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Sample records for antigen mage gage

  1. MAGE-A1, GAGE and NY-ESO-1 cancer/testis antigen expression during human gonadal development

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Kock, Kirsten; Nielsen, Ole;

    2007-01-01

    by single and double immunohistochemical staining. RESULTS: We found that GAGE was expressed in the primordial germ cells of the gonadal primordium, whereas MAGE-A1 and NY-ESO-1 were first detected in germ cells of both testis and ovary after sexual differentiation was initiated. The number of positive germ...

  2. MAGE-A Antigens and Cancer Immunotherapy

    Science.gov (United States)

    Zajac, Paul; Schultz-Thater, Elke; Tornillo, Luigi; Sadowski, Charlotte; Trella, Emanuele; Mengus, Chantal; Iezzi, Giandomenica; Spagnoli, Giulio C.

    2017-01-01

    MAGE-A antigens are expressed in a variety of cancers of diverse histological origin and germinal cells. Due to their relatively high tumor specificity, they represent attractive targets for active specific and adoptive cancer immunotherapies. Here, we (i) review past and ongoing clinical studies targeting these antigens, (ii) analyze advantages and disadvantages of different therapeutic approaches, and (iii) discuss possible improvements in MAGE-A-specific immunotherapies. PMID:28337438

  3. Distinct GAGE and MAGE-A expression during early human development indicate specific roles in lineage differentiation

    DEFF Research Database (Denmark)

    Gjerstorff, Morten; Harkness, Linda; Kassem, Moustapha

    2008-01-01

    and RT-PCR, we investigated the expression of CTAs in differentiated human embryonic stem cells (hESC) and in late embryos and early fetuses. RESULTS: We found that melanoma antigen A (MAGE-A) family members were expressed during differentiation of hESC to embryoid bodies and in teratomas, and overlapped...

  4. MAGE-A Cancer/Testis Antigens Inhibit MDM2 Ubiquitylation Function and Promote Increased Levels of MDM4.

    Directory of Open Access Journals (Sweden)

    Lynnette Marcar

    Full Text Available Melanoma antigen A (MAGE-A proteins comprise a structurally and biochemically similar sub-family of Cancer/Testis antigens that are expressed in many cancer types and are thought to contribute actively to malignancy. MAGE-A proteins are established regulators of certain cancer-associated transcription factors, including p53, and are activators of several RING finger-dependent ubiquitin E3 ligases. Here, we show that MAGE-A2 associates with MDM2, a ubiquitin E3 ligase that mediates ubiquitylation of more than 20 substrates including mainly p53, MDM2 itself, and MDM4, a potent p53 inhibitor and MDM2 partner that is structurally related to MDM2. We find that MAGE-A2 interacts with MDM2 via the N-terminal p53-binding pocket and the RING finger domain of MDM2 that is required for homo/hetero-dimerization and for E2 ligase interaction. Consistent with these data, we show that MAGE-A2 is a potent inhibitor of the E3 ubiquitin ligase activity of MDM2, yet it does not have any significant effect on p53 turnover mediated by MDM2. Strikingly, however, increased MAGE-A2 expression leads to reduced ubiquitylation and increased levels of MDM4. Similarly, silencing of endogenous MAGE-A expression diminishes MDM4 levels in a manner that can be rescued by the proteasomal inhibitor, bortezomid, and permits increased MDM2/MDM4 association. These data suggest that MAGE-A proteins can: (i uncouple the ubiquitin ligase and degradation functions of MDM2; (ii act as potent inhibitors of E3 ligase function; and (iii regulate the turnover of MDM4. We also find an association between the presence of MAGE-A and increased MDM4 levels in primary breast cancer, suggesting that MAGE-A-dependent control of MDM4 levels has relevance to cancer clinically.

  5. MAGE-A Cancer/Testis Antigens Inhibit MDM2 Ubiquitylation Function and Promote Increased Levels of MDM4

    Science.gov (United States)

    Marcar, Lynnette; Ihrig, Bianca; Hourihan, John; Bray, Susan E.; Quinlan, Philip R.; Jordan, Lee B.; Thompson, Alastair M.; Hupp, Ted R.; Meek, David W.

    2015-01-01

    Melanoma antigen A (MAGE-A) proteins comprise a structurally and biochemically similar sub-family of Cancer/Testis antigens that are expressed in many cancer types and are thought to contribute actively to malignancy. MAGE-A proteins are established regulators of certain cancer-associated transcription factors, including p53, and are activators of several RING finger-dependent ubiquitin E3 ligases. Here, we show that MAGE-A2 associates with MDM2, a ubiquitin E3 ligase that mediates ubiquitylation of more than 20 substrates including mainly p53, MDM2 itself, and MDM4, a potent p53 inhibitor and MDM2 partner that is structurally related to MDM2. We find that MAGE-A2 interacts with MDM2 via the N-terminal p53-binding pocket and the RING finger domain of MDM2 that is required for homo/hetero-dimerization and for E2 ligase interaction. Consistent with these data, we show that MAGE-A2 is a potent inhibitor of the E3 ubiquitin ligase activity of MDM2, yet it does not have any significant effect on p53 turnover mediated by MDM2. Strikingly, however, increased MAGE-A2 expression leads to reduced ubiquitylation and increased levels of MDM4. Similarly, silencing of endogenous MAGE-A expression diminishes MDM4 levels in a manner that can be rescued by the proteasomal inhibitor, bortezomid, and permits increased MDM2/MDM4 association. These data suggest that MAGE-A proteins can: (i) uncouple the ubiquitin ligase and degradation functions of MDM2; (ii) act as potent inhibitors of E3 ligase function; and (iii) regulate the turnover of MDM4. We also find an association between the presence of MAGE-A and increased MDM4 levels in primary breast cancer, suggesting that MAGE-A-dependent control of MDM4 levels has relevance to cancer clinically. PMID:26001071

  6. MAGE-A3/4 and NY-ESO-1 antigens expression in metastatic esophageal squamous cell carcinoma.

    Science.gov (United States)

    Bujas, T; Marusic, Z; Peric Balja, M; Mijic, A; Kruslin, B; Tomas, D

    2011-03-21

    In the present study we analyzed immunohistochemical expression of MAGE-A 3/4 and NY-ESO-1 in 55 samples of esophageal squamous cell carcinomas (ESCC) and their respective lymph node metastases. To our knowledge this is the first study to assess and compare the expression of these antigens in ESCC lymph node metastases. Fifty (90.9%) primary ESCC were positive for MAGE-A 3/4 and 53 (96.6%) were positive for NY-ESO-1. MAGE-A 3/4 was expressed in all lymph node metastases and the intensity of expression was high in a majority of cases. NY-ESO-1 was negative in 2 (7.1%) lymph nodes metastases, while the reaction was predominantly moderate in the positive group. In primary tumors MAGE-A 3/4 showed a significantly higher intensity of expression compared to NY-ESO-1 (P=0.047), while in lymph node metastases the intensity of expression was not significantly different (P=0.387). Primary tumors with and without lymph node metastases showed no significant differences in MAGE-A 3/4 (P=0.672) and NY-ESO-1 (P=0.444) expression. Intensity of MAGE-A 3/4 (P=0.461) and NY-ESO-1 (P=0.414) expression in primary tumors was not significantly different compared to the expression in their respective lymph nodes metastases. Expression of MAGE-A 3/4 in primary tumors showed significant positive correlation with primary tumor expression of NY-ESO-1 (P=0.021) but no significant correlation with the expression of MAGE-A 3/4 in lymph node metastases (P=0.056). Expression of NY-ESO-1 in primary tumors showed significant positive correlation with the expression of NY-ESO-1 in lymph node metastases (P=0.001) and significant negative correlation with patients’ age (PESO-1 in primary tumors and lymph node metastases showed no significant correlation with prognostic parameters such as tumor grade and TNM stage (P>0.05). We have shown different levels of MAGE-A 3/4 and NY-ESO-1 expression in almost all specimens of primary tumor and lymph node metastases, suggesting that ESCC may be possible target

  7. CT10: a new cancer-testis (CT) antigen homologous to CT7 and the MAGE family, identified by representational-difference analysis.

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    Güre, A O; Stockert, E; Arden, K C; Boyer, A D; Viars, C S; Scanlan, M J; Old, L J; Chen, Y T

    2000-03-01

    Assays relying on humoral or T-cell-based recognition of tumor antigens to identify potential targets for immunotherapy have led to the discovery of a significant number of immunogenic gene products, including cancer-testis (CT) antigens predominantly expressed in cancer cells and male germ cells. The search for cancer-specific antigens has been extended via the technique of representational-difference analysis and SK-MEL-37, a melanoma cell line expressing a broad range of CT antigens. Using this approach, we have isolated CT antigen genes, genes over-expressed in cancer, e. g., PRAME and KOC, and genes encoding neuro-ectodermal markers. The identified CT antigen genes include the previously defined MAGE-A6, MAGE-A4a, MAGE-A10, CT7/MAGE-C1, as well as a novel gene designated CT10, which shows strong homology to CT7/MAGE-C1 both at cDNA and at genomic levels. Chromosome mapping localized CT10 to Xq27, in close proximity to CT7/MAGE-C1 and MAGE-A genes. CT10 mRNA is expressed in testis and in 20 to 30% of various human cancers. A serological survey identified 2 melanoma patients with anti-CT10 antibody, demonstrating the immunogenicity of CT10 in humans.

  8. The role of GAGE cancer/testis antigen in metastasis

    DEFF Research Database (Denmark)

    Gjerstorff, Morten Frier; Terp, Mikkel Green; Hansen, Malene Bredahl;

    2016-01-01

    with migratory and invasive properties and were found to be upregulated in cancer cells with metastasizing potential in a gastric cancer model. METHODS: We have addressed the direct role of GAGE proteins in supporting metastasis using an isogenic metastasis model of human cancer, consisting of 4 isogenic cell......) and moderately metastatic clones (LM3), stable downregulation of GAGE expression did not affect the ability of CL16 cells to establish primary tumors and form metastasis in the lungs of immunodeficient mice. CONCLUSIONS: These results suggest that GAGE proteins per se do not support metastasis and that further...

  9. Centrosomal localisation of the cancer/testis (CT) antigens NY-ESO-1 and MAGE-C1 is regulated by proteasome activity in tumour cells.

    Science.gov (United States)

    Pagotto, Anna; Caballero, Otavia L; Volkmar, Norbert; Devalle, Sylvie; Simpson, Andrew J G; Lu, Xin; Christianson, John C

    2013-01-01

    The Cancer/Testis (CT) antigen family of genes are transcriptionally repressed in most human tissues but are atypically re-expressed in many malignant tumour types. Their restricted expression profile makes CT antigens ideal targets for cancer immunotherapy. As little is known about whether CT antigens may be regulated by post-translational processing, we investigated the mechanisms governing degradation of NY-ESO-1 and MAGE-C1 in selected cancer cell lines. Inhibitors of proteasome-mediated degradation induced the partitioning of NY-ESO-1 and MAGE-C1 into a detergent insoluble fraction. Moreover, this treatment also resulted in increased localisation of NY-ESO-1 and MAGE-C1 at the centrosome. Despite their interaction, relocation of either NY-ESO-1 or MAGE-C1 to the centrosome could occur independently of each other. Using a series of truncated fragments, the regions corresponding to NY-ESO-1(91-150) and MAGE-C1(900-1116) were established as important for controlling both stability and localisation of these CT antigens. Our findings demonstrate that the steady state levels of NY-ESO-1 and MAGE-C1 are regulated by proteasomal degradation and that both behave as aggregation-prone proteins upon accumulation. With proteasome inhibitors being increasingly used as front-line treatment in cancer, these data raise issues about CT antigen processing for antigenic presentation and therefore immunogenicity in cancer patients.

  10. Immunohistochemical expression of tumor antigens MAGE-A3/4 and NY-ESO-1 in renal oncocytoma and chromophobe renal cell carcinoma.

    Science.gov (United States)

    Demirović, Alma; Džombeta, Tihana; Tomas, Davor; Spajić, Borislav; Pavić, Ivana; Hudolin, Tvrtko; Milošević, Milan; Cupić, Hrvoje; Krušlin, Božo

    2010-10-15

    The distinction between renal oncocytoma (RO) and chromophobe renal cell carcinoma (ChRCC), especially the eosinophilic variant, can often be difficult. Our study has documented for the first time the expression of MAGE-A3/4 and NY-ESO-1 cancer testis antigens (CTAs) in these tumors. A total of 35 patients (17 ROs and 18 ChRCCs) were included in the study. Two antibodies were used for immunohistochemical staining: 57B recognizing multiple MAGE-A and D8.38 recognizing NY-ESO-1 CTAs. Fifteen (88.2%) samples of RO stained positively for both MAGE-A3/4 and NY-ESO-1 antigens. Regarding ChRCC, seven (38.9%) stained positively for MAGE-A3/4 and six (33.3%) for NY-ESO-1 antigens. Median MAGE-A3/4 expression was moderately positive in RO and negative in ChRCC. The difference in MAGE-A3/4 expression between two tumor groups was significant (P=0.0013). Median NY-ESO-1 expression was strongly positive in RO and negative in ChRCC. The difference in NY-ESO-1 expression between two tumor groups was also significant (P=0.0008). Our study has shown that RO had a significantly higher expression of both CTAs. However, additional research is needed to clarify their potential diagnostic implications.

  11. Efficient induction of anti-tumor immune response in esophageal squamous cell carcinoma via dendritic cells expressing MAGE-A3 and CALR antigens.

    Science.gov (United States)

    Liu, Xinli; Song, Na; Liu, Yu; Liu, Yang; Li, JiJia; Ding, Jianqiao; Tong, Zhuang

    2015-06-01

    Despite advances in the various treatment options for esophageal squamous cell carcinoma (ESCC), its prognosis is still very poor with a 5-year survival rate of only 14-22%. Recently, among the various therapeutic approaches, the focus has shifted to immunotherapy, specifically immunotherapy involving dendritic cells (DCs), which depends on their maturation and antigen presentation to effector immune cells. Recent studies have suggested that melanoma-associated antigen 3 (MAGE-A3) is a potential immunotherapeutic target and also a candidate for the development of an anti-tumor vaccine. Calreticulin (CALR) has been shown to support induction of DC maturation. Therefore, in this study, we overexpressed MAGE-A3 and CALR on DCs and studied their potential to generate anti-tumor immune responses. We observed that adenovirus (Ad)-infected DCs overexpressing CALR and MAGE-A3 showed enhanced expression of CD80, CD83, CD86, and HLA-DR markers. Also, these DCs secreted higher levels of interleukin (IL)-12, which induces the T helper type 1 cell (Th1) response, and a lower level of IL-10, a negative regulator of the Th1 response. Furthermore, CALR/MAGE-A3-infected DCs stimulated CD8(+) cytotoxic T lymphocytes, which in turn secreted higher levels of interferon-γ, which induced cytotoxic effects on ESCC cells expressing MAGE-A3. In conclusion, our results revealed the potential of CALR/MAGE-A3-infected DCs to elicit a MAGE-A3-specific anti-tumor immunogenic response in ESCC. This proof-of-principle study may promote the future design and development of DC-based effective immunotherapy against ESCC.

  12. Restriction of GAGE protein expression to subpopulations of cancer cells is independent of genotype and may limit the use of GAGE proteins as targets for cancer immunotherapy

    DEFF Research Database (Denmark)

    Gjerstorff, M F; Johansen, L E; Nielsen, O

    2006-01-01

    The GAGE cancer testis antigen gene family encodes products that can be recognized by autologous T cells, and GAGE proteins have been suggested as potential targets for cancer immunotherapy. Analysis of GAGE expression in tumours has primarily been performed at the level of gene transcription......, whereas little is known about GAGE expression at the protein level. To evaluate the potential of GAGE proteins as targets for cancer-specific immunotherapy, we studied the expression of these proteins in normal and malignant cells/tissues using a novel panel of monoclonal antibodies. Immunohistochemical...... analysis of more than 250 cancer specimens demonstrated that GAGE proteins were frequently expressed in numerous cancer types and correlated with the expression of the cancer testis antigens MAGE-A1 and NY-ESO-1. Significant intercellular and subcellular differences in GAGE protein levels were observed...

  13. Expression, purification and characterization of the cancer-germline antigen GAGE12I: a candidate for cancer immunotherapy

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Besir, Hüseyin; Larsen, Martin R

    2010-01-01

    for immunotherapy and candidates for cancer vaccines. Recombinant proteins may be superior to peptides as immunogens, since they have the potential to prime both CD4(+) and CD8(+) T cells and are not dependent on patient HLA-type. We have developed a method for production of highly pure recombinant GAGE12I......GAGE cancer-germline antigens are frequently expressed in a broad range of different cancers, while their expression in normal tissues is limited to the germ cells of the immune privileged organs, testis and ovary. GAGE proteins are immunogenic in humans, which make them promising targets...... filtration and formaldehyde cross-linking indicated that GAGE12I forms tetramers. The purified recombinant GAGE12I represents a candidate molecule for vaccination of cancer patients and will form the basis for further structural analysis of GAGE proteins....

  14. An overview of the GAGE cancer/testis antigen family with the inclusion of newly identified members

    DEFF Research Database (Denmark)

    Gjerstorff, M F; Ditzel, H J

    2008-01-01

    GAGE cancer/testis antigens are frequently expressed in many different types of cancer, whereas their expression in normal tissues is limited to the germ cells of the immune-privileged organs, testis and ovary. Thus, GAGE proteins may be attractive candidates for immunotherapy of cancer....... This review describes the structure and phylogeny of the GAGE family members and presents a revised nomenclature, which will enable a more clear distinction of genes and gene products. The GAGE gene locus at chromosome X p11.23 consists of at least 16 genes, each of which is located in one of an equal number...... cell biology. When expressed in tumor cells, GAGE proteins can elicit both cellular and humoral immune responses, indicating that they are appropriate targets for cancer immunotherapy. The potential use of GAGE proteins in cancer immunotherapy, including possible limitations, is also discussed....

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  16. 喉癌来源的MAGE-A3基因真核表达载体及其稳定表达模型的构建和鉴定%Construction and identification of laryngocarcinoma-derived melanoma antigen-encoding-A3 gene eukaryotic expression vector and steady expression model

    Institute of Scientific and Technical Information of China (English)

    吉晓滨; 吕景礼; 陈敬贤; 刘启才; 谢景华

    2012-01-01

    目的:克隆人黑色素瘤相关抗原MAGE-A3基因,构建真核表达载体,检测、鉴定其在细胞中的表达.方法:MAGE-A3基因进行PCR扩增,凝胶回收PCR产物片段并连接至pMD18-T载体.测序后将MAGE-A3基因片段亚克隆至真核表达载体,构建成pIRES2-EGFP/MAGE-A3重组质粒.经脂质体转染至293T细胞株后,荧光定量PCR、Western-blotting法鉴定MAGE-A3基因的表达.结果:MAGE-A3基因正确克隆在plRES2-EGFP/MAGE-A3,测序结果与GenBank公布的MAGE-A3序列一致.转染293T细胞后能检测到MAGE-A3基因和蛋白的表达.结论:成功构建plRES2-EGFP/MAGE-A3真核表达质粒,并能在293T细胞中有效表达MAGE-A3蛋白,奠定了其作为DNA疫苗应用的基础.%Objective; To construct human melanoma antigen-encoding gene ( MAGE-A3 ) eukaryotic expression vector, and to identify and determine the expression in cell lines. Methods; MAGE-A3 gene was amplified by using polymerase chain reaction (PCR) and was linked to pMD18-T vector after harvesting PCR products via gel extraction. After confirmation by sequencing, the gene segments of MAGE-A3 were subcloned into eukaryotic expression vector for construction of pIRES2-EGFP/MAGE-A3, the recombinant plasmid. This was followed by transfection into the 293 T cell lines using liposomes for further determination of MAGE-A3 gene expression via fluorescent quantitative PCR and Western blotting. Results; MAGE-A3 gene was successfully cloned in the plasmid pIRES2-EGFP/MAGE-A3 , showing identical sequence of MAGE-A3 as compared with that reported in GenBank. The expression of MAGE-A3 genes and proteins were identified after transfection into the 293T cells. Conclusion;The successful construction of eukaryotic expression plasmid pIRES2-EGFP/MAGE-A3 was associated with effective expression of MAGE-A3 protein in 293T cell lines. This may offer grounds for the application of pIRES2-EGFP/MAGE-A3 as a DNA vaccine candidate in laryngocarcinoma immunotherapy.

  17. Images du Mage, images pour le Mage

    Directory of Open Access Journals (Sweden)

    Daniel GREGORIO

    2007-01-01

    Full Text Available Les œuvres d’Alphonse X proposent diverses représentations du mage, qui en font, tour à tour, l’ennemi ou l’allié de la religion chrétienne. Il est vrai que parfois, comme le montre l’histoire de Simon le magicien, la pratique de la magie implique un commerce direct et néfaste avec les forces infernales. Néanmoins, les personnages de Merlin et des Rois Mages, tels qu’ils sont présentés par Alphonse X, démontrent que magie et religion peuvent cohabiter, à condition toutefois que le mage croit en la virginité de Marie et en l’Incarnation et que sa pratique magique soit bénéfique pour la communauté. Ce bénéfice requiert parfois la reconstruction de l’univers quotidien ; pour ce faire, le magicien doit savoir quand et comment utiliser des objets et des pentacles, qui lui permettront de soumettre les forces surnaturelles. Il doit donc posséder une connaissance approfondie du monde naturel et des esprits qui, conjuguée à sa foi religieuse, l’empêchera de tomber dans la démonolâtrie.Las obras alfonsíes proponen diversas aproximaciones al personaje del mago, generalmente considerado como un ser antagónico del hombre religioso. Es cierto que en algunas ocasiones, como ocurre con Simón el mago, la práctica de las artes mágicas significa un trato directo y nefasto con las fuerzas infernales. Sin embargo, personajes como Merlín o los Reyes Magos, tal y como los describe Alfonso X, subrayan una posible cohabitación entre magia y religión sin que la práctica de la una signifique la exclusión de la otra. Sólo hay que cumplir con dos condiciones : creer en la virginidad de María y que Dios se hizo hombre, y proporcionar a la comunidad un beneficio claro. Este beneficio requiere en ocasiones remodelar lo cotidiano, utilizando objetos y pentáculos, en circunstancias extremadamente determinadas, lo que implica un conocimiento exhaustivo tanto del mundo natural como del simbólico y de los espíritus. Es este

  18. Expression of MAGE-C1/CT7 and MAGE-C2/CT10 predicts lymph node metastasis in melanoma patients.

    Directory of Open Access Journals (Sweden)

    Alessandra Curioni-Fontecedro

    Full Text Available MAGE-C1/CT7 and MAGE-C2/CT10 are members of the large MAGE family of cancer-testis (CT antigens. CT antigens are promising targets for immunotherapy in cancer because their expression is restricted to cancer and germ line cells and a proportion of cancer patients presents with immune responses against CT antigens, which clearly demonstrates their immunogenicity. This study investigates the expression of MAGE-C1/CT7 and MAGE-C2/CT10 in primary and metastatic melanoma. Immunohistochemical staining of tissue microarrays that consisted of 59 primary malignant melanomas of the skin, 163 lymph node and distant melanoma metastases and 68 melanoma cell lines was performed. We found MAGE-C1/CT7 expression in 15 out of 50 (24% primary melanomas and 15 out of 50 (24% cell lines, whereas MAGE-C2/CT10 was detected in 17 out of 51 (33% primary melanomas and 14 out of 68 (17% cell lines. MAGE-C1/CT7 and MAGE-C2/CT10 were both detected in 40% of melanoma metastases. Patients with MAGE-C1/CT7 or MAGE-C2/CT10 positive primary melanoma had significantly more lymph node metastases (p = 0.005 and p<0.001, resp.. Prediction of lymph node metastasis by MAGE-C1/CT7 and MAGE-C2/CT10 was independent of tumor cell proliferation rate (Ki67 labeling index in a multivariate analysis (p = 0.01. Our results suggest that the expression of MAGE-C1/CT7 and MAGE-C2/CT10 in primary melanoma is a potent predictor of sentinel lymph node metastasis.

  19. In Vitro Assessment of the Expression and T Cell Immunogenicity of the Tumor-Associated Antigens BORIS, MUC1, hTERT, MAGE-A3 and Sp17 in Uterine Cancer

    Directory of Open Access Journals (Sweden)

    Anke Vanderstraeten

    2016-09-01

    Full Text Available Background: While immunotherapy moved to the forefront of treatment of various cancers, it remains underexplored for uterine cancer. This might be due to the small patient population with advanced endometrial carcinoma and uterine sarcoma. Data about immunotherapeutic targets are scarce in endometrial carcinoma and lacking in uterine sarcoma. Methods: Expression of five tumor-associated antigens (TAA (BORIS, MUC1, hTERT, MAGE-A3 and Sp17 was validated in uterine tumor samples by immunohistochemistry (IHC and/or quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR. TAA immunogenicity was analyzed by determining spontaneous T cell responses towards overlapping peptide pools covering the whole TAA in patient blood. Results: At mRNA level, MAGE-A3 and Sp17 were overexpressed in a minority of patients and BORIS was moderately overexpressed (26% in endometrial carcinoma and 62% in uterine sarcoma. hTERT was overexpressed in the vast majority of tumors. On protein level, MUC1 was upregulated in primary, recurrent and metastatic EMCAR and in metastatic US tumors. hTERT protein was highly expressed in both normal and malignant tissue. Spontaneous TAA-specific T cell responses were detected in a minority of patients, except for hTERT to which T cell responses occurred more frequently. Conclusions: These data point to MUC1 and hTERT as most suitable targets based on expression levels and T cell immunogenicity for use in immunotherapeutic regimens.

  20. Involvement of Maged1 in motor behaviour and drug addiction

    OpenAIRE

    De Backer, Jean-François

    2015-01-01

    Maged1 appartient à la famille des gènes Mage (pour Melanoma antigen gene). Bien que les gènes Mage aient tout d'abord été découverts dans des cellules tumorales, le gène Maged1 est également exprimé dans un grand nombre de tissus sains et particulièrement dans le système nerveux central, aussi bien au cours du développement que chez l'animal adulte. Les fonctions exercées par la protéine Maged1 dans le système nerveux restent actuellement fort méconnues bien que des études aient pu mettre en...

  1. Expression Patterns of Cancer-Testis Antigens in Human Embryonic Stem Cells and Their Cell Derivatives Indicate Lineage Tracks

    OpenAIRE

    Nadya Lifantseva; Anna Koltsova; Tatyana Krylova; Tatyana Yakovleva; Galina Poljanskaya; Olga Gordeeva

    2011-01-01

    Pluripotent stem cells can differentiate into various lineages but undergo genetic and epigenetic changes during long-term cultivation and, therefore, require regular monitoring. The expression patterns of cancer-testis antigens (CTAs) MAGE-A2, -A3, -A4, -A6, -A8, -B2, and GAGE were examined in undifferentiated human embryonic stem (hES) cells, their differentiated derivatives, teratocarcinoma (hEC) cells, and cancer cell lines of neuroectodermal and mesodermal origin. Undifferentiated hES ce...

  2. Full-length Cloning of Human Melanoma Antigen-encoding Gene D1 Using Rapid Amplification of cDNA Ends%采用RACE技术获得全长人新基因MAGE-D1

    Institute of Scientific and Technical Information of China (English)

    邢桂春; 张成岗; 魏汉东; 贺福初

    2001-01-01

    cDNA 末端快速扩增(RACE)技术是快速获得新基因5'和3'端未知序列的有效手段.鉴于新报导的人肿瘤基因MAGE家族成员之一MAGE-D1的cDNA序列不完全,从而拟用RACE技术获得MAGE-D1的全长cDNA序列.结果显示,MAGE-D1的cDNA全长为2 800个碱基,编码778个氨基酸.同时对RACE技术应用时的一些关键问题进行了讨论.

  3. Storage Gage Precipitation Observations

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A storage gage is a precipitation gage that requires reading and maintenance only monthly or seasonal intervals. This library includes reports from such gages,...

  4. Human MageB2 Protein Expression Enhances E2F Transcriptional Activity, Cell Proliferation, and Resistance to Ribotoxic Stress*

    Science.gov (United States)

    Peche, Leticia Y.; Ladelfa, María F.; Toledo, María F.; Mano, Miguel; Laiseca, Julieta E.; Schneider, Claudio; Monte, Martín

    2015-01-01

    MageB2 belongs to the melanoma antigen gene (MAGE-I) family of tumor-specific antigens. Expression of this gene has been detected in human tumors of different origins. However, little is known about the protein function and how its expression affects tumor cell phenotypes. In this work, we found that human MageB2 protein promotes tumor cell proliferation in a p53-independent fashion, as observed both in cultured cells and growing tumors in mice. Gene expression analysis showed that MageB2 enhances the activity of E2F transcription factors. Mechanistically, the activation of E2Fs is related to the ability of MageB2 to interact with the E2F inhibitor HDAC1. Cellular distribution of MageB2 protein includes the nucleoli. Nevertheless, ribotoxic drugs rapidly promote its nucleolar exit. We show that MageB2 counteracts E2F inhibition by ribosomal proteins independently of Mdm2 expression. Importantly, MageB2 plays a critical role in impairing cell cycle arrest in response to Actinomycin D. The data presented here support a relevant function for human MageB2 in cancer cells both under cycling and stressed conditions, presenting a distinct functional feature with respect to other characterized MAGE-I proteins. PMID:26468294

  5. Expression of MAGE-A and NY-ESO-1 in Primary and Metastatic Cancers.

    Science.gov (United States)

    Park, Tristen S; Groh, Eric M; Patel, Krishna; Kerkar, Sid P; Lee, Chyi-Chia Richard; Rosenberg, Steven A

    2016-01-01

    Melanoma-associated antigen-A (MAGE-A) and New York esophageal squamous cell cancer-1 (NY-ESO-1) are 2 cancer testis antigens (CTA) demonstrating potential for use in targeted immunotherapy. Clinical trials in melanoma and synovial sarcomas targeting these antigens in immune-based therapies have demonstrated durable tumor regression. Although protein expression of NY-ESO-1 has been assessed in a variety of cancer types, the expression of MAGE-A has not been studied in depth. In this study we analyzed MAGE-A and NY-ESO-1 expression in 314 melanoma specimens from 301 melanoma patients, 38 patients with squamous cell cancers and 111 patients with adenocarcinomas. Our results demonstrated higher expression of MAGE-A compared with NY-ESO-1 in melanomas (32% vs. 13%) and squamous cell carcinomas (45% vs. 7.9%), and higher expression of both CTAs in metastatic versus primary tumors. CTA expression in adenocarcinomas was low (MAGE-A: 10%, NY-ESO-1: 0.9%). In addition, we looked at concordance of expression among metastatic melanoma lesions within the same patient and found concordant expression in 38 of 47 patients for MAGE-A and 43 of 47 patients for NY-ESO-1. Our study demonstrated that the MAGE-A family may be of greater utility than NY-ESO-1 for targeted immunotherapy in a variety of cancer histologies, in particular metastatic melanomas and squamous cell carcinomas.

  6. CRMAGE: CRISPR Optimized MAGE Recombineering

    DEFF Research Database (Denmark)

    Ronda, Carlotta; Pedersen, Lasse Ebdrup; Sommer, Morten Otto Alexander

    2016-01-01

    A bottleneck in metabolic engineering and systems biology approaches is the lack of efficient genome engineering technologies. Here, we combine CRISPR/Cas9 and λ Red recombineering based MAGE technology (CRMAGE) to create a highly efficient and fast method for genome engineering of Escherichia coli...... that are assembled by a USER-cloning approach enabling quick and cost efficient gRNA replacement. CRMAGE furthermore utilizes CRISPR/Cas9 for efficient plasmid curing, thereby enabling multiple engineering rounds per day. To facilitate the design process, a web-based tool was developed to predict both the λ Red...

  7. Frequent MAGE mutations in human melanoma.

    Directory of Open Access Journals (Sweden)

    Otavia L Caballero

    Full Text Available BACKGROUND: Cancer/testis (CT genes are expressed only in the germ line and certain tumors and are most frequently located on the X-chromosome (the CT-X genes. Amongst the best studied CT-X genes are those encoding several MAGE protein families. The function of MAGE proteins is not well understood, but several have been shown to potentially influence the tumorigenic phenotype. METHODOLOGY/PRINCIPAL FINDINGS: We undertook a mutational analysis of coding regions of four CT-X MAGE genes, MAGEA1, MAGEA4, MAGEC1, MAGEC2 and the ubiquitously expressed MAGEE1 in human melanoma samples. We first examined cell lines established from tumors and matching blood samples from 27 melanoma patients. We found that melanoma cell lines from 37% of patients contained at least one mutated MAGE gene. The frequency of mutations in the coding regions of individual MAGE genes varied from 3.7% for MAGEA1 and MAGEA4 to 14.8% for MAGEC2. We also examined 111 fresh melanoma samples collected from 86 patients. In this case, samples from 32% of the patients exhibited mutations in one or more MAGE genes with the frequency of mutations in individual MAGE genes ranging from 6% in MAGEA1 to 16% in MAGEC1. SIGNIFICANCE: These results demonstrate for the first time that the MAGE gene family is frequently mutated in melanoma.

  8. Expression of MAGE-A1 and MAGE-A3 genes in human salivary gland carcinomas

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective To determine at the mRNA level whether the MAGE-A1 and -A3 genes are expressedin cancer cell lines from salivary glands and relevant clinical carcinomas, andthus to distinguish cancerous tissues from normal tissues and benign tumors in salivary glands.MethodsThe expression of the MEGE-A1 and MEGE-A3 genes at the mRNA level was determined by reverse transcription and polymerase chain reaction (RT-PCR) in 2 cell lines of human adenoid cyst carcinomas (ACC-2 and ACC-M), in 18 malignant tumors and 9 benign salivary gland tumors, and in 10 samples of normal salivary glandtissues.ResultsBoth MAGE-A1 and -A3 genes were expressed in ACC-2 and ACC-M cell lines. None of the 9 benign tumors or the 10 normal tissue samples of salivary glands expressed the genes. The MAGE-A1 and -A3 genes were expressed in 9 (50%) and 11 (61%) of 18 salivary gland carcinomas, respectively, and at least 1 of the 2 genes was expressed in 14 (78 %) of them. Of the 18 salivary gland carcinomas, 6 low-differentiated carcinomas (33%) expressed both genes, whereas 4 high-differentiated carcinomas (22%) expressed neither gene. ConclusionsThe MAGE-A1 and -A3 genes can be expressed in cancer cell lines of salivary glands and relevant clinical carcinomas in addition to other malignant tumors of various histological origins. The results suggest the possibility of immunotherapy against salivary gland carcinomas by using MAGE-gene-encoded products as target antigens for tumor-rejection.

  9. MAGED1 is a negative regulator of bone remodeling in mice.

    Science.gov (United States)

    Liu, Mei; Xu, Lijuan; Ma, Xiao; Xu, Jiake; Wang, Jing; Xian, Mengmeng; Zhou, Xiaotian; Wang, Min; Wang, Fang; Qin, An; Pan, Qiuhui; Wen, Chuanjun

    2015-10-01

    Melanoma antigen family D1 (MAGED1), an important adaptor protein, has been shown to ubiquitously express and play critical roles in many aspects of cellular events and physiological functions. However, its role in bone remodeling remains unknown. We, therefore, analyzed the bone phenotype of Maged1-deficient mice. Maged1-deficient mice displayed a significant osteoporotic phenotype with a marked decrease in bone density and deterioration of trabecular architecture. Histomorphometric analysis demonstrated an increased mineral apposition rate as well as increased osteoclast number and surface in Maged1 knockout mice. At the cellular level, Maged1-deficient osteoblasts exhibited an increased proliferation rate and accelerated differentiation. MAGED1 deficiency also caused a promotion in osteoclastogenesis, and that was attributed to the cell autonomous acceleration of differentiation in osteoclasts and an increased receptor activator of NF-κB ligand/osteoprotegerin ratio, a major index of osteoclastogenesis, in osteoblasts. Thus, we identified MAGED1 as a novel regulator of osteoblastogenesis, osteoclastogenesis, and bone remodeling in a mouse model.

  10. Pilot Study on MAGE-C2 as a Potential Biomarker for Triple-Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Qian Zhao

    2016-01-01

    Full Text Available Objective. In the current study, we measured the expression status of melanoma antigen gene c2 (MAGE-C2 in triple-negative breast cancer (TNBC and analyzed its prognostic with the clinical pathological features of patients with TNBC. Methods. The expressions statuses of MAGE-C2 were detected in TNBC tissues and paracarcinoma tissues by immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR, and western blotting. Then, we investigated the relationship of MAGE-C2 expression status and clinicopathological parameters of TNBC patients by the chi-squared test. Finally, we discussed the relations of MAGE-C2 expression state and prognosis of patients with TNBC by Kaplan-Meier method and Cox proportional hazards model. Results. High MAGE-C2 expression was found in 38.18% (42/110 of TNBC tissues. In adjacent tissues it was 9.09% (10/110. High MAGE-C2 expression in TNBC patients was closely associated with lymph node status, tumor node metastasis (TNM stage, and lymphovascular invasion (P<0.001. TNBC patients with high MAGE-C2 expression had significantly shorter survival time than low expression patients. We also found that age, lymph node status, TNM stage, lymphovascular invasion, and MAGE-C2 expression status were closely associated with overall survival of TNBC patients (P<0.05. Conclusion. High MAGE-C2 expression may serve as an independent prognostic factor for TNBC patients.

  11. MAGE-A is More Highly Expressed Than NY-ESO-1 in a Systematic Immunohistochemical Analysis of 3668 Cases.

    Science.gov (United States)

    Kerkar, Sid P; Wang, Zeng-Feng; Lasota, Jerzy; Park, Tristen; Patel, Krishna; Groh, Eric; Rosenberg, Steven A; Miettinen, Markku M

    2016-05-01

    Two cancer testis antigens, the New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and the melanoma-antigen family A (MAGE-A), represent promising immunotherapy targets due to the low expression of these antigens in nonmalignant tissue. To assess overexpression patterns in various cancers, we performed a systematic immunohistochemical analysis for NY-ESO-1 and MAGE-A on tissue array samples of 3668 common epithelial carcinomas (CA) and germ cell tumors of high prevalence and mortality. Here, we find significantly higher expression of MAGE-A (>50% on tumor cells) compared with NY-ESO-1 in several CAs including cutaneous squamous cell carcinomas (SCC) (52.8%/2.8%), esophageal SCC (50%/0%), head and neck SCC (41.1%/ESO-1, was seen in whole slide evaluations of an independent cohort of metastatic SCC (45.5%/3.6%) and metastatic CA (13.5%/0%) of various primaries with significantly higher expression of MAGE-A in metastatic SCC compared with other metastatic CA. MAGE-A is also more highly expressed in germ cell tumors, seminomas (69%/3.5%) and nonseminomas (40.1%/4.7%). In summary, MAGE-A is more highly expressed than NY-ESO-1 in a majority of human malignancies, and targeting MAGE-A may benefit a large number of patients.

  12. Development of a Quantitative Real-Time RT-PCR Assay for the Detection of MAGE-A3-Positive Tumors.

    Science.gov (United States)

    Gruselle, Olivier; Coche, Thierry; Louahed, Jamila

    2015-07-01

    Melanoma antigen A3 (MAGE-A3) is a member of the MAGE family of tumor antigens and a relevant candidate for use in cancer immunotherapy. However, not all tumors express MAGE-A3, and closely related members of the MAGE family can be co-expressed with MAGE-A3 in the same tumor. Therefore, in the frame of MAGE-A3 clinical trials, it appeared necessary to evaluate tumors for MAGE-A3 expression with a highly specific quantitative assay to select patients who are eligible for anti-MAGE-A3 immunotherapy treatment. Herein, we describe the development and validation of a quantitative real-time RT-PCR (RT-qPCR) assay for the determination of MAGEA3 gene expression in tumor tissues. In the early phases of development, the designed primers and probe were not able to distinguish between MAGE-A3 and MAGE-A6. To ensure the specificity for MAGE-A3 over MAGE-A6, our strategy was to use a 5'-nuclease probe (or hydrolysis probe). The final assay was shown to be specific and linear within the analytical range, with an acceptable CV for repeatability and intermediate precision. When compared with a reference semiquantitative RT-PCR assay, the two methods were in good agreement, with only 4.23% of the samples giving discordant results. In conclusion, we have developed a MAGE-A3-specific RT-qPCR assay, compatible with a high-throughput setting for the estimation of MAGEA3 gene expression in present and future clinical trials.

  13. MAGE-C2/CT10 protein expression is an independent predictor of recurrence in prostate cancer.

    Directory of Open Access Journals (Sweden)

    Lotta von Boehmer

    Full Text Available The cancer-testis (CT family of antigens is expressed in a variety of malignant neoplasms. In most cases, no CT antigen is found in normal tissues, except in testis, making them ideal targets for cancer immunotherapy. A comprehensive analysis of CT antigen expression has not yet been reported in prostate cancer. MAGE-C2/CT-10 is a novel CT antigen. The objective of this study was to analyze extent and prognostic significance of MAGE-C2/CT10 protein expression in prostate cancer. 348 prostate carcinomas from consecutive radical prostatectomies, 29 castration-refractory prostate cancer, 46 metastases, and 45 benign hyperplasias were immunohistochemically analyzed for MAGE-C2/CT10 expression using tissue microarrays. Nuclear MAGE-C2/CT10 expression was identified in only 3.3% primary prostate carcinomas. MAGE-C2/CT10 protein expression was significantly more frequent in metastatic (16.3% positivity and castration-resistant prostate cancer (17% positivity; p<0.001. Nuclear MAGE-C2/CT10 expression was identified as predictor of biochemical recurrence after radical prostatectomy (p = 0.015, which was independent of preoperative PSA, Gleason score, tumor stage, and surgical margin status in multivariate analysis (p<0.05. MAGE-C2/CT10 expression in prostate cancer correlates with the degree of malignancy and indicates a higher risk for biochemical recurrence after radical prostatectomy. Further, the results suggest MAGE-C2/CT10 as a potential target for adjuvant and palliative immunotherapy in patients with prostate cancer.

  14. Expression of MAGE-A3/6 in primary breast cancer is associated with hormone receptor negative status, high histologic grade, and poor survival.

    Science.gov (United States)

    Ayyoub, Maha; Scarlata, Clara-Maria; Hamaï, Ahmed; Pignon, Pascale; Valmori, Danila

    2014-01-01

    The cancer testis antigen (CTA), melanoma-associated antigen A3/6 (MAGE-A3/6), is expressed in human cancers of different histologic types, to variable extents, and is an important target for immunotherapy. In this study, to address the potential of MAGE-A3/6 as an immunotherapeutic target in breast cancer (BC), we assessed MAGE-A3/6 expression by PCR in a cohort of 362 primary BC tumors and analyzed the correlation between MAGE-A3/6 expression, tumors hormone receptor (HR) status, and other clinicopathologic features. We found expression of MAGE-A3/6 in 10% of primary BC tumors. MAGE-A3/6 expression was significantly correlated with estrogen receptor (ER) and progesterone receptor (PR) negative status and was frequent in ER (29%) and in PR (24%) tumors. MAGE-A3/6 expression was also significantly associated with high histologic grade but not with patients age, tumor size, tumor type, lymph-node invasion, and human epidermal growth factor receptor 2 (HER2) overexpression. Consistent with the associated poor clinicopathologic features, patients with MAGE-A3/6-expressing tumors had a worse disease-specific survival as compared with patients with MAGE-A3/6 tumors. The frequent expression of MAGE-A3/6 in tumors of patients with primary HR BC, who have, for a large part, limited therapeutic options, encourages the selection of BC patients bearing MAGE-A3/6-expressing tumors for targeted immunotherapy.

  15. [Preparation and application of melanoma-associated antigen D4 polyclonal antibody].

    Science.gov (United States)

    He, Shujia; Gu, Yongyao; Xiao, Shaowen; Zhang, Qingmei; Chen, Fang; Luo, Bin; Fu, Jun; Xie, Xiaoxun

    2017-01-01

    Objective To prepare the rabbit polyclonal antibody recognizing human melanoma-associated antigen D4 (MAGE-D4), and identify its immune characteristics for preliminary application. Methods MBP/MAGE-D4 fusion protein was expressed from pMAL-C2/MAGE-D4 recombinant plasmid constructed in the previous work. Then the purified MBP/MAGE-D4 protein was used to immunize the New Zealand white rabbits for generating polyclonal antibody. Subsequently, the anti-MAGE-D4 antibody was purified with protein A affinity chromatograph and identified by SDS-PAGE. The titer and specificity of the antibody were further detected by indirect ELISA and Western blotting, respectively. MAGE-D4 expression and localization of lung cancer tissues were analyzed by immunohistochemical staining. Results MAGE-D4 polyclonal antibody with high purity was obtained. Its titer was about 1:256 000. Western blot analysis demonstrated that the antibody could specifically react to the recombinant MAGE-D4 protein. Immunohistochemical staining showed that the antibody could recognize the endogenous MAGE-D4 protein in lung cancer tissues, and its positive rate was 69.6% (17/23). Conclusion The MAGE-D4 polyclonal antibody with high specificity and sensitivity has been successfully prepared.

  16. GAGES-II: Geospatial Attributes of Gages for Evaluating Streamflow

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This dataset, termed "GAGES II", an acronym for Geospatial Attributes of Gages for Evaluating Streamflow, version II, provides geospatial data and classifications...

  17. Epigenetic modulation of cancer-germline antigen gene expression in tumorigenic human mesenchymal stem cells: implications for cancer therapy

    DEFF Research Database (Denmark)

    Gjerstorff, Morten; Burns, Jorge S; Nielsen, Ole;

    2009-01-01

    Cancer-germline antigens are promising targets for cancer immunotherapy, but whether such therapies will also eliminate the primary tumor stem cell population remains undetermined. We previously showed that long-term cultures of telomerized adult human bone marrow mesenchymal stem cells can...... spontaneously evolve into tumor-initiating, mesenchymal stem cells (hMSC-TERT20), which have characteristics of clinical sarcoma cells. In this study, we used the hMSC-TERT20 tumor stem cell model to investigate the potential of cancer-germline antigens to serve as tumor stem cell targets. We found...... that tumorigenic transformation of hMSC-TERT20 cells induced the expression of members of several cancer-germline antigen gene families (ie, GAGE, MAGE-A, and XAGE-1), with promoter hypomethylation and histone acetylation of the corresponding genes. Both in vitro cultures and tumor xenografts derived from...

  18. Low-dose decitabine induces MAGE-A expression and inhibits invasion via suppression of NF-κB2 and MMP2 in Eca109 cells.

    Science.gov (United States)

    Liu, Wei-hua; Sang, Mei-xiang; Hou, Shu-yun; Zhang, Chao; Shan, Bao-en

    2014-07-01

    Decitabine, a demethylating drug, is the first-line treatment for myelodysplastic syndromes and gains better overall survival, which is based on epigenetic mechanism. Activated by promoter demethylation, melanoma-associated antigens-A (MAGE-A), cancer-testis antigens are attractive targets for immunotherapy. Our purpose was to investigate whether decitabine could show anti-tumor effects for esophageal cancer and explore its mechanism. In addition, we aimed to examine its modulation for most MAGE-A members. The results showed the baseline expression were MAGE-A2, -3,-9, and -10 in Eca109 cells and decitabine (0.5 μM) could induce MAGE-A8 and -A4 whereas reduce MAGE-A9 and -A10. Moreover, decitabine (0.5 μM) inhibited cell proliferation, migration and invasive ability by 15%, 34% and 47.2%, respectively and decreased expressions of NF-κB2 and MMP2. Our results demonstrated that low-dose decitabine induced the expression of MAGE-A8 and -A4, and inhibited cell invasion through decreasing expression of MMP2 and NF-κB2, which provides possibilities for combing decitabine with immunotherapy targeting MAGE-A to treat advanced esophageal squamous cell carcinoma.

  19. Clinical Benefit of Allogeneic Melanoma Cell Lysate-Pulsed Autologous Dendritic Cell Vaccine in MAGE-Positive Colorectal Cancer Patients

    DEFF Research Database (Denmark)

    Toh, Han Chong; Wang, Who-Whong; Chia, Whay Kuang

    2009-01-01

    PURPOSE: We evaluated the clinical benefit of an allogeneic melanoma cell lysate (MCL)-pulsed autologous dendritic cell (DC) vaccine in advanced colorectal cancer patients expressing at least one of six MAGE-A antigens overexpressed by the cell line source of the lysate. EXPERIMENTAL DESIGN: DCs ...

  20. The effect of MAGE-A1 gene on NIH3T3 cells

    Institute of Scientific and Technical Information of China (English)

    Jingjun Sun; Jin Zhu; Zhenning Qiu; Yuhua Li; Guipeng Ding; Yi Zhu; Zhenqing Feng; Xiaohong Guan

    2005-01-01

    Objective: Melanoma antigen genes(MAGE) genes have been found in many kinds of tumor tissue, but not in normal tissue except testis and placentas. The Ags encoded by MAGE genes therefore are strictly tumor-specific. The most current researches associated with these genes focus on the tumor vaccination using these Ags. Few reports are concerning these genes' functions. In this study, we investigated the role of MAGE-A1 gene on NIH3T3 cells after transferring with it. Methods: Clone the MAGE-A1 into the plasmids pEGFP-C3 and pcDNA3.1, then transfer the reconstructed plasmids and primary plasmids into the NIH3T3 cells using a new transfer reagent FuGENE 6. Selecting the positively transferred cells by G418. Identified by RT-PCR, Western blot, Immunocytochemistry,Laser Scanning Confocal Microscope and Fluoroscope. The cells mobile ability was measured with Millicell-PCF. The cell cycle and apoptosis were measured with Flow Cytometry. Results: The apoptosis rate of NIH3T3 cells that transferred with control plasmid pcDNA3.1was 13.4% and the raitos that stay in S phase and G2-M phase were 5.68% and 1.04% respectively. The apoptosis rate of NIH3T3 cells that transferred with pcDNA3.1-A1 was 0.90% and the ratios that stayed in S phase and G2-M phase were 19.31% and 13.47% respectively. The apoptosis rate of the cells that transferred with control plasmid pEGFP-C3 was 1.87 %, a little higher than 1.47 % of those transferred with pEGFP-C3-A1. Conclusion: The MAGE-A1 gene may enhance the cell cycle, inhibit the apoptosis and raise the mobile ability of NIH3T3 cells.

  1. High expression of MAGE-A9 in tumor and stromal cells of non-small cell lung cancer was correlated with patient poor survival.

    Science.gov (United States)

    Zhang, Siya; Zhai, Xiaolu; Wang, Gui; Feng, Jian; Zhu, Huijun; Xu, Liqin; Mao, Guoxin; Huang, Jianfei

    2015-01-01

    Melanoma associated antigen-A (MAGE-A) is an oncogene and correlated with tumor initiation and development. However the roles of MAGE-A9 in non-small cell lung cancer (NSCLC) are still unknown. We investigated MAGE-A9 mRNA expression in 18 tumor tissues of NSCLC by qRT-PCR and MAGE-A9 protein expression in 213 NSCLC samples of tissue arrays by immunohistochemical staining. We assessed the relationship between MAGE-A9 expression and clinical parameters. The results showed that the high expression of MAGE-A9 protein in NSCLC tumor cells were commonly present in squamous cell carcinomas (P = 0.030). It was also related to larger tumor diameter, lymph node metastasis and later stage grouping with TNM classification (all P cells was higher in squamous cell carcinomas as well. Cox regression univariate and multivariable analysis revealed that MAGE-A9 expression in tumor cells of NSCLC (P < 0.001) is an independent prognostic factor in five-year overall survival rate. We concluded that the molecular assessment of MAGEA9 could be considered to improve prognostic evaluation and to identify eligible patients for potential target therapy.

  2. MAGED1 is a novel regulator of a select subset of bHLH PAS transcription factors.

    Science.gov (United States)

    Sullivan, Adrienne E; Peet, Daniel J; Whitelaw, Murray L

    2016-09-01

    Transcription factors of the basic helix-loop-helix (bHLH) PER-ARNT-SIM (PAS) family generally have critical and nonredundant biological roles, but some bHLH PAS proteins compete for common cofactors or recognise similar DNA elements. Identifying factors that regulate function of bHLH PAS proteins, particularly in cells where multiple family members are coexpressed, is important for understanding bHLH PAS factor biology. This study identifies and characterises a novel interaction between melanoma-associated antigen D1 (MAGED1) and select members of the bHLH PAS transcription factor family. MAGED1 binds and positively regulates the transcriptional activity of family members SIM1, SIM2, NPAS4 and ARNT2, but does not interact with AhR, HIF1α and ARNT. This interaction is mediated by PAS repeat regions which also form the interface for bHLH PAS dimerisation, and accordingly MAGED1 is not found in complex with bHLH PAS dimers. We show that MAGED1 does not affect bHLH PAS protein levels and cannot be acting as a coactivator of transcriptionally active heterodimers, but rather appears to interact with nascent bHLH PAS proteins in the cytoplasm to enhance their function prior to nuclear import. As a selective regulator, MAGED1 may play an important role in the biology of these specific factors and in general bHLH PAS protein dynamics.

  3. Expression of MAGE-A3, NY-ESO-1, LAGE-1 and PRAME in urothelial carcinoma

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Zieger, K; Kissow Lildal, T;

    2012-01-01

    Background: The potential for cancer-testis (CT) antigens as targets for immunotherapy in cancer patients has been heavily investigated, and currently cancer vaccine trials based on the CT antigens, MAGE-A3 and NY-ESO-1, are being carried out. Methods: We used specific q-RT-PCR assays to analyse...... the expression of the CT genes MAGE-A3, NY-ESO-1 (CTAG1B), LAGE-1 (CTAG2) and PRAME in a panel of bladder tumours from 350 patients with long-term follow-up and detailed treatment information. Results: Overall, 43% of the tumours expressed MAGE-A3, 35% expressed NY-ESO-1, 27% expressed LAGE-1 and 20% expressed...... PRAME. In all, 56% of the tumours expressed at least one of the CT genes analysed. Univariate Cox regression analysis of CT gene expression in non-muscle-invasive tumours showed that expression of MAGE-A3 (P=0.026), LAGE-1 (P=0.001) and NY-ESO-1 (P=0.040) was significantly associated with a shorter...

  4. Promoter hypomethylation and reactivation of MAGE-A1 and MAGE-A3 genes in colorectal cancer cell lines and cancer tissues

    Institute of Scientific and Technical Information of China (English)

    Kyung-Hee Kim; Jin-Sung Choi; Il-Jin Kim; Ja-Lok Ku; Jae-Gahb Park

    2006-01-01

    AIM: To verify the expression and methylation status of the MAGE-A1 and MAGE-A3 genes in colorectal cancer tissues and cancer cell lines.METHODS: We evaluated promoter demethylation status of the MAGE-A1 and MAGE-A3 genes by RT-PCR analysis and methylation-specific PCR (MS-PCR), as well as sequencing analysis, after sodium bisulfite modification in 32 colorectal cancer cell lines and 87 cancer tissues.RESULTS: Of the 32 cell lines,MAGE-A1 and MAGE-A3 expressions were observed in 59% and 66%, respectively. Subsequent to sodium bisulfite modification and MSPCR analysis, the promoter hypomethylation of MAGE-A1 and MAGE-A3 was confirmed in both at 81% each.Promoter hypomethylation of MAGE-A1 and MAGE-A3 in colorectal cancer tissues was observed in 43% and 77%,respectively. Hypomethylation of MAGE-A1 and MAGE-A3 genes in corresponding normal tissues were observed in 2% and 6%, respectively.CONCLUSION: The promoter hypomethylation of MAGE genes up-regulates its expression in colorectal carcinomas as well as in gastric cancers and might play a significant role in the development and progression of human colorectal carcinomas.

  5. GAGES-II: Geospatial Attributes of Gages for Evaluating Streamflow

    Science.gov (United States)

    Falcone, James A.

    2011-01-01

    This dataset, termed "GAGES II", an acronym for Geospatial Attributes of Gages for Evaluating Streamflow, version II, provides geospatial data and classifications for 9,322 stream gages maintained by the U.S. Geological Survey (USGS). It is an update to the original GAGES, which was published as a Data Paper on the journal Ecology's website (Falcone and others, 2010b) in 2010. The GAGES II dataset consists of gages which have had either 20+ complete years (not necessarily continuous) of discharge record since 1950, or are currently active, as of water year 2009, and whose watersheds lie within the United States, including Alaska, Hawaii, and Puerto Rico. Reference gages were identified based on indicators that they were the least-disturbed watersheds within the framework of broad regions, based on 12 major ecoregions across the United States. Of the 9,322 total sites, 2,057 are classified as reference, and 7,265 as non-reference. Of the 2,057 reference sites, 1,633 have (through 2009) 20+ years of record since 1950. Some sites have very long flow records: a number of gages have been in continuous service since 1900 (at least), and have 110 years of complete record (1900-2009) to date. The geospatial data include several hundred watershed characteristics compiled from national data sources, including environmental features (e.g. climate – including historical precipitation, geology, soils, topography) and anthropogenic influences (e.g. land use, road density, presence of dams, canals, or power plants). The dataset also includes comments from local USGS Water Science Centers, based on Annual Data Reports, pertinent to hydrologic modifications and influences. The data posted also include watershed boundaries in GIS format. This overall dataset is different in nature to the USGS Hydro-Climatic Data Network (HCDN; Slack and Landwehr 1992), whose data evaluation ended with water year 1988. The HCDN identifies stream gages which at some point in their history had

  6. Expression of MAGE-A3, NY-ESO-1, LAGE-1 and PRAME in urothelial carcinoma

    Science.gov (United States)

    Dyrskjøt, L; Zieger, K; Kissow Lildal, T; Reinert, T; Gruselle, O; Coche, T; Borre, M; Ørntoft, T F

    2012-01-01

    Background: The potential for cancer-testis (CT) antigens as targets for immunotherapy in cancer patients has been heavily investigated, and currently cancer vaccine trials based on the CT antigens, MAGE-A3 and NY-ESO-1, are being carried out. Methods: We used specific q-RT-PCR assays to analyse the expression of the CT genes MAGE-A3, NY-ESO-1 (CTAG1B), LAGE-1 (CTAG2) and PRAME in a panel of bladder tumours from 350 patients with long-term follow-up and detailed treatment information. Results: Overall, 43% of the tumours expressed MAGE-A3, 35% expressed NY-ESO-1, 27% expressed LAGE-1 and 20% expressed PRAME. In all, 56% of the tumours expressed at least one of the CT genes analysed. Univariate Cox regression analysis of CT gene expression in non-muscle-invasive tumours showed that expression of MAGE-A3 (P=0.026), LAGE-1 (P=0.001) and NY-ESO-1 (P=0.040) was significantly associated with a shorter progression-free survival. In addition, we found that patients with tumours expressing PRAME responded poorly to chemotherapy (P=0.02, χ2-test). Conclusion: Cancer-testis genes are frequently expressed in bladder cancer and especially in tumours of high stage and grade. In addition, the CT gene expression may have both prognostic and predictive value. Development of specific immunotherapy against the CT antigens in bladder cancer may ultimately increase patient survival. PMID:22596240

  7. L-Rhamnose Enhances the Immunogenicity of Melanoma-Associated Antigen A3 for Stimulating Antitumor Immune Responses.

    Science.gov (United States)

    Zhang, Huajie; Wang, Bin; Ma, Zhongrui; Wei, Mohui; Liu, Jun; Li, Dong; Zhang, Houcheng; Wang, Peng George; Chen, Min

    2016-04-20

    Vaccines based on melanoma-associated antigens (MAGEs) present a promising strategy for tumor immunotherapy, albeit with weak immunogenicity. In this study, the xenoantigen L-rhamnose (Rha) was chemically conjugated with truncated MAGE-A3 (tMAGE-A3) to generate Rha-tMAGE-A3. The product showed good antigenicity with anti-Rha antibodies purified from human serum. FITC-labeled Rha-tMAGE-A3 was detected in THP-1 human macrophage cells via the anti-Rha antibody-dependent antigen uptake process. Furthermore, peripheral blood mononuclear cells (PBMCs) stimulated with Rha-tMAGE-A3 in the presence of anti-Rha antibodies showed better cytotoxicity toward A375 human melanoma cells surfaced by MAGE-A3 antigen compared to PBMCs stimulated with tMAGE-A3. All data reveal that linking of Rha epitopes to MAGE enhances the immunogenicity of MAGE by harnessing the immune effector functions of human naturally existing anti-Rha antibodies. Rha epitopes could become immunogenicity enhancers of tumor associated antigens in the development of tumor immunotherapies.

  8. Cancer testis antigen and immunotherapy

    Directory of Open Access Journals (Sweden)

    Krishnadas DK

    2013-04-01

    Full Text Available Deepa Kolaseri Krishnadas, Fanqi Bai, Kenneth G Lucas Department of Pediatrics, Division of Hematology/Oncology, University of Louisville, KY, USA Abstract: The identification of cancer testis (CT antigens has been an important advance in determining potential targets for cancer immunotherapy. Multiple previous studies have shown that CT antigen vaccines, using both peptides and dendritic cell vaccines, can elicit clinical and immunologic responses in several different tumors. This review details the expression of melanoma antigen family A, 1 (MAGE-A1, melanoma antigen family A, 3 (MAGE-A3, and New York esophageal squamous cell carcinoma-1 (NY-ESO-1 in various malignancies, and presents our current understanding of CT antigen based immunotherapy. Keywords: cancer testis antigens, immunotherapy, vaccine

  9. Clinical significance of MAGE-A3 and AKAP-4 in non-small cell lung carcinoma%探索MAGE-A3和AKAP-4在非小细胞肺癌中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    韩秀晶; 林云恩; 向波; 范婷婷; 赵晶晶; 廖伟娇

    2012-01-01

    目的 检测癌睾丸抗原(CTA) MAGE-A3 、AKAP-4在非小细胞肺癌(NSCLC)的表达及意义.方法 应用间接酶免疫组化技术检测MAGE-A3、AKAP-4在45例肺癌组织中的表达情况,分析其与组织类型及淋巴结转移的相关性.结果 45例标本中MAGE-A3、AKAP-4在NSCLC中的敏感度分别为62.2%和73.3%,联合两种抗原可显著提高敏感性,为91.1% (P< 0.05);MAGE-A3 、AKAP-4在鳞癌中的表达率显著高于腺癌,与性别、年龄、淋巴结有无转移不相关.结论 MAGE-A3、AKAP-4是较好的NSCLC辅助诊断指标,联合应用两种蛋白可提高诊断敏感性.%Objective To determine the expression of MAGE-A3 and AKAP-4 in patients with non-small cell lung carcinoma (NSCLC) and to evaluate the possibility of exploiting them as biomarkers for diagnosis. Methods Indirect enzyme immunohistochemical method was performed on paraffin-embedded tissues from 45 patients with NSCLC, and the correlations between antigens expression and histological types as well as lymph node metastasis were evaluated. Results In 45 tumor samples, the sensitive of MAGE-A3 and AKAP-4 detection was 62.2% and 73.3%, respectively. Combined detection of both MAGE-A3 and AKAP-4 can significantly increase the sensitivity to 91.1% (P<0.05). There was no significance difference in the expression of MAGE-A3 and AKAP-4 between lung adenocarcinoma and squamous cell lung carcinoma. The expression of MAGE-A3 and AKAP-4 was not related to lymph node metastasis. Conclusion Both MAGE-A3 and AKAP-4 can be used to further increase the sensitivity of NSCLC diagnosis.

  10. The antitumor immune responses induced by nanoemulsion-encapsulated MAGE1-HSP70/SEA complex protein vaccine following different administration routes.

    Science.gov (United States)

    Ge, Wei; Hu, Pei-Zhen; Huang, Yang; Wang, Xiao-Ming; Zhang, Xiu-Min; Sun, Yu-Jing; Li, Zeng-Shan; Si, Shao-Yan; Sui, Yan-Fang

    2009-10-01

    Our previous study showed that nanoemulsion-encapsulated MAGE1-HSP70/SEA (MHS) complex protein vaccine elicited MAGE-1 specific immune response and antitumor effects against MAGE-1-expressing tumor and nanoemulsion is a useful vehicle with possible important implications for cancer biotherapy. The purpose of this study was to compare the immune responses induced by nanoemulsion-encapsulated MAGE1-HSP70 and SEA as NE(MHS) vaccine following different administration routes and to find out the new and effective immune routes. Nanoemulsion vaccine was prepared using magnetic ultrasound methods. C57BL/6 mice were immunized with NE(MHS) via po., i.v., s.c. or i.p., besides mice s.c. injected with PBS or NE(-) as control. The cellular immunocompetence was detected by ELISpot assay and LDH release assay. The therapeutic and tumor challenge assay were also examined. The results showed that the immune responses against MAGE-1 expressing murine tumors elicited by NE(MHS) via 4 different routes were approximately similar and were all stronger than that elicited by PBS or NE(-), suggesting that this novel nanoemulsion carrier can exert potent antitumor immunity against antigens encapsulated in it. Especially, the present results indicated that nanoemulsion vaccine adapted to administration via different routes including peroral, and may have broader applications in the future.

