-Estrella, Rosario; Pantoja, Omar; Lee, Sang-Yeol; Bohnert, Hans J; Dassanayake, Maheshi

    2015-08-01

    Mesembryanthemum crystallinum (ice plant) exhibits extreme tolerance to salt. Epidermal bladder cells (EBCs), developing on the surface of aerial tissues and specialized in sodium sequestration and other protective functions, are critical for the plant's stress adaptation. We present the first transcriptome analysis of EBCs isolated from intact plants, to investigate cell type-specific responses during plant salt adaptation. We developed a de novo assembled, nonredundant EBC reference transcriptome. Using RNAseq, we compared the expression patterns of the EBC-specific transcriptome between control and salt-treated plants. The EBC reference transcriptome consists of 37 341 transcript-contigs, of which 7% showed significantly different expression between salt-treated and control samples. We identified significant changes in ion transport, metabolism related to energy generation and osmolyte accumulation, stress signalling, and organelle functions, as well as a number of lineage-specific genes of unknown function, in response to salt treatment. The salinity-induced EBC transcriptome includes active transcript clusters, refuting the view of EBCs as passive storage compartments in the whole-plant stress response. EBC transcriptomes, differing from those of whole plants or leaf tissue, exemplify the importance of cell type-specific resolution in understanding stress adaptive mechanisms. No claim to original US government works. New Phytologist © 2015 New Phytologist Trust.

  14. Mantle cell lymphoma of the gastrointestinal tract presenting with multiple intussusceptions – case report and review of literature

    Directory of Open Access Journals (Sweden)

    Abo Stephen M

    2009-07-01

    Full Text Available Abstract Background Mantle cell lymphoma (MCL is an aggressive type of B-cell non-Hodgkin's lymphoma that originates from small to medium sized lymphocytes located in the mantle zone of the lymph node. Extra nodal involvement is present in the majority of cases, with a peculiar tendency to invade the gastro-intestinal tract in the form of multiple lymphomatous polyposis. MCL can be accurately diagnosed with the use of the highly specific marker Cyclin D1. Few cases of mantle cell lymphoma presenting with intussuception have been reported. Here we present a rare case of multiple intussusceptions caused by mantle cell lymphoma and review the literature of this disease. Case presentation A 68-year-old male presented with pain, tenderness in the right lower abdomen, associated with nausea and non-bilious vomiting. CT scan of abdomen revealed ileo-colic intussusception. Laparoscopy confirmed multiple intussusceptions involving ileo-colic and ileo-ileal segments of gastrointestinal tract. A laparoscopically assisted right hemicolectomy and extended ileal resection was performed. Postoperative recovery was uneventful. The histology and immuno-histochemistry of the excised small and large bowel revealed mantle cell lymphoma with multiple lymphomatous polyposis and positivity to Cyclin D1 marker. The patient was successfully treated with Rituximab-CHOP chemotherapy and remains in complete remission at one-year follow-up. Conclusion This is a rare case of intestinal lymphomatous polyposis due to mantle cell lymphoma presenting with multiple small bowel intussusceptions. Our case highlights laparoscopic-assisted bowel resection as a potential and feasible option in the multi-disciplinary treatment of mantle cell lymphoma.

  15. [Molecular pathogenesis of peripheral T cell lymphoma (2): extranodal NK/T cell lymphoma, nasal type, adult T cell leukemia/lymphoma and enteropathy associated T cell lymphoma].

    Science.gov (United States)

    Couronné, Lucile; Bastard, Christian; Gaulard, Philippe; Hermine, Olivier; Bernard, Olivier

    2015-11-01

    Peripheral T-cell lymphomas (PTCL) belong to the group of non-Hodgkin lymphoma and particularly that of mature T /NK cells lymphoproliferative neoplasms. The 2008 WHO classification describes different PTCL entities with varying prevalence. With the exception of histologic subtype "ALK positive anaplastic large cell lymphoma", PTCL are characterized by a poor prognosis. The mechanisms underlying the pathogenesis of these lymphomas are not yet fully understood, but development of genomic high-throughput analysis techniques now allows to extensively identify the molecular abnormalities present in tumor cells. This review aims to summarize the current knowledge and recent advances about the molecular events occurring at the origin or during the natural history of main entities of PTCL. The first part published in the October issue was focused on the three more frequent entities, i.e. angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma, not otherwise specified, and anaplastic large cell lymphoma. The second part presented herein will describe other subtypes less frequent and of poor prognosis : extranodal NK/T-cell lymphoma, nasal type, adult T-cell leukemia/lymphoma, and enteropathy-associated T-cell lymphoma. © 2015 médecine/sciences – Inserm.

  16. Cell growth on different types of ultrananocrystalline diamond thin films.

    Science.gov (United States)

    Shi, Bing; Jin, Qiaoling; Chen, Liaohai; Woods, Amina S; Schultz, Albert J; Auciello, Orlando

    2012-08-16

    Unique functional materials provide a platform as scaffolds for cell/tissue regeneration. Investigation of cell-materials' chemical and biological interactions will enable the application of more functional materials in the area of bioengineering, which provides a pathway to the novel treatment for patients who suffer from tissue/organ damage and face the limitation of donation sources. Many studies have been made into tissue/organ regeneration. Development of new substrate materials as platforms for cell/tissue regeneration is a key research area. Studies discussed in this paper focus on the investigation of novel ultrananocrystalline diamond (UNCD) films as substrate/scaffold materials for developmental biology. Specially designed quartz dishes have been coated with different types of UNCD films and cells were subsequently seeded on those films. Results showed the cells' growth on UNCD-coated culture dishes are similar to cell culture dishes with little retardation, indicating that UNCD films have no or little inhibition on cell proliferation and are potentially appealing as substrate/scaffold materials. The mechanisms of cell adhesion on UNCD surfaces are proposed based on the experimental results. The comparisons of cell cultures on diamond-powder-seeded culture dishes and on UNCD-coated dishes with matrix-assisted laser desorption/ionization-time-of-flight mass spectroscopy (MALDI-TOF MS) and X-ray photoelectron spectroscopy (XPS) analyses provided valuable data to support the mechanisms proposed to explain the adhesion and proliferation of cells on the surface of the UNCD platform.

  17. Type I interferon is selectively required by dendritic cells for immune rejection of tumors.

    Science.gov (United States)

    Diamond, Mark S; Kinder, Michelle; Matsushita, Hirokazu; Mashayekhi, Mona; Dunn, Gavin P; Archambault, Jessica M; Lee, Hsiaoju; Arthur, Cora D; White, J Michael; Kalinke, Ulrich; Murphy, Kenneth M; Schreiber, Robert D

    2011-09-26

    Cancer immunoediting is the process whereby the immune system suppresses neoplastic growth and shapes tumor immunogenicity. We previously reported that type I interferon (IFN-α/β) plays a central role in this process and that hematopoietic cells represent critical targets of type I IFN's actions. However, the specific cells affected by IFN-α/β and the functional processes that type I IFN induces remain undefined. Herein, we show that type I IFN is required to initiate the antitumor response and that its actions are temporally distinct from IFN-γ during cancer immunoediting. Using mixed bone marrow chimeric mice, we demonstrate that type I IFN sensitivity selectively within the innate immune compartment is essential for tumor-specific T cell priming and tumor elimination. We further show that mice lacking IFNAR1 (IFN-α/β receptor 1) in dendritic cells (DCs; Itgax-Cre(+)Ifnar1(f/f) mice) cannot reject highly immunogenic tumor cells and that CD8α(+) DCs from these mice display defects in antigen cross-presentation to CD8(+) T cells. In contrast, mice depleted of NK cells or mice that lack IFNAR1 in granulocytes and macrophage populations reject these tumors normally. Thus, DCs and specifically CD8α(+) DCs are functionally relevant targets of endogenous type I IFN during lymphocyte-mediated tumor rejection.

  18. Acute renal failure and hepatocellular damage as presenting symptoms of type II aortic dissection

    National Research Council Canada - National Science Library

    Jovanovic, Ivana; Tesic, Milorad; Antonijevic, Nebojsa; Menkovic, Nemanja; Paunovic, Ivana; Ristic, Arsen; Vucicevic, Vera; Vujisic-Tesic, Bosiljka

    2016-01-01

    ..., while presenting with an acute renal and hepatic failure. After initial diagnostic uncertainties, and following final diagnosis of an acute aortic dissection, this patient underwent surgical aortic valve replacement with a satisfactory outcome. Conclusion...

  19. The Effects of Repetition and Presentation Type on the Coding of German Words in Semantic Memory

    OpenAIRE

    İbrahim And UYANIK; Coşkun, Hamit; UĞUR, Yunus; DURAKOĞLU, Abdullah

    2017-01-01

    The purpose of this study was to examinewhether or not the effect of rewriting concepts in foreign language, whichaimed to enhance working and semantic memory, would improve learning. Incognitive psychology, repetition has been suggested to improve memory traces inlong- term memory. However, whether this is valid or not in foreign language isstill unknown. In addition, the effect of presenting newly learned concepts invisual and written form was examined in this research. Visual presentation ...

  20. Thermodynamic efficiency of present types of internal combustion engines for aircraft

    Science.gov (United States)

    Lucke, Charles E

    1917-01-01

    Report presents requirements of internal combustion engines suitable for aircraft. Topics include: (1) service requirements for aeronautic engines - power versus weight, reliability, and adaptability factors, (2) general characteristics of present aero engines, (3) aero engine processes and functions of parts versus power-weight ratio, reliability, and adaptability factors, and (4) general arrangement, form, proportions, and materials of aero parts - power-weight ratio, reliability, and adaptability.

  1. Cell-type Phylogenetics and the Origin of Endometrial Stromal Cells

    Directory of Open Access Journals (Sweden)

    Koryu Kin

    2015-03-01

    Full Text Available A challenge of genome annotation is the identification of genes performing specific biological functions. Here, we propose a phylogenetic approach that utilizes RNA-seq data to infer the historical relationships among cell types and to trace the pattern of gene-expression changes on the tree. The hypothesis is that gene-expression changes coincidental with the origin of a cell type will be important for the function of the derived cell type. We apply this approach to the endometrial stromal cells (ESCs, which are critical for the initiation and maintenance of pregnancy. Our approach identified well-known regulators of ESCs, PGR and FOXO1, as well as genes not yet implicated in female fertility, including GATA2 and TFAP2C. Knockdown analysis confirmed that they are essential for ESC differentiation. We conclude that phylogenetic analysis of cell transcriptomes is a powerful tool for discovery of genes performing cell-type-specific functions.

  2. 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.

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

    Science.gov (United States)

    Goyvaerts, Cleo; Breckpot, Karine

    2015-01-01

    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. PMID:26583156

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

    Science.gov (United States)

    Goyvaerts, Cleo; Breckpot, Karine

    2015-01-01

    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.

  5. Clinical presentation of Griscelli syndrome type 2 and spectrum of RAB27A mutations

    DEFF Research Database (Denmark)

    Meeths, Marie; Bryceson, Yenan T; Rudd, Eva

    2010-01-01

    Griscelli syndrome type 2 (GS2) is an autosomal-recessive immunodeficiency caused by mutations in RAB27A, clinically characterized by partial albinism and haemophagocytic lymphohistocytosis (HLH). We evaluated the frequency of RAB27A mutations in 21 unrelated patients with haemophagocytic syndromes...... without mutations in familial HLH (FHL) causing genes or an established diagnosis of GS2. In addition, we report three patients with known GS2. Moreover, neurological involvement and RAB27A mutations in previously published patients with genetically verified GS2 are reviewed....

  6. Hypertriglyceridemia-induced acute pancreatitis with diabetic ketoacidosis: A rare presentation of type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Prabhat Kumar

    2017-01-01

    Full Text Available Diabetic ketoacidosis (DKA is a frequently encountered complication of diabetes mellitus. DKA is an insulin deficit state and results in moderate to severe hypertriglyceridemia (HTG. HTG is the third leading cause of acute pancreatitis (AP and often goes unnoticed. The triad of DKA, HTG, and AP is rarely seen, and literature on the same is sparse. We report a case of AP which was due to DKA-induced secondary HTG in an adult with previously undiagnosed type 1 diabetes. His HbA1c was significantly raised, and C-peptide level was low, confirming chronic hyperglycemia. He was treated successfully with insulin infusion, intravenous crystalloid, and analgesics.

  7. Small-cell carcinoma of the endometrium presenting as Cushing's syndrome.

    Science.gov (United States)

    Sato, Haruhiro; Kanai, Genta; Kajiwara, Hiroshi; Itoh, Johbu; Osamura, Robert Yoshiyuki

    2010-01-01

    Small-cell carcinoma (SCC) of neuroendocrine type is an uncommon tumor of the endometrium. No previous report has documented Cushing's syndrome due to ectopic ACTH production by SCC of the endometrium. We describe a 56-year-old Japanese woman with SCC of the endometrium and multiple lung metastases presenting as Cushing's syndrome. The patient was referred to our hospital because of general fatigue with facial and leg edema, and multiple nodular lesions in the bilateral lungs on chest X-ray examination. A physical examination revealed that the patient had moon face, buffalo hump, and truncal obesity. Endocrinological examinations confirmed ACTH-dependent Cushing's syndrome. Thoracic computed tomography imaging showed multiple nodular lesions in the bilateral lungs. Abdominal magnetic resonance imaging suggested a malignant tumor of the uterus. The patient received a lung tumor biopsy and surgical hysterectomy. The endometrial carcinoma was histologically a SCC admixed with endometrioid adenocarcinoma. The SCC of the endometrium showed immunoreactivity for pro-opiomelanocortin, ACTH, and vimentin, but not for thyroid transcription factor-1. The lung biopsy specimen had the same features. These findings indicated that the SCC originated from the endometrium, and the ectopic ACTH-producing tumor caused Cushing's syndrome. This study provides the evidence that SCC of endometrial origin was an ectopic ACTH-producing tumor causing Cushing's syndrome.

  8. Skin-resident antigen-presenting cells: Instruction manual for vaccine development

    Directory of Open Access Journals (Sweden)

    Cynthia M. Fehres

    2013-06-01

    Full Text Available The induction of antigen-specific effector T cells is driven by proper antigen presentation and co-stimulation by dendritic cells (DCs. For this reason strategies have been developed to instruct DCs for the induction of CD4+ and CD8+ T cell responses. Since DCs are localized, amongst other locations, in peripheral tissues such as the skin, new vaccines are aiming at targeting antigens to DCs in situ. Optimal skin-DC targeting in combination with adequate adjuvant delivery facilitates DC maturation and migration to draining lymph nodes and enhances antigen cross-presentation and T cell priming. In this review we describe what DC subsets populate the human skin, as well as current vaccination strategies based on targeting strategies and alternative administration for the induction of robust long-lived anti-cancer effector T cells.

  9. Conjunctival mass as an initial presentation of mantle cell lymphoma: a case report

    Directory of Open Access Journals (Sweden)

    Khanlari Mahsa

    2012-12-01

    Full Text Available Abstract Background To describe a rare manifestation of mantle cell lymphoma (MCL in conjunctiva, with clinical, hisologic, immunohistologic and genetic findings together with review of the Literature. Case presentation Most ocular adnexal lymphomas are extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT. A few cases of ocular adnexal mantle cell lymphomas have been reported in the literature. We present a case of mantle cell lymphoma presenting as right conjunctival mass of at least three months duration in a 64-year-old man. Histopathologic examination showed a proliferation of monomorphous small-to-medium-sized lymphoid cells with cleaved nuclei in the subconjunctiva. By immunohistochemistry, the infiltrate was positive for CD20, CD5, BCL-2, cyclin D1, and the transcription factor SOX11. Fluorescent in situ hybridization demonstrated the presence of IGH-CCND1 fusion indicating t(11;14. Conclusion A rigorous approach to initial diagnosis and staging of small cell lymphomas of the ocular adnexa is needed. The recognition of ocular MCL requires appropriate immunohistochemical staining and/or genetic confirmation to differentiate this rare form of presentation of MCL from other more frequent small cell lymphomas.

  10. Seizure as a presenting manifestation of vitamin D dependent rickets type 1

    Directory of Open Access Journals (Sweden)

    P Radha Rani

    2013-01-01

    Full Text Available There are two types of vitamin D dependent rickets (VDDR that cause rickets in children. VDDR type 1 (VDDR-I is caused by an inborn error of vitamin D metabolism, which interferes with renal conversion of calcidiol (25OHD to calcitriol (1,25(OH 2 D by the enzyme 1-α-hydroxylase. Patients with VDDR-I have mutations of chromosome 12 that affect the gene for the enzyme 1-α-hydroxylase, resulting in decreased levels of 1,25(OH vitamin D. Clinical features include growth failure, hypotonia, weakness, rachitic rosary, convulsions, tetany, open fontanels and pathologic fractures. We report a case of VDDR-I in 14-month-old male child. Establishing an early diagnosis of these genetic forms of rickets is challenging, especially in developing countries where nutritional rickets is the most common variety of the disease where genetic diagnosis is not always possible because of financial constraints. A prompt diagnosis is necessary to initiate adequate treatment, resolve biochemical features and prevent complications, such as severe deformities that may require surgical intervention.

  11. Uptake of T-2 Mycotoxin in Cultured Cells. Relationship to Sodium Fluoride and Cell Type

    Science.gov (United States)

    1986-10-20

    woC)) -13-7i3 , UFILE CORY UPTAKE OF T-2 MYCOTOXIN IN CULTURED CELLS. RELATIONSHIP TO SODIUM FLUORIDE AND CELL TYPE. S~DTIC’ Lynn R. Trusal and Lee...NUMBER &. TITLE (and SubettI.) 13&i.’TYPE Of RE PORT A PERIOD COVERED Uptake of T-2 Mycotoxin in Cultured Cells. Relationship to Sodium Fluoride and Cell...necees.m and ident~il by block member) T-2 mycotoxin cultured cells sodium fluoride 24k ANITRACT’ (Cmet i 0 09 6401D Nid urnews 001 edast~ biY10 block

  12. Meta-analysis reveals conserved cell cycle transcriptional network across multiple human cell types.

    Science.gov (United States)

    Giotti, Bruno; Joshi, Anagha; Freeman, Tom C

    2017-01-05

    Cell division is central to the physiology and pathology of all eukaryotic organisms. The molecular machinery underpinning the cell cycle has been studied extensively in a number of species and core aspects of it have been found to be highly conserved. Similarly, the transcriptional changes associated with this pathway have been studied in different organisms and different cell types. In each case hundreds of genes have been reported to be regulated, however there seems to be little consensus in the genes identified across different studies. In a recent comparison of transcriptomic studies of the cell cycle in different human cell types, only 96 cell cycle genes were reported to be the same across all studies examined. Here we perform a systematic re-examination of published human cell cycle expression data by using a network-based approach to identify groups of genes with a similar expression profile and therefore function. Two clusters in particular, containing 298 transcripts, showed patterns of expression consistent with cell cycle occurrence across the four human cell types assessed. Our analysis shows that there is a far greater conservation of cell cycle-associated gene expression across human cell types than reported previously, which can be separated into two distinct transcriptional networks associated with the G 1 /S-S and G 2 -M phases of the cell cycle. This work also highlights the benefits of performing a re-analysis on combined datasets.

  13. MAGI-1 expression is decreased in several types of human T-cell leukemia cell lines, including adult T-cell leukemia.

    Science.gov (United States)

    Kozakai, Takashi; Takahashi, Masahiko; Higuchi, Masaya; Hara, Toshifumi; Saito, Kousuke; Tanaka, Yuetsu; Masuko, Masayoshi; Takizawa, Jun; Sone, Hirohito; Fujii, Masahiro

    2018-03-01

    Membrane-associated guanylate kinase with inverted orientation protein 1 (MAGI-1) is a cytoplasmic scaffold protein that interacts with various signaling molecules; it negatively controls the cell growth of various types of cells and positively controls cell-cell interaction. In T cells, MAGI-1 has been shown to inhibit Akt activity through its interaction with PTEN and MEK1. In this study we found that MAGI-1 expression is decreased in multiple (9 out of 15) human T-cell leukemia cell lines, including adult T-cell leukemia (ATL), T-cell acute lymphoblastic leukemia and chronic T-cell lymphocytic leukemia. The overexpression of MAGI-1 protein in a MAGI-1-low ATL cell line reduced cellular growth. While the overexpression of MAGI-1 protein in a MAGI-1-low ATL cell line reduced the Akt and MEK activities, the knockdown of MAGI-1 in a MAGI-1-high ATL cell line augmented the Akt and MEK activities. Collectively, the findings of the present study suggest that the decreased expression of MAGI-1 in human T cells contributes to the development of several types of T-cell leukemia, partly through the stimulation of the Akt and MEK pathways.

  14. CD4+ T-Cell Reactivity to Orexin/Hypocretin in Patients With Narcolepsy Type 1.

    Science.gov (United States)

    Ramberger, Melanie; Högl, Birgit; Stefani, Ambra; Mitterling, Thomas; Reindl, Markus; Lutterotti, Andreas

    2017-03-01

    Narcolepsy type 1 is accompanied by a selective loss of orexin/hypocretin (hcrt) neurons in the lateral hypothalamus caused by yet unknown mechanisms. Epidemiologic and genetic associations strongly suggest an immune-mediated pathogenesis of the disease. We compared specific T-cell reactivity to orexin/hcrt peptides in peripheral blood mononuclear cells of narcolepsy type 1 patients to healthy controls by a carboxyfluorescein succinimidyl ester proliferation assay. Orexin/hcrt-specific T-cell reactivity was also determined by cytokine (interferon gamma and granulocyte-macrophage colony-stimulating factor) analysis. Individuals were considered as responders if the cell division index of CD3+CD4+ T cells and both stimulation indices of cytokine secretion exceeded the cutoff 3. Additionally, T-cell reactivity to orexin/hcrt had to be confirmed by showing reactivity to single peptides present in different peptide pools. Using these criteria, 3/15 patients (20%) and 0/13 controls (0%) showed orexin/hcrt-specific CD4+ T-cell proliferation (p = .2262). The heterogeneous reactivity pattern did not allow the identification of a preferential target epitope. A significant role of orexin/hcrt-specific T cells in narcolepsy type 1 patients could not be confirmed in this study. Further studies are needed to assess the exact role of CD4+ T cells and possible target antigens in narcolepsy type 1 patients.