  11. Genetic variants of immunoglobulin γ and κ chains influence humoral immunity to the cancer-testis antigen XAGE-1b (GAGED2a) in patients with non-small cell lung cancer.

    Science.gov (United States)

    Pandey, J P; Namboodiri, A M; Ohue, Y; Oka, M; Nakayama, E

    2014-04-01

    GM (γ marker) allotypes, genetic variants of immunoglobulin γ chains, have been reported to be associated strongly with susceptibility to lung cancer, but the mechanism(s) underlying this association is not known. One mechanism could involve their contribution to humoral immunity to lung tumour-associated antigens. In this study, we aimed to determine whether particular GM and KM (κ marker) allotypes were associated with antibody responsiveness to XAGE-1b, a highly immunogenic lung tumour-associated cancer-testis antigen. Sera from 89 patients with non-small cell lung cancer (NSCLC) were allotyped for eight GM and two KM determinants and characterized for antibodies to a synthetic XAGE-1b protein. The distribution of various GM phenotypes was significantly different between XAGE-1b antibody-positive and -negative patients (P = 0·023), as well as in the subgroup of XAGE-1b antigen-positive advanced NSCLC (P = 0·007). None of the patients with the GM 1,17 21 phenotype was positive for the XAGE-1b antibody. In patients with antigen-positive advanced disease, the prevalence of GM 1,2,17 21 was significantly higher in the antibody-positive group than in those who lacked the XAGE-1b antibody (P = 0·026). This phenotype also interacted with a particular KM phenotype: subjects with GM 1,2,17 21 and KM 3,3 phenotypes were almost four times (odds ratio = 3·8) as likely to be positive for the XAGE-1b antibody as the subjects who lacked these phenotypes. This is the first report presenting evidence for the involvement of immunoglobulin allotypes in immunity to a cancer-testis antigen, which has important implications for XAGE-1b-based immunotherapeutic interventions in lung adenocarcinoma.

  12. Streamflow Gaging Stations of the United States - Direct Download

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This map layer shows selected streamflow gaging stations of the United States, Puerto Rico, and the U.S. Virgin Islands, in 2013. Gaging stations, or gages, measure...

  13. Immune function of mage-3 gene vaccine in human melanoma based on human/mouse chimera model%基于人/鼠嵌合模型的人黑色素瘤mage-3基因疫苗的免疫学作用

    Institute of Scientific and Technical Information of China (English)

    姜曼; 吴玉章; 倪兵

    2004-01-01

    AIM:To evaluate the immune effect of mage-3 gene vaccine in human melanoma by human/mouse chimera model.METHODS:Trimera animal model was established and evaluated.It was immunized by recombinant plasmid mage-3/pCI neo as vaccine.Killing activity of splenocyte cytotoxic T Lymphocyte(CTL) and mage-3 antibody specific in blood serum of the immune animal was detected.RESULTS:Quantity of human lymphocyte was discovered in the spleen and abdominal cavity of the established Trimera model.After vaccination,mage-3 antibody specific with the potency of 1: 256 was presented in Trimera model.CTL killing experiments in vitro of the immune animal reveal that the maximum killing rate to target cell LB373 of Spleen lymphocyte of the Trimera mice was about 50% after vaccination comparing with that of below 10% in control mice group. CONCLUSION:Mage-3 is an ideal tumour vaccine.It can stimulate specific cell and body fluid immunisation in humanized animal model.Therefore,it provides an experimental gist for clinical therapies in all kinds of tumour cells,which share same mage-3 antigen.%目的 :利用人 /鼠嵌合模型评价人黑色素瘤基因 mage-3基因疫苗的免疫效果. 方法 :建立并鉴定 Trimera动物模型,并用重组质粒 mage-3/pCI neo作为基因疫苗对其进行免疫.检测免疫动物脾细胞 CTL的杀伤活性和血清中 mage-3特异性抗体. 结果 :构建的 Trimera模型脾脏和腹腔中出现了大量的人淋巴细胞.接种后, Trimera模型体内出现了效价为 1: 256的 mage-3特异抗体.免疫动物 CTL体外杀伤实验显示,注射基因疫苗的 Trimera小鼠脾脏淋巴细胞对靶细胞 LB373的最大杀伤率为 50%左右,而对照小鼠只有 10%以下的杀伤水平. 结论 :mage-3是一种理想的肿瘤疫苗,在人源化动物模型中能激发出特异的细胞和体液免疫,对共享 mage-3抗原的各种肿瘤细胞的临床治疗提供了实验依据.

  14. 46 CFR 197.458 - Gages and timekeeping devices.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Gages and timekeeping devices. 197.458 Section 197.458... § 197.458 Gages and timekeeping devices. The diving supervisor shall insure that— (a) Each depth gage and timekeeping device is tested or calibrated against a master reference gage or time-keeping...

  15. T-cell receptor gene therapy targeting melanoma-associated antigen-A4 inhibits human tumor growth in non-obese diabetic/SCID/γcnull mice.

    Science.gov (United States)

    Shirakura, Yoshitaka; Mizuno, Yukari; Wang, Linan; Imai, Naoko; Amaike, Chisaki; Sato, Eiichi; Ito, Mamoru; Nukaya, Ikuei; Mineno, Junichi; Takesako, Kazutoh; Ikeda, Hiroaki; Shiku, Hiroshi

    2012-01-01

    Adoptive cell therapy with lymphocytes that have been genetically engineered to express tumor-reactive T-cell receptors (TCR) is a promising approach for cancer immunotherapy. We have been exploring the development of TCR gene therapy targeting cancer/testis antigens, including melanoma-associated antigen (MAGE) family antigens, that are ideal targets for adoptive T-cell therapy. The efficacy of TCR gene therapy targeting MAGE family antigens, however, has not yet been evaluated in vivo. Here, we demonstrate the in vivo antitumor activity in immunodeficient non-obese diabetic/SCID/γc(null) (NOG) mice of human lymphocytes genetically engineered to express TCR specific for the MAGE-A4 antigen. Polyclonal T cells derived from human peripheral blood mononuclear cells were transduced with the αβ TCR genes specific for MAGE-A4, then adoptively transferred into NOG mice inoculated with MAGE-A4 expressing human tumor cell lines. The transferred T cells maintained their effector function in vivo, infiltrated into tumors, and inhibited tumor growth in an antigen-specific manner. The combination of adoptive cell therapy with antigen peptide vaccination enhanced antitumor activity, with improved multifunctionality of the transferred cells. These data suggest that TCR gene therapy with MAGE-A4-specific TCR is a promising strategy to treat patients with MAGE-A4-expressing tumors; in addition, the acquisition of multifunctionality in vivo is an important factor to predict the quality of the T-cell response during adoptive therapy with human lymphocytes.

  16. Dual active surface heat flux gage probe

    Science.gov (United States)

    Liebert, Curt H.; Kolodziej, Paul

    1995-02-01

    A unique plug-type heat flux gage probe was tested in the NASA Ames Research Center 2x9 turbulent flow duct facility. The probe was fabricated by welding a miniature dual active surface heat flux gage body to the end of a hollow metal cylindrical bolt containing a metal inner tube. Cooling air flows through the inner tube, impinges onto the back of the gage body and then flows out through the annulus formed between the inner tube and the hollow bolt wall. Heat flux was generated in the duct facility with a Huels arc heater. The duct had a rectangular cross section and one wall was fabricated from 2.54 centimeter thick thermal insulation rigid surface material mounted onto an aluminum plate. To measure heat flux, the probe was inserted through the plate and insulating materials with the from of the gage located flush with the hot gas-side insulation surface. Absorbed heat fluxes measured with the probe were compared with absorbed heat fluxes measured with six water-cooled reference calorimeters. These calorimeters were located in a water-cooled metal duct wall which was located across from the probe position. Correspondence of transient and steady heat fluxes measured with the reference calorimeters and heat flux gage probe was generally within a satisfactory plus or minus 10 percent. This good correspondence was achieved even though the much cooler probe caused a large surface temperature disruption of 1000K between the metal gage and the insulation. However, this temperature disruption did not seriously effect the accuracy of the heat flux measurement. A current application for dual active surface heat flux gages is for transient and steady absorbed heat flux, surface temperature and heat transfer coefficient measurements on the surface of an oxidizer turbine inlet deflector operating in a space shuttle test bed engine.

  17. GK-1 improves the immune response induced by bone marrow dendritic cells loaded with MAGE-AX in mice with melanoma.

    Science.gov (United States)

    Piñón-Zárate, Gabriela; Herrera-Enríquez, Miguel Ángel; Hernández-Téllez, Beatriz; Jarquín-Yáñez, Katia; Castell-Rodríguez, Andrés Eliú

    2014-01-01

    The aim of dendritic cell (DC) vaccination in cancer is to induce tumor-specific effector T cells that may reduce and control tumor mass. Immunostimulants that could drive a desired immune response are necessary to be found in order to generate a long lasting tumor immune response. GK-1 peptide, derived from Taenia crassiceps, induces not only increase in TNFα, IFNγ, and MCP-1 production in cocultures of DCs and T lymphocytes but also immunological protection against influenza virus. Moreover, the aim of this investigation is the use of GK-1 as a bone marrow DCs (BMDCs) immunostimulant targeted with MAGE antigen; thus, BMDC may be used as immunotherapy against murine melanoma. GK-1 induced in BMDCs a meaningful increment of CD86 and IL-12. In addition, the use of BMDCs TNFα/GK-1/MAGE-AX induced the highest survival and the smallest tumors in mice. Besides, the treatment helped to increase CD8 lymphocytes levels and to produce IFNγ in lymph nodes. Moreover, the histopathological analysis showed that BMDCs treated with GK-1/TNFα and loaded with MAGE-AX induced the apparition of more apoptotic and necrotic areas in tumors than in mice without treatment. These results highlight the properties of GK-1 as an immunostimulant of DCs and suggest as a potential candidate the use of this immunotherapy against cancer disease.

  18. GK-1 Improves the Immune Response Induced by Bone Marrow Dendritic Cells Loaded with MAGE-AX in Mice with Melanoma

    Directory of Open Access Journals (Sweden)

    Gabriela Piñón-Zárate

    2014-01-01

    Full Text Available The aim of dendritic cell (DC vaccination in cancer is to induce tumor-specific effector T cells that may reduce and control tumor mass. Immunostimulants that could drive a desired immune response are necessary to be found in order to generate a long lasting tumor immune response. GK-1 peptide, derived from Taenia crassiceps, induces not only increase in TNFα, IFNγ, and MCP-1 production in cocultures of DCs and T lymphocytes but also immunological protection against influenza virus. Moreover, the aim of this investigation is the use of GK-1 as a bone marrow DCs (BMDCs immunostimulant targeted with MAGE antigen; thus, BMDC may be used as immunotherapy against murine melanoma. GK-1 induced in BMDCs a meaningful increment of CD86 and IL-12. In addition, the use of BMDCs TNFα/GK-1/MAGE-AX induced the highest survival and the smallest tumors in mice. Besides, the treatment helped to increase CD8 lymphocytes levels and to produce IFNγ in lymph nodes. Moreover, the histopathological analysis showed that BMDCs treated with GK-1/TNFα and loaded with MAGE-AX induced the apparition of more apoptotic and necrotic areas in tumors than in mice without treatment. These results highlight the properties of GK-1 as an immunostimulant of DCs and suggest as a potential candidate the use of this immunotherapy against cancer disease.

  19. A Fast Response Thermal Conductivity Gage

    Science.gov (United States)

    1986-04-01

    NUMBER(s) N.ATOR(&) IM JAME~S 0. PILCiEIR, 11 MELINDA B. KRUZMPICH 9LPERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT. PROJECT. TASK AREA 6... area of the temperature gage. The gage was then removed and the beam 15 placed in im.ltipulse mode. The energy delivered by each pulse was calculated...Army AMCCOM, ARDC HQDA ATTN: SMCAR-SCMI- DAMA-ART-M SMCAR-SCS, B. Brodman Washington, D.C. 20310 SMCAR-SCS, T. Hung SMCAR-SCA, W. Cadomski Commander

  20. Curcumin improves the therapeutic efficacy of Listeria(at)-Mage-b vaccine in correlation with improved T-cell responses in blood of a triple-negative breast cancer model 4T1.

    Science.gov (United States)

    Singh, Manisha; Ramos, Ilyssa; Asafu-Adjei, Denise; Quispe-Tintaya, Wilber; Chandra, Dinesh; Jahangir, Arthee; Zang, Xingxing; Aggarwal, Bharat B; Gravekamp, Claudia

    2013-08-01

    Success of cancer vaccination is strongly hampered by immune suppression in the tumor microenvironment (TME). Interleukin (IL)-6 is particularly and highly produced by triple-negative breast cancer (TNBC) cells, and has been considered as an important contributor to immune suppression in the TME. Therefore, we hypothesized that IL-6 reduction may improve efficacy of vaccination against TNBC cancer through improved T-cell responses. To prove this hypothesis, we investigated the effect of curcumin, an inhibitor of IL-6 production, on vaccination of a highly attenuated Listeria monocytogenes (Listeria(at)), encoding tumor-associated antigens (TAA) Mage-b in a TNBC model 4T1. Two therapeutic vaccination strategies with Listeria(at)-Mage-b and curcumin were tested. The first immunization strategy involved all Listeria(at)-Mage-b vaccinations and curcumin after tumor development. As curcumin has been consumed all over the world, the second immunization strategy involved curcumin before and all therapeutic vaccinations with Listeria(at)-Mage-b after tumor development. Here, we demonstrate that curcumin significantly improves therapeutic efficacy of Listeria(at)-Mage-b with both immunization strategies particularly against metastases in a TNBC model (4T1). The combination therapy was slightly but significantly more effective against the metastases when curcumin was administered before compared to after tumor development. With curcumin before tumor development in the combination therapy, the production of IL-6 was significantly decreased and IL-12 increased by myeloid-derived suppressor cells (MDSC), in correlation with improved CD4 and CD8 T-cell responses in blood. Our study suggests that curcumin improves the efficacy of Listeria(at)-Mage-b vaccine against metastases in TNBC model 4T1 through reversal of tumor-induced immune suppression.

  1. Expression of tumor antigens on primary ovarian cancer cells compared to established ovarian cancer cell lines

    Science.gov (United States)

    Kloudová, Kamila; Hromádková, Hana; Partlová, Simona; Brtnický, Tomáš; Rob, Lukáš; Bartůňková, Jiřina; Hensler, Michal; Halaška, Michael J.; Špíšek, Radek; Fialová, Anna

    2016-01-01

    In order to select a suitable combination of cancer cell lines as an appropriate source of antigens for dendritic cell-based immunotherapy of ovarian cancer, we analyzed the expression level of 21 tumor associated antigens (BIRC5, CA125, CEA, DDX43, EPCAM, FOLR1, Her-2/neu, MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, MUC-1, NY-ESO-1, PRAME, p53, TPBG, TRT, WT1) in 4 established ovarian cancer cell lines and in primary tumor cells isolated from the high-grade serous epithelial ovarian cancer tissue. More than 90% of tumor samples expressed very high levels of CA125, FOLR1, EPCAM and MUC-1 and elevated levels of Her-2/neu, similarly to OVCAR-3 cell line. The combination of OV-90 and OVCAR-3 cell lines showed the highest overlap with patients' samples in the TAA expression profile. PMID:27323861

  2. Maged1, a new regulator of skeletal myogenic differentiation and muscle regeneration

    Directory of Open Access Journals (Sweden)

    Achouri Younes

    2010-07-01

    Full Text Available Abstract Background In normal adult skeletal muscle, cell turnover is very slow. However, after an acute lesion or in chronic pathological conditions, such as primary myopathies, muscle stem cells, called satellite cells, are induced to proliferate, then withdraw definitively from the cell cycle and fuse to reconstitute functional myofibers. Results We show that Maged1 is expressed at very low levels in normal adult muscle but is strongly induced after injury, during the early phase of myoblast differentiation. By comparing in vitro differentiation of myoblasts derived from wild-type or Maged1 knockout mice, we observed that Maged1 deficiency results in reduced levels of p21CIP1/WAF1, defective cell cycle exit and impaired myotube maturation. In vivo, this defect results in delayed regeneration of injured muscle. Conclusions These data demonstrate for the first time that Maged1 is an important factor required for proper skeletal myoblast differentiation and muscle healing.

  3. MageComet—web application for harmonizing existing large-scale experiment descriptions

    OpenAIRE

    Xue, Vincent; Burdett, Tony; Lukk, Margus,; Taylor, Julie; Brazma, Alvis; Parkinson, Helen

    2012-01-01

    Motivation: Meta-analysis of large gene expression datasets obtained from public repositories requires consistently annotated data. Curation of such experiments, however, is an expert activity which involves repetitive manipulation of text. Existing tools for automated curation are few, which bottleneck the analysis pipeline. Results: We present MageComet, a web application for biologists and annotators that facilitates the re-annotation of gene expression experiments in MAGE-TAB format. It i...

  4. TCR Gene Transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 Epitopes as Melanoma-Specific Immune Targets

    Directory of Open Access Journals (Sweden)

    Trudy Straetemans

    2012-01-01

    Full Text Available Adoptive therapy with TCR gene-engineered T cells provides an attractive and feasible treatment option for cancer patients. Further development of TCR gene therapy requires the implementation of T-cell target epitopes that prevent “on-target” reactivity towards healthy tissues and at the same time direct a clinically effective response towards tumor tissues. Candidate epitopes that meet these criteria are MAGE-C2336-344/HLA-A2 (MC2/A2 and MAGE-A3243-258/HLA-DP4 (MA3/DP4. We molecularly characterized TCRαβ genes of an MC2/A2-specific CD8 and MA3/DP4-specific CD4 T-cell clone derived from melanoma patients who responded clinically to MAGE vaccination. We identified MC2/A2 and MA3/DP4-specific TCR-Vα3/Vβ28 and TCR-Vα38/Vβ2 chains and validated these TCRs in vitro upon gene transfer into primary human T cells. The MC2 and MA3 TCR were surface-expressed and mediated CD8 T-cell functions towards melanoma cell lines and CD4 T-cell functions towards dendritic cells, respectively. We intend to start testing these MAGE-specific TCRs in phase I clinical trial.

  5. Sensitivity of hot-cathode ionization vacuum gages in several gases

    Science.gov (United States)

    Holanda, R.

    1972-01-01

    Four hot-cathode ionization vacuum gages were calibrated in 12 gases. The relative sensitivities of these gages were compared to several gas properties. Ionization cross section was the physical property which correlated best with gage sensitivity. The effects of gage accelerating voltage and ionization-cross-section energy level were analyzed. Recommendations for predicting gage sensitivity according to gage type were made.

  6. Melanoma-associated antigen expression and the efficacy of tyrosine kinase inhibitors in head and neck cancer

    DEFF Research Database (Denmark)

    Hartmann, Stefan; Brands, Roman C; Küchler, Nora;

    2015-01-01

    receptor (EGFR). The efficacy of tyrosine kinase inhibitors (TKI) in the context of melanoma-associated antigens is discussed in the present study. Five human squamous cell carcinoma cell lines were treated with the EGFR TKIs, erlotinib and gefitinib. The efficacy of these agents was measured using......Melanoma-associated antigen (MAGE) has been identified in a variety of types of cancer. The expression of several MAGE subgroups is correlated with poor prognosis and chemotherapeutic resistance. One target of chemotherapeutic treatment in head and neck cancer is the epidermal growth factor...... correlation between MAGE-A5 and -A11 and lower efficacy of EGFR TKIs. Pretreatment analysis of MAGE-A status may therefore aid improvement of chemoprevention using erlotinib and gefitinib in head and neck cancer....

  7. High temperature static strain gage development

    Science.gov (United States)

    Hulse, C. O.; Bailey, R. S.; Grant, H. P.; Anderson, W. L.; Przybyszewski, J. S.

    1991-01-01

    Final results are presented from a program to develop a thin film static strain gage for use on the blades and vanes of running, test stand gas turbine engines with goals of an 3 x 3 mm gage area and total errors of less than 10 pct. of + or - 2,000 microstrain after 50 hrs at 1250 K. Pd containing 13 Wt. pct. Cr was previously identified as a new strain sensor alloy that appeared to be potentially usable to 1250 K. Subsequently, it was discovered, in contrast with its behavior in bulk, that Pd-13Cr suffered from oxidation attack when prepared as a 4.5 micron thick thin film. Continuing problems with electrical leakage to the substrate and the inability of sputtered alumina overcoats to prevent oxidation led to the discovery that sputtered alumina contains appreciable amounts of entrapped argon. After the argon has been exsolved by heating to elevated temperatures, the alumina films undergo a linear shrinkage of about 2 pct. resulting in formation of cracks. These problems can be largely overcome by sputtering the alumina with the substrate heated to 870 K. With 2 micron thick hot sputtered alumina insulation and overcoat films, total 50 hr drifts of about 100 microstrain (2 tests) and about 500 microstrain (1 test) were observed at 1000 and 1100 K, respectively. Results of tests on complete strain gage systems on constant moment bend bars with Pd temperature compensation grids revealed that oxidation of the Pd grid was a major problem even when the grid was overcoated with a hot or cold sputtered alumina overcoat.

  8. Use of modified Magee equations and histologic criteria to predict the Oncotype DX recurrence score.

    Science.gov (United States)

    Turner, Bradley M; Skinner, Kristin A; Tang, Ping; Jackson, Mary C; Soukiazian, Nyrie; Shayne, Michelle; Huston, Alissa; Ling, Marilyn; Hicks, David G

    2015-07-01

    Oncotype DX (Genomic Health, Redwood City, CA, USA, current list price $4,350.00) is a multigene quantitative reverse transcription-polymerase chain reaction-based assay that estimates the risk of distant recurrence and predicts chemotherapy benefit for patients with estrogen receptor (ER)-positive breast cancers. Studies have suggested that standard histologic variables can provide similar information. Klein and Dabbs et al have shown that Oncotype DX recurrence scores can be estimated by incorporating standard histologic variables into equations (Magee equations). Using a simple modification of the Magee equation, we predict the Oncotype DX recurrence score in an independent set of 283 cases. The Pearson correlation coefficient (r) for the Oncotype DX and average modified Magee recurrence scores was 0.6644 (n=283; Pscore>30 (n=8) or an average modified Magee recurrence scorescore, respectively. 86% (38/44) of cases with an average modified Magee recurrence score≤12, and 89% (34/38) of low grade tumors (NSscore. Using an algorithmic approach to eliminate high and low risk cases, between 5% and 23% of cases would potentially not have been sent by our institution for Oncotype DX testing, creating a potential cost savings between $56,550.00 and $282,750.00. The modified Magee recurrence score along with histologic criteria may be a cost-effective alternative to the Oncotype DX in risk stratifying certain breast cancer patients. The information needed is already generated by many pathology laboratories during the initial assessment of primary breast cancer, and the equations are free.

  9. Strain Gage Selection Criteria for Textile Composite Materials

    Science.gov (United States)

    Masters, John E.

    1996-01-01

    This report will provide a review of efforts to establish a set of strain gage selection guidelines for textile reinforced composite materials. A variety of strain gages were evaluated in the study to determine the sensitivity of strain measurements to the size of the strain gage. The strain gages were chosen to provide a range of gage lengths and widths. The gage aspect ratio (the length-to-width ratio) was also varied. The gages were tested on a diverse collection of textile composite laminates. Test specimens featured eleven different textile architectures: four 2-D triaxial braids, six 3-D weaves, and one stitched uniweave architecture. All specimens were loaded in uniaxial tension. The materials' moduli were measured in both the longitudinal (parallel to the O deg. yarns) and the transverse (perpendicular to the O deg. yarns) directions. The results of these measurements were analyzed to establish performance levels for extensometers and strain gages on textile composite materials. Conclusions are expressed in a summary that discusses instrumentation practices and defines strain gage selection criteria.

  10. Buried wire gage for wall shear stress measurements

    Science.gov (United States)

    Murthy, V. S.; Rose, W. C.

    1978-01-01

    A buried wire gage for measuring wall shear stress in fluid flow was studied and further developed. Several methods of making this relatively new type of gage were examined to arrive at a successful technique that is well-suited for wind-tunnel testing. A series of measurements was made to demonstrate the adequacy of a two-point calibration procedure for these gages. The buried wire gage is also demonstrated to be ideally suited for quantitative measurement of wall shear stress in wind-tunnel testing.

  11. T Cells as Antigen Carriers for Anti-tumor Vaccination.

    Science.gov (United States)

    Traversari, Catia; Russo, Vincenzo

    2016-01-01

    The exploitation of the physiologic processing and presenting machinery of dendritic cells (DCs) by in vivo loading of tumor-associated antigens may improve the immunogenic potential and clinical efficacy of DC-based cancer vaccines. The approach developed by our group was based on the clinical observation that some patients treated with the infusion of donor lymphocytes transduced to express the HSV-TK suicide gene for relapse of hematologic malignancies, after allogeneic hematopoietic stem cell transplantation, developed a T cell-mediated immune response specifically directed against the HSV-TK gene product.We demonstrated that lymphocytes genetically modified to express HSV-TK as well as self/tumor antigens, acting as antigen carriers, efficiently target DCs in vivo in tumor-bearing mice. The infusion of TRP-2-transduced lymphocytes induced the establishment of protective immunity and long-term memory in tumor-bearing mice by cross-presentation of the antigen mediated by the CD11c(+)CD8a(+) DCs subset. A similar approach was applied in a clinical setting. Ten patients affected by MAGE-3(+) metastatic melanoma were treated with autologous lymphocytes retrovirally transduced to express the MAGE-3 tumor antigen. In three patients, the treatment led to the increase of MAGE-3 specific CD8+ and CD4+ effectors and the development of long-term memory, which ultimately correlated with a favorable clinical outcome. Transduced lymphocytes represent an efficient way for in vivo loading of tumor-associated antigens of DCs.

  12. 49 CFR 179.400-19 - Valves and gages.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Valves and gages. 179.400-19 Section 179.400-19...-19 Valves and gages. (a) Valves. Manually operated shut-off valves and control valves must be... liquid flow rates. All valves must be made from approved materials compatible with the lading and...

  13. 46 CFR 197.318 - Gages and timekeeping devices.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Gages and timekeeping devices. 197.318 Section 197.318... STANDARDS GENERAL PROVISIONS Commercial Diving Operations Equipment § 197.318 Gages and timekeeping devices... timekeeping device must be at each dive location....

  14. Expression of Mage-A1、A3 in Breast Cancer and Its Significance%Mage-A1、A3在乳腺癌中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    马全; 武正炎; 范萍; 郑伟; 王萱仪

    2004-01-01

    目的研究乳腺癌组织和细胞株中黑色素瘤抗原基因(Mage)的表达情况,为乳腺癌的免疫治疗提供依据.方法采用RT-PCR法检测33例乳腺癌组织和4株常用乳腺癌细胞株MCF-7、Sk-Br-3、MDA-MB-435s和TM40D中Mage基因的表达情况.结果 33例乳腺癌组织中9例(27.3%)至少表达1种Mage-A基因,4例(12.1%)Mage-A1阳性,7例(21.2%)Mage-A3阳性,细胞株MCF-7和Sk-Br-3中Mage-A1和Mage-A3呈阳性表达,MDA-MB-435s和TM40D中Mage-A3呈阳性表达.结论 Mage基因在乳腺癌中表达率较高,Mage蛋白有望成为乳腺癌免疫治疗的靶抗原.

  15. USGS Small-scale Dataset - Streamflow Gaging Stations of the United States 201403 Shapefile

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This map layer shows selected streamflow gaging stations of the United States, Puerto Rico, and the U.S. Virgin Islands, in 2013. Gaging stations, or gages, measure...

  16. Pyroxenes in Serra de Mage - Cooling history in comparison with Moama and Moore County

    Science.gov (United States)

    Harlow, G. E.; Prinz, M.; Nehru, C. E.; Taylor, G. J.; Keil, K.

    1979-01-01

    Thin sections and single grains of pyroxenes from the Serra de Mage feldspar cumulate eucrites were studied by X-ray crystallography, electron microprobe and optical techniques. It was concluded that the pyroxene crystallized as pigeonite. On cooling augite was exsolved along (001) and inverted to hypersthene, with exsolution of (100) augite from hypersthene during continued slow cooling. The estimated original bulk composition of the pigeonite pyroxene is Wo10En51Fs39. The compositional data, textural relations, and existence of P2 sub 1 ca hypersthene suggest very low cooling (about 0.0004 deg C/year) below 800 deg. The Serra de Mage augite lamellae were found to be as thick or thicker than those of Moore County and Moama meteorites.

  17. Manual for leveling at gaging stations in North Carolina

    Science.gov (United States)

    Thomas, N.O.; Jackson, N.M.

    1981-01-01

    This manual was prepared to serve several purposes in the U.S. Geological Survey North Carolina District. This manual sets forth District policy as to frequency of levels, accuracy criteria, procedures for checking the datum and setting of the various types of gages, general rules to follow in establishing the original datum of a gage, and contains sample notes to be used as guides in level notekeeping. The manual also serves as a training tool in that the reasoning behind District policy is explained and reasons are given for following the recommended techniques to assist in a better understanding of the purpose of levels and maintaining gage datum.

  18. Theory and Practice of Shear/Stress Strain Gage Hygrometry

    Science.gov (United States)

    Shams, Qamar A.; Fenner, Ralph L.

    2006-01-01

    Mechanical hygrometry has progressed during the last several decades from crude hygroscopes to state-of-the art strain-gage sensors. The strain-gage devices vary from different metallic beams to strain-gage sensors using cellulose crystallite elements, held in full shear restraint. This old technique is still in use but several companies are now actively pursuing development of MEMS miniaturized humidity sensors. These new sensors use polyimide thin film for water vapor adsorption and desorption. This paper will provide overview about modern humidity sensors.

  19. Vision system for dial gage torque wrench calibration

    Science.gov (United States)

    Aggarwal, Neelam; Doiron, Theodore D.; Sanghera, Paramjeet S.

    1993-11-01

    In this paper, we present the development of a fast and robust vision system which, in conjunction with the Dial Gage Calibration system developed by AKO Inc., will be used by the U.S. Army in calibrating dial gage torque wrenches. The vision system detects the change in the angular position of the dial pointer in a dial gage. The angular change is proportional to the applied torque. The input to the system is a sequence of images of the torque wrench dial gage taken at different dial pointer positions. The system then reports the angular difference between the different positions. The primary components of this vision system include modules for image acquisition, linear feature extraction and angle measurements. For each of these modules, several techniques were evaluated and the most applicable one was selected. This system has numerous other applications like vision systems to read and calibrate analog instruments.

  20. An Elastic Tube Gage for Measuring Static and Dynamic Pressures

    Science.gov (United States)

    1948-05-01

    25 grams of granulated celluloid No. 2346 dissolved ; on one pound of ethyl acetate. + For maximum stability of operation, gage current should be...Compounds such as beeswax or ceresin wax were first employed for waterproofing, but their brittleness at low temperatures was found to be ob- jectionable...Bitumastics such, as Qzite B Jhave sbeen superior in that respect, but are dissolved by hydraulic- fluids and oils, to which strain gages .may Be

  1. CD8+ TIL Recruitment May Revert the Association of MAGE A3 with Aggressive Features in Thyroid Tumors

    Directory of Open Access Journals (Sweden)

    Mariana Bonjiorno Martins

    2014-01-01

    Full Text Available Background. We aimed to investigate a possible role of MAGE A3 and its associations with infiltrated immune cells in thyroid malignancy, analyzing their utility as a diagnostic and prognostic marker. Materials and Methods. We studied 195 malignant tissues: 154 PTCs and 41 FTCs; 102 benign tissues: 51 follicular adenomas and 51 goiter and 17 normal thyroid tissues. MAGE A3 and immune cell markers (CD4 and CD8 were evaluated using immunohistochemistry and compared with clinical pathological features. Results. The semiquantitative analysis and ACIS III analysis showed similar results. MAGE A3 was expressed in more malignant than in benign lesions (P<0.0001, also helping to discriminate follicular-patterned lesions. It was also higher in tumors in which there was extrathyroidal invasion (P=0.0206 and in patients with stage II disease (P=0.0107. MAGE A3+ tumors were more likely to present CD8+ TIL (P=0.0346, and these tumors were associated with less aggressive features, that is, extrathyroidal invasion and small size. There was a trend of MAGE A3+ CD8+ tumors to evolve free of disease. Conclusion. We demonstrated that MAGE A3 and CD8+ TIL infiltration may play an important role in malignant thyroid nodules, presenting an interesting perspective for new researches on DTC immunotherapy.

  2. Strain gage selection in loads equations using a genetic algorithm

    Science.gov (United States)

    1994-01-01

    Traditionally, structural loads are measured using strain gages. A loads calibration test must be done before loads can be accurately measured. In one measurement method, a series of point loads is applied to the structure, and loads equations are derived via the least squares curve fitting algorithm using the strain gage responses to the applied point loads. However, many research structures are highly instrumented with strain gages, and the number and selection of gages used in a loads equation can be problematic. This paper presents an improved technique using a genetic algorithm to choose the strain gages used in the loads equations. Also presented are a comparison of the genetic algorithm performance with the current T-value technique and a variant known as the Best Step-down technique. Examples are shown using aerospace vehicle wings of high and low aspect ratio. In addition, a significant limitation in the current methods is revealed. The genetic algorithm arrived at a comparable or superior set of gages with significantly less human effort, and could be applied in instances when the current methods could not.

  3. 49 CFR 213.355 - Frog guard rails and guard faces; gage.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Frog guard rails and guard faces; gage. 213.355... Higher § 213.355 Frog guard rails and guard faces; gage. The guard check and guard face gages in frogs... distance between the gage line of a frog to the guard line 1 of its guard rail or guarding face,...

  4. Skin Friction Gage for Measurements in Hypersonic Flow

    Institute of Scientific and Technical Information of China (English)

    Francois Falempin; Marat Goldfeld; Roman Nestoulia

    2003-01-01

    A description and results of tests of a new small-scale gage for direct measurement of skin friction force are presented in the paper. The gage design provides separated measurement of longitudinal and transversal component of friction force. Application of this scheme provides high sensitivity and necessary high-frequency response of the gage. The tests of the gage were carried out in a blow down wind tunnel at Mach numbers of 2 and 4 within the range of Reynolds numbers Rex from 0.8 to 5 million and in the hot-shot wind tunnel at Mach number 6 and Reynolds numbers Rex= 2.5-10 million. The measurements of skin friction were carried out on a flat plate and on a ramp beyond the shock wave. Simultaneously with the direct measurement of friction in the blow down wind tunnel, the measurements of profiles of average velocities and mass flow rate pulsations were realised. Analysis of measurement errors has shown that the friction gage permits to measure skin friction coefficient on a flat plate with mistake not more than 10%.

  5. Expression of MAGE-A1, A2, A3, A4 in urinary transitional cell carcinoma tissue and cell lines%MAGE-A1,A2,A3,A4在膀胱移行细胞癌组织及细胞株中基因表达的研究

    Institute of Scientific and Technical Information of China (English)

    耿凛; 俞莉章; 那彦群

    2005-01-01

    目的:研究膀胱移行细胞癌(TCC)中黑色素瘤抗原(MAGE)基因表达.方法:逆转录聚合酶链反应(RT-PCR)技术检测20例膀胱TCC患者癌组织和3株膀胱TCC细胞株T24、EJ、BIU87中MAGE-A1、A2、A3、A4基因mRNA表达.结果:20例膀胱TCC癌组织中19例(95%)至少表达一种MAGE-A基因,12例MAGE-A1阳性(60%),16例MAGE-A2阳性(80%),11例MAGE-A3阳性(55%),18例MAGE-A4阳性(90%),MAGE-A1-4均阳性8例(40%).膀胱TCC细胞株T24中MAGE-A1-4基因均表达,EJ中MAGE-A3、A4基因表达,BIU87中MAGE-A2、A3、A4基因表达.结论:MAGE基因在膀胱TCC中有较高表达,可望成为膀胱TCC免疫治疗的靶基因.

  6. Effects of water molecules on the chemical stability of MAGeI3 perovskite explored from a theoretical viewpoint.

    Science.gov (United States)

    Sun, Ping-Ping; Chi, Wei-Jie; Li, Ze-Sheng

    2016-09-21

    The stability of perovskite in humid environments is one of the biggest obstacles for its potential applications in light harvesting and electroluminescent displays. Understanding the detailed degradation mechanism of MAGeI3 in moisture is a critical way to explore the practicability of MAGeI3 perovskite. In this study, we report a quantitative and systematic investigation of MAGeI3 degradation processes by exploring the effects of H2O molecules on the structural and electronic properties of the most stable MAGeI3(101) surface under various simulated environmental conditions with different water coverage based on first-principles calculations. The results show that H2O molecules can easily diffuse into the inner side of the perovskite and gradually corrode the structure as the number of H2O molecules increases. As a result of the interactions between perovskite and H2O molecules, a hydrated intermediate will be generated as the first step in the degradation mechanism; the perovskite will further decompose to HI and GeI2. In terms of one MAGeI3 molecule, it will be dissociated completely to GeI2 as a result of hydrolysis reactions with a minimum of 4H2O molecules. In addition, the degradation of the perovskite will also affect the electronic structure, causing a decrease in optical absorption across the visible region of the spectrum and a distinct deformation change in the crystal structure of the material. These findings further illustrate the degradation of the hydrolysis process of MAGeI3 perovskite in humid environments, which should be helpful to inspire experimentalists to take action to prolong the lifetimes of perovskite solar cells to achieve high conversion efficiency in their applications.

  7. GAGE12 mediates human gastric carcinoma growth and metastasis.

    Science.gov (United States)

    Lee, Eun Kyung; Song, Kyung-A; Chae, Ji-Hye; Kim, Kyoung-Mee; Kim, Seok-Hyung; Kang, Myung-Soo

    2015-05-15

    The spontaneous metastasis from human gastric carcinoma (GC) remains poorly reproduced in animal models. Here, we established an experimental mouse model in which GC progressively developed in the orthotopic stomach wall and metastasized to multiple organs; the tumors colonized in the ovary exhibited typical characteristics of Krukenberg tumor. The expression of mesenchymal markers was low in primary tumors and high in those in intravasating and extravasating veins. However, the expression of epithelial markers did not differ, indicating that the acquisition of mesenchymal markers without a concordant loss of typical epithelial markers was associated with metastasis. We identified 35 differentially expressed genes (DEGs) in GC cells metastasized to ovary, among which overexpression of GAGE12 family genes, the top-ranked DEGs, were validated. In addition, knockdown of the GAGE12 gene family affected transcription of many of the aforementioned 35 DEGs and inhibited trans-well migration, tumor sphere formation in vitro and tumor growth in vivo. In accordance, GAGE12 overexpression augmented migration, tumor sphere formation and sustained in vivo tumor growth. Taken together, the GAGE12 gene family promotes GC growth and metastasis by modulating the expression of GC metastasis-related genes.

  8. High temperature strain gage technology for gas turbine engines

    Science.gov (United States)

    Fichtel, Edward J.; McDaniel, Amos D.

    1994-08-01

    This report summarizes the results of a six month study that addressed specific issues to transfer the Pd-13Cr static strain sensor to a gas turbine engine environment. The application issues that were addressed include: (1) evaluation of a miniature, variable potentiometer for use as the ballast resistor, in conjunction with a conventional strain gage signal conditioning unit; (2) evaluation of a metal sheathed, platinum conductor leadwire assembly for use with the three-wire sensor; and (3) subjecting the sensor to dynamic strain cyclic testing to determine fatigue characteristics. Results indicate a useful static strain gage system at all temperature levels up to 1350 F. The fatigue characteristics also appear to be very promising, indicating a potential use in dynamic strain measurement applications. The procedure, set-up, and data for all tests are presented in this report. This report also discusses the specific strain gage installation technique for the Pd-13Cr gage because of its potential impact on the quality of the output data.

  9. USGS Small-scale Dataset - Streamflow Gaging Stations of the United States 201403 FileGDB 10.1

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This map layer shows selected streamflow gaging stations of the United States, Puerto Rico, and the U.S. Virgin Islands, in 2013. Gaging stations, or gages, measure...

  10. Development and characterization of PdCr temperature-compensated wire resistance strain gage

    Science.gov (United States)

    Lei, Jih-Fen

    1989-01-01

    A temperature-compensated resistance static strain gage with potential to be used to 600 C was recently developed. Gages were fabricated from specially developed palladium-13 w/o chromium (Pd-13Cr) wire and platinum (Pt) compensator. When bonded to high temperature Hastelloy X, the apparent strain from room temperature to 600 C was within 400 microstrain for gages with no preheat treatment and within 3500 microstrain for gages with 16 hours prestabilization at 640 C. The apparent strain versus temperature relationship of stabilized PdCr gages were repeatable with the reproducibility within 100 microstrain during three thermal cycles to 600 C and an 11 hours soak at 600 C. The gage fabrication, construction and installation is described. Also, the coating system used for this compensated resistance strain gage is explained. The electrical properties of the strain sensing element and main characteristics of the compensated gage including apparent strain, drift and reproducibility are discussed.

  11. Development and calibration of buried wire gages for wall shear stress measurements in fluid flow

    Science.gov (United States)

    Murthy, Sreedhara V.; Steinle, Frank W.

    1988-01-01

    Special methods were developed to arrange 'Buried Wire Gage' inserts flush to the contoured flow surfaces of instrument plugs of a boundary-layer flow apparatus. The fabrication process was aimed at producing proper bonding of the sensor wire to the substrate surface, without causing excessive surface waviness. A large number of gages were built and first calibrated for the resistance-temperature characteristics. The gages were then installed in a flow calibration apparatus and operated from a constant temperature anemometer system for a series of flow settings to derive the calibration constants of each of the gages. The flow settings included a range of subsonic freestream Mach numbers in order to help establish the gage calibration characteristics for compressible flow fields. This paper provides a description of the buried wire gage technique, an explanation of the method evolved for making proper gages, the procedure for calibrating the gages and the results of measurements performed for determining the calibration constants.

  12. Development and characterization of PdCr temperature-compensated wire resistance strain gage

    Science.gov (United States)

    Lei, Jih-Fen

    1989-10-01

    A temperature-compensated resistance static strain gage with potential to be used to 600 C was recently developed. Gages were fabricated from specially developed palladium-13 w/o chromium (Pd-13Cr) wire and platinum (Pt) compensator. When bonded to high temperature Hastelloy X, the apparent strain from room temperature to 600 C was within 400 microstrain for gages with no preheat treatment and within 3500 microstrain for gages with 16 hours prestabilization at 640 C. The apparent strain versus temperature relationship of stabilized PdCr gages were repeatable with the reproducibility within 100 microstrain during three thermal cycles to 600 C and an 11 hours soak at 600 C. The gage fabrication, construction and installation is described. Also, the coating system used for this compensated resistance strain gage is explained. The electrical properties of the strain sensing element and main characteristics of the compensated gage including apparent strain, drift and reproducibility are discussed.

  13. Study of MAGE-3 gene expression in different lung cells%肺来源的不同细胞中MAGE-3基因表达情况的初步研究

    Institute of Scientific and Technical Information of China (English)

    杨明夏; 俞小卫; 郭红荣; 黄秋生

    2010-01-01

    目的 分析人肺来源的不同细胞中MAGE-3基因在mRNA水平的表达情况,为肺部良恶性肿瘤的早期鉴别诊断提供研究基础.方法 将人支气管上皮细胞(HBE)、人肺成纤维细胞(HFLF)、原代培养的人肺动脉平滑肌细胞(HPASMC)及人肺腺癌细胞LTEP-a-2同步化培养后,加完全培养基培养24 h后,同步提取各组细胞细胞总RNA,运用实时定量PCR方法分析各细胞中MAGE-3基因在mRNA水平的表达情况.结果 在人肺来源的不同细胞中,正常肺部来源的HBE、HFLF和HPASMC细胞中MAGE-3基因在mRNA的表达水平极低,而人肺腺癌细胞LTEP-a-2中表达丰度明显升高;肺癌细胞中MAGE-3基因在mRNA的表达水平明显高于正常细胞表达水平,差异倍数在20倍以上.结论 肺癌细胞LTEP-a-2中MAGE-3基因mRNA表达水平明显高于肺部正常细胞,可探讨其作为鉴别肺部良恶性病变诊断的恶性病变早期检测指标.%Objective To provide research basis for the early differential diagnosis of benign and malignant tumor in lung by analyzing MAGE-3 mRNA expression in different human lung cells. Methods The human bronchial epithelial cells (HBE), human lung fibroblasts (HFLF), primary cultured human pulmonary artery smooth muscle cells (HPASMC) and human lung adenocarcinoma cells (LTEP-a-2)were synchronized cultured with complete medium for 24 hours,the total cellular RNA was simultaneously extracted,and MAGE-3 mRNA expression was analyzed by real-time polymerase chain reaction. Results MAGE-3 mRNA expression was extremely low in HBE, HFLF and HPASMC,and significantly increased in LTEP-a-2. MAGE-3 mRNA expression in lung cancer cells was significantly higher than that in normal cells. Conclusions MAGE-3 mRNA expression in LTEP-a-2 is significantly higher than that in normal lung cells,which could be an early detection indicator for differential diagnosis of benign and malignant lung lesions.

  14. 溶氧反馈-补料分批技术高密度培养基因重组MAGE1/HSP70/MAGE3工程菌%Preparation of gene recombinant MAGE1/HSP70/MAGE3 by high cell density culture of E.coli.with DO fed-back control of nutrient feeding

    Institute of Scientific and Technical Information of China (English)

    胡沛臻; 温江田; 路凡; 王孝功; 李侠; 司少艳; 葛伟; 黄杨; 张秀敏; 隋延仿

    2007-01-01

    目的 建立人黑色素瘤抗原MAGE1/HSP70/MAGE3融合蛋白基因重组工程菌E.coli.BL21/pET-MHM的高密度发酵工艺.方法 以摇瓶发酵结果为基础,扩大至NBS Bioflo Ⅳ 20 L发酵罐发酵,利用溶氧反馈-补料分批培养技术,对影响工程菌生长及目的蛋白表达的因素如发酵培养基、活化时间、诱导浓度及时间、pH值及分批补加营养物质等进行优化.结果 保持培养过程中40%的溶解氧,采用半合成培养基、活化至对数生长期时0.2 mmol/L IPTG诱导5 h以及以甘油为碳源连续流加补料的条件发酵,连续3批重复发酵,最终菌密度D(600)均达45~50时,菌体量可提高至70 g/L以上,目的蛋白的表达量占菌体蛋白总量的38%以上.结论 确定了周期短、产率高且稳定可靠的发酵工艺.

  15. 49 CFR 213.143 - Frog guard rails and guard faces; gage.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Frog guard rails and guard faces; gage. 213.143... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION TRACK SAFETY STANDARDS Track Structure § 213.143 Frog guard rails and guard faces; gage. The guard check and guard face gages in frogs shall be within the...

  16. Method of predicting ionization-type vacuum gage sensitivity for various gases

    Science.gov (United States)

    Holanda, R.

    1973-01-01

    Sensitivity of gage for one gas can be correlated to its sensitivity for other gases by the ratio of gas ionization cross sections. Ionization cross sections which best correlate with gage sensitivites vary according to gage type and ionization cross section energy level.

  17. Alumina Encapsulated Strain Gage Not Mechanically Attached To The Substrate, Used to Temperature Compensate an Active High Temperature Gage In A Half-Bridge Configuration

    Science.gov (United States)

    Piazza, Anthony (Inventor)

    2001-01-01

    A temperature compensation element for a high-temperature strain gage and the method of fabricating the same. Preferably, the element is a "dummy" strain gage not mechanically attached to the substrate. The element is encapsulated in an insulative material and used to compensate an active high-temperature strain gage and wired in a half-bridge configuration. The temperature compensation element and high-temperature strain gage are fabricated using the method of the present invention. This method includes temporarily adhering the element to a heat sink, encapsulated in an insulative material and then removed from the heat sink. Next, the element is either stacked or placed near the active gage. Ideally, the element and the active gage have substantially similar heat transfer and electrical properties.

  18. Analysis of strain gage reliability in F-100 jet engine testing at NASA Lewis Research Center

    Science.gov (United States)

    Holanda, R.

    1983-01-01

    A reliability analysis was performed on 64 strain gage systems mounted on the 3 rotor stages of the fan of a YF-100 engine. The strain gages were used in a 65 hour fan flutter research program which included about 5 hours of blade flutter. The analysis was part of a reliability improvement program. Eighty-four percent of the strain gages survived the test and performed satisfactorily. A post test analysis determined most failure causes. Five failures were caused by open circuits, three failed gages showed elevated circuit resistance, and one gage circuit was grounded. One failure was undetermined.

  19. Differences between nipher and slter shielded rain gages at two Colorado deposition monitoring sites

    Science.gov (United States)

    Bigelow, David S.; Denning, A. Scott

    1990-01-01

    In the last decade the United States and Canada have made significant progress in establishing spatial ad temporal estimates of atmospheric deposition throughout North America. Fundamental to the wet-deposition portion of these estimates is the accurate and precise measurement of precipitation amount. Goodison and others (I-3) have reported on a new type of shielded snow gage known as the Canadian MSC Nipher shielded snow gage. Because this shielded snow gage has been shown to be superior to other precipitation gages for the estimation of snowfall amount, its design was adapted to the Universal Belfort precipitation gage (4), the dominant precipitation gage used at deposition monitoring sites in the United States. Favorable results taken from monitoring sites using this modified Nipher shielded snow gage (3-6) have prompted the U.S. Environmental Protection Agency and the Electric Power Research Institute to adopt the Nipher shielded Belfort gage as a standard piece of equipment in the Acid MODES and Operational Evaluation Network (OEN) monitoring programs and to propose that is be included as a standard snow gage in other North American deposition monitoring programs. This communication details preliminary results from two of nine NADP/NTN deposition monitoring sites selected by the Environmental Protection Agency to compare Nipher shielded Belfort precipitation gage volumes to volumes obtained from the standard Belfort gage used in the NADP/NTN monitoring program.

  20. Standard test method for ambient temperature fatigue life of metallic bonded resistance strain gages

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2003-01-01

    1.1 This test method covers a uniform procedure for the determination of strain gage fatigue life at ambient temperature. A suggested testing equipment design is included. 1.2 This test method does not apply to force transducers or extensometers that use bonded resistance strain gages as sensing elements. 1.3 Strain gages are part of a complex system that includes structure, adhesive, gage, leadwires, instrumentation, and (often) environmental protection. As a result, many things affect the performance of strain gages, including user technique. A further complication is that strain gages, once installed, normally cannot be reinstalled in another location. Therefore, it is not possible to calibrate individual strain gages; performance characteristics are normally presented on a statistical basis. 1.4 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety and health practices ...

  1. Efficient lysis of epithelial ovarian cancer cells by MAGE-A3-induced cytotoxic T lymphocytes using rAAV-6 capsid mutant vector.

    Science.gov (United States)

    Batchu, Ramesh B; Gruzdyn, Oksana V; Moreno-Bost, Amberly M; Szmania, Susann; Jayandharan, Giridhararao; Srivastava, Arun; Kolli, Bala K; Weaver, Donald W; van Rhee, Frits; Gruber, Scott A

    2014-02-12

    MAGE-A3 is highly expressed in epithelial ovarian cancer (EOC), making it a promising candidate for immunotherapy. We investigated whether dendritic cells (DCs) transduced with a rAAV-6 capsid mutant vector Y445F could elicit effective MAGE-A3-specific anti-tumor cytotoxic T lymphocyte (CTL) responses in vitro. MAGE-A3 was cloned and rAAV-6-MAGE-A3 purified, followed by proviral genome detection using real-time PCR. Immunofluorescence detection of rAAV-6-Y445F-MAGE-A3-transduced DCs demonstrated 60% transduction efficiency. Fluorescent in situ hybridization analysis confirmed chromosomal integration of rAAV vectors. Flow cytometric analysis of transduced DCs showed unaltered expression of critical monocyte-derived surface molecules with retention of allo-stimulatory activity. Co-culture of autologous T lymphocytes with MAGE-A3-expressing DCs produced CTLs that secreted IFN-γ, and efficiently killed MAGE-A3+ EOC cells. This form of rAAV-based DC immunotherapy, either alone or more likely in combination with other immune-enhancing protocols, may prove useful in the clinical setting for management of EOC.

  2. Limited SP17 expression within tumors diminishes its therapeutic potential

    DEFF Research Database (Denmark)

    Gjerstorff, M F; Ditzel, H J

    2012-01-01

    In this study, we have investigated the expression of the tumor antigen sperm protein 17 (SP17) in a large panel of human cancers and compared it with the expression of two well-characterized families of tumor antigens, melanoma-associated antigen-A (MAGE-A) and G antigen (GAGE). We found that SP17...... positive tumors in contrast to MAGE-A and GAGE proteins, which were homogenously expressed in large foci. Our results suggest that SP17 may not be an optimal target for cancer vaccines....

  3. La récession de 2008-2009 a-t-elle accru la part structurelle du chômage en zone euro ?

    OpenAIRE

    HAINCOURT, S.; M. Mogliani.

    2012-01-01

    La courbe dite « de Beveridge » illustre la relation entre taux de chômage et taux d’emplois vacants. En ce qui concerne la zone euro, le redressement du taux de chômage et la hausse des difficultés de recrutement depuis la récession de 2008-2009 témoignent d’un risque d’accroissement du chômage structurel. Au niveau national, ce risque est principalement localisé en Espagne, mais des signaux négatifs apparaissent également en France.

  4. Strain gage installation and survivability on geosynthetics used in flexible pavements

    Science.gov (United States)

    Brooks, Jeremy A.

    The use of foil type strain gages on geosynthetics is poorly documented. In addition, very few individuals are versed in proper installation techniques or calibration methods. Due to the limited number of knowledgeable technicians there is no information regarding the susceptibility of theses gages to errors in installation by inexperienced installers. Also lacking in the documentation related to the use of foil type strain gages on geosynthetics is the survivability of the gages in field conditions. This research documented procedures for installation, calibration, and survivability used by the project team to instruments a full scale field installation in Marked Tree, AR. This research also addressed sensitivity to installation errors on both geotextile and geogrid. To document the process of gage installation an experienced technician, Mr. Joe Ables, formerly of the UASCE Waterways Experiment Station, was consulted. His techniques were combined with those discovered in related literature and those developed by the research team to develop processes that were adaptable to multiple gage geometries and parent geosynthetics. These processes were described and documented in a step by step manner with accompanying photographs, which should allow virtually anyone with basic electronics knowledge to install these gages properly. Calibration of the various geosynthetic / strain gage combinations was completed using wide width tensile testing on multiple samples of each material. The tensile testing process was documented and analyzed using digital photography to analyze strain on the strain gage itself. Calibration factors for each geosynthtics used in the full scale field testing were developed. In addition, the process was thoroughly documented to allow future researchers to calibrate additional strain gage and geosynthetic combinations. The sensitivity of the strain gages to installation errors was analyzed using wide width tensile testing and digital photography to

  5. MAGE-A和NY-ESO-1的表达与子宫颈癌临床病理特征及预后关系探讨

    Institute of Scientific and Technical Information of China (English)

    杨碧辉; 梁利斌

    2013-01-01

    Objective To explore the relationship between the expression of MAGE-A,NY-ESO-1 and the clinical pathologic features and prognosis of cervical cancer and to observe the influence of neoadjuvant chemotherapy on the expression of MAGE-A and NY-ESO-1. Methods 82 cases were divided into two groups. Group A,34 patients of FIGO Ⅰa1-Ⅰb1, who received hysterectomy. Group B,48 patients of FIGO Ⅰb2-Ⅳa,who received neoadjuvant chemotherapy followed by hysterectomy. Immunohistochemistry was used to detect the expressions of MAGE-A,NY-ESO-1 in 82 cases of cervical cancer. Analysis the relationship between the expression of MAGE-A,NY-ESO-1 and pathological properties or prognosis. Results In group A,the positive expression reates of MAGE-A and NY-ESO-1 were 44.1% and 58.8%. In group B,the positive expression reates of MAGE-A and NY-ESO-1 were 56.3% and 54.2% before neoadjuvant chemotherapy. After neoadjuvant chemotherapy, the positive expression reates of MAGE-A and NY-ESO-1 were 53.5% and 55.8%. The positive expression reates of MAGE-A and NY-ESO-1 of tumor diameter ≥2cm were higher than <2cm in group A. The expression of MAGE-A was related with N stage. The survival time of patient with MAGE-A positive was lower than negative(P<0.05). Conclusion MAGE-A and NY-ESO-1 frequently express in cervical cancer. Drugs of chemotherapy were not influence the expression of MAGE-A and NY-ESO-1. MAGE-A is related with tumor diameter and lymph node metastases.%  目的探讨子宫颈癌肿瘤组织中MAGE-A、NY-ESO-1的表达及与临床病理特征、预后关系。方法82例子宫颈癌患者分为两组。A组34例,FIGOⅠa1-Ⅰb1,接受根治性子宫切除术;B组48例,FIGOⅠb2-Ⅳa,接受新辅助化疗方案后行根治性子宫切除术。免疫组化法检测82例患者肿瘤组织中MAGE-A、NY-ESO-1的表达,并与患者临床病理特征及生存时间分析比较。结果 A组MAGE-A、NY-ESO-1阳性率分别为44.1%(15/34)和58.8%(20/34)。B

  6. Near Net Manufacturing Using Thin Gage Friction Stir Welding

    Science.gov (United States)

    Takeshita, Jennifer; Potter, David; Holquin, Michael

    2006-01-01

    Friction Stir Welding (FSW) and near net spin forming of FSW aluminumn blanks were investigated for large-scale pressure vessel applications. With a specific focus on very thin gage 2xxx and 7xxx aluminum alloys, the program concentrated on the following: the criteria used for material selection, a potential manufacturing flow, and the effectiveness and associated risks of near net spin forming. Discussion will include the mechanical properties of the friction stir welds and the parent material from before and after the spin forming process. This effort was performed under a NASA Space Exploration initiative focused on increasing the affordability, reliability and performance of pressure vessels larger than 10 ft. diameter.

  7. Development of buried wire gages for measurement of wall shear stress in Blastane experiments

    Science.gov (United States)

    Murthy, S. V.; Steinle, F. W.

    1986-01-01

    Buried Wire Gages operated from a Constant Temperature Anemometer System are among the special types of instrumentation to be used in the Boundary Layer Apparatus for Subsonic and Transonic flow Affected by Noise Environment (BLASTANE). These Gages are of a new type and need to be adapted for specific applications. Methods were developed to fabricate Gage inserts and mount those in the BLASTANE Instrumentation Plugs. A large number of Gages were prepared and operated from a Constant Temperature Anemometer System to derive some of the calibration constants for application to fluid-flow wall shear-stress measurements. The final stage of the calibration was defined, but could not be accomplished because of non-availability of a suitable flow simulating apparatus. This report provides a description of the Buried Wire Gage technique, an explanation of the method evolved for making proper Gages and the calibration constants, namely Temperature Coefficient of Resistance and Conduction Loss Factor.

  8. Prospective assessment of a gene signature potentially predictive of clinical benefit in metastatic melanoma patients following MAGE-A3 immunotherapeutic (PREDICT)

    Science.gov (United States)

    Saiag, P.; Gutzmer, R.; Ascierto, P. A.; Maio, M.; Grob, J.-J.; Murawa, P.; Dreno, B.; Ross, M.; Weber, J.; Hauschild, A.; Rutkowski, P.; Testori, A.; Levchenko, E.; Enk, A.; Misery, L.; Vanden Abeele, C.; Vojtek, I.; Peeters, O.; Brichard, V. G.; Therasse, P.

    2016-01-01

    Background Genomic profiling of tumor tissue may aid in identifying predictive or prognostic gene signatures (GS) in some cancers. Retrospective gene expression profiling of melanoma and non-small-cell lung cancer led to the characterization of a GS associated with clinical benefit, including improved overall survival (OS), following immunization with the MAGE-A3 immunotherapeutic. The goal of the present study was to prospectively evaluate the predictive value of the previously characterized GS. Patients and methods An open-label prospective phase II trial (‘PREDICT’) in patients with MAGE-A3-positive unresectable stage IIIB-C/IV-M1a melanoma. Results Of 123 subjects who received the MAGE-A3 immunotherapeutic, 71 (58.7%) displayed the predictive GS (GS+). The 1-year OS rate was 83.1%/83.3% in the GS+/GS− populations. The rate of progression-free survival at 12 months was 5.8%/4.1% in GS+/GS− patients. The median time-to-treatment failure was 2.7/2.4 months (GS+/GS−). There was one complete response (GS−) and two partial responses (GS+). The MAGE-A3 immunotherapeutic was similarly immunogenic in both populations and had a clinically acceptable safety profile. Conclusion Treatment of patients with MAGE-A3-positive unresectable stage IIIB-C/IV-M1a melanoma with the MAGE-A3 immunotherapeutic demonstrated an overall 1-year OS rate of 83.5%. GS− and GS+ patients had similar 1-year OS rates, indicating that in this study, GS was not predictive of outcome. Unexpectedly, the objective response rate was lower in this study than in other studies carried out in the same setting with the MAGE-A3 immunotherapeutic. Investigation of a GS to predict clinical benefit to adjuvant MAGE-A3 immunotherapeutic treatment is ongoing in another melanoma study. This study is registered at www.clinicatrials.gov NCT00942162. PMID:27502712

  9. THE COS-HALOS SURVEY: KECK LRIS AND MAGELLAN MagE OPTICAL SPECTROSCOPY

    Energy Technology Data Exchange (ETDEWEB)

    Werk, Jessica K.; Prochaska, J. Xavier [UCO/Lick Observatory, University of California, Santa Cruz, CA (United States); Thom, Christopher; Tumlinson, Jason [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD (United States); Tripp, Todd M.; Meiring, Joseph D. [Department of Astronomy, University of Massachusetts, Amherst, MA (United States); O' Meara, John M., E-mail: jwerk@ucolick.org [Department of Chemistry and Physics, Saint Michael' s College, Colchester, VT (United States)

    2012-01-01

    We present high signal-to-noise optical spectra for 67 low-redshift (0.1 < z < 0.4) galaxies that lie within close projected distances (5 kpc < {rho} < 150 kpc) of 38 background UV-bright QSOs. The Keck LRIS and Magellan MagE data presented here are part of a survey that aims to construct a statistically sampled map of the physical state and metallicity of gaseous galaxy halos using the Cosmic Origins Spectrograph (COS) on the Hubble Space Telescope. We provide a detailed description of the optical data reduction and subsequent spectral analysis that allow us to derive the physical properties of this uniquely data-rich sample of galaxies. The galaxy sample is divided into 38 pre-selected L {approx} L*, z {approx} 0.2 'target' galaxies and 29 'bonus' galaxies that lie in close proximity to the QSO sightlines. We report galaxy spectroscopic redshifts accurate to {+-}30 km s{sup -1}, impact parameters, rest-frame colors, stellar masses, total star formation rates (SFRs), and gas-phase interstellar medium oxygen abundances. When we compare the distribution of these galaxy characteristics to those of the general low-redshift population, we find good agreement. The L {approx} L* galaxies in this sample span a diverse range of color (1.0 < u - r < 3.0), stellar mass (10{sup 9.5} < M/M{sub Sun} < 10{sup 11.5}), and SFRs (0.01-20 M{sub Sun} yr{sup -1}). These optical data, along with the COS UV spectroscopy, comprise the backbone of our efforts to understand how halo gas properties may correlate with their host galaxy properties, and ultimately to uncover the processes that drive gas outflow and/or are influenced by gas inflow.

  10. In-situ shear stress indicator using heated strain gages at the flow boundary

    Science.gov (United States)

    Yeh, Chi-An; Yang, Fuling

    2011-11-01

    This work borrows the concept of hot-wire anemometry and sketch a technique that uses local heat transfer to infer the flow field and the corresponding stress. Conventional strain gages were mounted at the flow solid boundary as the heat source and acrylic boundary was chosen for its low thermal conductivity ensuring heat accumulation when a gage is energized. The gage would now work in slightly overheated state and its self-heating leads to an additional thermal strain. When exposed to a flow field, heat is brought away by local forced convection, resulting in deviations in gage signal from that developed in quiescent liquid. We have developed a facility to achieve synchronous gage measurements at different locations on a solid boundary. Three steady flow motions were considered: circular Couette flow, rectilinear uniform flow, and rectilinear oscillating flow. Preliminary tests show the gage reading does respond to the imposed flow through thermal effects and greater deviation was measured in flows of higher shear strain rates. The correlation between the gage signals and the imposed flow field is further examined by theoretical analysis. We also introduced a second solid boundary to the vicinity of the gage in the two rectilinear flows. The gage readings demonstrate rises in its magnitudes indicating wall amplification effect on the local shear strain, agreeing to the drag augmentation by a second solid boundary reported in many multiphase flow literatures.

  11. Field manual for the collection of Navajo Nation streamflow-gage data

    Science.gov (United States)

    Hart, Robert J.; Fisk, Gregory G.

    2014-01-01

    The Field Manual for the Collection of Navajo Nation Streamflow-Gage Data (Navajo Field Manual) is based on established (standard) U.S. Geological Survey streamflow-gaging methods and provides guidelines specifically designed for the Navajo Department of Water Resources personnel who establish and maintain streamflow gages. The Navajo Field Manual addresses field visits, including essential field equipment and the selection of and routine visits to streamflow-gaging stations, examines surveying methods for determining peak flows (indirect measurements), discusses safety considerations, and defines basic terms.

  12. Clinical implications of expression of MAGE-1 and NY-ESO-1 mRNAs in gastrointestinal stromal tumors%肿瘤-睾丸抗原MAGE-1和NY-ESO-1 mRNA在胃肠间质瘤中的表达

    Institute of Scientific and Technical Information of China (English)

    赖斌; 朱培谦; 朱胜昌; 罗洪亮

    2010-01-01

    目的:探讨肿瘤-睾丸抗原(CTA)MAGE-1和NY-ESO-1作为胃肠间质瘤(GISTs)免疫治疗特异性靶点及MAGE-1和NY-ESO-1 mRNA作为辅助GISTs危险度分级指标的可能性.及其与GISTs生物学行为的关系.方法:采用逆转录-聚合酶链反应(RT-PCR)技术,检测30例GISTs中MAGE-1和NY-ESO-1mRNA的表达,并取正常胃肠道组织作为阴性对照组,同时分析MAGE-1和NY-ESO-1mRNA表达与病理特征的关系.结果:正常对照组中无阳性表达,30例GISTs中,18例至少表达一种CTA,MAGE-1和NY-ESO-1 mRNA在GISTs中的表达率分别为30%和47%.MAGE-1和NY-ESO-1 mRNA表达与患者年龄、性别和病理类型无关,而与肿瘤生长部位、肿瘤大小及危险度分级有关(P0.05).结论:MAGE-1和NY-ESO-1 mRNA在GISTs中的高特异性表达,其抗原有望成为GISTs免疫治疗特异性的靶点:MAGE-1和NY-ESO-1 mRNA表达与GISTs危险度分级有关,MAGE-1和NY-ESO-1 mRNA有望成为辅助GISTs危险度分级的诊断指标.

  13. Non-clinical safety evaluation of single and repeated intramuscular administrations of MAGE-A3 Cancer Immunotherapeutic in rabbits and cynomolgus monkeys.

    Science.gov (United States)

    Destexhe, Eric; Grosdidier, Emilie; Baudson, Nathalie; Forster, Roy; Gerard, Catherine; Garçon, Nathalie; Segal, Lawrence

    2015-07-01

    The MAGE-A3 recombinant protein combined with AS15 immunostimulant (MAGE-A3 Cancer Immunotherapeutic) is under development by GlaxoSmithKline for the treatment of lung cancer and melanoma. We performed non-clinical safety studies evaluating potential local and systemic toxic effects induced by MAGE-A3 Cancer Immunotherapeutic in rabbits (study 1) and cynomolgus monkeys (study 2). Animals were allocated to two groups to receive a single (rabbits) or 25 repeated (every 2 weeks) injections (monkeys) of MAGE-A3 Cancer Immunotherapeutic (treatment groups) or saline (control groups). All rabbits were sacrificed 3 days post-injection and monkeys 3 days following last injection (3/5 per gender per group) or after a 3-month treatment-free period (2/5 per gender per group). Local and systemic reactions and MAGE-A3-specific immune responses (monkeys) were assessed. Macroscopic and microscopic (for rabbits, injection site only) post-mortem examinations were performed on all animals. No systemic toxicity or unscheduled mortalities were recorded. Single (rabbits) and repeated (monkeys; up to four times at the same site) injections were well tolerated. Following five to seven repeated injections, limb circumferences increased up to 26% (5 h post-injection), but returned to normal after 1-8 days. Three days after the last injection, enlargements of iliac, popliteal, axillary and inguinal lymph nodes, and increased incidence or severity of mononuclear inflammatory cell infiltrates was observed in injected muscles of treated monkeys. No treatment-related macroscopic findings were recorded after the treatment-free period. MAGE-A3-specific antibody and T-cell responses were raised in all treated monkeys, confirming test item exposure. Single or repeated intramuscular injections of MAGE-A3 Cancer Immunotherapeutic were well tolerated in rabbits and monkeys.

  14. Matilda Joslyn Gage: A Nineteenth-Century Women's Rights Historian Looks at Witchcraft.

    Science.gov (United States)

    Corey, Mary E.

    2003-01-01

    Explores the ideas of the nineteenth century female historian, Matilda Joslyn Gage, who authored the book, "Woman, Church, and State." Focuses on Gage's ideas about women's history, particularly related to the role of the church and women persecuted for witchcraft. (CMK)

  15. An evaluation of Idaho stream-gaging networks

    Science.gov (United States)

    Quillian, E.W.; Harenberg, W.A.

    1982-01-01

    Network Analysis for Regional Information (NARI) and the Cost-Effectiveness Procedure were tested by applying them to stream-gaging networks in Idaho. NARI was used to determine network design strategies that would maximize the value of additional data. Value of data was measured as the decrease in the probable true standards error of regional regression equations. NARI indicated that no significant decrease in regression error can be achieved by the collection of additional data and that better models should be sought. No major modifications to NARI are necessary to make it widely applicable. The Cost-Effectiveness Procedure was used to determine optimal network operation strategies. It showed network uncertainty can be reduced when six- or one-visit per year minimum constraints are in force. Sensitivity to various cost factors was examined. Attempts to model networks that included sites for collection of groundwater and water-quality data were unsuccessful. (USGS)

  16. Durability investigation of a group of strain gage pressure transducers

    Science.gov (United States)

    Lederer, P. S.; Hilten, J. S.

    1972-01-01

    A durability investigation was conducted on a group of eighteen bonded-wire strain gage pressure transducers with ranges of 0 to 15 psig and 0 to 100 psig using an improved version of a previously developed technique. Some of the transducers were subjected to 40 million pressure cycles at a 5-Hz rate at laboratory ambient conditions, others were cycled at a temperature of 150 F (65.6 C). The largest change in sensitivity observed was 0.22% for a 100-psig transducer subjected to 40 million pressure cycles at 150 F. The largest change in zero pressure output observed was 0.91% FS for the same transducer. None of the transducers failed completely as a result of cycling at or below full scale pressure.

  17. Simultaneous cytoplasmic and nuclear protein expression of melanoma antigen-A family and NY-ESO-1 cancer-testis antigens represents an independent marker for poor survival in head and neck cancer.

    Science.gov (United States)

    Laban, Simon; Atanackovic, Djordje; Luetkens, Tim; Knecht, Rainald; Busch, Chia-Jung; Freytag, Marcus; Spagnoli, Giulio; Ritter, Gerd; Hoffmann, Thomas K; Knuth, Alexander; Sauter, Guido; Wilczak, Waldemar; Blessmann, Marco; Borgmann, Kerstin; Muenscher, Adrian; Clauditz, Till S

    2014-09-01

    The prognosis of head and neck squamous cell carcinoma (HNSCC) patients remains poor. The identification of high-risk subgroups is needed for the development of custom-tailored therapies. The expression of cancer-testis antigens (CTAs) has been linked to a worse prognosis in other cancer types; however, their prognostic value in HNSCC is unclear because only few patients have been examined and data on CTA protein expression are sparse. A tissue microarray consisting of tumor samples from 453 HNSCC patients was evaluated for the expression of CTA proteins using immunohistochemistry. Frequency of expression and the subcellular expression pattern (nuclear, cytoplasmic, or both) was recorded. Protein expression of melanoma antigen (MAGE)-A family CTA, MAGE-C family CTA and NY-ESO-1 was found in approximately 30, 7 and 4% of tumors, respectively. The subcellular expression pattern in particular had a marked impact on the patients' prognosis. Median overall survival (OS) of patients with (i) simultaneous cytoplasmic and nuclear expression compared to (ii) either cytoplasmic or nuclear expression and (iii) negative patients was 23.0 versus 109.0 versus 102.5 months, for pan-MAGE (p < 0.0001), 46.6 versus 50.0 versus 109.0 for MAGE-A3/A4 (p = 0.0074) and 13.3 versus 50.0 versus 100.2 months for NY-ESO-1 (p = 0.0019). By multivariate analysis, these factors were confirmed as independent markers for poor survival. HNSCC patients showing protein expression of MAGE-A family members or NY-ESO-1 represent a subgroup with an extraordinarily poor survival. The development of immunotherapeutic strategies targeting these CTA may, therefore, be a promising approach to improve the outcome of HNSCC patients.

  18. 黑色素瘤抗原A家族与肿瘤的关系%Melanoma antigen-A family in tumor

    Institute of Scientific and Technical Information of China (English)

    丁春艳; 桑梅香

    2010-01-01

    As a tumor-specific antigen highly expressed in various types of tumors, MACE-A does not exist in normal adult tissues, except for testis and placenta. Therefore MAGE-A antigens are regarded. tumor specific antigen,and have significant significance for cancer immunotherapy.%黑色素瘤抗原A(MAGE-A)基因家族在正常人中除在睾丸和胎盘组织中有表达外,在其他组织中均不表达,而在许多恶性肿瘤组织中却呈高表达状态,被认为是一种肿瘤特异性抗原,在肿瘤免疫治疗中具有重要意义.

  19. Response of hot element wall shear stress gages in laminar oscillating flows

    Science.gov (United States)

    Cook, W. J.; Murphy, J. D.; Giddings, T. A.

    1986-01-01

    An experimental investigation of the time-dependent response of hot element wall shear stress gages in unsteady periodic air flows is reported. The study has focused on wall shear stress in laminar oscillating flows produced on a flat plate by a free stream velocity composed of a mean component and a superposed sinusoidal variation. Two types of hot element gages, platinum film and flush wire, were tested for values of reduced frequency ranging from 0.14 to 2.36. Values of the phase angle of the wall shear stress variation relative to the free stream velocity, as indicated by the hot element gages, are compared with numerical prediction. The comparisons show that the gages indicate a wall shear stress variation that lags the true variation, and that the gages will also not indicate the correct wall shear stress variation in periodic turbulent flows.

  20. High-Temperature Extensometry and PdCr Temperature-Compensated Wire Resistance Strain Gages Compared

    Science.gov (United States)

    1997-01-01

    A detailed experimental evaluation is underway at the NASA Lewis Research Center to compare and contrast the performance of the PdCr/Pt dual-element temperature-compensated wire resistance strain gage with that of conventional high-temperature extensometry. The advanced PdCr gage, developed by researchers at Lewis, exhibits desirable properties and a relatively small and repeatable apparent strain to 800 C. This gage represents a significant advance in technology because existing commercial resistance strain gages are not reliable for quasi-static strain measurements above approx. 400 C. Various thermal and mechanical loading spectra are being applied by a high-temperature thermomechanical uniaxial testing system to evaluate the two strain-measurement systems. This is being done not only to compare and contrast the two strain sensors, but also to investigate the applicability of the PdCr strain gage to the coupon-level specimen testing environment typically employed when the high-temperature mechanical behavior of structural materials is characterized. Strain measurement capabilities to 800 C are being investigated with a nickel-base superalloy, Inconel 100 (IN 100), substrate material and application to TMC's is being examined with the model system, SCS-6/Ti-15-3. Furthermore, two gage application techniques are being investigated in the comparison study: namely, flame-sprayed and spot welding. The apparent strain responses of both the weldable and flame-sprayed PdCr wire strain gages were found to be cyclically repeatable on both IN 100 and SCS-6/Ti-15-3 [0]_8. In general, each gage exhibited some uniqueness with respect to apparent strain behavior. Gages mounted on the IN 100 specimens tended to show a repeatable apparent strain within the first few cycles, because the thermal response of IN 100 was stable. This was not the case, however, for the TMC specimens, which typically required several thermal cycles to stabilize the thermal strain response. Thus

  1. Modèle d'aide à la gestion des eaux souterraines (MAGES). 2. Validation numérique du modèle de transport

    Science.gov (United States)

    Porel, Gilles; Delay, Frédérick; Banton, Olivier

    1998-11-01

    MAGES is a software developed at INRS-Eau (Canada) for forecasting pollution hazards in groundwater. The transport model uses stationary truncated temporal moment equations instead of the classical time dependent advection-dispersion equation. The aim of this work is to propose a numerical validation of the method by comparison with both analytical solutions in homogeneous medium and a sophisticated lagrangian model of transport in heterogeneous medium. It is shown that the temporal moment equations perform well, while saving on computation. This gives MAGES some abilities in water management problems which compensate for the poor knowledge of the transport parameters through numerous stochastic simulations.

  2. Drainage basin delineations for selected USGS streamflow-gaging stations in Virginia (Drainage_Basin)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — The Drainage_Basin polygon feature class was created as a digital representation of drainage basins for more than 1,650 continuous-record streamflow-gaging stations,...

  3. U.S. Geological Survey Stream Gages located in the Central Valley, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This digital dataset contains the locations of, and links to USGS gages on the surface-water network for the Central Valley Hydrologic Model (CVHM). The Central...

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

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

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

  5. Levels at Streamflow Gaging Stations--A CD-ROM Based Training Class

    Science.gov (United States)

    Nolan, K. Michael; Jacobson, Nathan; Erickson, Robert; Landon, Stanley

    2003-01-01

    Streamgages record the elevation of the water surface above some reference surface, or datum. This datum is assumed to remain unchanged throughout the life of the gage. However, the elevation of gages and their supporting structures often change over time as a result of earthmovement, floods, ice, and debris. The surveying practice of leveling is used to establish datum for new gage structures and to check for vertical movement of those structures over time. Vertical changes in gage structures can affect stage-discharge relations and, thus, could result in incorrect discharge determinations. Datum checks are used to correct stage-discharge relations and allow the USGS to document gage datum throughout the life of a gage. This training presentation describes methods currently used by the U.S. Geological Survey to run levels at gaging stations. The presentation is narrated, but you control the pace of the presentation. If the computer you are using can view 'MPEG' videos you will be able to take advantage of videos found within the presentation. A test, found at the end of the presentation, can be taken to assess how well you understood the training material. The class is registered as class SW1307 with the National Training Center of the U.S. Geologcial Survey. The presentation was developed using Macromedia Director 8.5(1) and is contained in the file 'WRI-4002.exe', which should auto-launch after the CD-ROM is inserted in the PC. The program only runs on a windows-based personal computer (PC). A sound card and speakers are necessary to take advantage of the narration that accompanies the presentation. Text of narrations is provided, if you are unable to listen to the narrations. Instructions for installing and running the presentation are included in the file ' Intro.html'. The file 'Intro.html' is on the CD-ROM containing the presentation and is available from the presentation's help menu.

  6. Vacuum gage calibration system for 10 to the minus 8th power to 10 torr

    Science.gov (United States)

    Holanda, R.

    1969-01-01

    Calibration system consists of a gas source, a source pressure gage, source volume, transfer volume and test chamber, plus appropriate piping, valves and vacuum source. It has been modified to cover as broad a range as possible while still providing accuracy and convenience.

  7. Nuclear Technology. Course 27: Metrology. Module 27-3, Gage Blocks, Mechanical Comparators and Electronic Comparators.

    Science.gov (United States)

    Selleck, Ben; Espy, John

    This third in a series of eight modules for a course titled Metrology describes gage blocks and mechanical and electronic comparators. The module follows a typical format that includes the following sections: (1) introduction, (2) module prerequisites, (3) objectives, (4) notes to instructor/student, (5) subject matter, (6) materials needed, (7)…

  8. Nuclear Technology. Course 27: Metrology. Module 27-2, Fixed Gages, Dividers, Calipers, and Micrometers.

    Science.gov (United States)

    Selleck, Ben; Espy, John

    This second in a series of eight modules for a course titled Metrology dscribes fixed gages, dividers, calipers, vernier and dial calipers, and micrometers. The module follows a typical format that includes the following sections: (l) introduction, (2) module prerequisites, (3) objectives, (4) notes to instructor/student, (5) subject matter, (6)…

  9. Cancer-testis antigen expression in digestive tract carcinomas: frequent expression in esophageal squamous cell carcinoma and its precursor lesions.

    Science.gov (United States)

    Chen, Yao-Tseng; Panarelli, Nicole C; Piotti, Kathryn C; Yantiss, Rhonda K

    2014-05-01

    Cancer-testis (CT) antigens are attractive tumor antigens for cancer immunotherapy. They comprise a group of proteins normally expressed in germ cells and aberrantly activated in a variety of human cancers. The protein expression of eight cancer-testis antigens [MAGEA, NY-ESO-1, GAGE, MAGEC1 (CT7), MAGEC2 (CT10), CT45, SAGE1, and NXF2] was evaluated by immunohistochemistry in 61 esophageal carcinomas (40 adenocarcinoma and 21 squamous cell carcinoma), 50 gastric carcinomas (34 diffuse and 16 intestinal type), and 141 colorectal carcinomas. The highest frequency of expression was found in esophageal squamous cell carcinomas: Positive staining for MAGEA, CT45, CT7, SAGE1, GAGE, NXF2, NY-ESO-1, and CT10 was observed in 57%, 38%, 33%, 33%, 29%, 29%, 19%, and 14% of squamous cell carcinomas, respectively. Similar staining patterns were observed in squamous dysplasias. Expression frequencies of cancer-testis antigens were seen in 2% to 24% of gastroesophageal adenocarcinomas and were not significantly different between adenocarcinomas of the stomach versus the esophagus, or between diffuse and intestinal types of gastric adenocarcinomas. Colorectal cancers did not express NY-ESO-1, CT7, CT10, or GAGE, and only infrequently expressed SAGE1 (0.7%) MAGEA (1.4%), CT45 (3.5%), and NXF2 (8.5%). We conclude that cancer-testis antigens are frequently expressed in esophageal squamous neoplasms. Although cancer-testis antigens are generally considered to be expressed later in tumor progression, they are found in squamous dysplasias, suggesting a potential diagnostic role for cancer-testis antigens in the evaluation of premalignant squamous lesions.

  10. Combined Load Diagram for a Wind Tunnel Strain-Gage Balance

    Science.gov (United States)

    Ulbrich, N.

    2010-01-01

    Combined Load Diagrams for Direct-Read, Force, and Moment Balances are discussed in great detail in the paper. The diagrams, if compared with a corresponding combined load plot of a balance calibration data set, may be used to visualize and interpret basic relationships between the applied balance calibration loads and the load components at the forward and aft gage of a strain-age balance. Lines of constant total force and moment are identified in the diagrams. In addition, the lines of pure force and pure moment are highlighted. Finally, lines of constant moment arm are depicted. It is also demonstrated that each quadrant of a Combined Load Diagram has specific regions where the applied total calibration force is at, between, or outside of the balance gage locations. Data from the manual calibration of a Force Balance is used to illustrate the application of a Combined Load Diagram to a realistic data set.

  11. High temperature static strain gage development contract, tasks 1 and 2

    Science.gov (United States)

    Hulse, C. O.; Bailey, R. S.; Grant, H. P.; Przybyszewski, J. S.

    1987-07-01

    Results are presented for the first two tasks to develop resistive strain gage systems for use up to 1250 K on blades and vanes in gas turbine engines under tests. The objective of these two tasks was to further improve and evaluate two static strain gage alloys identified as candidates in a previous program. Improved compositions were not found for either alloy. Further efforts on the Fe-11.9Al-10.6Cr weigth percent alloy were discontinued because of time dependent drift problems at 1250 K in air. When produced as a 6.5 micrometer thick sputtered film, the Pd-13Cr weight percent alloys is not sufficiently stable for this use in air at 1250 K and a protective overcoat system will need to be developed.

  12. Solar furnace for flux gage calibration and thermal-effects testing

    Science.gov (United States)

    Edgar, R. M.; Richards, E. H.; Mulholland, G. P.

    A solar furnace to calculate gauge flux and thermal effects was studied. The solar furnace consists of a 7.4 m square heliostat, a 6.7 m diameter concentrator, an attenuator designed to vary the flux density at the test area, and a three axis positioning table at the test area. Its primary function is the calibration of flux gages but other tasks and/or experiments will be considered as time permits.

  13. Design, analysis, and initial testing of a fiber-optic shear gage for three-dimensional, high-temperature flows

    Science.gov (United States)

    Orr, Matthew W.

    This investigation concerns the design, analysis, and initial testing of a new, two-component wall shear gage for 3D, high-temperature flows. This gage is a direct-measuring, non-nulling design with a round head surrounded by a small gap. Two flexure wheels are used to allow small motions of the floating head. Fiber-optic displacement sensors measure how far the polished faces of counterweights on the wheels move in relation to a fixed housing as the primary measurement system. No viscous damping was required. The gage has both fiber-optic instrumentation and strain gages mounted on the flexures for validation of the newer fiber optics. The sensor is constructed of Haynes RTM 230RTM, a high-temperature nickel alloy. The gage housing is made of 316 stainless steel. All components of the gage in pure fiber-optic form can survive to a temperature of 1073 K. The bonding methods of the backup strain gages limit their maximum temperature to 473 K. The dynamic range of the gage is from 0--500 Pa (0--10g) and higher shears can be measured by changing the floating head size. Extensive use of finite element modeling was critical to the design and analysis of the gage. Static structural, modal, and thermal analyses were performed on the flexures using the ANSYS finite element package. Static finite element analysis predicted the response of the flexures to a given load, and static calibrations using a direct force method confirmed these results. Finite element modal analysis results were within 16.4% for the first mode and within 30% for the second mode when compared with the experimentally determined modes. Vibration characteristics of the gage were determined from experimental free vibration data after the gage was subjected to an impulse. Uncertainties in the finished geometry make this level of error acceptable. A transient thermal analysis examined the effects of a very high heat flux on the exposed head of the gage. The 100,000 W/m2 heat flux used in this analysis is

  14. No major role for insulin-degrading enzyme in antigen presentation by MHC molecules.

    Directory of Open Access Journals (Sweden)

    Slobodan Culina

    Full Text Available Antigen presentation by MHC class I molecules requires degradation of epitope source proteins in the cytosol. Although the preeminent role of the proteasome is clearly established, evidence suggesting a significant role for proteasome-independent generation of class I ligands has been reported repeatedly. However, an enzyme responsible for such a role has not been identified. Recently insulin-degrading enzyme (IDE was shown to produce an antigenic peptide derived from the tumor antigen MAGE-A3 in an entirely proteasome-independent manner, raising the question of the global impact of IDE in MHC class I antigen processing. Here we report that IDE knockdown in human cell lines, or knockout in two different mouse strains, has no effect on cell surface expression of various MHC class I molecules, including allomorphs such as HLA-A3 and HLA-B27 suggested to be loaded in an at least a partly proteasome-independent manner. Moreover, reduced or absent IDE expression does not affect presentation of five epitopes including epitopes derived from beta amyloid and proinsulin, two preferred IDE substrates. Thus, IDE does not play a major role in MHC class I antigen processing, confirming the dominant and almost exclusive role of the proteasome in cytosolic production of MHC class I ligands.

  15. No major role for insulin-degrading enzyme in antigen presentation by MHC molecules.

    Science.gov (United States)

    Culina, Slobodan; Mauvais, François-Xavier; Hsu, Hsiang-Ting; Burgevin, Anne; Guénette, Suzanne; Moser, Anna; van Endert, Peter

    2014-01-01

    Antigen presentation by MHC class I molecules requires degradation of epitope source proteins in the cytosol. Although the preeminent role of the proteasome is clearly established, evidence suggesting a significant role for proteasome-independent generation of class I ligands has been reported repeatedly. However, an enzyme responsible for such a role has not been identified. Recently insulin-degrading enzyme (IDE) was shown to produce an antigenic peptide derived from the tumor antigen MAGE-A3 in an entirely proteasome-independent manner, raising the question of the global impact of IDE in MHC class I antigen processing. Here we report that IDE knockdown in human cell lines, or knockout in two different mouse strains, has no effect on cell surface expression of various MHC class I molecules, including allomorphs such as HLA-A3 and HLA-B27 suggested to be loaded in an at least a partly proteasome-independent manner. Moreover, reduced or absent IDE expression does not affect presentation of five epitopes including epitopes derived from beta amyloid and proinsulin, two preferred IDE substrates. Thus, IDE does not play a major role in MHC class I antigen processing, confirming the dominant and almost exclusive role of the proteasome in cytosolic production of MHC class I ligands.

  16. A New Load Residual Threshold Definition for the Evaluation of Wind Tunnel Strain-Gage Balance Data

    Science.gov (United States)

    Ulbrich, N.; Volden, T.

    2016-01-01

    A new definition of a threshold for the detection of load residual outliers of wind tunnel strain-gage balance data was developed. The new threshold is defined as the product between the inverse of the absolute value of the primary gage sensitivity and an empirical limit of the electrical outputs of a strain{gage. The empirical limit of the outputs is either 2.5 microV/V for balance calibration or check load residuals. A reduced limit of 0.5 microV/V is recommended for the evaluation of differences between repeat load points because, by design, the calculation of these differences removes errors in the residuals that are associated with the regression analysis of the data itself. The definition of the new threshold and different methods for the determination of the primary gage sensitivity are discussed. In addition, calibration data of a six-component force balance and a five-component semi-span balance are used to illustrate the application of the proposed new threshold definition to different types of strain{gage balances. During the discussion of the force balance example it is also explained how the estimated maximum expected output of a balance gage can be used to better understand results of the application of the new threshold definition.

  17. Detection of serum autoantibody against GAGE-7 in patients with esophageal squamous cell carcinoma%GAGE-7自身抗体在食管鳞状细胞癌中的表达

    Institute of Scientific and Technical Information of China (English)

    王皓; 钟理; 徐家馨; 张小刚; 王建飞

    2010-01-01

    目的:检测癌-睾丸抗原GAGE-7的自身抗体在食管鳞状细胞癌患者和正常人血清中表达的差异,评价GAGE家族作为肿瘤诊断标志物的可行性.方法:在原核细菌中表达并纯化重组GAGE-7蛋白.采用ELISA检测GAGE-7自身抗体在105份食管鳞状细胞癌患者血清和86份正常人血清中的表达水平.同时检测各血清中总IgG的表达量,计算GAGE-7自身抗体在总IgG中所占比例的差异.结果:血清中GAGE-7抗体在食管鳞状细胞癌中的含量与正常组比较差异显著(P<0.001),而GAGE-7抗体与总IgG比例,患者组明显高于正常组,逻辑回归模型分析c值为0.717,敏感性和特异性分别达到0.72和0.62,且差异显著(P<0.0001).结论:癌-睾丸抗原GAGE-7的自身抗体在食管鳞状细胞癌血清中有较高表达,且与正常组比较有显著差异,其表达特性可被看做是较为理想的癌症检测标志物.

  18. Rapid Binary Gage Function to Extract a Pulsed Signal Buried in Noise

    Directory of Open Access Journals (Sweden)

    Bagaria William J

    2004-01-01

    Full Text Available The type of signal studied in this paper is a periodic pulse, with the pulse length short compared to the period, and the signal is buried in noise. If standard techniques such as the fast Fourier transform are used to study the signal, the data record needs to be very long. Additionally, there would be a very large number of calculations. The rapid binary gage function was developed to quickly determine the period of the signal, and the start time of the first pulse in the data. Once these two parameters are determined, the pulsed signal can be recovered using a standard data folding and adding technique.

  19. Real-time PCR analysis of genes encoding tumor antigens in esophageal tumors and a cancer vaccine

    DEFF Research Database (Denmark)

    Weinert, Brian T; Krishnadath, Kausilia K; Milano, Francesca

    2009-01-01

    Tumor antigens are the primary target of therapeutic cancer vaccines. We set out to define and compare the expression pattern of tumor antigen genes in esophagus carcinoma biopsies and in an allogeneic tumor lysate-based cancer vaccine, MelCancerVac. Cells used for vaccine production were treated...... in the production of the vaccine. Quantitative PCR was used to assay 74 tumor antigen genes in patients with squamous cell carcinoma of the esophagus. 81% (13/16) of tumors expressed more than five cancer/testis (CT) antigens. A total of 96 genes were assayed in the tumor cell clone (DDM1.7) used to make tumor cell...... lysate for vaccine preparation. Gene expression in DDM1.7 cells was compared with three normal tissues; 16 tumor antigen genes were induced more than ten-fold relative to normal tissues. Treatment with 5-aza-CdR induced expression of an additional 15 tumor antigens to a total of 31. MAGE-A protein...

  20. MAGE (M-file/Mif Automatic GEnerator): A graphical interface tool for automatic generation of Object Oriented Micromagnetic Framework configuration files and Matlab scripts for results analysis

    Science.gov (United States)

    Chęciński, Jakub; Frankowski, Marek

    2016-10-01

    We present a tool for fully-automated generation of both simulations configuration files (Mif) and Matlab scripts for automated data analysis, dedicated for Object Oriented Micromagnetic Framework (OOMMF). We introduce extended graphical user interface (GUI) that allows for fast, error-proof and easy creation of Mifs, without any programming skills usually required for manual Mif writing necessary. With MAGE we provide OOMMF extensions for complementing it by mangetoresistance and spin-transfer-torque calculations, as well as local magnetization data selection for output. Our software allows for creation of advanced simulations conditions like simultaneous parameters sweeps and synchronic excitation application. Furthermore, since output of such simulation could be long and complicated we provide another GUI allowing for automated creation of Matlab scripts suitable for analysis of such data with Fourier and wavelet transforms as well as user-defined operations.

  1. Eosinofil Sel Penyaji Antigen

    Directory of Open Access Journals (Sweden)

    Safari Wahyu Jatmiko

    2015-04-01

    Full Text Available Sel eosinofil merupakan jenis sel lekosit yang terlibat dalam berbagai patogenesis penyakit. Sel eosinofil pada awalnya dikenal sebagai sel efektor  dari sistem imunitas alamiah. Akan tetapi, kemampuan sel eosinofil dalam memfagositosis patogen menimbulkan dugaan bahwa sel eosinofil ikut berperan sebagai sel penyaji antigen. Hal ini dianalogikan dengan sel makrofag dan sel dendritik yang bisa memfagositosis dan menyajikan antigen sebagai hasil dari degradasi patogen yang difagositosis. Untuk menjawab permasalahan ini, penulis melakukan penelusuran artikel tentang eosinofil sebagai sel penyaji antigen melalui US National Library of Medicine National Institute of Healthdengan kata kunci eoshinophil dan antigen presenting cell. Hasil penelusuran adalah ditemukannya 10 artikel yang relevan dengan topik. Hasil dari sintesis kesepuluh jurnal tersebut adalah sel eosinofil mampu berperan sebagai sel penyaji antigen yang profesional (professionalantigenpresentng cell

  2. A curvature based approach using long-gage fiber optic sensors

    Science.gov (United States)

    Kliewer, Kaitlyn; Glisic, Branko

    2016-04-01

    Fiber Bragg grating (FBG) sensors offer a significant advantage for structural health monitoring due to their ability to simultaneously monitor both static and dynamic strain while being durable, lightweight, capable of multiplexing, and immune to electro-magnetic interference. Drawing upon the benefits of FBG sensors, this research explores the use of a series of long-gage fiber optic sensors for damage detection of a structure through dynamic strain measurements and curvature analysis. Typically structural monitoring relies upon detecting structural changes through frequency and acceleration based analysis. However, curvature and strain based analysis may be a more reliable means for structural monitoring as they show more sensitivity to damage compared to modal parameters such as displacement mode shapes and natural frequency. Additionally, long gage FBG strain sensors offer a promising alternative to traditional dynamic measurement methods as the curvature can be computed directly from the FBG strain measurements without the need for numerical differentiation. Small scale experimental testing was performed using an aluminum beam instrumented with a series of FBG optical fiber sensors. Dynamic strain measurements were obtained as the aluminum beam was subjected to various loading and support conditions. From this, a novel normalized parameter based on the curvature from the dynamic strain measurements has been identified as a potential damage sensitive feature. Theoretical predictions and experimental data were compared and conclusions carried out. The results demonstrated the potential of the novel normalized parameter to facilitate dynamic monitoring at both the local and global scale, thus allowing assessment of the structures health.

  3. Les objets sous contrainte. Gages, saisies, confiscations, vols,pillages, recel au Moyen Âge

    Directory of Open Access Journals (Sweden)

    Laurent Feller

    2010-10-01

    Full Text Available Du jeudi 20 au samedi 21 novembre 2009, à l’initiative d’Ana Rodriguez et de Laurent Feller, s’est tenu à Auxerre, dans la maison du Coche d’Eau, un séminaire d’études international portant sur Les objets sous contrainte. Gages, saisies, confiscation, vol, pillage, recel au Moyen Âge. Organisée conjointement par le Lamop, l’université de Paris 1 et le CCHS (CSIC de Madrid, partiellement financée par un projet Picasso de l’association Égide, l’opération a bénéficié du soutien de l’université ...

  4. Review of Trackside Monitoring Solutions: From Strain Gages to Optical Fibre Sensors

    Directory of Open Access Journals (Sweden)

    Georges Kouroussis

    2015-08-01

    Full Text Available A review of recent research on structural monitoring in railway industry is proposed in this paper, with a special focus on stress-based solutions. After a brief analysis of the mechanical behaviour of ballasted railway tracks, an overview of the most common monitoring techniques is presented. A special attention is paid on strain gages and accelerometers for which the accurate mounting position on the track is requisite. These types of solution are then compared to another modern approach based on the use of optical fibres. Besides, an in-depth discussion is made on the evolution of numerical models that investigate the interaction between railway vehicles and tracks. These models are used to validate experimental devices and to predict the best location(s of the sensors. It is hoped that this review article will stimulate further research activities in this continuously expanding field.

  5. Assessment of the Uniqueness of Wind Tunnel Strain-Gage Balance Load Predictions

    Science.gov (United States)

    Ulbrich, N.

    2016-01-01

    A new test was developed to assess the uniqueness of wind tunnel strain-gage balance load predictions that are obtained from regression models of calibration data. The test helps balance users to gain confidence in load predictions of non-traditional balance designs. It also makes it possible to better evaluate load predictions of traditional balances that are not used as originally intended. The test works for both the Iterative and Non-Iterative Methods that are used in the aerospace testing community for the prediction of balance loads. It is based on the hypothesis that the total number of independently applied balance load components must always match the total number of independently measured bridge outputs or bridge output combinations. This hypothesis is supported by a control volume analysis of the inputs and outputs of a strain-gage balance. It is concluded from the control volume analysis that the loads and bridge outputs of a balance calibration data set must separately be tested for linear independence because it cannot always be guaranteed that a linearly independent load component set will result in linearly independent bridge output measurements. Simple linear math models for the loads and bridge outputs in combination with the variance inflation factor are used to test for linear independence. A highly unique and reversible mapping between the applied load component set and the measured bridge output set is guaranteed to exist if the maximum variance inflation factor of both sets is less than the literature recommended threshold of five. Data from the calibration of a six{component force balance is used to illustrate the application of the new test to real-world data.

  6. A Universal Threshold for the Assessment of Load and Output Residuals of Strain-Gage Balance Data

    Science.gov (United States)

    Ulbrich, N.; Volden, T.

    2017-01-01

    A new universal residual threshold for the detection of load and gage output residual outliers of wind tunnel strain{gage balance data was developed. The threshold works with both the Iterative and Non{Iterative Methods that are used in the aerospace testing community to analyze and process balance data. It also supports all known load and gage output formats that are traditionally used to describe balance data. The threshold's definition is based on an empirical electrical constant. First, the constant is used to construct a threshold for the assessment of gage output residuals. Then, the related threshold for the assessment of load residuals is obtained by multiplying the empirical electrical constant with the sum of the absolute values of all first partial derivatives of a given load component. The empirical constant equals 2.5 microV/V for the assessment of balance calibration or check load data residuals. A value of 0.5 microV/V is recommended for the evaluation of repeat point residuals because, by design, the calculation of these residuals removes errors that are associated with the regression analysis of the data itself. Data from a calibration of a six-component force balance is used to illustrate the application of the new threshold definitions to real{world balance calibration data.

  7. The effect of machining the gage section on Biaxial Tension/Shear plasticity experiments of DP780 sheet steel

    NARCIS (Netherlands)

    Walters, C.L.

    2013-01-01

    An experimental approach for determining the effect of machining the gage section of specimens for quasi-static, biaxial tension/shear testing of sheet steels is described. This method is demonstrated by comparing the results found by an existing testing method with a reduced thickness (Mohr and Osw

  8. Nuclear Technology. Course 27: Metrology. Module 27-4, Angle Measurement Instruments, Optical Projections and Surface Texture Gages.

    Science.gov (United States)

    Selleck, Ben; Espy, John

    This fourth in a series of eight modules for a course titled Metrology describes the universal bevel protractor and the sine bar, the engineering microscope and optical projector, and several types of surface texture gages. The module follows a typical format that includes the following sections: (1) introduction, (2) module prerequisites, (3)…

  9. The Brown Dwarf Kinematics Project (BDKP). IV. Radial Velocities of 85 Late-M and L dwarfs with MagE

    CERN Document Server

    Burgasser, Adam J; Gagne, Jonathan; Bochanski, John J; Faherty, Jaqueline K; West, Andrew A; Mamajek, Eric E; Schmidt, Sarah J; Cruz, Kelle L

    2015-01-01

    Radial velocity measurements are presented for 85 late M- and L-type very low mass stars and brown dwarfs obtained with the Magellan Echellette (MagE) spectrograph. Targets primarily have distances within 20 pc of the Sun, with more distant sources selected for their unusual spectral energy distributions. We achieved precisions of 2--3 km/s, and combined these with astrometric and spectrophotometric data to calculate $UVW$ velocities. Most are members of the thin disk of the Galaxy, and velocity dispersions indicate a mean age of 5.2$\\pm$0.2 Gyr for sources within 20 pc. We find significantly different kinematic ages between late-M dwarfs (4.0$\\pm$0.2 Gyr) and L dwarfs (6.5$\\pm$0.4 Gyr) in our sample that are contrary to predictions from prior simulations. This difference appears to be driven by a dispersed population of unusually blue L dwarfs which may be more prevalent in our local volume-limited sample than in deeper magnitude-limited surveys. The L dwarfs exhibit an asymmetric $U$ velocity distribution w...

  10. Proteomic profiling of triple-negative breast carcinomas in combination with a three-tier orthogonal technology approach identifies Mage-A4 as potential therapeutic target in estrogen receptor negative breast cancer

    DEFF Research Database (Denmark)

    Cabezón, Teresa; Gromova, Irina; Gromov, Pavel

    2013-01-01

    receptor 2 (Her2)-positive breast tumors. However, a significant proportion of primary breast cancers are negative for ER, progesterone receptor (PgR), and Her2, comprising the triple negative breast cancer (TNBC) group. Women with TNBC have a poor prognosis because of the aggressive nature of these tumors......-amenable sub-groups of TNBCs. We present here our results, including a large cumulative database of proteins based on the analysis of 78 TNBCs, and the identification and validation of one specific protein, Mage-A4, which was expressed in a significant fraction of TNBC and Her2-positive/ER negative lesions...... its presence in serum suggest novel management options for TNBC and human epidermal growth factor receptor 2 positive/estrogen receptor negative patients bearing Mage-A4 positive tumors....

  11. In situ measurements of atmospheric methane at GAGE/AGAGE sites during 1985-2000 and resulting source inferences

    Science.gov (United States)

    Cunnold, D. M.; Steele, L. P.; Fraser, P. J.; Simmonds, P. G.; Prinn, R. G.; Weiss, R. F.; Porter, L. W.; O'Doherty, S.; Langenfelds, R. L.; Krummel, P. B.; Wang, H. J.; Emmons, L.; Tie, X. X.; Dlugokencky, E. J.

    2002-07-01

    Continuous measurements of methane since 1986 at the Global Atmospherics Gases Experiment/Advanced Global Atmospherics Gases Experiment (GAGE/AGAGE) surface sites are described. The precisions range from approximately 10 ppb at Mace Head, Ireland, during GAGE to better than 2 ppb at Cape Grim, Tasmania, during AGAGE (i.e., since 1993). The measurements exhibit good agreement with coincident measurements of air samples from the same locations analyzed by Climate Monitoring and Diagnostics Laboratory (CMDL) except for differences of approximately 5 ppb before 1989 (GAGE lower) and about 4 ppb from 1991 to 1995 (GAGE higher). These results are obtained before applying a factor of 1.0119 to the GAGE/AGAGE values to place them on the Tohoku University scale. The measurements combined with a 12-box atmospheric model and an assumed atmospheric lifetime of 9.1 years indicates net annual emissions (emissions minus soil sinks) of 545 Tg CH4 with a variability of only +/-20 Tg from 1985 to 1997 but an increase in the emissions in 1998 of 37 +/- 10 Tg. The effect of OH changes inferred by Prinn et al. [2001] is to increase the estimated methane emissions by approximately 20 Tg in the mid-1980s and to reduce them by 20 Tg in 1997 and by more thereafter. Using a two-dimensional (2-D), 12-box model with transport constrained by the GAGE/AGAGE chlorofluorocarbon measurements, we calculate that the proportion of the emissions coming from the Northern Hemisphere is between 73 and 81%, depending on the OH distribution used. However, this result includes an adjustment of 5% derived from a simulation of the 2-D estimation procedure using the 3-D MOZART model. This adjustment is needed because of the very different spatial emission distributions of the chlorofluorocarbons and methane which makes chlorofluorocarbons derived transport rates inaccurate for the 2-D simulation of methane. The 2-D model combined with the annual cycle in OH from Spivakovsky et al. [2000] provide an acceptable

  12. Flexible Riser Monitoring Using Hybrid Magnetic/Optical Strain Gage Techniques through RLS Adaptive Filtering

    Directory of Open Access Journals (Sweden)

    Pipa Daniel

    2010-01-01

    Full Text Available Flexible riser is a class of flexible pipes which is used to connect subsea pipelines to floating offshore installations, such as FPSOs (floating production/storage/off-loading unit and SS (semisubmersible platforms, in oil and gas production. Flexible risers are multilayered pipes typically comprising an inner flexible metal carcass surrounded by polymer layers and spiral wound steel ligaments, also referred to as armor wires. Since these armor wires are made of steel, their magnetic properties are sensitive to the stress they are subjected to. By measuring their magnetic properties in a nonintrusive manner, it is possible to compare the stress in the armor wires, thus allowing the identification of damaged ones. However, one encounters several sources of noise when measuring electromagnetic properties contactlessly, such as movement between specimen and probe, and magnetic noise. This paper describes the development of a new technique for automatic monitoring of armor layers of flexible risers. The proposed approach aims to minimize these current uncertainties by combining electromagnetic measurements with optical strain gage data through a recursive least squares (RLSs adaptive filter.

  13. A stream-gaging network analysis for the 7-Day, 10-year annual low flow in New Hampshire streams

    Science.gov (United States)

    Flynn, Robert H.

    2003-01-01

    The 7-day, 10-year (7Q10) low-flow-frequency statistic is a widely used measure of surface-water availability in New Hampshire. Regression equations and basin-characteristic digital data sets were developed to help water-resource managers determine surface-water resources during periods of low flow in New Hampshire streams. These regression equations and data sets were developed to estimate streamflow statistics for the annual and seasonal low-flow-frequency, and period-of-record and seasonal period-of-record flow durations. generalized-least-squares (GLS) regression methods were used to develop the annual 7Q10 low-flow-frequency regression equation from 60 continuous-record stream-gaging stations in New Hampshire and in neighboring States. In the regression equation, the dependent variables were the annual 7Q10 flows at the 60 stream-gaging stations. The independent (or predictor) variables were objectively selected characteristics of the drainage basins that contribute flow to those stations. In contrast to ordinary-least-squares (OLS) regression analysis, GLS-developed estimating equations account for differences in length of record and spatial correlations among the flow-frequency statistics at the various stations. A total of 93 measurable drainage-basin characteristics were candidate independent variables. On the basis of several statistical parameters that were used to evaluate which combination of basin characteristics contribute the most to the predictive power of the equations, three drainage-basin characteristics were determined to be statistically significant predictors of the annual 7Q10: (1) total drainage area, (2) mean summer stream-gaging station precipitation from 1961 to 90, and (3) average mean annual basinwide temperature from 1961 to 1990. To evaluate the effectiveness of the stream-gaging network in providing regional streamflow data for the annual 7Q10, the computer program GLSNET (generalized-least-squares NETwork) was used to analyze the

  14. MAGE基因在肺癌疫苗研究进展%Research progress of MAGE gene in lung cancer vaccine

    Institute of Scientific and Technical Information of China (English)

    刘帮助; 刘超

    2012-01-01

    As the tumor to evade immune surveillance mechanism for the continuous in-depth research,immunotherapy has become a promising new method for treatment of cancer. One cancer vaccine as a tumor-specific active immunotherapy of lung cancer becomes a very attractive strategy of targeted therapy,especially for patients with completely resected adjuvant therapy. In recent years,cancer vaccines is the use of MAGE peptides,genes,and dendritic cells in patients with lung cancer,tumor immune response and mitigation have been observed in phase Ⅰ / Ⅱ clinical trials,and good clinical evaluation achieved.Ongoing international multi-center clinical study will demonstrate it.%随着对肿瘤逃避免疫监视机制研究的不断深入,免疫治疗已成为一种有希望治疗肿瘤的新方法.其中肿瘤疫苗作为肿瘤的特异性主动免疫治疗成为肺癌非常有吸引力的靶向治疗策略之一,尤其适用于完全切除术后患者的辅助治疗.近年来肿瘤疫苗是采用MAGE多肽、基因和树突状细胞等方法来免疫肺癌患者,在Ⅰ/Ⅱ期临床试验中已观察到免疫反应和肿瘤的缓解,并取得了较好的临床疗效评价.目前正在进行国际多中心临床研究进行论证.

  15. A preliminary biomechanical assessment of a polymer composite hip implant using an infrared thermography technique validated by strain gage measurements.

    Science.gov (United States)

    Bougherara, Habiba; Rahim, Ehsan; Shah, Suraj; Dubov, Anton; Schemitsch, Emil H; Zdero, Rad

    2011-07-01

    With the resurgence of composite materials in orthopaedic applications, a rigorous assessment of stress is needed to predict any failure of bone-implant systems. For current biomechanics research, strain gage measurements are employed to experimentally validate finite element models, which then characterize stress in the bone and implant. Our preliminary study experimentally validates a relatively new nondestructive testing technique for orthopaedic implants. Lock-in infrared (IR) thermography validated with strain gage measurements was used to investigate the stress and strain patterns in a novel composite hip implant made of carbon fiber reinforced polyamide 12 (CF/PA12). The hip implant was instrumented with strain gages and mechanically tested using average axial cyclic forces of 840 N, 1500 N, and 2100 N with the implant at an adduction angle of 15 deg to simulate the single-legged stance phase of walking gait. Three-dimensional surface stress maps were also obtained using an IR thermography camera. Results showed almost perfect agreement of IR thermography versus strain gage data with a Pearson correlation of R(2) = 0.96 and a slope = 1.01 for the line of best fit. IR thermography detected hip implant peak stresses on the inferior-medial side just distal to the neck region of 31.14 MPa (at 840 N), 72.16 MPa (at 1500 N), and 119.86 MPa (at 2100 N). There was strong correlation between IR thermography-measured stresses and force application level at key locations on the implant along the medial (R(2) = 0.99) and lateral (R(2) = 0.83 to 0.99) surface, as well as at the peak stress point (R(2) = 0.81 to 0.97). This is the first study to experimentally validate and demonstrate the use of lock-in IR thermography to obtain three-dimensional stress fields of an orthopaedic device manufactured from a composite material.

  16. Estimating Low-Flow Frequency Statistics and Hydrologic Analysis of Selected Streamflow-Gaging Stations, Nooksack River Basin, Northwestern Washington and Canada

    Science.gov (United States)

    Curran, Christopher A.; Olsen, Theresa D.

    2009-01-01

    Low-flow frequency statistics were computed at 17 continuous-record streamflow-gaging stations and 8 miscellaneous measurement sites in and near the Nooksack River basin in northwestern Washington and Canada, including the 1, 3, 7, 15, 30, and 60 consecutive-day low flows with recurrence intervals of 2 and 10 years. Using these low-flow statistics, 12 regional regression equations were developed for estimating the same low-flow statistics at ungaged sites in the Nooksack River basin using a weighted-least-squares method. Adjusted R2 (coefficient of determination) values for the equations ranged from 0.79 to 0.93 and the root-mean-squared error (RMSE) expressed as a percentage ranged from 77 to 560 percent. Streamflow records from six gaging stations located in mountain-stream or lowland-stream subbasins of the Nooksack River basin were analyzed to determine if any of the gaging stations could be removed from the network without significant loss of information. Using methods of hydrograph comparison, daily-value correlation, variable space, and flow-duration ratios, and other factors relating to individual subbasins, the six gaging stations were prioritized from most to least important as follows: Skookum Creek (12209490), Anderson Creek (12210900), Warm Creek (12207750), Fishtrap Creek (12212050), Racehorse Creek (12206900), and Clearwater Creek (12207850). The optimum streamflow-gaging station network would contain all gaging stations except Clearwater Creek, and the minimum network would include Skookum Creek and Anderson Creek.

  17. Internships and UNAVCO: Training the Future Geoscience Workforce Through the NSF GAGE Facility

    Science.gov (United States)

    Morris, A. R.; MacPherson-Krutsky, C. C.; Charlevoix, D. J.; Bartel, B. A.

    2015-12-01

    Facilities are uniquely positioned to both serve a broad, national audience and provide unique workforce experience to students and recent graduates. Intentional efforts dedicated to broadening participation in the future geoscience workforce at the NSF GAGE (Geodesy Advancing Geosciences and EarthScope) Facility operated by UNAVCO, are designed to meet the needs of the next generation of students and professionals. As a university-governed consortium facilitating research and education in the geosciences, UNAVCO is well-situated to both prepare students for geoscience technical careers and advanced research positions. Since 1998, UNAVCO has offered over 165 student assistant or intern positions including engineering, data services, education and outreach, and business support. UNAVCO offers three formal programs: the UNAVCO Student Internship Program (USIP), Research Experiences in Solid Earth Science for Students (RESESS), and the Geo-Launchpad (GLP) internship program. Interns range from community college students up through graduate students and recent Masters graduates. USIP interns gain real-world work experience in a professional setting, collaborate with teams toward a common mission, and contribute their knowledge, skills, and abilities to the UNAVCO community. RESESS interns conduct authentic research with a scientist in the Front Range area as well as participate in a structured professional development series. GLP students are in their first 2 years of higher education and work alongside UNAVCO technical staff gaining valuable work experience and insight into the logistics of supporting scientific research. UNAVCO's efforts in preparing the next generation of scientists largely focuses on increasing diversity in the geosciences, whether continuing academic studies or moving into the workforce. To date, well over half of our interns and student assistants come from backgrounds historically underrepresented in the geosciences. Over 80% of former interns

  18. Flight Test Results from the Rake Airflow Gage Experiment on the F-15B

    Science.gov (United States)

    Frederick, Michael; Ratnayake, Nalin

    2011-01-01

    The results are described of the Rake Airflow Gage Experiment (RAGE), which was designed and fabricated to support the flight test of a new supersonic inlet design using Dryden's Propulsion Flight Test Fixture (PFTF) and F-15B testbed airplane (see figure). The PFTF is a unique pylon that was developed for flight-testing propulsion-related experiments such as inlets, nozzles, and combustors over a range of subsonic and supersonic flight conditions. The objective of the RAGE program was to quantify the local flowfield at the aerodynamic interface plane of the Channeled Centerbody Inlet Experiment (CCIE). The CCIE is a fixed representation of a conceptual mixed-compression supersonic inlet with a translating biconic centerbody. The primary goal of RAGE was to identify the relationship between free-stream and local Mach number in the low supersonic regime, with emphasis on the identification of the particular free-stream Mach number that produced a local Mach number of 1.5. Measurements of the local flow angularity, total pressure distortion, and dynamic pressure over the interface plane were also desired. The experimental data for the RAGE program were obtained during two separate research flights. During both flights, local flowfield data were obtained during straight and level acceleration segments out to steady-state test points. The data obtained from the two flights showed small variations in Mach number, flow angularity, and dynamic pressure across the interface plane at all flight conditions. The data show that a free-stream Mach number of 1.65 will produce the desired local Mach number of 1.5 for CCIE. The local total pressure distortion over the interface plane at this condition was approximately 1.5%. At this condition, there was an average of nearly 2 of downwash over the interface plane. This small amount of downwash is not expected to adversely affect the performance of the CCIE inlet.

  19. Direct measurements of wall shear stress by buried wire gages in a shock-wave boundary-layer interaction region

    Science.gov (United States)

    Murthy, V. S.; Rose, W. C.

    1977-01-01

    Detailed measurements of wall shear stress (skin friction) were made with specially developed buried wire gages in the interaction regions of a Mach 2.9 turbulent boundary layer with externally generated shocks. Separation and reattachment points inferred by these measurements support the findings of earlier experiments which used a surface oil flow technique and pitot profile measurements. The measurements further indicate that the boundary layer tends to attain significantly higher skin-friction values downstream of the interaction region as compared to upstream. Comparisons between measured wall shear stress and published results of some theoretical calculation schemes show that the general, but not detailed, behavior is predicted well by such schemes.

  20. Force Reconstruction from Ejection Tests of Stores from Aircraft Used for Model Predictions and Missing/Bad Gages

    Energy Technology Data Exchange (ETDEWEB)

    Ross, Michael; Cap, Jerome S.; Starr, Michael J.; Urbina, Angel; Brink, Adam Ray

    2015-12-01

    One of the more severe environments for a store on an aircraft is during the ejection of the store. During this environment it is not possible to instrument all component responses, and it is also likely that some instruments may fail during the environment testing. This work provides a method for developing these responses from failed gages and uninstrumented locations. First, the forces observed by the store during the environment are reconstructed. A simple sampling method is used to reconstruct these forces given various parameters. Then, these forces are applied to a model to generate the component responses. Validation is performed on this methodology.

  1. 电阻应变计用UV胶盖面方案浅析%Shallowly talking about using spraying UV cured resin to encapsulate the stain gage

    Institute of Scientific and Technical Information of China (English)

    梁昌锐

    2012-01-01

    Nowadays when people produce resistance strain gages, the encapsulating process is very complex, and to cure the encapsulating resin using the clip will produce internal stress, will take a long time to be released. Our new concept using spraying UV cured resin to encapsulate the strain gage facilitates the automation of production, not only greatly enhance the production efficiency, reduce the cost, but also can reduce the internal stress of the strain gage. Choosing good UV cured resin can also improve the protective performance of the encapsulated strain gage, improve the quality of strain gage.%现在生产电阻应变计盖面时工艺很复杂,而且固化时要上夹子会产生应力,需要一定的时日才能释放出来,新概念改用喷Uv胶的方法盖面,便于自动化大生产,不仅大大提高了生产效率,降低了成本,还可以减小盖面时应变计的内部应力,选择良好的Uv胶还可以改进盖面胶的防护性能,提高应变计的质量。

  2. Antigen antibody interactions

    CERN Document Server

    DeLisi, Charles

    1976-01-01

    1. 1 Organization of the Immune System One of the most important survival mechanisms of vertebrates is their ability to recognize and respond to the onslaught of pathogenic microbes to which they are conti- ously exposed. The collection of host cells and molecules involved in this recognition­ 12 response function constitutes its immune system. In man, it comprises about 10 cells 20 (lymphocytes) and 10 molecules (immunoglobulins). Its ontogenic development is c- strained by the requirement that it be capable of responding to an almost limitless variety of molecular configurations on foreign substances, while simultaneously remaining inert to those on self components. It has thus evolved to discriminate, with exquisite precision, between molecular patterns. The foreign substances which induce a response, called antigens, are typically large molecules such as proteins and polysaccharides. The portions of these with which immunoglobulins interact are called epitopes or determinants. A typical protein epitope m...

  3. Antigenic Variation in Bacterial Pathogens.

    Science.gov (United States)

    Palmer, Guy H; Bankhead, Troy; Seifert, H Steven

    2016-02-01

    Antigenic variation is a strategy used by a broad diversity of microbial pathogens to persist within the mammalian host. Whereas viruses make use of a minimal proofreading capacity combined with large amounts of progeny to use random mutation for variant generation, antigenically variant bacteria have evolved mechanisms which use a stable genome, which aids in protecting the fitness of the progeny. Here, three well-characterized and highly antigenically variant bacterial pathogens are discussed: Anaplasma, Borrelia, and Neisseria. These three pathogens display a variety of mechanisms used to create the structural and antigenic variation needed for immune escape and long-term persistence. Intrahost antigenic variation is the focus; however, the role of these immune escape mechanisms at the population level is also presented.

  4. Radioimmunoassays of hidden viral antigens

    Energy Technology Data Exchange (ETDEWEB)

    Neurath, A.R. (Lindsley F. Kimbell Research Inst., New York, NY); Strick, N.; Baker, L.; Krugman, S.

    1982-07-01

    Antigens corresponding to infectious agents may be present in biological specimens only in a cryptic form bound to antibodies and, thus, may elude detection. We describe a solid-phase technique for separation of antigens from antibodies. Immune complexes are precipitated from serum by polyethylene glycol, dissociated with NaSCN, and adsorbed onto nitrocellulose or polystyrene supports. Antigens remain topographically separated from antibodies after removal of NaSCN and can be detected with radiolabeled antibodies. Genomes from viruses immobilized on nitrocellulose can be identified by nucleic acid hybridization. Nanogram quantities of sequestered hepatitis B surface and core antigens and picogram amounts of hepatitis B virus DNA were detected. Antibody-bound adenovirus, herpesvirus, and measles virus antigens were discerned by the procedure.

  5. Radioimmunoassays of hidden viral antigens.

    Science.gov (United States)

    Neurath, A R; Strick, N; Baker, L; Krugman, S

    1982-01-01

    Antigens corresponding to infectious agents may be present in biological specimens only in a cryptic form bound to antibodies and, thus, may elude detection. We describe a solid phase technique for separation of antigens from antibodies. Immune complexes are precipitated from serum by polyethylene glycol, dissociated with NaSCN, and adsorbed onto nitrocellulose or polystyrene supports. Antigens remain topographically separated from antibodies after removal of NaSCN and can be detected with radiolabeled antibodies. Genomes from viruses immobilized on nitrocellulose can be identified by nucleic acid hybridization. Nanogram quantities of sequestered hepatitis B surface and core antigens and picogram amounts of hepatitis B virus DNA were detected. Antibody-bond adenovirus, herpesvirus, and measles virus antigens were discerned by the procedure. Images PMID:6956871

  6. COLONOSCOPY AND CARCINOEMBRYONIC ANTIGEN VARIATIONS

    Directory of Open Access Journals (Sweden)

    Rita G SOUSA

    2014-03-01

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

  7. Reliability analysis of forty-five strain-gage systems mounted on the first fan stage of a YF-100 engine

    Science.gov (United States)

    Holanda, R.; Frause, L. M.

    1977-01-01

    The reliability of 45 state-of-the-art strain gage systems under full scale engine testing was investigated. The flame spray process was used to install 23 systems on the first fan rotor of a YF-100 engine; the others were epoxy cemented. A total of 56 percent of the systems failed in 11 hours of engine operation. Flame spray system failures were primarily due to high gage resistance, probably caused by high stress levels. Epoxy system failures were principally erosion failures, but only on the concave side of the blade. Lead-wire failures between the blade-to-disk jump and the control room could not be analyzed.

  8. Expression mechanism regulation and related applications of melanoma associated antigen A3 gene in the cancer%黑色素瘤相关抗原A3基因在肿瘤中的表达、机制调控及相关应用

    Institute of Scientific and Technical Information of China (English)

    李宁; 吉晓滨

    2016-01-01

    黑色素瘤相关抗原A3(melanoma-associated antigen A3,MAGE-A3)表达于多种恶性肿瘤,而在正常组织中不表达(除睾丸和胎盘外),具有肿瘤特异性,也是肿瘤特异性免疫治疗的理想靶点。在恶性肿瘤中MAGE-A3表达调控机制尚不明确,通过基因甲基化/脱甲基化、抑制抑癌基因p53的转录活性、调控caspase作用、作为靶基因接受成纤维细胞生长因子受体2信号通路的作用等,使其发挥生物学功能。未来,利用其制备多基因联合修饰的肿瘤基因工程疫苗,精确地诊断、判断预后,并且在肿瘤疾病中做功能性靶向治疗等值得期待。本文就黑色素瘤相关抗原A3基因在肿瘤中的表达、机制调控及相关应用进行综述。%The melanoma associated antigen A3(MAGE-A3) is expressed in various types of malignant tumors,but not in normal cells except testis and placenta,with tumor specificity.It has been recognized as an ideal target for specific immunotherapy because which the antigen can cause specific immune to MAGE-A3 positive tumor cells in vivo. The regulation mechanism of MAGE-A3 expression is still undeifned in malignant tumor, through methylation/demethylation of gene,inhibition of Transcriptional activity of tumor suppressor gene p53, functionary regulation of the caspase,and acception to the role of signaling pathways of ifbroblast growth factor receptor 2 (FGRF2) as a target gene,etc,make its biological functions. In the future, by use of MAGE-A3,tumor genetic engineering vaccine modiifed federatively by multiple gene is going to be prepared,accurate diagnosis and prognosis judgement are going to be realized,and functional targeted therapy of tumor disease is worth expectation. In this paper, reviewed the expression, mechanism of regulation and related application of the melanoma antigen A3 gene in tumor.

  9. Oncogenic cancer/testis antigens

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  10. The development of a bearing spectral analyzer and algorithms to detect turbopump bearing wear from deflectometer and strain gage data

    Science.gov (United States)

    Martinez, Carol L.

    1992-07-01

    Over the last several years, Rocketdyne has actively developed condition and health monitoring techniques and their elements for rocket engine components, specifically high pressure turbopumps. Of key interest is the development of bearing signature analysis systems for real-time monitoring of the cryogen-cooled turbopump shaft bearings, which spin at speeds up to 36,000 RPM. These system elements include advanced bearing vibration sensors, signal processing techniques, wear mode algorithms, and integrated control software. Results of development efforts in the areas of signal processing and wear mode identification and quantification algorithms based on strain gage and deflectometer data are presented. Wear modes investigated include: inner race wear, cage pocket wear, outer race wear, differential ball wear, cracked inner race, and nominal wear.

  11. Evaluating a slope-stability model for shallow rain-induced landslides using gage and satellite data

    Science.gov (United States)

    Yatheendradas, S.; Kirschbaum, D.; Baum, Rex L.; Godt, Jonathan W.

    2014-01-01

    Improving prediction of landslide early warning systems requires accurate estimation of the conditions that trigger slope failures. This study tested a slope-stability model for shallow rainfall-induced landslides by utilizing rainfall information from gauge and satellite records. We used the TRIGRS model (Transient Rainfall Infiltration and Grid-based Regional Slope-stability analysis) for simulating the evolution of the factor of safety due to rainfall infiltration. Using a spatial subset of a well-characterized digital landscape from an earlier study, we considered shallow failure on a slope adjoining an urban transportation roadway near the Seattle area in Washington, USA.We ran the TRIGRS model using high-quality rain gage and satellite-based rainfall data from the Tropical Rainfall Measuring Mission (TRMM). Preliminary results with parameterized soil depth values suggest that the steeper slope values in this spatial domain have factor of safety values that are extremely close to the failure limit within an extremely narrow range of values, providing multiple false alarms. When the soil depths were constrained using a back analysis procedure to ensure that slopes were stable under initial condtions, the model accurately predicted the timing and location of the landslide observation without false alarms over time for gage rain data. The TRMM satellite rainfall data did not show adequately retreived rainfall peak magnitudes and accumulation over the study period, and as a result failed to predict the landslide event. These preliminary results indicate that more accurate and higher-resolution rain data (e.g., the upcoming Global Precipitation Measurement (GPM) mission) are required to provide accurate and reliable landslide predictions in ungaged basins.

  12. Bayesian WLS/GLS regression for regional skewness analysis for regions with large crest stage gage networks

    Science.gov (United States)

    Veilleux, Andrea G.; Stedinger, Jery R.; Eash, David A.

    2012-01-01

    This paper summarizes methodological advances in regional log-space skewness analyses that support flood-frequency analysis with the log Pearson Type III (LP3) distribution. A Bayesian Weighted Least Squares/Generalized Least Squares (B-WLS/B-GLS) methodology that relates observed skewness coefficient estimators to basin characteristics in conjunction with diagnostic statistics represents an extension of the previously developed B-GLS methodology. B-WLS/B-GLS has been shown to be effective in two California studies. B-WLS/B-GLS uses B-WLS to generate stable estimators of model parameters and B-GLS to estimate the precision of those B-WLS regression parameters, as well as the precision of the model. The study described here employs this methodology to develop a regional skewness model for the State of Iowa. To provide cost effective peak-flow data for smaller drainage basins in Iowa, the U.S. Geological Survey operates a large network of crest stage gages (CSGs) that only record flow values above an identified recording threshold (thus producing a censored data record). CSGs are different from continuous-record gages, which record almost all flow values and have been used in previous B-GLS and B-WLS/B-GLS regional skewness studies. The complexity of analyzing a large CSG network is addressed by using the B-WLS/B-GLS framework along with the Expected Moments Algorithm (EMA). Because EMA allows for the censoring of low outliers, as well as the use of estimated interval discharges for missing, censored, and historic data, it complicates the calculations of effective record length (and effective concurrent record length) used to describe the precision of sample estimators because the peak discharges are no longer solely represented by single values. Thus new record length calculations were developed. The regional skewness analysis for the State of Iowa illustrates the value of the new B-WLS/BGLS methodology with these new extensions.