  15. Trans-presentation of IL-15 by intestinal epithelial cells drives development of CD8αα IELs1

    Science.gov (United States)

    Ma, Lisa J.; Acero, Luis F.; Zal, Tomasz; Schluns, Kimberly S.

    2009-01-01

    IL-15 is crucial for the development of intestinal intraepithelial lymphocytes (IEL) and delivery is mediated by a unique mechanism known as trans-presentation. Parenchymal cells have a major role in the trans-presentation of IL-15 to IELs, but the specific identity of this cell type is unknown. To investigate whether the intestinal epithelial cells (IEC) are the parenchymal cell type involved, a mouse model that expresses IL-15Rα exclusively by the IECs (Villin/IL-15Rα Tg) was generated. Exclusive expression of IL-15Rα by the IECs restored all the deficiencies in the CD8αα+TCRαβ+and CD8αα+TCRγδ+ subsets that exist in the absence of IL-15Rα. Interestingly, most of the IEL recovery was due to the preferential increase in Thy1lo IELs, which compose a majority of the IEL population. The differentiation of Thy1hiCD4−CD8− thymocytes into Thy1−CD8αα IELs was found to require IL-15Rα expression specifically by IECs and thus, provides evidence that differentiation of Thy1lo IELs is one function of trans-presentation of IL-15 in the intestines. In addition to effects in IEL differentiation, trans-presentation of IL-15 by IECs also resulted in an increase in IEL numbers that was accompanied by increases in Bcl-2, but not proliferation. Collectively, this study demonstrates that trans-presentation of IL-15 by IECs alone is completely sufficient to direct the IL-15-mediated development of CD8αα+ T cell populations within the IEL compartment, which now includes a newly identified role of IL-15 in the differentiation of Thy1lo IELs. PMID:19553528

  16. Trans-presentation of IL-15 by intestinal epithelial cells drives development of CD8alphaalpha IELs.

    Science.gov (United States)

    Ma, Lisa J; Acero, Luis F; Zal, Tomasz; Schluns, Kimberly S

    2009-07-15

    IL-15 is crucial for the development of intestinal intraepithelial lymphocytes (IEL) and delivery is mediated by a unique mechanism known as trans-presentation. Parenchymal cells have a major role in the trans-presentation of IL-15 to IELs, but the specific identity of this cell type is unknown. To investigate whether the intestinal epithelial cells (IEC) are the parenchymal cell type involved, a mouse model that expresses IL-15Ralpha exclusively by the IECs (Villin/IL-15Ralpha Tg) was generated. Exclusive expression of IL-15Ralpha by the IECs restored all the deficiencies in the CD8alphaalpha(+)TCRalphabeta(+)and CD8alphaalpha(+)TCRgammadelta(+) subsets that exist in the absence of IL-15Ralpha. Interestingly, most of the IEL recovery was due to the preferential increase in Thy1(low) IELs, which compose a majority of the IEL population. The differentiation of Thy1(high)CD4(-)CD8(-) thymocytes into Thy1(-)CD8alphaalpha IELs was found to require IL-15Ralpha expression specifically by IECs and thus, provides evidence that differentiation of Thy1(low) IELs is one function of trans-presentation of IL-15 in the intestines. In addition to effects in IEL differentiation, trans-presentation of IL-15 by IECs also resulted in an increase in IEL numbers that was accompanied by increases in Bcl-2, but not proliferation. Collectively, this study demonstrates that trans-presentation of IL-15 by IECs alone is completely sufficient to direct the IL-15-mediated development of CD8alphaalpha(+) T cell populations within the IEL compartment, which now includes a newly identified role of IL-15 in the differentiation of Thy1(low) IELs.

  17. A patient presenting with a perivascular epithelioid cell tumor in the broad ligament: a case report

    Directory of Open Access Journals (Sweden)

    Ross Claire

    2011-08-01

    Full Text Available Abstract Introduction Perivascular epithelioid cell tumors are a family of rare mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. They can originate in any visceral organ or soft tissue and include a range of lesions such as angiomyolipoma, clear cell 'sugar' tumor of the lung, lymphangioleiomyomatosis and clear cell myomelanocytic tumors of the falciparum ligament/ligament teres. Due to their rarity and varied sites and presentation, management of these tumors remains highly challenging. Case Presentation A 46-year-old para 2 Caucasian woman initially presented to the general surgeons at our hospital in North West London with abdominal pain. Laparoscopy revealed a right broad ligament hematoma, which was thought to be iatrogenic in origin, from insertion of the Veress needle at the time of surgery, and was managed conservatively. Upon her re-presentation two months later with severe pain, ultrasound scanning revealed the hematoma had increased in size and she underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Histology results from necrotic tissue from the hematoma led to a diagnosis of perivascular epithelioid cell tumor. She was then referred to a tertiary oncology center, where she underwent several further operations in an attempt to debulk the tumor for symptomatic relief of her pain, with limited success. She is now taking the immunosuppressive drug sirolimus, which has produced a modest reduction in tumor size. She is now 47 months on from initial presentation. Conclusions A literature search has revealed only six other case reports of broad ligament perivascular epithelioid cell tumors, with varied presentations and management. The longest duration of follow-up was 21 months. Only five other cases of perivascular epithelioid cell tumor managed with sirolimus have been reported. We therefore feel that this report highlights some of the

  18. Cell Growth on Different Types of Ultrananocrystalline Diamond Thin Films

    Directory of Open Access Journals (Sweden)

    Orlando Auciello

    2012-08-01

    Full Text Available Unique functional materials provide a platform as scaffolds for cell/tissue regeneration. Investigation of cell-materials’ chemical and biological interactions will enable the application of more functional materials in the area of bioengineering, which provides a pathway to the novel treatment for patients who suffer from tissue/organ damage and face the limitation of donation sources. Many studies have been made into tissue/organ regeneration. Development of new substrate materials as platforms for cell/tissue regeneration is a key research area. Studies discussed in this paper focus on the investigation of novel ultrananocrystalline diamond (UNCD films as substrate/scaffold materials for developmental biology. Specially designed quartz dishes have been coated with different types of UNCD films and cells were subsequently seeded on those films. Results showed the cells’ growth on UNCD-coated culture dishes are similar to cell culture dishes with little retardation, indicating that UNCD films have no or little inhibition on cell proliferation and are potentially appealing as substrate/scaffold materials. The mechanisms of cell adhesion on UNCD surfaces are proposed based on the experimental results. The comparisons of cell cultures on diamond-powder-seeded culture dishes and on UNCD-coated dishes with matrix-assisted laser desorption/ionization—time-of-flight mass spectroscopy (MALDI-TOF MS and X-ray photoelectron spectroscopy (XPS analyses provided valuable data to support the mechanisms proposed to explain the adhesion and proliferation of cells on the surface of the UNCD platform.

  19. Linking form to function: Biophysical aspects of artificial antigen presenting cell design.

    Science.gov (United States)

    Perica, Karlo; Kosmides, Alyssa K; Schneck, Jonathan P

    2015-04-01

    Artificial antigen presenting cells (aAPCs) are engineered platforms for T cell activation and expansion, synthesized by coupling T cell activating proteins to the surface of cell lines or biocompatible particles. They can serve both as model systems to study the basic aspects of T cell signaling and translationally as novel approaches for either active or adoptive immunotherapy. Historically, these reductionist systems have not been designed to mimic the temporally and spatially complex interactions observed during endogenous T cell-APC contact, which include receptor organization at both micro- and nanoscales and dynamic changes in cell and membrane morphologies. Here, we review how particle size and shape, as well as heterogenous distribution of T cell activating proteins on the particle surface, are critical aspects of aAPC design. In doing so, we demonstrate how insights derived from endogenous T cell activation can be applied to optimize aAPC, and in turn how aAPC platforms can be used to better understand endogenous T cell stimulation. This article is part of a Special Issue entitled: Nanoscale membrane organisation and signalling. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Discovery of cell-type specific DNA motif grammar in cis-regulatory elements using random Forest.

    Science.gov (United States)

    Wang, Xin; Lin, Peijie; Ho, Joshua W K

    2018-01-19

    It has been observed that many transcription factors (TFs) can bind to different genomic loci depending on the cell type in which a TF is expressed in, even though the individual TF usually binds to the same core motif in different cell types. How a TF can bind to the genome in such a highly cell-type specific manner, is a critical research question. One hypothesis is that a TF requires co-binding of different TFs in different cell types. If this is the case, it may be possible to observe different combinations of TF motifs - a motif grammar - located at the TF binding sites in different cell types. In this study, we develop a bioinformatics method to systematically identify DNA motifs in TF binding sites across multiple cell types based on published ChIP-seq data, and address two questions: (1) can we build a machine learning classifier to predict cell-type specificity based on motif combinations alone, and (2) can we extract meaningful cell-type specific motif grammars from this classifier model. We present a Random Forest (RF) based approach to build a multi-class classifier to predict the cell-type specificity of a TF binding site given its motif content. We applied this RF classifier to two published ChIP-seq datasets of TF (TCF7L2 and MAX) across multiple cell types. Using cross-validation, we show that motif combinations alone are indeed predictive of cell types. Furthermore, we present a rule mining approach to extract the most discriminatory rules in the RF classifier, thus allowing us to discover the underlying cell-type specific motif grammar. Our bioinformatics analysis supports the hypothesis that combinatorial TF motif patterns are cell-type specific.

  1. Present status of the Cauchois-type Compton Scattering Spectrometer at SPring-8

    CERN Document Server

    Itou, M; Ohata, T; Mizumaki, M; Deb, A; Sakurai, Y; Sakai, N

    2001-01-01

    A new X-ray spectrometer has been installed in the BL08W beamline at SPring-8 for high-resolution Compton scattering measurements using 90-120 keV X-rays. The spectrometer consists of a Cauchois-type triple-crystal analyzer and a quasi position sensitive detector with four slits. The detector works not only as a position-sensitive detector but also as an energy sensitive detector, which allows for low background noise measurements. An overall resolution of 0.10 atomic units in momentum space has been achieved at the incident X-ray energy of 115 keV. Compton profiles of niobium have been measured along the [1 0 0] and [1 1 0] directions in order to demonstrate the performance of the spectrometer.

  2. Type I choledochal cyst – an atypical presentation and an unusual association with single umbilical artery

    Directory of Open Access Journals (Sweden)

    Nga T

    2014-11-01

    Full Text Available Telema Nga,1,2 Neelofar Abdullah,1,2 Garrett Levin1,2 1Department of Pediatrics, Texas Tech University Health Sciences Center, El Paso, TX, USA; 2El Paso Children's Hospital, El Paso, TX, USA Abstract: A unique case of an asymptomatic newborn with type I choledochal cyst and a single umbilical artery is reported. Ultrasound imaging was used as a screening tool and magnetic resonance cholangiopancreatography as a method of adequate visualization. On day 8 of life, the patient had a laparotomy with resection of choledochal cyst, cholecystectomy, and reconstruction using a jejunal Roux-en-Y to portal plate. Keywords: choledochal cyst, single umbilical artery, cholecystectomy

  3. Type XVII collagen (BP180) and LAD-1 are present as separate trimeric complexes

    NARCIS (Netherlands)

    Pas, HH; Kloosterhuis, GJ; Nijenhuis, Albertine; de Jong, MCJM; van der Meer, JB; Jonkman, MF

    This study characterized the high molecular mass BP180 complex that is observed when unheated sodium dodecyl sulfate extracts of human skin or keratinocytes are subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. In heated extracts BP180 is present as a monomer

  4. Terminological Multifaceted Educational Dictionary of Active Type as a Possible Way of Special Discourse Presentation

    Science.gov (United States)

    Fatkullina, Flyuza; Morozkina, Eugenia; Suleimanova, Almira; Khayrullina, Rayca

    2016-01-01

    The purpose of this article is to disclose the scientific basis of the author's academic terminological dictionary for future oil industry experts. Multifaceted terminological dictionary with several different entries is considered to be one of the possible ways to present a special discourse in the classroom. As a result of the study the authors…

  5. Single-cell LEP-type cavity on measurement stand

    CERN Document Server

    CERN PhotoLab

    1982-01-01

    A single-cell cavity, made of copper, with tapered connectors for impedance measurements. It was used as a model of LEP-type superconducting cavities, to investigate impedance and higher-order modes and operated at around 600 MHz (the LEP acceleration frequency was 352.2 MHz). See 8202500.

  6. Transcriptome atlas of eight liver cell types uncovers effects of ...

    Indian Academy of Sciences (India)

    Eight liver cell types were isolated using the methods of Percoll density gradient centrifugation and immunomagnetic beads to explore effects of histidine catabolites on rat liver regeneration. Rat Genome 230 2.0 Array was used to detect the expression profiles of genes associated with metabolism of histidine and its ...

  7. Single cell-type comparative metabolomics of epidermal bladder cells from the halophyte Mesembryanthemum crystallinum.

    Directory of Open Access Journals (Sweden)

    Bronwyn Jane Barkla

    2015-06-01

    Full Text Available One of the remarkable adaptive features of the halophyte and facultative CAM plant Mesembryathemum crystallinum are the specialized modified trichomes called epidermal bladder cells (EBC which cover the leaves, stems, and peduncle of the plant. They are present from an early developmental stage but upon salt stress rapidly expand due to the accumulation of water and sodium. This particular plant feature makes it an attractive system for single cell type studies, with recent proteomics and transcriptomics studies of the EBC establishing that these cells are metabolically active and have roles other than sodium sequestration. To continue our investigation into the function of these unusual cells we carried out a comprehensive global analysis of the metabolites present in the EBC extract by gas chromatography Time-of-Flight mass spectrometry (GC-TOF and identified 194 known and 722 total molecular features. Statistical analysis of the metabolic changes between control and salt-treated samples was used to identify 352 significantly differing metabolites (268 after correction for FDR. Principal components analysis provided an unbiased evaluation of the data variance structure. Biochemical pathway enrichment analysis suggested significant perturbations in 13 biochemical pathways as defined in KEGG. More than 50% of the metabolites that show significant changes in the EBC, can be classified as compatible solutes and include sugars, sugar alcohols, protein and non-protein amino acids, and organic acids, highlighting the need to maintain osmotic homeostasis to balance the accumulation of Na and Cl ions. Overall, the comparison of metabolic changes in salt treated relative to control samples suggest large alterations in Mesembryanthemum crystallinum epidermal bladder cells.

  8. Single cell-type comparative metabolomics of epidermal bladder cells from the halophyte Mesembryanthemum crystallinum.

    Science.gov (United States)

    Barkla, Bronwyn J; Vera-Estrella, Rosario

    2015-01-01

    One of the remarkable adaptive features of the halophyte Mesembryanthemum crystallinum are the specialized modified trichomes called epidermal bladder cells (EBC) which cover the leaves, stems, and peduncle of the plant. They are present from an early developmental stage but upon salt stress rapidly expand due to the accumulation of water and sodium. This particular plant feature makes it an attractive system for single cell type studies, with recent proteomics and transcriptomics studies of the EBC establishing that these cells are metabolically active and have roles other than sodium sequestration. To continue our investigation into the function of these unusual cells we carried out a comprehensive global analysis of the metabolites present in the EBC extract by gas chromatography Time-of-Flight mass spectrometry (GC-TOF) and identified 194 known and 722 total molecular features. Statistical analysis of the metabolic changes between control and salt-treated samples identified 352 significantly differing metabolites (268 after correction for FDR). Principal components analysis provided an unbiased evaluation of the data variance structure. Biochemical pathway enrichment analysis suggested significant perturbations in 13 biochemical pathways as defined in KEGG. More than 50% of the metabolites that show significant changes in the EBC, can be classified as compatible solutes and include sugars, sugar alcohols, protein and non-protein amino acids, and organic acids, highlighting the need to maintain osmotic homeostasis to balance the accumulation of Na(+) and Cl(-) ions. Overall, the comparison of metabolic changes in salt treated relative to control samples suggests large alterations in M. crystallinum epidermal bladder cells.

  9. Assessing genetic polymorphisms using DNA extracted from cells present in saliva samples

    Directory of Open Access Journals (Sweden)

    Nemoda Zsofia

    2011-12-01

    Full Text Available Abstract Background Technical advances following the Human Genome Project revealed that high-quality and -quantity DNA may be obtained from whole saliva samples. However, usability of previously collected samples and the effects of environmental conditions on the samples during collection have not been assessed in detail. In five studies we document the effects of sample volume, handling and storage conditions, type of collection device, and oral sampling location, on quantity, quality, and genetic assessment of DNA extracted from cells present in saliva. Methods Saliva samples were collected from ten adults in each study. Saliva volumes from .10-1.0 ml, different saliva collection devices, sampling locations in the mouth, room temperature storage, and multiple freeze-thaw cycles were tested. One representative single nucleotide polymorphism (SNP in the catechol-0-methyltransferase gene (COMT rs4680 and one representative variable number of tandem repeats (VNTR in the serotonin transporter gene (5-HTTLPR: serotonin transporter linked polymorphic region were selected for genetic analyses. Results The smallest tested whole saliva volume of .10 ml yielded, on average, 1.43 ± .77 μg DNA and gave accurate genotype calls in both genetic analyses. The usage of collection devices reduced the amount of DNA extracted from the saliva filtrates compared to the whole saliva sample, as 54-92% of the DNA was retained on the device. An "adhered cell" extraction enabled recovery of this DNA and provided good quality and quantity DNA. The DNA from both the saliva filtrates and the adhered cell recovery provided accurate genotype calls. The effects of storage at room temperature (up to 5 days, repeated freeze-thaw cycles (up to 6 cycles, and oral sampling location on DNA extraction and on genetic analysis from saliva were negligible. Conclusions Whole saliva samples with volumes of at least .10 ml were sufficient to extract good quality and quantity DNA. Using

  10. Assessing genetic polymorphisms using DNA extracted from cells present in saliva samples

    Science.gov (United States)

    2011-01-01

    Background Technical advances following the Human Genome Project revealed that high-quality and -quantity DNA may be obtained from whole saliva samples. However, usability of previously collected samples and the effects of environmental conditions on the samples during collection have not been assessed in detail. In five studies we document the effects of sample volume, handling and storage conditions, type of collection device, and oral sampling location, on quantity, quality, and genetic assessment of DNA extracted from cells present in saliva. Methods Saliva samples were collected from ten adults in each study. Saliva volumes from .10-1.0 ml, different saliva collection devices, sampling locations in the mouth, room temperature storage, and multiple freeze-thaw cycles were tested. One representative single nucleotide polymorphism (SNP) in the catechol-0-methyltransferase gene (COMT rs4680) and one representative variable number of tandem repeats (VNTR) in the serotonin transporter gene (5-HTTLPR: serotonin transporter linked polymorphic region) were selected for genetic analyses. Results The smallest tested whole saliva volume of .10 ml yielded, on average, 1.43 ± .77 μg DNA and gave accurate genotype calls in both genetic analyses. The usage of collection devices reduced the amount of DNA extracted from the saliva filtrates compared to the whole saliva sample, as 54-92% of the DNA was retained on the device. An "adhered cell" extraction enabled recovery of this DNA and provided good quality and quantity DNA. The DNA from both the saliva filtrates and the adhered cell recovery provided accurate genotype calls. The effects of storage at room temperature (up to 5 days), repeated freeze-thaw cycles (up to 6 cycles), and oral sampling location on DNA extraction and on genetic analysis from saliva were negligible. Conclusions Whole saliva samples with volumes of at least .10 ml were sufficient to extract good quality and quantity DNA. Using 10 ng of DNA per

  11. Investigating the interaction forces between T cells and antigen-presenting cells using an optical trapping system

    Science.gov (United States)

    Wright, Amanda J.; Benson, Robert A.; Bowman, Richard W.; Gibson, Graham M.; Padgett, Miles J.; Girkin, John M.; Brewer, James; Garside, Paul

    2011-10-01

    The interactions between T cells and antigen-presenting cells (APCs) are crucial in triggering a successful antigenspecific, adaptive immune response leading to protection against a particular pathogen or disease. At present very little is known about the magnitudes of the forces involved in these interactions. We present results showing for the first time that optical tweezers can be used to measure these cell-cell interaction forces. We were able to see a significant difference in the force distributions taken with and without antigen, as evidenced by a Mann-Whitney U-test. The T cells of interest were trapped directly and no exogenous beads were added to the sample. Interaction forces between T cells and APCs in the presence of specific antigen ranged from 0-6.5 pN, whereas, when the specific antigen was absent the interaction forces ranged from 0-1.5 pN. The accuracy of the system will be discussed in terms of how we tracked the position of the optically trapped cell and the methods we used to minimise cell roll.

  12. Measuring antigen presentation in mouse brain endothelial cells ex vivo and in vitro.

    Science.gov (United States)

    Howland, Shanshan W; Gun, Sin Yee; Claser, Carla; Poh, Chek Meng; Rénia, Laurent

    2015-12-01

    We have recently demonstrated that brain endothelial cells cross-present parasite antigen during mouse experimental cerebral malaria (ECM). Here we describe a 2-d protocol to detect cross-presentation by isolating the brain microvessels and incubating them with a reporter cell line that expresses lacZ upon detection of the relevant peptide-major histocompatibility complex. After X-gal staining, a typical positive result consists of hundreds of blue spots, compared with fewer than 20 spots from a naive brain. The assay is generalizable to other disease contexts by using reporter cells that express appropriate specific T cell receptors. Also described is the protocol for culturing endothelial cells from brain microvessels isolated from naive mice. After 7-10 d, an in vitro cross-presentation assay can be performed by adding interferon-γ, antigen (e.g., Plasmodium berghei-infected red blood cells) and reporter cells in sequence over 3 d. This is useful for comparing different antigen forms or for probing the effects of various interventions.