  13. Influence of the Testing Gage Length on the Strength, Young's Modulus and Weibull Modulus of Carbon Fibres and Glass Fibres

    Directory of Open Access Journals (Sweden)

    Luiz Claudio Pardini

    2002-10-01

    Full Text Available Carbon fibres and glass fibres are reinforcements for advanced composites and the fiber strength is the most influential factor on the strength of the composites. They are essentially brittle and fail with very little reduction in cross section. Composites made with these fibres are characterized by a high strength/density ratio and their properties are intrisically related to their microstructure, i.e., amount and orientation of the fibres, surface treatment, among other factors. Processing parameters have an important role in the fibre mechanical behaviour (strength and modulus. Cracks, voids and impurities in the case of glass fibres and fibrillar misalignments in the case of carbon fibres are created during processing. Such inhomogeneities give rise to an appreciable scatter in properties. The most used statistical tool that deals with this characteristic variability in properties is the Weibull distribution. The present work investigates the influence of the testing gage length on the strength, Young's modulus and Weibull modulus of carbon fibres and glass fibres. The Young's modulus is calculated by two methods: (i ASTM D 3379M, and (ii interaction between testing equipment/specimen The first method resulted in a Young modulus of 183 GPa for carbon fibre, and 76 GPa for glass fibre. The second method gave a Young modulus of 250 GPa for carbon fibre and 50 GPa for glass fibre. These differences revelead differences on how the interaction specimen/testing machine can interfere in the Young modulus calculations. Weibull modulus can be a tool to evaluate the fibre's homogeneity in terms of properties and it is a good quality control parameter during processing. In the range of specimen gage length tested the Weibull modulus for carbon fibre is ~ 3.30 and for glass fibres is ~ 5.65, which indicates that for the batch of fibres tested, the glass fibre is more uniform in properties.

  14. SSX2-4 expression in early-stage non-small cell lung cancer

    DEFF Research Database (Denmark)

    Greve, K B V; Pøhl, M; Olsen, K E

    2014-01-01

    The expression of cancer/testis antigens SSX2, SSX3, and SSX4 in non-small cell lung cancers (NSCLC) was examined, since they are considered promising targets for cancer immunotherapy due to their immunogenicity and testis-restricted normal tissue expression. We characterized three SSX antibodies...... was only detected in 5 of 143 early-stage NSCLCs, which is rare compared to other cancer/testis antigens (e.g. MAGE-A and GAGE). However, further studies are needed to determine whether SSX can be used as a prognostic or predictive biomarker in NSCLC....

  15. Actes du séminaire européen 'Syndicats, chômage et exclusion sociale' / Proceedings of the European seminar 'Trade unions, unemployment and social exclusion

    OpenAIRE

    1995-01-01

    Les syndicats européens sont engagés dans bon nombre de projets et d’actions de lutte contre l’exclusion du marché du travail. Certains d’entre eux ont constitué, sous l’impulsion de la Confédération européenne des Syndicats, le réseau ‘Syndicats contre l’exclusion’. Ce séminaire a permis aux acteurs de présenter les différents aspects du travail engagé (conseil, formation, création d’entreprises d’insertion, plans locaux de développement, politique générale de lutte contre le chômage...), de...

  16. Streamflow characteristics based on data through water year 2009 for selected streamflow-gaging stations in or near Montana: Chapter E in Montana StreamStats

    Science.gov (United States)

    McCarthy, Peter M.

    2016-04-05

    Chapter E of this Scientific Investigations Report documents results from a study by the U.S. Geological Survey, in cooperation with the Montana Department of Environmental Quality and the Montana Department of Natural Resources and Conservation, to provide an update of statewide streamflow characteristics based on data through water year 2009 for streamflow-gaging stations in or near Montana. Streamflow characteristics are presented for 408 streamflow-gaging stations in Montana and adjacent areas having 10 or more years of record. Data include the magnitude and probability of annual low and high streamflow, the magnitude and probability of low streamflow for three seasons (March–June, July–October, and November–February), streamflow duration statistics for monthly and annual periods, and mean streamflows for monthly and annual periods. Streamflow is considered to be regulated at streamflow-gaging stations where dams or other large-scale human modifications affect 20 percent or more of the contributing drainage basin. Separate streamflow characteristics are presented for the unregulated and regulated periods of record for streamflow-gaging stations with sufficient data.

  17. Quantification of uncertainties in the 100-year flow at an ungaged site near a gaged station and its application in Georgia

    Science.gov (United States)

    Cho, Huidae; Bones, Emma

    2016-08-01

    The Federal Emergency Management Agency has introduced the concept of the "1-percent plus" flow to incorporate various uncertainties in estimation of the 100-year or 1-percent flow. However, to the best of the authors' knowledge, no clear directions for calculating the 1-percent plus flow have been defined in the literature. Although information about standard errors of estimation and prediction is provided along with the regression equations that are often used to estimate the 1-percent flow at ungaged sites, uncertainty estimation becomes more complicated when there is a nearby gaged station because regression flows and the peak flow estimate from a gage analysis should be weighted to compute the weighted estimate of the 1-percent flow. In this study, an equation for calculating the 1-percent plus flow at an ungaged site near a gaged station is analytically derived. Also, a detailed process is introduced for calculating the 1-percent plus flow for an ungaged site near a gaged station in Georgia as an example and a case study is performed. This study provides engineers and practitioners with a method that helps them better assess flood risks and develop mitigation plans accordingly.

  18. Flood of April 2007 and Flood-Frequency Estimates at Streamflow-Gaging Stations in Western Connecticut

    Science.gov (United States)

    Ahearn, Elizabeth A.

    2009-01-01

    A spring nor'easter affected the East Coast of the United States from April 15 to 18, 2007. In Connecticut, rainfall varied from 3 inches to more than 7 inches. The combined effects of heavy rainfall over a short duration, high winds, and high tides led to widespread flooding, storm damage, power outages, evacuations, and disruptions to traffic and commerce. The storm caused at least 18 fatalities (none in Connecticut). A Presidential Disaster Declaration was issued on May 11, 2007, for two counties in western Connecticut - Fairfield and Litchfield. This report documents hydrologic and meteorologic aspects of the April 2007 flood and includes estimates of the magnitude of the peak discharges and peak stages during the flood at 28 streamflow-gaging stations in western Connecticut. These data were used to perform flood-frequency analyses. Flood-frequency estimates provided in this report are expressed in terms of exceedance probabilities (the probability of a flood reaching or exceeding a particular magnitude in any year). Flood-frequency estimates for the 0.50, 0.20, 0.10, 0.04, 0.02, 0.01, and 0.002 exceedance probabilities (also expressed as 50-, 20-, 10-, 4-, 2-, 1-, and 0.2- percent exceedance probability, respectively) were computed for 24 of the 28 streamflow-gaging stations. Exceedance probabilities can further be expressed in terms of recurrence intervals (2-, 5-, 10-, 25-, 50-, 100-, and 500-year recurrence interval, respectively). Flood-frequency estimates computed in this study were compared to the flood-frequency estimates used to derive the water-surface profiles in previously published Federal Emergency Management Agency (FEMA) Flood Insurance Studies. The estimates in this report update and supersede previously published flood-frequency estimates for streamflowgaging stations in Connecticut by incorporating additional years of annual peak discharges, including the peaks for the April 2007 flood. In the southwest coastal region of Connecticut, the

  19. Concepts and applications for influenza antigenic cartography

    Science.gov (United States)

    Cai, Zhipeng; Zhang, Tong; Wan, Xiu-Feng

    2011-01-01

    Influenza antigenic cartography projects influenza antigens into a two or three dimensional map based on immunological datasets, such as hemagglutination inhibition and microneutralization assays. A robust antigenic cartography can facilitate influenza vaccine strain selection since the antigenic map can simplify data interpretation through intuitive antigenic map. However, antigenic cartography construction is not trivial due to the challenging features embedded in the immunological data, such as data incompleteness, high noises, and low reactors. To overcome these challenges, we developed a computational method, temporal Matrix Completion-Multidimensional Scaling (MC-MDS), by adapting the low rank MC concept from the movie recommendation system in Netflix and the MDS method from geographic cartography construction. The application on H3N2 and 2009 pandemic H1N1 influenza A viruses demonstrates that temporal MC-MDS is effective and efficient in constructing influenza antigenic cartography. The web sever is available at http://sysbio.cvm.msstate.edu/AntigenMap. PMID:21761589

  20. Hydrography - HYDROGRAPHY_HIGHRES_POINT_NHD_USGS: Gaging Stations, Gates, Lock Chambers, Reservoirs, Springs, Seeps, Sinks, Rises, Waterfalls, and Wells in Watersheds of Indiana (U.S. Geological Survey, 1:24,000, Point Shapefile)

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — HYDROGRAPHY_HIGHRES_POINT_NHD_USGS.SHP is a point shapefile that contains locations of gaging stations, gates, lock chambers, reservoirs, springs, seeps, sinks,...

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

    Science.gov (United States)

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

    2016-01-13

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

  2. THE LYMPH SELF ANTIGEN REPERTOIRE

    Directory of Open Access Journals (Sweden)

    Laura eSantambrogio

    2013-12-01

    Full Text Available The lymphatic fluid originates from the interstitial fluid which bathes every parenchymal organ and reflects the omic composition of the tissue from which it originates in its physiological or pathological signature. Several recent proteomic analyses have mapped the proteome-degradome and peptidome of this immunologically relevant fluid pointing to the lymph as an important source of tissue-derived self-antigens. A vast array of lymph-circulating peptides have been mapped deriving from a variety of processing pathways including caspases, cathepsins, MMPs, ADAMs, kallikreins, calpains and granzymes, among others. These self peptides can be directly loaded on circulatory dendritic cells and expand the self-antigenic repertoire available for central and peripheral tolerance.

  3. Bacterial phospholipide antigens and their taxonomic significance.

    Science.gov (United States)

    Karalnik, B V; Razbash, M P; Akhmetova, E A

    1981-01-01

    The investigation of interrelationships between the phospholipides of various microorganisms (33 strains of corynebacteria, mycobacteria and staphylococci) using crossed antibody neutralization reactions with phospholipide antigenic erythrocyte diagnostic was used for the assessment of the degree of antigenic propinquity and antigenic differences between the phospholipides of bacteria of the same species, genus, and of different genera. The role of the determinants of the corresponding (their own) and "foreign" genera in the antigenic differences between the phospholipides of the microorganisms investigated was established. On the basis of the results obtained the conclusion has been drawn that the method of assessment of antigenic interrelationships between phospholipides can be used for the study of some taxonomic problems.

  4. [HLA antigens in juvenile rheumatoid arthritis].

    Science.gov (United States)

    Rumba, I V; Sochnev, A M; Kukaĭne, E M; Burshteĭn, A M; Benevolenskaia, L I

    1990-01-01

    Antigens of I class HLA system (locus A and B) were investigated in 67 patients of Latvian nationality suffering from juvenile rheumatoid arthritis (JRA). Associations of HLA antigens with juvenile rheumatoid arthritis partially coincided with the ones revealed earlier. Typing established an increased incidence of antigen B27 (p less than 0.01) and gaplotype A2, B40 (p less than 0.01). Antigen B15 possessed a protective action with respect to JRA. Interlocus combinations demonstrated a closer association with the disease than a single antigen. The authors also revealed markers of various clinico-anatomical variants of JRA.

  5. Merenje torzionih oscilacija pomoću mernih traka / Measurement of torsional vibrations by using strain gages

    Directory of Open Access Journals (Sweden)

    Dragan Trifković

    2005-05-01

    Full Text Available U ovom radu prikazan je metod merenja torzionih oscilacija mehaničkih sistema na osnovu merenja torzionog napona pomoću mernih traka. Ovaj metod naročito je pogodan za proveru nivoa naprezanja elemenata sistema, koji prenose promenljive obrtne momente i torziono osciluju. Osim toga, mogu se određivati i kritične brzine obrtanja elemenata sistema, pri kojima se javljaju rezonantna naprezanja i otkazi sistema, kao što su: pojačana buka, trošenje zupčanika, zamor materijala, oštećenja i lomovi vratila, spojnica i si. Predložen je merni lanac u kojem centralno mesto zauzima suvremeni mobilni merni sistem Spider 8, koji omogućava merenje, obradu i prikaz rezultata pomoću računara. / In this work the measuring method of torsion vibrations is presented according to the measurement of torsion stress using strain gages. This method is particularly suitable in checking the system elements strain level that transfers changeable torsion moments and oscillate torsionally. Besides that, the system elements critical velocity rotation can be estimated, folio-wed by the resonant strain and problems in the function of that system such as: amplified noise, -wearing-out of gears, fatigue crack, damage and break of shafts and junctions etc. The measuring chain is proposed in -which the central part is a contemporary mobile system Spider 8, -which enables measurement, processing and displays measured results on a computer.

  6. Pre-Test Assessment of the Use Envelope of the Normal Force of a Wind Tunnel Strain-Gage Balance

    Science.gov (United States)

    Ulbrich, N.

    2016-01-01

    The relationship between the aerodynamic lift force generated by a wind tunnel model, the model weight, and the measured normal force of a strain-gage balance is investigated to better understand the expected use envelope of the normal force during a wind tunnel test. First, the fundamental relationship between normal force, model weight, lift curve slope, model reference area, dynamic pressure, and angle of attack is derived. Then, based on this fundamental relationship, the use envelope of a balance is examined for four typical wind tunnel test cases. The first case looks at the use envelope of the normal force during the test of a light wind tunnel model at high subsonic Mach numbers. The second case examines the use envelope of the normal force during the test of a heavy wind tunnel model in an atmospheric low-speed facility. The third case reviews the use envelope of the normal force during the test of a floor-mounted semi-span model. The fourth case discusses the normal force characteristics during the test of a rotated full-span model. The wind tunnel model's lift-to-weight ratio is introduced as a new parameter that may be used for a quick pre-test assessment of the use envelope of the normal force of a balance. The parameter is derived as a function of the lift coefficient, the dimensionless dynamic pressure, and the dimensionless model weight. Lower and upper bounds of the use envelope of a balance are defined using the model's lift-to-weight ratio. Finally, data from a pressurized wind tunnel is used to illustrate both application and interpretation of the model's lift-to-weight ratio.

  7. Stable solid-phase Rh antigen.

    Science.gov (United States)

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

    1997-12-01

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

  8. Common antigens between hydatid cyst and cancers

    Directory of Open Access Journals (Sweden)

    Shima Daneshpour

    2016-01-01

    Full Text Available Background: Different research groups reported a negative correlation between cancers and parasitical infections. As an example, the prevalence of a hydatid cyst among patients with cancer was significantly lower than its prevalence among normal population. Tn antigens exist both in cancer and hydatid cyst. This common antigen may be involved in the effect of parasite on cancer growth. So in this work, common antigens between hydatid cyst and cancers have been investigated. Materials and Methods: Different hydatid cyst antigens including hydatid fluid, laminated and germinal layer antigens, and excretory secretory antigens of protoscolices were run in SDS PAGE and transferred to NCP paper. In western immunoblotting, those antigens were probed with sera of patients with different cancer and also sera of non-cancer patients. Also, cross reaction among excretory secretory products of cancer cells and antisera raised against different hydatid cyst antigen was investigated. Results: In western immunoblotting, antisera raised against laminated and germinal layers of hydatid cyst reacted with excretory secretory products of cancer cells. Also, a reaction was detected between hydatid cyst antigens and sera of patients with some cancers. Conclusion: Results of this work emphasize existence of common antigens between hydatid cyst and cancers. More investigation about these common antigens is recommended.

  9. Common antigens between hydatid cyst and cancers

    Science.gov (United States)

    Daneshpour, Shima; Bahadoran, Mehran; Hejazi, Seyed Hossein; Eskandarian, Abas Ali; Mahmoudzadeh, Mehdi; Darani, Hossein Yousofi

    2016-01-01

    Background: Different research groups reported a negative correlation between cancers and parasitical infections. As an example, the prevalence of a hydatid cyst among patients with cancer was significantly lower than its prevalence among normal population. Tn antigens exist both in cancer and hydatid cyst. This common antigen may be involved in the effect of parasite on cancer growth. So in this work, common antigens between hydatid cyst and cancers have been investigated. Materials and Methods: Different hydatid cyst antigens including hydatid fluid, laminated and germinal layer antigens, and excretory secretory antigens of protoscolices were run in SDS PAGE and transferred to NCP paper. In western immunoblotting, those antigens were probed with sera of patients with different cancer and also sera of non-cancer patients. Also, cross reaction among excretory secretory products of cancer cells and antisera raised against different hydatid cyst antigen was investigated. Results: In western immunoblotting, antisera raised against laminated and germinal layers of hydatid cyst reacted with excretory secretory products of cancer cells. Also, a reaction was detected between hydatid cyst antigens and sera of patients with some cancers. Conclusion: Results of this work emphasize existence of common antigens between hydatid cyst and cancers. More investigation about these common antigens is recommended. PMID:26962511

  10. Determination of Baseline Periods of Record for Selected Streamflow-Gaging Stations in New Jersey for Determining Ecologically Relevant Hydrologic Indices (ERHI)

    Science.gov (United States)

    Esralew, Rachel A.; Baker, Ronald J.

    2008-01-01

    Hydrologic changes in New Jersey stream basins resulting from human activity can affect the flow and ecology of the streams. To assess future changes in streamflow resulting from human activity an understanding of the natural variability of streamflow is needed. The natural variability can be classified using Ecologically Relevant Hydrologic Indices (ERHIs). ERHIs are defined as selected streamflow statistics that characterize elements of the flow regime that substantially affect biological health and ecological sustainability. ERHIs are used to quantitatively characterize aspects of the streamflow regime, including magnitude, duration, frequency, timing, and rate of change. Changes in ERHI values can occur as a result of human activity, and changes in ERHIs over time at various stream locations can provide information about the degree of alteration in aquatic ecosystems at or near those locations. New Jersey streams can be divided into four classes (A, B, C, or D), where streams with similar ERHI values (determined from cluster analysis) are assigned the same stream class. In order to detect and quantify changes in ERHIs at selected streamflow-gaging stations, a 'baseline' period is needed. Ideally, a baseline period is a period of continuous daily streamflow record at a gaging station where human activity along the contributing stream reach or in the stream's basin is minimal. Because substantial urbanization and other development had already occurred before continuous streamflow-gaging stations were installed, it is not possible to identify baseline periods that meet this criterion for many reaches in New Jersey. Therefore, the baseline period for a considerably altered basin can be defined as a period prior to a substantial human-induced change in the drainage basin or stream reach (such as regulations or diversions), or a period during which development did not change substantially. Index stations (stations with minimal urbanization) were defined as streamflow-gaging

  11. Peak-Flow Frequency Estimates Based on Data through Water Year 2001 for Selected Streamflow-Gaging Stations in South Dakota

    Science.gov (United States)

    Sando, Steven K.; Driscoll, Daniel G.; Parrett, Charles

    2008-01-01

    Numerous users, including the South Dakota Department of Transportation, have continuing needs for peak-flow information for the design of highway infrastructure and many other purposes. This report documents results from a cooperative study between the South Dakota Department of Transportation and the U.S. Geological Survey to provide an update of peak-flow frequency estimates for South Dakota. Estimates of peak-flow magnitudes for 2-, 5-, 10-, 25-, 50-, 100-, 200-, and 500-year recurrence intervals are reported for 272 streamflow-gaging stations, which include most gaging stations in South Dakota with 10 or more years of systematic peak-flow records through water year 2001. Recommended procedures described in Bulletin 17B were used as primary guidelines for developing peak-flow frequency estimates. The computer program PEAKFQ developed by the U.S. Geological Survey was used to run the frequency analyses. Flood frequencies for all stations were initially analyzed by using standard Bulletin 17B default procedures for fitting the log-Pearson III distribution. The resulting preliminary frequency curves were then plotted on a log-probability scale, and fits of the curves with systematic data were evaluated. In many cases, results of the default Bulletin 17B analyses were determined to be satisfactory. In other cases, however, the results could be improved by using various alternative procedures for frequency analysis. Alternative procedures for some stations included adjustments to skew coefficients or use of user-defined low-outlier criteria. Peak-flow records for many gaging stations are strongly influenced by low- or zero-flow values. This situation often results in a frequency curve that plots substantially above the systematic record data points at the upper end of the frequency curve. Adjustments to low-outlier criteria reduced the influence of very small peak flows and generally focused the analyses on the upper parts of the frequency curves (10- to 500-year

  12. [Antigenic relationships between Debaryomyces strains (author's transl)].

    Science.gov (United States)

    Aksoycan, N

    1980-01-01

    The results of the agglutinations between homologous and heterologous Debaryomyces strains and their agglutinating sera are shown in table I. According to these findings, D. hansenii and D. marama are antigenically different from other Debaryomyces strains in this genus. In a previous study Aksoycan et al. have shown a common antigenic factor between D. hansenii, D. marama strains and Salmonella 0:7 antigen. This factor was not present in other six strains of Debaryomyces. These results also show that D. tamarii does not have any antigenic relationship with the other seven species of Debaryomyces in this genus.

  13. Adjusted peak-flow frequency estimates for selected streamflow-gaging stations in or near Montana based on data through water year 2011: Chapter D in Montana StreamStats

    Science.gov (United States)

    Sando, Steven K.; Sando, Roy; McCarthy, Peter M.; Dutton, DeAnn M.

    2016-04-05

    The climatic conditions of the specific time period during which peak-flow data were collected at a given streamflow-gaging station (hereinafter referred to as gaging station) can substantially affect how well the peak-flow frequency (hereinafter referred to as frequency) results represent long-term hydrologic conditions. Differences in the timing of the periods of record can result in substantial inconsistencies in frequency estimates for hydrologically similar gaging stations. Potential for inconsistency increases with decreasing peak-flow record length. The representativeness of the frequency estimates for a short-term gaging station can be adjusted by various methods including weighting the at-site results in association with frequency estimates from regional regression equations (RREs) by using the Weighted Independent Estimates (WIE) program. Also, for gaging stations that cannot be adjusted by using the WIE program because of regulation or drainage areas too large for application of RREs, frequency estimates might be improved by using record extension procedures, including a mixed-station analysis using the maintenance of variance type I (MOVE.1) procedure. The U.S. Geological Survey, in cooperation with the Montana Department of Transportation and the Montana Department of Natural Resources and Conservation, completed a study to provide adjusted frequency estimates for selected gaging stations through water year 2011.The purpose of Chapter D of this Scientific Investigations Report is to present adjusted frequency estimates for 504 selected streamflow-gaging stations in or near Montana based on data through water year 2011. Estimates of peak-flow magnitudes for the 66.7-, 50-, 42.9-, 20-, 10-, 4-, 2-, 1-, 0.5-, and 0.2-percent annual exceedance probabilities are reported. These annual exceedance probabilities correspond to the 1.5-, 2-, 2.33-, 5-, 10-, 25-, 50-, 100-, 200-, and 500-year recurrence intervals, respectively.The at-site frequency estimates were

  14. Blastogenic response of human lymphocytes to early antigen(s) of human cytomegalovirus.

    OpenAIRE

    Waner, J L; Kong, N; Biano, S

    1983-01-01

    The lymphocytes of asymptomatic, seropositive donors demonstrated blastogenic responses to early antigens of human cytomegalovirus whether or not antibodies to early antigens were detectable. The lymphocytes of six of nine patients with active cytomegalovirus infections gave stimulation indexes of greater than or equal to 2.00 with antigens of productively infected cells, whereas only two patients demonstrated comparable stimulation indexes with early antigens. Four patients with stimulation ...

  15. A computational framework for influenza antigenic cartography.

    Directory of Open Access Journals (Sweden)

    Zhipeng Cai

    Full Text Available Influenza viruses have been responsible for large losses of lives around the world and continue to present a great public health challenge. Antigenic characterization based on hemagglutination inhibition (HI assay is one of the routine procedures for influenza vaccine strain selection. However, HI assay is only a crude experiment reflecting the antigenic correlations among testing antigens (viruses and reference antisera (antibodies. Moreover, antigenic characterization is usually based on more than one HI dataset. The combination of multiple datasets results in an incomplete HI matrix with many unobserved entries. This paper proposes a new computational framework for constructing an influenza antigenic cartography from this incomplete matrix, which we refer to as Matrix Completion-Multidimensional Scaling (MC-MDS. In this approach, we first reconstruct the HI matrices with viruses and antibodies using low-rank matrix completion, and then generate the two-dimensional antigenic cartography using multidimensional scaling. Moreover, for influenza HI tables with herd immunity effect (such as those from Human influenza viruses, we propose a temporal model to reduce the inherent temporal bias of HI tables caused by herd immunity. By applying our method in HI datasets containing H3N2 influenza A viruses isolated from 1968 to 2003, we identified eleven clusters of antigenic variants, representing all major antigenic drift events in these 36 years. Our results showed that both the completed HI matrix and the antigenic cartography obtained via MC-MDS are useful in identifying influenza antigenic variants and thus can be used to facilitate influenza vaccine strain selection. The webserver is available at http://sysbio.cvm.msstate.edu/AntigenMap.

  16. A computational framework for influenza antigenic cartography.

    Science.gov (United States)

    Cai, Zhipeng; Zhang, Tong; Wan, Xiu-Feng

    2010-10-07

    Influenza viruses have been responsible for large losses of lives around the world and continue to present a great public health challenge. Antigenic characterization based on hemagglutination inhibition (HI) assay is one of the routine procedures for influenza vaccine strain selection. However, HI assay is only a crude experiment reflecting the antigenic correlations among testing antigens (viruses) and reference antisera (antibodies). Moreover, antigenic characterization is usually based on more than one HI dataset. The combination of multiple datasets results in an incomplete HI matrix with many unobserved entries. This paper proposes a new computational framework for constructing an influenza antigenic cartography from this incomplete matrix, which we refer to as Matrix Completion-Multidimensional Scaling (MC-MDS). In this approach, we first reconstruct the HI matrices with viruses and antibodies using low-rank matrix completion, and then generate the two-dimensional antigenic cartography using multidimensional scaling. Moreover, for influenza HI tables with herd immunity effect (such as those from Human influenza viruses), we propose a temporal model to reduce the inherent temporal bias of HI tables caused by herd immunity. By applying our method in HI datasets containing H3N2 influenza A viruses isolated from 1968 to 2003, we identified eleven clusters of antigenic variants, representing all major antigenic drift events in these 36 years. Our results showed that both the completed HI matrix and the antigenic cartography obtained via MC-MDS are useful in identifying influenza antigenic variants and thus can be used to facilitate influenza vaccine strain selection. The webserver is available at http://sysbio.cvm.msstate.edu/AntigenMap.

  17. Research on the Traceability Value Methord of Tyre Pattern Depth Gage%轮胎花纹深度检测尺量值溯源方法研究

    Institute of Scientific and Technical Information of China (English)

    张建群; 林景星

    2012-01-01

    Recently, there is no domestic specification of verification or calibration on the tyre pattern depth gage (hereinafter referred as the" depth gage "). In order to ensure an accurate and reliable traeebility value of the depth gage and its testing data, according to its working principle and measurement characteristics, this paper puts forward a calibration method on it and an uncertainty evaluation method of the depth gage, thus as a technical referrence of calibration of the depth gage.%目前国内尚无检定或校准轮胎花纹深度检测尺(以下简称“深度尺”)的计量检定规程或校准技术规范,为了确保开展深度尺量值溯源与检测数据准确可靠,根据其工作原理与计量特性,本文提出深度尺的校准方法及其校准结果的不确定度评定方法,作为开展深度尺校准使用的技术依据。

  18. Antigen/Antibody Analyses in Leishmaniasis.

    Science.gov (United States)

    1983-09-01

    antibodies in human sera with antigens of protozoan parasites . It was found that enzyme substrate reactions had distinct advantages over typical...autoradiographic procedures. Analyses of various sera identified a number of antigens of protozoan parasites which may be useful in discriminating infections

  19. Virosomes for antigen and DNA delivery

    NARCIS (Netherlands)

    Daemen, T; de Mare, A; Bungener, L; de Jonge, J; Huckriede, A; Wilschut, J

    2005-01-01

    Specific targeting and delivery as well as the display of antigens on the surface of professional antigen-presenting cells (APCs) are key issues in the design and development of new-generation vaccines aimed at the induction of both humoral and cell-mediated immunity. Prophylactic vaccination agains

  20. Statistical summaries of streamflow data for selected gaging stations on and near the Idaho National Engineering Laboratory, Idaho, through September 1990

    Energy Technology Data Exchange (ETDEWEB)

    Stone, M.A.J.; Mann, L.J.; Kjelstrom, L.C.

    1993-11-01

    Statistical summaries and graphs of streamflow data were prepared for 13 gaging stations with 5 or more years of continuous record on and near the Idaho National Engineering Laboratory. Statistical summaries of streamflow data for the Big and Little Lost Rivers and Birch Creek were analyzed as a requisite for a comprehensive evaluation of the potential for flooding of facilities at the Idaho National Engineering Laboratory. The type of statistical analyses performed depended on the length of streamflow record for a gaging station. Streamflow statistics generated for stations with 5 to 9 years of record were: Magnitudes of monthly and annual flows; duration of daily mean flows; and maximum, median, and minimum daily mean flows. Streamflow statistics generated for stations with 10 or more years of record were: Magnitudes of monthly and annual flows; magnitudes and frequencies of daily low, high, instantaneous peak (flood frequency), and annual mean flows; duration of daily mean flows; exceedance probabilities of annual low, high, instantaneous peak, and mean annual flows; maximum, median, and minimum daily mean flows; and annual mean and mean annual flows.

  1. Protein antigen delivery by gene gun-mediated epidermal antigen incorporation (EAI).

    Science.gov (United States)

    Scheiblhofer, Sandra; Ritter, Uwe; Thalhamer, Josef; Weiss, Richard

    2013-01-01

    The gene gun technology can not only be employed for efficient transfer of gene vaccines into upper layers of the skin, but also for application of protein antigens. As a tissue rich in professional antigen presenting cells, the skin represents an attractive target for immunizations. In this chapter we present a method for delivery of the model antigen ovalbumin into the skin of mice termed epidermal antigen incorporation and describe in detail how antigen-specific proliferation in draining lymph nodes can be followed by flow cytometry.

  2. Tumor antigens as related to pancreatic cancer.

    Science.gov (United States)

    Chu, T M; Holyoke, E D; Douglass, H O

    1980-01-01

    Data are presented suggesting the presence of pancreas tumor-associated antigens. Slow progress has been made during the past few years in the identification of pancreatic tumor antigens that may be of clinical usefulness and it seems unlikely that many of the practical problems now being faced in identification and isolation of these antigens and in development of a specific, sensitive assay will be solved by conventional immunochemical approaches. The study of antigen and/or antibody purified from immune complexes in the host and the application of leukocyte adherence inhibition techniques to immunodiagnosis of pancreatic cancer are among the new approaches that may provide effective alternatives in the study of pancreatic tumor antigens.

  3. Temporal trends and stationarity in annual peak flow and peak-flow timing for selected long-term streamflow-gaging stations in or near Montana through water year 2011: Chapter B in Montana StreamStats

    Science.gov (United States)

    Sando, Steven K.; McCarthy, Peter M.; Sando, Roy; Dutton, DeAnn M.

    2016-04-05

    A large-scale study by the U.S. Geological Survey, in cooperation with the Montana Department of Transportation and the Montana Department of Natural Resources and Conservation, was done to investigate general patterns in peak-flow temporal trends and stationarity through water year 2011 for 24 long-term streamflow-gaging stations (hereinafter referred to as gaging stations) in Montana. Hereinafter, all years refer to water years; a water year is the 12-month period from October 1 through September 30 and is designated by the year in which it ends. The primary focus of the study was to identify general patterns in peak-flow temporal trends and stationarity that are relevant to application of peak-flow frequency analyses within a statewide gaging-station network.

  4. 一款微型汽车塑料保险杠专用检具通用化设计%Universal design A miniature car plastic bumper special gage

    Institute of Scientific and Technical Information of China (English)

    黄好; 谭克京

    2012-01-01

    This paper focuses on the basis of a miniature car plastic rear bumper special gage, combined with the inspection requirements of the new rear bumper design, universal design and alteration for the existing special gage to meet the gage design and manufacturing requirements, shorten new product development cycle, reduce the cost of new product develop- ment%本文重点分析了在现有的一款微型汽车塑料后保险杠专用检具的基础上,结合新设计的保险杠产品检测要求,对现有的专用检具进行通用化设计和改造,满足检具的设计和制造要求,缩短新产品开发周期,降低新产品开发成本。

  5. Antigen clasping by two antigen-binding sites of an exceptionally specific antibody for histone methylation

    Science.gov (United States)

    Hattori, Takamitsu; Lai, Darson; Dementieva, Irina S.; Montaño, Sherwin P.; Kurosawa, Kohei; Zheng, Yupeng; Akin, Louesa R.; Świst-Rosowska, Kalina M.; Grzybowski, Adrian T.; Koide, Akiko; Krajewski, Krzysztof; Strahl, Brian D.; Kelleher, Neil L.; Ruthenburg, Alexander J.; Koide, Shohei

    2016-01-01

    Antibodies have a well-established modular architecture wherein the antigen-binding site residing in the antigen-binding fragment (Fab or Fv) is an autonomous and complete unit for antigen recognition. Here, we describe antibodies departing from this paradigm. We developed recombinant antibodies to trimethylated lysine residues on histone H3, important epigenetic marks and challenging targets for molecular recognition. Quantitative characterization demonstrated their exquisite specificity and high affinity, and they performed well in common epigenetics applications. Surprisingly, crystal structures and biophysical analyses revealed that two antigen-binding sites of these antibodies form a head-to-head dimer and cooperatively recognize the antigen in the dimer interface. This “antigen clasping” produced an expansive interface where trimethylated Lys bound to an unusually extensive aromatic cage in one Fab and the histone N terminus to a pocket in the other, thereby rationalizing the high specificity. A long-neck antibody format with a long linker between the antigen-binding module and the Fc region facilitated antigen clasping and achieved both high specificity and high potency. Antigen clasping substantially expands the paradigm of antibody–antigen recognition and suggests a strategy for developing extremely specific antibodies. PMID:26862167

  6. Estimating peak-flow frequency statistics for selected gaged and ungaged sites in naturally flowing streams and rivers in Idaho

    Science.gov (United States)

    Wood, Molly S.; Fosness, Ryan L.; Skinner, Kenneth D.; Veilleux, Andrea G.

    2016-06-27

    -central Idaho (average standard error of prediction=46.4 percent; pseudo-R2>92 percent) and region 5 in central Idaho (average standard error of prediction=30.3 percent; pseudo-R2>95 percent). Regression model fit was poor for region 7 in southern Idaho (average standard error of prediction=103 percent; pseudo-R2equations if peak-flow estimates are desired at an ungaged site that is close to a streamgage selected for inclusion in this study. The alternative drainage area ratio-adjustment method is appropriate for use when the drainage area ratio between the ungaged and gaged sites is between 0.5 and 1.5.The updated regional peak-flow regression equations had lower total error (standard error of prediction) than all regression equations presented in a 1982 study and in four of six regions presented in 2002 and 2003 studies in Idaho. A more extensive streamgage screening process used in the current study resulted in fewer streamgages used in the current study than in the 1982, 2002, and 2003 studies. Fewer streamgages used and the selection of different explanatory variables were likely causes of increased error in some regions compared to previous studies, but overall, regional peak‑flow regression model fit was generally improved for Idaho. The revised statistical procedures and increased streamgage screening applied in the current study most likely resulted in a more accurate representation of natural peak-flow conditions.The updated, regional peak-flow regression equations will be integrated in the U.S. Geological Survey StreamStats program to allow users to estimate basin and climatic characteristics and peak-flow statistics at ungaged locations of interest. StreamStats estimates peak-flow statistics with quantifiable certainty only when used at sites with basin and climatic characteristics within the range of input variables used to develop the regional regression equations. Both the regional regression equations and StreamStats should be used to estimate peak

  7. Estimating peak-flow frequency statistics for selected gaged and ungaged sites in naturally flowing streams and rivers in Idaho

    Science.gov (United States)

    Wood, Molly S.; Fosness, Ryan L.; Skinner, Kenneth D.; Veilleux, Andrea G.

    2016-06-27

    -central Idaho (average standard error of prediction=46.4 percent; pseudo-R2>92 percent) and region 5 in central Idaho (average standard error of prediction=30.3 percent; pseudo-R2>95 percent). Regression model fit was poor for region 7 in southern Idaho (average standard error of prediction=103 percent; pseudo-R2<78 percent) compared to other regions because few streamgages in region 7 met the criteria for inclusion in the study, and the region’s semi-arid climate and associated variability in precipitation patterns causes substantial variability in peak flows.A drainage area ratio-adjustment method, using ratio exponents estimated using generalized least-squares regression, was presented as an alternative to the regional regression equations if peak-flow estimates are desired at an ungaged site that is close to a streamgage selected for inclusion in this study. The alternative drainage area ratio-adjustment method is appropriate for use when the drainage area ratio between the ungaged and gaged sites is between 0.5 and 1.5.The updated regional peak-flow regression equations had lower total error (standard error of prediction) than all regression equations presented in a 1982 study and in four of six regions presented in 2002 and 2003 studies in Idaho. A more extensive streamgage screening process used in the current study resulted in fewer streamgages used in the current study than in the 1982, 2002, and 2003 studies. Fewer streamgages used and the selection of different explanatory variables were likely causes of increased error in some regions compared to previous studies, but overall, regional peak‑flow regression model fit was generally improved for Idaho. The revised statistical procedures and increased streamgage screening applied in the current study most likely resulted in a more accurate representation of natural peak-flow conditions.The updated, regional peak-flow regression equations will be integrated in the U.S. Geological Survey StreamStats program to allow

  8. Antigen-specific memory B cell development.

    Science.gov (United States)

    McHeyzer-Williams, Louise J; McHeyzer-Williams, Michael G

    2005-01-01

    Helper T (Th) cell-regulated B cell immunity progresses in an ordered cascade of cellular development that culminates in the production of antigen-specific memory B cells. The recognition of peptide MHC class II complexes on activated antigen-presenting cells is critical for effective Th cell selection, clonal expansion, and effector Th cell function development (Phase I). Cognate effector Th cell-B cell interactions then promote the development of either short-lived plasma cells (PCs) or germinal centers (GCs) (Phase II). These GCs expand, diversify, and select high-affinity variants of antigen-specific B cells for entry into the long-lived memory B cell compartment (Phase III). Upon antigen rechallenge, memory B cells rapidly expand and differentiate into PCs under the cognate control of memory Th cells (Phase IV). We review the cellular and molecular regulators of this dynamic process with emphasis on the multiple memory B cell fates that develop in vivo.

  9. Platelet antigens and antibodies. Literature review

    Directory of Open Access Journals (Sweden)

    N. V. Mineeva

    2014-07-01

    Full Text Available Platelet antigens structure, role of platelet antibodies in the pathogenesis of various clinical conditions, characteristic of modern antibodies detection methods are presented in this article.

  10. Platelet antigens and antibodies. Literature review

    Directory of Open Access Journals (Sweden)

    N. V. Mineeva

    2013-01-01

    Full Text Available Platelet antigens structure, role of platelet antibodies in the pathogenesis of various clinical conditions, characteristic of modern antibodies detection methods are presented in this article.

  11. Vertical datum conversion process for the inland and coastal gage network located in the New England, Mid-Atlantic, and South Atlantic-Gulf hydrologic regions

    Science.gov (United States)

    Rydlund, Jr., Paul H.; Noll, Michael L.

    2017-03-07

    Datum conversions from the National Geodetic Vertical Datum of 1929 to the North American Vertical Datum of 1988 among inland and coastal gages throughout the hydrologic regions of New England, the Mid-Atlantic, and the South Atlantic-Gulf have implications among river and storm surge forecasting, general commerce, and water-control operations. The process of data conversions may involve the application of a recovered National Geodetic Vertical Datum of 1929–North American Vertical Datum of 1988 offset, a simplistic datum transformation using VDatum or VERTCON software, or a survey, depending on a gaging network datum evaluation, anticipated uncertainties for data use among the cooperative water community, and methods used to derive the conversion. Datum transformations from National Geodetic Vertical Datum of 1929 to North American Vertical Datum of 1988 using VERTCON purport errors of ± 0.13 foot at the 95 percent confidence level among modeled points, claiming more consistency along the east coast. Survey methods involving differential and trigonometric leveling, along with observations using Global Navigation Satellite System technology, afford a variety of approaches to establish or perpetuate a datum during a survey. Uncertainties among leveling approaches are generally process is initiated with an evaluation of the inland and coastal gage network datum, beginning with altitude datum components and the history of those components queried through the U.S. Geological Survey Groundwater Site Inventory database. Subsequent edits to the Groundwater Site Inventory database may be required and a consensus reached among the U.S. Geological Survey Water Science Centers to identify the outstanding workload categorized as in-office datum transformations or offset applications versus out-of-office survey efforts. Datum conversions or datum establishment for the inland or coastal gaging network should meet datum uncertainty requirements among other Federal agencies

  12. Presentation of antigen by B cells subsets. Pt. 2. The role of CD5 B cells in the presentation of antigen to antigen-specific T cells

    Energy Technology Data Exchange (ETDEWEB)

    Zimecki, Michal [Polish Academy of Sciences, Wroclaw (Poland). Institute of Immunology and Experimental Therapy; Kapp, Judith A. [Emory Univ., Atlanta, GA (United States). School of Medicine

    1994-12-31

    We demonstrate that peritoneal B cells have a much higher ability to present antigen to antigen-specific T cell lines splenic B cells. Presentation of antigen by B cells is abrogated or drastically reduced after removal of Lyb-5{sup +} cells from the population of splenic or peritoneal B cells. Peritoneal B cells, precultured for 7 days prior to the antigen presentation assay, retain their antigen presenting cell (APC) function. Enrichment for CD5{sup +} cells in the peritoneal B cell population results in a more effective antigen presentation. Lastly, stimulation of B cells via CD5 antigen, by treatment of cells with anti-CD5 antibodies or cross-linking of CD5 receptors, enhances APC function of these cells. The results indicate, both indirectly and directly, that CD5{sup +} B cells play a predominant role in the presentation of conventional antigens to antigen-specific T cells. (author). 30 refs, 6 tabs.

  13. Expression and Antigenic Evaluation of VacA Antigenic Fragment of Helicobacter Pylori

    Directory of Open Access Journals (Sweden)

    Leila Hasanzadeh

    2013-07-01

    Full Text Available Objective(s: Helicobacter pylori, a human specific gastric pathogen is a causative agent of chronic active gastritis. The vacuolating cytotoxin (VacA is an effective virulence factor involved in gastric injury. The aim of this study was to construct a recombinant protein containing antigenic region of VacA gene and determine its antigenicity.   Materials and Methods: The antigenic region of VacA gene was detected by bioinformatics methods. The polymerase chain reaction method was used to amplify a highly antigenic region of VacA gene from chromosomal DNA of H. pylori. The eluted product was cloned into the prokaryotic expression vector pET32a. The target protein was expressed in the Escherichia coli BL21 (DE3 pLysS. The bacteria including pET32a-VacA plasmids were induced by IPTG. The antigenicity was finally studied by western blotting using sera of 15 H. pylori infected patients after purification. Results: Enzyme digestion analysis, PCR and DNA sequencing results showed that the target gene was inserted correctly into the recombinant vector. The expressed protein was purified successfully via affinity chromatography. Data indicated that antigenic region of VacA protein from Helicobacter pylori was recognized by all 15 patient’s sera. Conclusion : Our data showed that antigenic region of VacA protein can be expressed by in E. co.li. This protein was recognized by sera patients suffering from H. pylori infection. the recombinant protein has similar epitopes and close antigenic properties to the natural form of this antigen. Recombinant antigenic region of VacA protein also seems to be a promising antigen for protective and serologic diagnosis .

  14. Antigen cross-presentation of immune complexes.

    Science.gov (United States)

    Platzer, Barbara; Stout, Madeleine; Fiebiger, Edda

    2014-01-01

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

  15. Seroreactivity of Salmonella-infected cattle herds against a fimbrial antigen in comparison with lipopolysaccharide antigens

    DEFF Research Database (Denmark)

    Hoorfar, Jeffrey; Lind, Peter; Bell, M.M.

    1996-01-01

    The IgG seroreaction of Salmonella-infected cattle herds against a fimbrial antigen (SEF14) was compared with that against lipopolysaccharide (LPS) antigens. Sera from 23 dairy herds (n = 205) from an island with no occurrence of salmonellosis, four herds (n = 303) with recent outbreaks of S...

  16. The antigenic relationship between Brettanomyces-Debaryomyces strains and the Salmonella cholerae-suis O antigen.

    Science.gov (United States)

    Aksoycan, N; Sağanak, I; Wells, G

    1978-01-01

    The immune sera for Brettanomyces lambicus, B. claussenii, Debaryomyces hansenii and D. marama agglutinated Salmonella cholerae-suis (0:6(2), 7). The immune serum for S. cholerae-suis agglutinated B. lambicus, B. clausenni, D. hansenii and D. marama. Absorption and agglutination cross-tested demonstrated common antigen factor(s) in the tested yeasts and Salmonella 0:7 antigen.

  17. Superexpression of tuberculosis antigens in plant leaves.

    Science.gov (United States)

    Dorokhov, Yuri L; Sheveleva, Anna A; Frolova, Olga Y; Komarova, Tatjana V; Zvereva, Anna S; Ivanov, Peter A; Atabekov, Joseph G

    2007-05-01

    Recent developments in genetic engineering allow the employment of plants as factories for 1/foreign protein production. Thus, tuberculosis (TB) ESAT6 antigen was expressed in different plant systems, but the level of vaccine protein accumulation was extremely low. We describe the technology for superexpression of TB vaccine proteins (Ag85B, ESAT6, and ESAT6:Ag85B fusion) in plant leaves which involves: (i) construction of tobacco mosaic virus-based vectors with the coat protein genes substituted by those for TB antigens; (ii) Agrobacterium-mediated delivery to plant leaf tissues of binary vectors containing the cDNA copy of the vector virus genome; and (iii) replication of virus vectors in plant cells under conditions suppressing the virus-induced gene silencing. This technology enables efficient production of the TB vaccine proteins in plants; in particular, the level of Ag85B antigen accumulation was not less than 800 mg/kg of fresh leaves. Expression of TB antigens in plant cells as His(6)-tagged proteins promoted their isolation and purification by Ni-NTA affinity chromatography. Deletion of transmembrane domains from Ag85B caused a dramatic increase in its intracellular stability. We propose that the strategy of TB antigens superproduction in a plant might be used as a basis for the creation of prophylactic and therapeutic vaccine against TB.

  18. Antigen presentation by MHC-dressed cells

    Directory of Open Access Journals (Sweden)

    Masafumi eNakayama

    2015-01-01

    Full Text Available Professional antigen presenting cells (APCs such as conventional dendritic cells (DCs process protein antigens to MHC-bound peptides and then present the peptide-MHC complexes to T cells. In addition to this canonical antigen presentation pathway, recent studies have revealed that DCs and non-APCs can acquire MHC class I (MHCI and/or MHC class II (MHCII from neighboring cells through a process of cell-cell contact-dependent membrane transfer called trogocytosis. These MHC-dressed cells subsequently activate or regulate T cells via the preformed antigen peptide-MHC complexes without requiring any further processing. In addition to trogocytosis, intercellular transfer of MHCI and MHCII can be mediated by secretion of membrane vesicles such as exosomes from APCs, generating MHC-dressed cells. This review focuses on the physiological role of antigen presentation by MHCI- or MHCII-dressed cells, and also discusses differences and similarities between trogocytosis and exosome-mediated transfer of MHC.

  19. Antigenic typing Polish isolates of canine parvovirus

    Energy Technology Data Exchange (ETDEWEB)

    Mizak, B. [National Veterinary Research Institute, Pulawy (Poland); Plucienniczak, A. [Polish Academy ofd Sciences. Microbiology and Virology Center, Lodz (Poland)

    1995-12-31

    Polish strains of canine parvovirus isolated between 1982 and 1993 were examined to determine the extent to which the virus has evolved antigenically and genetically over eleven years. Two CPV isolates obtained in Warsaw in 1982 and Pulawy in 1993, were examined using monoclonal antibody typing, restriction analysis and sequencing VP-2 protein gene. Five other isolates from Warsaw and Pulawy were tested with the panel of monoclonal antibodies specific to CPV-2, CPV-2a and common for canine parvovirus, feline panleukopenia virus and milk enteritis virus. Results of the studies demonstrated that all isolates tested represented CPV-2a antigenic type. Rapid antigenic strain replacement recorded by Parrish and Senda in the U.S.A and Japan was not confirmed in Poland. (author). 30 refs, 2 tabs.

  20. Harnessing Dendritic Cells for Tumor Antigen Presentation

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-04-26

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

  1. Design of a sediment-monitoring gaging network on ephemeral tributaries of the Colorado River in Glen, Marble, and Grand Canyons, Arizona

    Science.gov (United States)

    Griffiths, Ronald E.; Topping, David J.; Anderson, Robert S.; Hancock, Gregory S.; Melis, Theodore S.

    2014-01-01

    Management of sediment in rivers downstream from dams requires knowledge of both the sediment supply and downstream sediment transport. In some dam-regulated rivers, the amount of sediment supplied by easily measured major tributaries may overwhelm the amount of sediment supplied by the more difficult to measure lesser tributaries. In this first class of rivers, managers need only know the amount of sediment supplied by these major tributaries. However, in other regulated rivers, the cumulative amount of sediment supplied by the lesser tributaries may approach the total supplied by the major tributaries. The Colorado River downstream from Glen Canyon has been hypothesized to be one such river. If this is correct, then management of sediment in the Colorado River in the part of Glen Canyon National Recreation Area downstream from the dam and in Grand Canyon National Park may require knowledge of the sediment supply from all tributaries. Although two major tributaries, the Paria and Little Colorado Rivers, are well documented as the largest two suppliers of sediment to the Colorado River downstream from Glen Canyon Dam, the contributions of sediment supplied by the ephemeral lesser tributaries of the Colorado River in the lowermost Glen Canyon, and Marble and Grand Canyons are much less constrained. Previous studies have estimated amounts of sediment supplied by these tributaries ranging from very little to almost as much as the amount supplied by the Paria River. Because none of these previous studies relied on direct measurement of sediment transport in any of the ephemeral tributaries in Glen, Marble, or Grand Canyons, there may be significant errors in the magnitudes of sediment supplies estimated during these studies. To reduce the uncertainty in the sediment supply by better constraining the sediment yield of the ephemeral lesser tributaries, the U.S. Geological Survey Grand Canyon Monitoring and Research Center established eight sediment-monitoring gaging

  2. Antigenic variation of Streptococcus mutans colonizing gnotobiotic rats.

    Science.gov (United States)

    Bratthall, D; Gibbons, R J

    1975-12-01

    Strains of Streptococcus mutans representative of serotypes b and d exhibited antigenic variation in both the oral cavity and in the intestinal canal of gnotobiotic rats. Laboratory-maintained cultures did not vary. The antigenic alterations observed were: (i) loss of detectable levels of both weakly reacting "strain" antigens and the type antigen; (ii) decreased production of the type antigen; (ii) production of altered type antigen; and (iv) production of an antigen not possessed by the parent strain. Immunization of animals before monoinfection with S. mutans strain Bob-1 (serotype d) appeared to increase the rate of emergence of antigenically altered mutants in the intestinal canal, and more diversely altered isolates were obtained. Antigenic variation may account in part for the variation noted by several investigators in attempting to immunize animals against S. mutans-induced dental caries.

  3. Properties of glycolipid-enriched membrane rafts in antigen presentation.

    Science.gov (United States)

    Rodgers, William; Smith, Kenneth

    2005-01-01

    Presentation of antigen to T cells represents one of the central events in the engagement of the immune system toward the defense of the host against pathogens. Accordingly, understanding the mechanisms by which antigen presentation occurs is critical toward our understanding the properties of host defense against foreign antigen, as well as insight into other features of the immune system, such as autoimmune disease. The entire antigen-presentation event is complex, and many features of it remain poorly understood. However, recent studies have provided evidence showing that glycolipid-enriched membrane rafts are important for efficient antigen presentation; the studies suggest that one such function of rafts is trafficking of antigen-MHC II complexes to the presentation site on the surface of the antigen-presenting cell. Here, we present a critical discussion of rafts and their proposed functions in antigen presentation. Emerging topics of rafts and antigen presentation that warrant further investigation are also highlighted.

  4. Classification of human leukocyte antigen (HLA) supertypes

    DEFF Research Database (Denmark)

    Wang, Mingjun; Claesson, Mogens H

    2014-01-01

    Identification of new antigenic peptides, derived from infectious agents or cancer cells, which bind to human leukocyte antigen (HLA) class I and II molecules, is of importance for the development of new effective vaccines capable of activating the cellular arm of the immune response. However...... this complexity is to group thousands of different HLA molecules into several so-called HLA supertypes: a classification that refers to a group of HLA alleles with largely overlapping peptide binding specificities. In this chapter, we focus on the state-of-the-art classification of HLA supertypes including HLA...

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

    Science.gov (United States)

    Gota, F

    1980-01-01

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

  6. HLA antigens and asthma in Greeks.

    Science.gov (United States)

    Apostolakis, J; Toumbis, M; Konstantopoulos, K; Kamaroulias, D; Anagnostakis, J; Georgoulias, V; Fessas, P; Zervas, J

    1996-04-01

    HLA-A and -B antigens were determined in a group of 76 Greek asthmatic patients: 35 children (1.5-15 years) and 41 adults (18-73 years). The results were compared to those of 400 healthy unrelated controls from the same population. The standard NIH lymphocytotoxicity test was applied. When all 76 patients were compared to the controls, a statistically significant lower frequency of HLA-B5 and -B35 antigens was noted. When adults were analysed alone, an increased frequency of HLA-B8 was found. On the other hand, in the asthmatic children sub-group, the HLA-A10 antigen was significantly higher and the HLA-B5 was significantly lower than in the controls. These data imply that different HLA antigens may be involved in the pathogenesis of several clinical forms of asthma and that, in order to study the role of immunogenetic factor(s) in the pathogenesis of this disease, more adequate grouping criteria are needed.

  7. Prostate-specific antigen (PSA) blood test

    Science.gov (United States)

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

  8. A NEW SYNTHETIC FUNCTIONALIZED ANTIGEN CARRIER

    NARCIS (Netherlands)

    DRIJFHOUT, JW; BLOEMHOFF, W

    1991-01-01

    A new synthetic functionalized antigen carrier is described. It consists of a core of seven branched lysine residues, of which each of the four N-terminal lysine residues contains two N-(S-acetylmercaptoacetyl)-glutamyl residues. After removal of the protecting S-acetyl groups affording eight thiol

  9. STAINING OF VACCINIA ANTIGEN BY IMMUNOURANIUM TECHNIQUE,

    Science.gov (United States)

    An attempt to follow morphologically the development of vaccinia antigen in helium-lanthanum ( HeLa ) cells is reported. The conversion of rabbit...antisera to vaccinia virus and the preparation of vaccinia-infected HeLa cells for electron microscopy are described. With specific staining, viral

  10. A new crank arm based load cell, with built-in conditioning circuit and strain gages, to measure the components of the force applied by a cyclist.

    Science.gov (United States)

    Pigatto, Andre V; Moura, Karina O A; Favieiro, Gabriela W; Balbinot, Alexandre; Pigatto, Andre V; Moura, Karina O A; Favieiro, Gabriela W; Balbinot, Alexandre; Moura, Karina O A; Favieiro, Gabriela W; Balbinot, Alexandre; Pigatto, Andre V

    2016-08-01

    This report describes the development of a force platform based on instrumented load cells with built-in conditioning circuit and strain gages to measure and acquire the components of the force that is applied to the bike crank arm during pedaling in real conditions, and save them on a SD Card. To accomplish that, a complete new crank arm 3D solid model was developed in the SolidWorks, with dimensions equivalent to a commercial crank set and compatible with a conventional road bike, but with a compartment to support all the electronics necessary to measure 3 components of the force applied to the pedal during pedaling. After that, a 6082 T6 Aluminum Crankset based on the solid model was made and instrumented with three Wheatstone bridges each. The signals were conditioned on a printed circuit board, made on SMD technology, and acquired using a microcontroller with a DAC. Static deformation analysis showed a linearity error below 0.6% for all six channels. Dynamic analysis showed a natural frequency above 136Hz. A one-factor experiment design was performed with 5 amateur cyclists. ANOVA showed that the cyclist weight causes significant variation on the force applied to the bicycle pedal and its bilateral symmetry.

  11. Rational antigen modification as a strategy to upregulate or downregulate antigen recognition.

    Science.gov (United States)

    Abrams, S I; Schlom, J

    2000-02-01

    Recent and rapid advances in our understanding of the cellular and molecular mechanisms of antigen recognition by CD8(+) and CD4(+) T lymphocytes have led to the birth of possibilities for site-directed, rational modification of cognate antigenic determinants. This immunologic concept has vast biomedical implications for regulation of host immunity against the pathogenesis of diverse disease processes. The upregulation of antigen-specific T-cell responses by 'agonistic' peptides would be most desirable in response to invasive pathogenic challenges, such as infectious and neoplastic disease, while the downregulation of antigen-specific T-cell responses by 'antagonistic' peptides would be most efficacious during inappropriate pathologic consequences, such as autoimmunity. The capacity to experimentally manipulate intrinsic properties of cognate peptide ligands to appropriately alter the nature, course and potency of cellular immune interactions has important potential in both preventive and therapeutic clinical paradigms.

  12. Dengue viruses cluster antigenically but not as discrete serotypes

    NARCIS (Netherlands)

    L. Katzelnick (Leah); J.M. Fonville (Judith); G.D. Gromowski (Gregory D.); J.B. Arriaga (Jose Bustos); A. Green (Angela); S.L. James (Sarah ); L. Lau (Louis); M. Montoya (Magelda); C. Wang (Chunling); L.A. Van Blargan (Laura A.); C.A. Russell (Colin); H.M. Thu (Hlaing Myat); T.C. Pierson (Theodore C.); P. Buchy (Philippe); J.G. Aaskov (John G.); J.L. Muñoz-Jordán (Jorge L.); N. Vasilakis (Nikos); R.V. Gibbons (Robert V.); R.B. Tesh (Robert B.); A.D.M.E. Osterhaus (Albert); R.A.M. Fouchier (Ron); A. Durbin (Anna); C.P. Simmons (Cameron P.); E.C. Holmes (Edward C.); E. Harris (Eva); S.S. Whitehead (Stephen S.); D.J. Smith (Derek James)

    2015-01-01

    textabstractThe four genetically divergent dengue virus (DENV) types are traditionally classified as serotypes. Antigenic and genetic differences among the DENV types influence disease outcome, vaccine-induced protection, epidemic magnitude, and viral evolution.We scharacterized antigenic diversity

  13. Cysteine proteases as potential antigens in antiparasitic DNA vaccines

    DEFF Research Database (Denmark)

    Jørgensen, Louise von Gersdorff; Buchmann, Kurt

    2011-01-01

    En litteraturgennemgang af muligheder for at bruge cystein proteaser som antigener i antiparasitære vacciner.......En litteraturgennemgang af muligheder for at bruge cystein proteaser som antigener i antiparasitære vacciner....

  14. Comparison of E and NS1 antigens capture ELISA to detect dengue viral antigens from mosquitoes

    Directory of Open Access Journals (Sweden)

    Day-Yu Chao

    2015-01-01

    Interpretation & conclusion: With the future potential of antigen capture ELISA to be used in the resource deprived regions, the study showed that E-ELISA has similar sensitivity and antigen stability as NS1 Ag kit to complement the current established virological surveillance in human. The improvement of the sensitivity in detecting DENV-3/4 will be needed to incorporate this method into routine mosquito surveillance system.

  15. Comparison of Schistosoma mansoni soluble cercarial antigens and soluble egg antigens for serodiagnosing schistosome infections.

    Directory of Open Access Journals (Sweden)

    Huw Smith

    Full Text Available A Schistosoma mansoni cercarial antigen preparation (cercarial transformation fluid--SmCTF was evaluated for detection of anti-schistosome antibodies in human sera in 4 collaborating laboratories. The performance of SmCTF was compared with that of S. mansoni egg antigens (SmSEA in an indirect enzyme-immunoassay (ELISA antigen assay, the latter being used routinely in 3 of the 4 participating laboratories to diagnose S. mansoni and S. haematobium infections. In the fourth laboratory the performance of SmCTF was compared with that of S. japonicum egg antigens (SjSEA in ELISA for detection of anti-S. japonicum antibodies. In all 4 laboratories the results given by SmCTF in ELISA were very similar to those given by the antigen preparation routinely used in the respective laboratory to detect anti-schistosome antibodies in human infection sera. In so far as the ELISA results from SmCTF are thus so little different from those given by schistosome egg antigens and also cheaper to produce, the former is a potentially useful new diagnostic aid for schistosomiasis.

  16. Mapping antigenic motifs in the trypomastigote small surface antigen from Trypanosoma cruzi.

    Science.gov (United States)

    Balouz, Virginia; Cámara, María de Los Milagros; Cánepa, Gaspar E; Carmona, Santiago J; Volcovich, Romina; Gonzalez, Nicolás; Altcheh, Jaime; Agüero, Fernán; Buscaglia, Carlos A

    2015-03-01

    The trypomastigote small surface antigen (TSSA) is a mucin-like molecule from Trypanosoma cruzi, the etiological agent of Chagas disease, which displays amino acid polymorphisms in parasite isolates. TSSA expression is restricted to the surface of infective cell-derived trypomastigotes, where it functions as an adhesin and engages surface receptors on the host cell as a prerequisite for parasite internalization. Previous results have established TSSA-CL, the isoform encoded by the CL Brener clone, as an appealing candidate for use in serology-based diagnostics for Chagas disease. Here, we used a combination of peptide- and recombinant protein-based tools to map the antigenic structure of TSSA-CL at maximal resolution. Our results indicate the presence of different partially overlapping B-cell epitopes clustering in the central portion of TSSA-CL, which contains most of the polymorphisms found in parasite isolates. Based on these results, we assessed the serodiagnostic performance of a 21-amino-acid-long peptide that spans TSSA-CL major antigenic determinants, which was similar to the performance of the previously validated glutathione S-transferase (GST)-TSSA-CL fusion molecule. Furthermore, the tools developed for the antigenic characterization of the TSSA antigen were also used to explore other potential diagnostic applications of the anti-TSSA humoral response in Chagasic patients. Overall, our present results provide additional insights into the antigenic structure of TSSA-CL and support this molecule as an excellent target for molecular intervention in Chagas disease.

  17. Antigenic community between Schistosoma mansoni and Biomphalaria glabrata: on the search of candidate antigens for vaccines

    Directory of Open Access Journals (Sweden)

    N Chacón

    2002-10-01

    Full Text Available We have previously confirmed the presence of common antigens between Schistosoma mansoni and its vector, Biomphalaria glabrata. Cross-reactive antigens may be important as possible candidates for vaccine and diagnosis of schistosomiasis. Sera from outbred mice immunized with a soluble Biomphalaria glabrata antigen (SBgA of non-infected B. glabrata snails recognized molecules of SBgA itself and S. mansoni AWA by Western blot. Recognition of several molecules of the SBgA were inhibited by pre-incubation with AWA (16, 30, 36, 60 and 155 kDa. The only specific molecule of AWA, inhibited by SBgA, was a 120 kDa protein. In order to determine which epitopes of SBgA were glycoproteins, the antigen was treated with sodium metaperiodate and compared with non-treated antigen. Molecules of 140, 60 and 24 kDa in the SBgA appear to be glycoproteins. Possible protective effects of the SBgA were evaluated immunizing outbred mice in two different experiments using Freund's Adjuvant. In the first one (12 mice/group, we obtained a significant level of protection (46% in the total worm load, with a high variability in worm recovery. In the second experiment (22 mice/group, no significant protection was observed, neither in worm load nor in egg production per female. Our results suggest that SBgA constitutes a rich source of candidate antigens for diagnosis and prophylactic studies.

  18. Synthetic antigens reveal dynamics of BCR endocytosis during inhibitory signaling.

    Science.gov (United States)

    Courtney, Adam H; Bennett, Nitasha R; Zwick, Daniel B; Hudon, Jonathan; Kiessling, Laura L

    2014-01-17

    B cells detect foreign antigens through their B cell antigen receptor (BCR). The BCR, when engaged by antigen, initiates a signaling cascade. Concurrent with signaling is endocytosis of the BCR complex, which acts to downregulate signaling and facilitate uptake of antigen for processing and display on the cell surface. The relationship between signaling and BCR endocytosis is poorly defined. Here, we explore the interplay between BCR endocytosis and antigens that either promote or inhibit B cell activation. Specifically, synthetic antigens were generated that engage the BCR alone or both the BCR and the inhibitory co-receptor CD22. The lectin CD22, a member of the Siglec family, binds sialic acid-containing glycoconjugates found on host tissues, inhibiting BCR signaling to prevent erroneous B cell activation. At low concentrations, antigens that can cocluster the BCR and CD22 promote rapid BCR endocytosis; whereas, slower endocytosis occurs with antigens that bind only the BCR. At higher antigen concentrations, rapid BCR endocytosis occurs upon treatment with either stimulatory or inhibitory antigens. Endocytosis of the BCR, in response to synthetic antigens, results in its entry into early endocytic compartments. Although the CD22-binding antigens fail to activate key regulators of antigen presentation (e.g., Syk), they also promote BCR endocytosis, indicating that inhibitory antigens can be internalized. Together, our observations support a functional role for BCR endocytosis in downregulating BCR signaling. The reduction of cell surface BCR levels in the absence of B cell activation should raise the threshold for BCR subsequent activation. The ability of the activating synthetic antigens to trigger both signaling and entry of the BCR into early endosomes suggests strategies for targeted antigen delivery.

  19. Sharing the burden: antigen transport and firebreaks in immune responses

    OpenAIRE

    Handel, Andreas; Yates, Andrew; Pilyugin, Sergei S.; Antia, Rustom

    2008-01-01

    Communication between cells is crucial for immune responses. An important means of communication during viral infections is the presentation of viral antigen on the surface of an infected cell. Recently, it has been shown that antigen can be shared between infected and uninfected cells through gap junctions, connexin-based channels, that allow the transport of small molecules. The uninfected cell receiving antigen can present it on its surface. Cells presenting viral antigen are detected and ...

  20. Peak-flow frequency analyses and results based on data through water year 2011 for selected streamflow-gaging stations in or near Montana: Chapter C in Montana StreamStats

    Science.gov (United States)

    Sando, Steven K.; McCarthy, Peter M.; Dutton, DeAnn M.

    2016-04-05

    Chapter C of this Scientific Investigations Report documents results from a study by the U.S. Geological Survey, in cooperation with the Montana Department of Transportation and the Montana Department of Natural Resources, to provide an update of statewide peak-flow frequency analyses and results for Montana. The purpose of this report chapter is to present peak-flow frequency analyses and results for 725 streamflow-gaging stations in or near Montana based on data through water year 2011. The 725 streamflow-gaging stations included in this study represent nearly all streamflowgaging stations in Montana (plus some from adjacent states or Canadian Provinces) that have at least 10 years of peak-flow records through water year 2011. For 29 of the 725 streamflow-gaging stations, peak-flow frequency analyses and results are reported for both unregulated and regulated conditions. Thus, peak-flow frequency analyses and results are reported for a total of 754 analyses. Estimates of peak-flow magnitudes for 66.7-, 50-, 42.9-, 20-, 10-, 4-, 2-, 1-, 0.5-, and 0.2-percent annual exceedance probabilities are reported. These annual exceedance probabilities correspond to 1.5-, 2-, 2.33-, 5-, 10-, 25-, 50-, 100-, 200-, and 500-year recurrence intervals.

  1. Immunity to intracellular Salmonella depends on surface-associated antigens.

    Directory of Open Access Journals (Sweden)

    Somedutta Barat

    Full Text Available Invasive Salmonella infection is an important health problem that is worsening because of rising antimicrobial resistance and changing Salmonella serovar spectrum. Novel vaccines with broad serovar coverage are needed, but suitable protective antigens remain largely unknown. Here, we tested 37 broadly conserved Salmonella antigens in a mouse typhoid fever model, and identified antigen candidates that conferred partial protection against lethal disease. Antigen properties such as high in vivo abundance or immunodominance in convalescent individuals were not required for protectivity, but all promising antigen candidates were associated with the Salmonella surface. Surprisingly, this was not due to superior immunogenicity of surface antigens compared to internal antigens as had been suggested by previous studies and novel findings for CD4 T cell responses to model antigens. Confocal microscopy of infected tissues revealed that many live Salmonella resided alone in infected host macrophages with no damaged Salmonella releasing internal antigens in their vicinity. In the absence of accessible internal antigens, detection of these infected cells might require CD4 T cell recognition of Salmonella surface-associated antigens that could be processed and presented even from intact Salmonella. In conclusion, our findings might pave the way for development of an efficacious Salmonella vaccine with broad serovar coverage, and suggest a similar crucial role of surface antigens for immunity to both extracellular and intracellular pathogens.

  2. Antigen-specific active immunotherapy for ovarian cancer

    NARCIS (Netherlands)

    Leffers, N.; Daemen, T.; Helfrich, W.; Boezen, H. M.; Cohlen, B. J.; Melief, Cornelis; Nijman, H. W.

    2010-01-01

    BACKGROUND: Despite advances in chemotherapy, prognosis of ovarian cancer remains poor. Antigen-specific active immunotherapy aims to induce a tumour-antigen-specific anti-tumour immune responses as an alternative treatment for ovarian cancer. OBJECTIVES: To assess feasibility of antigen-specific ac

  3. 21 CFR 660.40 - Hepatitis B Surface Antigen.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Hepatitis B Surface Antigen. 660.40 Section 660.40...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.40 Hepatitis B Surface Antigen. (a) Proper name and definition. The proper name of this...

  4. Recovery of antigenically reactive HIV-2 cores.

    Science.gov (United States)

    Chrystie, I L; Almeida, J D

    1989-03-01

    Negative staining studies of human immunodeficiency virus (HIV) have been hampered by the fragile nature of the particles. Although detergent treatment is capable of releasing cores from HIV-2 particles, these are unstable and do not retain morphological integrity. Addition of glutaraldehyde will stabilise these structures but, if used at too high a concentration, will destroy their antigenicity. This study shows that if both detergent and glutaraldehyde are used in correct proportions, antigenically reactive cores can be recovered from HIV-2 cell cultures. More specifically we show that a mixture of 0.1% Nonidet P40 and 0.1% glutaraldehyde produces preparations of HIV-2 cores that are suitable for immune electron microscopy. These cores reacted positively, that is, formed immune complexes, with both human HIV-2 antisera and a mouse monoclonal antibody that, although directed against p24 (HIV-1), reacts also with p25 (HIV-2).

  5. Evaluation of melanoma antigen gene A3 expression in drug resistance of epidermal growth factor receptor-tyrosine kinase inhibitors in advanced nonsmall cell lung cancer treatment

    Directory of Open Access Journals (Sweden)

    Ju Jin

    2015-01-01

    Conclusion: MAGE-A3 expression in EGFR-TKIs target therapy in NSCLC patient suggests that there might be EGFR-TKIs drug resistance, and the higher the level of expression, the shorter the time of acquired drug resistance.

  6. Tumor Immunity by Hydrophobic Bearing Antigens

    Science.gov (United States)

    2004-07-01

    protooncogene; TAL, tumor-associated lymphocyte; Perf, perforn, MRT, mean fluorescence intensity; IFN-g= Interferon gamma , FS= Forward scatter; Key words...Badovinac, V. P., T vinnereim, A. R., and Harty, J. T, Regulation of antigen-specific CD8+ Tcell homeostasis by perforin and interferon - gamma . Science...Cancer Res 2003; 63: 2535-45, 17. Zanussi, S., Vaceher, E., Caffau, C., et al. Interferon - gamma secretion and perforinexpression are impaired in CD8+ T

  7. Low-flow analysis and selected flow statistics representative of 1930-2002 for streamflow-gaging stations in or near West Virginia

    Science.gov (United States)

    Wiley, Jeffrey B.

    2006-01-01

    Five time periods between 1930 and 2002 are identified as having distinct patterns of annual minimum daily mean flows (minimum flows). Average minimum flows increased around 1970 at many streamflow-gaging stations in West Virginia. Before 1930, however, there might have been a period of minimum flows greater than any period identified between 1930 and 2002. The effects of climate variability are probably the principal causes of the differences among the five time periods. Comparisons of selected streamflow statistics are made between values computed for the five identified time periods and values computed for the 1930-2002 interval for 15 streamflow-gaging stations. The average difference between statistics computed for the five time periods and the 1930-2002 interval decreases with increasing magnitude of the low-flow statistic. The greatest individual-station absolute difference was 582.5 percent greater for the 7-day 10-year low flow computed for 1970-1979 compared to the value computed for 1930-2002. The hydrologically based low flows indicate approximately equal or smaller absolute differences than biologically based low flows. The average 1-day 3-year biologically based low flow (1B3) and 4-day 3-year biologically based low flow (4B3) are less than the average 1-day 10-year hydrologically based low flow (1Q10) and 7-day 10-year hydrologic-based low flow (7Q10) respectively, and range between 28.5 percent less and 13.6 percent greater. Seasonally, the average difference between low-flow statistics computed for the five time periods and 1930-2002 is not consistent between magnitudes of low-flow statistics, and the greatest difference is for the summer (July 1-September 30) and fall (October 1-December 31) for the same time period as the greatest difference determined in the annual analysis. The greatest average difference between 1B3 and 4B3 compared to 1Q10 and 7Q10, respectively, is in the spring (April 1-June 30), ranging between 11.6 and 102.3 percent

  8. Study of serum Helicobacter pylori soluble antigen

    Institute of Scientific and Technical Information of China (English)

    吴勤动; 朱永良

    2002-01-01

    Objective:to explore a new serological method for detecting Helicobacter pylori(H.pylori) infection.Methods:Serum soluble antigen of H.pylori was detected by using avidin-biotin ELISA technique to evaluate the status of H.pylori infection and for comparison with rapid urease test(RUT).histologic examination and serology,Results:The sensitivity,specificity,positive predictive value and negative predictive value were 77.46% ,91.07%,91.67% and 76.12%,respectively.The prevalence rate of werum H. pylori soluble antigen in 138 patients undergong endoscopy was similar to the rate obtained by 14 C-UBT methods(P>0.05).Conclusions:The detection of serum H.pylori soluble antigen(HpSAg) could be used as a new serological method which is accurate,and convenient,not affected by the memorizing raction of serum antibody;is more sensitive,more specific and suitable for dinical diagriosis,and evaluation of eradication and for follow-up of H.pylori as well as for detection in children and pregnant women.

  9. Study of serum Helicobacter pylori soluble antigen

    Institute of Scientific and Technical Information of China (English)

    吴勤动; 朱永良

    2002-01-01

    Objective: to explore a new serological method for detecting Helicobac ter pylori ( H. pylori ) infection. Methods: Serum soluble antigen of H. p ylor i was detected by using avidin-biotin ELISA technique to evaluate the status of H. pylori infection and for comparison with rapid urease test ( RUT ), histo logi c examination and serology. Results: The sensitivity, specificity, positive pred ictive value and negative predictive value were 77.46%, 91.07%, 91.67% a nd 76.12 %, respectively. The prevalence rate of serum H. pylori soluble antigen in 138 patients undergoing endoscopy was similar to the rate obtained by 14 C-UBT met hods ( P>0.05 ). Conclusions: The detection of serum H. pylori solub le antigen( HpSAg) could be used as a new serological method which is accurate, and convenie nt, not affected by the memorizing reaction of serum antibody; is more sensitive , m ore specific and suitable for clinical diagnosis, and evaluation of eradication and for follow-up of H. pylori as well as for detection in children and pre gnant women.

  10. Limited antigenic variation in the Trypanosoma cruzi candidate vaccine antigen TSA-1.

    Science.gov (United States)

    Knight, J M; Zingales, B; Bottazzi, M E; Hotez, P; Zhan, B

    2014-12-01

    Chagas disease (American trypanosomiasis caused by Trypanosoma cruzi) is one of the most important neglected tropical diseases in the Western Hemisphere. The toxicities and limited efficacies of current antitrypanosomal drugs have prompted a search for alternative technologies such as a therapeutic vaccine comprised of T. cruzi antigens, including a recombinant antigen encoding the N-terminal 65 kDa portion of Trypomastigote surface antigen-1 (TSA-1). With at least six known genetically distinct T. cruzi lineages, variability between the different lineages poses a unique challenge for the development of broadly effective therapeutic vaccine. The variability across the major lineages in the current vaccine candidate antigen TSA-1 has not previously been addressed. To assess the variation in TSA-1, we cloned and sequenced TSA-1 from several different T. cruzi strains representing three of the most clinically relevant lineages. Analysis of the different alleles showed limited variation in TSA-1 across the different strains and fit with the current theory for the evolution of the different lineages. Additionally, minimal variation in known antigenic epitopes for the HLA-A 02 allele suggests that interlineage variation in TSA-1 would not impair the range and efficacy of a vaccine containing TSA-1.

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

    Directory of Open Access Journals (Sweden)

    Christopher A MacRaild

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

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

    Science.gov (United States)

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

    2015-01-01

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

  13. Expression, purification and antigenicity of Neospora caninum-antigens using silkworm larvae targeting for subunit vaccines.

    Science.gov (United States)

    Otsuki, Takahiro; Dong, Jinhua; Kato, Tatsuya; Park, Enoch Y

    2013-02-18

    Infection of Neospora caninum causes abortion in cattle, which has a serious worldwide impact on the economic performance of the dairy and beef industries. Now, inexpensive and efficacious vaccines are required to protect cattle from neosporosis in livestock industry. In this study, N. caninum surface antigen 1 (SAG1) and SAG1-related sequence 2 (SRS2) were expressed in hemolymph of silkworm larvae as a soluble form. Expressed SAG1 and SRS2 clearly showed antigenicity against N. caninum-positive sera of cow. SAG1 and SRS2 were purified to near homogeneity from hemolymph of silkworm larvae using anti-FLAG M2 antibody agarose: approximately 1.7 mg of SAG1 from 10 silkworm larvae and 370 μg of SRS2 from 17 silkworm larvae. Mice that were injected by antigens induced antibodies against SAG1 and SRS2. This study indicates that it is possible that this silkworm expression system leads to a large-scale production of N. caninum-antigens with biological function and low production cost. Bombyx mori nucleopolyhedrovirus (BmNPV) bacmid expression system paves the way to produce largely and rapidly these recombinant antigens for its application to subunit vaccines against neosporosis in cattle.

  14. Modulation of antigenicity of mycelial antigens during developmental cycle of Karnal bunt (Tilletia indica) of wheat.

    Science.gov (United States)

    Rai, G; Kumar, A; Singh, A; Garg, G K

    2000-05-01

    Indirect enzyme linked immunosorbent assays (ELISA) were developed using polyclonal antibodies against soluble cytoplasmic (SCA) and insoluble cell wall antigens (ICWA) for monitoring modulation of mycelial antigens during growth cycle of T. indica. With SCA, continuous decrease in ELISA reactivity was observed in maturing fungus cultures, suggesting that SCA were expressed predominantly during early vegetative phase and their decreasing role was apparent as the fungus matures possibly towards sporogenous mycelium. In case of ICWA, the reaction profile showed an increase up to exponential phase of growth probably due to increase in the cell division and branching of mycelium. But later, ICWA antibody reactivity was decreased which may be due to conversion of mycelial phase to sporogenous phase, a quiescent stage of growth. Characterization of changes in antigenic configuration during developmental cycle of Tilletia indica by these antibodies could prove to be useful in identification of developmentally related and virulence marker(s).

  15. Genetic diversity and antigenicity variation of Babesia bovis merozoite surface antigen-1 (MSA-1) in Thailand.

    Science.gov (United States)

    Tattiyapong, Muncharee; Sivakumar, Thillaiampalam; Takemae, Hitoshi; Simking, Pacharathon; Jittapalapong, Sathaporn; Igarashi, Ikuo; Yokoyama, Naoaki

    2016-07-01

    Babesia bovis, an intraerythrocytic protozoan parasite, causes severe clinical disease in cattle worldwide. The genetic diversity of parasite antigens often results in different immune profiles in infected animals, hindering efforts to develop immune control methodologies against the B. bovis infection. In this study, we analyzed the genetic diversity of the merozoite surface antigen-1 (msa-1) gene using 162 B. bovis-positive blood DNA samples sourced from cattle populations reared in different geographical regions of Thailand. The identity scores shared among 93 msa-1 gene sequences isolated by PCR amplification were 43.5-100%, and the similarity values among the translated amino acid sequences were 42.8-100%. Of 23 total clades detected in our phylogenetic analysis, Thai msa-1 gene sequences occurred in 18 clades; seven among them were composed of sequences exclusively from Thailand. To investigate differential antigenicity of isolated MSA-1 proteins, we expressed and purified eight recombinant MSA-1 (rMSA-1) proteins, including an rMSA-1 from B. bovis Texas (T2Bo) strain and seven rMSA-1 proteins based on the Thai msa-1 sequences. When these antigens were analyzed in a western blot assay, anti-T2Bo cattle serum strongly reacted with the rMSA-1 from T2Bo, as well as with three other rMSA-1 proteins that shared 54.9-68.4% sequence similarity with T2Bo MSA-1. In contrast, no or weak reactivity was observed for the remaining rMSA-1 proteins, which shared low sequence similarity (35.0-39.7%) with T2Bo MSA-1. While demonstrating the high genetic diversity of the B. bovis msa-1 gene in Thailand, the present findings suggest that the genetic diversity results in antigenicity variations among the MSA-1 antigens of B. bovis in Thailand.

  16. New diagnostic antigens for early trichinellosis: the excretory-secretory antigens of Trichinella spiralis intestinal infective larvae.

    Science.gov (United States)

    Sun, Ge Ge; Liu, Ruo Dan; Wang, Zhong Quan; Jiang, Peng; Wang, Li; Liu, Xiao Lin; Liu, Chun Yin; Zhang, Xi; Cui, Jing

    2015-12-01

    The excretory-secretory (ES) antigens from Trichinella spiralis muscle larvae (ML) are the most commonly used diagnostic antigens for trichinellosis, but anti-Trichinella IgG antibodies cannot be detected until 2-3 weeks after infection; there is an obvious window period between Trichinella infection and antibody positivity. Intestinal infective larvae (IIL) are the first invasive stage during Trichinella infection, and their ES antigens are firstly exposed to the immune system and might be the early diagnostic markers of trichinellosis. The aim of this study was to evaluate the early diagnostic values of IIL ES antigens for trichinellosis. The IIL were collected from intestines of infected mice at 6 h postinfection (hpi), and IIL ES antigens were prepared by incubation for 18 h. Anti-Trichinella IgG antibodies in mice infected with 100 ML were detectable by ELISA with IIL ES antigens as soon as 10 days postinfection (dpi), but ELISA with ML ES antigens did not permit detection of infected mice before 12 dpi. When the sera of patients with trichinellosis at 19 dpi were assayed, the sensitivity (100 %) of ELISA with IIL ES antigens was evidently higher than 75 % of ELISA with ML ES antigens (P < 0.05) The specificity (96.86 %) of ELISA with IIL ES antigens was also higher than 89.31 % of ELISA with ML ES antigens (P < 0.05). The IIL ES antigens provided a new source of diagnostic antigens and could be considered as a potential early diagnostic antigen for trichinellosis.

  17. Overlapping antigenic repertoires of variant antigens expressed on the surface of erythrocytes infected by Plasmodium falciparum

    DEFF Research Database (Denmark)

    Giha, H A; Staalsoe, T; Dodoo, D;

    1999-01-01

    Antibodies against variable antigens expressed on the surface of Plasmodium falciparum-infected erythrocytes are believed to be important for protection against malaria. A target for these antibodies is the P. falciparum erythrocyte membrane protein 1, PfEMP1, which is encoded by around 50 var...... genes and undergoes clonal variation. Using agglutination and mixed agglutination tests and flow cytometry to analyse the recognition of variant antigens on parasitized erythrocytes by plasma antibodies from individuals living in Daraweesh in eastern Sudan, an area of seasonal and unstable malaria...

  18. Protamine-based nanoparticles as new antigen delivery systems.

    Science.gov (United States)

    González-Aramundiz, José Vicente; Peleteiro Olmedo, Mercedes; González-Fernández, África; Alonso Fernández, María José; Csaba, Noemi Stefánia

    2015-11-01

    The use of biodegradable nanoparticles as antigen delivery vehicles is an attractive approach to overcome the problems associated with the use of Alum-based classical adjuvants. Herein we report, the design and development of protamine-based nanoparticles as novel antigen delivery systems, using recombinant hepatitis B surface antigen as a model viral antigen. The nanoparticles, composed of protamine and a polysaccharide (hyaluronic acid or alginate), were obtained using a mild ionic cross-linking technique. The size and surface charge of the nanoparticles could be modulated by adjusting the ratio of the components. Prototypes with optimal physicochemical characteristics and satisfactory colloidal stability were selected for the assessment of their antigen loading capacity, antigen stability during storage and in vitro and in vivo proof-of-concept studies. In vitro studies showed that antigen-loaded nanoparticles induced the secretion of cytokines by macrophages more efficiently than the antigen in solution, thus indicating a potential adjuvant effect of the nanoparticles. Finally, in vivo studies showed the capacity of these systems to trigger efficient immune responses against the hepatitis B antigen following intramuscular administration, suggesting the potential interest of protamine-polysaccharide nanoparticles as antigen delivery systems.

  19. Tissue polypeptide antigen activity in cerebrospinal fluid

    DEFF Research Database (Denmark)

    Bach, F; Söletormos, Georg; Dombernowsky, P

    1991-01-01

    in the CSF and neurological clinical function. TPpA concentrations decreased in parallel with the clinical response and increased prior to CNS disease progression. As a marker for CNS metastases, the level of TPpA in the CSF in breast cancer patients appears to be superior to the level of protein, lactate......Tissue polypeptide antigen (TPpA) in the cerebrospinal fluid (CSF) was measured in 59 consecutive breast cancer patients with suspected central nervous system (CNS) metastases. Subsequently, we determined that 13 patients had parenchymal brain metastases, 10 had leptomeningeal carcinomatosis...

  20. Biofunctionalizing nanofibers with carbohydrate blood group antigens.

    Science.gov (United States)

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

    2016-11-01

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

  1. Studies on the Antigenic Relationship among Phleboviruses

    Science.gov (United States)

    1982-01-01

    was easily differentiated by this method. Rift Valley fever virus was shown to be antigenically related to Candiru, Frijoles , Karimabad and Punta... Frijoles VP-161A HS(3) _-90% plaque reduction were recorded as positive. Gabek Forest Sud An 754-61 RS(3) Gordil Dak An B 496d MAF(4) Icoaraci Be An...10 10 0 0 80 0 0 2,60 0 40 0 0 CHILIBRE ង ង ង ង ង ង ង ង ង ង 1,280 ង ង ង FRIJOLES 0 0 0 0 0 0 0 0 0 0 0 10,240 0 0 GABEK

  2. Protective antibody titres and antigenic competition in multivalent Dichelobacter nodosus fimbrial vaccines using characterised rDNA antigens.

    Science.gov (United States)

    Raadsma, H W; O'Meara, T J; Egerton, J R; Lehrbach, P R; Schwartzkoff, C L

    1994-03-01

    The relationship between K-agglutination antibody titres and protection against experimental challenge with Dichelobacter nodosus, the effect of increasing the number of D. nodosus fimbrial antigens, and the importance of the nature of additional antigens in multivalent vaccines on antibody response and protection against experimental challenge with D. nodosus were examined in Merino sheep. A total of 204 Merino sheep were allocated to one of 12 groups, and vaccinated with preparations containing a variable number of rDNA D. nodosus fimbrial antigens. The most complex vaccine contained ten fimbrial antigens from all major D. nodosus serogroups, while the least complex contained a single fimbrial antigen. In addition to D. nodosus fimbrial antigens, other bacterial rDNA fimbrial antigens (Moraxella bovis Da12d and Escherichia coli K99), and bovine serum albumin (BSA) were used in some vaccines. Antibody titres to fimbrial antigens and BSA were measured by agglutination and ELISA tests, respectively. Antibody titres were determined on five occasions (Weeks 0, 3, 6, 8, and 11 after primary vaccination). All sheep were exposed to an experimental challenge with virulent isolates of D. nodosus from either serogroup A or B, 8 weeks after primary vaccination. For D. nodosus K-agglutinating antibody titres, a strong negative correlation between antibody titre and footrot lesion score was observed. This relationship was influenced by the virulence of the challenge strain. Increasing the number of fimbrial antigens in experimental rDNA D. nodosus fimbrial vaccines resulted in a linear decrease in K-agglutinating antibody titres to individual D. nodosus serogroups. Similarly, a linear decrease in protection to challenge with homologous serogroups was observed as the number of D. nodosus fimbrial antigens represented in the vaccine increased. The reduction in antibody titres in multicomponent vaccines is thought to be due to antigenic competition. The level of competition

  3. Antigen-induced and non-antigen-induced histamine release from rat mast cells sensitized with mouse antiserum.

    Directory of Open Access Journals (Sweden)

    Kurose,Masao

    1981-10-01

    Full Text Available Marked IgE-mediated histamine release from rat mast cells sensitized in vitro with mouse antiserum occurs in the presence of added Ca++ and phosphatidylserine (PS, although a considerable degree of antigen-induced histamine release which may utilize intracellular or cell-bound calcium is also observed. The decay in the responsiveness to Ca++ of the sensitized cells stimulated by antigen in Ca++-free medium in the presence of PS is relatively slow, and maximum release is produced by Ca++ added 1 min after antigen. Histamine release also occurs when Ca++ is added after PS in the absence of antigen to the sensitized cells suspended in Ca++-free medium. Unlike the antigen-induced release, the intensity of this non-antigen-induced release varies depending on both mast-cell and antiserum pools. A heat-labile factor(s, which is different from antigen-specific IgE antibody and is also contained in normal mouse serum, is involved in this reaction. In the antigen-nondependent (PS + Ca++-induced release, no decay in the responsiveness to Ca++ is observed after PS addition. Both the antigen-induced and non-antigen-induced release are completed fairly rapidly and are dependent of temperature, pH and energy.

  4. Antigen presentation for priming T cells in central system.

    Science.gov (United States)

    Dasgupta, Shaoni; Dasgupta, Subhajit

    2017-01-01

    Generation of myelin antigen-specific T cells is a major event in neuroimmune responses that causes demyelination. The antigen-priming of T cells and its location is important in chronic and acute inflammation. In autoimmune multiple sclerosis, the effector T cells are considered to generate in periphery. However, the reasons for chronic relapsing-remitting events are obscure. Considering mechanisms, a feasible aim of research is to investigate the role of antigen-primed T cells in lupus cerebritis. Last thirty years of investigations emphasize the relevance of microglia and infiltrated dendritic cells/macrophages as antigen presenting cells in the central nervous system. The recent approach towards circulating B-lymphocytes is an important area in the context. Here, we analyze the existing findings on antigen presentation in the central nervous system. The aim is to visualize signaling events of myelin antigen presentation to T cells and lead to the strategy of future goals on immunotherapy research.

  5. Human Ia-like antigens in non-lymphoid organs.

    Science.gov (United States)

    Koyama, K; Fukunishi, T; Barcos, M; Tanigaki, N; Pressman, D

    1979-01-01

    Human Ia-like antigens in liver and kidney were shown by the immunofluorescence assay to be present mostly in the endothelial-mesenchymal cells of these organs. The parenchymal cells apparently contained no human Ia-like antigens. The antigens in liver and kidney were purified and shown to have the same subunit structure as human Ia-like antigens of cultured B-lymphoid cells. The human Ia-like antigens in non-lymphoid organs, not only in liver and kidney but also in testis, heart, muscle and brain, carried all the xenoantigenic characteristics of human Ia-like antigens expressed on lymphoid cells of B-cell lineage. Images Figure 1 PMID:389786

  6. Tissue distribution of histo-blood group antigens

    DEFF Research Database (Denmark)

    Ravn, V; Dabelsteen, Erik

    2000-01-01

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

  7. Strategies to enhance immunogenicity of cDNA vaccine encoded antigens by modulation of antigen processing

    NARCIS (Netherlands)

    Platteel, Anouk C M; Marit de Groot, A; Andersen, Peter; Ovaa, Huib; Kloetzel, Peter M; Mishto, Michele; Sijts, Alice J A M

    2016-01-01

    Most vaccines are based on protective humoral responses while for intracellular pathogens CD8(+) T cells are regularly needed to provide protection. However, poor processing efficiency of antigens is often a limiting factor in CD8(+) T cell priming, hampering vaccine efficacy. The multistage cDNA va

  8. Mycobacterium leprae antigens involved in human immune responses. I. Identification of four antigens by monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Britton, W.J.; Hellqvist, L.; Basten, A.; Raison, R.L.

    1985-12-01

    Four distinct antigens were identified in soluble sonicates of Mycobacterium leprae by using a panel of 11 monoclonal antibodies. Cross-reactivity studies with other mycobacterial species were conducted by using ELISA and immunoblot assays, and demonstrated that determinants on two of the antigens were present in many mycobacteria, whereas the other two were limited in distribution. Competitive inhibition experiments with radiolabeled monoclonal antibodies showed cross-inhibition between antibodies identifying two of the four antigenicbands. These two bands, of M/sub tau/ 4.5 to 6 KD and 30 to 40 KD, were resistant to protease treatment after immunoblotting. In contrast the two other bands of 16 and 70 KD were protease-sensitive. Although all four bands reacted with some human lepromatous leprosy sera in immunoblots, the 4.5 to 6 KD and 30 to 40 KD bands were most prominent. Lepromatous leprosy sera also inhibited the binding of radiolabeled monoclonal antibodies to each of the four antigens, with the mean titer causing 50% inhibition being higher for antibodies reacting with the 4.5 to 6 KD and 30 to 40 KD bands. These findings indicated that all four antigens were involved in the human B cell response to M. leprae.

  9. Glycoconjugates as target antigens in peripheral neuropathies

    Directory of Open Access Journals (Sweden)

    Ljubica Suturkova

    2014-12-01

    Full Text Available Identification and characterization of antigens present at the human peripheral nerve is a great challenge in the field of neuroimmunology. The latest investigations are focused on the understanding of the biology of glycoconjugates present at the peripheral nerve, and their immunological reactivity. Increased titers of antibodies that recognize carbohydrate determinants of glycoconjugates (glycolipids and glycoproteins are associated with distinct neuropathic syndromes. There is considerable cross-reactivity among anti-ganglioside antibodies, resulting from shared oligosaccharide epitopes, possibly explaining the overlap in syndromes observed in many affected patients. Sera from patients with neuropathies (GBS, chronic inflammatory demielynating polyneuropathy - CIDP, multifocal motor neuropathy - MMN, cross-react with glycoproteins isolated from human peripheral nerve and from Campylobacter jejuni O:19. The frequency of occurrence of antibodies against these glycoproteins is different, depending of the type of neuropathy. Identification of the cross-reactive glycoproteins and possible additional auto antigens could be useful in laboratory evaluation of peripheral neuropathies and help to develop a more effective therapeutic approach.

  10. Antigen epitope of Helicobacter pylorivacuolating cytotoxin A

    Institute of Scientific and Technical Information of China (English)

    Xiu-Li Liu; Shu-Qin Li; Chun-Jie Liu; Hao-Xia Tao; Zhao-Shan Zhang

    2004-01-01

    AIM: To construct and select antigen epitopes of vacuolating cytotoxin A (VacA) for nontoxic VacA vaccine against Helicobacter pylori (H pylori) infection.METHODS: Eleven VacA epitopes were predicted according to VacA antigenic bioinformatics. Three candidates of VacA epitope were constructed through different combined epitopes. The candidate was linked with E. coli heat-labile enterotoxin B (LTB) by a linker of 7 amino acids, and cloned into plasmid pQE-60 in which fusion LTB-VacA epitope was efficiently expressed. To test the antigencity of the candidate, 6 BALB/c mice were treated with the fusion LTB-VacA epitope through intraperitoneal injection. To explore the ability of inhibiting the toxicity of VacA, cantiserum against the candidate was used to counteract VacA that induced HeLa cells to produce cell vacuoles in vitro.RESULTS: Serum IgG against the candidate was induced in the BALB/c mice. In vitro, the three antisera against the candidate efficiently counteracted the toxicity of VacA, and decreased the number of cell vacuoles by 14.17%, 20.20%and 30.41% respectively.CONCLUSION: Two of the three candidates, LZ-VacA1and LZ-VacA2, can be used to further study the mechanism of vacuolating toxicity of VacA, and to construct nontoxic VacA vaccine against H pylori infection.

  11. Immunoregulation by Taenia crassiceps and Its Antigens

    Directory of Open Access Journals (Sweden)

    Alberto N. Peón

    2013-01-01

    Full Text Available Taenia crassiceps is a cestode parasite of rodents (in its larval stage and canids (in its adult stage that can also parasitize immunocompromised humans. We have studied the immune response elicited by this helminth and its antigens in mice and human cells, and have discovered that they have a strong capacity to induce chronic Th2-type responses that are primarily characterized by high levels of Th2 cytokines, low proliferative responses in lymphocytes, an immature and LPS-tolerogenic profile in dendritic cells, the recruitment of myeloid-derived suppressor cells and, specially, alternatively activated macrophages. We also have utilized the immunoregulatory capabilities of this helminth to successfully modulate autoimmune responses and the outcome of other infectious diseases. In the present paper, we review the work of others and ourselves with regard to the immune response induced by T. crassiceps and its antigens, and we compare the advances in our understanding of this parasitic infection model with the knowledge that has been obtained from other selected models.

  12. Detection of peste des petits ruminants virus antigen using immunofiltration and antigen-competition ELISA methods.

    Science.gov (United States)

    Raj, G Dhinakar; Rajanathan, T M C; Kumar, C Senthil; Ramathilagam, G; Hiremath, Geetha; Shaila, M S

    2008-06-22

    Peste des petits ruminants (PPR) is one of the most economically important diseases affecting sheep and goats in India. An immunofiltration-based test has been developed using either mono-specific serum/monoclonal antibodies (mAb) prepared against a recombinant truncated nucleocapsid protein of rinderpest virus (RPV) cross-reactive with PPR virus. This method consists of coating ocular swab eluate from suspected animals onto a nitrocellulose membrane housed in a plastic module, which is allowed to react with suitable dilutions of a mAb or a mono-specific polyclonal antibody. The antigen-antibody complex formed on the membrane is then detected by protein A-colloidal gold conjugate, which forms a pink colour. In the immunofiltration test, concordant results were obtained using either PPRV mAb or mono-specific serum. Another test, an antigen-competition ELISA which relies on the competition between plate-coated recombinant truncated 'N' protein of RPV and the PPRV 'N' protein present in ocular swab eluates (sample) for binding to the mono-specific antibody against N protein of RPV (in liquid phase) was developed. The cut-off value for this test was established using reverse transcription polymerase chain reaction (RT-PCR) positive and negative oculo-nasal swab samples. Linear correlation between percent inhibition (PI) values in antigen-competition ELISA and virus infectivity titres was 0.992. Comparison of the immunofiltration test with the antigen-competition ELISA yielded a sensitivity of 80% and specificity of 100%. These two tests can serve as a screening (immunofiltration) and confirmatory (antigen-competition ELISA) test, respectively, in the diagnosis of PPR in sheep or goats.

  13. СAPSULAR ANTIGEN OF YERSINIA PESTIS

    Directory of Open Access Journals (Sweden)

    L. A. Kadnikova

    2015-01-01

    Full Text Available Plague is a zoonosis caused by gram-negative bacteria Yersinia pestis, which, as a rule, is transmitted to humans from septicemic rodents by the bites of infected fleas. This microbe killed more people than all of the wars in the human history. Y. pestis circulation in the natural plague foci is ensured by the whole number of pathogenicity factors with differing functional orientation. This review is devoted to one of them, Y. pestis capsular antigen (F1 or Caf1. The history of its discovery and studying of its genetic control, biosynthesis, isolation and purification, and physicochemical properties are reviewed. Its roles in plague pathogenesis and its application as a main component of plague vaccines are also discussed. Y. pestis capsule under light microscopy is visually amorphous, while high-resolution electron microscopy displays the structure formed from separate fimbria-like cords up to 200 nm long, diverging from the bacterial surface in different directions. At 37°C Y. pestis produce 800–1000 times more capsular antigen than at 28°C. Genes coding for 17.6-kD Caf1 protein, which contains 170 amino acids, are located in caf1 operon of pFra plasmid. Analysis of caf1 operon nucleotide sequence testified its close phylogenetic relationship with the gene clusters coding for pilus adhesins that were secreted with the help of chaperone/usher systems in enterobacteria including six additional adhesins in Y. pestis. Y. pestis multiplication within macrophages is the obligatory stage of plague pathogenesis, and the plague pathogen virulence correlates not with resistance to phagocyte ingesting but with bacterial ability to survive and multiply within phagolysosomes of phagocytes due to neutralization of antibacterial functions of eukaryotic cells. The capsule formed out of the Caf1 aggregates protects Y. pestis from ingestion by naïve host’s phagocytes and prevents from initiation of the alternative pathway of the complement system

  14. Identification of protective antigens for vaccination against systemic salmonellosis

    Directory of Open Access Journals (Sweden)

    Dirk eBumann

    2014-08-01

    Full Text Available There is an urgent medical need for improved vaccines with broad serovar coverage and high efficacy against systemic salmonellosis. Subunit vaccines offer excellent safety profiles but require identification of protective antigens, which remains a challenging task. Here, I review crucial properties of Salmonella antigens that might help to narrow down the number of potential candidates from more than 4000 proteins encoded in Salmonella genomes, to a more manageable number of 50-200 most promising antigens. I also discuss complementary approaches for antigen identification and potential limitations of current pre-clinical vaccine testing.

  15. Cancer-germline antigen vaccines and epigenetic enhancers

    DEFF Research Database (Denmark)

    Gjerstorff, Morten Frier; Burns, Jorge; Ditzel, Henrik Jorn

    2010-01-01

    can be achieved using epigenetic modifiers. AREAS COVERED IN THIS REVIEW: We provide an overview of the potential of CG antigens as targets for cancer immunotherapy, including advantages and disadvantages. We also discuss the current state of development of CG antigen vaccines, and the potential...... synergistic effect of combining CG antigen immunotherapeutic strategies with epigenetic modifiers. WHAT THE READER WILL GAIN: The reader will gain an overview of the past, present and future role of CG antigens in cancer immunotherapy. TAKE HOME MESSAGE: Chemoimmunotherapy using epigenetic drugs and CG...

  16. Bayesian nonparametric clustering in phylogenetics: modeling antigenic evolution in influenza.

    Science.gov (United States)

    Cybis, Gabriela B; Sinsheimer, Janet S; Bedford, Trevor; Rambaut, Andrew; Lemey, Philippe; Suchard, Marc A

    2017-01-18

    Influenza is responsible for up to 500,000 deaths every year, and antigenic variability represents much of its epidemiological burden. To visualize antigenic differences across many viral strains, antigenic cartography methods use multidimensional scaling on binding assay data to map influenza antigenicity onto a low-dimensional space. Analysis of such assay data ideally leads to natural clustering of influenza strains of similar antigenicity that correlate with sequence evolution. To understand the dynamics of these antigenic groups, we present a framework that jointly models genetic and antigenic evolution by combining multidimensional scaling of binding assay data, Bayesian phylogenetic machinery and nonparametric clustering methods. We propose a phylogenetic Chinese restaurant process that extends the current process to incorporate the phylogenetic dependency structure between strains in the modeling of antigenic clusters. With this method, we are able to use the genetic information to better understand the evolution of antigenicity throughout epidemics, as shown in applications of this model to H1N1 influenza. Copyright © 2017 John Wiley & Sons, Ltd.

  17. MHC structure and function – antigen presentation. Part 1

    Science.gov (United States)

    Goldberg, Anna Carla; Rizzo, Luiz Vicente

    2015-01-01

    The setting for the occurrence of an immune response is that of the need to cope with a vast array of different antigens from both pathogenic and non-pathogenic sources. When the first barriers against infection and innate defense fail, adaptive immune response enters the stage for recognition of the antigens by means of extremely variable molecules, namely immunoglobulins and T-cell receptors. The latter recognize the antigen exposed on cell surfaces, in the form of peptides presented by the HLA molecule. The first part of this review details the central role played by these molecules, establishing the close connection existing between their structure and their antigen presenting function. PMID:25807245

  18. Do FY antigens act as minor histocompatibility antigens in the graft-versus-host disease paradigm after human leukocyte antigen-identical sibling hematopoietic stem cell transplantation?

    Science.gov (United States)

    Sellami, Mohamed Hichem; Chaabane, Manel; Kaabi, Houda; Torjemane, Lamia; Ladeb, Saloua; Ben Othmane, Tarek; Hmida, Slama

    2012-03-01

    FY antigens are candidate minor histocompatibility antigens relevant to renal allograft rejection, but no data have been reported about their role in graft-versus-host disease (GVHD) incidence after human leukocyte antigen (HLA)-identical siblings hematopoietic stem cell transplantation (HSCT). The aim of this study was to examine the effect of donor/recipient disparity at FY antigens on the incidence of GVHD in Tunisian patients receiving an HLA-identical HSCT. This work enrolled 105 Tunisian pairs of recipients and their HLA-identical sibling donors of HSCs. FY genotyping was performed with the polymerase chain reaction-sequence-specific primer method and donor/recipient disparity for these antigens was analyzed at two levels: incompatibility and nonidentity. The case-control analyses showed no significant correlation between FY disparity and the incidence of either acute or chronic GVHD. Sample size calculation showed that 572 cases and 1716 controls would be necessary to be able to detect a significant association with 80% power and two-sided type I error level of 5% (α=0.05). The lack of association in the studied cohort may be explained by the low immunogenicity of FY antigens in HSCT context, compared with other antigens such as HA-1 and CD31.

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

    DEFF Research Database (Denmark)

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

    1988-01-01

    The processing of a protein antigen is a multi-step event taking place in antigen-presenting cells. Processing is a prerequisite for the recognition of most antigens by T lymphocytes. The antigen is ingested by endocytosis, transported to an acid cellular compartment and subjected to proteolytic ...

  20. A universal computational model for predicting antigenic variants of influenza A virus based on conserved antigenic structures

    Science.gov (United States)

    Peng, Yousong; Wang, Dayan; Wang, Jianhong; Li, Kenli; Tan, Zhongyang; Shu, Yuelong; Jiang, Taijiao

    2017-01-01

    Rapid determination of the antigenicity of influenza A virus could help identify the antigenic variants in time. Currently, there is a lack of computational models for predicting antigenic variants of some common hemagglutinin (HA) subtypes of influenza A viruses. By means of sequence analysis, we demonstrate here that multiple HA subtypes of influenza A virus undergo similar mutation patterns of HA1 protein (the immunogenic part of HA). Further analysis on the antigenic variation of influenza A virus H1N1, H3N2 and H5N1 showed that the amino acid residues’ contribution to antigenic variation highly differed in these subtypes, while the regional bands, defined based on their distance to the top of HA1, played conserved roles in antigenic variation of these subtypes. Moreover, the computational models for predicting antigenic variants based on regional bands performed much better in the testing HA subtype than those did based on amino acid residues. Therefore, a universal computational model, named PREDAV-FluA, was built based on the regional bands to predict the antigenic variants for all HA subtypes of influenza A viruses. The model achieved an accuracy of 0.77 when tested with avian influenza H9N2 viruses. It may help for rapid identification of antigenic variants in influenza surveillance. PMID:28165025

  1. A Role For Mitochondria In Antigen Processing And Presentation.

    Science.gov (United States)

    Bonifaz, Lc; Cervantes-Silva, Mp; Ontiveros-Dotor, E; López-Villegas, Eo; Sánchez-García, Fj

    2014-09-23

    Immune synapse formation is critical for T lymphocyte activation, and mitochondria have a role in this process, by localizing close to the immune synapse, regulating intracellular calcium concentration, and providing locally required ATP. The interaction between antigen presenting cells (APCs) and T lymphocytes is a two-way signaling process. However, the role of mitochondria in antigen presenting cells during this process remains unknown. For APCs to be able to activate T lymphocytes, they must first engage in an antigen-uptake, -processing, and -presentation process. Here we show that HEL-loaded B lymphocytes, as a type of APCs, undergo a small but significant mitochondrial depolarization by 1-2 h following antigen exposure thus suggesting an increase in their metabolic demands. Inhibition of ATP synthase (oligomycin) or mitochondrial Ca(2+) uniporter (MCU) (Ruthenium red) had no effect on antigen uptake. Therefore, antigen processing and antigen presentation were further analyzed. Oligomycin treatment reduced the amount of specific MHC-peptide complexes but not total MHC II on the cell membrane of B lymphocytes which correlated with a decrease in antigen presentation. However, oligomycin also reduced antigen presentation by B lymphocytes that endogenously express HEL and by B lymphocytes loaded with the HEL48-62 peptide, although to a lesser extent. ATP synthase inhibition and MCU inhibition had a clear inhibitory effect on antigen processing (DQ-OVA). Taking together these results suggest that ATP synthase and MCU are relevant for antigen processing and presentation. Finally, APCs mitochondria were found to re-organize towards the APC-T immune synapse. This article is protected by copyright. All rights reserved.

  2. Engineering antigen-specific immunological tolerance.

    Energy Technology Data Exchange (ETDEWEB)

    Kontos, Stephan; Grimm, Alizee J.; Hubbell, Jeffrey A.

    2015-05-01

    Unwanted immunity develops in response to many protein drugs, in autoimmunity, in allergy, and in transplantation. Approaches to induce immunological tolerance aim to either prevent these responses or reverse them after they have already taken place. We present here recent developments in approaches, based on engineered peptides, proteins and biomaterials, that harness mechanisms of peripheral tolerance both prophylactically and therapeutically to induce antigenspecific immunological tolerance. These mechanisms are based on responses of B and T lymphocytes to other cells in their immune environment that result in cellular deletion or ignorance to particular antigens, or in development of active immune regulatory responses. Several of these approaches are moving toward clinical development, and some are already in early stages of clinical testing.

  3. Germinal center reaction: antigen affinity and presentation explain it all.

    Science.gov (United States)

    Oropallo, Michael A; Cerutti, Andrea

    2014-07-01

    The selection and expansion of B cells undergoing affinity maturation in the germinal center is a hallmark of humoral immunity. A recent paper in Nature provides new insights into the relationships between the affinity of the immunoglobulin receptor for antigen, the ability of B cells to present antigen to T cells, and the processes of selection, mutation, and clonal expansion in the germinal center.

  4. Protein antigen adsorption to the DDA/TDB liposomal adjuvant

    DEFF Research Database (Denmark)

    Hamborg, Mette; Jorgensen, Lene; Bojsen, Anders Riber;

    2013-01-01

    Understanding the nature of adjuvant-antigen interactions is important for the future design of efficient and safe subunit vaccines, but remains an analytical challenge. We studied the interactions between three model protein antigens and the clinically tested cationic liposomal adjuvant composed...

  5. 21 CFR 866.3402 - Plasmodium species antigen detection assays.

    Science.gov (United States)

    2010-04-01

    ... is a device that employs antibodies for the detection of specific malaria parasite antigens.... These devices are used for testing specimens from individuals who have signs and symptoms consistent with malaria infection. The detection of these antigens aids in the clinical laboratory diagnosis...

  6. Pneumocystis carinii from pigs and humans are antigenically distinct

    DEFF Research Database (Denmark)

    Christensen, C B; Settnes, Osvald Peter; Bille-Hansen, Vivi;

    1996-01-01

    The antigens of Pneumocystis carinii cysts isolated from pigs and humans were compared by the Western immunoblotting technique. Convalescent pig serum reacted with two antigens (approximately 78 kDa and 32.5 kDa) of porcine P. carinii cysts, whereas convalescent serum from humans did not react wi...

  7. Expression of Treponema pallidum Antigens in Escherichia coli

    Science.gov (United States)

    Walfield, Alan M.; Hanff, Philip A.; Lovett, Michael A.

    1982-04-01

    Treponema pallidum DNA was cloned in a bacteriophage. Clones were screened for expression of Treponema pallidum antigens by an in situ radio-immunoassay on nitrocellulose, with the use of subsequent reactions with syphilitic serum and radioiodinated Staphylococcus aureus protein A. One clone, which gave a strong signal, codes for at least seven antigens that react specifically with human antibodies to Treponema pallidum.

  8. Antigen Loss Variants: Catching Hold of Escaping Foes

    Science.gov (United States)

    Vyas, Maulik; Müller, Rolf; Pogge von Strandmann, Elke

    2017-01-01

    Since mid-1990s, the field of cancer immunotherapy has seen steady growth and selected immunotherapies are now a routine and preferred therapeutic option of certain malignancies. Both active and passive cancer immunotherapies exploit the fact that tumor cells express specific antigens on the cell surface, thereby mounting an immune response specifically against malignant cells. It is well established that cancer cells typically lose surface antigens following natural or therapy-induced selective pressure and these antigen-loss variants are often the population that causes therapy-resistant relapse. CD19 and CD20 antigen loss in acute lymphocytic leukemia and chronic lymphocytic leukemia, respectively, and lineage switching in leukemia associated with mixed lineage leukemia (MLL) gene rearrangements are well-documented evidences in this regard. Although increasing number of novel immunotherapies are being developed, majority of these do not address the control of antigen loss variants. Here, we review the occurrence of antigen loss variants in leukemia and discuss the therapeutic strategies to tackle the same. We also present an approach of dual-targeting immunoligand effectively retargeting NK cells against antigen loss variants in MLL-associated leukemia. Novel immunotherapies simultaneously targeting more than one tumor antigen certainly hold promise to completely eradicate tumor and prevent therapy-resistant relapses. PMID:28286501

  9. Acid test: lipid antigens get into the groove.

    Science.gov (United States)

    Kronenberg, Mitchell; Sullivan, Barbara A

    2008-06-01

    How do CD1 molecules load lipid antigens? In this issue of Immunity, Relloso et al. (2008) uncover how lysosomal pH targets amino acids in CD1b, causing it to open and attain a conformation more receptive to lipid antigens.

  10. Immunochemical analysis of Taenia taeniaeformis antigens expressed in Escherichia coli.

    Science.gov (United States)

    Bowtell, D D; Saint, R B; Rickard, M D; Mitchell, G F

    1986-12-01

    Previously we reported the isolation of several Escherichia coli clones expressing fragments of Taenia taeniaeformis antigens as beta-galactosidase fused proteins (Bowtell, Saint, Rickard & Mitchell, 1984). Here we describe the isolation of additional antigen-expressing clones from a larval cDNA library and the assignment of these clones to 7 antigen families. These were isolated with a polyspecific rabbit antiserum raised to the oncosphere. Since this serum was capable of reacting with a large number of antigens, it was important to develop techniques for rapidly determining the identity of the native T. taeniaeformis molecule corresponding to a cloned antigen gene. These included active immunization of rabbits with fused proteins and several techniques involving affinity purification on immobilized fused proteins. The reactivity of the antigen-positive clones with sera from humans infected with related parasites was also assessed. Finally, immunization of mice with several fused proteins failed to protect against subsequent infection, although antigens previously identified as candidate host-protective antigens (Bowtell, Mitchell, Anders, Lightowlers & Rickard, 1983) have yet to be identified in the expression library.

  11. Complex Antigens Drive Permissive Clonal Selection in Germinal Centers.

    Science.gov (United States)

    Kuraoka, Masayuki; Schmidt, Aaron G; Nojima, Takuya; Feng, Feng; Watanabe, Akiko; Kitamura, Daisuke; Harrison, Stephen C; Kepler, Thomas B; Kelsoe, Garnett

    2016-03-15

    Germinal center (GC) B cells evolve toward increased affinity by a Darwinian process that has been studied primarily in genetically restricted, hapten-specific responses. We explored the population dynamics of genetically diverse GC responses to two complex antigens-Bacillus anthracis protective antigen and influenza hemagglutinin-in which B cells competed both intra- and interclonally for distinct epitopes. Preferred VH rearrangements among antigen-binding, naive B cells were similarly abundant in early GCs but, unlike responses to haptens, clonal diversity increased in GC B cells as early "winners" were replaced by rarer, high-affinity clones. Despite affinity maturation, inter- and intraclonal avidities varied greatly, and half of GC B cells did not bind the immunogen but nonetheless exhibited biased VH use, V(D)J mutation, and clonal expansion comparable to antigen-binding cells. GC reactions to complex antigens permit a range of specificities and affinities, with potential advantages for broad protection.

  12. Mosaic VSGs and the scale of Trypanosoma brucei antigenic variation.

    Directory of Open Access Journals (Sweden)

    James P J Hall

    Full Text Available A main determinant of prolonged Trypanosoma brucei infection and transmission and success of the parasite is the interplay between host acquired immunity and antigenic variation of the parasite variant surface glycoprotein (VSG coat. About 0.1% of trypanosome divisions produce a switch to a different VSG through differential expression of an archive of hundreds of silent VSG genes and pseudogenes, but the patterns and extent of the trypanosome diversity phenotype, particularly in chronic infection, are unclear. We applied longitudinal VSG cDNA sequencing to estimate variant richness and test whether pseudogenes contribute to antigenic variation. We show that individual growth peaks can contain at least 15 distinct variants, are estimated computationally to comprise many more, and that antigenically distinct 'mosaic' VSGs arise from segmental gene conversion between donor VSG genes or pseudogenes. The potential for trypanosome antigenic variation is probably much greater than VSG archive size; mosaic VSGs are core to antigenic variation and chronic infection.

  13. The global antigenic diversity of swine influenza A viruses

    DEFF Research Database (Denmark)

    Lewis, Nicola S; Russell, Colin A; Langat, Pinky;

    2016-01-01

    Swine influenza presents a substantial disease burden for pig populations worldwide and poses a potential pandemic threat to humans. There is considerable diversity in both H1 and H3 influenza viruses circulating in swine due to the frequent introductions of viruses from humans and birds coupled...... with geographic segregation of global swine populations. Much of this diversity is characterized genetically but the antigenic diversity of these viruses is poorly understood. Critically, the antigenic diversity shapes the risk profile of swine influenza viruses in terms of their epizootic and pandemic potential....... Here, using the most comprehensive set of swine influenza virus antigenic data compiled to date, we quantify the antigenic diversity of swine influenza viruses on a multi-continental scale. The substantial antigenic diversity of recently circulating viruses in different parts of the world adds...

  14. Tumor Antigen-Derived Peptides Delivery for Cancer Immunotherapy.

    Science.gov (United States)

    Wenxue, Ma

    2014-02-05

    Tumor antigenic peptides therapeutics is a promising field for cancer immunotherapy. Benefits include the ease and rapid synthesis of antigenic peptides and capacity for modifications. In the past years, many peptide-based cancer vaccines have been tested in clinical trials with a limited success because of the difficulties associated with peptide stability and delivery approaches, consequently, resulting in inefficient antigen presentation and low response rates in patients with cancer. The development of suitable and efficient vaccine carrier systems still remains a major challenge. This article aims to describe a new delivery approach for tumor antigenic peptides and rationales of dendritic cells (DCs)-based vaccination. In order to elicit enhanced immune responses, poly(DL-lactide-co-glycolide) (PLGA), which has been approved by the US Food and Drug Administration (FDA) for the use of drug delivery, diagnostics and other applications of clinical and basic science research were employed for the formulation of making nanoparticles (NPs) while delivering tumor antigenic peptides.

  15. Antibodies anti granulocytic antigens in IBD: from microscopic morphology to antigenic specificity

    Directory of Open Access Journals (Sweden)

    A. Montanelli

    2011-09-01

    Full Text Available Objective: ANCA (p-ANCA and x-ANCA have been documented to occur in many inflammatory disorders. The specific ANCA antigens and the clinical correlation of a positive ANCA test in these disorders are still for the most part obscure. The aim of the present study was to investigate the prevalence of and the target antigens for ANCA in patients with IBD. Methods: 104 patients (67 age between 3-18 years, mean age 8+3 and 37 age between 25-70 years, mean age 48+15 clinically and hystopathologically diagnosed as: 67 ulcerative colitis, 16 Crohn’ disease, 21 other colitis (7 indeterminate colitis were enrolled in our study. ANCA were determined by ELISA and IIF methods. Results: We observed a good performance in terms of sensibility and specificity of ANCA, and a good correlation between the two methods used; as regard ELISA determination the antigen frequently found in our cases was lactoferrin (60%. Conclusions: Is still unclear the role of these “minor antigens” in the diagnosis and pathogenesis of IBD, but is clear that only morphologic evaluation is no more sufficient.

  16. Antigenic Relationships among Human Pathogenic Orientia tsutsugamushi Isolates from Thailand.

    Directory of Open Access Journals (Sweden)

    Sarah L James

    2016-06-01

    Full Text Available Scrub typhus is a common cause of undiagnosed febrile illness in certain tropical regions, but can be easily treated with antibiotics. The causative agent, Orientia tsutsugamushi, is antigenically variable which complicates diagnosis and efforts towards vaccine development.This study aimed to dissect the antigenic and genetic relatedness of O. tsutsugamushi strains and investigate sero-diagnostic reactivities by titrating individual patient sera against their O. tsutsugamushi isolates (whole-cell antigen preparation, in homologous and heterologous serum-isolate pairs from the same endemic region in NE Thailand. The indirect immunofluorescence assay was used to titrate Orientia tsutsugamushi isolates and human sera, and a mathematical technique, antigenic cartography, was applied to these data to visualise the antigenic differences and cross-reactivity between strains and sera. No functional or antigen-specific analyses were performed. The antigenic variation found in clinical isolates was much less pronounced than the genetic differences found in the 56kDa type-specific antigen genes. The Karp-like sera were more broadly reactive than the Gilliam-like sera.Antigenic cartography worked well with scrub typhus indirect immunofluorescence titres. The data from humoral responses suggest that a Karp-like strain would provide broader antibody cross-reactivity than a Gilliam-like strain. Although previous exposure to O. tsutsugamushi could not be ruled out, scrub typhus patient serum antibody responses were characterised by strong homologous, but weak heterologous antibody titres, with little evidence for cross-reactivity by Gilliam-like sera, but a broader response from some Karp-like sera. This work highlights the importance of antigenic variation in O. tsutsugamushi diagnosis and determination of new serotypes.

  17. Strategies for designing and monitoring malaria vaccines targeting diverse antigens

    Directory of Open Access Journals (Sweden)

    Alyssa E Barry

    2014-07-01

    Full Text Available After more than 50 years of intensive research and development, only one malaria vaccine candidate, RTS,S, has progressed to Phase 3 clinical trials. Despite only partial efficacy, this candidate is now forecast to become the first licensed malaria vaccine. Hence, more efficacious second-generation malaria vaccines that can significantly reduce transmission are urgently needed. This review will focus on a major obstacle hindering development of effective malaria vaccines: parasite antigenic diversity. Despite extensive genetic diversity in leading candidate antigens, vaccines have been and continue to be formulated using recombinant antigens representing only one or two strains. These vaccine strains represent only a small fraction of the diversity circulating in natural parasite populations, leading to escape of non-vaccine strains and challenging investigators’ abilities to measure strain-specific efficacy in vaccine trials. Novel strategies are needed to overcome antigenic diversity in order for vaccine development to succeed. Many studies have now catalogued the global diversity of leading Plasmodium falciparum and Plasmodium vivax vaccine antigens. In this review, we describe how population genetic approaches can be applied to this rich data source to predict the alleles that best represent antigenic diversity, polymorphisms that contribute to it, and to identify key polymorphisms associated with antigenic escape. We also suggest an approach to summarise the known global diversity of a given antigen to predict antigenic diversity, how to select variants that best represent the strains circulating in natural parasite populations and how to investigate the strain-specific efficacy of vaccine trials. Use of these strategies in the design and monitoring of vaccine trials will not only shed light on the contribution of genetic diversity to the antigenic diversity of malaria, but will also maximise the potential of future malaria vaccine

  18. Antigenic Relationships among Human Pathogenic Orientia tsutsugamushi Isolates from Thailand

    Science.gov (United States)

    Nawtaisong, Pruksa; Tanganuchitcharnchai, Ampai; Smith, Derek J.; Day, Nicholas P. J.; Paris, Daniel H.

    2016-01-01

    Background Scrub typhus is a common cause of undiagnosed febrile illness in certain tropical regions, but can be easily treated with antibiotics. The causative agent, Orientia tsutsugamushi, is antigenically variable which complicates diagnosis and efforts towards vaccine development. Methodology/Principal Findings This study aimed to dissect the antigenic and genetic relatedness of O. tsutsugamushi strains and investigate sero-diagnostic reactivities by titrating individual patient sera against their O. tsutsugamushi isolates (whole-cell antigen preparation), in homologous and heterologous serum-isolate pairs from the same endemic region in NE Thailand. The indirect immunofluorescence assay was used to titrate Orientia tsutsugamushi isolates and human sera, and a mathematical technique, antigenic cartography, was applied to these data to visualise the antigenic differences and cross-reactivity between strains and sera. No functional or antigen-specific analyses were performed. The antigenic variation found in clinical isolates was much less pronounced than the genetic differences found in the 56kDa type-specific antigen genes. The Karp-like sera were more broadly reactive than the Gilliam-like sera. Conclusions/Significance Antigenic cartography worked well with scrub typhus indirect immunofluorescence titres. The data from humoral responses suggest that a Karp-like strain would provide broader antibody cross-reactivity than a Gilliam-like strain. Although previous exposure to O. tsutsugamushi could not be ruled out, scrub typhus patient serum antibody responses were characterised by strong homologous, but weak heterologous antibody titres, with little evidence for cross-reactivity by Gilliam-like sera, but a broader response from some Karp-like sera. This work highlights the importance of antigenic variation in O. tsutsugamushi diagnosis and determination of new serotypes. PMID:27248711

  19. Case of rhesus antigen weak D type 4.2. (DAR category detection

    Directory of Open Access Journals (Sweden)

    L. L. Golovkina

    2015-01-01

    Full Text Available Serological methods of Rhesus antigens identification in humans cannot identify D-antigen variants. In this article the serological characteristics of Rhesus antigen D weak type 4.2. (Category DAR are described.

  20. Recognition of antigen-specific B-cell receptors from chronic lymphocytic leukemia patients by synthetic antigen surrogates.

    Science.gov (United States)

    Sarkar, Mohosin; Liu, Yun; Morimoto, Jumpei; Peng, Haiyong; Aquino, Claudio; Rader, Christoph; Chiorazzi, Nicholas; Kodadek, Thomas

    2014-12-18

    In patients with chronic lymphocytic leukemia (CLL), a single neoplastic antigen-specific B cell accumulates and overgrows other B cells, leading to immune deficiency. CLL is often treated with drugs that ablate all B cells, leading to further weakening of humoral immunity, and a more focused therapeutic strategy capable of targeting only the pathogenic B cells would represent a significant advance. One approach to this would be to develop synthetic surrogates of the CLL antigens allowing differentiation of the CLL cells and healthy B cells in a patient. Here, we describe nonpeptidic molecules capable of targeting antigen-specific B cell receptors with good affinity and selectivity using a combinatorial library screen. We demonstrate that our hit compounds act as synthetic antigen surrogates and recognize CLL cells and not healthy B cells. Additionally, we argue that the technology we developed can be used to identify other classes of antigen surrogates.

  1. Atomic structure of anthrax protective antigen pore elucidates toxin translocation.

    Science.gov (United States)

    Jiang, Jiansen; Pentelute, Bradley L; Collier, R John; Zhou, Z Hong

    2015-05-28

    Anthrax toxin, comprising protective antigen, lethal factor, and oedema factor, is the major virulence factor of Bacillus anthracis, an agent that causes high mortality in humans and animals. Protective antigen forms oligomeric prepores that undergo conversion to membrane-spanning pores by endosomal acidification, and these pores translocate the enzymes lethal factor and oedema factor into the cytosol of target cells. Protective antigen is not only a vaccine component and therapeutic target for anthrax infections but also an excellent model system for understanding the mechanism of protein translocation. On the basis of biochemical and electrophysiological results, researchers have proposed that a phi (Φ)-clamp composed of phenylalanine (Phe)427 residues of protective antigen catalyses protein translocation via a charge-state-dependent Brownian ratchet. Although atomic structures of protective antigen prepores are available, how protective antigen senses low pH, converts to active pore, and translocates lethal factor and oedema factor are not well defined without an atomic model of its pore. Here, by cryo-electron microscopy with direct electron counting, we determine the protective antigen pore structure at 2.9-Å resolution. The structure reveals the long-sought-after catalytic Φ-clamp and the membrane-spanning translocation channel, and supports the Brownian ratchet model for protein translocation. Comparisons of four structures reveal conformational changes in prepore to pore conversion that support a multi-step mechanism by which low pH is sensed and the membrane-spanning channel is formed.

  2. Standardization and characterization of antigens for the diagnosis of aspergillosis.

    Science.gov (United States)

    Stopiglia, Cheila Denise Ottonelli; Arechavala, Alicia; Carissimi, Mariana; Sorrentino, Julia Medeiros; Aquino, Valério Rodrigues; Daboit, Tatiane Caroline; Kammler, Luana; Negroni, Ricardo; Scroferneker, Maria Lúcia

    2012-04-01

    The aim of this study was to develop and characterize antigens for the diagnosis of aspergillosis. Nine strains of Aspergillus species Aspergillus fumigatus , Aspergillus flavus , and Aspergillus niger were grown in Sabouraud and Smith broth to produce exoantigens. The antigens were tested by immunodiffusion against sera from patients with aspergillosis and other systemic mycoses. The protein fraction of the antigens was detected by SDS-PAGE; Western blot and representative bands were assessed by mass spectrometry coupled to a nano Acquity UltraPerformance LC and analyzed by the Mascot search engine. Concurrently, all sera were tested with Platelia Aspergillus EIA. The most reactive antigens to sera from patients infected by A. fumigatus were produced by A. fumigatus MG2 Sabouraud and pooled A. fumigatus Sabouraud samples, both with a sensitivity of 93% and specificity of 100% and 97%, respectively. Aspergillus niger and A. flavus antigens were reactive against A. niger and A. flavus sera, each one with a sensitivity and specificity of 100%. Two proteins, probably responsible for antigenic activity, β-glucosidase in A. fumigatus and α-amylase in A. niger were attained. The commercial kit had a specificity of 22%, sensitivity of 100%, positive predictive value of 48%, and negative predictive value of 100%. The antigens produced showed high sensitivity and specificity and can be exploited for diagnostics of aspergilloma.