  13. Cell Death Induction By Streptococcus Pyogenes in Four Types of Malignant Cell Llines

    Directory of Open Access Journals (Sweden)

    Hamid Mollaii

    2010-02-01

    Full Text Available Background:The interest in using bacteria as anti- cancer therapeutic agents dates back to the end of the19th century. Some bacteria like Salmonella and Listeria replicate effectively inside malignant cell lines and suppress their growth. The bacterium Streptococcus pyogenes has become medically famous as a flesh-eating pathogen since mid-1980s. It is the causative agent of a life threatening clinical condition called necrotizing fasciitis. S. pyogenes usually produces a range of lytic enzymes that promote bacterial pathogenesis. With these characters, could this bacteria. be employed as a curing agent for certain cancers? The aim of this study was to determine the influence of S. pyogenes on malignant cellular death (apoptosis or necrosis- in an ex-vivo "experimental- interventional" study.Methods: The cytotoxicity of fifteen internalized streptococcal strains( including 12 clinical isolates, 2 known M types [M1, M3] and standard strain, on four types of malignant cell lines- A549, BT-20, PC-3, L-929- were tested by Trypan blue exclusion, DNAfragmentation and WST-1 methods. The streptococcal protease, lipase, DNase and serum opacity factor (SOF were tested concurrently. The standard strain of Streptococcus (Enterococcus faecalis was employed as negative control. The results were analyzed by statistical Minitab software.   Results: The overall cytotoxicity rate of -internalized- S. pyogenes was 57% by trypan blue method and 50 % by DNA electrophoresis. False positive results occurred for the negative control in WST-1; therefore this test did not present reasonable results. The correlation between production of SOF, lipase, DNase and cytotoxicity of S. pyogenes was not significant (p > 0.05. However, 67% of the protease positive strains induced cellular death in at least one type of - malignant cell line (p

  14. 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.

  15. Primary cilia are present on human blood and bone marrow cells and mediate Hedgehog signaling.

    Science.gov (United States)

    Singh, Mohan; Chaudhry, Parvesh; Merchant, Akil A

    2016-12-01

    Primary cilia are nonmotile, microtubule-based organelles that are present on the cellular membrane of all eukaryotic cells. Functional cilia are required for the response to developmental signaling pathways such as Hedgehog (Hh) and Wnt/β-catenin. Although the Hh pathway has been shown to be active in leukemia and other blood cancers, there have been no reports describing the presence of primary cilia in human blood or leukemia cells. In the present study, we show that nearly all human blood and bone marrow cells have primary cilia (97-99%). In contrast, primary cilia on AML cell lines (KG1, KG1a, and K562) were less frequent (10-36% of cells) and were often shorter and dysmorphic, with less well-defined basal bodies. Finally, we show that treatment of blood cells with the Hh pathway ligand Sonic Hedgehog (SHh) causes translocation of Smoothened (SMO) to the primary cilia and activation of Hh target genes, demonstrating that primary cilia in blood cells are functional and participate in Hh signaling. Loss of primary cilia on leukemia cells may have important implications for aberrant pathway activation and response to SMO inhibitors currently in clinical development. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  16. Dysfunctional fat cells, lipotoxicity and type 2 diabetes.

    Science.gov (United States)

    DeFronzo, R A

    2004-10-01

    Type 2 diabetes is characterized by insulin resistance and impaired insulin secretion. Considerable evidence implicates altered fat topography and defects in adipocyte metabolism in the pathogenesis of type 2 diabetes. In individuals who develop type 2 diabetes, fat cells tend to be enlarged. Enlarged fat cells are resistant to the antilipolytic effects of insulin, leading to day-long elevated plasma free fatty acid (FFA) levels. Chronically increased plasma FFA stimulates gluconeogenesis, induces hepatic and muscle insulin resistance, and impairs insulin secretion in genetically predisposed individuals. These FFA-induced disturbances are referred to as lipotoxicity. Enlarged fat cells also have diminished capacity to store fat. When adipocyte storage capacity is exceeded, lipid 'overflows' into muscle and liver, and possibly the beta-cells of the pancreas, exacerbating insulin resistance and further impairing insulin secretion. In addition, dysfunctional fat cells produce excessive amounts of insulin resistance-inducing, inflammatory and atherosclerosis-provoking cytokines, and fail to secrete normal amounts of insulin-sensitizing cytokines. As more evidence emerges, there is a stronger case for targeting adipose tissue in the treatment of type 2 diabetes. Peroxisome-proliferator activated receptor gamma (PPARgamma) agonists, for example the thiazolidinediones, redistribute fat within the body (decrease visceral and hepatic fat; increase subcutaneous fat) and have been shown to enhance adipocyte insulin sensitivity, inhibit lipolysis, reduce plasma FFA and favourably influence the production of adipocytokines. This article examines in detail the role of adipose tissue in the pathogenesis of type 2 diabetes and highlights the potential of PPAR agonists to improve the management of patients with the condition.

  17. Color vision abnormality as an initial presentation of the complete type of congenital stationary night blindness

    Directory of Open Access Journals (Sweden)

    Tan X

    2013-08-01

    Full Text Available Xue Tan, Aya Aoki, Yasuo YanagiDepartment of Ophthalmology, University of Tokyo School of Medicine, Hongo, Bunkyo-ku, Tokyo, JapanAbstract: Patients with the complete form of congenital stationary night blindness (CSNB often have reduced visual acuity, myopia, impaired night vision, and sometimes nystagmus and strabismus, however, they seldom complain of color vision abnormality. A 17-year-old male who was at technical school showed abnormalities in the color perception test for employment, and was referred to our hospital for a detailed examination. He had no family history of color vision deficiency and no other symptoms. During the initial examination, his best-corrected visual acuity was 1.2 in both eyes. His fundus showed no abnormalities except for somewhat yellowish reflex in the fovea of both eyes. Electroretinogram (ERG showed a good response in cone ERG and 30 Hz flicker ERG, however, the bright flash, mixed rod and cone ERG showed a negative type with a reduced b-wave (positive deflection. There was no response in the rod ERG, either. From the findings of the typical ERG, the patient was diagnosed with complete congenital stationary night blindness. This case underscores the importance of ERG in order to diagnose the cause of a color vision anomaly.Keywords: congenital stationary night blindness, CSNB, electroretinogram, ERG, color vision defect

  18. Medical treatment in neurofibromatosis type 2. Review of the literature and presentation of clinical reports.

    Science.gov (United States)

    Goutagny, S; Kalamarides, M

    2017-02-02

    The understanding of the molecular pathways underlying tumor development in neurofibromatosis type 2 (NF2) is increasing. Thus, repositioning drugs, drug therapies that are already clinically available for various cancers, appear potentially promising for NF2 patients. Based on preclinical data from in vitro or animal models, five different treatments have been proposed for selected NF2 cases. Evaluation of bevacizumab, a monoclonal antibody against VEGF has mainly been reported in retrospective studies; it has been reported to induce hearing improvement and tumor shrinkage in more than 50% of progressive vestibular schwannomas (VS). In our experience with 16 patients, bevacizumab is associated with an increase of median time to tumor progression of VS from 5.6 months before bevacizumab onset, to more than 29.3 months. The need for intravenous injections and long term adverse events (hypertension, proteinuria, hemorrhage) are the main drawbacks. Lapatinib seemed promising in a single phase II trial with a volumetric response observed in 4/17 patients and a hearing response in 4/13, but is not currently used in clinical practice. Erlotinib has not been associated with radiographic or hearing responses in a phase II trial. Everolimus has been evaluated in 3 phase II trials. Everolimus did not induced tumor shrinkage, but seems to be able to increase time to tumor progression in selected cases. Currently, bevacizumab is the only drug proposed to selected NF2 patients. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Extracellular matrix type modulates cell migration on mechanical gradients.

    Science.gov (United States)

    Hartman, Christopher D; Isenberg, Brett C; Chua, Samantha G; Wong, Joyce Y

    2017-10-15

    Extracellular matrix composition and stiffness are known to be critical determinants of cell behavior, modulating processes including differentiation, traction generation, and migration. Recent studies have demonstrated that the ECM composition can modulate how cells migrate in response to gradients in environmental stiffness, altering a cell's ability to undergo durotaxis. These observations were limited to single varieties of extracellular matrix, but typically cells are exposed to environments containing complex mixtures of extracellular matrix proteins. Here, we investigate migration of NIH 3T3 fibroblasts on mechanical gradients coated with one or more type of extracellular matrix protein. Our results show that NIH 3T3 fibroblasts exhibit durotaxis on fibronectin-coated mechanical gradients but not on those coated with laminin, demonstrating that extracellular matrix type can act as a regulator of cell response to mechanical gradients. Interestingly, NIH 3T3 fibroblasts were also observed to migrate randomly on gradients coated with a mixture of both fibronectin and laminin, suggesting that there may be a complex interplay in the cellular response to mechanical gradients in the presence of multiple extracellular matrix signals. These findings indicate that specific composition of available adhesion ligands is a critical determinant of a cell's migratory response to mechanical gradients. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Fluorescence exclusion: A simple versatile technique to calculate cell volumes and local heights (Conference Presentation)

    Science.gov (United States)

    Thouvenin, Olivier; Fink, Mathias; Boccara, A. Claude

    2017-02-01

    Understanding volume regulation during mitosis is technically challenging. Indeed, a very sensitive non invasive imaging over time scales ranging from seconds to hours and over large fields is required. Therefore, Quantitative Phase Imaging (QPI) would be a perfect tool for such a project. However, because of asymmetric protein segregation during mitosis, an efficient separation of the refractive index and the height in the phase signal is required. Even though many strategies to make such a separation have been developed, they usually are difficult to implement, have poor sensitivity, or cannot be performed in living cells, or in a single shot. In this paper, we will discuss the use of a new technique called fluorescence exclusion to perform volume measurements. By coupling such technique with a simultaneous phase measurement, we were also able to recover the refractive index inside the cells. Fluorescence exclusion is a versatile and powerful technique that allows the volume measurement of many types of cells. A fluorescent dye, which cannot penetrate inside the cells, is mixed with the external medium in a confined environment. Therefore, the fluorescent signal depends on the inverse of the object's height. We could demonstrate both experimentally and theoretically that fluorescence exclusion can accurately measure cell volumes, even for cells much higher than the depth of focus of the objective. A local accurate height and RI measurement can also be obtained for smaller cells. We will also discuss the way to optimize the confinement of the observation chamber, either mechanically or optically.

  1. Discovering cell types in flow cytometry data with random matrix theory

    Science.gov (United States)

    Shen, Yang; Nussenblatt, Robert; Losert, Wolfgang

    Flow cytometry is a widely used experimental technique in immunology research. During the experiments, peripheral blood mononuclear cells (PBMC) from a single patient, labeled with multiple fluorescent stains that bind to different proteins, are illuminated by a laser. The intensity of each stain on a single cell is recorded and reflects the amount of protein expressed by that cell. The data analysis focuses on identifying specific cell types related to a disease. Different cell types can be identified by the type and amount of protein they express. To date, this has most often been done manually by labelling a protein as expressed or not while ignoring the amount of expression. Using a cross correlation matrix of stain intensities, which contains both information on the proteins expressed and their amount, has been largely ignored by researchers as it suffers from measurement noise. Here we present an algorithm to identify cell types in flow cytometry data which uses random matrix theory (RMT) to reduce noise in a cross correlation matrix. We demonstrate our method using a published flow cytometry data set. Compared with previous analysis techniques, we were able to rediscover relevant cell types in an automatic way. Department of Physics, University of Maryland, College Park, MD 20742.

  2. Complex Regional Pain Syndrome-Type 1 Presenting as deQuervain's Stenosing Tenosynovitis.

    Science.gov (United States)

    Vas, Lakshmi; Pai, Renuka

    2016-01-01

    To report the presentation of complex regional pain syndrome-1 (CRPS-1) as deQuervain's stenosing tenosynovitis (DQST). A 24-year-old woman presented with 3-year history of clinical diagnostic criteria (CDC) of CRPS-1. Conservative and surgical treatment for this as DQST had failed to relieve her. We diagnosed the problem as CRPS-1with CDC as inflammatory manifestations of a mechanical tendinoses of all her 5 digital tendons caused by movement of the fingers and hand tethered by agonist (flexor)/ antagonist (extensor) muscles in co-contraction. Ultrasound guided dry needling (USGDN) relaxed the muscles, replacing the abnormal agonist/antagonist co-contraction with normal agonist/antagonist coordination. Resolution of tendinoses reversed the inflammation causing the CDC. Six months later she leads normal personal and professional life, with reduction of scores of painDetect (from 21 to 5), Patient Health Questionnaire (from 13 to 4), Disability of arm, shoulder and hand from 70.8 to 25 and reversal of muscle abnormality characteristic of CRPS-1 on Musculoskeletal Ultrasonography (MSKUSG). We believe the primary pathology of CRPS-1 to be co-contraction of agonist (flexor)/antagonist(extensor) muscles of digits resulting in tendinoses akin to DQST. CDC of CRPS are actually inflammatory manifestations of tendinoses amenable to reversal by USGDN which also addresses the disability, a hallmark of CRPS.

  3. Type II NKT-TFH cells against Gaucher lipids regulate B-cell immunity and inflammation.

    Science.gov (United States)

    Nair, Shiny; Boddupalli, Chandra Sekhar; Verma, Rakesh; Liu, Jun; Yang, Ruhua; Pastores, Gregory M; Mistry, Pramod K; Dhodapkar, Madhav V

    2015-02-19

    Chronic inflammation including B-cell activation is commonly observed in both inherited (Gaucher disease [GD]) and acquired disorders of lipid metabolism. However, the cellular mechanisms underlying B-cell activation in these settings remain to be elucidated. Here, we report that β-glucosylceramide 22:0 (βGL1-22) and glucosylsphingosine (LGL1), 2 major sphingolipids accumulated in GD, can be recognized by a distinct subset of CD1d-restricted human and murine type II natural killer T (NKT) cells. Human βGL1-22- and LGL1-reactive CD1d tetramer-positive T cells have a distinct T-cell receptor usage and genomic and cytokine profiles compared with the classical type I NKT cells. In contrast to type I NKT cells, βGL1-22- and LGL1-specific NKT cells constitutively express T-follicular helper (TFH) phenotype. Injection of these lipids leads to an increase in respective lipid-specific type II NKT cells in vivo and downstream induction of germinal center B cells, hypergammaglobulinemia, and production of antilipid antibodies. Human βGL1-22- and LGL1-specific NKT cells can provide efficient cognate help to B cells in vitro. Frequency of LGL1-specific T cells in GD mouse models and patients correlates with disease activity and therapeutic response. Our studies identify a novel type II NKT-mediated pathway for glucosphingolipid-mediated dysregulation of humoral immunity and increased risk of B-cell malignancy observed in metabolic lipid disorders. © 2015 by The American Society of Hematology.

  4. Unusual presentation of unilateral intra-orbital optic nerve pilocytic astrocytoma of the juvenile type in a geriatric patient.

    Science.gov (United States)

    Dua, Sonal; Sharma, Kanika; Juneja, Rakesh; Kalakoti, Piyush; Kamble, Mala; Subramanian, Prem

    2016-03-01

    Optic nerve gliomas (ONG) are rare and seldom encountered in clinical practice. The pilocytic (astrocytoma) variant of ONG almost always presents during the first two decades of life. In this report, the authors discuss an unusual presentation of pilocytic astrocytoma of the juvenile type in an elderly Indian male. With this unusual presentation, ONG affecting the visual pathway should be considered as a possible differential of visual diminution in the elderly population. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Antibody production by injection of living cells expressing non self antigens as cell surface type II transmembrane fusion protein.

    Science.gov (United States)

    Nizet, Yannick; Gillet, Laurent; Schroeder, Hélène; Lecuivre, Corinne; Louahed, J; Renauld, J-C; Gianello, Pierre; Vanderplasschen, Alain

    2011-03-31

    Antigen expression and purification are laborious, time consuming and frequently difficult steps in the process of antibody production. In the present study, we developed a method avoiding these two steps. This method relies on the injection of histocompatible living cells stably expressing the antigen as a cell surface type II transmembrane fusion protein. A vector, nicknamed pCD1-CD134L, was constructed to express the antigen fused at the carboxyterminal end of the human CD134 ligand (CD134L) type II transmembrane protein on the surface of eucaryotic cells. This vector was shown to induce cell surface expression of epitopes from human c-Myc (soluble protein), uterogloblin-related protein 1 (secreted protein) and CD94 (type II transmembrane protein). Using this vector, we developed a method to produce antibodies without antigen production. The flowchart of this method is as follows: (i) cloning of the antigen in the pCD1-CD134L vector; (ii) production of a histocompatible cell line stably expressing the CD134L-antigen fusion protein; (iii) testing for cell surface expression of the fusion protein by targeting the CD134L carrier; and (iv) prime-boost immunisation with living cells expressing the fusion protein. This method was successfully used for production of polyclonal antibodies raised against Ixodes ricinus calreticulin (secreted protein) in mice and for production of monoclonal antibodies raised against an epitope of Vaccinia virus A56 (type I transmembrane protein) protein in rat. The present study is the first to demonstrate the use of a type II transmembrane protein as a carrier for cell surface display of antigens. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Distinct types of glial cells populate the Drosophila antenna

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    Jhaveri Dhanisha

    2005-11-01

    Full Text Available Abstract Background The development of nervous systems involves reciprocal interactions between neurons and glia. In the Drosophila olfactory system, peripheral glial cells arise from sensory lineages specified by the basic helix-loop-helix transcription factor, Atonal. These glia wrap around the developing olfactory axons early during development and pattern the three distinct fascicles as they exit the antenna. In the moth Manduca sexta, an additional set of central glia migrate to the base of the antennal nerve where axons sort to their glomerular targets. In this work, we have investigated whether similar types of cells exist in the Drosophila antenna. Results We have used different P(Gal4 lines to drive Green Fluorescent Protein (GFP in distinct populations of cells within the Drosophila antenna. Mz317::GFP, a marker for cell body and perineural glia, labels the majority of peripheral glia. An additional ~30 glial cells detected by GH146::GFP do not derive from any of the sensory lineages and appear to migrate into the antenna from the brain. Their appearance in the third antennal segment is regulated by normal function of the Epidermal Growth Factor receptor and small GTPases. We denote these distinct populations of cells as Mz317-glia and GH146-glia respectively. In the adult, processes of GH146-glial cells ensheath the olfactory receptor neurons directly, while those of the Mz317-glia form a peripheral layer. Ablation of GH146-glia does not result in any significant effects on the patterning of the olfactory receptor axons. Conclusion We have demonstrated the presence of at least two distinct populations of glial cells within the Drosophila antenna. GH146-glial cells originate in the brain and migrate to the antenna along the newly formed olfactory axons. The number of cells populating the third segment of the antenna is regulated by signaling through the Epidermal Growth Factor receptor. These glia share several features of the sorting

  7. Live cell imaging using Au-NNP (Nanobridged Nanogap Particles) (Presentation Recording)

    Science.gov (United States)

    Suh, Yung Doug

    2015-08-01

    Single-particle tracking Live-Cell imaging using Au-NNP(Nanobridged Nanogap Particles) will be presented. Due to a stable plasmonic amplification of Raman signal from the intra-nanogap of Au-NNP, we have a stable and strong Raman signal enough for single particle imaging of Au-NNP in live cell. Multiplex imaging by encoding different Raman dyes into this nanogap and its application will be also discussed.

  8. Genes affecting β-cell function in type 1 diabetes

    DEFF Research Database (Denmark)

    Fløyel, Tina; Kaur, Simranjeet; Pociot, Flemming

    2015-01-01

    Type 1 diabetes (T1D) is a multifactorial disease resulting from an immune-mediated destruction of the insulin-producing pancreatic β cells. Several environmental and genetic risk factors predispose to the disease. Genome-wide association studies (GWAS) have identified around 50 genetic regions...... that affect the risk of developing T1D, but the disease-causing variants and genes are still largely unknown. In this review, we discuss the current status of T1D susceptibility loci and candidate genes with focus on the β cell. At least 40 % of the genes in the T1D susceptibility loci are expressed in human...... islets and β cells, where they according to recent studies modulate the β-cell response to the immune system. As most of the risk variants map to noncoding regions of the genome, i.e., promoters, enhancers, intergenic regions, and noncoding genes, their possible involvement in T1D pathogenesis as gene...

  9. Endothelial-monocyte activating polypeptide II disrupts alveolar epithelial type II to type I cell transdifferentiation

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    Chen Yao

    2012-01-01

    Full Text Available Abstract Background Distal alveolar morphogenesis is marked by differentiation of alveolar type (AT-II to AT-I cells that give rise to the primary site of gas exchange, the alveolar/vascular interface. Endothelial-Monocyte Activating Polypeptide (EMAP II, an endogenous protein with anti-angiogenic properties, profoundly disrupts distal lung neovascularization and alveolar formation during lung morphogenesis, and is robustly expressed in the dysplastic alveolar regions of infants with Bronchopulmonary dysplasia. Determination as to whether EMAP II has a direct or indirect affect on ATII→ATI trans-differentiation has not been explored. Method In a controlled nonvascular environment, an in vitro model of ATII→ATI cell trans-differentiation was utilized to demonstrate the contribution that one vascular mediator has on distal epithelial cell differentiation. Results Here, we show that EMAP II significantly blocked ATII→ATI cell transdifferentiation by increasing cellular apoptosis and inhibiting expression of ATI markers. Moreover, EMAP II-treated ATII cells displayed myofibroblast characteristics, including elevated cellular proliferation, increased actin cytoskeleton stress fibers and Rho-GTPase activity, and increased nuclear:cytoplasmic volume. However, EMAP II-treated cells did not express the myofibroblast markers desmin or αSMA. Conclusion Our findings demonstrate that EMAP II interferes with ATII → ATI transdifferentiation resulting in a proliferating non-myofibroblast cell. These data identify the transdifferentiating alveolar cell as a possible target for EMAP II's induction of alveolar dysplasia.