  3. Molecular mimics of the tumour antigen MUC1.

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    Tharappel C James

    Full Text Available A key requirement for the development of cancer immunotherapy is the identification of tumour-associated antigens that are differentially or exclusively expressed on the tumour and recognized by the host immune system. However, immune responses to such antigens are often muted or lacking due to the antigens being recognized as "self", and further complicated by the tumour environment and regulation of immune cells within. In an effort to circumvent the lack of immune responses to tumour antigens, we have devised a strategy to develop potential synthetic immunogens. The strategy, termed mirror image phage display, is based on the concept of molecular mimicry as demonstrated by the idiotype/anti-idiotype paradigm in the immune system. Here as 'proof of principle' we have selected molecular mimics of the well-characterised tumour associated antigen, the human mucin1 protein (MUC1 from two different peptide phage display libraries. The putative mimics were compared in structure and function to that of the native antigen. Our results demonstrate that several of the mimic peptides display T-cell stimulation activity in vitro when presented by matured dendritic cells. The mimic peptides and the native MUC1 antigenic epitopes can cross-stimulate T-cells. The data also indicate that sequence homology and/or chemical properties to the original epitope are not the sole determining factors for the observed immunostimulatory activity of the mimic peptides.

  4. Antigenic variation with a twist--the Borrelia story.

    Science.gov (United States)

    Norris, Steven J

    2006-06-01

    A common mechanism of immune evasion in pathogenic bacteria and protozoa is antigenic variation, in which genetic or epigenetic changes result in rapid, sequential shifts in a surface-exposed antigen. In this issue of Molecular Microbiology, Dai et al. provide the most complete description to date of the vlp/vsp antigenic variation system of the relapsing fever spirochaete, Borrelia hermsii. This elaborate, plasmid-encoded system involves an expression site that can acquire either variable large protein (vlp) or variable small protein (vsp) surface lipoprotein genes from 59 different archival copies. The archival vlp and vsp genes are arranged in clusters on at least five different plasmids. Gene conversion occurs through recombination events at upstream homology sequences (UHS) found in each gene copy, and at downstream homology sequences (DHS) found periodically among the vlp/vsp archival genes. Previous studies have shown that antigenic variation in relapsing fever Borrelia not only permits the evasion of host antibody responses, but can also result in changes in neurotropism and other pathogenic properties. The vlsE antigenic variation locus of Lyme disease spirochaetes, although similar in sequence to the relapsing fever vlp genes, has evolved a completely different antigenic variation mechanism involving segmental recombination from a contiguous array of vls silent cassettes. These two systems thus appear to represent divergence from a common precursor followed by functional convergence to create two distinct antigenic variation processes.

  5. Effects of interference of DNA methyltransferases in re-expression of cancer/testis antigens in hepatocellular carcinoma cells%DNA甲基转移酶基因干扰对HepG2细胞癌-睾丸抗原再表达的影响

    Institute of Scientific and Technical Information of China (English)

    李宏涛; 梁后杰; 李文梅; 肖文华

    2009-01-01

    目的 探讨抑制甲基转移酶(DNMT1、DNMT3a和DNMT3b)对肝细胞癌细胞中癌-睾丸抗原表达的影响及相关机制.方法 分别采用针对DNMT1、DNMT3a和DNMT3b的siRNA(DNMT1+3a+3b),针对DNMT1和DNMT3a的siRNA(DNMT1+3a),针对DNMT1和DNMT3b的siRNA(DNMTl+3b)以及针对DNMT3a和DNMT3b的siRNA(DNMT3a+3b)转染HepG2细胞,并以使用5-杂氮脱氧胞嘧啶(5-Aza-dC)处理的细胞作为阳性对照,采用RT-PCR、实时定量PCR和Western blotting检测细胞中DN-MT及癌-睾丸抗原的表达情况,并采用甲基化特异PCR(MSP)检测部分癌-睾丸抗原基因启动子的甲基化状态.结果 经siRNA干扰后,细胞中DNMT1、DNMT3a和DNMT3b的表达量均明显降低.癌-睾丸抗原CT10和SSX1在转染DNMT1+3a和DNMT1+3b的细胞中出现再表达,而MAGE1及MAGE3在各siRNA转染细胞中均有表达,且无明显差异.CT10的启动子区发生了去甲基化,但MAGE1启动子区处于非甲基化状态.结论 在HepG2细胞中,干扰DNMT可使癌-睾丸抗原基因的启动子区发生去甲基化,后者可使由甲基化导致的不能表达的癌-睾丸抗原基因发生再表达.%Objective To explore the effects and the underlying mechanisms of inhibiting three kinds of DNA methyltransferases (DNMT1, DNMT3a and DNMT3b) on the re-expression of cancer/testis antigen (CTA) in hepatic cells. Methods Transient transfection of HepG2 cells with siRNA was targeted against DNMT1, DNMT3a and DNMT3b (DNMT1+3a+3b), DNMT1 and DNMT3a (DNMT1 +3a), DNMT1 and DNMT3b (DNMTl + 3b), DNMT3a and DNMT3b (DNMT3a+3b), respectively. The other batch of cells was treated with 5-aza-deoxycytidine (5-aza-dC) as positive control. Real-time PCR and Western blotting were used to detect the expressions of DNMTs and CTAsm, and the promoter methylation of partial CTA genes was detected with methylation specific PCR (MSP). Results Expressions of DNMT1, DNMT3a and DNMT3b declined significantly after siRNA interference in HepG2 cells. Two CTAs, CT10 and SSX1, re

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

    DEFF Research Database (Denmark)

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

    1987-01-01

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

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

    DEFF Research Database (Denmark)

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

    1993-01-01

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

  8. Monocytic HLA DR antigens in schizophrenic patients.

    Science.gov (United States)

    Krause, Daniela; Wagner, Jenny; Matz, Judith; Weidinger, Elif; Obermeier, Michael; Riedel, Michael; Gruber, Rudolf; Schwarz, Markus; Mueller, Norbert

    2012-01-01

    A genetic association of specific human leukocyte antigens (HLA) DR genes and schizophrenia has recently been shown. These HLA play a fundamental role in the control of immune responses. Furthermore infectious agents have been proposed to be involved in the pathogenesis of schizophrenia. In this study we investigated the rate of HLA DR positive monocytes in schizophrenic patients compared to controls with a special focus on the adaption to in vitro stimulation with toll-like receptor ligands. Patients with schizophrenia and matched controls were included. For each individual, we evaluated the rate of HLA DR positive monocytes (either incubated at 37 °C or after stimulation with lipopolysaccharide or Poly I:C). We found a significantly higher percentage of schizophrenic patients with elevated HLA DR positive cells (p=0.045) as compared to controls. The adjustment rate from baseline levels of monocytic HLA DR positive cells to stimulation with Poly I:C was significantly lower in schizophrenic patients (p=0.038). The increased monocytic HLA DR in schizophrenic patients and the maladjustment of their monocytic HLA DR levels to an infectious stimulus might be a sign for a disturbed monocytic immune balance in schizophrenic individuals.

  9. Immunofluorescence antigen mapping for hereditary epidermolysis bullosa

    Directory of Open Access Journals (Sweden)

    Raghavendra Rao

    2012-01-01

    Full Text Available Epidermolysis bullosa (EB is a group of inherited, mechanobullous disorders that are caused by mutations in the structural proteins in the epidermis or dermoepidermal junction. Characteristic clinical picture is the presence of blisters at trauma prone areas of the body, which develops at or soon after birth. Availability of specific monoclonal antibodies against the target proteins together with advances in the molecular genetics have led to the revision in the classification of EB. Now four major types of EB are recognized depending upon the level of blister and the location of target protein: EB simplex (epidermolytic, junctional EB (lucidolytic, dystrophic EB (dermolytic and Kindler′s syndrome (mixed cleavage plane. The laboratory tests not only help to confirm the diagnosis of EB but are also an important tool to classify (and subtype EB. These include immunofluorescence antigen mapping (IFM, transmission electron microscopy (TEM and mutation analysis. IFM is the most preferred method for final diagnosis of EB worldwide. It is relatively easy to perform and results can be obtained rapidly. This article describes the technicalities and significance of IFM in various types of EB.

  10. Engineering less immunogenic and antigenic FVIII proteins

    Science.gov (United States)

    Pratt, Kathleen P.

    2017-01-01

    The development of neutralizing antibodies against blood coagulation factor VIII (FVIII), referred to clinically as “inhibitors”, is the most challenging and deleterious adverse event to occur following intravenous infusions of FVIII to treat hemophilia A. Inhibitors occlude FVIII surfaces that must bind to activated phospholipid membranes, the serine proteinase factor IXa, and other components of the ‘intrinsic tenase complex’ in order to carry out its important role in accelerating blood coagulation. Inhibitors develop in up to one of every three patients, yet remarkably, a substantial majority of severe hemophilia A patients, who circulate no detectable FVIII antigen or activity, acquire immune tolerance to FVIII during initial infusions or else after intensive FVIII therapy to overcome their inhibitor. The design of less immunogenic FVIII proteins through identification and modification (“de-immunization”) of immunodominant T-cell epitopes is an important goal. For patients who develop persistent inhibitors, modification of B-cell epitopes through substitution of surface-exposed amino acid side chains and/or attachment of bulky moieties to interfere with FVIII attachment to antibodies and memory B cells is a promising approach. Both experimental and computational methods are being employed to achieve these goals. Future therapies for hemophilia A, as well as other monogenic deficiency diseases, are likely to involve administration of less immunogenic proteins in conjunction with other novel immunotherapies to promote a regulatory cellular environment promoting durable immune tolerance. PMID:26566286

  11. Hepatitis B Virus e Antigen Variants

    Directory of Open Access Journals (Sweden)

    2005-01-01

    Full Text Available More than 300 million people worldwide are chronically infected with hepatitis B virus (HBV. Considering the very short generation time for a virus, and the high error rate associated with the reverse transcription step of HBV replication, decades of HBV infection are probably equivalent to million years of human evolution. The most important selective force during the natural course of HBV infection appears to be the immune response. The development of anti-HBe antibody in hepatitis B patients usually correlates with reduction of HBV viremia. As a consequence, escape mutants of anti-HBe are selected. The core promoter mutants express less HBe antigen (HBeAg through transcriptional down regulation, while precore mutants express truncated products. We recently identified additional mutations that modulate HBeAg translation initiation, proteolytic cleavage, and secondary structure maintenance through a disulfide bond. The core promoter mutants have been associated with the development of fulminant hepatitis during acute infection and liver cancer during chronic infection. Consistent with their enhanced pathogenicity, core promoter mutants were found to replicate at up to 10-fold higher levels in transfected human hepatoma cells than the wild-type virus. Moreover, some core promoter mutants are impaired in virion secretion due to missense mutations in the envelope gene. These virological properties may help explain enhanced pathogenicity of core promoter mutants in vivo.

  12. Isolation and purification of antigenic components of Cryptococcus.

    Science.gov (United States)

    Wozniak, Karen L; Levitz, Stuart M

    2009-01-01

    The encapsulated fungal pathogens Cryptococcus neoformans and Cryptococcus gattii are significant agents of life-threatening infections, particularly in persons with suppressed cell-mediated immunity. This chapter provides detailed methodology for the purification of two of the major antigen fractions of C. neoformans: glucuronoxylomannan (GXM) and mannoprotein (MP). GXM is the primary component of the polysaccharide capsule, which is the major cryptococcal virulence factor. In contrast, MPs have been identified as key antigens that stimulate T-cell responses. Purification of GXM and MP should assist investigators studying the antigenic, biochemical, and virulence properties of Cryptococcus species.

  13. Simple mucin-type carbohydrate antigens in major salivary glands

    DEFF Research Database (Denmark)

    Therkildsen, M H; Mandel, U; Thorn, J

    1994-01-01

    -defined monoclonal antibodies (MAb) on frozen and paraffin-embedded normal salivary gland tissue from 22 parotid, 14 submandibular, six sublingual, and 13 labial glands to elucidate the simple mucin-type glycosylation pattern in relation to cyto- and histodifferentiation. The investigated carbohydrate structures......Simple mucin-type carbohydrate antigens Tn, sialosyl-Tn and T are often markers of neoplastic transformation and have very limited expression in normal tissues. We performed an immunohistological study of simple mucin-type carbohydrate antigens, including H and A variants, with well...... antigens indicates that these structures may be of value as markers of salivary gland tumors....

  14. Alanine mutagenesis of the primary antigenic escape residue cluster, c1, of apical membrane antigen 1.

    Science.gov (United States)

    Dutta, Sheetij; Dlugosz, Lisa S; Clayton, Joshua W; Pool, Christopher D; Haynes, J David; Gasser, Robert A; Batchelor, Adrian H

    2010-02-01

    Antibodies against apical membrane antigen 1 (AMA1) inhibit invasion of Plasmodium merozoites into red cells, and a large number of single nucleotide polymorphisms on AMA1 allow the parasite to escape inhibitory antibodies. The availability of a crystal structure makes it possible to test protein engineering strategies to develop a monovalent broadly reactive vaccine. Previously, we showed that a linear stretch of polymorphic residues (amino acids 187 to 207), localized within the C1 cluster on domain 1, conferred the highest level of escape from inhibitory antibodies, and these were termed antigenic escape residues (AER). Here we test the hypothesis that immunodampening the C1 AER will divert the immune system toward more conserved regions. We substituted seven C1 AER of the FVO strain Plasmodium falciparum AMA1 with alanine residues (ALA). The resulting ALA protein was less immunogenic than the native protein in rabbits. Anti-ALA antibodies contained a higher proportion of cross-reactive domain 2 and domain 3 antibodies and had higher avidity than anti-FVO. No overall enhancement of cross-reactive inhibitory activity was observed when anti-FVO and anti-ALA sera were compared for their ability to inhibit invasion. Alanine mutations at the C1 AER had shifted the immune response toward cross-strain-reactive epitopes that were noninhibitory, refuting the hypothesis but confirming the importance of the C1 cluster as an inhibitory epitope. We further demonstrate that naturally occurring polymorphisms that fall within the C1 cluster can predict escape from cross-strain invasion inhibition, reinforcing the importance of the C1 cluster genotype for antigenic categorization and allelic shift analyses in future phase 2b trials.

  15. Estimating flood magnitude and frequency at gaged and ungaged sites on streams in Alaska and conterminous basins in Canada, based on data through water year 2012

    Science.gov (United States)

    Curran, Janet H.; Barth, Nancy A.; Veilleux, Andrea G.; Ourso, Robert T.

    2016-03-16

    -based geographic information system application that facilitates retrieval of streamflow statistics and associated information. StreamStats retrieves published data for gaged sites and, for user-selected ungaged sites, delineates drainage areas from topographic and hydrographic data, computes basin characteristics, and computes flood frequency estimates using the regional regression equations.

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

    Science.gov (United States)

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

    1993-01-01

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

  17. Characterization of O-antigen delivered by Generalized Modules for Membrane Antigens (GMMA) vaccine candidates against nontyphoidal Salmonella.

    Science.gov (United States)

    De Benedetto, G; Alfini, R; Cescutti, P; Caboni, M; Lanzilao, L; Necchi, F; Saul, A; MacLennan, C A; Rondini, S; Micoli, F

    2017-01-11

    Invasive nontyphoidal Salmonella disease (iNTS) is a leading cause of death and morbidity in Africa. The most common pathogens are Salmonella enterica serovars Typhimurium and Enteritidis. The O-antigen portion of their lipopolysaccharide is a target of protective immunity and vaccines targeting O-antigen are currently in development. Here we investigate the use of Generalized Modules for Membrane Antigens (GMMA) as delivery system for S. Typhimurium and S. Enteritidis O-antigen. Gram-negative bacteria naturally shed outer membrane in a blebbing process. By deletion of the tolR gene, the level of shedding was greatly enhanced. Further genetic modifications were introduced into the GMMA-producing strains in order to reduce reactogenicity, by detoxifying the lipid A moiety of lipopolysaccharide. We found that genetic mutations can impact on expression of O-antigen chains. All S. Enteritidis GMMA characterized had an O-antigen to protein w/w ratio higher than 0.6, while the ratio was 0.7 for S. Typhimurium ΔtolR GMMA, but decreased to less than 0.1 when further mutations for lipid A detoxification were introduced. Changes were also observed in O-antigen chain length and level and/or position of O-acetylation. When tested in mice, the GMMA induced high levels of anti-O-antigen-specific IgG functional antibodies, despite variation in density and O-antigen structural modifications. In conclusion, simplicity of manufacturing process and low costs of production, coupled with encouraging immunogenicity data, make GMMA an attractive strategy to further investigate for the development of a vaccine against iNTS.

  18. Presensitization to Ascaris antigens promotes induction of mite-specific IgE upon mite antigen inhalation in mice

    Directory of Open Access Journals (Sweden)

    Mayu Suzuki

    2016-01-01

    Conclusions: We demonstrated that the immunization of naïve mice with Ascaris antigens induced production of antibodies and differentiation of Th2 cells, which were cross-reactive to HDM antigens, and accelerated induction of serum HDM-specific IgE upon subsequent airway exposure to HDM antigens in mice. These results suggest that sensitization to HDM towards IgE-mediated allergic diseases is faster in individuals with a previous history of Ascaris infection than in those without presensitization to Ascaris.

  19. Use of Recombinant Antigens for the Diagnosis of Invasive Candidiasis

    Directory of Open Access Journals (Sweden)

    Ana Laín

    2008-01-01

    Full Text Available Invasive candidiasis is a frequent and often fatal complication in immunocompromised and critically ill patients. Unfortunately, the diagnosis of invasive candidiasis remains difficult due to the lack of specific clinical symptoms and a definitive diagnostic method. The detection of antibodies against different Candida antigens may help in the diagnosis. However, the methods traditionally used for the detection of antibodies have been based on crude antigenic fungal extracts, which usually show low-reproducibility and cross-reactivity problems. The development of molecular biology techniques has allowed the production of recombinant antigens which may help to solve these problems. In this review we will discuss the usefulness of recombinant antigens in the diagnosis of invasive candidiasis.

  20. 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.

  1. Immune activation by casein dietary antigens in bipolar disorder

    NARCIS (Netherlands)

    Severance, E.G.; Dupont, D.; Dickerson, F.B.; Stallings, C.R.; Origoni, A.E.; Krivogorsky, B.; Yang, S.; Haasnoot, W.; Yolken, R.H.

    2010-01-01

    Objectives: Inflammation and other immune processes are increasingly linked to psychiatric diseases. Antigenic triggers specific to bipolar disorder are not yet defined. We tested whether antibodies to bovine milk caseins were associated with bipolar disorder, and whether patients recognized differe

  2. The Synthesis of a Novel Phosphorus Containing Antigen

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Antigen 12, containing a phosphonyl peptide hapten with free C-terminal carboxylic group, was synthesized by 11 reaction steps. The design of the hapten was based on the transition state of peptide hydrolysis catalyzed by carboxypeptidase A.

  3. Antigen-specific lymphocyte transformation in patients with recent yersiniosis.

    Science.gov (United States)

    Vuento, R

    1983-04-01

    Lymphocyte transformation in patients with recent yersiniosis was studied. A micromethod using washed blood cells and Yersinia enterocolitica antigen was employed. The washed blood cells were incubated in the presence of various dilutions of heat-treated whole bacteria; these proved as antigen superior to gentamicin- or formalin-treated bacteria. Patients with recent yersiniosis had a significantly higher response against Yersinia antigen as compared to 20 healthy controls, who had either no response or a low response. No difference could be observed in responses against PPD or streptokinase-streptodornase, or in the mitogen responses between these two groups. A marked cross-reaction was observed between Yersinia and Escherichia coli antigen. The results show that patients with recent yersiniosis develop lymphocyte transformation response against Yersinia. Lymphocyte transformation test can be used in the study of host responses against infecting Yersinia in patients with different clinical pictures of yersiniosis.

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

    DEFF Research Database (Denmark)

    Dabelsteen, Erik

    2002-01-01

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

  5. Chlamydia trachomatis antigen in female genital tract infection

    Directory of Open Access Journals (Sweden)

    Badrinath S

    1996-01-01

    Full Text Available Thirty cases of female genital tract infection were investigated for the presence of Chlamydia trachomatis antigen. Endocervical swabs obtained were subjected to antigen detection by enzyme immunoassay. Rabbit antiserum to chlamydial lipopolysaccharide was used in a card test. Anti rabbit immunoglobulin G conjugated to alkaline phosphatase with a chromogenic substrate 5 bromo-4 chloro-3-indolyl phosphate and nitro blue tetrazolium were used for the enzymatic reaction. Chlamydial antigen could be detected in four out of thirty samples (13.3%. In contrast direct immunofluorescence detected 5 cases (16.6%. Although less sensitive, enzyme immunoassay can be used as a rapid diagnostic tool in detecting Chlamydia trachomatis antigen in genital infections.

  6. Instability of induction cooker (electromagnetic stove) antigen retrieval in immunohistochemistry.

    Science.gov (United States)

    Ding, Wei; Zheng, Xiang-Yi

    2012-03-01

    An induction cooker is a modern electric cooker that takes electromagnetic induction principle to heat. As it has high efficiency, no open flame, and is safe and convenient, more and more laboratories use it as an antigen retrieval heating tool in immunohistochemistry. We found that there was still some instability with the induction cooker, because with certain antigens the power change influenced the results of immunohistochemistry staining, showing weaker staining intensity or decreased number of positive cells, but which were not entirely negative. For some antigens, it had no influence on results. The instability of this heating tool for antigen retrieval was caused partly by negligent operators, and which may influence the experimental results and the pathologic diagnosis.

  7. Photoaffinity antigens for human γδ T cells1

    Science.gov (United States)

    Sarikonda, Ghanashyam; Wang, Hong; Puan, Kia-Joo; Liu, Xiao-hui; Lee, Hoi K.; Song, Yongcheng; Distefano, Mark D.; Oldfield, Eric; Prestwich, Glenn D.; Morita, Craig T.

    2009-01-01

    Vγ2Vδ2 T cells comprise the major subset of peripheral blood γ δ T cells in humans and expand during infections by recognizing small, nonpeptide prenyl pyrophosphates. These molecules include (E)-4-hydroxy-3-methyl-but-2-enyl-pyrophosphate (HMBPP), a microbial isoprenoid intermediate, and isopentenyl pyrophosphate (IPP), an endogenous isoprenoid intermediate. Recognition of these nonpeptide antigens is mediated by the Vγ2Vδ2 T cell antigen receptor (TCR). Several findings suggest that prenyl pyrophosphates are presented by an antigen presenting molecule: contact between T cells and APCs is required; the antigens do not bind the Vγ2Vδ2 TCR directly; and antigen recognition is abrogated by TCR mutations in CDRs distant from the putative antigen recognition site. Identification of the putative antigen presenting molecule, however, has been hindered by the inability to achieve stable association of nonpeptide prenyl pyrophosphate antigens with the presenting molecule. In this study, we show that photoaffinity analogs of HMBPP, meta/para-benzophenone-(methylene)-prenyl pyrophosphates (m/p-BZ-(C)-C5-OPP), can cross-link to the surface of tumor cell lines and be presented as antigens to γ δ T cells. Mutant tumor cell lines lacking MHC class I, MHC class II, β2-microglobulin, and CD1, as well as tumor cell lines from a variety of tissues and individuals, will all crosslink to and present m-BZ-C5-OPP. Finally, pulsing of BZ-(C)-C5-OPP is inhibited by IPP and an inactive analog, suggesting that they bind to the same molecule. Taken together, these results suggest that nonpeptide antigens are presented by a novel antigen presenting molecule that is widely distributed, non-polymorphic, but not classical MHC class I, MHC class II, or CD1. This is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (AAI), publisher of The JI, holds the copyright to this manuscript

  8. Melanocyte antigen triggers autoimmunity in human psoriasis.

    Science.gov (United States)

    Arakawa, Akiko; Siewert, Katherina; Stöhr, Julia; Besgen, Petra; Kim, Song-Min; Rühl, Geraldine; Nickel, Jens; Vollmer, Sigrid; Thomas, Peter; Krebs, Stefan; Pinkert, Stefan; Spannagl, Michael; Held, Kathrin; Kammerbauer, Claudia; Besch, Robert; Dornmair, Klaus; Prinz, Jörg C

    2015-12-14

    Psoriasis vulgaris is a common T cell-mediated inflammatory skin disease with a suspected autoimmune pathogenesis. The human leukocyte antigen (HLA) class I allele, HLA-C*06:02, is the main psoriasis risk gene. Epidermal CD8(+) T cells are essential for psoriasis development. Functional implications of HLA-C*06:02 and mechanisms of lesional T cell activation in psoriasis, however, remained elusive. Here we identify melanocytes as skin-specific target cells of an HLA-C*06:02-restricted psoriatic T cell response. We found that a Vα3S1/Vβ13S1 T cell receptor (TCR), which we had reconstituted from an epidermal CD8(+) T cell clone of an HLA-C*06:02-positive psoriasis patient specifically recognizes HLA-C*06:02-positive melanocytes. Through peptide library screening, we identified ADAMTS-like protein 5 (ADAMTSL5) as an HLA-C*06:02-presented melanocytic autoantigen of the Vα3S1/Vβ13S1 TCR. Consistent with the Vα3S1/Vβ13S1-TCR reactivity, we observed numerous CD8(+) T cells in psoriasis lesions attacking melanocytes, the only epidermal cells expressing ADAMTSL5. Furthermore, ADAMTSL5 stimulation induced the psoriasis signature cytokine, IL-17A, in CD8(+) T cells from psoriasis patients only, supporting a role as psoriatic autoantigen. This unbiased analysis of a TCR obtained directly from tissue-infiltrating CD8(+) T cells reveals that in psoriasis HLA-C*06:02 directs an autoimmune response against melanocytes through autoantigen presentation. We propose that HLA-C*06:02 may predispose to psoriasis via this newly identified autoimmune pathway.

  9. Tumor markers cancer antigen 15.3, carcinoembryonic antigen, and tissue polypeptide antigen for monitoring metastatic breast cancer during first-line chemotherapy and follow-up

    DEFF Research Database (Denmark)

    Sölétormos, G; Nielsen, D; Schiøler, V;

    1996-01-01

    follow-up. Each sample was analyzed for cancer antigen 15.3, carcinoembryonic antigen, and tissue polypeptide antigen. The efficiency for identifying progression and nonprogression was 94% during therapy and 85% during follow-up, with no false-positive marker results for progressive disease. At clinical......We investigated whether model systems integrating stochastic variation into criteria for marker assessment could be used for monitoring metastatic breast cancer. A total of 3989 serum samples was obtained from 204 patients receiving first-line chemotherapy and from 112 of these patients during...... progressive disease, the median positive lead time was 35 days during therapy and 76 days during follow-up. Tumor marker assessment may document that a therapy is effective and ought to be continued in spite of adverse toxic effects, and that a treatment is ineffective and should be stopped to prevent...

  10. Partial purification of protective antigens from Nippostrongylus brasiliensis in mice.

    Science.gov (United States)

    Rhalem, A; Bourdieu, C; Luffau, G; Pery, P

    1988-01-01

    The purification of antigens from Nippostrongylus brasiliensis, through their ability to provoke cellular proliferation of immune cells and through their recognition by antibodies, led to an antigenic preparation which was extracted from adult worms and which contained only two proteins (MW 14 and 43 Kd). Mice which were vaccinated by the oral route after the entrapment of these two proteins in liposomes were strongly protected.

  11. Dynamic quantification of antigen molecules with flow cytometry

    Science.gov (United States)

    Moskalensky, A.E.; Chernyshev, A.V.; Yurkin, M.A.; Nekrasov, V.M.; Polshchitsin, A.A.; Parks, D.R.; Moore, W.A.; Herzenberg, L.A.; Filatenkov, A.; Maltsev, V.P.; Orlova, D.Y.

    2015-01-01

    Traditional methods for estimating the number of expressed molecules, based on the detection of target antigens bound with fluorescently labeled antibodies, assume that the antigen-antibody reaction reaches equilibrium. A calibration procedure is used to convert the intensity of the fluorescence signal to the number of target molecules. Along with the different limitations of every calibration system, this substantially limits the applicability of the traditional approaches especially in the case of low affinity antibodies. We address this problem here with studies in which we demonstrate a new approach to the antigen molecule quantification problem. Instead of using a static calibration system, we analyzed mean fluorescence values over time by flow cytometry during antibody-antigen binding. Experimental data obtained with an LSRII cytometer were fitted by a diffusion-reaction mathematical model using the Levenberg–Marquardt nonlinear least squares curve-fitting algorithm in order to obtain the number of target antigen molecules per cell. Results were compared with the Quanti-BRITE calibration system. We conclude that, instead of using experiment-specific calibration, the value of the binding rate constant for each particular antibody-antigen reaction can be used to quantify antigen molecules with flow cytometry. The radius of CD8 antibody molecule binding site was found, that allows recalculating the binding rate constant for other conditions (different sizes of reagent molecules, fluorescent label, medium viscosity and temperature). This approach is independent of specially prepared calibration beads, antibody reagents and the specific dye and can be applied to both low and high affinity antibodies, under both saturating and non-saturating binding conditions. The method was demonstrated on a human blood sample dataset investigating CD8α antigen on T cells in stable binding conditions. PMID:25687877

  12. Microbial antigenic variation mediated by homologous DNA recombination

    OpenAIRE

    2012-01-01

    Pathogenic microorganisms employ numerous molecular strategies in order to delay or circumvent recognition by the immune system of their host. One of the most widely used strategies of immune evasion is antigenic variation, in which immunogenic molecules expressed on the surface of a microorganism are continuously modified. As a consequence, the host is forced to constantly adapt its humoral immune response against this pathogen. An antigenic change thus provides the microorganism with an opp...

  13. Duality of β-glucan microparticles: antigen carrier and immunostimulants

    Directory of Open Access Journals (Sweden)

    Baert K

    2016-05-01

    Full Text Available Kim Baert,1 Bruno G De Geest,2 Henri De Greve,3,4 Eric Cox,1,* Bert Devriendt1,* 1Department of Virology, Parasitology and Immunology, 2Department of Pharmaceutics, Ghent University, Merelbeke, Ghent, Belgium; 3Structural Biology Research Centre, VIB, Brussels, Belgium; 4Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium *These authors contributed equally to this work Abstract: Designing efficient recombinant mucosal vaccines against enteric diseases is still a major challenge. Mucosal delivery of recombinant vaccines requires encapsulation in potent immunostimulatory particles to induce an efficient immune response. This paper evaluates the capacity of β-glucan microparticles (GPs as antigen vehicles and characterizes their immune-stimulatory effects. The relevant infectious antigen FedF was chosen to be loaded inside the microparticles. The incorporation of FedF inside the particles was highly efficient (roughly 85% and occurred without antigen degradation. In addition, these GPs have immunostimulatory effects as well, demonstrated by the strong reactive oxygen species (ROS production by porcine neutrophils upon their recognition. Although antigen-loaded GPs still induce ROS production, antigen loading decreases this production by neutrophils for reasons yet unknown. However, these antigen-loaded GPs are still able to bind their specific β-glucan receptor, demonstrated by blocking complement receptor 3, which is the major β-glucan receptor on porcine neutrophils. The dual character of these particles is confirmed by a T-cell proliferation assay. FedF-loaded particles induce a significantly higher FedF-specific T-cell proliferation than soluble FedF. Taken together, these results show that GPs are efficient antigen carriers with immune-stimulatory properties. Keywords: β-glucan microparticles, FedF, antigen delivery vehicle, immunostimulants

  14. Serological diagnosis with recombinant N antigen for hantavirus infection.

    Science.gov (United States)

    Yoshimatsu, Kumiko; Arikawa, Jiro

    2014-07-17

    Hantaviruses are causative agents of two rodent-borne zoonoses, hemorrhagic fever with renal syndrome (HFRS) and nephropathia epidemica (NE) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. Serological examinations to detect hantavirus antibodies have been most widely used for surveillance among humans and rodent reservoirs. Here, we will review antigenic structure of nucleocapsid (N) protein of hantaviruses and application of recombinant N protein as diagnostic antigen for screening and serotyping.

  15. Surface antigens of metacyclic trypomastigotes of Trypanosoma cruzi.

    OpenAIRE

    1983-01-01

    The surface antigen makeup of metacyclic trypomastigote forms of strain G of Trypanosoma cruzi, which produce a subpatent infection in mice, differed from those of the virulent strains Y and CL. A 100,000-molecular-weight protein, barely detectable on the Y or CL cell surface, appeared as the main surface antigen of the G metacyclic trypomastigotes. In addition, the G metacyclic forms differed from those of the virulent strains in their susceptibility to complement-mediated immunolysis.

  16. Prostate Tumor Antigen Discovery: Development of a Novel Genetic Approach

    Science.gov (United States)

    2000-07-01

    recognizing the ovarian carcinoma antigen CA125 encapsulated in biodegradable microspheres. Cancer Immunology , Immunotherapy, 1998. 47(1): p. 13-20. 37...Morganelli, K. Wardwell and A.L. Howell, Increased potency of Fc-receptor-targeted antigens. Cancer Immunology , Immunotherapy, 1997. 45(3-4): p. 146...Urology, 1999. I61(35: p. 984-9. 72. Curnow, R.T., Clinical experience with CD64-dirccred immunotherapy. An overview. Cancer Immunology , Immunotherapy

  17. Antigen-specific immune reactions to ischemic stroke

    Directory of Open Access Journals (Sweden)

    Xabier eUrra

    2014-09-01

    Full Text Available Brain proteins are detected in the CSF and blood of stroke patients and their concentration is related to the extent of brain damage. Antibodies against brain antigens develop after stroke, suggesting a humoral immune response to the brain injury. Furthermore, induced immune tolerance is beneficial in animal models of cerebral ischemia. The presence of circulating T cells sensitized against brain antigens, and antigen presenting cells (APCs carrying brain antigens in draining lymphoid tissue of stroke patients support the notion that stroke might induce antigen-specific immune responses. After stroke, brain proteins that are normally hidden from the periphery, inflammatory mediators, and danger signals can exit the brain through several efflux routes. They can reach the blood after leaking out of the damaged blood-brain barrier or following the drainage of interstitial fluid to the dural venous sinus, or reach the cervical lymph nodes through the nasal lymphatics following CSF drainage along the arachnoid sheaths of nerves across the nasal submucosa. The route and mode of access of brain antigens to lymphoid tissue could influence the type of response. Central and peripheral tolerance prevents autoimmunity, but the actual mechanisms of tolerance to brain antigens released into the periphery in the presence of inflammation, danger signals, and APCs, are not fully characterized. Stroke does not systematically trigger autoimmunity, but under certain circumstances, such as pronounced systemic inflammation or infection, autoreactive T cells could escape the tolerance controls. Further investigation is needed to elucidate whether antigen-specific immune events could underlie neurological complications impairing stroke outcome.

  18. Conservation of Meningococcal Antigens in the Genus Neisseria

    OpenAIRE

    Muzzi, Alessandro; Mora, Marirosa; Pizza, Mariagrazia; Rappuoli, Rino; Donati, Claudio

    2013-01-01

    ABSTRACT Neisseria meningitidis, one of the major causes of bacterial meningitis and sepsis, is a member of the genus Neisseria, which includes species that colonize the mucosae of many animals. Three meningococcal proteins, factor H-binding protein (fHbp), neisserial heparin-binding antigen (NHBA), and N. meningitidis adhesin A (NadA), have been described as antigens protective against N. meningitidis of serogroup B, and they have been employed as vaccine components in preclinical and clinic...

  19. Fibroblasts as Efficient Antigen-Presenting Cells in Lymphoid Organs

    Science.gov (United States)

    Kundig, Thomas M.; Bachmann, Martin F.; Dipaolo, Claudio; Simard, John J. L.; Battegay, Manuel; Lother, Heinz; Gessner, Andre; Kuhlcke, Klaus; Ohashi, Pamela S.; Hengartner, Hans; Zinkernagel, Rolf M.

    1995-06-01

    Only so-called "professional" antigen-presenting cells (APCs) of hematopoietic origin are believed capable of inducing T lymphocyte responses. However, fibroblasts transfected with viral proteins directly induced antiviral cytotoxic T lymphocyte responses in vivo, without involvement of host APCs. Fibroblasts induced T cells only in the milieu of lymphoid organs. Thus, antigen localization affects self-nonself discrimination and cell-based vaccine strategies.

  20. Prevalence of Weak D Antigen In Western Indian Population

    Directory of Open Access Journals (Sweden)

    Tanvi Sadaria

    2015-12-01

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

  1. Trypanosoma cruzi as an effective cancer antigen delivery vector.

    Science.gov (United States)

    Junqueira, Caroline; Santos, Luara I; Galvão-Filho, Bruno; Teixeira, Santuza M; Rodrigues, Flávia G; DaRocha, Wanderson D; Chiari, Egler; Jungbluth, Achim A; Ritter, Gerd; Gnjatic, Sacha; Old, Lloyd J; Gazzinelli, Ricardo T

    2011-12-06

    One of the main challenges in cancer research is the development of vaccines that induce effective and long-lived protective immunity against tumors. Significant progress has been made in identifying members of the cancer testis antigen family as potential vaccine candidates. However, an ideal form for antigen delivery that induces robust and sustainable antigen-specific T-cell responses, and in particular of CD8(+) T lymphocytes, remains to be developed. Here we report the use of a recombinant nonpathogenic clone of Trypanosoma cruzi as a vaccine vector to induce vigorous and long-term T cell-mediated immunity. The rationale for using the highly attenuated T. cruzi clone was (i) the ability of the parasite to persist in host tissues and therefore to induce a long-term antigen-specific immune response; (ii) the existence of intrinsic parasite agonists for Toll-like receptors and consequent induction of highly polarized T helper cell type 1 responses; and (iii) the parasite replication in the host cell cytoplasm, leading to direct antigen presentation through the endogenous pathway and consequent induction of antigen-specific CD8(+) T cells. Importantly, we found that parasites expressing a cancer testis antigen (NY-ESO-1) were able to elicit human antigen-specific T-cell responses in vitro and solid protection against melanoma in a mouse model. Furthermore, in a therapeutic protocol, the parasites expressing NY-ESO-1 delayed the rate of tumor development in mice. We conclude that the T. cruzi vector is highly efficient in inducing T cell-mediated immunity and protection against cancer cells. More broadly, this strategy could be used to elicit a long-term T cell-mediated immunity and used for prophylaxis or therapy of chronic infectious diseases.

  2. Regulator T cells: specific for antigen and/or antigen receptors?

    Science.gov (United States)

    Rubin, B; de Durana, Y Diaz; Li, N; Sercarz, E E

    2003-05-01

    Adaptive immune responses are regulated by many different molecular and cellular effectors. Regulator T cells are coming to their rights again, and these T cells seem to have ordinary alpha/beta T-cell receptors (TCRs) and to develop in the thymus. Autoimmune responses are tightly regulated by such regulatory T cells, a phenomenon which is beneficial to the host in autoimmune situations. However, the regulation of autoimmune responses to tumour cells is harmful to the host, as this regulation delays the defence against the outgrowth of neoplastic cells. In the present review, we discuss whether regulatory T cells are specific for antigen and/or for antigen receptors. Our interest in these phenomena comes from the findings that T cells produce many more TCR-alpha and TCR-beta chains than are necessary for surface membrane expression of TCR-alphabeta heterodimers with CD3 complexes. Excess TCR chains are degraded by the proteasomes, and TCR peptides thus become available to the assembly pathway of major histocompatibility complex class I molecules. Consequently, do T cells express two different identification markers on the cell membrane, the TCR-alphabeta clonotype for recognition by B-cell receptors and clonotypic TCR-alphabeta peptides for recognition by T cells?

  3. Isolation and characterization of human rhinovirus antigenic variants

    Energy Technology Data Exchange (ETDEWEB)

    Watson, D.G.

    1985-01-01

    Isolation of antigenic variants of human rhinovirus types 2, 14, and 17 was attempted by plaquing untreated virus (P-isolates), selecting variants in the presence of homologous antiserum (C-isolates), and by selecting variants in the presence of antibody following 5-fluorouracil mutagenesis (M-isolates). All viruses were triple-plaque purified and purity neutralization tested prior to isolate selection. Based on a fourfold reduction in neutralizing antibody titer to homologous antiserum, no antigenic variation was found in P-isolates from the three serotypes examined. Antigenic variants of all three serotypes could be isolated by the antiserum selection method (C-isolates). However, antigenic variants of RV17 were isolated at a much higher frequency and showed a larger degree of variation than those of RV2 and RV14. At least two of the variants selected, RV17 (C301) and RV2 (M803), failed to be neutralized by the known 89 rhinovirus antiserum. SDS-polyacrylamide gel electrophoresis of (/sup 35/S) methionine-labelled virion polypeptides revealed that each serotype had a characteristic pattern and that selected RV2 and RV17 isolates had patterns identical to those of the prototype strains. By isoelectric focusing an antigenic variant of RV2 was shown to contain altered virion polypeptides VP1 and VP2 whereas two RV17 antigenic variants demonstrated alterations only in the VP1 polypeptide.

  4. Targeting novel antigens in the arterial wall in thromboangiitis obliterans.

    Directory of Open Access Journals (Sweden)

    Murat Akkus

    2010-06-01

    Full Text Available Thromboangiitis obliterans is an inflammatory disease possibly resulting from cigarette smoking as a primary etiologic factor, perhaps as a delayed type of hypersensitivity or toxic angiitis. As little is known about the pathogenesis of the disease, we aimed to determine novel antigens that might be responsible from the local inflammatory reactions and structural changes observed in this disease. An indirect immunoperoxidase technique is used to examine the tissue samples obtained from the dorsalis pedis artery of affected individuals with twenty monoclonal antibodies. Among these several antigens which are not previously reported in TAO like CD34, CD44 and CD90 were determined in the tissue samples examined. On the other hand, many other antigens like cytokine/chemokine receptors, several enzymes and leukocyte/lymphocyte antigens were lacking giving some clues about the local pathological reactions. We briefly discussed our findings for several critical antigens those first described in the present work, possibly having roles in the development of the disease. Expression of the CD90/CD11c receptor/ligand pair seems to play an important role in mononuclear cell recruitment to the damage site. Vascular invasion of not only tunica intima but also the tunica media in affected vessels is clearly demonstrated using endothelial cell specific antigens.

  5. Urine antigen detection for the diagnosis of human neurocysticercosis.

    Science.gov (United States)

    Castillo, Yesenia; Rodriguez, Silvia; García, Hector H; Brandt, Jef; Van Hul, Anke; Silva, Maria; Rodriguez-Hidalgo, Richar; Portocarrero, Mylagritos; Melendez, D Paolo; Gonzalez, Armando E; Gilman, Robert H; Dorny, Pierre

    2009-03-01

    Neurocysticercosis (NCC) is a major cause of seizures and epilepsy. Diagnosis is based on brain imaging, supported by immunodiagnosis in serum or cerebrospinal fluid (CSF). Lumbar puncture is invasive and painful. Blood sampling is slightly painful and poorly accepted. Urine antigen detection has been used for other parasites and tried in NCC with suboptimal performance. We used a monoclonal antibody-based ELISA to detect Taenia solium antigens in urine from 87 Peruvian neurocysticercosis patients (viable cysts, N = 34; subarachnoid cysticercosis, N = 10; degenerating parasites, N = 7; calcified lesions, N = 36) and 32 volunteers from a non-endemic area of Peru. Overall sensitivity of urine antigen detection for viable parasites was 92%, which decreased to 62.5% in patients with a single cyst. Most patients (30/36, 83%) with only calcified cysticercosis were urine antigen negative. Antigen levels in paired serum/urine samples (evaluated in 19 patients) were strongly correlated. Non-invasive urine testing for T. solium antigens provides a useful alternative for NCC diagnosis.

  6. Kinetics of antigen expression and epitope presentation during virus infection.

    Directory of Open Access Journals (Sweden)

    Nathan P Croft

    2013-01-01

    Full Text Available Current knowledge about the dynamics of antigen presentation to T cells during viral infection is very poor despite being of fundamental importance to our understanding of anti-viral immunity. Here we use an advanced mass spectrometry method to simultaneously quantify the presentation of eight vaccinia virus peptide-MHC complexes (epitopes on infected cells and the amounts of their source antigens at multiple times after infection. The results show a startling 1000-fold range in abundance as well as strikingly different kinetics across the epitopes monitored. The tight correlation between onset of protein expression and epitope display for most antigens provides the strongest support to date that antigen presentation is largely linked to translation and not later degradation of antigens. Finally, we show a complete disconnect between the epitope abundance and immunodominance hierarchy of these eight epitopes. This study highlights the complexity of viral antigen presentation by the host and demonstrates the weakness of simple models that assume total protein levels are directly linked to epitope presentation and immunogenicity.

  7. Determination of Diagnostic Antigens in Cattle Amphistomiasis Using Western Blotting

    Directory of Open Access Journals (Sweden)

    A Halajian

    2009-05-01

    Full Text Available "nBackground: Mixed infection with amphistomes seems common in native cattle of Iran. The aim of this study was to determine diagnostic antigens in cattle mixed amphistomiasis."nMethods: Specific antigens of Cotylophoron cotylophorum, Gastrothylax crumenifer and Paramphisto­mum cervi (mixed infection, the most common species, were collected from cattle was deter­mined. Adult trematodes were collected from the rumen of naturally infected cattle at meat inspec­tion. After their homogenization and centrifugation, somatic antigens were prepared and ana­lyzed by SDS-PAGE. Specific antigens were determinated by western blot with homologous and heterolo­gous sera. SDS-PAGE of whole worms extract was performed at different concentrations and subse­quent gels staining. Immunoblotting analysis using sera from cattle naturally infected with am­phistomes, Dicrocoelium dendriticum, Fasciola spp. and hydatid cyst was performed."nResults: Electrophorese analysis of somatic antigens revealed the presence of 10 and 21 protein bands at 4 µgr/ml and 8 µgr/ml with molecular weights ranging from 25-120 and 25-150 kDa, respectively. The best result was taken at 8 mg/ml concentration. Although western blot of these proteins demon­strate 5 major antigenic polypeptides ranging from 50 to 100 kDa which were recognized by serum of cat­tle naturally infected with mixed amphistomes.

  8. Antigen specificity of invariant natural killer T-cells

    Directory of Open Access Journals (Sweden)

    Alysia M. Birkholz

    2015-12-01

    Full Text Available Natural killer T-cells, with an invariant T-cell antigen receptor α-chain (iNKT cells, are unique and conserved subset of lymphocytes capable of altering the immune system through their rapid and potent cytokine responses. They are reactive to lipid antigens presented by the CD1d molecule, an antigen-presenting molecule that is not highly polymorphic. iNKT cell responses frequently involve mixtures of cytokines that work against each other, and therefore attempts are underway to develop synthetic antigens that elicit only strong interferon-gamma (IFNγ or only strong interleukin-4 responses but not both. Strong IFNγ responses may correlate with tighter binding to CD1d and prolonged stimulation of iNKT cells, and this may be useful for vaccine adjuvants and for stimulating anti-tumor responses. iNKT cells are self-reactive although the structure of the endogenous antigen is controversial. By contrast, bacterial and fungal lipids that engage the T-cell receptor and activate IFNγ from iNKT cells have been identified from both pathogenic and commensal organisms and the responses are in some cases highly protective from pathogens in mice. It is possible that the expanding knowledge of iNKT cell antigens and iNKT cell activation will provide the basis for therapies for patients suffering from infectious and immune diseases and cancer.

  9. Antigen specificity of invariant natural killer T-cells.

    Science.gov (United States)

    Birkholz, Alysia M; Kronenberg, Mitchell

    2015-12-01

    Natural killer T-cells, with an invariant T-cell antigen receptor α-chain (iNKT cells), are unique and conserved subset of lymphocytes capable of altering the immune system through their rapid and potent cytokine responses. They are reactive to lipid antigens presented by the CD1d molecule, an antigen-presenting molecule that is not highly polymorphic. iNKT cell responses frequently involve mixtures of cytokines that work against each other, and therefore attempts are underway to develop synthetic antigens that elicit only strong interferon-gamma (IFNγ) or only strong interleukin-4 responses but not both. Strong IFNγ responses may correlate with tighter binding to CD1d and prolonged stimulation of iNKT cells, and this may be useful for vaccine adjuvants and for stimulating anti-tumor responses. iNKT cells are self-reactive although the structure of the endogenous antigen is controversial. By contrast, bacterial and fungal lipids that engage the T-cell receptor and activate IFNγ from iNKT cells have been identified from both pathogenic and commensal organisms and the responses are in some cases highly protective from pathogens in mice. It is possible that the expanding knowledge of iNKT cell antigens and iNKT cell activation will provide the basis for therapies for patients suffering from infectious and immune diseases and cancer.

  10. Proteome serological determination of tumor-associated antigens in melanoma.

    Directory of Open Access Journals (Sweden)

    Michael Forgber

    Full Text Available Proteome serology may complement expression library-based approaches as strategy utilizing the patients' immune responses for the identification pathogenesis factors and potential targets for therapy and markers for diagnosis. Melanoma is a relatively immunogenic tumor and antigens recognized by melanoma-specific T cells have been extensively studied. The specificities of antibody responses to this malignancy have been analyzed to some extent by molecular genetic but not proteomics approaches. We screened sera of 94 melanoma patients for anti-melanoma reactivity and detected seropositivity in two-thirds of the patients with 2-6 antigens per case detected by 1D and an average of 2.3 per case by 2D Western blot analysis. For identification, antigen spots in Western blots were aligned with proteins in 2-DE and analyzed by mass spectrometry. 18 antigens were identified, 17 of which for the first time for melanoma. One of these antigens, galectin-3, has been related to various oncogenic processes including metastasis formation and invasiveness. Similarly, enolase has been found deregulated in different cancers. With at least 2 of 18 identified proteins implicated in oncogenic processes, the work confirms the potential of proteome-based antigen discovery to identify pathologically relevant proteins.

  11. The chicken erythrocyte-specific MHC antigen. Characterization and purification of the B-G antigen by monoclonal antibodies

    DEFF Research Database (Denmark)

    Salomonsen, J; Skjødt, K; Crone, M

    1987-01-01

    Mouse monoclonal antibodies with B-G antigen (major histocompatibility complex class IV) specificity were obtained after immunization with erythrocytes or partially purified B-G antigen. The specificities of the hybridoma antibodies were determined by precipitation of B-G antigens from 125I...... of purified B-G antigen with Endoglycosidase-F or trifluoromethanesulfonic acid. Two-way sequential immunoprecipitation studies of erythrocyte membrane extracts with anti-B-G alloantisera and monoclonal antibodies revealed only one population of B-G molecules. Pulse-chase experiments have shown B...... from the affinity chromatography step was 3-4 micrograms B-G/ml blood, calculated from Coomassie-stained SDS-PAGE of B-G using ovalbumin standards. The monoclonal antibodies were also used to identify the B-G (class IV) precipitation arc in crossed immunoelectrophoresis. No common precipitate...

  12. Chemokine programming dendritic cell antigen response: part I - select chemokine programming of antigen uptake even after maturation.

    Science.gov (United States)

    Park, Jaehyung; Wu, Cindy T; Bryers, James D

    2013-05-01

    Here, we report on the successful programming of dendritic cells (DCs) using selectively applied mixtures of chemokines as a novel protocol for engineering vaccine efficiency. Antigen internalization by DCs is a pivotal step in antigen uptake/presentation for bridging innate and adaptive immunity and in exogenous gene delivery used in vaccine strategies. Contrary to most approaches to improve vaccine efficiency, active enhancement of antigen internalization by DCs as a vaccine strategy has been less studied because DCs naturally down-regulate antigen internalization upon maturation. Whereas chemokines are mainly known as signal proteins that induce leucocyte chemotaxis, very little research has been carried out to identify any additional effects of chemokines on DCs following maturation. Here, immature DCs are pre-treated with select chemokines before intentional maturation using lipopolysaccharide (LPS). When pre-treated with a mixture of CCL3 and CCL19 in a 7 : 3 ratio, then matured with LPS, chemokine pre-treated DCs exhibited 36% higher antigen uptake capacity than immature DCs and 27% higher antigen-processing capacity than immature DCs treated only with LPS. Further, CCL3 : CCL19 (7 : 3) pre-treatment of DCs modulated MHC molecule expression and secretion of various cytokines of DCs. Collectively, DC programming was feasible using a specific chemokine combination and these results provide a novel strategy for enhancing DC-based vaccine efficiency. In Part II, we report on the phenotype changes and antigen presentation capacity of chemokine pre-treated murine bone marrow-derived DCs examined in long-term co-culture with antigen-specific CD4(+) T cells.

  13. Single antigen flow beads for identification of human leukocyte antigen antibody specificities in hypersensitized patients with chronic renal failure

    OpenAIRE

    Soyöz, Mustafa; Kılıçaslan-Ayna, Tülay; Özkızılcık-Koçyiğit, Aslı; Güleç, Derya; Pirim, İbrahim

    2016-01-01

    Aims of this study Aims of this study were to identify class I and class II antibodies in highly sensitized patients by flow cytometry single antigen bead (FC-SAB) assay and to evaluate according to donor HLA type in order to increase their kidney transplantation chance. Material and methods We analyzed 60 hypersensitive patients of 351 individuals, who applied to our laboratory for PRA test in November 2013-December 2014. Flow cytometric PRA screening and single antigen bead commercial kits ...

  14. A Rapid and Sensitive Method for the Quantitation of Legionella Pneumophila Antigen from Human Urine.

    Science.gov (United States)

    1980-11-12

    reverse% passive hemagglutination test was developed to assay concentrations of solubl4 antigen of Legionnaires’ Disease ( Legionella pneumophila ) in... Legionella pneumophila Antigen from Humanl Urine JOSEPH A. MANGIAFICO, KENNETH W. HEDLUND, AND ALLEN R. KNOTT Running title: L. PNEUMOPHILA ANTIGEN IN...Approved for public release; distribution unlimited A Rapid and Sensitive Method for the Quantitation of Legionella pneumophila Antigen from Human

  15. 21 CFR 660.1 - Antibody to Hepatitis B Surface Antigen.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Antibody to Hepatitis B Surface Antigen. 660.1... Hepatitis B Surface Antigen § 660.1 Antibody to Hepatitis B Surface Antigen. (a) Proper name and definition. The proper name of this product shall be Antibody to Hepatitis B Surface Antigen. The product...

  16. Molecular cloning of Taenia taeniaeformis oncosphere antigen genes.

    Science.gov (United States)

    Cougle, W G; Lightowlers, M W; Bogh, H O; Rickard, M D; Johnson, K S

    1991-03-01

    Infection of mice with the cestode Taenia taeniaeformis exhibits several important features common to other cestode infections, including the ability to vaccinate with crude antigen mixtures. Partial purification of the protective oncosphere antigens has been reported with a cutout from deoxycholate (DOC) acrylamide gels; this cutout was called fraction II (FII), and comprises approximately 10% of total DOC-soluble oncosphere antigen. Western blots of DOC gels probed with anti-FII antisera revealed a series of 3-5 discrete bands within the FII region. Further fractionation of the FII antigens on DOC gels was impractical due to limitations in supply of oncospheres, so a cDNA library was constructed from 150 ng of oncosphere mRNA and screened with alpha-FII antisera. Two distinct clone families were identified, oncA and oncB. Antibodies affinity-purified on either of two representative members, oncA1 and oncB1, recognised all the FII bands. Individual FII bands excised from a DOC gel resolved into an overlapping series of molecules when re-run on SDS-PAGE, indicating that each FII band consisted of several polypeptides of differing molecular weight. Immunoprecipitates resolved on SDS-PAGE revealed that alpha-FII recognised 3 major oncosphere antigens, of 62, 34 and 25 kDa; antisera against oncB precipitated both the 34- and 25-kDa antigens, whereas alpha-oncA antisera precipitated the 62-kDa antigen. We conclude that oncA and oncB encode the major antigens in the FII complex. The 62-kDa antigen encoded by oncA1 was the only common antigen precipitated by anti-FII and two other antisera raised against different protective extracts, suggesting that it may be a protective component in all three. Southern blot results indicate that oncA and oncB are distinct genes present at low copy number in the genome. Evidence is also presented suggesting that some cestode mRNAs, including oncA, may use variant polyadenylation signals.

  17. Conservation of a protective surface antigen of Tritrichomonas foetus.

    Science.gov (United States)

    Ikeda, J S; BonDurant, R H; Campero, C M; Corbeil, L B

    1993-12-01

    Bovine trichomoniasis is a sexually transmitted disease caused by the flagellated protozoan Tritrichomonas foetus. A protective surface antigen was previously identified and immunoaffinity purified from T. foetus isolate D1 with cross-reactive monoclonal antibodies (MAbs) TF1.15 and TF1.17 (BonDurant, R. H., R. R. Corbeil, and L. B. Corbeil, Infect. Immun. 61:1385-1394, 1993). This antigen elicited antibody responses in the serum and cervicovaginal mucus of heifers. Thus, it may be useful as an immunodiagnostic reagent as well as a subunit vaccine. Conservation of the antigen in all strains would be crucial for either application. We investigated the conservation of this antigen among 36 isolates of T. foetus from Argentina, Costa Rica, and the United States using MAbs TF1.15 and TF1.17 in an enzyme-linked immunosorbent assay. MAb TF1.17 reacted with 32 of the 36 isolates, whereas MAb TF1.15 reacted with all of the isolates tested. One of the isolates which did not react with MAb TF1.17 (i.e., D1#3) was investigated further by Western blotting (immunoblotting) to determine the reason for the lack of reactivity with one of the two cross-reactive MAbs. The antigenic band that was reactive with MAb TF1.15 had a molecular mass slightly lower than that of the corresponding band from isolate D1, which reacted with both MAbs TF1.15 and TF1.17. Thus, at least a major portion of the antigen appeared to be conserved. This was confirmed in a study of heifers infected with isolate D1#3. The vaginal immunoglobulin A antibodies of these infected heifers reacted with the antigen of isolate D1 that was immunoaffinity purified with MAb TF1.17. Therefore, even though the epitope recognized by MAb TF1.17 was missing in the challenge isolate (D1#3), the heifers developed an immune response to the rest of the molecule. These results indicate that the major portion of the previously described protective antigen is conserved in different isolates of T. foetus. This portion contains the

  18. Comparison of antigen-specific T-cell responses of tuberculosis patients using complex or single antigens of Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Mustafa, A S; Amoudy, H A; Wiker, H G;

    1998-01-01

    GroES, rPstS, rGroEL and rDnaK) antigens of Mycobacterium tuberculosis. The responses of PBMC to these defined antigens were compared with the corresponding results obtained with complex antigens, such as whole-cell M. tuberculosis, M. tuberculosis culture filtrate (MT-CF) and cell wall antigens, as well...... as the vaccine strain, Mycobacterium bovis bacillus Calmette-Guerin (BCG). In addition, M. tuberculosis and MT-CF-induced T-cell lines were tested in the same assays against the panel of purified and complex antigens. The compiled data from PBMC and T-cell lines tested for antigen-induced proliferation and IFN......We have screened peripheral blood mononuclear cells (PBMC) from tuberculosis (TB) patients for proliferative reactivity and interferon-gamma (IFN-gamma) secretion against a panel of purified recombinant (r) and natural (n) culture filtrate (rESAT-6, nMPT59, nMPT64 and nMPB70) and somatic-derived (r...

  19. Rapid profiling of the antigen regions recognized by serum antibodies using massively parallel sequencing of antigen-specific libraries.

    KAUST Repository

    Domina, Maria

    2014-12-04

    There is a need for techniques capable of identifying the antigenic epitopes targeted by polyclonal antibody responses during deliberate or natural immunization. Although successful, traditional phage library screening is laborious and can map only some of the epitopes. To accelerate and improve epitope identification, we have employed massive sequencing of phage-displayed antigen-specific libraries using the Illumina MiSeq platform. This enabled us to precisely identify the regions of a model antigen, the meningococcal NadA virulence factor, targeted by serum antibodies in vaccinated individuals and to rank hundreds of antigenic fragments according to their immunoreactivity. We found that next generation sequencing can significantly empower the analysis of antigen-specific libraries by allowing simultaneous processing of dozens of library/serum combinations in less than two days, including the time required for antibody-mediated library selection. Moreover, compared with traditional plaque picking, the new technology (named Phage-based Representation OF Immuno-Ligand Epitope Repertoire or PROFILER) provides superior resolution in epitope identification. PROFILER seems ideally suited to streamline and guide rational antigen design, adjuvant selection, and quality control of newly produced vaccines. Furthermore, this method is also susceptible to find important applications in other fields covered by traditional quantitative serology.

  20. Immunization of rabbits with nematode Ascaris lumbricoides antigens induces antibodies cross-reactive to house dust mite Dermatophagoides farinae antigens.

    Science.gov (United States)

    Nakazawa, Takuya; Khan, Al Fazal; Yasueda, Hiroshi; Saito, Akemi; Fukutomi, Yuma; Takai, Toshiro; Zaman, Khalequz; Yunus, Md; Takeuchi, Haruko; Iwata, Tsutomu; Akiyama, Kazuo

    2013-01-01

    There are controversial reports on the relationship between helminthic infection and allergic diseases. Although IgE cross-reactivity between nematode Ascaris antigens and house dust-mite allergens in allergic patients have been reported, whether Ascaris or the mite is the primary sensitizer remains unknown. Here we found that immunization of naïve animals with Ascaris lumbricoides (Al) antigens induced production of antibodies cross-reactive to mite antigens from Dermatophagoides farinae (Df). Sera from Bangladeshi children showed IgE reactivity to Ascaris and mite extracts. IgG from rabbits immunized with Al extract exhibited reactivity to Df antigens. Treatment of the anti-Al antibody with Df antigen-coupled beads eliminated the reactivity to Df antigens. In immunoblot analysis, an approximately 100-kDa Df band was the most reactive to anti-Al IgG. The present study is the first step towards the establishment of animal models to study the relationship between Ascaris infection and mite-induced allergic diseases.

  1. Rapid profiling of the antigen regions recognized by serum antibodies using massively parallel sequencing of antigen-specific libraries.

    Directory of Open Access Journals (Sweden)

    Maria Domina

    Full Text Available There is a need for techniques capable of identifying the antigenic epitopes targeted by polyclonal antibody responses during deliberate or natural immunization. Although successful, traditional phage library screening is laborious and can map only some of the epitopes. To accelerate and improve epitope identification, we have employed massive sequencing of phage-displayed antigen-specific libraries using the Illumina MiSeq platform. This enabled us to precisely identify the regions of a model antigen, the meningococcal NadA virulence factor, targeted by serum antibodies in vaccinated individuals and to rank hundreds of antigenic fragments according to their immunoreactivity. We found that next generation sequencing can significantly empower the analysis of antigen-specific libraries by allowing simultaneous processing of dozens of library/serum combinations in less than two days, including the time required for antibody-mediated library selection. Moreover, compared with traditional plaque picking, the new technology (named Phage-based Representation OF Immuno-Ligand Epitope Repertoire or PROFILER provides superior resolution in epitope identification. PROFILER seems ideally suited to streamline and guide rational antigen design, adjuvant selection, and quality control of newly produced vaccines. Furthermore, this method is also susceptible to find important applications in other fields covered by traditional quantitative serology.

  2. Original encounter with antigen determines antigen-presenting cell imprinting of the quality of the immune response in mice.

    Directory of Open Access Journals (Sweden)

    Valérie Abadie

    Full Text Available BACKGROUND: Obtaining a certain multi-functionality of cellular immunity for the control of infectious diseases is a burning question in immunology and in vaccine design. Early events, including antigen shuttling to secondary lymphoid organs and recruitment of innate immune cells for adaptive immune response, determine host responsiveness to antigens. However, the sequence of these events and their impact on the quality of the immune response remain to be elucidated. Here, we chose to study Modified Vaccinia virus Ankara (MVA which is now replacing live Smallpox vaccines and is proposed as an attenuated vector for vaccination strategies against infectious diseases. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed in vivo mechanisms triggered following intradermal (i.d. and intramuscular (i.m. Modified Vaccinia virus Ankara (MVA administration. We demonstrated significant differences in the antigen shuttling to lymphoid organs by macrophages (MPhis, myeloid dendritic cells (DCs, and neutrophils (PMNs. MVA i.d. administration resulted in better antigen distribution and more sustained antigen-presenting cells (APCs recruitment into draining lymph nodes than with i.m. administration. These APCs, which comprise both DCs and MPhis, were differentially involved in T cell priming and shaped remarkably the quality of cytokine-producing virus-specific T cells according to the entry route of MVA. CONCLUSIONS/SIGNIFICANCE: This study improves our understanding of the mechanisms of antigen delivery and their consequences on the quality of immune responses and provides new insights for vaccine development.

  3. Comparison of antigen-specific T-cell responses of tuberculosis patients using complex or single antigens of Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Mustafa, A S; Amoudy, H A; Wiker, H G

    1998-01-01

    We have screened peripheral blood mononuclear cells (PBMC) from tuberculosis (TB) patients for proliferative reactivity and interferon-gamma (IFN-gamma) secretion against a panel of purified recombinant (r) and natural (n) culture filtrate (rESAT-6, nMPT59, nMPT64 and nMPB70) and somatic-derived (r......GroES, rPstS, rGroEL and rDnaK) antigens of Mycobacterium tuberculosis. The responses of PBMC to these defined antigens were compared with the corresponding results obtained with complex antigens, such as whole-cell M. tuberculosis, M. tuberculosis culture filtrate (MT-CF) and cell wall antigens, as well...... as the vaccine strain, Mycobacterium bovis bacillus Calmette-Guerin (BCG). In addition, M. tuberculosis and MT-CF-induced T-cell lines were tested in the same assays against the panel of purified and complex antigens. The compiled data from PBMC and T-cell lines tested for antigen-induced proliferation and IFN...

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

    DEFF Research Database (Denmark)

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

    1986-01-01

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

  5. Comparison of Excretory-Secretory and Somatic Antigens of Ornithobilharzia turkestanicum in Agar Gel Diffusion Test

    Directory of Open Access Journals (Sweden)

    H Miranzadeh

    2008-12-01

    Full Text Available Background: Ornithobilharziosis as one of the parasitic infections may give rise to serious economic problems in animal husbandry. The Aim of the study was to prepare and compare the somatic and excretory-secretory (ES antigens of O. tur­kestanicum in gel diffusion test. Methods: Excretory-secretory (ES and somatic antigens of Ornithobilharzia turkestanicum were prepared from collected worms from mesentric blood vessels of infected sheep. The laboratory bred rabbits were immunized with antigens and then antisera were prepared. The reaction of antigens and antisera was observed in gel diffusion test. Results: ES antigens of this species showed positive reaction with antisera raised against ES and also somatic antigens. Somatic antigens also showed positive reaction with antisera raised against somatic and also ES antigens. Conclusion: The antigenicity of O. turkestanicum ES and somatic antigens is the same in gel diffusion test.

  6. mage Mining using Content Based Image Retrieval System

    OpenAIRE

    Rajshree S. Dubey; Niket Bhargava; Rajnish Choubey

    2010-01-01

    The image depends on the Human perception and is also based on the Machine Vision System. The Image Retrieval is based on the color Histogram, texture. The perception of the Human System of Image is based on the Human Neurons which hold the 1012 of Information; the Human brain continuously learns with the sensory organs like eye which transmits the Image to the brain which interprets the Image. The research challenge is that how the brain processes the informationin the semantic manner is hot...

  7. O-antigen modulates infection-induced pain states.

    Directory of Open Access Journals (Sweden)

    Charles N Rudick

    Full Text Available The molecular initiators of infection-associated pain are not understood. We recently found that uropathogenic E. coli (UPEC elicited acute pelvic pain in murine urinary tract infection (UTI. UTI pain was due to E. coli lipopolysaccharide (LPS and its receptor, TLR4, but pain was not correlated with inflammation. LPS is known to drive inflammation by interactions between the acylated lipid A component and TLR4, but the function of the O-antigen polysaccharide in host responses is unknown. Here, we examined the role of O-antigen in pain using cutaneous hypersensitivity (allodynia to quantify pelvic pain behavior and using sacral spinal cord excitability to quantify central nervous system manifestations in murine UTI. A UPEC mutant defective for O-antigen biosynthesis induced chronic allodynia that persisted long after clearance of transient infections, but wild type UPEC evoked only acute pain. E. coli strains lacking O-antigen gene clusters had a chronic pain phenotype, and expressing cloned O-antigen gene clusters altered the pain phenotype in a predictable manner. Chronic allodynia was abrogated in TLR4-deficient mice, but inflammatory responses in wild type mice were similar among E. coli strains spanning a wide range of pain phenotypes, suggesting that O-antigen modulates pain independent of inflammation. Spinal cords of mice with chronic allodynia exhibited increased spontaneous firing and compromised short-term depression, consistent with centralized pain. Taken together, these findings suggest that O-antigen functions as a rheostat to modulate LPS-associated pain. These observations have implications for an infectious etiology of chronic pain and evolutionary modification of pathogens to alter host behaviors.

  8. Identification of Antigenic Proteins of the Nosocomial Pathogen Klebsiella pneumoniae

    Science.gov (United States)

    Hoppe, Sebastian; Bier, Frank F.; von Nickisch-Rosenegk, Markus

    2014-01-01

    The continuous expansion of nosocomial infections around the globe has become a precarious situation. Key challenges include mounting dissemination of multiple resistances to antibiotics, the easy transmission and the growing mortality rates of hospital-acquired bacterial diseases. Thus, new ways to rapidly detect these infections are vital. Consequently, researchers around the globe pursue innovative approaches for point-of-care devices. In many cases the specific interaction of an antigen and a corresponding antibody is pivotal. However, the knowledge about suitable antigens is lacking. The aim of this study was to identify novel antigens as specific diagnostic markers. Additionally, these proteins might be aptly used for the generation of vaccines to improve current treatment options. Hence, a cDNA-based expression library was constructed and screened via microarrays to detect novel antigens of Klebsiella pneumoniae, a prominent agent of nosocomial infections well-known for its extensive antibiotics resistance, especially by extended-spectrum beta-lactamases (ESBL). After screening 1536 clones, 14 previously unknown immunogenic proteins were identified. Subsequently, each protein was expressed in full-length and its immunodominant character examined by ELISA and microarray analyses. Consequently, six proteins were selected for epitope mapping and three thereof possessed linear epitopes. After specificity analysis, homology survey and 3d structural modelling, one epitope sequence GAVVALSTTFA of KPN_00363, an ion channel protein, was identified harboring specificity for K. pneumoniae. The remaining epitopes showed ambiguous results regarding the specificity for K. pneumoniae. The approach adopted herein has been successfully utilized to discover novel antigens of Campylobacter jejuni and Salmonella enterica antigens before. Now, we have transferred this knowledge to the key nosocomial agent, K. pneumoniae. By identifying several novel antigens and their linear

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

    OpenAIRE

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

    2001-01-01

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

  10. Advances in identification and application of tumor antigen inducing anti-cancer responses

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    @@ Tumor antigen is one of the important bases of tumor immunotherapy[1]. With the discovery of novel tumor antigens, interest in specific immunotherapy for treatment of malignancies has increased substantially. Nowadays more and more scientists paid close attention to various tumor antigens with their roles or/and applications in anti-cancer immune responses, immune tolerance, tumor markers, tumor immunotherapy and so on. Here we discussed the classification of tumor antigens and summarized the technologies of identification and application of tumor antigens.

  11. Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity

    NARCIS (Netherlands)

    Kreutz, M.; Giquel, B.; Hu, Q.; Abuknesha, R.; Uematsu, S.; Akira, S.; Nestle, F.O.; Diebold, S.S.

    2012-01-01

    Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC) by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is par

  12. Les politiques d’employabilité en Belgique : traitement clinique des chômeurs et traitement statistique du chômage The Politics of Employability in Belgium : Clinical Treatment of the Unemployed and Statistical Treatment of Unemployment

    Directory of Open Access Journals (Sweden)

    Jean-François Orianne

    2011-03-01

    Full Text Available Cet article interroge la mise en œuvre et le suivi des politiques européennes d’employabilité en Belgique à la lumière de la sociologie de Norbert Elias, en reliant les dimensions sociogénétiques et psychogénétiques de la construction européenne. Le traitement clinique des chômeurs, qui repose principalement sur la construction professionnelle de troubles de l’employabilité, contribue à l’intériorisation de normes à grande échelle, à la socialisation de la population active au marché du travail et renforce la concurrence entre les actifs occupés et les actifs inoccupés (principale condition de stabilité de la monnaie unique. Parallèlement, le traitement statistique du chômage, qui consiste en un jeu rationnel entre États (et Régions de maximisation des indicateurs de résultats, renforce la compétition territoriale pour attirer les investisseurs et encadre, légitime, dynamise ce mouvement incertain d’harmonisation ou d’intégration des systèmes de protection sociale en Europe.This article investigates the setting up and follow-up of European employment politics in Belgium, in light of the sociology of Norbert Elias, in blending the socio-genetic and psycho-genetic dimensions of European construction. The clinical treatment of the unemployed, principally based on the professional construction of employability troubles, contributes to the internalization of standards on a vast scale, to the socialization of the active population on the job market and reinforcing competition between occupied actives and unoccupied actives (a principal condition for the stability of a unique currency. At the same time, the statistical treatment of unemployment, consisting in a deliberate game between States (and Regions of maximization of result indicators, reinforces a territorial competition aimed at attracting investors as well as organizing, legitimating and dynamizing the unsteady movement toward harmonization or

  13. Viral immune evasion: Lessons in MHC class I antigen presentation.

    Science.gov (United States)

    van de Weijer, Michael L; Luteijn, Rutger D; Wiertz, Emmanuel J H J

    2015-03-01

    The MHC class I antigen presentation pathway enables cells infected with intracellular pathogens to signal the presence of the invader to the immune system. Cytotoxic T lymphocytes are able to eliminate the infected cells through recognition of pathogen-derived peptides presented by MHC class I molecules at the cell surface. In the course of evolution, many viruses have acquired inhibitors that target essential stages of the MHC class I antigen presentation pathway. Studies on these immune evasion proteins reveal fascinating strategies used by viruses to elude the immune system. Viral immunoevasins also constitute great research tools that facilitate functional studies on the MHC class I antigen presentation pathway, allowing the investigation of less well understood routes, such as TAP-independent antigen presentation and cross-presentation of exogenous proteins. Viral immunoevasins have also helped to unravel more general cellular processes. For instance, basic principles of ER-associated protein degradation via the ubiquitin-proteasome pathway have been resolved using virus-induced degradation of MHC class I as a model. This review highlights how viral immunoevasins have increased our understanding of MHC class I-restricted antigen presentation.

  14. Generation of monoclonal antibodies against highly conserved antigens.

    Directory of Open Access Journals (Sweden)

    Hongzhe Zhou

    Full Text Available BACKGROUND: Therapeutic antibody development is one of the fastest growing areas of the pharmaceutical industry. Generating high-quality monoclonal antibodies against a given therapeutic target is very crucial for the success of the drug development. However, due to immune tolerance, some proteins that are highly conserved between mice and humans are not very immunogenic in mice, making it difficult to generate antibodies using a conventional approach. METHODOLOGY/PRINCIPAL FINDINGS: In this report, the impaired immune tolerance of NZB/W mice was exploited to generate monoclonal antibodies against highly conserved or self-antigens. Using two highly conserved human antigens (MIF and HMGB1 and one mouse self-antigen (TNF-alpha as examples, we demonstrate here that multiple clones of high affinity, highly specific antibodies with desired biological activities can be generated, using the NZB/W mouse as the immunization host and a T cell-specific tag fused to a recombinant antigen to stimulate the immune system. CONCLUSIONS/SIGNIFICANCE: We developed an efficient and universal method for generating surrogate or therapeutic antibodies against "difficult antigens" to facilitate the development of therapeutic antibodies.

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

    Directory of Open Access Journals (Sweden)

    Shashi Ashok Gujar

    2014-04-01

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

  16. Sharing the burden: antigen transport and firebreaks in immune responses.

    Science.gov (United States)

    Handel, Andreas; Yates, Andrew; Pilyugin, Sergei S; Antia, Rustom

    2009-05-06

    Communication between cells is crucial for immune responses. An important means of communication during viral infections is the presentation of viral antigen on the surface of an infected cell. Recently, it has been shown that antigen can be shared between infected and uninfected cells through gap junctions, connexin-based channels, that allow the transport of small molecules. The uninfected cell receiving antigen can present it on its surface. Cells presenting viral antigen are detected and killed by cytotoxic T lymphocytes. The killing of uninfected cells can lead to increased immunopathology. However, the immune response might also profit from killing those uninfected bystander cells. One benefit might be the removal of future 'virus factories'. Another benefit might be through the creation of 'firebreaks', areas void of target cells, which increase the diffusion time of free virions, making their clearance more likely. Here, we use theoretical models and simulations to explore how the mechanism of gap junction-mediated antigen transport (GMAT) affects the dynamics of the virus and immune response. We show that under the assumption of a well-mixed system, GMAT leads to increased immunopathology, which always outweighs the benefit of reduced virus production due to the removal of future virus factories. By contrast, a spatially explicit model leads to quite different results. Here we find that the firebreak mechanism reduces both viral load and immunopathology. Our study thus shows the potential benefits of GMAT and illustrates how spatial effects may be crucial for the quantitative understanding of infection dynamics and immune responses.

  17. Prediction of antigenic determinants of trichosanthin by molecular modeling

    Institute of Scientific and Technical Information of China (English)

    HEYONGNING; ZONGXIANGXIA; 等

    1996-01-01

    The antigenic determinants of trichosanthin were predicted by molecular modeling.First,the threedimensional structure model of the antigen-binding fragment of anti-trichosanthin immunoglobulin E was built on the basis of its amino-acid sequence and the known three-dimensional structure of an antibody with similar sequence.Secondly,the preferable antigen-antibody interactions were obtained based on the known three-dimensional structure of trichosanthin and of the hypervariable regions of anti-trichosanthin immunoglobulin E.Two regions in the molecular surface of trichosanthin were found to form extensive interactions with the hypervariable regions of the antibody and have been predicted to be the possible antigenic determinants:one is composed of two polypeptide segments,Ile201-Glu210 and Ile225-Asp229,which are close to each other in the three-dimensional structure;and the other is the segment Lys173-Thr178.The former region seems to be the more reasonable antigenic determinant than the latter one.

  18. Successive Administration of Streptococcus Type 5 Group A Antigens and S. typhimurium Antigenic Complex Corrects Elevation of Serum Cytokine Concentration and Number of Bone Marrow Stromal Pluripotent Cells in CBA Mice Induced by Each Antigen Separately.

    Science.gov (United States)

    Gorskaya, Yu F; Danilova, T A; Grabko, V I; Nesterenko, V G

    2015-12-01

    Administration of bacterial antigens to CBA mice induced an increase in serum concentration of virtually all cytokines with a peak in 4 h after administration of S. typhimurium antigens and in 7 h after administration of streptococcus antigens. In 20 h, cytokine concentrations returned to the control level or were slightly below it. In 4 h after administration of S. typhimurium antigens preceded 3 h before by administration of streptococcus antigens, we observed a significant decrease in serum concentrations of IFN-γ, IL-10, GM-CSF, IL-12, and TNF-α, in comparison with injection S. typhimurium antigens alone and IL-5, IL-10, GM-CSF, and TNF-α in comparison with injection of streptococcus antigens alone; the concentrations of IL-2 and IFN-γ, in contrast, increased by 1.5 times in this case. In 20 h after administration of S. typhimurium antigens, the number of multipotential stromal cells (MSC) in the bone marrow and their cloning efficiency (ECF-MSC) increased by 4.8 and 4.4 times, respectively, in comparison with the control, while after administration of streptococcus antigens by 2.6 and 2.4 times, respectively. In 20 h after administration of S. typhimurium antigens preceded 3 h before by administration of streptococcus antigens, these parameters increased by 3.2 and 2.9 times, respectively, in comparison with the control, i.e. the observed increase in the level of MSC count and ECF-MSC is more consistent with the response of the stromal tissue to streptococcus antigens. Thus, successive administration of two bacterial antigens corrected both serum cytokine profiles and MSC response to administration of each antigen separately, which indicates changeability of the stromal tissue in response to changes in the immune response.

  19. BIOCHEMICAL STUDIES ON SO-CALLED SYPHILIS ANTIGEN.

    Science.gov (United States)

    Noguchi, H; Bronfenbrenner, J

    1911-01-01

    The liver tissues of man and certain animals (dogs, rabbits, guinea pigs, etc.) yield, upon alcoholic extraction, various substances which may be divided by their physical and chemical properties into several groups. While many substances are present in the alcoholic extract, the ones possessing antigenic properties are comparatively few. The latter are responsible for the antigenic properties exhibited by the whole alcoholic extract. The substances extracted with alcohol were fractionated into the following four groups. (a) Substances Insoluble in Ether and Hot Alcohol.-These are chiefly proteins and salts. The proteins are probably the minute particles of larger molecules held in apparent suspension in alcohol until all other substances are removed. The water extracted from the tissues and admixed with alcohol is also an essential factor in extracting these particles in an alcoholic solution. The salts present are the usual physiological constituents of the liver, notably, sodium chloride. The quantity of these substances extracted with alcohol varies greatly with different specimens. Biologically considered, they are neither markedly hemolytic nor anticomplementary and possess no antigenic property for the Wassermann reaction. It is important, however, to note that the proteins bind complement when mixed with certain active human sera. For this reason a preparation of antigen containing this group of substances is unsuitable for use in combination with an active serum, and should, therefore, be rejected. (b) Substances Insoluble in Ether and Soluble in Hot Alcohol.-This group contains soaps, cleavage products of proteins, and small amounts of the bile salts. Soaps and bile salts are very strongly hemolytic and are absolutely unfit for use as antigen. Moreover, their antigenic properties are very slight. It is best to eliminate this group of substances from the preparation of antigen. The quantity of the substances of this group extracted from different specimens

  20. Immunological Properties of Hepatitis B Core Antigen Fusion Proteins

    Science.gov (United States)

    Francis, Michael J.; Hastings, Gillian Z.; Brown, Alan L.; Grace, Ken G.; Rowlands, David J.; Brown, Fred; Clarke, Berwyn E.

    1990-04-01

    The immunogenicity of a 19 amino acid peptide from foot-and-mouth disease virus has previously been shown to approach that of the inactivated virus from which it was derived after multimeric particulate presentation as an N-terminal fusion with hepatitis B core antigen. In this report we demonstrate that rhinovirus peptide-hepatitis B core antigen fusion proteins are 10-fold more immunogenic than peptide coupled to keyhole limpet hemocyanin and 100-fold more immunogenic than uncoupled peptide with an added helper T-cell epitope. The fusion proteins can be readily administered without adjuvant or with adjuvants acceptable for human and veterinary application and can elicit a response after nasal or oral dosing. The fusion proteins can also act as T-cell-independent antigens. These properties provide further support for their suitability as presentation systems for "foreign" epitopes in the development of vaccines.

  1. Heterogeneous antigen recognition behavior of induced polyspecific antibodies.

    Science.gov (United States)

    Dimitrov, Jordan D; Planchais, Cyril; Kang, Jonghoon; Pashov, Anastas; Vassilev, Tchavdar L; Kaveri, Srinivas V; Lacroix-Desmazes, Sebastien

    2010-07-23

    Polyspecific antibodies represent a significant fraction of the antibody repertoires in healthy animals and humans. Interestingly, certain antibodies only acquire a polyspecific antigen-binding behavior after exposure to protein-modifying conditions, such as those found at inflammation sites, or used in small- and large-scale immunoglobulin purification. This phenomenon is referred to as "criptic polyspecificity". In the present study, we compare the potential of different chemical agents to induce IgG polyspecificity. Depending on the treatment used, quantitative and qualitative differences in the recognition of individual antigens from a standard panel were observed. Antibodies with cryptic polyspecificity utilized common mechanisms for the recognition of structurally unrelated antigens when exposed to a particular inductor of polyspecificity. Our study contributes to the understanding of the mechanisms underlying the cryptic polyspecificity.

  2. Characterization of oligosaccharides from an antigenic mannan of Saccharomyces cerevisiae.

    Science.gov (United States)

    Young, M; Davies, M J; Bailey, D; Gradwell, M J; Smestad-Paulsen, B; Wold, J K; Barnes, R M; Hounsell, E F

    1998-08-01

    Mannans of the yeast Saccharomyces cerevisiae have been implicated as containing the allergens to which bakers and brewers are sensitive and also the antigen recognized by patients with Crohn's disease. A fraction of S. cerevisiae mannan, Sc500, having high affinity for antibodies in Crohn's patients has been characterized by NMR spectroscopy followed by fragmentation using alkaline elimination, partial acid hydrolysis and acetolysis. The released oligosaccharides were separated by gel filtration on a Biogel P4 column and analyzed by fluorescence labeling, HPLC and methylation analysis. The relationship between structure and antigen activity was measured by competitive ELISA. The antigenic activity of the original high molecular weight mannan could be ascribed to terminal Manalpha1-->3Manalpha1-->2 sequences which are rarely found in human glycoproteins but were over-represented in Sc500 compared to other yeast mannans.

  3. Oxidative stress can alter the antigenicity of immunodominant peptides

    DEFF Research Database (Denmark)

    Weiskopf, Daniela; Schwanninger, Angelika; Weinberger, Birgit

    2010-01-01

    APCs operate frequently under oxidative stress induced by aging, tissue damage, pathogens, or inflammatory responses. Phagocytic cells produce peroxides and free-radical species that facilitate pathogen clearance and can in the case of APCs, also lead to oxidative modifications of antigenic...... molecule is not impaired. Additionally, we show that CD8(+) T cells have a decreased proliferation and IFN-gamma production when stimulated with oxidized CMVpp65(495-503) peptide. Spectratyping the antigen-binding site of the TCR of responding T cells demonstrates that the CMVpp65(495-503) and the CMVoxpp...... of antigenic peptides may affect T cell responses severely by binding T cell clones with different affinity. This may lead to an altered immune response against infectious agents as well as against tumor or autoantigens under oxidative stress conditions....

  4. COTA (colon-ovarian tumor antigen). An immunohistochemical study.

    Science.gov (United States)

    Pant, K D; Fenoglio-Preiser, C M; Berry, C O; Zamora, P O; Ram, M D; Fulks, R M; Rhodes, B A

    1986-07-01

    A goat anti-serum was prepared against mucinous ovarian cyst fluid and absorbed with normal colon and a variety of normal tissues until the only residual immunoreactivity was directed against colon cancer and ovarian tumor mucin. The set of antigenic determinants defined by this anti-serum has been called COTA, standing for colon-ovarian-tumor-antigen. This highly absorbed anti-serum (anti-COTA) was used for immunohistochemical staining of 42 different tissues in parallel with staining with a goat anti-CEA, which was also highly absorbed. The results suggest that COTA is a highly sensitive and specific antigen for colon carcinoma and may have potential for the early detection of malignant changes predictive of cancer of the colon.

  5. Regulatory T Cells Are Dispensable for Tolerance to RBC Antigens.

    Science.gov (United States)

    Richards, Amanda L; Kapp, Linda M; Wang, Xiaohong; Howie, Heather L; Hudson, Krystalyn E

    2016-01-01

    Autoimmune hemolytic anemia (AIHA) occurs when pathogenic autoantibodies against red blood cell (RBC) antigens are generated. While the basic disease pathology of AIHA is well studied, the underlying mechanism(s) behind the failure in tolerance to RBC autoantigens are poorly understood. Thus, to investigate the tolerance mechanisms required for the establishment and maintenance of tolerance to RBC antigens, we developed a novel murine model. With this model, we evaluated the role of regulatory T cells (Tregs) in tolerance to RBC-specific antigens. Herein, we show that neither sustained depletion of Tregs nor immunization with RBC-specific proteins in conjunction with Treg depletion led to RBC-specific autoantibody generation. Thus, these studies demonstrate that Tregs are not required to prevent autoantibodies to RBCs and suggest that other tolerance mechanisms are likely involved.

  6. Regulatory T cells are Dispensable for Tolerance to RBC Antigens

    Directory of Open Access Journals (Sweden)

    Amanda L Richards

    2016-09-01

    Full Text Available Autoimmune hemolytic anemia (AIHA occurs when pathogenic autoantibodies against red blood cell (RBC antigens are generated. Whilst the basic disease pathology of AIHA is well studied, the underlying mechanism(s behind the failure in tolerance to RBC autoantigens are poorly understood. Thus, to investigate the tolerance mechanisms required for the establishment and maintenance of tolerance to RBC antigens, we developed a novel murine model. With this model, we evaluated the role of regulatory T cells (Tregs in tolerance to RBC-specific antigens. Herein, we show that neither sustained depletion of Tregs nor immunization with RBC-specific proteins in conjunction with Treg depletion led to RBC-specific autoantibody generation. Thus, these studies demonstrate that Tregs are not required to prevent autoantibodies to RBCs and suggest that other tolerance mechanisms are likely involved.

  7. MHC Class I Antigen Presentation- Recently Trimmed and Well Presented

    Institute of Scientific and Technical Information of China (English)

    BarryFlutter; BinGao

    2004-01-01

    Presentation of antigenic peptide to T cells by major histocompatibility complex (MHC) class I molecules is the key to the cellular immune response. Non-self intracellular proteins are processed into short peptides and transported into endoplasmic reticulum (ER) where they are assembled with class I molecules assisted by several chaperone proteins to form trimeric complex. MHC class I complex loaded with optimised peptides travels to the cell surface of antigen presentation cells to be recognised by T cells. The cells presenting non-self peptides are cleared by CD8 positive T cells. In order to ensure that T cells detect an infection or mutation within the target cells the process of peptide loading and class I expression must be carefully regulated. Many of the cellular components involved in antigen processing and class I presentation are known and their various functions are now becoming clearer. Cellular & Molecular Immunology. 2004;1(1):22-30.

  8. MHC Class Ⅰ Antigen Presentation- Recently Trimmed and Well Presented

    Institute of Scientific and Technical Information of China (English)

    Barry Flutter; Bin Gao

    2004-01-01

    Presentation of antigenic peptide to T cells by major histocompatibility complex (MHC) class Ⅰ molecules is the key to the cellular immune response. Non-self intracellular proteins are processed into short peptides and transported into endoplasmic reticulum (ER) where they are assembled with class Ⅰ molecules assisted by several chaperone proteins to form trimeric complex. MHC class Ⅰ complex loaded with optimised peptides travels to the cell surface of antigen presentation cells to be recognised by T cells. The cells presenting non-self peptides are cleared by CD8 positive T cells. In order to ensure that T cells detect an infection or mutation within the target cells the process of peptide loading and class Ⅰ expression must be carefully regulated. Many of the cellular components involved in antigen processing and class Ⅰ presentation are known and their various functions are now becoming clearer. Cellular & Molecular Immunology. 2004;1(1):22-30.

  9. Comparative analysis of minor histocompatibility antigens genotyping methods

    Directory of Open Access Journals (Sweden)

    A. S. Vdovin

    2016-01-01

    Full Text Available The wide range of techniques could be employed to find mismatches in minor histocompatibility antigens between transplant recipients and their donors. In the current study we compared three genotyping methods based on polymerase chain reaction (PCR for four minor antigens. Three of the tested methods: allele-specific PCR, restriction fragment length polymorphism and real-time PCR with TaqMan probes demonstrated 100% reliability when compared to Sanger sequencing for all of the studied polymorphisms. High resolution melting analysis was unsuitable for genotyping of one of the tested minor antigens (HA-1 as it has linked synonymous polymorphism. Obtained data could be used to select the strategy for large-scale clinical genotyping.

  10. Antigenic breadth: a missing ingredient in HSV-2 subunit vaccines?

    Science.gov (United States)

    Halford, William P

    2014-06-01

    The successful human papillomavirus and hepatitis B virus subunit vaccines contain single viral proteins that represent 22 and 12%, respectively, of the antigens encoded by these tiny viruses. The herpes simplex virus 2 (HSV-2) genome is >20 times larger. Thus, a single protein subunit represents 1% of HSV-2's total antigenic breadth. Antigenic breadth may explain why HSV-2 glycoprotein subunit vaccines have failed in clinical trials, and why live HSV-2 vaccines that express 99% of HSV-2's proteome may be more effective. I review the mounting evidence that live HSV-2 vaccines offer a greater opportunity to stop the spread of genital herpes, and I consider the unfounded 'safety concerns' that have kept live HSV-2 vaccines out of U.S. clinical trials for 25 years.

  11. Stem cell antigen 2 expression in adult and developing mice.

    Science.gov (United States)

    Antica, M; Wu, L; Scollay, R

    1997-01-01

    Stem cell antigen 2 (Sca-2) expression can distinguish the most immature T-lymphocyte precursors in the thymus from the hemopoietic stem cells. Sequence analysis of the Sca-2 protein showed that Sca-2 is a glycosylphosphatidylinositol (GPI) anchored molecule that shares some characteristics with the members of the Ly-6 multigene family, and that it is the same as the thymic shared antigen-1 (TSA-1). Here we extend these studies and critically reassess the expression of the Sca-2/TSA-1 antigen in hematopoietic tissues of adult and developing mice. With more sensitive methods we show that the distribution of Sca-2/TSA-1 differs from existing reports. We find especially high expression of Sca-2/TSA1 at day 14 of fetal development.

  12. MHC structure and function − antigen presentation. Part 2

    Science.gov (United States)

    Goldberg, Anna Carla; Rizzo, Luiz Vicente

    2015-01-01

    The second part of this review deals with the molecules and processes involved in the processing and presentation of the antigenic fragments to the T-cell receptor. Though the nature of the antigens presented varies, the most significant class of antigens is proteins, processed within the cell to be then recognized in the form of peptides, a mechanism that confers an extraordinary degree of precision to this mode of immune response. The efficiency and accuracy of this system is also the result of the myriad of mechanisms involved in the processing of proteins and production of peptides, in addition to the capture and recycling of alternative sources aiming to generate further diversity in the presentation to T-cells. PMID:25807243

  13. An iron-binding Trypanosoma cruzi urinary antigen.

    Science.gov (United States)

    Corral, R S; Bertot, G M; Petray, P B; Altcheh, J M; Singh, M; Orn, A; Rapoport, M F; Grinstein, S

    1995-12-01

    An 80-kDa Trypanosoma cruzi urinary antigen (UAg) was affinity-purified from the urine of infected dogs. We demonstrated that UAg is structurally and functionally related to proteins belonging to the transferrin family, as shown by amino acid sequence and iron binding experiments. Nevertheless, monoclonal antibodies raised against UAg specifically and selectively recognized this parasite's circulating antigen. The existence of an 80-kDa T. cruzi antigen co-migrating with UAg could be confirmed when epimastigotes were metabolically labelled with [35S] methionine and then immunoprecipitated with the above mentioned antibodies. We conclude that UAg is an iron-binding T. cruzi component eliminated in the urine of the infected host.

  14. Development of the Artificial Antigens for the Organophosphorus Insecticide chlorpyrifos

    Institute of Scientific and Technical Information of China (English)

    ZHU Guo-nian; WU Gang; WU Hui-ming

    2004-01-01

    This study reported that the hapten of the organophosphorus insecticide chlorpyrifos,O,Odiethyl-O-[3,5-dichloro-6-(2-carboxyethyl)thio-2-pyridyl]phosphorothioate(named AR) was synthesized by using technical grade chlorpyrifos reacted with 3-marcapropanoic acid in hot alkaline solution.The hapten was conjugated to bovine serum albumin (BSA) with the modified active ester method to form artificial immune antigen.The ratio of AR:BSA was 39:1.The artificial coating antigen for chlorpyrifos was synthesized by conjugating AR to ovalbumin (OVA) with the mixed-anhydride method,and the ratio was 13:1.The anti-chlorpyrifos polyclonal antibodies were obtained by using the artificial immune antigen (AR-BSA) to immune in the rabbits.

  15. Gallium arsenide exposure impairs processing of particulate antigen by macrophages: modification of the antigen reverses the functional defect.

    Science.gov (United States)

    Hartmann, Constance B; McCoy, Kathleen L

    2004-06-11

    Gallium arsenide (GaAs), a semiconductor used in the electronics industry, causes systemic immunosuppression in animals. The chemical's impact on macrophages to process the particulate antigen, sheep red blood cells (SRBC), for a T cell response in culture was examined after in vivo exposure of mice. GaAs-exposed splenic macrophages were defective in activating SRBC-primed lymph node T cells that could not be attributed to impaired phagocytosis. Modified forms of SRBC were generated to examine the compromised function of GaAs-exposed macrophages. SRBC were fixed to maintain their particulate nature and subsequently delipidated with detergent. Delipidation of intact SRBC was insufficient to restore normal antigen processing in GaAs-exposed macrophages. However, chemically exposed cells efficiently processed soluble sheep proteins. These findings suggest that the problem may lie in the release of sequestered sheep protein antigens, which then could be effectively cleaved to peptides. Furthermore, opsonization of SRBC with IgG compensated for the macrophage processing defect. The influence of signal transduction and phagocytosis via Fcgamma receptors on improved antigen processing could be dissociated. Immobilized anti-Fcgamma receptor antibody activated macrophages to secrete a chemokine, but did not enhance processing of unmodified SRBC by GaAs-exposed macrophages. Restoration of normal processing of particulate SRBC by chemically exposed macrophages involved phagocytosis through Fcgamma receptors. Hence, initial immune responses may be very sensitive to GaAs exposure, and the chemical's immunosuppression may be averted by opsonized particulate antigens.

  16. Antigen, allele, and haplotype frequencies report of the ASHI minority antigens workshops: part 1, African-Americans.

    Science.gov (United States)

    Zachary, A A; Bias, W B; Johnson, A; Rose, S M; Leffell, M S

    2001-10-01

    HLA typing was performed on 977 African Americans residing throughout most of the United States. Class I and class II antigens and class II alleles were defined for all individuals and class I alleles were determined for a subset of individuals. The occurrence of 854 of the individuals in family groups permitted direct counting of allele and haplotype frequencies. The data were analyzed for antigen, allele, and haplotype frequencies; recombination frequencies; segregation distortion; distribution of haplotype frequencies; linkage disequilibria; and geographic distribution of DR antigens. Tables of the antigen, allele, the most common two and three point haplotypes, and 88 extended haplotypes that include class I and class II alleles are presented. Notable findings include a lower than expected frequency of recombination between the B and DR loci (theta= 0.0013), lower than expected frequency of inheritance (44.5% vs 54.5%) of the DRB1*1503; DQB1*0602 haplotype, lower than anticipated linkage disequilibrium values for DR; DQ haplotypes, and a skewed geographic distribution of DR antigens.

  17. Continual Antigenic Diversification in China Leads to Global Antigenic Complexity of Avian Influenza H5N1 Viruses

    Science.gov (United States)

    Peng, Yousong; Li, Xiaodan; Zhou, Hongbo; Wu, Aiping; Dong, Libo; Zhang, Ye; Gao, Rongbao; Bo, Hong; Yang, Lei; Wang, Dayan; Lin, Xian; Jin, Meilin; Shu, Yuelong; Jiang, Taijiao

    2017-01-01

    The highly pathogenic avian influenza (HPAI) H5N1 virus poses a significant potential threat to human society due to its wide spread and rapid evolution. In this study, we present a comprehensive antigenic map for HPAI H5N1 viruses including 218 newly sequenced isolates from diverse regions of mainland China, by computationally separating almost all HPAI H5N1 viruses into 15 major antigenic clusters (ACs) based on their hemagglutinin sequences. Phylogenetic analysis showed that 12 of these 15 ACs originated in China in a divergent pattern. Further analysis of the dissemination of HPAI H5N1 virus in China identified that the virus’s geographic expansion was co-incident with a significant divergence in antigenicity. Moreover, this antigenic diversification leads to global antigenic complexity, as typified by the recent HPAI H5N1 spread, showing extensive co-circulation and local persistence. This analysis has highlighted the challenge in H5N1 prevention and control that requires different planning strategies even inside China. PMID:28262734

  18. Antigenic relatedness of equine herpes virus types 1 and 3.

    Science.gov (United States)

    Gutekunst, D E; Malmquist, W A; Becvar, C S

    1978-01-01

    Antiserums prepared in specific pathogen free (SPF) ponies were used in direct and indirect immunofluorescence, immunodiffusion, complement fixation and serum neutralization procedures to study the interrelationships of the three types of equine herpes viruses (EHV-1, EHV-2, and EHV-3). Equine cell cultures infected with each type virus fluoresced when stained with homologous conjugated antiserum. In reciprocal tests EHV-1 and EHV-3 cross-fluoresced, but EHV-2 did not cross-fluoresce. Non-infected cell cultures did not fluoresce when stained with the 3 conjugates. EHV-1 and EHV-3 cross-fluoresced in reciprocal indirect fluorescent antibody tests, but no cross-fluorescence was shown with EHV-2. Antigens representing each type of equine herpes virus reacted with their homologous antiserum in the immunodiffusion test. In reciprocal tests, a common line(s) of identity formed with EHV-1 and EHV-3; however, the precipitin line(s) was not common with EHV-2. Antigen prepared from noninfected embryonic mule skin (EMS) cell cultures did not react with any of the antiserums. Specific complement-fixing antibodies were present in antiserums when tested against their homologous antigens. In reciprocal complement fixation tests EHV-1 and EHV-3 crossreacted, but no cross-reactivity was shown with EHV-2. Significant levels of neutralizing antibody were in an antiserum when tested against homologous virus, whereas cross-neutralization was not detectable in reciprocal tests. These studies indicate that each type of equine herpes virus contains specific antigenic components, and EHV-1 and EHV-3 share a common antigen(s) that is not shared with EHV-2.

  19. Antigenic properties of avian hepatitis E virus capsid protein.

    Science.gov (United States)

    Zhao, Qin; Syed, Shahid Faraz; Zhou, En-Min

    2015-10-22

    Avian hepatitis E virus (HEV) is the main causative agent of big liver and spleen disease and hepatitis-splenomegaly syndrome in chickens, and is genetically and antigenically related to mammalian HEVs. HEV capsid protein contains immunodominant epitopes and induces a protective humoral immune response. A better understanding of the antigenic composition of this protein is critically important for the development of effective vaccine and sensitive and specific serological assays. To date, six linear antigenic domains (I-VI) have been characterized in avian HEV capsid protein and analyzed for their applications in the serological diagnosis and vaccine design. Domains I and V induce strong immune response in chickens and are common to avian, human, and swine HEVs, indicating that the shared epitopes hampering differential diagnosis of avian HEV infection. Domains III and IV are not immunodominant and elicit a weak immune response. Domain VI, located in the N-terminal region of the capsid protein, can also trigger an intense immune response, but the anti-domain VI antibodies are transient. The protection analysis showed that the truncated capsid protein containing the C-terminal 268 amino acid residues expressed by the bacterial system can provide protective immunity against avian HEV infection in chickens. However, the synthetic peptides incorporating the different linear antigenic domains (I-VI) and epitopes are non-protective. The antigenic composition of avian HEV capsid protein is altogether complex. To develop an effective vaccine and accurate serological diagnostic methods, more conformational antigenic domains or epitopes are to be characterized in detail.

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

    Directory of Open Access Journals (Sweden)

    Ewa Łukasik

    2016-03-01

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

  1. Cross-reactive Legionella antigens and the antibody response during infection

    DEFF Research Database (Denmark)

    Bangsborg, Jette Marie; Shand, G; Pearlman, E;

    1991-01-01

    In order to define cross-reactive Legionella antigens suitable for diagnostic purposes, we investigated sonicate antigens from two Legionella species, including two serogroups of L. pneumophila. The antigens were reacted with heterologous and homologous rabbit antisera in Western blot. Sera from...... seven patients with culture-verified L. pneumophila infection and nine patients with serologically confirmed L. micdadei infection were also investigated for reactivity with the corresponding antigens. Among the cross-reactive Legionella antigens defined, non-specific reactivity in patients' sera...... with the 58-kDa common antigen (CA) was noted. Specific reactions were observed with the Legionella flagellum antigen and with the macrophage infectivity potentiator (Mip) protein; with both antigens, however, the reactive sera were too few to suggest the use of a single antigen in a diagnostic test....

  2. Preparation of Somatic Antigen from Fusarium Solani for Serological Diagnosis of Fusariosis

    Directory of Open Access Journals (Sweden)

    M.R. Aghamirian

    2005-10-01

    Full Text Available Introduction & Objective: Fusariosis is one of the most important systemic mycosis, often caused by Fusarium Solani and resist to antifungal drugs. The appropriate F. Solani antigen preparation could be useful in serodiagnosis of fusariosis. Materials & Methods : The extraction procedure was preformed using F.Solani strain 7419 UAMH. The antigenic extract was obtained through grinding of fungal mass yielding from broth culture medium. Results : Following fractionation of somatic antigen, two different component, that is, crude antigen as well as antigenic fractions (12,28 were collected. The antigenic fractions in comparison with the crude antigen, demonstrated more effective antibody responses using ELISA method. Conclusion: Availability of a suitable antigenic source could play a key role for serologic detecting of opportunistic fungal disease including fusariosis. Injection of this antigenic preparation in Rabbit resulted antibody response.

  3. Antigens in human glioblastomas and meningiomas: Search for tumour and onco-foetal antigens. Estimation of S-100 and GFA protein

    DEFF Research Database (Denmark)

    Dittmann, L; Axelsen, N H; Norgaard-Pedersen, B

    1977-01-01

    Extracts of glioblastomas and meningiomas were analysed by quantitative immunoelectrophoresis for the presence of foetal brain antigens and tumour-associated antigens, and levels of 2 normal brain-specific proteins were also determined. The following antibodies were used: monospecific anti-S-100......-alpha-foetoprotein; and monospecific anti-ferritin. Using the antibodies raised against the tumours, several antigens not present in foetal or adult normal brain were found in the glioblastomas and the meningiomas. These antigens cross-reacted with antigens present in normal liver and were therefore not tumour-associated. S-100...

  4. High throughput production of mouse monoclonal antibodies using antigen microarrays

    DEFF Research Database (Denmark)

    De Masi, Federico; Chiarella, P.; Wilhelm, H.;

    2005-01-01

    Recent advances in proteomics research underscore the increasing need for high-affinity monoclonal antibodies, which are still generated with lengthy, low-throughput antibody production techniques. Here we present a semi-automated, high-throughput method of hybridoma generation and identification....... Monoclonal antibodies were raised to different targets in single batch runs of 6-10 wk using multiplexed immunisations, automated fusion and cell-culture, and a novel antigen-coated microarray-screening assay. In a large-scale experiment, where eight mice were immunized with ten antigens each, we generated...

  5. Cloning of the Protective Antigen Gene of Bacillus anthracis

    Science.gov (United States)

    1983-09-01

    of the complicated precedents of duplicate toxin genes in chro- muumm mosomall and plasmid DNA of B. thuringiensis (Schnepf and Whitely, 1981; Klier...OiL V4. 34. S-W7. SW 1v 99 CwI 0193 by MT 0 009-7483/06O-002.00/0 mU"- - 1*;)-0Cloning of the Protective Antigen Gene OCT 19 MI L Sof Bacillus ...Sumnler uncertain, it is probably caused by other Bacillus antigens, 4 t which may include LF and EF. PA produced from recom- A The - "w t of a

  6. HLA ANTIGENS AND VOGT-KOYANAGI- HARADA'S DISEASE

    Institute of Scientific and Technical Information of China (English)

    1991-01-01

    Thirty patients with Vogt-Koyanagi-Haradas disease were typed for HLA-A and HLA-B antigenic determinants by a microlymphocytotoxicity technique. HLA-B22 antigen showed an increased frequency of 43.3% in the patient group(relative risk=8.69; exact P<0.0001; corrected P<0.0025) compared with normal control group(frequency=7.69%). This association suggests that immunogenetic factor may play an important role in the pathogenesis of Vogt-Koyanagi-Harada's disease.

  7. Relationship between Asthma and Allergic Antigens in Rural Houses

    Institute of Scientific and Technical Information of China (English)

    DUEn-Chun; LIZhng-Min; 等

    1993-01-01

    Asthma is one of the most frequent and common diseases in China.It seriously threatens the health of the population.It is evident that mites present in rural houses may serve as an allergic antigen.In our survey,we have found several kindos of mites in farmers' houses in the northeastern part of China which have very close relation with asthmatic diseases.Investigations in rural houses further proved that the cause of asthma is certainly related with the allergic antigen of mites.The methods of prevention and contorl of mites are enumerated.

  8. State of the Art in Tumor Antigen and Biomarker Discovery

    Energy Technology Data Exchange (ETDEWEB)

    Even-Desrumeaux, Klervi; Baty, Daniel; Chames, Patrick, E-mail: patrick.chames@inserm.fr [INSERM U624, 163 avenue de Luminy, 13288 Marseille Cedex 09 (France)

    2011-06-09

    Our knowledge of tumor immunology has resulted in multiple approaches for the treatment of cancer. However, a gap between research of new tumors markers and development of immunotherapy has been established and very few markers exist that can be used for treatment. The challenge is now to discover new targets for active and passive immunotherapy. This review aims at describing recent advances in biomarkers and tumor antigen discovery in terms of antigen nature and localization, and is highlighting the most recent approaches used for their discovery including “omics” technology.

  9. State of the Art in Tumor Antigen and Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    Patrick Chames

    2011-06-01

    Full Text Available Our knowledge of tumor immunology has resulted in multiple approaches for the treatment of cancer. However, a gap between research of new tumors markers and development of immunotherapy has been established and very few markers exist that can be used for treatment. The challenge is now to discover new targets for active and passive immunotherapy. This review aims at describing recent advances in biomarkers and tumor antigen discovery in terms of antigen nature and localization, and is highlighting the most recent approaches used for their discovery including “omics” technology.

  10. Self-antigen presentation by dendritic cells in autoimmunity

    Directory of Open Access Journals (Sweden)

    Ann-Katrin eHopp

    2014-02-01

    Full Text Available The operation of both central and peripheral tolerance ensures the prevention of autoimmune diseases. The maintenance of peripheral tolerance requires self-antigen presentation by professional antigen presenting cells (APCs. Dendritic cells (DCs are considered as major APCs involved in this process. The current review discusses the role of DCs in autoimmune diseases, the various factors involved in the induction and maintenance of tolerogenic DC phenotype and pinpoints their therapeutic capacity as well as potential novel targets for future clinical studies.

  11. Mite antigen and allergen contents of house dust samples.

    Directory of Open Access Journals (Sweden)

    Ishii,Akira

    1988-02-01

    Full Text Available The house dust mite (Dermatophagoides pteronyssinus antigen and allergen contents were measured by enzyme-linked immunosorbent assay (ELISA with enzyme-labelled anti-human IgE and anti-mite rabbit IgG antibodies. Antigen content was high in dust samples from homes of patients with allergy but not in samples from homes of patients with Kawasaki disease or of normal control subjects. Allergen content was high in dust samples from homes of Kawasaki disease patients. However, the values overlapped, and we considered these differences to be of little ecological significance, although the assay method itself is useful.

  12. Subdominant Outer Membrane Antigens in Anaplasma marginale: Conservation, Antigenicity, and Protective Capacity Using Recombinant Protein.

    Directory of Open Access Journals (Sweden)

    Deirdre R Ducken

    Full Text Available Anaplasma marginale is a tick-borne rickettsial pathogen of cattle with a worldwide distribution. Currently a safe and efficacious vaccine is unavailable. Outer membrane protein (OMP extracts or a defined surface protein complex reproducibly induce protective immunity. However, there are several knowledge gaps limiting progress in vaccine development. First, are these OMPs conserved among the diversity of A. marginale strains circulating in endemic regions? Second, are the most highly conserved outer membrane proteins in the immunogens recognized by immunized and protected animals? Lastly, can this subset of OMPs recognized by antibody from protected vaccinates and conserved among strains recapitulate the protection of outer membrane vaccines? To address the first goal, genes encoding OMPs AM202, AM368, AM854, AM936, AM1041, and AM1096, major subdominant components of the outer membrane, were cloned and sequenced from geographically diverse strains and isolates. AM202, AM936, AM854, and AM1096 share 99.9 to 100% amino acid identity. AM1041 has 97.1 to 100% and AM368 has 98.3 to 99.9% amino acid identity. While all four of the most highly conserved OMPs were recognized by IgG from animals immunized with outer membranes, linked surface protein complexes, or unlinked surface protein complexes and shown to be protected from challenge, the highest titers and consistent recognition among vaccinates were to AM854 and AM936. Consequently, animals were immunized with recombinant AM854 and AM936 and challenged. Recombinant vaccinates and purified outer membrane vaccinates had similar IgG and IgG2 responses to both proteins. However, the recombinant vaccinates developed higher bacteremia after challenge as compared to adjuvant-only controls and outer membrane vaccinates. These results provide the first evidence that vaccination with specific antigens may exacerbate disease. Progressing from the protective capacity of outer membrane formulations to

  13. Subdominant Outer Membrane Antigens in Anaplasma marginale: Conservation, Antigenicity, and Protective Capacity Using Recombinant Protein.

    Science.gov (United States)

    Ducken, Deirdre R; Brown, Wendy C; Alperin, Debra C; Brayton, Kelly A; Reif, Kathryn E; Turse, Joshua E; Palmer, Guy H; Noh, Susan M

    2015-01-01

    Anaplasma marginale is a tick-borne rickettsial pathogen of cattle with a worldwide distribution. Currently a safe and efficacious vaccine is unavailable. Outer membrane protein (OMP) extracts or a defined surface protein complex reproducibly induce protective immunity. However, there are several knowledge gaps limiting progress in vaccine development. First, are these OMPs conserved among the diversity of A. marginale strains circulating in endemic regions? Second, are the most highly conserved outer membrane proteins in the immunogens recognized by immunized and protected animals? Lastly, can this subset of OMPs recognized by antibody from protected vaccinates and conserved among strains recapitulate the protection of outer membrane vaccines? To address the first goal, genes encoding OMPs AM202, AM368, AM854, AM936, AM1041, and AM1096, major subdominant components of the outer membrane, were cloned and sequenced from geographically diverse strains and isolates. AM202, AM936, AM854, and AM1096 share 99.9 to 100% amino acid identity. AM1041 has 97.1 to 100% and AM368 has 98.3 to 99.9% amino acid identity. While all four of the most highly conserved OMPs were recognized by IgG from animals immunized with outer membranes, linked surface protein complexes, or unlinked surface protein complexes and shown to be protected from challenge, the highest titers and consistent recognition among vaccinates were to AM854 and AM936. Consequently, animals were immunized with recombinant AM854 and AM936 and challenged. Recombinant vaccinates and purified outer membrane vaccinates had similar IgG and IgG2 responses to both proteins. However, the recombinant vaccinates developed higher bacteremia after challenge as compared to adjuvant-only controls and outer membrane vaccinates. These results provide the first evidence that vaccination with specific antigens may exacerbate disease. Progressing from the protective capacity of outer membrane formulations to recombinant vaccines

  14. Molecular cloning of cDNA for the human tumor-associated antigen CO-029 and identification of related transmembrane antigens

    Energy Technology Data Exchange (ETDEWEB)

    Szala, S.; Kasai, Yasushi; Steplewski, Z.; Rodeck, U.; Koprowski, H.; Linnenbach, A.J. (Wistar Inst. of Anatomy and Biology, Philadelphia, PA (USA))

    1990-09-01

    The human tumor-associated antigen CO-029 is a monoclonal antibody-defined cell surface glycoprotein of 27-34 kDa. By using the high-efficiency COS cell expression system, a full-length cDNA clone for CO-029 was isolated. When transiently expressed in COS cells, the cDNA clone directed the synthesis of an antigen reactive to monoclonal antibody CO-029 in mixed hemadsorption and immunoblot assays. Sequence analysis revealed that CO-029 belongs to a family of cell surface antigens that includes the melanoma-associated antigen ME491, the leukocyte cell surface antigen CD37, and the Sm23 antigen of the parasitic helminth Schistosoma mansoni. CO-029 and ME491 antigen expression and the effect of their corresponding monoclonal antibodies on cell growth were compared in human tumor cell lines of various histologic origins.

  15. Identification of a highly antigenic linear B cell epitope within Plasmodium vivax apical membrane antigen 1 (AMA-1.

    Directory of Open Access Journals (Sweden)

    Lilian Lacerda Bueno

    Full Text Available Apical membrane antigen 1 (AMA-1 is considered to be a major candidate antigen for a malaria vaccine. Previous immunoepidemiological studies of naturally acquired immunity to Plasmodium vivax AMA-1 (PvAMA-1 have shown a higher prevalence of specific antibodies to domain II (DII of AMA-1. In the present study, we confirmed that specific antibody responses from naturally infected individuals were highly reactive to both full-length AMA-1 and DII. Also, we demonstrated a strong association between AMA-1 and DII IgG and IgG subclass responses. We analyzed the primary sequence of PvAMA-1 for B cell linear epitopes co-occurring with intrinsically unstructured/disordered regions (IURs. The B cell epitope comprising the amino acid sequence 290-307 of PvAMA-1 (SASDQPTQYEEEMTDYQK, with the highest prediction scores, was identified in domain II and further selected for chemical synthesis and immunological testing. The antigenicity of the synthetic peptide was identified by serological analysis using sera from P. vivax-infected individuals who were knowingly reactive to the PvAMA-1 ectodomain only, domain II only, or reactive to both antigens. Although the synthetic peptide was recognized by all serum samples specific to domain II, serum with reactivity only to the full-length protein presented 58.3% positivity. Moreover, IgG reactivity against PvAMA-1 and domain II after depletion of specific synthetic peptide antibodies was reduced by 18% and 33% (P = 0.0001 for both, respectively. These results suggest that the linear epitope SASDQPTQYEEEMTDYQK is highly antigenic during natural human infections and is an important antigenic region of the domain II of PvAMA-1, suggesting its possible future use in pre-clinical studies.

  16. A melanoma immune response signature including Human Leukocyte Antigen-E.

    Science.gov (United States)

    Tremante, Elisa; Ginebri, Agnese; Lo Monaco, Elisa; Benassi, Barbara; Frascione, Pasquale; Grammatico, Paola; Cappellacci, Sandra; Catricalà, Caterina; Arcelli, Diego; Natali, Pier Giorgio; Di Filippo, Franco; Mottolese, Marcella; Visca, Paolo; Benevolo, Maria; Giacomini, Patrizio

    2014-01-01

    Paired cultures of early-passage melanoma cells and melanocytes were established from metastatic lesions and the uninvolved skin of five patients. In this stringent autologous setting, cDNA profiling was used to analyze a subset of 1477 genes selected by the Gene Ontology term 'immune response'. Human Leukocyte Antigen E (HLA-E) was ranked 19th among melanoma-overexpressed genes and was embedded in a transformation signature including its preferred peptide ligand donors HLA-A, HLA-B, HLA-C, and HLA-G. Mostly undetectable in normal skin and 39 nevi (including rare and atypical lesions), HLA-E was detected by immunohistochemistry in 17/30 (57%) and 32/48 (67%) primary and metastatic lesions, respectively. Accordingly, surface HLA-E was higher on melanoma cells than on melanocytes and protected the former (6/6 cell lines) from lysis by natural killer (NK) cells, functionally counteracting co-expressed triggering ligands. Although lacking HLA-E, melanocytes (4/4 cultures) were nevertheless (and surprisingly) fully protected from NK cell lysis.

  17. Detection of Fasciola hepatica and Fasciola gigantica common and uncommon antigens, using rabbit hyper immune serum raised against their excretory-secretory and somatic antigens.

    Science.gov (United States)

    Abdolahi Khabisi, S; Sarkari, B

    2016-12-01

    Fasciolosis is an important neglected helminth disease caused by two liver flukes, Fasciola hepatica and Fasciola gigantica. The two species of Fasciola are usually different in their morphological and molecular features. They have also common and uncommon antigens in both their somatic and excretory secretory metabolites. In this study, we compared somatic and excretory-secretory (ES) antigens of F. hepatica and F. gigantica, by using rabbit hyper immune serum raised against these antigens. Adult worms were collected from bile ducts of infected animals and species of the fluke was confirmed by RFLP-PCR. ES and somatic antigens of both species were prepared. Rabbits were subcutaneously immunized with either ES or somatic antigens to produce antibodies against these antigens. SDS-PAGE pattern of F. hepatica and F. gigantica somatic antigens was similar and both of them revealed 30 protein bands, ranging from 18 to 180 kDa. In contrast, SDS-PAGE pattern of ES antigen of the two species was different. While protein bands with molecular weight of 18, 27, 29, 48, and 62 kDa were common in both species, bands of 19, 45, 55 and 58 kDa were only noticed in F. hepatica ES antigen. Rabbit polyclonal antibodies, raised against F. hepatica and F. gigantica ES antigen, reacted with main five protein bands, 25, 27, 29, 62 and 67 kDa and polyclonal antibodies raised against somatic antigens of both species reacted with three protein bands, 25, 27 and 72 kDa. Thus, the 25, 27 and 29 kDa protein bands may serve as immunodominant antigens, which might be considered for serodiagnosis of fasciolosis. Moreover, bands of 62 and 67 kDa in ES antigen and 72 kDa in somatic antigens of both species were immunodominant and might be suitable candidate for development of serological assays for diagnosis of fasciolosis.

  18. Role of metalloproteases in vaccinia virus epitope processing for transporter associated with antigen processing (TAP)-independent human leukocyte antigen (HLA)-B7 class I antigen presentation.

    Science.gov (United States)

    Lorente, Elena; García, Ruth; Mir, Carmen; Barriga, Alejandro; Lemonnier, François A; Ramos, Manuel; López, Daniel

    2012-03-23

    The transporter associated with antigen processing (TAP) translocates the viral proteolytic peptides generated by the proteasome and other proteases in the cytosol to the endoplasmic reticulum lumen. There, they complex with nascent human leukocyte antigen (HLA) class I molecules, which are subsequently recognized by the CD8(+) lymphocyte cellular response. However, individuals with nonfunctional TAP complexes or tumor or infected cells with blocked TAP molecules are able to present HLA class I ligands generated by TAP-independent processing pathways. Herein, using a TAP-independent polyclonal vaccinia virus-polyspecific CD8(+) T cell line, two conserved vaccinia-derived TAP-independent HLA-B*0702 epitopes were identified. The presentation of these epitopes in normal cells occurs via complex antigen-processing pathways involving the proteasome and/or different subsets of metalloproteinases (amino-, carboxy-, and endoproteases), which were blocked in infected cells with specific chemical inhibitors. These data support the hypothesis that the abundant cellular proteolytic systems contribute to the supply of peptides recognized by the antiviral cellular immune response, thereby facilitating immunosurveillance. These data may explain why TAP-deficient individuals live normal life spans without any increased susceptibility to viral infections.

  19. A "new" primed lymphocyte typing (PLT) defined DP-antigen associated with a private HLA--DR antigen

    DEFF Research Database (Denmark)

    Morling, N; Jakobsen, B K; Platz, P

    1980-01-01

    We have recently described a "new" private HLA-DR antigen, DR"LTM", which has a frequency of approximately 0.6% in Danes. Primed Lymphocyte Typing (PLT) cells directed towards DR"LTM"-associated determinants were generated in vitro by haplotype primings in two unrelated families with DR"LTM" posi......We have recently described a "new" private HLA-DR antigen, DR"LTM", which has a frequency of approximately 0.6% in Danes. Primed Lymphocyte Typing (PLT) cells directed towards DR"LTM"-associated determinants were generated in vitro by haplotype primings in two unrelated families with DR...

  20. Differential expression of the Escherichia coli autoaggregation factor antigen 43

    DEFF Research Database (Denmark)

    Schembri, Mark; Hjerrild, Louise; Gjermansen, Morten

    2003-01-01

    Antigen 43 (Ag43) is a self-recognizing surface adhesin found in most Escherichia coli strains. Due to its excellent cell-to-cell aggregation characteristics, Ag43 expression confers clumping and fluffing of cells and promotes biofilm formation. Ag43 expression is repressed by the cellular redox...

  1. Human leukocyte antigen (HLA)-G during pregnancy part II

    DEFF Research Database (Denmark)

    Dahl, Mette; Klitkou, Louise; Christiansen, Ole B;

    2015-01-01

    Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expressed on the extra-villous trophoblast and seems to have immunomodulatory functions during pregnancy. Studies have linked HLA-G polymorphisms to pregnancy complications such as preeclampsia and recurren...

  2. ANTIGEN MG7 IN GASTRIC CANCER AND GASTRIC PRECANCEROUS LESIONS

    Institute of Scientific and Technical Information of China (English)

    郭冬丽; 宁佩芳; 袁媛

    2004-01-01

    Objective: To study the dynamic change and its diagnostic significance of MG7 expression in the process of gastric cancer development. Methods: The expression level of antigen MG7 was determined by immunohistochemistry method in 406 cases of gastric mucosa. The classification of intestinal metaplasia of gastric mucosa was determined by histochemistry method in 82 cases. Results: The positive rate of MG7 expression in normal gastric mucosa, intestinal metaplasia and dysplasia of gastric mucosa and gastric cancer were increased gradually (P<0.01). The positive rate of MG7 expression in superficial gastritis, atrophic gastritis and gastric cancer were increased on sequence (P<0.01). The positive rate of antigen MG7 expression in type Ⅲ intestinal metaplasia of gastric mucosa had significant difference,compared with that in type Ⅰ an Ⅱ intestinal metaplasia (P<0.05). Conclusion: MG7 antigen had close relationship with gastric cancer. Type Ⅲ intestinal metaplasia, atrophic gastritis and dysplasia should be followed up in order to improve the early detection of gastric cancer. MG7 antigen had great clinical value in the dynamic follow-up of gastric precursors.

  3. 42 CFR 410.68 - Antigens: Scope and conditions.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Antigens: Scope and conditions. 410.68 Section 410.68 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Medical and Other Health Services §...

  4. Glycan bioengineering in immunogen design for tumor T antigen immunotargeting

    DEFF Research Database (Denmark)

    Sendra, Victor G; Zlocowski, Natacha; Ditamo, Yanina;

    2009-01-01

    MM2 energy function showed that pentalysine (Lys5) linker and benzyl (Bzl) residue enhance TFD rigidity of the glycosidic bond. Antibodies raised against BzlalphaTFD-Lys5 immunogen recognize tumor T antigen. Competitive assays confirm that TFD-related structures are the main glycan epitope...

  5. Identification of Schistosoma mansoni candidate antigens for diagnosis of schistosomiasis

    Directory of Open Access Journals (Sweden)

    Gardenia Braz Figueiredo Carvalho

    2011-11-01

    Full Text Available The development of a more sensitive diagnostic test for schistosomiasis is needed to overcome the limitations of the use of stool examination in low endemic areas. Using parasite antigens in enzyme linked immunosorbent assay is a promising strategy, however a more rational selection of parasite antigens is necessary. In this study we performed in silico analysis of the Schistosoma mansoni genome, using SchistoDB database and bioinformatic tools for screening immunogenic antigens. Based on evidence of expression in all parasite life stage within the definitive host, extracellular or plasmatic membrane localization, low similarity to human and other helminthic proteins and presence of predicted B cell epitopes, six candidates were selected: a glycosylphosphatidylinositol-anchored 200 kDa protein, two putative cytochrome oxidase subunits, two expressed proteins and one hypothetical protein. The recognition in unidimensional and bidimensional Western blot of protein with similar molecular weight and isoelectric point to the selected antigens by sera from S. mansoni infected mice indicate a good correlation between these two approaches in selecting immunogenic proteins.

  6. Autologous peptides constitutively occupy the antigen binding site on Ia

    DEFF Research Database (Denmark)

    Buus, S; Sette, A; Colon, S M;

    1988-01-01

    Low molecular weight material associated with affinity-purified class II major histocompatibility complex (MHC) molecules of mouse (Ia) had the expected properties of peptides bound to the antigen binding site of Ia. Thus, the low molecular weight material derived from the I-Ad isotype...

  7. The systems biology of MHC class II antigen presentation

    NARCIS (Netherlands)

    Paul, Petra

    2012-01-01

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

  8. Cocktail of Theileria equi antigens for detecting infection in equines

    Institute of Scientific and Technical Information of China (English)

    Shimaa; Abd; El-Salam; El-Sayed; Mohamed; Abdo; Rizk; Mohamed; Alaa; Terkawi; Ahmed; Mousa; El; Said; El; Shirbini; El; Said; Gehad; Elsayed; Mohamed; Fouda; Naoaki; Yokoyama; Ikuo; Igarashi

    2015-01-01

    Objective:To use two diagnostic antigens belonging to the frequently associated in Theileria domain,Theileria equi(T.equi)protein 82(Te 82)and T.equi 104 k Da microneme-rhoptry antigen precursor(Te 43),to diagnose T.equi infection in horses as compared with equi merozoite antigen-2(EMA-2).Methods:In the current study,we applied a cocktail-ELISA containing two antigens(EMA-2+Te 82)to diagnose T.equi infection either in experimentally infected horses or in field infection.Results:Our findings have revealed that a cocktail formula of EMA-2+Te 82 provided a more practical and sensitive diagnostic candidate for diagnosing T.equi infection in horses as compared with Te 82 or Te 43 alone.Conclusions:The ELISA technique using a cocktail formula of EMA-2+Te 82 offers a practical and sensitive diagnostic tool for diagnosing T.equi infection in horses and using of this promising cocktail formula will be applicable for epidemiological surveys and will help control the infection in horses.