  10. Graphene oxide, but not fullerenes, targets immunoproteasomes and suppresses antigen presentation by dendritic cells.

    Science.gov (United States)

    Tkach, Alexey V; Yanamala, Naveena; Stanley, Shyla; Shurin, Michael R; Shurin, Galina V; Kisin, Elena R; Murray, Ashley R; Pareso, Samantha; Khaliullin, Timur; Kotchey, Gregg P; Castranova, Vincent; Mathur, Sanjay; Fadeel, Bengt; Star, Alexander; Kagan, Valerian E; Shvedova, Anna A

    2013-05-27

    Graphene oxide (GO) and C60 - or C60 -TRIS fullerenes, internalized by murine dendritic cells (DCs), differently affect their abilities to present antigens to T-cells. While C60 -fullerenes stimulate the ovalbumin-specific MHC class I-restricted T-cell response, GO impairs the stimulatory potential of DCs. In contrast to C60 -fullerenes, GO decreases the intracellular levels of LMP7 immunoproteasome subunits required for processing of protein antigens. This is important for the development of DC-based vaccines. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. "Person in the barrel" syndrome: Unusual heralding presentation of squamous cell carcinoma of the lung

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    Rajesh Verma

    2016-01-01

    Full Text Available Paraneoplastic neurological syndromes (PNS are rare and relatively unusual in day to day clinical practice. Occasionally, PNS may be the heralding manifestation of the malignancy. Paraneoplastic syndromes are most commonly associated with small cell lung carcinoma and are rarely seen with non small cell lung carcinoma. In this case, we report a non-smoker, middle aged lady, who presented with "person in the barrel" syndrome due to myelo radiculoplexopathy as the first clinical manifestation of squamous cell carcinoma of the lung.

  12. Solid oxide fuels cells past present and future perspectives for SOFC technologies

    CERN Document Server

    Irvine, John TS

    2012-01-01

    Solid Oxide Fuel Cells (SOFCs) operate at high temperatures allowing more fuel flexibility and also useful heat output and so increase total efficiency, but does give some interesting engineering challenges. Solid Oxide Fuels Cells: Facts and Figures provides clear and accurate data for a selection of SOFC topics from the specific details of Ni cermet anodes, chemical expansion in materials, and the measuring and modelling of mechanical stresses, to the broader scope of the history and present design of cells, to SOFC systems and the future of SOFC. Celebrating Ulf Bossel s work on Solid Oxide

  13. Small Cell Carcinoma of the Ovary: Report of a Case with Unusual and Aggressive Presentation

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    Fatemeh Sadat Najib

    2017-07-01

    Full Text Available Small cell carcinoma of the ovary is an aggressive malignant tumor with no standard treatment. Despite surgery, chemotherapy and radiation, this tumor has a poor prognosis with rapid progression. The authors report a case of small cell carcinoma of the ovary in a 37-year-old woman who presented twice with an acute abdomen and unstable hemodynamics which led to two urgent laparatomies. The patient died two months after her diagnosis of small cell carcinoma of the ovary and one course of chemotherapy.

  14. Atypical presentation of isolated peripheral T-cell lymphoma in the hand: case report.

    Science.gov (United States)

    Kung, Theodore A; Smith, Lauren B; Chung, Kevin C

    2014-04-01

    Peripheral T-cell lymphoma is a rare malignancy that characteristically demonstrates generalized lymphadenopathy and extranodal involvement. We describe an atypical case of peripheral T-cell lymphoma manifesting as isolated hand swelling without evidence of nodal disease or systemic symptoms. This report emphasizes the highly variable clinical presentation of T-cell lymphomas and the importance of expeditious incisional biopsy in the setting of an undiagnosed hand mass. Copyright © 2014 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  15. Paediatric anaplastic large cell lymphoma with leukaemic presentation in children: a report of nine French cases.

    Science.gov (United States)

    Spiegel, Alexandra; Paillard, Catherine; Ducassou, Stephane; Perel, Yves; Plantaz, Dominique; Strullu, Marion; Eischen, Alice; Lutz, Patrick; Lamant, Laurence; Le Deley, Marie-Cécile; Brugières, Laurence

    2014-05-01

    This study aimed to describe the clinical features and outcome of anaplastic large cell lymphoma (ALCL) with leukaemic presentation in children. Among 267 patients included in the French paediatric ALCL database between 1989 and 2012, nine (3%) were described as having cytologically detectable circulating tumour cells. Clinical features combined fever (8/9), nodal and extra-nodal disease (9/9), including hepato-splenic (9/9) and lung involvement (7/9). The level of hyperleucocytosis ranged from 30 to 120 × 10(9) /l, with 12-90% of tumour cells. Diagnosis relied on a lymph node biopsy, with a positive ALK+ antibody immunostain in all nine cases, a T-cell immunophenotype in 7/9 cases and CD3 positivity in 5/9 cases. A small cell component was present in 6/9 cases. Only four patients achieved a complete remission with first-line therapy and 3/4 relapsed. Four patients are alive with a median follow-up of 31 months, two of them after allogeneic haematopoietic stem cell transplantation (HSCT), and five patients died, two of them of disease. In conclusion, ALCL with leukaemic presentation is very unusual and should be considered as high-risk lymphoma requiring new therapeutic strategies. The respective role of new agents and allogeneic HSCT in first complete remission still has to be assessed. © 2014 John Wiley & Sons Ltd.

  16. p-Type semiconducting nickel oxide as an efficiency-enhancing anodal interfacial layer in bulk heterojunction solar cells

    Science.gov (United States)

    Irwin, Michael D; Buchholz, Donald B; Marks, Tobin J; Chang, Robert P. H.

    2014-11-25

    The present invention, in one aspect, relates to a solar cell. In one embodiment, the solar cell includes an anode, a p-type semiconductor layer formed on the anode, and an active organic layer formed on the p-type semiconductor layer, where the active organic layer has an electron-donating organic material and an electron-accepting organic material.

  17. Universal cell type identifier based on number theory.

    Science.gov (United States)

    Cosma, Antonio

    2018-02-23

    Cell type classification and handling is a key issue for understanding biological systems. The advent of high multiplexing technologies increased the complexity of the classification process and new tools are needed to support the organization of this knowledge. I propose a classification based on both prime numbers and the fundamental theorem of arithmetic. As a not limiting example, I show the application of this method to unambiguously define any existing cell type using the CD nomenclature established by the Human Leukocyte Differentiation Antigens Workshops. This system allows for the unique identification of any possible combination of markers hence any cell population without previous knowledge and without the need to increment the system. This method can be the future basis of any database and ontology system dealing with cell types and beyond the biological field applies to the description of any entity characterized by a list of discrete qualities. © 2018 International Society for Advancement of Cytometry. © 2018 International Society for Advancement of Cytometry.

  18. An unusual Case of Transitional Cell Carcinoma of Renal Pelvis Presenting with Brain Metastases

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    MR Razzaghi

    2009-04-01

    Full Text Available ABSTRACT: Introduction & Objective: Transitional cell carcinoma of renal pelvis presenting with brain metastases is a very rare case which should be diagnosed and treated in order to prevent further damages. Case: We report a rare case, who had presented with a constellation of neurological symptoms (due to multiple brain metastases, but without any urological symptoms. During evaluation of patient, we found transitional cell carcinoma (TCC of left renal pelvis, for which palliative radical nephroureterectomy was performed . Conclusion: Although transitional cell carcinoma of renal pelvis presenting with brain metastases is a very rare case, but the patient was managed with gamma knife stereotactic radiosurgery for the metastatic lesions. Afterward he received four cycles of paclitaxel and carboplatin chemotherapy. The patient is alive with stable disease at 32- months’ follow-up.

  19. Inferring cell type innovations by phylogenetic methods-concepts, methods, and limitations.

    Science.gov (United States)

    Kin, Koryu

    2015-12-01

    Multicellular organisms are composed of distinct cell types that have specific roles in the body. Each cell type is a product of two kinds of historical processes-development and evolution. Although the concept of a cell type is difficult to define, the cell type concept based on the idea of the core regulatory network (CRN), a gene regulatory network that determines the identity of a cell type, illustrates the essential aspects of the cell type concept. The first step toward elucidating cell type evolution is to reconstruct the evolutionary relationships of cell types, or the cell type tree. The sister cell type model assumes that a new cell type evolves through divergence from a multifunctional ancestral cell type, creating tree-like evolutionary relationships between cell types. The process of generating a cell type tree can also be understood as the sequential addition of a new branching point on an ancestral cell differentiation hierarchy in evolution. A cell type tree thus represents an intertwined history of cell type evolution and development. Cell type trees can be reconstructed from high-throughput sequencing data, and the reconstruction of a cell type tree leads to the discovery of genes that are functionally important for a cell type. Although many issues including the lack of cross-species comparisons and the lack of a proper model for cell type evolution remain, the study of the origin of a new cell type using phylogenetic methods offers a promising new research avenue in developmental evolution. J. Exp. Zool. (Mol. Dev. Evol.) 324B: 653-661, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  20. T-helper Cell Type-1 Transcription Factor T-Bet Is Down-regulated in Type 1 Diabetes.

    Science.gov (United States)

    Vaseghi, Hajar; Sanati, Mohammad Hossein; Jadali, Zohreh

    2016-10-01

    T cells have been identified as key players in the pathogenesis of type 1 diabetes. However, the exact role of T-cell subpopulations in this pathway is presently unknown. The purpose of this study was to assess the expression pattern of two lineage-specifying transcription factors GATA-3 and T-bet, which are important in T helper type 1 (Th1) and Th2 cell development, respectively. Gene expression analysis of peripheral blood mononuclear cells (PBMCs) was performed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Plasma levels of IFN-γ and IL-4 were also determined by ELISA. T-bet and IFN-γ gene expression was significantly lower in patients group compared with healthy controls (p<0.05). The expression of GATA-3 was relatively similar in patients and controls; however, IL-4 mRNAs were significantly increased in the PBMCs from patients as compared with normal controls (p<0.05). In addition, a marked increase in plasma IL-4 levels were observed in patient group compared with controls (p<0.001). To the contrary, IFN-γ protein levels were decreased in patients in comparison with controls (p<0.001). These data suggest additional implications of the role of Th1/Th2 imbalance for the immunopathogenesis of type 1 diabetes.

  1. [Intrathyroidal location of parathyroid glands. Atypical presentation of multiple endocrine neoplasia type 1 syndrome].

    Science.gov (United States)

    de la Fuente-Bartolomé, Marta; Moreno-Bargueiras, Alejando; Osorio-Silla, Irene; Martínez-Pueyo, José Ignacio; de la Cruz-Vigo, Felipe; Gutiérrez-Ashling, Lara

    2017-12-01

    The most common manifestation of MEN 1 syndrome is primary hyperparathyroidism (PHPT) with parathyroid multiglandular affectation. The intrathyroidal situation represents 3-4% of all glands, and it is the second most frequent location in the cervical ectopias. 11 year old patient, with a family history of MEN1 syndrome and carrier of this same mutation. Patient presents HPTP with osteopenia. The cervical ultrasound shows three compatible images with pathological parathyroid glands (bilateral lower and upper left). The Scan and MRI are normal. Bone densitometry displays data on osteopenia. The patient is surgically intervened, only the upper parathyroid glands are located and removed, after this implantation is performed on the forearm, to prevent the possible devascularization in the dissection of the other glands. However, osteopenia persists and an elevated PTH, therefore new diagnostic tests are held which seem to show two lower parathyroid glands with intrathyroidal location. The patient is reoperated. A subtotal parathyroidectomy of the lower right gland and the resection of the left gland is performed, with the use of intraoperative ultrasound and placement of harpoon. The intraoperative pathology study confirms parathyroid tissue in both cases. It is necessary to locate the parathyroid glands preoperatively in order to alert us of the existence of topographical and ectopia abnormalities, as well as their intrathyroidal location (0.5-3.6%). The intraoperative ultrasound can be a complement to the experience of the endocrine surgeon for the localization of the parathyroid glands and therefore can help determine the best surgical strategy for each clinical case. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  2. New World hantaviruses activate IFNlambda production in type I IFN-deficient vero E6 cells.

    Science.gov (United States)

    Prescott, Joseph; Hall, Pamela; Acuna-Retamar, Mariana; Ye, Chunyan; Wathelet, Marc G; Ebihara, Hideki; Feldmann, Heinz; Hjelle, Brian

    2010-06-17

    Hantaviruses indigenous to the New World are the etiologic agents of hantavirus cardiopulmonary syndrome (HCPS). These viruses induce a strong interferon-stimulated gene (ISG) response in human endothelial cells. African green monkey-derived Vero E6 cells are used to propagate hantaviruses as well as many other viruses. The utility of the Vero E6 cell line for virus production is thought to owe to their lack of genes encoding type I interferons (IFN), rendering them unable to mount an efficient innate immune response to virus infection. Interferon lambda, a more recently characterized type III IFN, is transcriptionally controlled much like the type I IFNs, and activates the innate immune system in a similar manner. We show that Vero E6 cells respond to hantavirus infection by secreting abundant IFNlambda. Three New World hantaviruses were similarly able to induce IFNlambda expression in this cell line. The IFNlambda contained within virus preparations generated with Vero E6 cells independently activates ISGs when used to infect several non-endothelial cell lines, whereas innate immune responses by endothelial cells are specifically due to viral infection. We show further that Sin Nombre virus replicates to high titer in human hepatoma cells (Huh7) without inducing ISGs. Herein we report that Vero E6 cells respond to viral infection with a highly active antiviral response, including secretion of abundant IFNlambda. This cytokine is biologically active, and when contained within viral preparations and presented to human epithelioid cell lines, results in the robust activation of innate immune responses. We also show that both Huh7 and A549 cell lines do not respond to hantavirus infection, confirming that the cytoplasmic RNA helicase pathways possessed by these cells are not involved in hantavirus recognition. We demonstrate that Vero E6 actively respond to virus infection and inhibiting IFNlambda production in these cells might increase their utility for virus

  3. Identification of XMRV infection-associated microRNAs in four cell types in culture.

    Directory of Open Access Journals (Sweden)

    Ketha V K Mohan

    Full Text Available INTRODUCTION: XMRV is a gammaretrovirus that was thought to be associated with prostate cancer (PC and chronic fatigue syndrome (CFS in humans until recently. The virus is culturable in various cells of human origin like the lymphocytes, NK cells, neuronal cells, and prostate cell lines. MicroRNAs (miRNA, which regulate gene expression, were so far not identified in cells infected with XMRV in culture. METHODS: Two prostate cell lines (LNCaP and DU145 and two primary cells, Peripheral Blood Lymphocytes [PBL] and Monocyte-derived Macrophages [MDM] were infected with XMRV. Total mRNA was extracted from mock- and virus-infected cells at 6, 24 and 48 hours post infection and evaluated for microRNA profile in a microarray. RESULTS: MicroRNA expression profiles of XMRV-infected continuous prostate cancer cell lines differ from that of virus-infected primary cells (PBL and MDMs. miR-193a-3p and miRPlus-E1245 observed to be specific to XMRV infection in all 4 cell types. While miR-193a-3p levels were down regulated miRPlus-E1245 on the other hand exhibited varied expression profile between the 4 cell types. DISCUSSION: The present study clearly demonstrates that cellular microRNAs are expressed during XMRV infection of human cells and this is the first report demonstrating the regulation of miR193a-3p and miRPlus-E1245 during XMRV infection in four different human cell types.

  4. New World hantaviruses activate IFNlambda production in type I IFN-deficient vero E6 cells.

    Directory of Open Access Journals (Sweden)

    Joseph Prescott

    Full Text Available Hantaviruses indigenous to the New World are the etiologic agents of hantavirus cardiopulmonary syndrome (HCPS. These viruses induce a strong interferon-stimulated gene (ISG response in human endothelial cells. African green monkey-derived Vero E6 cells are used to propagate hantaviruses as well as many other viruses. The utility of the Vero E6 cell line for virus production is thought to owe to their lack of genes encoding type I interferons (IFN, rendering them unable to mount an efficient innate immune response to virus infection. Interferon lambda, a more recently characterized type III IFN, is transcriptionally controlled much like the type I IFNs, and activates the innate immune system in a similar manner.We show that Vero E6 cells respond to hantavirus infection by secreting abundant IFNlambda. Three New World hantaviruses were similarly able to induce IFNlambda expression in this cell line. The IFNlambda contained within virus preparations generated with Vero E6 cells independently activates ISGs when used to infect several non-endothelial cell lines, whereas innate immune responses by endothelial cells are specifically due to viral infection. We show further that Sin Nombre virus replicates to high titer in human hepatoma cells (Huh7 without inducing ISGs.Herein we report that Vero E6 cells respond to viral infection with a highly active antiviral response, including secretion of abundant IFNlambda. This cytokine is biologically active, and when contained within viral preparations and presented to human epithelioid cell lines, results in the robust activation of innate immune responses. We also show that both Huh7 and A549 cell lines do not respond to hantavirus infection, confirming that the cytoplasmic RNA helicase pathways possessed by these cells are not involved in hantavirus recognition. We demonstrate that Vero E6 actively respond to virus infection and inhibiting IFNlambda production in these cells might increase their utility

  5. Type of cell death induced by alpha-trifluoromethyl acyloins in oral squamous cell carcinoma.

    Science.gov (United States)

    Ideo, Atsushi; Hashimoto, Ken; Shimada, Jun; Kawase, Masami; Sakagami, Hiroshi

    2009-01-01

    We previously reported that alpha-trifluoromethyl acyloins (TFs) induced various types of cell death, depending on the target cancer cell line. We investigated here what type of cell death is induced by a-trifluoromethyl acyloins in two human oral squamous cell carcinoma cell lines (HSC-2, HSC-4). TFs produced few TUNEL-positive cells. TFs induced annexin V/PI-double positive HSC-2 cells and annexin V-positive/PI-negative HSC-4 cells, respectively, but failed to activate caspase-3, capase-8 and caspase-9 in both HSC-2 and HSC-4 cells. On the other hand, TFs induced the formation of acidic organelles (detected by acridine orange staining) in both HSC-2 and HSC-4 cells. When HSC-2 and HSC-4 cells that had been transfected with expression vector encording the microtubule-associated protein 1 light chain 3 (LC3) gene fused to green fluorescent protein (GFP) were treated with TFs, LC3-GFP fusion protein was accumulated as granular dots in autophagosomes. Pretreatment with 3-methyladenine, an inhibitor of autophagy, partially inhibited the cytotoxicity of TFs, the formation of acidic organelles and LC3 accumulation in the autophagosome. These data suggest that alpha-trifluoromethyl acyloins may induce autophagic cell death in HSC-2 and HSC-4 cells following the early stage of necrosis or apoptosis, respectively.

  6. 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

  7. Development of coin-type cell and engineering of its compartments for rechargeable seawater batteries

    Science.gov (United States)

    Han, Jinhyup; Hwang, Soo Min; Go, Wooseok; Senthilkumar, S. T.; Jeon, Donghoon; Kim, Youngsik

    2018-01-01

    Cell design and optimization of the components, including active materials and passive components, play an important role in constructing robust, high-performance rechargeable batteries. Seawater batteries, which utilize earth-abundant and natural seawater as the active material in an open-structured cathode, require a new platform for building and testing the cells other than typical Li-ion coin-type or pouch-type cells. Herein, we present new findings based on our optimized cell. Engineering the cathode components-improving the wettability of cathode current collector and seawater catholyte flow-improves the battery performance (voltage efficiency). Optimizing the cell component and design is the key to identifying the electrochemical processes and reactions of active materials. Hence, the outcome of this research can provide a systematic study of potentially active materials used in seawater batteries and their effectiveness on the electrochemical performance.

  8. Nuclear DNA Content Varies with Cell Size across Human Cell Types

    Science.gov (United States)

    Gillooly, James F.; Hein, Andrew; Damiani, Rachel

    2015-01-01

    Variation in the size of cells, and the DNA they contain, is a basic feature of multicellular organisms that affects countless aspects of their structure and function. Within humans, cell size is known to vary by several orders of magnitude, and differences in nuclear DNA content among cells have been frequently observed. Using published data, here we describe how the quantity of nuclear DNA across 19 different human cell types increases with cell volume. This observed increase is similar to intraspecific relationships between DNA content and cell volume in other species, and interspecific relationships between diploid genome size and cell volume. Thus, we speculate that the quantity of nuclear DNA content in somatic cells of humans is perhaps best viewed as a distribution of values that reflects cell size distributions, rather than as a single, immutable quantity. PMID:26134319

  9. Nuclear DNA Content Varies with Cell Size across Human Cell Types.

    Science.gov (United States)

    Gillooly, James F; Hein, Andrew; Damiani, Rachel

    2015-07-01

    Variation in the size of cells, and the DNA they contain, is a basic feature of multicellular organisms that affects countless aspects of their structure and function. Within humans, cell size is known to vary by several orders of magnitude, and differences in nuclear DNA content among cells have been frequently observed. Using published data, here we describe how the quantity of nuclear DNA across 19 different human cell types increases with cell volume. This observed increase is similar to intraspecific relationships between DNA content and cell volume in other species, and interspecific relationships between diploid genome size and cell volume. Thus, we speculate that the quantity of nuclear DNA content in somatic cells of humans is perhaps best viewed as a distribution of values that reflects cell size distributions, rather than as a single, immutable quantity. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  10. Breast Cancer Mimic: Cutaneous B-Cell Lymphoma Presenting as an Isolated Breast Mass

    Directory of Open Access Journals (Sweden)

    Margaret Taghavi

    2014-10-01

    Full Text Available Background: Primary cutaneous B-cell lymphoma typically localizes to the skin, and dissemination to internal organs is rare. Lymphomatous involvement of the breasts is also rare. We describe the clinical and radiological findings of an unusual case of primary cutaneous B-cell lymphoma presenting as an isolated breast mass without associated skin changes. Case Presentation: The patient was a 55-year-old Caucasian female who initially presented with cutaneous B-cell lymphoma around her eyes and forehead with recurrence involving the skin between her breasts. Three years after terminating treatment due to a lack of symptoms, she presented for an annual screening mammogram that found a new mass in her upper inner right breast without imaging signs of cutaneous extension. On physical examination, there were no corresponding skin findings. Due to the suspicious imaging features of the mass that caused concern for primary breast malignancy, she underwent a core biopsy which revealed cutaneous B-cell lymphoma. Conclusion: When evaluating patients with a systemic disease who present with findings atypical for that process, it is important to still consider the systemic disease as a potential etiology, particularly with lymphoma given its reputation as a great mimicker.

  11. Frequency patterns of T-cell exposed motifs in immunoglobulin heavy chain peptides presented by MHCs

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    Robert D. Bremel

    2014-10-01

    Full Text Available Immunoglobulins are highly diverse protein sequences that are processed and presented to T-cells by B-cells and other antigen presenting cells. We examined a large dataset of immunoglobulin heavy chain variable regions (IGHV to assess the diversity of T-cell exposed motifs (TCEM. TCEM comprise those amino acids in a MHC-bound peptide which face outwards, surrounded by the MHC histotope, and which engage the T-cell receptor. Within IGHV there is a distinct pattern of predicted MHC class II binding and a very high frequency of re-use of the TCEMs. The re-use frequency indicates that only a limited number of different cognate T-cells are required to engage many different clonal B-cells. The amino acids in each outward-facing TCEM are intercalated with the amino acids of inward-facing MHC groove-exposed motifs (GEM. Different GEM may have differing, allele-specific, MHC binding affinities. The intercalation of TCEM and GEM in a peptide allows for a vast combinatorial repertoire of epitopes, each eliciting a different response. Outcome of T-cell receptor binding is determined by overall signal strength, which is a function of the number of responding T-cells and the duration of engagement. Hence, the frequency of T-cell exposed motif re-use appears to be an important determinant of whether a T-cell response is stimulatory or suppressive. The frequency distribution of TCEMs implies that somatic hypermutation is followed by clonal expansion that develop along repeated pathways. The observations of TCEM and GEM derived from immunoglobulins suggest a relatively simple, yet powerful, mechanism to correlate T-cell polyspecificity, through re-use of TCEMs, with a very high degree of specificity achieved by combination with a diversity of GEMs. The frequency profile of TCEMs also points to an economical mechanism for maintaining T-cell memory, recall, and self-discrimination based on an endogenously generated profile of motifs.

  12. Cell penetrable-mouse forkhead box P3 suppresses type 1 T helper cell-mediated immunity in a murine model of delayed-type hypersensitivity.

    Science.gov (United States)

    Liu, Xia; Wang, Jun; Wang, Hui; Zhou, Chen; Yu, Qihong; Yin, Lei; Wu, Weijiang; Xia, Sheng; Shao, Qixiang

    2017-02-01

    Forkhead box P3 (FOXP3), which is a transcription factor, has a primary role in the development and function of regulatory T cells, and thus contributes to homeostasis of the immune system. A previous study generated a cell-permeable fusion protein of mouse FOXP3 conjugated to a protein transduction domain (PTD-mFOXP3) that successfully blocked differentiation of type 17 T helper cells in vitro and alleviated experimental arthritis in mice. In the present study, the role of PTD-mFOXP3 in type 1 T helper (Th1) cell-mediated immunity was investigated and the possible mechanisms for its effects were explored. Under Th1 polarization conditions, cluster of differentiation 4(+) T cells were treated with PTD-mFOXP3 and analyzed by flow cytometry in vitro, which revealed that PTD-mFOXP3 blocked Th1 differentiation in vitro. Mice models of delayed type hypersensitivity (DTH) reactions were generated by subcutaneous sensitization and challenge with ovalbumin (OVA) to the ears of mice. PTD-mFOXP3, which was administered via local subcutaneous injection, significantly reduced DTH-induced inflammation, including ear swelling (ear swelling, P<0.001; pinnae weight, P<0.05 or P<0.01 with 0.25 and 1.25 mg/kg PTD-mFOXP3, respectively), infiltration of T cells, and expression of interferon-γ at local inflammatory sites (mRNA level P<0.05) compared with the DTH group. The results of the present study demonstrated that PTD-mFOXP3 may attenuate DTH reactions by suppressing the infiltration and activity of Th1 cells.

  13. Cell types and their status in Chlamydomonas-like algae (Chlorophyceae on agar medium culture

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    M.М. Pavlovska

    2014-04-01

    Full Text Available The classification of cell types under agar culture was proposed. Six cell morphotypes were allocated. The statuses were identified depending on the reduction of monade attributes of cells. The variants of transition from one cell morphotype to another under dissolving mucilage were shown. The monade, cocciod, palmeloid and gloeocysta morphotypes approximately equally represented in all clades. The asterococcus and mucogleocysta morphotypes presented only in Reinhardtinia аnd Oogamochlamydinia clades. Any morphotype isn’t typical for all clades of Chlamydomonas-like algae at once. The most of morphotypes numbers (5 from 6 are presented in Reinhardtinia clade. This demonstrates the diversity of the Reinhardtinia clade species. There are only one morphotype presented in Polytominia and Monadinia clades. There are four morphotypes presented in Oogamochlamydinia clade, three – in Moewusinia, two morphotypes – in Chloromonadinia.

  14. Polyamines are present in mast cell secretory granules and are important for granule homeostasis.

    Science.gov (United States)

    García-Faroldi, Gianni; Rodríguez, Carlos E; Urdiales, José L; Pérez-Pomares, José M; Dávila, José C; Pejler, Gunnar; Sánchez-Jiménez, Francisca; Fajardo, Ignacio

    2010-11-30

    Mast cell secretory granules accommodate a large number of components, many of which interact with highly sulfated serglycin proteoglycan (PG) present within the granules. Polyamines (putrescine, spermidine and spermine) are absolutely required for the survival of the vast majority of living cells. Given the reported ability of polyamines to interact with PGs, we investigated the possibility that polyamines may be components of mast cell secretory granules. Spermidine was released by mouse bone marrow derived mast cells (BMMCs) after degranulation induced by IgE/anti-IgE or calcium ionophore A23187. Additionally, both spermidine and spermine were detected in isolated mouse mast cell granules. Further, depletion of polyamines by culturing BMMCs with α-difluoromethylornithine (DFMO) caused aberrant secretory granule ultrastructure, impaired histamine storage, reduced serotonin levels and increased β-hexosaminidase content. A proteomic approach revealed that DFMO-induced polyamine depletion caused an alteration in the levels of a number of proteins, many of which are connected either with the regulated exocytosis or with the endocytic system. Taken together, our results show evidence that polyamines are present in mast cell secretory granules and, furthermore, indicate an essential role of these polycations during the biogenesis and homeostasis of these organelles.

  15. Polyamines are present in mast cell secretory granules and are important for granule homeostasis.

    Directory of Open Access Journals (Sweden)

    Gianni García-Faroldi

    2010-11-01

    Full Text Available Mast cell secretory granules accommodate a large number of components, many of which interact with highly sulfated serglycin proteoglycan (PG present within the granules. Polyamines (putrescine, spermidine and spermine are absolutely required for the survival of the vast majority of living cells. Given the reported ability of polyamines to interact with PGs, we investigated the possibility that polyamines may be components of mast cell secretory granules.Spermidine was released by mouse bone marrow derived mast cells (BMMCs after degranulation induced by IgE/anti-IgE or calcium ionophore A23187. Additionally, both spermidine and spermine were detected in isolated mouse mast cell granules. Further, depletion of polyamines by culturing BMMCs with α-difluoromethylornithine (DFMO caused aberrant secretory granule ultrastructure, impaired histamine storage, reduced serotonin levels and increased β-hexosaminidase content. A proteomic approach revealed that DFMO-induced polyamine depletion caused an alteration in the levels of a number of proteins, many of which are connected either with the regulated exocytosis or with the endocytic system.Taken together, our results show evidence that polyamines are present in mast cell secretory granules and, furthermore, indicate an essential role of these polycations during the biogenesis and homeostasis of these organelles.

  16. Parotid small cell carcinoma presenting with long-term survival after surgery alone: a case report

    Directory of Open Access Journals (Sweden)

    Kanazawa Takeharu

    2012-12-01

    Full Text Available Abstract Introduction Primary involvement of the salivary glands in small cell carcinoma is rare, and has one of the worst prognoses of salivary gland neoplasms. However, it has been reported that some cases have a favorable outcome, although the prognostic factors are still under consideration. Multidisciplinary therapy was usually required to achieve long-term survival. Recently, a resemblance of some small cell carcinomas of the salivary gland to cutaneous Merkel cell carcinoma was suggested; the latter have the potential for spontaneous regression, which is related to a favorable clinical outcome. Case presentation We present a locoregional advanced parotid small cell carcinoma with multiple lymph node metastases in an 87-year-old Asian woman. The tumor was controlled by surgery alone, and nine-year disease-free survival was achieved without any adjunctive therapy. To the best of our knowledge, this is the longest reported follow-up of head and neck small cell carcinoma. Conclusion We believe this to be the first case of small cell carcinoma with involvement of the salivary glands reported in the literature with a good outcome after surgery alone without any adjunctive therapy.

  17. IgE-mediated enhancement of CD4+ T cell responses in mice requires antigen presentation by CD11c+ cells and not by B cells.

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    Frida Henningsson

    Full Text Available IgE antibodies, administered to mice together with their specific antigen, enhance antibody and CD4(+ T cell responses to this antigen. The effect is dependent on the low affinity receptor for IgE, CD23, and the receptor must be expressed on B cells. In vitro, IgE-antigen complexes are endocytosed via CD23 on B cells, which subsequently present the antigen to CD4(+ T cells. This mechanism has been suggested to explain also IgE-mediated enhancement of immune responses in vivo. We recently found that CD23(+ B cells capture IgE-antigen complexes in peripheral blood and rapidly transport them to B cell follicles in the spleen. This provides an alternative explanation for the requirement for CD23(+ B cells. The aim of the present study was to determine whether B-cell mediated antigen presentation of IgE-antigen complexes explains the enhancing effect of IgE on immune responses in vivo. The ability of spleen cells, taken from mice 1-4 h after immunization with IgE-antigen, to present antigen to specific CD4(+ T cells was analyzed. Antigen presentation was intact when spleens were depleted of CD19(+ cells (i.e., primarily B cells but was severely impaired after depletion of CD11c(+ cells (i.e., primarily dendritic cells. In agreement with this, the ability of IgE to enhance proliferation of CD4(+ T cells was abolished in CD11c-DTR mice conditionally depleted of CD11c(+ cells. Finally, the lack of IgE-mediated enhancemen of CD4(+ T cell responses in CD23(-/- mice could be rescued by transfer of MHC-II-compatible as well as by MHC-II-incompatible CD23(+ B cells. These findings argue against the idea that IgE-mediated enhancement of specific CD4(+ T cell responses in vivo is caused by increased antigen presentation by B cells. A model where CD23(+ B cells act as antigen transporting cells, delivering antigen to CD11c(+ cells for presentation to T cells is consistent with available experimental data.

  18. Myositis in Griscelli syndrome type 2 treated with hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Born, Alfred Peter; Müller, Klaus; Marquart, Hanne Vibeke

    2010-01-01

    Griscelli syndrome is an autosomal recessive disorder characterized by pigmentary dilution and is occasionally associated with a hemophagocytic syndrome (type 2). We present a 13-year-old girl with Griscelli syndrome type 2, who developed a hemophagocytic syndrome along with marked muscle weakness...... and elevated plasma creatine kinase. Muscle biopsy showed massive inflammatory changes in some fascicles, while other fascicles were relatively spared. Clinical symptoms and biopsy changes resolved after immunosuppression and allogeneic hematopoietic cell transplantation. Our results suggest that muscle...

  19. 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.

  20. Ectopic expression of HLA-DO in mouse dendritic cells diminishes MHC class II antigen presentation.

    Science.gov (United States)

    Fallas, Jennifer L; Tobin, Helen M; Lou, Olivia; Guo, Donglin; Sant'Angelo, Derek B; Denzin, Lisa K

    2004-08-01

    The MHC class II-like molecule HLA-DM (DM) (H-2M in mice) catalyzes the exchange of CLIP for antigenic peptides in the endosomes of APCs. HLA-DO (DO) (H-2O in mice) is another class II-like molecule that is expressed in B cells, but not in other APCs. Studies have shown that DO impairs or modifies the peptide exchange activity of DM. To further evaluate the role of DO in Ag processing and presentation, we generated transgenic mice that expressed the human HLA-DOA and HLA-DOB genes under the control of a dendritic cell (DC)-specific promoter. Our analyses of DCs from these mice showed that as DO levels increased, cell surface levels of A(b)-CLIP also increased while class II-peptide levels decreased. The presentation of some, but not all, exogenous Ags to T cells or T hybridomas was significantly inhibited by DO. Surprisingly, H-2M accumulated in DO-expressing DCs and B cells, suggesting that H-2O/DO prolongs the half-life of H-2M. Overall, our studies showed that DO expression impaired H-2M function, resulting in Ag-specific down-modulation of class II Ag processing and presentation.

  1. The Paracoccidioides cell wall: past and present layers towards understanding interaction with the host

    Directory of Open Access Journals (Sweden)

    Rosana ePuccia

    2011-12-01

    Full Text Available The cell wall of pathogenic fungi plays import roles in interaction with the host, so that its composition and structure may determine the course of infection. Here we present an overview of the current and past knowledge on the cell wall constituents of Paracoccidioides brasiliensis and P. lutzii. These are temperature-dependent dimorphic fungi that cause paracoccidioidomycosis, a systemic granulomatous and debilitating disease. Focus is given on cell wall carbohydrate and protein contents, their immune-stimulatory features, adhesion properties, drug target characteristics, and morphological phase specificity. We offer a journey towards the future understanding of the dynamic life that takes place in the cell wall and of the changes that it may suffer when living in the human host.

  2. Mantle Cell Lymphoma of Intestine Presenting as Multiple Lymphomatous Polyposis with Intussusception

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    Meena N. Jadhav

    2015-01-01

    Full Text Available Mantle Cell Lymphoma (MCL is a distinct clinicopathological subtype of B-cell non-Hodgkin's lymphoma (NHL accounting for 2-10% of all NHL cases. Gastrointestinal tract (GIT is the predominant site of extranodal MCL which commonly presents as Multiple Lymphomatous Polyposis (MLP. A 60 year old male presented with pain abdomen, diarrhea and weight loss of two months duration. On colonoscopy multiple polyps were found in the entire colon and rectum. Computed tomography revealed ileo-colic intussusception with nodularity in the lead point. Histopathology suggested features of MCL. On immunohistochemistry, the tumor cells were positive for CD20, CD5, Cyclin D1, negative for CD3, CD10, CD23, and CD45 RO

  3. Primary Pure Squamous Cell Carcinoma of Gallbladder Presenting as Acute Cholecystitis

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    Massood Hosseinzadeh

    2012-12-01

    Full Text Available Squamous cell carcinoma of the gallbladder is rare and constitutes only 0.5-3% of all malignancies of this organ. Most of the reported cases have had a component of adenocarcinoma. We report a 70-year-old man who presented with acute onset right upper quadrant pain. He operated on based on a presumptive diagnosis of acute cholecystitis according to clinical and ultrasonographic findings. Histopathological examination of the infiltrating mass of the gallbladder revealed well differentiated keratinized squamous cell carcinoma invading full wall thickness. Thorough evaluations revealed no other primary site for the tumor. Pure primary squamous cell carcinoma of the gallbladder is rarely reported. Clinicians and pathologists must be aware of its vague clinical presentations.

  4. Macropinocytosis in Phagocytes: Regulation of MHC Class-II-Restricted Antigen Presentation in Dendritic Cells

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    Zhenzhen eLiu

    2015-01-01

    Full Text Available AbstractDendritic cells (DCs are outstanding antigen presenting cells (APCs due to their robust ability to internalize extracellular antigens using endocytic processes such as receptor-mediated endocytosis, phagocytosis, and macropinocytosis. Macropinocytosis mediates the non-specific uptake of soluble antigens and occurs in DCs constitutively. Macropinocytosis plays a key role in DC-mediated antigen presentation to T cells against pathogens and the efficiency of macropinocytosis in antigen capture is regulated during the process of DC maturation. Here, we review the methods to study macropinocytosis, describe our current knowledge of the regulatory mechanisms of antigen uptake via macropinocytosis and the intracellular trafficking route followed by macropinocytosed antigens, and discuss the significance of macropinocytosis for DC function.

  5. Macropinocytosis in phagocytes: regulation of MHC class-II-restricted antigen presentation in dendritic cells.

    Science.gov (United States)

    Liu, Zhenzhen; Roche, Paul A

    2015-01-01

    Dendritic cells (DCs) are outstanding antigen presenting cells (APCs) due to their robust ability to internalize extracellular antigens using endocytic processes such as receptor-mediated endocytosis, phagocytosis, and macropinocytosis. Macropinocytosis mediates the non-specific uptake of soluble antigens and occurs in DCs constitutively. Macropinocytosis plays a key role in DC-mediated antigen presentation to T cells against pathogens and the efficiency of macropinocytosis in antigen capture is regulated during the process of DC maturation. Here, we review the methods to study macropinocytosis, describe our current knowledge of the regulatory mechanisms of antigen uptake via macropinocytosis and the intracellular trafficking route followed by macropinocytosed antigens, and discuss the significance of macropinocytosis for DC function.

  6. A homodimeric complex of HLA-G on normal trophoblast cells modulates antigen-presenting cells via LILRB1.

    Science.gov (United States)

    Apps, Richard; Gardner, Lucy; Sharkey, Andrew M; Holmes, Nick; Moffett, Ashley

    2007-07-01

    In healthy individuals, the non-classical MHC molecule HLA-G is only expressed on fetal trophoblast cells that invade the decidua during placentation. We show that a significant proportion of HLA-G at the surface of normal human trophoblast cells is present as a disulphide-linked homodimer of the conventional beta(2)m-associated HLA-I complex. HLA-G is a ligand for leukocyte immunoglobulin-like receptors (LILR), which bind much more efficiently to dimeric HLA-G than to conventional HLA-I molecules. We find that a LILRB1-Fc fusion protein preferentially binds the dimeric form of HLA-G on trophoblast cells. We detect LILRB1 expression on decidual myelomonocytic cells; therefore, trophoblast HLA-G may modulate the function of these cells. Co-culture with HLA-G(+) cells does not inhibit monocyte-derived dendritic cell up-regulation of HLA-DR and costimulatory molecules on maturation, but did increase production of IL-6 and IL-10. Furthermore, proliferation of allogeneic lymphocytes was inhibited by HLA-G binding to LILRB1/2 on responding antigen-presenting cells (APC). As HLA-G is the only HLA-I molecule that forms beta(2)m-associated dimers with increased avidity for LILRB1, this interaction could represent a placental-specific signal to decidual APC. We suggest that the placenta is modulating maternal immune responses locally in the uterus through HLA-G, a trophoblast-specific, monomorphic signal present in almost every pregnancy. See accompanying commentary: (http://dx.doi.org/10.1002/eji.200737515).

  7. Aedes aegypti saliva alters leukocyte recruitment and cytokine signaling by antigen-presenting cells during West Nile virus infection.

    Directory of Open Access Journals (Sweden)

    Bradley S Schneider

    2010-07-01

    Full Text Available West Nile virus (WNV is transmitted during mosquito bloodfeeding. Consequently, the first vertebrate cells to contact WNV are cells in the skin, followed by those in the draining lymph node. Macrophages and dendritic cells are critical early responders in host defense against WNV infection, not just because of their role in orchestrating the immune response, but also because of their importance as sites of early peripheral viral replication. Antigen-presenting cell (APC signals have a profound effect on host antiviral responses and disease severity. During transmission, WNV is intimately associated with mosquito saliva. Due to the ability of mosquito saliva to affect inflammation and immune responses, and the importance of understanding early events in WNV infection, we investigated whether mosquito saliva alters APC signaling during arbovirus infection, and if alterations in cell recruitment occur when WNV infection is initiated with mosquito saliva. Accordingly, experiments were performed with cultured dendritic cells and macrophages, flow cytometry was used to characterize infiltrating cell types in the skin and lymph nodes during early infection, and real-time RT-PCR was employed to evaluate virus and cytokine levels. Our in vitro results suggest that mosquito saliva significantly decreases the expression of interferon-beta and inducible nitric oxide synthase in macrophages (by as much as 50 and 70%, respectively, whilst transiently enhancing interleukin-10 (IL-10 expression. In vivo results indicate that the predominate effect of mosquito feeding is to significantly reduce the recruitment of T cells, leading the inoculation site of mice exposed to WNV alone to have up to 2.8 fold more t cells as mice infected in the presence of mosquito saliva. These shifts in cell population are associated with significantly elevated IL-10 and WNV (up to 4.0 and 10 fold, respectively in the skin and draining lymph nodes. These results suggest that mosquito

  8. Cell differentiation defines acute and chronic infection cell types in Staphylococcus aureus

    Science.gov (United States)

    García-Betancur, Juan-Carlos; Goñi-Moreno, Angel; Horger, Thomas; Schott, Melanie; Sharan, Malvika; Eikmeier, Julian; Wohlmuth, Barbara; Zernecke, Alma; Ohlsen, Knut; Kuttler, Christina

    2017-01-01

    A central question to biology is how pathogenic bacteria initiate acute or chronic infections. Here we describe a genetic program for cell-fate decision in the opportunistic human pathogen Staphylococcus aureus, which generates the phenotypic bifurcation of the cells into two genetically identical but different cell types during the course of an infection. Whereas one cell type promotes the formation of biofilms that contribute to chronic infections, the second type is planktonic and produces the toxins that contribute to acute bacteremia. We identified a bimodal switch in the agr quorum sensing system that antagonistically regulates the differentiation of these two physiologically distinct cell types. We found that extracellular signals affect the behavior of the agr bimodal switch and modify the size of the specialized subpopulations in specific colonization niches. For instance, magnesium-enriched colonization niches causes magnesium binding to S. aureusteichoic acids and increases bacterial cell wall rigidity. This signal triggers a genetic program that ultimately downregulates the agr bimodal switch. Colonization niches with different magnesium concentrations influence the bimodal system activity, which defines a distinct ratio between these subpopulations; this in turn leads to distinct infection outcomes in vitro and in an in vivo murine infection model. Cell differentiation generates physiological heterogeneity in clonal bacterial infections and helps to determine the distinct infection types. PMID:28893374

  9. Morbidity and CD4+ Cell Counts at Initial Presentation of a Cohort of ...

    African Journals Online (AJOL)

    Objective: To describe the CD4+ cell counts, opportunistic infections and laboratory parameters of a cohort of HIV positive, HAART-naive patients at first presentation. Design: Cross sectional, prospective, descriptive, consecutive entry study. Setting: Kisumu District Hospital wards (medical, surgical) and medical outpatient ...

  10. Red Dot Basal Cell Carcinoma: Report of Cases and Review of This Unique Presentation of Basal Cell Carcinoma.

    Science.gov (United States)

    Cohen, Philip R

    2017-03-22

    Red dot basal cell carcinoma is a unique variant of basal cell carcinoma. Including the three patients described in this report, red dot basal cell carcinoma has only been described in seven individuals. This paper describes the features of two males and one female with red dot basal cell carcinoma and reviews the characteristics of other patients with this clinical subtype of basal cell carcinoma. A 70-year-old male developed a pearly-colored papule with a red dot in the center on his nasal tip. A 71-year-old male developed a red dot surrounded by a flesh-colored papule on his left nostril. Lastly, a 74-year-old female developed a red dot within an area of erythema on her left mid back. Biopsy of the lesions all showed nodular and/or superficial basal cell carcinoma. Correlation of the clinical presentation and pathology established the diagnosis of red dot basal cell carcinoma. The tumors were treated by excision using the Mohs surgical technique. Pubmed was searched with the keyword: basal, cell, cancer, carcinoma, dot, red, and skin. The papers generated by the search and their references were reviewed. Red dot basal cell carcinoma has been described in three females and two males; the gender was not reported in two patients. The tumor was located on the nose (five patients), back (one patient) and thigh (one patient). Cancer presented as a solitary small red macule or papule; often, the carcinoma was surrounded by erythema or a flesh-colored papule. Although basal cell carcinomas usually do not blanch after a glass microscope slide is pressed against them, the red dot basal cell carcinoma blanched after diascopy in two of the patients, resulting in a delay of diagnosis in one of these individuals. Dermoscopy may be a useful non-invasive modality for evaluating skin lesions when the diagnosis of red dot basal cell carcinoma is considered. Mohs surgery is the treatment of choice; in some of the patients, the ratio of the area of the postoperative wound to that

  11. Red Dot Basal Cell Carcinoma: Report of Cases and Review of This Unique Presentation of Basal Cell Carcinoma

    Science.gov (United States)

    2017-01-01

    Red dot basal cell carcinoma is a unique variant of basal cell carcinoma. Including the three patients described in this report, red dot basal cell carcinoma has only been described in seven individuals. This paper describes the features of two males and one female with red dot basal cell carcinoma and reviews the characteristics of other patients with this clinical subtype of basal cell carcinoma. A 70-year-old male developed a pearly-colored papule with a red dot in the center on his nasal tip. A 71-year-old male developed a red dot surrounded by a flesh-colored papule on his left nostril. Lastly, a 74-year-old female developed a red dot within an area of erythema on her left mid back. Biopsy of the lesions all showed nodular and/or superficial basal cell carcinoma. Correlation of the clinical presentation and pathology established the diagnosis of red dot basal cell carcinoma. The tumors were treated by excision using the Mohs surgical technique. Pubmed was searched with the keyword: basal, cell, cancer, carcinoma, dot, red, and skin. The papers generated by the search and their references were reviewed. Red dot basal cell carcinoma has been described in three females and two males; the gender was not reported in two patients. The tumor was located on the nose (five patients), back (one patient) and thigh (one patient). Cancer presented as a solitary small red macule or papule; often, the carcinoma was surrounded by erythema or a flesh-colored papule. Although basal cell carcinomas usually do not blanch after a glass microscope slide is pressed against them, the red dot basal cell carcinoma blanched after diascopy in two of the patients, resulting in a delay of diagnosis in one of these individuals. Dermoscopy may be a useful non-invasive modality for evaluating skin lesions when the diagnosis of red dot basal cell carcinoma is considered. Mohs surgery is the treatment of choice; in some of the patients, the ratio of the area of the postoperative wound to that

  12. New type of cells with multiple chromosome rearrangements

    Energy Technology Data Exchange (ETDEWEB)

    Aseeva, Elena A. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation); Snigiryova, Galina P. [Russian Scientific Centre of Roentgenology and Radiology, ul. Profsoyuznaya 86, 117997 Moscow (Russian Federation); Neverova, Anna L. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation); Bogomazova, Alexandra N.; Novitskaya, Natalia N.; Khazins, Eva D. [Russian Scientific Centre of Roentgenology and Radiology, ul. Profsoyuznaya 86, 117997 Moscow (Russian Federation); Domracheva, Elena V. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation)], E-mail: dom@blood.ru

    2010-04-15

    A comparative analysis of the distribution and the frequency of multiaberrant cells (MAC) among lymphocytes in different categories of low dose (up to 0.5 Gy) irradiated people was carried out. The highest MAC frequency was observed in people exposed to {alpha}-radiation (Pu, Rn) and in cosmonauts. This fact allows MAC to be considered as an indicator of a high-energy local exposure. A new type of cells with multiple chromosome rearrangements was discovered in the course of analysis of stable aberrations by the fluorescence in situ hybridization (FISH) method. The biological consequences of MAC formation and possibility of revealing the whole diversity of cells with multiple aberrations by means of modern molecular-cytogenetic methods are discussed.

  13. Single-cell messenger RNA sequencing reveals rare intestinal cell types

    NARCIS (Netherlands)

    Grün, Dominic; Lyubimova, Anna; Kester, Lennart; Wiebrands, Kay; Basak, Onur; Sasaki, Nobuo; Clevers, Hans; van Oudenaarden, Alexander

    2015-01-01

    Understanding the development and function of an organ requires the characterization of all of its cell types. Traditional methods for visualizing and isolating subpopulations of cells are based on messenger RNA or protein expression of only a few known marker genes. The unequivocal identification

  14. Different Types of Cell Death Induced by Enterotoxins

    Directory of Open Access Journals (Sweden)

    Ming-Yuan Hong

    2010-08-01

    Full Text Available The infection of bacterial organisms generally causes cell death to facilitate microbial invasion and immune escape, both of which are involved in the pathogenesis of infectious diseases. In addition to the intercellular infectious processes, pathogen-produced/secreted enterotoxins (mostly exotoxins are the major weapons that kill host cells and cause diseases by inducing different types of cell death, particularly apoptosis and necrosis. Blocking these enterotoxins with synthetic drugs and vaccines is important for treating patients with infectious diseases. Studies of enterotoxin-induced apoptotic and necrotic mechanisms have helped us to create efficient strategies to use against these well-characterized cytopathic toxins. In this article, we review the induction of the different types of cell death from various bacterial enterotoxins, such as staphylococcal enterotoxin B, staphylococcal alpha-toxin, Panton-Valentine leukocidin, alpha-hemolysin of Escherichia coli, Shiga toxins, cytotoxic necrotizing factor 1, heat-labile enterotoxins, and the cholera toxin, Vibrio cholerae. In addition, necrosis caused by pore-forming toxins, apoptotic signaling through cross-talk pathways involving mitochondrial damage, endoplasmic reticulum stress, and lysosomal injury is discussed.

  15. Cinnamon extract suppresses experimental colitis through modulation of antigen-presenting cells.

    Science.gov (United States)

    Kwon, Ho-Keun; Hwang, Ji-Sun; Lee, Choong-Gu; So, Jae-Seon; Sahoo, Anupama; Im, Chang-Rok; Jeon, Won Kyung; Ko, Byoung Seob; Lee, Sung Haeng; Park, Zee Yong; Im, Sin-Hyeog

    2011-02-28

    To investigate the anti-inflammatory effects of cinnamon extract and elucidate its mechanisms for targeting the function of antigen presenting cells. Cinnamon extract was used to treat murine macrophage cell line (Raw 264.7), mouse primary antigen-presenting cells (APCs, MHCII(+)) and CD11c(+) dendritic cells to analyze the effects of cinnamon extract on APC function. The mechanisms of action of cinnamon extract on APCs were investigated by analyzing cytokine production, and expression of MHC antigens and co-stimulatory molecules by quantitative real-time PCR and flow cytometry. In addition, the effect of cinnamon extract on antigen presentation capacity and APC-dependent T-cell differentiation were analyzed by [H(3)]-thymidine incorporation and cytokine analysis, respectively. To confirm the anti-inflammatory effects of cinnamon extract in vivo, cinnamon or PBS was orally administered to mice for 20 d followed by induction of experimental colitis with 2,4,6 trinitrobenzenesulfonic acid. The protective effects of cinnamon extract against experimental colitis were measured by checking clinical symptoms, histological analysis and cytokine expression profiles in inflamed tissue. Treatment with cinnamon extract inhibited maturation of MHCII(+) APCs or CD11c(+) dendritic cells (DCs) by suppressing expression of co-stimulatory molecules (B7.1, B7.2, ICOS-L), MHCII and cyclooxygenase (COX)-2. Cinnamon extract induced regulatory DCs (rDCs) that produce low levels of pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, IL-12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α] while expressing high levels of immunoregulatory cytokines (IL-10 and transforming growth factor-β). In addition, rDCs generated by cinnamon extract inhibited APC-dependent T-cell proliferation, and converted CD4(+) T cells into IL-10(high) CD4(+) T cells. Furthermore, oral administration of cinnamon extract inhibited development and progression of intestinal colitis by inhibiting expression

  16. Establishment and characterization of a cell based artificial antigen-presenting cell for expansion and activation of CD8+ T cells ex vivo.

    Science.gov (United States)

    Gong, Weijuan; Ji, Mingchun; Cao, Zhengfeng; Wang, Liheng; Qian, Yayun; Hu, Maozhi; Qian, Li; Pan, Xingyuan

    2008-02-01

    Artificial antigen-presenting cells are expected to stimulate the expansion and acquisition of optimal therapeutic features of T cells before infusion. Here CD32 that binds to a crystallizable fragment of IgG monoclonal antibody was genetically expressed on human K562 leukemia cells to provide a ligand for T-cell receptor. CD86 and 4-1BBL, which are ligands of co-stimulating receptors of CD28 and 4-1BB, respectively, were also expressed on K562 cells. Then we accomplished the artificial antigen-presenting cells by coupling K32/CD86/4-1BBL cell with OKT3 monoclonal antibody against CD3, named K32/CD86/4-1BBL/OKT3 cells. These artificial modified cells had the abilities of inducing CD8+ T cell activation, promoting CD8+ T cell proliferation, division, and long-term growth, inhibiting CD8+ T cell apoptosis, and enhancing CD8+ T cell secretion of IFN-gamma and perforin. Furthermore, antigen-specific cytotoxic T lymphocytes could be retained in the culture stimulated with K32/CD86/4-1BBL/OKT3 cells at least within 28 days. This approach was robust, simple, reproducible and economical for expansion and activation of CD8+ T cells and may have important therapeutic implications for adoptive immunotherapy.

  17. Cell type specific DNA methylation in cord blood: A 450K-reference data set and cell count-based validation of estimated cell type composition

    NARCIS (Netherlands)

    Gervin, K. (Kristina); Page, C.M. (Christian Magnus); H.C.D. Aass (Hans Christian Dalsbotten); M.A.E. Jansen (Michelle A.E.); Fjeldstad, H.E. (Heidi Elisabeth); B.K. Andreassen (Bettina Kulle); L. Duijts (Liesbeth); J.B.J. van Meurs (Joyce); M.C. van Zelm (Menno); V.W.V. Jaddoe (Vincent); Nordeng, H. (Hedvig); Knudsen, G.P. (Gunn Peggy); P. Magnus (Per); W. Nystad (Wenche); Staff, A.C. (Anne Cathrine); J.F. Felix (Janine); R. Lyle (Robert)

    2016-01-01

    textabstractEpigenome-wide association studies of prenatal exposure to different environmental factors are becoming increasingly common. These studies are usually performed in umbilical cord blood. Since blood comprises multiple cell types with specific DNA methylation patterns, confounding caused

  18. The caspase-8/RIPK3 signaling axis in antigen presenting cells controls the inflammatory arthritic response.

    Science.gov (United States)

    Dominguez, Salina; Montgomery, Anna B; Haines, G Kenneth; Bloomfield, Christina L; Cuda, Carla M

    2017-10-04

    Caspase-8 is a well-established initiator of apoptosis and suppressor of necroptosis, but maintains functions beyond cell death that involve suppression of receptor-interacting serine-threonine kinases (RIPKs). A genome-wide association study meta-analysis revealed an SNP associated with risk of rheumatoid arthritis (RA) development within the locus containing the gene encoding for caspase-8. Innate immune cells, like macrophages and dendritic cells, are gaining momentum as facilitators of autoimmune disease pathogenesis, and, in particular, RA. Therefore, we examined the involvement of caspase-8 within these antigen-presenting cell populations in the pathogenesis of an arthritis model that resembles the RA effector phase. Cre LysM Casp8 flox/flox and Cre CD11c Casp8 flox/flox mice were bred via a cross between Casp8 flox/flox and Cre LysM or Cre CD11c mice. RIPK3 -/- Cre LysM Casp8 flox/flox and RIPK3 -/- Cre CD11c Casp8 flox/flox mice were generated to assess RIPK3 contribution. Mice were subjected to K/BxN serum-transfer-induced arthritis. Luminex-based assays were used to measure cytokines/chemokines. Histological analyses were utilized to examine joint damage. Mixed bone marrow chimeras were generated to assess synovial cell survival. Flow cytometric analysis was employed to characterize cellular distribution. For arthritis, differences between the groups were assessed using two-way analysis of variance (ANOVA) for repeated measurements. All other data were compared by the Mann-Whitney test. We show that intact caspase-8 signaling maintains opposing roles in lysozyme-M- and CD11c-expressing cells in the joint; namely, caspase-8 is crucial in CD11c-expressing cells to delay arthritis induction, while caspase-8 in lysozyme M-expressing cells hinders arthritis resolution. Caspase-8 is also implicated in the maintenance of synovial tissue-resident macrophages that can limit arthritis. Global loss of RIPK3 in both caspase-8 deletion constructs causes the response

  19. Electrochemical reduction of CO2 and H2O into fuels: Cell types and kinetic barriers

    DEFF Research Database (Denmark)

    Mogensen, Mogens Bjerg

    2013-01-01

    of production rate/cost. Production rate is determined mainly by electrode kinetics. Therefore, parallel to improving the electrodes of these electrolyser cells, other cell types, which have faster electrode kinetics, can electrolyse CO2 and have potential lower investment costs, are being researched......), and may be operated above 800 °C. A short review of the various types is presented, and the limitations of the kinetics are described. The pros and cons of high temperature and pressure as measures to increase the electrode kinetics are discussed. Naturally, the reaction rates increase with temperature...

  20. Mannosylation of virus-like particles enhances internalization by antigen presenting cells.

    Directory of Open Access Journals (Sweden)

    Farah Al-Barwani

    Full Text Available Internalization of peptides by antigen presenting cells is crucial for the initiation of the adaptive immune response. Mannosylation has been demonstrated to enhance antigen uptake through mannose receptors, leading to improved immune responses. In this study we test the effect of surface mannosylation of protein-based virus-like particles (VLP derived from Rabbit hemorrhagic disease virus (RHDV on uptake by murine and human antigen presenting cells. A monomannoside and a novel dimannoside were synthesized and successfully conjugated to RHDV VLP capsid protein, providing approximately 270 mannose groups on the surface of each virus particle. VLP conjugated to the mannoside or dimannoside exhibited significantly enhanced binding and internalization by murine dendritic cells, macrophages and B cells as well as human dendritic cells and macrophages. This uptake was inhibited by the inclusion of mannan as a specific inhibitor of mannose specific uptake, demonstrating that mannosylation of VLP targets mannose receptor-based uptake. Consistent with mannose receptor-based uptake, partial retargeting of the intracellular processing of RHDV VLP was observed, confirming that mannosylation of VLP provides both enhanced uptake and modified processing of associated antigens.

  1. Species, biotype, and bacteriophage type determinations compared with cell envelope protein profiles for typing Acinetobacter strains.

    Science.gov (United States)

    Bouvet, P J; Jeanjean, S; Vieu, J F; Dijkshoorn, L

    1990-02-01

    Species, biotypes, and phage types were determined for 120 Acinetobacter strains from clinical or environmental sources or from culture collections. These characteristics were compared with cell envelope protein profiles obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in previous studies. A considerable heterogeneity of species and types was observed by use of the various methods, in particular among strains from different sources. Acinetobacter baumannii was the most commonly found species in isolates from clinical sources, followed by Acinetobacter species 3. Nine biotypes were observed among A. baumannii strains. Further differentiation within most species and biotypes was achieved by protein profile typing and, to some extent, phage typing. Of 120 strains, 49 (41%) were not typeable by phages. Consistent results for the various classification methods were obtained for strains from common sources. Biotyping seemed an appropriate method for the screening of strains, whereas protein profile and phage typing could serve as additional methods to establish the identity or nonidentity of strains. Results of this study suggest that the combination of the typing methods is useful in epidemiological studies.

  2. Nevoid basal cell carcinoma syndrome presenting with neck pits and café au lait patches.

    Science.gov (United States)

    Balasundram, Sathesh; Kovilpillai, Ferdinand Jesudian; Hopper, Colin

    2010-01-01

    A 10- year-old patient presented with a slow growing jaw swelling. The initial general examination did not reveal any significant findings. Conservative enucleation of the cyst confirmed it to be an odontogenic keratocyst. The patient remained asymptomatic for the following 2 years and subsequently presented cystic lesions in jaws with displaced teeth. These cysts were enucleated and were confirmed to be odontogenic keratocysts . The patient has been on regular follow up since then and subsequent scans have shown further occurrence of cysts in the jaws with displacement of the third molars. Clinical examination also revealed macrocephaly, fronto-parietal bossing, pitting on palmar and plantar surfaces, calcification of falx cerebri and splayed ribs, confirming the diagnosis of nevoid basal cell carcinoma syndrome. He also presented with a cafi au lait patch and skin pits on the neck. The family history was negative for features of nevoid basal cell carcinoma syndrome. Nevoid basal cell carcinoma syndrome is a condition that can cause significant morbidity if not detected early. Over the years this syndrome has presented with many other non specific phenotype presentation, of which the current finding may be one of This calls for meticulous assessment and examination of patients and a standardized protocol in screening and managing these patients that may facilitate a more beneficial outcome for the patient.

  3. Biomimetic Magnetosomes as Versatile Artificial Antigen-Presenting Cells to Potentiate T-Cell-Based Anticancer Therapy.

    Science.gov (United States)

    Zhang, Qianmei; Wei, Wei; Wang, Peilin; Zuo, Liping; Li, Feng; Xu, Jin; Xi, Xiaobo; Gao, Xiaoyong; Ma, Guanghui; Xie, Hai-Yan

    2017-09-20

    Adoptive T-cell transfer for cancer therapy relies on both effective ex vivo T-cell expansion and in vivo targeting performance. One promising but challenging method for accomplishing this purpose is to construct multifunctional artificial antigen-presenting cells (aAPCs). We herein developed biomimetic magnetosomes as versatile aAPCs, wherein magnetic nanoclusters were coated with azide-engineered leucocyte membranes and then decorated with T-cell stimuli through copper-free click chemistry. These nano aAPCs not only exhibited high performance for antigen-specific cytotoxic T-cell (CTL) expansion and stimulation but also visually and effectively guided reinfused CTLs to tumor tissues through magnetic resonance imaging and magnetic control. The persisting T cells were able to delay tumor growth in a murine lymphoma model, while the systemic toxicity was not notable. These results together demonstrated the excellent potential of this "one-but-all" aAPC platform for T-cell-based anticancer immunotherapy.

  4. Mechanisms of lipid-antigen generation and presentation to T cells.

    Science.gov (United States)

    De Libero, Gennaro; Mori, Lucia

    2006-10-01

    The presentation of lipid antigens by CD1 molecules follows precise rules imposed by the biochemical nature of lipids. The structures of CD1-lipid complexes are elucidating how T-cell receptors interact with hydrophobic antigens. The mechanism of lipid uptake and the pathways followed by lipids embedded in the cell membrane contribute to the efficient presentation of exogenous and self-lipids. Lipid presentation is further regulated by the trafficking route of CD1 proteins and their precise membrane localization within endosomal vesicles. Moreover, the generation of immunogenic lipids might require adequate processing, which occurs in the presence of lipid-binding proteins, including CD1e. Here, we review recent experimental evidence that has revealed new protagonists involved in generating immunogenic lipids and has indicated unexpected biological mechanisms contributing to immune recognition.

  5. Intravascular large B-cell lymphoma presenting with fulminant pseudomembranous colitis.

    Science.gov (United States)

    Wang, Tao; Ghaffar, Hasan; Grin, Andrea

    2013-05-01

    Intravascular large B-cell lymphoma is a rare entity that usually presents in late stages with non-specific symptoms. We present a case of an incidentally discovered intravascular large B-cell lymphoma in a 78-year-old man who underwent colectomy for medically refractory pseudomembranous colitis. The malignant lymphocytes were preferentially localized to small colonic submucosal vasculature, without any evidence of an extravascular tumor mass. The gastrointestinal system is an exceeding rare initial diagnostic site for intravascular lymphoma, and presentation with pseudomembranous colitis has not been previously reported. We discuss the current definition of intravascular lymphoma, clinicopathological variants, differential diagnoses, as well as current therapy. Copyright © 2013 Elsevier GmbH. All rights reserved.

  6. Acute secondary adrenal insufficiency as the presenting manifestation of small-cell lung carcinoma.

    Science.gov (United States)

    Shah, Kinjal K; Anderson, Robert J

    2014-02-14

    A 66-year-old man, chronic smoker, presented with episodes of syncope, hypotension and constitutional symptoms. Initial evaluation revealed pre-renal azotaemia and acute secondary adrenal insufficiency.MRI performed was interpreted as a pituitary macroadenoma with enlargement of the infundibulum (stalk). Further endocrinological tests performed suggested central hypothyroidism and hypogonadism. Subsequent development of haemoptysis, headache and diplopia warranted further investigations, which revealed stage IV small-cell lung carcinoma with adrenal metastases. Subsequent brain imaging showed lesions in the brain parenchyma, pituitary and stalk, characteristic of metastases. Thus, we present a very atypical case of pituitary metastases presenting with acute secondary adrenal insufficiency.

  7. The first Danish family reported with an AQP5 mutation presenting diffuse non-epidermolytic palmoplantar keratoderma of Bothnian type, hyperhidrosis and frequent Corynebacterium infections

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Hetland, Liv Eline; Clemmensen, Ole

    2016-01-01

    in the epidermis of the palms and soles. CASE PRESENTATION: We report the first Danish family diagnosed with diffuse non-epidermolytic palmoplantar keratoderma of Bothnian type in which fourteen individuals are potentially affected. The proband, a 36-year-old male had since childhood been affected by pronounced......BACKGROUND: An autosomal dominant form of diffuse non-epidermolytic palmoplantar keratoderma, palmoplantar keratoderma of Bothnian type, is caused by mutations in the AQP5 gene encoding the cell-membrane water channel protein aquaporin 5 leading to defective epidermal-water-barrier function...... recurrent fungal infections, a wellknown feature of the condition, but also periodic worsening with pitted keratolysis and malodour due to bacterial infections. CONCLUSIONS: Palmoplantar keratoderma of Bothnian type, which may be associated with hyperhidrosis, is frequently complicated by fungal infections...

  8. 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.

  9. Small Cell Lung Cancer Presenting as Severe Thrombocytopenia and Refractory Hypokalemia

    Directory of Open Access Journals (Sweden)

    Rohan Mandaliya

    2014-01-01

    Full Text Available A 70-year-old female with a history of mild cirrhosis was referred by her primary care provider for a platelet count of 36,000/μL which had dropped from 47,000/μL in a week along with mild pain in extremities. Serum potassium was low (2.9 mEq/L in spite of the patient being recently started on potassium supplement on outpatient for hypokalemia. Initially thrombocytopenia was attributed to cirrhosis. However, platelet counts continued to drop to a nadir of 9000/μL in spite of several platelet transfusions. Hypokalemia was refractory to potassium supplements. Subsequent bone marrow biopsy revealed extensive marrow necrosis with a focus of small cell tumor cells of pulmonary origin. CT scan of the chest showed a spiculated left lung mass. The ACTH level was high, with normal rennin and aldosterone levels. The patient likely had ectopic ACTH syndrome from small cell lung cancer. She died within few days of diagnosis. Severe thrombocytopenia and refractory hypokalemia can rarely be initial presentations of small cell lung cancer. Thrombocytopenia should prompt an evaluation for bone marrow metastases and a search for undiagnosed systemic malignancy. In severe cases of metastases, bone marrow necrosis can be present. Refractory hypokalemia can be the sole presentation of ectopic ACTH production.

  10. Unique presentation of blastic plasmacytoid dendritic cell neoplasm: a single-center experience and literature review.

    Science.gov (United States)

    Paluri, Ravi; Nabell, Lisle; Borak, Samuel; Peker, Deniz

    2015-12-01

    Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematological malignancy derived from precursors of plasmacytoid dendritic cells. Very few cases of BPDCN have been described with lack of skin manifestations at the time of diagnosis. Here we report two rare non-cutaneous presentations of BPDCN without obvious skin lesions at our institution and also the literature review. Our first patient had a unique presentation of BPDCN confined to the sinonasal region with central nervous system involvement. The second patient we report is also atypical with regard to widespread disease that uncharacteristically spared the skin and bone marrow. BPDCN is a rare hematological malignancy involving immature plasmacytoid dendritic cells. It poses a diagnostic challenge requiring multidisciplinary approach to manage this disease. It is important to identify effective therapies for both cutaneous and non-cutaneous presentations of BPDCN, since most cases are uniformly fatal with conventional chemotherapy alone. High-dose induction therapy based on acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) regimens, to achieve complete remission followed by allo-hematopoietic stem cell transplantation from related or unrelated donors is recommended to improve long-term survival in these patients. Larger scale studies are warranted to understand the pathophysiology of the disease and the important prognostic indicators for optimal management. Copyright © 2014 John Wiley & Sons, Ltd.

  11. Interaction of T-cell and antigen presenting cell co-stimulatory genes in childhood IgE.

    NARCIS (Netherlands)

    Bottema, R.W.B.; Postma, D.S.; Reijmerink, N.E.; Thijs, C.; Stelma, F.F.; Smit, H.A.; van Schayck, C.P.; Brunekreef, B.; Koppelman, G.H.; Kerkhof, M.

    2010-01-01

    It is likely that multiple genes contribute to immunoglobulin (Ig)E production. Co-stimulatory molecules are crucial for the cross-talk between antigen presenting cells and T-lymphocytes which drives the IgE response. We evaluated gene-gene interactions of haplotype tagging polymorphisms in a

  12. Interaction of T-cell and antigen presenting cell co-stimulatory genes in childhood IgE

    NARCIS (Netherlands)

    Bottema, R. W. B.; Postma, D. S.; Reijmerink, N. E.; Thijs, C.; Stelma, F. F.; Simit, H. A.; van Schayck, C. P.; Brunekreef, B.; Koppelman, G. H.; Kerkhof, M.

    It is likely that multiple genes contribute to immunoglobulin (Ig)E production. Costimulatory molecules are crucial for the cross-talk between antigen presenting cells and T-lymphocytes which drives the IgE response. We evaluated gene-gene interactions of haplotype tagging polymorphisms in a pathway

  13. Langerhans' cell histiocytosis presenting with an intracranial epidural hematoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, K.-W. [Department of Pediatrics, Loma Linda Children' s Hospital and University Medical Center, Loma Linda, CA (United States); McLeary, M.S. [Div. of Pediatric Radiology, Loma Linda Children' s Hospital and University Medical Center, Loma Linda, CA (United States); Zuppan, C.W. [Dept. of Pathology, Loma Linda Children' s Hospital and University Medical Center, Loma Linda, CA (United States); Won, D.J. [Div. of Pediatric Neurosurgery, Loma Linda University Children' s Hospital, Loma Linda, CA (United States)

    2000-05-01

    An 8-year-old boy developed vomiting and severe headache following minor head trauma. A CT scan of the head demonstrated a lytic lesion of the skull and adjacent epidural hematoma. Surgical evacuation and removal of the skull lesion and hematoma were carried out, and pathologic evaluation resulted in a diagnosis of Langerhans' cell histiocytosis (LCH). Epidural involvement of Langerhans' cell histiocytosis is very rare, and we report the first case of LCH presenting as an intracranial epidural hematoma. (orig.)

  14. 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...... 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...

  15. Pathogenic CD4 T cells in type 1 diabetes recognize epitopes formed by peptide fusion

    Science.gov (United States)

    Delong, Thomas; Wiles, Timothy A.; Baker, Rocky L.; Bradley, Brenda; Barbour, Gene; Reisdorph, Richard; Kumar, Nitesh; Elso, Colleen M.; Armstrong, Michael; Powell, Roger L.; Reisdorph, Nichole; DeNicola, Megan; Bottino, Rita; Powers, Alvin C.; Harlan, David M.; Kent, Sally C.; Mannering, Stuart I.; Haskins, Kathryn

    2016-01-01

    Type 1 diabetes (T1D) is caused by T cell mediated destruction of the insulin-producing β cells. CD4 T cell responses play a central role in β-cell destruction but the identity of the epitopes recognized by pathogenic CD4 T cells remains unknown. To address this we used a panel of diabetes triggering CD4 T cell clones isolated from non-obese diabetic (NOD) mice. Here we show that these pathogenic CD4 T cells target peptide ligands that are formed by covalent crosslinking of proinsulin peptides to other peptides present in β-cell secretory granules. These hybrid insulin peptides (HIPs) are highly antigenic for CD4 T cells and can be detected by mass spectrometry in β-cells. CD4 T cells from the residual pancreatic islets of two organ donors who had T1D also recognize HIPs. The discovery that autoreactive T cells target hybrid peptides may explain how immune tolerance is broken in T1D. PMID:26912858

  16. An in silico analysis of nanoparticle/cell diffusive transfer: application to nano-artificial antigen-presenting cell:T-cell interaction.

    Science.gov (United States)

    Labowsky, Michael; Lowenthal, Justin; Fahmy, Tarek M

    2015-05-01

    Polymeric nanoparticles (nano-paAPCs) modified with T-cell antigens and encapsulating immunostimulatory or immunoinhibitory factors may act as artificial antigen-presenting cells to circulating immune cells, improving the selective delivery of encapsulated drug or cytokine to antigen-specific T-cells. Paracrine delivery of encapsulated agents from these nanoparticles to adjacent cells facilitate sustained delivery lowering the overall administered dose, thus enhancing the overall drug efficacy while reducing toxicity of pleiotropic factors. Little is known mathematically regarding the local concentration of released agent that accumulates around a nanoparticle that is near or embeds in a cell. These concentration fields are calculated here in an attempt to understand paracrine efficacy of these nano-paAPC systems. The significant factor accumulation that can occur if the particles were to embed in the cell membrane may explain observed experimental data regarding enhanced T-cell activation and nanoparticle-mediated improvement in the drug delivery process to non-internalizing cellular targets. In this interesting article, the authors utilized nanosized polymeric artificial presenting cells (nano-paAPC) that released cytokine to study the effects after interaction with T cells. It was found that nano-paAPC were able to embed into cell membrane, with subsequent enhanced T-cell activation. The findings provide further understanding of immune cell interaction and are considered to be important for designing nanoparticles engineered to deliver cytokines or immumodulatory factors to specific immune cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Small-molecule inhibitor which reactivates p53 in human T-cell leukemia virus type 1-transformed cells.

    Science.gov (United States)

    Jung, Kyung-Jin; Dasgupta, Arindam; Huang, Keven; Jeong, Soo-Jin; Pise-Masison, Cynthia; Gurova, Katerina V; Brady, John N

    2008-09-01

    Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of the aggressive and fatal disease adult T-cell leukemia. Previous studies have demonstrated that the HTLV-1-encoded Tax protein inhibits the function of tumor suppressor p53 through a Tax-induced NF-kappaB pathway. Given these attributes, we were interested in the activity of small-molecule inhibitor 9-aminoacridine (9AA), an anticancer drug that targets two important stress response pathways, NF-kappaB and p53. In the present study, we have examined the effects of 9AA on HTLV-1-transformed cells. Treatment of HTLV-1-transformed cells with 9AA resulted in a dramatic decrease in cell viability. Consistent with these results, we observed an increase in the percentage of cells in sub-G(1) and an increase in the number of cells positive by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling assay following treatment of HTLV-1-transformed cells with 9AA. In each assay, HTLV-1-transformed cells C8166, Hut102, and MT2 were more sensitive to treatment with 9AA than control CEM and peripheral blood mononuclear cells. Analyzing p53 function, we demonstrate that treatment of HTLV-1-transformed cells with 9AA resulted in an increase in p53 protein and activation of p53 transcription activity. Of significance, 9AA-induced cell death could be blocked by introduction of a p53 small interfering RNA, linking p53 activity and cell death. These results suggest that Tax-repressed p53 function in HTLV-1-transformed cells is "druggable" and can be restored by treatment with 9AA. The fact that 9AA induces p53 and inhibits NF-kappaB suggests a promising strategy for the treatment of HTLV-1-transformed cells.

  18. Laquinimod, a quinoline-3-carboxamide, induces type II myeloid cells that modulate central nervous system autoimmunity.

    Directory of Open Access Journals (Sweden)

    Ulf Schulze-Topphoff

    Full Text Available Laquinimod is a novel oral drug that is currently being evaluated for the treatment of relapsing-remitting (RR multiple sclerosis (MS. Using the animal model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE, we examined how laquinimod promotes immune modulation. Oral laquinimod treatment reversed established RR-EAE and was associated with reduced central nervous system (CNS inflammation, decreased Th1 and Th17 responses, and an increase in regulatory T cells (Treg. In vivo laquinimod treatment inhibited donor myelin-specific T cells from transferring EAE to naive recipient mice. In vivo laquinimod treatment altered subpopulations of myeloid antigen presenting cells (APC that included a decrease in CD11c(+CD11b(+CD4(+ dendritic cells (DC and an elevation of CD11b(hiGr1(hi monocytes. CD11b(+ cells from these mice exhibited an anti-inflammatory type II phenotype characterized by reduced STAT1 phosphorylation, decreased production of IL-6, IL-12/23 and TNF, and increased IL-10. In adoptive transfer, donor type II monocytes from laquinimod-treated mice suppressed clinical and histologic disease in recipients with established EAE. As effects were observed in both APC and T cell compartments, we examined whether T cell immune modulation occurred as a direct effect of laquinimod on T cells, or as a consequence of altered APC function. Inhibition of Th1 and Th17 differentiation was observed only when type II monocytes or DC from laquinimod-treated mice were used as APC, regardless of whether myelin-specific T cells were obtained from laquinimod-treated or untreated mice. Thus, laquinimod modulates adaptive T cell immune responses via its effects on cells of the innate immune system, and may not influence T cells directly.

  19. Silent Crooke's cell corticotroph adenoma of the pituitary gland presenting as delayed puberty.

    Science.gov (United States)

    Giri, Dinesh; Roncaroli, Federico; Sinha, Ajay; Didi, Mohammed; Senniappan, Senthil

    2017-01-01

    Corticotroph adenomas are extremely rare in children and adolescents. We present a 15-year-old boy who was investigated for delayed puberty (A1P2G1, bilateral testicular volumes of 3 mL each). There was no clinical or laboratory evidence suggestive of chronic illness, and the initial clinical impression was constitutional delay in puberty. Subsequently, MRI scan of the brain revealed the presence of a mixed cystic and solid pituitary lesion slightly displacing the optic chiasma. The lesion was removed by transphenoidal surgery and the biopsy confirmed the lesion to be pituitary adenoma. Furthermore, the adenoma cells also had Crooke's hyaline changes and were intensely positive for ACTH. However there was no clinical/biochemical evidence of ACTH excess. There was a spontaneous pubertal progression twelve months after the surgery (A2P4G4, with bilateral testicular volume of 8 mL). Crooke's cell adenoma is an extremely rare and aggressive variant of corticotroph adenoma that can uncommonly present as a silent corticotroph adenoma in adults. We report for the first time Crooke's cell adenoma in an adolescent boy presenting with delayed puberty. Constitutional delay of growth and puberty (CDGP) is a diagnosis of exclusion; hence a systematic and careful review should be undertaken while assessing boys with delayed puberty.Crooke's cell adenomas are a group of corticotroph adenomas that can rarely present in childhood and adolescence with delayed puberty.Crooke's cell adenomas can be clinically silent but are potentially aggressive tumours that require careful monitoring.

  20. Cell type-specific neuroprotective activity of untranslocated prion protein.

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    Elena Restelli

    2010-10-01

    Full Text Available A key pathogenic role in prion diseases was proposed for a cytosolic form of the prion protein (PrP. However, it is not clear how cytosolic PrP localization influences neuronal viability, with either cytotoxic or anti-apoptotic effects reported in different studies. The cellular mechanism by which PrP is delivered to the cytosol of neurons is also debated, and either retrograde transport from the endoplasmic reticulum or inefficient translocation during biosynthesis has been proposed. We investigated cytosolic PrP biogenesis and effect on cell viability in primary neuronal cultures from different mouse brain regions.Mild proteasome inhibition induced accumulation of an untranslocated form of cytosolic PrP in cortical and hippocampal cells, but not in cerebellar granules. A cyclopeptolide that interferes with the correct insertion of the PrP signal sequence into the translocon increased the amount of untranslocated PrP in cortical and hippocampal cells, and induced its synthesis in cerebellar neurons. Untranslocated PrP boosted the resistance of cortical and hippocampal neurons to apoptotic insults but had no effect on cerebellar cells.These results indicate cell type-dependent differences in the efficiency of PrP translocation, and argue that cytosolic PrP targeting might serve a physiological neuroprotective function.

  1. CD47 Enhances In Vivo Functionality of Artificial Antigen-Presenting Cells.

    Science.gov (United States)

    Bruns, Heiko; Bessell, Catherine; Varela, Juan Carlos; Haupt, Carl; Fang, Jerry; Pasemann, Shirin; Mackensen, Andreas; Oelke, Mathias; Schneck, Jonathan P; Schütz, Christian

    2015-05-01

    Artificial antigen-presenting cells, aAPC, have successfully been used to stimulate antigen-specific T-cell responses in vitro as well as in vivo. Although aAPC compare favorably with autologous dendritic cells in vitro, their effect in vivo might be diminished through rapid clearance by macrophages. Therefore, to prevent uptake and minimize clearance of aAPC by macrophages, thereby increasing in vivo functionality, we investigated the efficiency of "don't eat me" three-signal aAPC compared with classical two-signal aAPC. To generate "don't eat me" aAPC, CD47 was additionally immobilized onto classical aAPC (aAPC(CD47+)). aAPC and aAPC(CD47+) were analyzed in in vitro human primary T-cell and macrophage cocultures. In vivo efficiency was compared in a NOD/SCID T-cell proliferation and a B16-SIY melanoma model. This study demonstrates that aAPC(CD47+) in coculture with human macrophages show a CD47 concentration-dependent inhibition of phagocytosis, whereas their ability to generate and expand antigen-specific T cells was not affected. Furthermore, aAPC(CD47+)-generated T cells displayed equivalent killing abilities and polyfunctionality when compared with aAPC-generated T cells. In addition, in vivo studies demonstrated an enhanced stimulatory capacity and tumor inhibition of aAPC(CD47+) over normal aAPC in conjunction with diverging biodistribution in different organs. Our data for the first time show that aAPC functionalized with CD47 maintain their stimulatory capacity in vitro and demonstrate enhanced in vivo efficiency. Thus, these next-generation aAPC(CD47+) have a unique potential to enhance the application of the aAPC technology for future immunotherapy approaches. ©2015 American Association for Cancer Research.

  2. Gene-regulatory interactions in embryonic stem cells represent cell-type specific gene regulatory programs.

    Science.gov (United States)

    Ha, Misook; Hong, Soondo

    2017-10-13

    Pluripotency, the ability of embryonic stem cells to differentiate into specialized cell types, is determined by ESC-specific gene regulators such as transcription factors and chromatin modification factors. It is not well understood how ESCs are poised for differentiation, however, and methods are needed for prognosis of the molecular changes in the differentiation of ESCs into specific organs. We describe a new approach to infer cell-type specific gene regulatory programs based on gene regulatory interactions in ESCs. Our method infers the molecular logic of gene regulatory mechanisms by mapping the position-specific combinatory patterns of numerous regulators in ESCs into cell-type specific gene regulations. We validate the proposed approach by recapitulating the RNA-seq and microarray data of neuronal progenitor cells, adult liver cells, and ESCs from the integrated patterns of diverse gene regulators in ESCs. We find that the collective functions of diverse gene regulators in ESCs represent distinct gene regulatory programs in specialized cell types. Our new approach expands our understanding of the differential gene regulatory information in developments encoded in regulatory networks of ESCs. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Epidermal growth factor receptor mutation type III transfected into a small cell lung cancer cell line is predominantly localized at the cell surface and enhances the malignant phenotype.

    Science.gov (United States)

    Damstrup, Lars; Wandahl Pedersen, Mikkel; Bastholm, Lone; Elling, Folmer; Skovgaard Poulsen, Hans

    2002-01-01

    In the present study we transfected the epidermal growth factor receptor (EGFR)-negative small cell lung cancer cell line, GLC3, with the type III EGFR mutation (EGFRvIII). The EGFRvIII protein could be detected by Western blot analysis as a 145-kDa protein, which by immunohistochemistry appeared to be localized at the cell surface. Ultrastructurally EGFRvIII was expressed mainly at the cell surface with clusters at cell-cell contacts. In the in vitro invasion assay, GLC3-EGFRvIII cells had a approximately 5-fold increased invasion compared with uninduced GLC3-EGFRvIII, GLC3-Tet-On and the parental cell line. GLC3-Tet-On appeared uniform in size with adherence junctions at cell-cell contacts. In uninduced GLC3-EGFRvIII cells adherence junctions were also present but less distinct. In doxycycline-pretreated GLC3-EGFRvIII cells, adherence junctions were absent. We conclude that the expression of EGFRvIII results in a more malignant phenotype. This effect appears to involve the disruption of adherence junctions. Copyright 2002 Wiley-Liss, Inc.

  4. EBV driven natural killer cell disease of the central nervous system presenting as subacute cognitive decline.

    Science.gov (United States)

    Brett, Francesca M; Flavin, Richard; Chen, Daphne; Loftus, Teresa; Looby, Seamus; McCarthy, Allan; de Gascun, Cillian; Jaffe, Elaine S; Nor, Nurul; Javadpour, Mohsen; McCabe, Dominick

    2017-11-01

    Brain biopsy in patients presenting with subacute encephalopathyis never straightforward and only undertaken when a 'treatable condition' is a realistic possibility. This 63 year old right handed, immunocompetent Caucasian woman presented with an 8 month history of rapidly progressive right-sided hearing impairment, a 4 month history of intermittent headaches, tinnitus, 'dizziness', dysphagia, nausea and vomiting, with the subsequent evolution of progressive gait ataxia and a subacute global encephalopathy. The possibility of CJD was raised. Brain biopsy was carried out. Western blot for prion protein was negative. She died 9 days later and autopsy brain examination confirmed widespread subacute infarction due to an EBV positive atypical NK/T-cell infiltrate with positivity for CD3, CD56, granzyme B, perforin and EBER with absence of CD4, CD5 and CD8 expression. Molecular studies for T-cell clonality were attempted but failed due to insufficient DNA quality. Serology was consistent with past EBV infection (EBV VCA and EBNA IgG Positive). There was no evidence of disease outside the CNS. Primary central nervous system NK/T-cell lymphoma is extremely rare. The rare reported cases all present with a discrete intracranial mass, unlike the diffuse infiltrative pattern in this case. Whilst the diffuse interstitial pattern is reminiscent of chronic active EBV infection (CAEBV) seen in other organ systems such as the liver and bone marrow, the clinical presentation and epidemiologic profile are not typical for CAEBV.

  5. Differential alteration of lipid antigen presentation to NKT cells due to imbalances in lipid metabolism.

    Science.gov (United States)

    Schümann, Jens; Facciotti, Federica; Panza, Luigi; Michieletti, Mario; Compostella, Federica; Collmann, Anthony; Mori, Lucia; De Libero, Gennaro

    2007-06-01

    Deficiencies in enzymes of the lysosomal glycosphingolipid degradation pathway or in lysosomal lipid transfer proteins cause an imbalance in lipid metabolism and induce accumulation of certain lipids. A possible impact of such an imbalance on the presentation of lipid antigens to lipid-reactive T cells has only been hypothesized but not extensively studied so far. Here we demonstrate that presentation of lipid antigens to, and development of, lipid-reactive CD1d-restricted NKT cells, are impaired in mice deficient in the lysosomal enzyme beta-galactosidase (betaGal) or the lysosomal lipid transfer protein Niemann-Pick C (NPC) 2. Importantly, the residual populations of NKT cells selected in betaGal-/- and NPC2-/- mice showed differential TCR and CD4 repertoire characteristics, suggesting that differential selecting CD1d:lipid antigen complexes are formed. Furthermore, we provide direct evidence that accumulation of lipids impairs lipid antigen presentation in both cases. However, the mechanisms by which imbalanced lipid metabolism affected lipid antigen presentation were different. Based on these results, the impact of lipid accumulation should be generally considered in the interpretation of immunological deficiencies found in mice suffering from lipid metabolic disorders.

  6. Establishment and evaluation of a stable cattle type II alveolar epithelial cell line.

    Directory of Open Access Journals (Sweden)

    Feng Su

    Full Text Available Macrophages and dendritic cells are recognized as key players in the defense against mycobacterial infection. Recent research has confirmed that alveolar epithelial cells (AECs also play important roles against mycobacterium infections. Thus, establishing a stable cattle AEC line for future endogenous immune research on bacterial invasion is necessary. In the present study, we first purified and immortalized type II AECs (AEC II cells by transfecting them with a plasmid containing the human telomerase reverse trancriptase gene. We then tested whether or not the immortalized cells retained the basic physiological properties of primary AECs by reverse-transcription polymerase chain reaction and Western blot. Finally, we tested the secretion capacity of immortalized AEC II cells upon stimulation by bacterial invasion. The cattle type II alveolar epithelial cell line (HTERT-AEC II that we established retained lung epithelial cell characteristics: the cells were positive for surfactants A and B, and they secreted tumor necrosis factor-α and interleukin-6 in response to bacterial invasion. Thus, the cell line we established is a potential tool for research on the relationship between AECs and Mycobacterium tuberculosis.

  7. Inhibitory activity of cranberry juice on adherence of type 1 and type P fimbriated Escherichia coli to eucaryotic cells.

    Science.gov (United States)

    Zafriri, D; Ofek, I; Adar, R; Pocino, M; Sharon, N

    1989-01-01

    Inhibition of bacterial adherence to bladder cells has been assumed to account for the beneficial action ascribed to cranberry juice and cranberry juice cocktail in the prevention of urinary tract infections (A. E. Sobota, J. Urol. 131:1013-1016, 1984). We have examined the effect of the cocktail and juice on the adherence of Escherichia coli expressing surface lectins of defined sugar specificity to yeasts, tissue culture cells, erythrocytes, and mouse peritoneal macrophages. Cranberry juice cocktail inhibited the adherence of urinary isolates expressing type 1 fimbriae (mannose specific) and P fimbriae [specific for alpha-D-Gal(1----4)-beta-D-Gal] but had no effect on a diarrheal isolate expressing a CFA/I adhesin. The cocktail also inhibited yeast agglutination by purified type 1 fimbriae. The inhibitory activity for type 1 fimbriated E. coli was dialyzable and could be ascribed to the fructose present in the cocktail; this sugar was about 1/10 as active as methyl alpha-D-mannoside in inhibiting the adherence of type 1 fimbriated bacteria. The inhibitory activity for the P fimbriated bacteria was nondialyzable and was detected only after preincubation of the bacteria with the cocktail. Cranberry juice, orange juice, and pineapple juice also inhibited adherence of type 1 fimbriated E. coli, most likely because of their fructose content. However, the two latter juices did not inhibit the P fimbriated bacteria. We conclude that cranberry juice contains at least two inhibitors of lectin-mediated adherence of uropathogens to eucaryotic cells. Further studies are required to establish whether these inhibitors play a role in vivo.

  8. Dexamethasone inhibits the antigen presentation of dendritic cells in MHC class II pathway.

    Science.gov (United States)

    Pan, J; Ju, D; Wang, Q; Zhang, M; Xia, D; Zhang, L; Yu, H; Cao, X

    2001-04-02

    Glucocorticoids (GC) are physiological inhibitors of inflammatory responses and are widely used as anti-inflammatory and immunosuppressive agents in treatment of many autoimmune and allergic diseases. In the present study, we demonstrated that one of the mechanisms by which GC can suppress the immune responses is to inhibit the differentiation and antigen presentation of dendritic cells (DC). DC were differentiated from murine bone marrow hematopoietic progenitor cells by culture with GM-CSF and IL-4 with or without dexamethasone (Dex). Our data showed that Dex, in a dose dependent manner, down-regulated surface expression of CD86, CD40, CD54 and MHC class II molecules by DC, but the expression of MHC class I, CD80, CD95 and CD95L were not affected. In addition, Dex-treated DC showed an impaired function to activate alloreactive T cells and to secrete IL-Ibeta and IL-12p70. Moreover, Dex inhibited DC to present antigen by MHC class II pathway. However, the endocytotic activity of DC was not affected. The inhibitory effect of Dex on the expression of costimulatory molecules and the antigen-presenting capacity of DC could be blocked by the addition of RU486, a potent steroid hormone antagonist, suggesting the requirement of binding to cytosolic receptors in the above-described action of Dex. Since DC have the unique property to present antigen to responding naive T cells and are required in the induction of a primary response, the functional suppression of DC by Dex may be one of the mechanisms by which GC regulate immune responses in vivo.

  9. Evaluation of surgical margins according to the histological type of basal cell carcinoma.

    Science.gov (United States)

    Godoy, Charles Antonio Pires de; Neta, Alice Lima de Oliveira; Leão, Sofia Silveira de Souza; Dantas, Raul Lima; Carvalho, Valeska Oliveira Fonseca; Silva, Samuel Freire da

    2017-01-01

    Basal cell carcinoma is the most common skin cancer in the world. The aim of this study was to evaluate the surgical margin of basal cell carcinoma and correlate this with its histologic subtype. A retrospective analysis of pathology laboratory records from 1990 to 2000 was performed and the following data was collected: age, sex, race, anatomical location, histological type, and state of the excision margins in 1,428 histopathological reports of basal cell carcinoma. Ages ranged from 6 to 99 years, with an average of 57. There was a slight predominance of lesions in white women patients, and the most common histological subtype was the nodular, followed by the superficial. The most common locations were in the head and neck, with highest prevalence appeared in the nose. Surgical margins revealed a lateral involvement of 20.14% and a deep involvement of 12.47%. The fibrosing basal cell carcinoma is the histological type that most often presented positive surgical margins.

  10. Renal epithelioid angiomyolipoma presenting clinically as renal cell carcinoma – A case report

    Directory of Open Access Journals (Sweden)

    M.S. Johnson

    2014-12-01

    Full Text Available We describe a 22-year old female who presented with a 5-year history of a palpable, painless mass in the right flank. Computerized tomography demonstrated a solid renal mass measuring 18 cm × 13 cm with peripheral calcification, areas of vascularity and necrosis. The appearance suggested renal cell carcinoma or nephroblastoma, but percutaneous renal biopsy suggested an adrenal origin. At right radical nephrectomy, the adrenal gland was completely normal. Histology showed sheets and nests of epithelioid cells with abundant eosinophilic to clear cytoplasm, confirming a diagnosis of epithelioid angiomyolipoma (EAML, a rare mesenchymal tumor belonging to the perivascular epithelioid cell tumor family (PEComas. At 33 months followup, there was no evidence of recurrence or metastases.

  11. Challenges Considering the Degradation of Cell Components in Commercial Lithium-Ion Cells: A Review and Evaluation of Present Systems.

    Science.gov (United States)

    Kleiner, Karin; Ehrenberg, Helmut

    2017-06-01

    individual cell components. Although the degradation of materials is the key consideration in achieving lower costs, a higher safety standard, higher energy densities and a longer lifetime, the degradation of the individual cell components in dependence on the operation conditions has hardly been investigated and is poorly understood. The present work reviews known material degradations in commercial lithium-ion cells, shows a way to analyze such degradations in dependence on the operation conditions and describes how these degradation processes lead to observed performance drops.

  12. Stressful Presentations: Mild Chronic Cold Stress in Mice Influences Baseline Properties of Dendritic Cells

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    Kathleen Marie Kokolus

    2014-02-01

    Full Text Available The ability of dendritic cells to stimulate and regulate T cells is critical to effective anti-tumor immunity. Therefore, it is important to fully recognize any inherent factors which may influence DC function under experimental conditions, especially in laboratory mice since they are used so heavily to study immune responses. Physiological stress is well recognized to impair several arms of immune protection. The goals of this report are to briefly summarize previous work revealing how DCs respond to various forms of physiologically relevant stress and to present new data highlighting the potential for chronic mild cold stress inherent in mice housed at standard ambient temperatures required for laboratory mice to influence baseline DCs properties. Since recent data from our group shows that CD8+ T cell function is altered by mild chronic cold stress and since DC function is crucial for CD8+ T cell activation, we wondered whether mild cold stress may also be influencing DC properties. We found increased numbers of splenic DCs (CD11c+ in cold stressed mice compared to mice housed at a thermoneutral temperature, which significantly reduces cold stress. However, many of the DCs which are expanded in cold stressed mice express an immature phenotype. We also found that antigen presentation and ability of splenocytes to activate T cells were impaired compared to that seen in DCs isolated from mice at thermoneutrality. The new data presented here strongly suggest that the housing temperature of mice can affect fundamental properties of DC function which in turn could be influencing the response of DCs to added experimental stressors or other treatments.

  13. Cell type specific alterations in interchromosomal networks across the cell cycle.

    Directory of Open Access Journals (Sweden)

    Andrew J Fritz

    2014-10-01

    Full Text Available The interchromosomal organization of a subset of human chromosomes (#1, 4, 11, 12, 16, 17, and 18 was examined in G1 and S phase of human WI38 lung fibroblast and MCF10A breast epithelial cells. Radial positioning of the chromosome territories (CTs was independent of gene density, but size dependent. While no changes in radial positioning during the cell cycle were detected, there were stage-specific differences between cell types. Each CT was in close proximity (interaction with a similar number of other CT except the gene rich CT17 which had significantly more interactions. Furthermore, CT17 was a member of the highest pairwise CT combinations with multiple interactions. Major differences were detected in the pairwise interaction profiles of MCF10A versus WI38 including cell cycle alterations from G1 to S. These alterations in interaction profiles were subdivided into five types: overall increase, overall decrease, switching from 1 to ≥2 interactions, vice versa, or no change. A global data mining program termed the chromatic median determined the most probable overall association network for the entire subset of CT. This probabilistic interchromosomal network was nearly completely different between the two cell lines. It was also strikingly altered across the cell cycle in MCF10A, but only slightly in WI38. We conclude that CT undergo multiple and preferred interactions with other CT in the nucleus and form preferred -albeit probabilistic- interchromosomal networks. This network of interactions is altered across the cell cycle and between cell types. It is intriguing to consider the relationship of these alterations to the corresponding changes in the gene expression program across the cell cycle and in different cell types.

  14. A homodimeric complex of HLA-G on normal trophoblast cells modulates antigen-presenting cells via LILRB1

    OpenAIRE

    Apps, Richard; Gardner, Lucy; Sharkey, Andrew M.; Holmes, Nick; Moffett, Ashley

    2007-01-01

    In healthy individuals, the non-classical MHC molecule HLA-G is only expressed on fetal trophoblast cells that invade the decidua during placentation. We show that a significant proportion of HLA-G at the surface of normal human trophoblast cells is present as a disulphide-linked homodimer of the conventional ?2m-associated HLA-I complex. HLA-G is a ligand for leukocyte immunoglobulin-like receptors (LILR), which bind much more efficiently to dimeric HLA-G than to conventional HLA-I molecules...

  15. Large Cell Neuroendocrine Carcinoma of the Rectum Presenting with Extensive Metastatic Disease

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    Vinay Minocha

    2014-01-01

    Full Text Available Introduction. Rectal large cell neuroendocrine carcinoma (LCNEC is a poorly differentiated neoplasm that is very rare and belongs within the poorest prognostic subgroup among primary colorectal neoplasms. Here, we describe a case of LCNEC of the rectum, which highlights the aggressive clinical course and poor prognosis associated with this disease. Case Presentation. We report a case of a 63-year-old male who presented to our hospital with a one-month history of lower abdominal pain, constipation, and weight loss. A computed tomography (CT scan of the chest, abdomen, and pelvis revealed a rectal mass as well as metastatic disease of the liver and lung. Flexible sigmoidoscopy revealed a fungating, ulcerated and partially obstructing rectal mass located 6 cm from the anal verge. This mass was biopsied and pathological examination of the resected specimen revealed features consistent with a large cell neuroendocrine carcinoma. Conclusion. Rectal large cell neuroendocrine carcinomas are rare and have a significantly worse prognosis than adenocarcinomas. At diagnosis, a higher stage and metastatic disease are likely to be found. It is important to differentiate large cell, poorly differentiated neuroendocrine carcinomas from adenocarcinomas of the colon and rectum pathologically because patients may benefit from alternative cytotoxic chemotherapeutic regimens.

  16. Effects of aspirin on small-cell lung cancer mortality and metastatic presentation.

    Science.gov (United States)

    Maddison, Paul

    2017-04-01

    Although meta-analysis data have shown that taking regular aspirin may reduce lung cancer mortality, individual trial data results are conflicting, and the data on the effects of aspirin on different histological subtypes of lung tumours, in particular small-cell lung cancer, are sparse. We conducted a prospective observational study of 313 patients with a new diagnosis of small-cell lung cancer and recorded use of aspirin before and after tumour diagnosis. Seventy-one (23%) patients were taking regular daily aspirin for more than 2 years at the time of tumour diagnosis. We found that regular use of aspirin had no effect on survival nor metastatic presentation compared to data from small-cell lung cancer patients not taking aspirin. The lack of survival benefit in patients with small-cell lung cancer taking long-term aspirin may be due to the low expression of cyclooxygenase-2 in small-cell lung cancer tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Intravascular Large B-Cell Lymphoma Presenting as Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Elham Vali Khojeini

    2014-01-01

    Full Text Available Intravascular large B-cell lymphoma (IVLBL is a rare subtype of diffuse large B-cell lymphoma that resides in the lumen of blood vessels. Patients typically present with nonspecific findings, particularly bizarre neurologic symptoms, fever, and skin lesions. A woman presented with shortness of breath and a chest CT scan showed diffuse interstitial thickening and ground glass opacities suggestive of an interstitial lung disease. On physical exam she was noted to have splenomegaly. The patient died and at autopsy was found to have an IVLBL in her lungs as well as nearly all her organs that were sampled. Although rare, IVLBL should be included in the differential diagnosis of interstitial lung disease and this case underscores the importance of the continuation of autopsies.

  18. An unusual co-presentation of rhinolithiasis and squamous cell carcinoma in the nasal cavity.

    Science.gov (United States)

    Özdemir, Süleyman; Görgülü, Orhan; Akbaş, Yücel; Selçuk, Tahsin; Sayar, Hamide; Tarkan, Özgür

    2012-07-01

    Rhinoliths are nasal stones that result from mineralisation of salts around an endogenous or exogenous nidus within the nasal cavity. They are uncommon nasal masses and usually unilateral and single, situated in the floor of the nose. The patient typically presents with nasal obstruction, facial pain and foul-smelling nasal secretion. To the best of our knowledge, the occurrence of squamous cell carcinoma with rhinolithiasis has not been previously reported in the English-language literature. In this article, we present a 63-year-old man, who had unilateral rhinolithiasis with squamous cell carcinoma within the nasal cavity. Copyright © 2011 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  19. The Vif accessory protein alters the cell cycle of human immunodeficiency virus type 1 infected cells.

    Science.gov (United States)

    Wang, Jiangfang; Shackelford, Jason M; Casella, Carolyn R; Shivers, Debra K; Rapaport, Eric L; Liu, Bindong; Yu, Xiao-Fang; Finkel, Terri H

    2007-03-15

    The viral infectivity factor gene (vif) of HIV-1 increases the infectivity of viral particles by inactivation of cellular anti-viral factors, and supports productive viral replication in primary human CD4 T cells and in certain non-permissive T cell lines. Here, we demonstrate that Vif also contributes to the arrest of HIV-1 infected cells in the G(2) phase of the cell cycle. Viruses deleted in Vif or Vpr induce less cell cycle arrest than wild-type virus, while cells infected with HIV-1 deleted in both Vif and Vpr have a cell cycle profile equivalent to that of uninfected cells. Furthermore, expression of Vif alone induces accumulation of cells in the G(2) phase of the cell cycle. These data demonstrate a novel role for Vif in cell cycle regulation and suggest that Vif and Vpr independently drive G(2) arrest in HIV-1 infected cells. Our results may have implications for the actions and interactions of key HIV-1 accessory proteins in AIDS pathogenesis.

  20. Comparing n- and p-type polycrystalline silicon absorbers in thin-film solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Deckers, J. [imec, Kapeldreef 75, B-3001 Heverlee, Leuven (Belgium); ESAT, KU Leuven, Kardinaal Mercierlaan 94, B-3001 Heverlee, Leuven (Belgium); Bourgeois, E. [Institute for Materials Research (IMO), Hasselt University, Wetenschapspark 1, B-3590 Diepenbeek (Belgium); IMOMEC, IMEC vzw, Wetenschapspark 1, B-3590 Diepenbeek (Belgium); Jivanescu, M. [Department of Physics and Astronomy, University of Leuven, Celestijnenlaan 200D, B-3001 Heverlee, Leuven (Belgium); Abass, A. [Photonics Research Group (INTEC), Ghent University-imec, Sint-Pietersnieuwstraat 41, B-9000 Ghent (Belgium); Van Gestel, D.; Van Nieuwenhuysen, K.; Douhard, B. [imec, Kapeldreef 75, B-3001 Heverlee, Leuven (Belgium); D' Haen, J.; Nesladek, M.; Manca, J. [Institute for Materials Research (IMO), Hasselt University, Wetenschapspark 1, B-3590 Diepenbeek (Belgium); IMOMEC, IMEC vzw, Wetenschapspark 1, B-3590 Diepenbeek (Belgium); Gordon, I.; Bender, H. [imec, Kapeldreef 75, B-3001 Heverlee, Leuven (Belgium); Stesmans, A. [Department of Physics and Astronomy, University of Leuven, Celestijnenlaan 200D, B-3001 Heverlee, Leuven (Belgium); Mertens, R.; Poortmans, J. [imec, Kapeldreef 75, B-3001 Heverlee, Leuven (Belgium); ESAT, KU Leuven, Kardinaal Mercierlaan 94, B-3001 Heverlee, Leuven (Belgium)

    2015-03-31

    We have investigated fine grained polycrystalline silicon thin films grown by direct chemical vapor deposition on oxidized silicon substrates. More specifically, we analyze the influence of the doping type on the properties of this model polycrystalline silicon material. This includes an investigation of defect passivation and benchmarking of minority carrier properties. In our investigation, we use a variety of characterization techniques to probe the properties of the investigated polycrystalline silicon thin films, including Fourier Transform Photoelectron Spectroscopy, Electron Spin Resonance, Conductivity Activation, and Suns-Voc measurements. Amphoteric silicon dangling bond defects are identified as the most prominent defect type present in these layers. They are the primary recombination center in the relatively lowly doped polysilicon thin films at the heart of the current investigation. In contrast with the case of solar cells based on Czochralski silicon or multicrystalline silicon wafers, we conclude that no benefit is found to be associated with the use of n-type dopants over p-type dopants in the active absorber of the investigated polycrystalline silicon thin-film solar cells. - Highlights: • Comparison of n- and p-type absorbers for thin-film poly-Si solar cells • Extensive characterization of the investigated layers' characteristics • Literature review pertaining the use of n-type and p-type dopants in silicon.