  9. Cocktail of Theileria equi antigens for detecting infection in equines

    Institute of Scientific and Technical Information of China (English)

    Shimaa Abd El-Salam El-Sayed; Mohamed Abdo Rizk; Mohamed Alaa Terkawi; Ahmed Mousa; El Said El Shirbini El Said; Gehad Elsayed; Mohamed Fouda; Naoaki Yokoyama; Ikuo Igarashi

    2015-01-01

    Objective: To use two diagnostic antigens belonging to the frequently associated in Theileria domain, Theileria equi (T. equi) protein 82 (Te 82) and T. equi 104 kDa microneme-rhoptry antigen precursor (Te 43), to diagnose T. equi infection in horses as compared with equi merozoite antigen-2 (EMA-2). Methods: In the current study, we applied a cocktail-ELISA containing two antigens (EMA-2+Te 82) to diagnose T. equi infection either in experimentally infected horses or in field infection. Results: Our findings have revealed that a cocktail formula of EMA-2+Te 82 provided a more practical and sensitive diagnostic candidate for diagnosing T. equi infection in horses as compared with Te 82 or Te 43 alone. Conclusions: The ELISA technique using a cocktail formula of EMA-2+Te 82 offers a practical and sensitive diagnostic tool for diagnosing T. equi infection in horses and using of this promising cocktail formula will be applicable for epidemiological surveys and will help control the infection in horses.

  10. Identifying coevolutionary patterns in human leukocyte antigen (HLA) molecules.

    Science.gov (United States)

    Jiang, Xiaowei; Fares, Mario A

    2010-05-01

    The antigenic peptide, major histocompatibility complex molecule (MHC; also called human leukocyte antigen, HLA), coreceptor CD8, or CD4 and T-cell receptor (TCR) function as a complex to initiate effectors' mechanisms of the immune system. The tight functional and physical interaction among these molecules may have involved strong coevolution links among domains within and between proteins. Despite the importance of unraveling such dependencies to understand the arms race of host-pathogen interaction, no previous studies have aimed at achieving such an objective. Here, we perform an exhaustive coevolution analysis and show that indeed such dependencies are strongly shaping the evolution and probably the function of these molecules. We identify intramolecular coevolution in HLA class I and II at domains important for their immune activity. Most of the amino acid sites identified to be coevolving in HLAI have been also detected to undergo positive Darwinian selection highlighting therefore their adaptive value. We also identify coevolution among antigen-binding pockets (P1-P9) and among these and TCR-binding sites. Conversely to HLAI, coevolution is weaker in HLAII. Our results support that such coevolutionary patterns are due to selective pressures of host-pathogen coevolution and cooperative binding of TCRs, antigenic peptides, and CD8/CD4 to HLAI and HLAII.

  11. Microbial antigenic variation mediated by homologous DNA recombination

    NARCIS (Netherlands)

    C. Vink (Cornelis); L. Rudenko (Larisa); H.S. Seifert (H. Steven)

    2012-01-01

    textabstractPathogenic microorganisms employ numerous molecular strategies in order to delay or circumvent recognition by the immune system of their host. One of the most widely used strategies of immune evasion is antigenic variation, in which immunogenic molecules expressed on the surface of a mic

  12. Analysis of cell surface antigens by Surface Plasmon Resonance imaging

    NARCIS (Netherlands)

    Stojanovic, I.; Schasfoort, R.B.M.; Terstappen, L.W.M.M.

    2013-01-01

    Surface Plasmon Resonance (SPR) is most commonly used to measure bio-molecular interactions. SPR is used significantly less frequent for measuring whole cell interactions. Here we introduce a method to measure whole cells label free using the specific binding of cell surface antigens expressed on th

  13. Thrombin Increases Expression of Fibronectin Antigen on the Platelet Surface

    Science.gov (United States)

    Ginsberg, Mark H.; Painter, Richard G.; Forsyth, Jane; Birdwell, Charles; Plow, Edward F.

    1980-02-01

    Fibronectins (fn) are adhesive glycoproteins which bind to collagen and to fibrin and appear to be important in cellular adhesion to other cells or surfaces. Fn-related antigen is present in human platelets, suggesting a possible role for fn in the adhesive properties of platelets. We have studied the localization of fn in resting and thrombin-stimulated platelets by immunofluorescence and quantitative binding of radiolabeled antibody. In resting fixed platelets, variable light surface staining for fn was observed. When these cells were made permeable to antibody with detergent, staining for fn was markedly enhanced and was present in a punctate distribution, suggesting intracellular localization. Stimulation with thrombin, which is associated with increased platelet adhesiveness, resulted in increased staining for fn antigen on intact platelets. These stimulated cells did not leak 51Cr nor did they stain for F-actin, thus documenting that the increased fn staining was not due to loss of plasma membrane integrity. The thrombin-induced increase in accessible platelet fn antigen was confirmed by quantitative antibody binding studies in which thrombin-stimulated platelets specifically bound 15 times as much radiolabeled F(ab')2 anti-fn as did resting cells. Thus, thrombin stimulation results in increased expression of fn antigen on the platelet surface. Here it may participate in interactions with fibrin, connective tissue, or other cells.

  14. Tumor antigens as proteogenomic biomarkers in invasive ductal carcinomas

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn; Campos, Benito; Winther, Ole;

    2014-01-01

    to be perturbed. Conclusion: Tumor antigens are a group of proteins recognized by the cells of the immune system. Specifically, they are recognized in tumor cells where they are present in larger than usual amounts, or are physiochemically altered to a degree at which they no longer resemble native human proteins...

  15. The antigen specific composition of melanoma tumor infiltrating lymphocytes?

    DEFF Research Database (Denmark)

    Hadrup, Sine Reker

    2012-01-01

    Large numbers of tumor associated antigens has been characterized, but only a minor fraction of these are recognized by tumor infiltrating lymphocytes of melanoma, although these have shown the ability to recognize tumor and provide tumor regression upon adoptive transfer. Thus the peptide...

  16. Radioimmunoprecipitation polyethylene glycol assay for circulating Entamoeba histolytica antigens

    Energy Technology Data Exchange (ETDEWEB)

    Pillai, S.; Mohimen, A.; Mehra, S. (Calcutta Medical Research Inst., Calcutta (India). Kothari Centre of Gastroenterology)

    1982-12-17

    An assay capable of detecting circulating Entamoeba histolytica antigens in amoebiasis is described. This assay utilised a radiolabelled affinity purified rabbit anti-E. histolytica antibody that had been depleted of antibodies that cross-react with human serum proteins, and a polyethylene glycol precipitation step.

  17. Lewis Y Antigen as a Target for Breast Cancer Therapy

    Science.gov (United States)

    1998-09-01

    template structures. Sequences for BR96, TE33, BV04, and B03i2 are from deposited PDB files in the Brookhaven repository ( Berstein etal., 1977...appropriately con- (DAMD17-94-J-4310) Breast Cancer Initiative. 21 Springer H, Carls , antigen safe in advance References Cancer I Hakomori S: Aberrant glyco- 7

  18. Proteomic selection of immunodiagnostic antigens for Trypanosoma congolense.

    Directory of Open Access Journals (Sweden)

    Jennifer R Fleming

    2014-06-01

    Full Text Available Animal African Trypanosomosis (AAT presents a severe problem for agricultural development in sub-Saharan Africa. It is caused by several trypanosome species and current means of diagnosis are expensive and impractical for field use. Our aim was to discover antigens for the detection of antibodies to Trypanosoma congolense, one of the main causative agents of AAT. We took a proteomic approach to identify potential immunodiagnostic parasite protein antigens. One hundred and thirteen proteins were identified which were selectively recognized by infected cattle sera. These were assessed for likelihood of recombinant protein expression in E. coli and fifteen were successfully expressed and assessed for their immunodiagnostic potential by ELISA using pooled pre- and post-infection cattle sera. Three proteins, members of the invariant surface glycoprotein (ISG family, performed favorably and were then assessed using individual cattle sera. One antigen, Tc38630, evaluated blind with 77 randomized cattle sera in an ELISA assay gave sensitivity and specificity performances of 87.2% and 97.4%, respectively. Cattle immunoreactivity to this antigen diminished significantly following drug-cure, a feature helpful for monitoring the efficacy of drug treatment.

  19. Brug af undersøgelse for prostataspecifikt antigen

    DEFF Research Database (Denmark)

    Mukai, Thomas; Bro, Flemming; Pedersen, Knud Venborg;

    2010-01-01

    Introduktion: Cancer prostatae (CP) er den hyppigste kræftform blandt danske mænd, og incidensen er stigende. CP er ofte asymptomatisk, hvilket vanskeliggør klinisk diagnosticering. I udredningen for CP kan man benytte en prøve for prostataspecifikt antigen (PSA)-niveau. Dansk Urologisk Selskab har...

  20. Monoclonal Antibody Production against Human Spermatozoal Surface Antigens

    Directory of Open Access Journals (Sweden)

    M Jedi-Tehrani

    2005-10-01

    Full Text Available Introduction: As monoclonal antibodies are potential tools for characterization of soluble or cellular surface antigens, use of these proteins has always been considered in infertility and reproduction research. Therefore, in this study, monoclonal antibodies against human sperm surface antigens were produced. Material and Methods: To produce specific clones against human sperm surface antigens, proteins were extracted using solubilization methods. Balb/c mice were immunized intraperitoneally with the proteins using complete Freund’s adjuvant in the first injection and incomplete Adjuvant in the following booster injections. Hybridoma cells producing ASA were cloned by limiting dilution. Results: Five stable ASA producing hybridoma clones were achieved and their antibody isotypes were determined by ELISA. All the isotypes were of IgG class. Their cross reactivity with rat and mice spermatozoa was examined but they did not have any cross reactivity. Conclusion: The produced antibodies can be used in further studies to characterize and evaluate each of the antigens present on human sperm surface and determining their role in fertilization.

  1. HLA-DP antigens in HIV-infected individuals

    DEFF Research Database (Denmark)

    Ødum, Niels; Georgsen, J; Fugger, L;

    1991-01-01

    We studied the distribution of HLA-DP antigens in 74 HIV-infected Danish homosexual men and 188 ethnically matched healthy individuals, using the primed lymphocyte typing (PLT) technique. Forty of the patients developed AIDS within 3 years after diagnosis, whereas the remaining 34 were healthy...

  2. HLA-DP antigens in patients with alopecia areata

    DEFF Research Database (Denmark)

    Ødum, Niels; Morling, N; Georgsen, J;

    1990-01-01

    The distribution of HLA-DP antigens were studied in 41 patients with alopecia areata (AA) and 188 ethnically matched controls. An increase of DR4 and possibly DR5 in 24 of these patients has previously been reported. HLA-DP typing for DPw1 through w6 and the local specificity, CDP HEI, was perfor...

  3. Chitosan-based delivery systems for protein therapeutics and antigens

    NARCIS (Netherlands)

    Amidi, M.; Mastrobattista, E.; Jiskoot, W.; Hennink, W.E.

    2010-01-01

    Therapeutic peptides/proteins and protein-based antigens are chemically and structurally labile compounds, which are almost exclusively administered by parenteral injections. Recently, non-invasive mucosal routes have attracted interest for administration of these biotherapeutics. Chitosan-based del

  4. Intra-uterine exposure of horses to Sarcocystis spp. antigens

    Directory of Open Access Journals (Sweden)

    A.M. Antonello

    2016-04-01

    Full Text Available The aim of this study was to examine the intra-uterine exposure to Sarcocystis spp. antigens, determining the number of foals with detectable concentrations of antibodies against these agents in the serum, before colostrum ingestion and collect data about exposure of horses to the parasite. Serum samples were collected from 195 thoroughbred mares and their newborns in two farms from southern Brazil. Parasite specific antibody responses to Sarcocystis antigens were detected using the indirect immunofluorescent antibody test (IFAT and immunoblot analysis. In 84.1% (159/189 of the pregnant mares and in 7.4% (14/189 of foals we detected antibodies anti-Sarcocystis spp. by IFAT. All samples seropositive from foals were also positive in their respective mares. Serum samples of seropositive foals by IFAT, showed no reactivity on the immunoblot, having as antigens S. neurona merozoites. In conclusion, the intra-uterine exposure to Sarcocystis spp. antigens in horses was demonstrated, with occurrence not only in mares, but also in their foals, before colostrum ingestion these occurrences were reduced.

  5. Serum levels of fetal antigen 1 in extreme nutritional States

    DEFF Research Database (Denmark)

    Andries, Alin; Niemeier, Andreas; Støving, Rene K

    2012-01-01

    Objective. Recent data suggest that fetal antigen (FA1) is linked to disorders of body weight. Thus, we measured FA1 serum levels in two extreme nutritional states of morbid obesity (MO) and anorexia nervosa (AN) and monitored its response to weight changes. Design. FA1 and insulin serum...

  6. Immune control of tumors by antigen presentation improvement.

    Science.gov (United States)

    Remedi, María Mónica; Bonacci, Gustavo; Vides, Miguel Angel; Donadio, Ana Carolina

    2003-01-01

    Tumor cells cannot activate T lymphocytes, since they do not usually express major histocompatibility complex (MHC) class II molecules. Thus, tumor antigens can only be presented indirectly to T cells through professional antigen-presenting cells (APC). In our laboratory, we have treated a tumor cell line (Tu1-A) - derived from an induced rat mammary sarcoma - in order to increase the expression of MHC class I and class II molecules. In our tumor model, the transference of these induced cells into normal rats generated a tumor mass that exhibited a lower tumor growth rate and an earlier regression as compared to those observed in rats inoculated with wild-type Tu1-A cells. This earlier tumor regression was associated with the development of an antigen-specific immune response. 85-87% of the rats in both groups rejected the tumor and were alive at day 60 after tumor cell inoculation. However, in rats treated with wild-type cells the rejection was delayed and took place after tumor ulceration. Rats that had rejected tumors were rechallenged with wild-type cells in order to assay the presence of a long-lived antitumor immunity. All the animals were resistant to the second tumor challenge. We conclude that the development of a specific immune response could be achieved by the superexpression of MHC molecules on tumor cells or when tumor ulceration promotes APC to take up necrotic cells and tumor antigens are presented to T lymphocytes.

  7. The universal detection of antigens from one skin biopsy specimen.

    NARCIS (Netherlands)

    Velden, H.M.J. van der; Kerkhof, P.C.M. van de; Pasch, M.C.; Boer-van Huizen, R.T. de; Lingen, R.G. van; Erp, P.E.J. van

    2009-01-01

    BACKGROUND: Immunohistochemistry is an important tool in dermatology but is limited. Certain antigens can only be preserved in formalin-fixed paraffin-embedded sections, while others can only be detected on frozen sections, resulting in situations where two biopsies are needed. We aimed to develop a

  8. Glycosylation of the major human Pneumocystis carinii surface antigen

    DEFF Research Database (Denmark)

    Lundgren, Bettina; Koch, C; Mathiesen, Lars Reinhardt;

    1993-01-01

    It has recently been shown that the major rat P. carinii surface antigen is important for initial host-organism attachment, possibly through binding to fibronectin, mannose-binding protein, or surfactant protein A. Since a carbohydrate/lectin interaction may be involved in adhesion, we undertook...

  9. [HL-A antigens in dust allergy in children].

    Science.gov (United States)

    Seignalet, J; Levallois, C; Lapinski, H; Jean, R

    1976-12-01

    The distribution of 29 HLA antigens has been compared in 60 unrelated children presenting a dust allergy and in 300 healthy controls. We observed an increased frequency for HLA-Aw19 and HLA-B5 in patients. Yet, the differences are not very significant and there is probably no association between one HLA gene and the dust allergy.

  10. Cell wall anchoring of the Campylobacter antigens to Lactococcus lactis

    Directory of Open Access Journals (Sweden)

    Patrycja Anna Kobierecka

    2016-02-01

    Full Text Available Campylobacter jejuni is the most frequent cause of human food-borne gastroenteritis and chicken meat is the main source of infection. Recent studies showed that broiler chicken immunization against Campylobacter should be the most efficient way to lower the number of human infections by this pathogen. Induction of the mucosal immune system after oral antigen administration should provide protective immunity to chickens. In this work we tested the usefulness of Lactococcus lactis, the most extensively studied lactic acid bacterium, as a delivery vector for Campylobacter antigens. First we constructed hybrid protein – CjaA antigen presenting CjaD peptide epitopes on its surface. We showed that specific rabbit anti-rCjaAD serum reacted strongly with both CjaA and CjaD produced by a wild type Campylobacter jejuni strain. Next, rCjaAD and CjaA were fused to the C-terminus of the L. lactis YndF containing the LPTXG motif. The genes expressing these proteins were transcribed under control of the L. lactis Usp45 promoter and their products contain the Usp45 signal sequences. This strategy ensures a cell surface location of both analysed proteins, which was confirmed by immunofluorescence assay. In order to evaluate the impact of antigen location on vaccine prototype efficacy, a L. lactis strain producing cytoplasm-located rCjaAD was also generated. Animal experiments showed a decrease of Campylobacter cecal load in vaccinated birds as compared with the control group and showed that the L. lactis harboring the surface-exposed rCjaAD antigen afforded greater protection than the L. lactis producing cytoplasm-located rCjaAD. To the best of our knowledge, this is the first attempt to employ LAB (Lactic Acid Bacteria strains as a mucosal delivery vehicle for chicken immunization. Although the observed reduction of chicken colonization by Campylobacter resulting from vaccination was rather moderate, the experiments showed that LAB strains can be considered

  11. ANTIGENICITY OF COW'S MILK PROTEINS IN TWO ANIMAL MODELS

    Directory of Open Access Journals (Sweden)

    T.R. Neyestani

    2000-08-01

    Full Text Available Antigenicity of proteins found in cow's milk is age dependent. This is primarily due to infants possessing a more permeable intestinal wall than that in adults. Thus infants may acquire cow's milk allergy during their first year of life. While milk antigen specific IgE may cause allergy in susceptible subjects, there is some evidence indicating that milk antigen specific IgG may play some role in chronic disease development. The puropose of this study was to determine the antigenicity of cow's milk proteins in two animal models and to recommend the more sensitivie one, as an evaluation tool, to assess the antigenicity of a poteintial hypoallergenic formula. A crude extract of cow's milk was injected either to young male rabbits or BALB/C mice in four doses. Pure standard proteins of cow's milk were also injected to separate groups of animals to use their anti sera in later stages. The polyclonal pooled serum was then used to evaluate the antigenicity of the extract by indirect enzyme-linked immunossorbeni assay (LEISA. and Western blotting. Both the rabbit and BALB/C murine mode! demonstrated strong ELISA titres against casein and BSA proteins. However, the rabbit model also had a high antibody response against beta-lactoglobulin (/Mg. The lowest antibody response was found against alpha-kictalbumin («-la in both animal models and no response against immunoglobulins (Igs in either model. In Western blotting, rabbit antiserum showed four bands («-la, /Mg, caseins and BSA compared to two bands (caseins and BSA for mouse antiserum. Considering the allergenicity of these proteins in genetically prone subjects, it may be wise to exclude food sources of caseins as well as major whey proteins (BSA, from the diet of infants with a family history of atopy during the first year of life. The rabbit hyperimmunization model was more sensitive than the murine mode! in detecting antibodies against milk proteins. Thus, the rabbii model should be employed when

  12. Analysis on Management of Tank Ullage Gaging under Marketing-by-Liter Mode%升进升出管理模式下罐车空高的计量管理

    Institute of Scientific and Technical Information of China (English)

    赵兴伟

    2011-01-01

    Oil tank ullage gaging plays an important role in the process of oil product loading, handover, and discharging. Because of the characteristics of oil product, the temperature and density can affect it greatly. Based on the consideration of some issues ab%为了使经油罐车运送到加油站油品的数量得到保证,在升进升出的计量管理模式下,探索了油罐车在油库装油后采用油罐车空高计量的管理方法,介绍了在某油库实施该方法所做的数据采集、整理、汇总等基础工作和计算机程序的编写、数据库的建立以及相应的油罐车空高计量管理办法等,经过两年的工作,相关加油站反映效果不错,但仍需对相关制度进行强化和完善。

  13. Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination.

    Science.gov (United States)

    Mahan, Alison E; Jennewein, Madeleine F; Suscovich, Todd; Dionne, Kendall; Tedesco, Jacquelynne; Chung, Amy W; Streeck, Hendrik; Pau, Maria; Schuitemaker, Hanneke; Francis, Don; Fast, Patricia; Laufer, Dagna; Walker, Bruce D; Baden, Lindsey; Barouch, Dan H; Alter, Galit

    2016-03-01

    Antibody effector functions, such as antibody-dependent cellular cytotoxicity, complement deposition, and antibody-dependent phagocytosis, play a critical role in immunity against multiple pathogens, particularly in the absence of neutralizing activity. Two modifications to the IgG constant domain (Fc domain) regulate antibody functionality: changes in antibody subclass and changes in a single N-linked glycan located in the CH2 domain of the IgG Fc. Together, these modifications provide a specific set of instructions to the innate immune system to direct the elimination of antibody-bound antigens. While it is clear that subclass selection is actively regulated during the course of natural infection, it is unclear whether antibody glycosylation can be tuned, in a signal-specific or pathogen-specific manner. Here, we show that antibody glycosylation is determined in an antigen- and pathogen-specific manner during HIV infection. Moreover, while dramatic differences exist in bulk IgG glycosylation among individuals in distinct geographical locations, immunization is able to overcome these differences and elicit antigen-specific antibodies with similar antibody glycosylation patterns. Additionally, distinct vaccine regimens induced different antigen-specific IgG glycosylation profiles, suggesting that antibody glycosylation is not only programmable but can be manipulated via the delivery of distinct inflammatory signals during B cell priming. These data strongly suggest that the immune system naturally drives antibody glycosylation in an antigen-specific manner and highlights a promising means by which next-generation therapeutics and vaccines can harness the antiviral activity of the innate immune system via directed alterations in antibody glycosylation in vivo.  .

  14. Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination.

    Directory of Open Access Journals (Sweden)

    Alison E Mahan

    2016-03-01

    Full Text Available Antibody effector functions, such as antibody-dependent cellular cytotoxicity, complement deposition, and antibody-dependent phagocytosis, play a critical role in immunity against multiple pathogens, particularly in the absence of neutralizing activity. Two modifications to the IgG constant domain (Fc domain regulate antibody functionality: changes in antibody subclass and changes in a single N-linked glycan located in the CH2 domain of the IgG Fc. Together, these modifications provide a specific set of instructions to the innate immune system to direct the elimination of antibody-bound antigens. While it is clear that subclass selection is actively regulated during the course of natural infection, it is unclear whether antibody glycosylation can be tuned, in a signal-specific or pathogen-specific manner. Here, we show that antibody glycosylation is determined in an antigen- and pathogen-specific manner during HIV infection. Moreover, while dramatic differences exist in bulk IgG glycosylation among individuals in distinct geographical locations, immunization is able to overcome these differences and elicit antigen-specific antibodies with similar antibody glycosylation patterns. Additionally, distinct vaccine regimens induced different antigen-specific IgG glycosylation profiles, suggesting that antibody glycosylation is not only programmable but can be manipulated via the delivery of distinct inflammatory signals during B cell priming. These data strongly suggest that the immune system naturally drives antibody glycosylation in an antigen-specific manner and highlights a promising means by which next-generation therapeutics and vaccines can harness the antiviral activity of the innate immune system via directed alterations in antibody glycosylation in vivo.  .

  15. Oral vaccination of fish- antigen preparations, uptake and immune induction

    Directory of Open Access Journals (Sweden)

    Stephen eMutoloki

    2015-10-01

    Full Text Available The oral route offers the most attractive approach of immunization of fish for a number of reasons: the ease of administration of antigens, it is less stressful than parenteral delivery and in principle, it is applicable to small and large sized fish; it also provides a procedure for oral boosting during grow-out periods in cages or ponds. There are however not many commercial vaccines available at the moment due to lack of efficacy and challenges associated with production of large quantities of antigens. These are required to stimulate an effective immune response locally and systemically, and need to be protected against degradation before they reach the sites where immune induction occurs. The hostile stomach environment is believed to be particularly important with regard to degradation of antigens in certain species. There is also a poor understanding about the requirements for proper immune induction following oral administration on one side, and the potential for induction of tolerance on the other. To what extent primary immunization via the oral route will elicit both local and systemic responses is not understood in detail. Furthermore, to what extent parenteral delivery will protect mucosal/gut surfaces and vice-versa is also not fully understood. We review the work that has been done on the subject and discuss it in light of recent advances that include mass production of antigens including the use of plant systems. Different encapsulation techniques that have been developed in the quest to protect antigens against digestive degradation, as well as to target them for appropriate immune induction are also highlighted.

  16. Proteome sampling by the HLA class I antigen processing pathway.

    Directory of Open Access Journals (Sweden)

    Ilka Hoof

    Full Text Available The peptide repertoire that is presented by the set of HLA class I molecules of an individual is formed by the different players of the antigen processing pathway and the stringent binding environment of the HLA class I molecules. Peptide elution studies have shown that only a subset of the human proteome is sampled by the antigen processing machinery and represented on the cell surface. In our study, we quantified the role of each factor relevant in shaping the HLA class I peptide repertoire by combining peptide elution data, in silico predictions of antigen processing and presentation, and data on gene expression and protein abundance. Our results indicate that gene expression level, protein abundance, and rate of potential binding peptides per protein have a clear impact on sampling probability. Furthermore, once a protein is available for the antigen processing machinery in sufficient amounts, C-terminal processing efficiency and binding affinity to the HLA class I molecule determine the identity of the presented peptides. Having studied the impact of each of these factors separately, we subsequently combined all factors in a logistic regression model in order to quantify their relative impact. This model demonstrated the superiority of protein abundance over gene expression level in predicting sampling probability. Being able to discriminate between sampled and non-sampled proteins to a significant degree, our approach can potentially be used to predict the sampling probability of self proteins and of pathogen-derived proteins, which is of importance for the identification of autoimmune antigens and vaccination targets.

  17. Monoclonal antibodies against human granulocytes and myeloid differentiation antigens.

    Science.gov (United States)

    Mannoni, P; Janowska-Wieczorek, A; Turner, A R; McGann, L; Turc, J M

    1982-12-01

    Monoclonal antibodies (MCA) were obtained by immunizing BALB/c mice with 99% pure granulocytes from normal donors or with a whole leukocyte suspension obtained from a chronic myelogenous leukemia (CML) patient, and then fusing the mouse spleen cells with a 315-43 myeloma cell clone. Four MCA were selected and studied using ELISA, immunofluorescence, cytotoxicity assays, and FACS analysis. Antibodies 80H.1, 80H.3, and 80H.5 (from normals) and 81H.1 (from CML) detected antigens expressed on neutrophils. Antibodies 80H.1 and 80H.3 (IgG) also reacted with monocytes but not with other blood cell subsets. Antibodies 80H.5 and 81H.1 (IgM) were cytotoxic and reacted strongly with most of the cells of the neutrophil maturation sequence, i.e., myeloblasts, promyelocytes, myelocytes, and mature granulocytes. Antibodies 80H.5 and 81H.1 also inhibited CFU-GM growth stimulated by leukocyte feeder layers or placental conditioned media, but did not inhibit BFU-E and CFU-E. Antigens recognized by 80H.3, 80H.5, and 81H.1 were expressed both on a proportion of cells from HL.60, KG.1, ML.1, and K562 myeloid cell lines, and on a proportion of blast cells isolated from patients with acute myelogenous leukemia. They were not found on lymphoid cell lines or lymphoid leukemia cells. These MCA recognize either late differentiation antigens expressed on mature neutrophils and monocytes (80H.1 and 80H.3) or early differentiation antigens (80H.5 and 81H.1) specific to the granulocytic lineage. They may be useful for a better definition of those antigens specific to hematopoietic stem cells and their relationship with normal or neoplastic hematopoiesis.

  18. Existence of a squamous cell carcinoma antigen-immunoglobulin complex causes a deviation between squamous cell carcinoma antigen concentrations determined using two different immunoassays: first report of squamous cell carcinoma antigen coupling with immunoglobulin A.

    Science.gov (United States)

    Mori, Eriko; Kurano, Makoto; Tobita, Akiko; Shimosaka, Hironori; Yatomi, Yutaka

    2017-01-01

    Background Squamous cell carcinoma antigen is used as a tumour marker and is routinely measured in clinical laboratories. We validated two different immunoassays and found three cases in which the squamous cell carcinoma antigen concentrations deviated greatly between the two immunoassays. Here, we aimed to elucidate the mechanisms responsible for these deviations. Methods The squamous cell carcinoma antigen concentrations were determined using the ARCHITECT SCC (CLIA method) and the ST AIA-PACK SCC (FEIA method). We performed polyethylene glycol precipitation and size exclusion chromatography to assess the molecular weight and spike recovery and absorption tests to examine the presence of an autoantibody. Results Both methods exhibited good performances for the measurement of squamous cell carcinoma antigen, although a correlation test showed large differences in the squamous cell carcinoma antigen concentrations measured using the two methods in three cases. The results of polyethylene glycol treatment and size exclusion chromatography indicated the existence of a large molecular weight squamous cell carcinoma antigen in these three cases. The spike recovery tests suggested the possible presence of an autoantibody against squamous cell carcinoma antigen. Moreover, the absorption test revealed that large squamous cell carcinoma antigen complexes were formed by the association of squamous cell carcinoma antigen with IgG in two cases and with both IgG and IgA in one case. Conclusions This study describes the existence of large molecular weight squamous cell carcinoma antigen that has complexed with immunoglobulin in the serum samples. The reason for the deviations between the two immunoassays might be due to differences of their reactivities against the squamous cell carcinoma antigen immune complexes with their autoantibody. To our knowledge, this is the first report to describe the coupling of squamous cell carcinoma antigen with IgA.

  19. Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity.

    Directory of Open Access Journals (Sweden)

    Martin Kreutz

    Full Text Available Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is paramount. However, co-administration of unlinked adjuvant cannot ensure that all cells targeted by the antibody conjugates are appropriately activated. Furthermore, antigen-presenting cells (APC that do not present the desired antigen are equally strongly activated and could prime undesired responses against self-antigens. We, therefore, were interested in exploring targeted co-delivery of antigen and adjuvant in cis in form of antibody-antigen-adjuvant conjugates for the induction of anti-tumour immunity. In this study, we report on the assembly and characterization of conjugates consisting of DEC205-specific antibody, the model antigen ovalbumin (OVA and CpG oligodeoxynucleotides (ODN. We show that such conjugates are more potent at inducing cytotoxic T lymphocyte (CTL responses than control conjugates mixed with soluble CpG. However, our study also reveals that the nucleic acid moiety of such antibody-antigen-adjuvant conjugates alters their binding and uptake and allows delivery of the antigen and the adjuvant to cells partially independently of DEC205. Nevertheless, antibody-antigen-adjuvant conjugates are superior to antibody-free antigen-adjuvant conjugates in priming CTL responses and efficiently induce anti-tumour immunity in the murine B16 pseudo-metastasis model. A better understanding of the role of the antibody moiety is required to inform future conjugate vaccination strategies for efficient induction of anti-tumour responses.

  20. Colocalization of Fc gamma RI-targeted antigen with class I MHC: implications for antigen processing.

    Science.gov (United States)

    Guyre, C A; Barreda, M E; Swink, S L; Fanger, M W

    2001-02-15

    The high-affinity receptor for IgG (CD64 or FcgammaRI) is constitutively expressed exclusively on professional APCs (monocytes, macrophages, and dendritic cells). When Ag is targeted specifically to FcgammaRI, Ag presentation is markedly enhanced, although the mechanism of this enhancement is unknown. In an effort to elucidate the pathways involved in FcgammaRI targeting, we developed a model targeted Ag using enhanced green fluorescent protein (eGFP). This molecule, wH22xeGFP, consists of the entire humanized anti-FcgammaRI mAb H22 with eGFP genetically fused to the C-terminal end of each CH3 domain. wH22xeGFP binds within the ligand-binding region by its Fc end, as well as outside the ligand-binding region by its Fab ends, thereby cross-linking FcgammaRI. Confocal microscopy studies revealed that wH22xeGFP was rapidly internalized by the high-FcgammaRI-expressing cell line U937 10.6, but did not associate with intracellular proteins Rab4, Rab5a, or Lamp-1, suggesting that the targeted fusion protein was not localized in early endosomes, recycling vesicles, or lysosomes. Interestingly, wH22xeGFP was found colocalized with intracellular MHC class I, suggesting that FcgammaRI-targeted Ags may converge upon a class I processing pathway. These data are in agreement with studies in the mouse showing that FcgammaRI targeting can lead to Ag-specific activation of cytotoxic T cells. Data obtained from these studies should lead to a better understanding of how Ags targeted to FcgammaRI are processed and under what conditions they lead to presentation of antigenic peptides in MHC class I, as a foundation for the use of FcgammaRI-targeted Ags as vaccines.

  1. Association of human leukocyte antigen class I antigens in Iranian patients with pemphigus vulgaris.

    Science.gov (United States)

    Mortazavi, Hossein; Amirzargar, Ali Akbar; Esmaili, Nafiseh; Toofan, Hesam; Ehsani, Amir Hooshang; Hosseini, Seyed Hamed; Rezaei, Nima

    2013-04-01

    There are a limited number of reports indicating the role of human leukocyte antigen (HLA) class I alleles in pemphigus vulgaris. This study was designed to highlight the association of HLA class I alleles with pemphigus vulgaris in Iran. Fifty patients with pemphigus vulgaris, diagnosed based on clinical, histological and direct immunofluorescence findings were enrolled into this study. The control group consisted of 50 healthy, age- and sex-matched individuals. HLA typing of class I (A, B and C alleles) was carried out using polymerase chain reaction based on the sequence-specific primer method. This study showed the higher frequency of HLA-B*44:02 (P = 0.007), -C*04:01 (P pemphigus vulgaris was significantly lower than the controls. Regarding the linkage disequilibrium between HLA class I alleles, the HLA-A*03:01, -B*51:01, -C*16:02 haplotype (4% vs 0%, P = 0.04) is suggested to be a predisposing factor, whereas HLA-A*26:01, -B*38, -C*12:03 haplotype (0% vs 6%, P = 0.01) is suggested to be a protective factor. In conclusion, it is suggested that HLA-B*44:02, -C*04:01, -C*15:02 alleles and HLA-A*03:01, -B*51:01, -C*16:02 haplotype are susceptibility factors for development of pemphigus vulgaris in the Iranian population, while HLA-C*06:02, -C*18:01 alleles and HLA-A*26:01, -B*38, -C*12:03 haplotype may be considered as protective alleles.

  2. Extraction of Ku antigen and anti-Ku antibody assay in various autoimmune connective tissue diseases

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To extract Ku antigen and to detect anti-Ku antibody in connective tissue diseases (CTDs). Methods: Ku antigen was prepared from rabbit thymus acetone powder. Anti-Ku antibodies were tested in 50 normal controls and 438 patients

  3. 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

    , identified morphologically and by their expression of specific cell markers, included Langerhans cells, macrophages, follicular dendritic cells, and interdigitating reticulum cells of the paracortex of lymph nodes. These cells expressed MHC class II antigens and contained Leishmania antigen. Since some...

  4. Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination.

    Science.gov (United States)

    Tam, Hok Hei; Melo, Mariane B; Kang, Myungsun; Pelet, Jeisa M; Ruda, Vera M; Foley, Maria H; Hu, Joyce K; Kumari, Sudha; Crampton, Jordan; Baldeon, Alexis D; Sanders, Rogier W; Moore, John P; Crotty, Shane; Langer, Robert; Anderson, Daniel G; Chakraborty, Arup K; Irvine, Darrell J

    2016-10-25

    Natural infections expose the immune system to escalating antigen and inflammation over days to weeks, whereas nonlive vaccines are single bolus events. We explored whether the immune system responds optimally to antigen kinetics most similar to replicating infections, rather than a bolus dose. Using HIV antigens, we found that administering a given total dose of antigen and adjuvant over 1-2 wk through repeated injections or osmotic pumps enhanced humoral responses, with exponentially increasing (exp-inc) dosing profiles eliciting >10-fold increases in antibody production relative to bolus vaccination post prime. Computational modeling of the germinal center response suggested that antigen availability as higher-affinity antibodies evolve enhances antigen capture in lymph nodes. Consistent with these predictions, we found that exp-inc dosing led to prolonged antigen retention in lymph nodes and increased Tfh cell and germinal center B-cell numbers. Thus, regulating the antigen and adjuvant kinetics may enable increased vaccine potency.

  5. PULSED ELECTROCHEMICAL TECHNIQUE FOR MONITORING ANTIBODY-ANTIGEN REACTIONS AT INTERFACES. (R825323)

    Science.gov (United States)

    AbstractThe mechanism of pulsed potential waveform for monitoring antibody¯antigen interactions at immunosensor interfaces is discussed. Some examples of antibody¯antigen interactions at quartz crystal microbalance and polymer-modified ...

  6. The incidence of HLA-SD antigens in recessive retinitis pigmentosa.

    Science.gov (United States)

    Chen, M C; Marak, G E; Pilkerton, A R

    1978-01-01

    Eighteen patients with recessive retinitis pigmentosa were tissue typed for HLA-SD antigens. There was no evidence that a particular HLA-SD antigen was associated with autosomal recessive retinitis pigmentosa. PMID:638110

  7. Serologic responses to somatic O and colonization-factor antigens of enterotoxigenic Escherichia coli in travelers.

    Science.gov (United States)

    Deetz, T R; Evans, D J; Evans, D G; DuPont, H L

    1979-07-01

    To improve the retrospective diagnoses of enterotoxigenic Escherichia coli (ETEC) as a cause of travelers' diarrhea, as well as to determine the presence of colonization-factor antigens in these infections, a study of serologic responses to antigens of ETEC was done. Paired sera from 60 United States students in Cholula, Puebla, Mexico, were analyzed for rises in titer of antibody to heat-labile toxin, eight somatic antigen O serogroups associated with ETEC, and two colonization-factor antigens, CFA/I and CFA/II. Only 9% had a response to O antigens, while 20% had responses to the colonization-factor antigens. Response to the colonization-factor antigens correlated significantly with response to the heat-labile toxin and with culture evidence of ETEC infection. Serologic studies confirmed that colonization-factor antigen has a role in naturally acquired cases of travelers' diarrhea and that it can be used as an additional determinant of infection with ETEC.

  8. Restricted diversity of antigen binding residues of antibodies revealed by computational alanine scanning of 227 antibody-antigen complexes.

    Science.gov (United States)

    Robin, Gautier; Sato, Yoshiteru; Desplancq, Dominique; Rochel, Natacha; Weiss, Etienne; Martineau, Pierre

    2014-11-11

    Antibody molecules are able to recognize any antigen with high affinity and specificity. To get insight into the molecular diversity at the source of this functional diversity, we compiled and analyzed a non-redundant aligned collection of 227 structures of antibody-antigen complexes. Free energy of binding of all the residue side chains was quantified by computational alanine scanning, allowing the first large-scale quantitative description of antibody paratopes. This demonstrated that as few as 8 residues among 30 key positions are sufficient to explain 80% of the binding free energy in most complexes. At these positions, the residue distribution is not only different from that of other surface residues but also dependent on the role played by the side chain in the interaction, residues participating in the binding energy being mainly aromatic residues, and Gly or Ser otherwise. To question the generality of these binding characteristics, we isolated an antibody fragment by phage display using a biased synthetic repertoire with only two diversified complementarity-determining regions and solved its structure in complex with its antigen. Despite this restricted diversity, the structure demonstrated that all complementarity-determining regions were involved in the interaction with the antigen and that the rules derived from the natural antibody repertoire apply to this synthetic binder, thus demonstrating the robustness and universality of our results.

  9. Molecular aspects of antibody-antigen interactions : size reduction of a herpes simplex virus neutralizing antibody and its antigen

    NARCIS (Netherlands)

    Schellekens, Gerardus Antonius

    1996-01-01

    Antibody molecules, produced as a response against foreign substances, interact with their antigen in a very specific manner. Antibodies with a predetermined specificity (monoclonal antibodies) can be produced and are widely used in medicine and science as indicator molecules. Genetic engineering of

  10. Correlation of urine cytology with ABO(H) antigenicity in transitional cell carcinoma of the bladder.

    OpenAIRE

    1988-01-01

    Cell surface ABO(H) antigenicity of superficial bladder tumours was assessed by the indirect immunoperoxidase test in 49 patients. Good correlation was obtained between surface antigenicity of tumours and the results of urine cytology. Malignant cells were detected cytologically in 22(56%) of cases with ABO(H) antigen negative tumours which are known to behave more aggressively than ABO(H) antigen positive ones. In contrast, malignant cells were found in the urine cytology of only one (10%) o...

  11. Studies on mechanism of Sialy Lewis-X antigen in liver metastases of human colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Xiao Wei Li; Yan Qing Ding; Jun Jie Cai; Shao Qing Yang; Lian Bing An; Dong Fang Qiao

    2001-01-01

    @@INTRODUCTION Sialyl Lewis-X antigen ,correlated with carcinoma, is a group of carbohydrate antigen containing oligosaccharide expressed of embryonic tisue and glycoproteins on cell surface of embryonic tissue[1].The SLeX antigen located on cell surface is synthesized principally by two enzymes ,al ,3fucosyltransfrease and a2, 3sialyctransferase.In adults ,SLeX antigen is expressed principally on the surfaces of granulocytic cells and some tumor cells .

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  13. A multiplex method for the detection of serum antibodies against in silico-predicted tumor antigens

    NARCIS (Netherlands)

    Reuschenbach, M.; Dorre, J.; Waterboer, T.; Kopitz, J.; Schneider, M.; Hoogerbrugge, N.; Jager, E.; Kloor, M.; Knebel Doeberitz, M. von

    2014-01-01

    Humoral immune responses against tumor antigens are studied as indirect markers of antigen exposure and in cancer vaccine studies. An increasing number of tumor antigens potentially translated from mutant genes is identified by advances in genomic sequencing. They represent an interesting source for

  14. 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

  15. Antigen loading on dendritic cells affects the lell function in stimulating T cells.

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To study the effect of antigen loading on dendritic cells (DC). Methods: DCs collected from peripheral blood monocytes were loaded with a tumor antigen from XG-7 cell line. These DCs were then co-cultured with allogeneic T cells and were compared with those DCs without antigen exposure.

  16. Neuroinvasive Cryptococcosis in an Immunocompetent Patient with a Negative Spinal Fluid Cryptococcus Antigen

    Directory of Open Access Journals (Sweden)

    Rocio C. Garcia-Santibanez

    2015-01-01

    Full Text Available 58-year-old man presented with headache, nausea, vomiting, and gait disturbance. Brain MRI showed meningeal enhancement and herniation. Serum Cryptococcus antigen was positive but spinal fluid antigen and cultures were negative. A cerebellar biopsy revealed nonencapsulated Cryptococcus. He completed antifungal therapy. Serum Cryptococcus antigen titer decreased. He had a full neurological recovery.

  17. [Immunoglobulin genes encoding antibodies directed to oncodevelopmental carbohydrate antigens].

    Science.gov (United States)

    Zenita, K; Yago, K; Fujimoto, E; Kannagi, R

    1990-07-01

    We investigated the immunoglobulin genes which encode the variable region of the monoclonal antibodies directed to the onco-developmental carbohydrate antigens such SSEA-1, fucosyl SSEA-1, SSEA-3 and SSEA-4. The VH region of these antibodies was preferentially encoded by the gene members of the X24, VH7183 and Q52 families, the families which are known to be located at the 3'-end region of the murine germ line VH gene. This result is interesting particularly when considering that the members of the 3'-end VH families are known to be preferentially expressed in embryonic B lymphocytes by an intrinsic genetic program. The comparative study of the nucleic acid sequences of mRNAs encoding these antibodies and the sequences of the corresponding germ line VH genes disclosed that the sequences encoding the antibodies contain no mutation from the germ line VH genes, or contain only a few somatic mutations, which are thought to be insignificant for the reactivity of the antibodies to the nominal antigens. These results imply that some of the embryonic B lymphocytes that express the unmutated germ line VH genes of the 3'-end families can be reactive with embryonic carbohydrate antigens, albeit rearranged with appropriate D-JH gene segments, and coupled with proper light chains. The VH region of the syngenic monoclonal anti-idiotypic antibodies directed to these anti-carbohydrate antibodies were also encoded preferentially by the members of the 3'-end VH families. We propose here that a part of the virgin embryonic B lymphocytes, which express the antibody encoded by the gene members of the 3'-end VH families at the cell surface, will be stimulated by the embryonic carbohydrate antigens which are abundantly present in the internal milieu of the embryo. The clonally expanded B lymphocytes, in turn, will facilitate the proliferation of other populations of embryonic B lymphocytes expressing the corresponding anti-idiotypic antibodies, which are also encoded by the gene members

  18. Real-time prostate-specific antigen detection with prostate-specific antigen imprinted capacitive biosensors

    Energy Technology Data Exchange (ETDEWEB)

    Ertürk, Gizem [Department of Biotechnology, Lund University, Lund (Sweden); Department of Biology, Hacettepe University, Ankara (Turkey); Hedström, Martin [Department of Biotechnology, Lund University, Lund (Sweden); CapSenze HB, Medicon Village, SE-223 63 Lund (Sweden); Tümer, M. Aşkın [Department of Biology, Hacettepe University, Ankara (Turkey); Denizli, Adil [Department of Chemistry, Hacettepe University, Ankara (Turkey); Mattiasson, Bo, E-mail: Bo.Mattiasson@biotek.lu.se [Department of Biotechnology, Lund University, Lund (Sweden); CapSenze HB, Medicon Village, SE-223 63 Lund (Sweden)

    2015-09-03

    Prostate specific antigen (PSA) is a valuable biomarker for early detection of prostate cancer, the third most common cancer in men. Ultrasensitive detection of PSA is crucial to screen the prostate cancer in an early stage and to detect the recurrence of the disease after treatment. In this report, microcontact-PSA imprinted (PSA-MIP) capacitive biosensor chip was developed for real-time, highly sensitive and selective detection of PSA. PSA-MIP electrodes were prepared in the presence of methacrylic acid (MAA) as the functional monomer and ethylene glycol dimethacrylate (EGDMA) as the cross-linker via UV polymerization. Immobilized Anti-PSA antibodies on electrodes (Anti-PSA) for capacitance measurements were also prepared to compare the detection performances of both methods. The electrodes were characterized by atomic force microscopy (AFM), scanning electron microscopy (SEM) and cyclic voltammetry (CV) and real-time PSA detection was performed with standard PSA solutions in the concentration range of 10 fg mL{sup −1}–100 ng mL{sup −1}. The detection limits were found as 8.0 × 10{sup −5} ng mL{sup −1} (16 × 10{sup −17} M) and 6.0 × 10{sup −4} ng mL{sup −1} (12 × 10{sup −16} M) for PSA-MIP and Anti-PSA electrodes, respectively. Selectivity studies were performed against HSA and IgG and selectivity coefficients were calculated. PSA detection was also carried out from diluted human serum samples and finally, reproducibility of the electrodes was tested. The results are promising and show that when the sensitivity of the capacitive system is combined with the selectivity and reproducibility of the microcontact-imprinting procedure, the resulting system might be used successfully for real-time detection of various analytes even in very low concentrations. - Highlights: • Microcontact imprinting method was used for preparing the sensor chip for capacitive biosensing. • High sensitivity was obtained. • Good selectivity was

  19. Liposome-coupled antigens are internalized by antigen-presenting cells via pinocytosis and cross-presented to CD8 T cells.

    Directory of Open Access Journals (Sweden)

    Yuriko Tanaka

    Full Text Available We have previously demonstrated that antigens chemically coupled to the surface of liposomes consisting of unsaturated fatty acids were cross-presented by antigen-presenting cells (APCs to CD8+ T cells, and that this process resulted in the induction of antigen-specific cytotoxic T lymphocytes. In the present study, the mechanism by which the liposome-coupled antigens were cross-presented to CD8+ T cells by APCs was investigated. Confocal laser scanning microscopic analysis demonstrated that antigens coupled to the surface of unsaturated-fatty-acid-based liposomes received processing at both MHC class I and class II compartments, while most of the antigens coupled to the surface of saturated-fatty-acid-based liposomes received processing at the class II compartment. In addition, flow cytometric analysis demonstrated that antigens coupled to the surface of unsaturated-fatty-acid-liposomes were taken up by APCs even in a 4°C environment; this was not true of saturated-fatty-acid-liposomes. When two kinds of inhibitors, dimethylamiloride (DMA and cytochalasin B, which inhibit pinocytosis and phagocytosis by APCs, respectively, were added to the culture of APCs prior to the antigen pulse, DMA but not cytochalasin B significantly reduced uptake of liposome-coupled antigens. Further analysis of intracellular trafficking of liposomal antigens using confocal laser scanning microscopy revealed that a portion of liposome-coupled antigens taken up by APCs were delivered to the lysosome compartment. In agreement with the reduction of antigen uptake by APCs, antigen presentation by APCs was significantly inhibited by DMA, and resulted in the reduction of IFN-γ production by antigen-specific CD8+ T cells. These results suggest that antigens coupled to the surface of liposomes consisting of unsaturated fatty acids might be pinocytosed by APCs, loaded onto the class I MHC processing pathway, and presented to CD8+ T cells. Thus, these liposome-coupled antigens

  20. Specificity of the proteasome cleavage to the antigen protein

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    In the MHC classⅠmolecule binding antigenic peptides processing and presentation pathway,the ubiquitin-proteasome system plays a key role in degrading the protein substrate.For the purpose of studying the specificities of proteasomal cleavage sites,partial least squares method is used to predict the proteasomal cleavage sites,and the predictive accuracy of the model is 82.8%.The specificities of the cleavage sites and the adjacent positions come from the contribution of the amino acids of the samples to the cleavage sites,showing the information of proteasome interacting with antigen protein.It demonstrates that the proteasome cleaving to target protein is selective,but not random.

  1. Antigenic structures stably expressed by recombinant TGEV-derived vectors.

    Science.gov (United States)

    Becares, Martina; Sanchez, Carlos M; Sola, Isabel; Enjuanes, Luis; Zuñiga, Sonia

    2014-09-01

    Coronaviruses (CoVs) are positive-stranded RNA viruses with potential as immunization vectors, expressing high levels of heterologous genes and eliciting both secretory and systemic immune responses. Nevertheless, its high recombination rate may result in the loss of the full-length foreign gene, limiting their use as vectors. Transmissible gastroenteritis virus (TGEV) was engineered to express porcine reproductive and respiratory syndrome virus (PRRSV) small protein domains, as a strategy to improve heterologous gene stability. After serial passage in tissue cultures, stable expression of small PRRSV protein antigenic domains was achieved. Therefore, size reduction of the heterologous genes inserted in CoV-derived vectors led to the stable expression of antigenic domains. Immunization of piglets with these TGEV vectors led to partial protection against a challenge with a virulent PRRSV strain, as immunized animals showed reduced clinical signs and lung damage. Further improvement of TGEV-derived vectors will require the engineering of vectors with decreased recombination rate.

  2. Constraints on the Genetic and Antigenic Variability of Measles Virus.

    Science.gov (United States)

    Beaty, Shannon M; Lee, Benhur

    2016-04-21

    Antigenic drift and genetic variation are significantly constrained in measles virus (MeV). Genetic stability of MeV is exceptionally high, both in the lab and in the field, and few regions of the genome allow for rapid genetic change. The regions of the genome that are more tolerant of mutations (i.e., the untranslated regions and certain domains within the N, C, V, P, and M proteins) indicate genetic plasticity or structural flexibility in the encoded proteins. Our analysis reveals that strong constraints in the envelope proteins (F and H) allow for a single serotype despite known antigenic differences among its 24 genotypes. This review describes some of the many variables that limit the evolutionary rate of MeV. The high genomic stability of MeV appears to be a shared property of the Paramyxovirinae, suggesting a common mechanism that biologically restricts the rate of mutation.

  3. Gallium-68 Prostate-Specific Membrane Antigen PET Imaging.

    Science.gov (United States)

    Hofman, Michael S; Iravani, Amir

    2017-04-01

    The role of gallium-68 ((68)Ga) prostate-specific membrane antigen (PSMA) PET imaging is evolving and finding its place in the imaging armamentarium for prostate cancer (PCa). Despite the progress of conventional imaging strategies, significant limitations remain, including identification of small-volume disease and assessment of bone. Clinical studies have demonstrated that (68)Ga-PSMA is a promising tracer for detection of PCa metastases, even in patients with low prostate-specific antigen. To provide an accurate interpretation of (68)Ga-PSMA PET/computed tomography, nuclear medicine specialists and radiologists should be familiar with physiologic (68)Ga-PSMA uptake, common variants, patterns of locoregional and distant spread of PCa, and inherent pitfalls.

  4. Human Leukocyte Antigen Diversity: A Southern African Perspective

    Directory of Open Access Journals (Sweden)

    Mqondisi Tshabalala

    2015-01-01

    Full Text Available Despite the increasingly well-documented evidence of high genetic, ethnic, and linguistic diversity amongst African populations, there is limited data on human leukocyte antigen (HLA diversity in these populations. HLA is part of the host defense mechanism mediated through antigen presentation to effector cells of the immune system. With the high disease burden in southern Africa, HLA diversity data is increasingly important in the design of population-specific vaccines and the improvement of transplantation therapeutic interventions. This review highlights the paucity of HLA diversity data amongst southern African populations and defines a need for information of this kind. This information will support disease association studies, provide guidance in vaccine design, and improve transplantation outcomes.

  5. Detection of C. difficile common antigen: comparison of methods

    Directory of Open Access Journals (Sweden)

    Maria Giuliana Brunelli

    2011-09-01

    Full Text Available In order to identify and define a diagnostic algorithm for the diagnosis of C. difficile infection, a comparative study was carried out at the Microbiology Laboratory of “Maggiore della Carità” Hospital in Novara.We compared the system currently in use in the laboratory “TECHLAB C.difficile Quik Chek Complete (Inverness Medical, USA”, an immunoenzymatic assay for the simultaneous detection of C. difficile common antigen (GDH and Toxins A&B, with the new ImmunoCard Clostridium difficile GDH (Meridian Bioscience, USA, which identifies the C. difficile Common Antigen GDH. The results proved identical between the two assays: of 100 samples, 82 resulted negative with both tests, 18 were GDH positive with both tests. Out of the 18 GDH positives, 9 resulted positive for the Toxins portion of the TechLab test.

  6. Synthesis and Identification of Artificial Antigen for Imidacloprid

    Institute of Scientific and Technical Information of China (English)

    ZHU Guo-nian; GUI Wen-jun; ZHENG Zun-tao; CHENG Jing-li; WU Gang

    2006-01-01

    This study reported that a hapten of imidacloprid, 1-[(6-Carboxylethylthio-3- pyridinyl)methyl]-N -nitro-imidazolidinimine was synthesized using technical material of imidacloprid to react with 3-mercaptopropionic acid in hot alkaline solution.The hapten was conjugated to bovine serum albumin (BSA) and ovalbumin (OVA) to form the immuno-antigens and the coating antigen, respectively. The antibody with high titer (2.56 x 104) was obtained after immuning rabbits. The results showed that the antibody had a high affinity to imidacloprid tested by enzyme-linked immunosorbent assay (ELISA),which IC50 and IC20 were 20.7 and 1.1 μg L-1; and the cross reactibilities to those compounds related with imidacloprid were less than 1.4%.

  7. Uptake of antigen-antibody complexes by human dendritic cells.

    Science.gov (United States)

    Fanger, N A; Guyre, P M; Graziano, R F

    2001-01-01

    Fc receptors specific for IgG (FcγR) potentiate the immune response by facilitating the interaction between myeloid cells and antibody-coated targets (1-3). Monocyte and neutrophil FcyR engagement can lead to the induction of lytic-type mechanisms associated with innate responses. FcyR triggering can also play a key role in adaptive immune responses. For example, FcyR-directed capture and uptake of antigens (Ag) by dendritic cells (DC) results in processing and presentation to naive Ag-specific T cells, leading to their expansion and maturation into effector T-cell populations. This chapter describes methodology currently in use to explore and manipulate antigen-antibody (Ag-Ab) uptake by FcyR expressed on DC.

  8. [Isolation and physico-chemical characteristics of human cancerocerebral antigen].

    Science.gov (United States)

    Prokopenko, P G; Borisenko, S A; Tatarinov, Iu S

    1984-01-01

    During gel filtration on Sephadex G-200 human cancerocerebral antigen (CCA) was eluted as two protein fractions with molecular mass of 135,000 and 270.000 daltons. Only one band of protein with molecular mass of about 15,000 daltons was noted after electrophoresis in 10% polyacrylamide gel containing SDS. As characteristic properties of CCA were recognized an electrophoretic polymorphism and a distinct trend to polymerization and isomeria. The antigen was not stained with dyes designed for staining base proteins, lipo-,glyco- and ferroproteins; CCA was thermostable (5 min at 80 degrees), it was inactivated by trypsin and protease but was resistant to pronase, hexokinase, alpha-amylase and beta-glucuronidase. A procedure was developed for isolation of CCA from brain, including fractionation with ammonium sulfate, ion exchange chromatography on DEAE-Sephadex A-50. The procedure enabled to obtain the CCA preparations suitable for radioimmunological, immunobiological assays and amino acid analyses.

  9. Dissection of T-cell antigen specificity in human melanoma

    DEFF Research Database (Denmark)

    Andersen, Rikke Sick; Albæk Thrue, Charlotte; Junker, Niels

    2012-01-01

    Tumor-infiltrating lymphocytes (TIL) isolated from melanoma patients and expanded in vitro by interleukin (IL)-2 treatment can elicit therapeutic response after adoptive transfer, but the antigen specificities of the T cells transferred have not been determined. By compiling all known melanoma......-associated antigens and applying a novel technology for high-throughput analysis of T-cell responses, we dissected the composition of melanoma-restricted T-cell responses in 63 TIL cultures. T-cell reactivity screens against 175 melanoma-associated epitopes detected 90 responses against 18 different epitopes...... from different fragments of resected melanoma lesions. In summary, our findings provide an initial definition of T-cell populations contributing to tumor recognition in TILs although the specificity of many tumor-reactive TILs remains undefined....

  10. [ELISA method for the determination of factor VII antigen].

    Science.gov (United States)

    Jorquera, J I; Aznar, J A; Monteagudo, J; Montoro, J M; Casaña, P; Pascual, I; Bañuls, E; Curats, R; Llopis, F

    1989-12-01

    The low plasma concentration of clotting factor VII makes it difficult to assay its antigenic fraction by the conventional methods of precipitation with specific antigens. Simple and peroxidase-conjugated antisera are currently available from commercial sources, thus allowing one to determine F VII:Ag by enzyme immunoassay. An ELISA method has been developed in this laboratory which provides sensitivity limits about 0.1% of the plasma concentration of F VII and correlates significantly with its functional activity (r = 0.603, n = 44, p less than 0.001). This technique can be highly helpful in characterising molecular variants of F VII, as well as in detecting acquired deficiencies of this factor.

  11. Autoantibodies against tumor-associated antigens fordetection of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the mostcommon tumors worldwide. The survival rate after theonset of symptoms is generally less than one year forthe late presentation of HCC, and reliable tools for earlydiagnosis are lacking. Therefore, novel biomarkers forthe early detection of HCC are urgently required. Recentstudies show that the abnormal release of proteins bytumor cells can elicit humoral immune responses toself-antigens called tumor-associated antigens (TAAs).The corresponding autoantibodies can be detectedbefore the clinical diagnosis of cancer. Therefore, thereis growing interest in using serum autoantibodies ascancer biomarkers. In this review, we focus on theadvances in research on autoantibodies against TAAs asserum biomarker for detection of HCC, the mechanismof the production of TAAs, and the association ofautoantibodies with patients' clinical characteristics.

  12. Basophil degranulation induced by oral poison ivy antigen.

    Science.gov (United States)

    Shelley, W B; Resnik, S S

    1965-08-01

    Seven subjects shown by patch test to be sensitive to poison ivy oleoresin were challenged with graded oral doses of ivy extract. In each instance the circulating basophil leukocytes showed significant degranulation within one hour of challenge. This finding was interpreted as evidence of the presence of immediate-type circulating antibody to ivy antigen in these subjects. No drop in the absolute basophil count was noted, but with higher oral doses the degranulation persisted for several days. Thirteen control subjects showed no change in the basophil morphology or count, indicating that the resin at these levels was not toxic to this cell. All but one of the sensitive subjects showed objective patch test evidence of hyposensitization following the intensive three-week course of oral poison ivy antigen.

  13. Lambda-Display: A Powerful Tool for Antigen Discovery

    Directory of Open Access Journals (Sweden)

    Nicola Gargano

    2011-04-01

    Full Text Available Since its introduction in 1985, phage display technology has been successfully used in projects aimed at deciphering biological processes and isolating molecules of practical value in several applications. Bacteriophage lambda, representing a classical molecular cloning and expression system has also been exploited for generating large combinatorial libraries of small peptides and protein domains exposed on its capsid. More recently, lambda display has been consistently and successfully employed for domain mapping, antigen discovery and protein interaction studies or, more generally, in functional genomics. We show here the results obtained by the use of large libraries of cDNA and genomic DNA for the molecular dissection of the human B-cell response against complex pathogens, including protozoan parasites, bacteria and viruses. Moreover, by reviewing the experimental work performed in recent investigations we illustrate the potential of lambda display in the diagnostics field and for identifying antigens useful as targets for vaccine development.

  14. Preparation of immunoliposomes directed against CD34 antigen as target.

    Science.gov (United States)

    Mercadal, M; Carrion, C; Domingo, J C; Petriz, J; Garcia, J; de Madariaga, M A

    1998-04-22

    The My-10 monoclonal antibody has facilitated the search of haematopoietic stem cells by recognizing selectively the human CD34 antigen. In the present work, My-10 immunoliposomes directed specifically against CD34+ cells were prepared, characterized and tested in vitro. Binding to target cells at 4 degreesC of immunoliposomes containing carboxyfluorescein as aqueous marker was evaluated by flow cytometry and fluorescence microscopy. These immunoliposomes demonstrated their capacity to bind specifically to CD34+ cells. Studies have shown that 9 antibodies/vesicle were sufficient to obtain a good binding efficiency. The product was stable over one month at 4 degreesC in terms of leakage of encapsulated carboxyfluorescein, particle size and antigen binding capacity.

  15. Synthesis and evaluation of artificial antigens for astragaloside IV

    Directory of Open Access Journals (Sweden)

    Sheng-lan Yu

    2014-06-01

    Full Text Available The objective of this study was to produce artificial antigens for astragaloside IV that could be used to prepare antibodies against astragaloside IV screened in Radix astragali (Astragalus membranaceus (Fisch Bunge, Fabaceae and its preparations, using an indirect ELISA. Astragaloside IV was coupled to carrier proteins, bovine serum albumin and ovalbumin using the sodium periodate method and was then evaluated using SDS-PAGE, MALDI-TOF MS and animal immunizations. The coupling ratio of astragaloside IV to bovine serum albumin ratio was determined to be thirteen, and the indirect ELISA demonstrated that three groups of mice immunized with astragaloside IV-bovine serum albumin produced anti-astragaloside IV- bovine serum albumin-specific antibody, with a minimum serum titer of 1:9600. A method for synthesizing highly immunogenic astragaloside IV artificial antigens was successfully developed thus indicating its feasibility in the establishment of a fast immunoassay for astragaloside IV content determination in Radix astragali and its products.

  16. P System antigenic determiners expression in Ascaris lumbricoides

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    Ponce De León Patricia

    2003-01-01

    Full Text Available The P System antigens have been detected in numerous parasites, bacterias and viruses, nevertheless the clinical significance is still unknown. The aim was to study the presence of P1 antigenic determiners in A. lumbricoides extracts by means of the use of 6 different monoclonal antibodies of well-known concentrations and Ig class. We worked with 14 A. lumbricoides extracts. Inhibition Agglutination Test was made in a bromelin enzymatic medium and 4 masculineC temperature. Titre, Score and Sensitivity Parameter were determined for each monoclonal antibody against red cells suspension used as revealing system. Ten extracts inhibited the agglutination of all anti P1 monoclonal antibodies. The 4 remaining extracts only inhibited the agglutination of some of them. It is demonstrated that the extracts have P1 activity. This activity is independent of titre, Score, Sensitivity Parameter, concentration and Ig class and it depends on the epitope at which the monoclonal antibody is directed.

  17. Viral hepatitis and hepatitis B antigen: recent advances

    Science.gov (United States)

    Krugman, Saul

    1974-01-01

    Recent advances in hepatitis research have shed new light on the etiology, pathogenesis, epidemiology and prevention of type B hepatitis infection. The so-called ‘Dane’ particle is probably the complete hepatitis B virion; its outer coat is the hepatitis B (Australia) antigen (HB Ag) and its inner core is an immunologically distinct particle. Subtypes of HB Ag (a, d, y, w and r) are useful indices for epidemiological surveys. Concepts of epidemiology have changed: type B hepatitis is transmissible by contact as well as by inoculation. The presence of HB Ag in blood is indicative of the presence of hepatitis B virus. Tests to detect antigen and use of voluntary blood donors have played a major role in the decreased incidence of post transfusion hepatitis. A special hepatitis B gammaglobulin preparation and a heat-inactivated hepatitis B vaccine have proved to be effective in preliminary studies. PMID:4219230

  18. Original Antigenic Sin Response to RNA Viruses and Antiviral Immunity

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    Park, Mee Sook; Kim, Jin Il; Park, Sehee; Lee, Ilseob

    2016-01-01

    The human immune system has evolved to fight against foreign pathogens. It plays a central role in the body's defense mechanism. However, the immune memory geared to fight off a previously recognized pathogen, tends to remember an original form of the pathogen when a variant form subsequently invades. This has been termed 'original antigenic sin'. This adverse immunological effect can alter vaccine effectiveness and sometimes cause enhanced pathogenicity or additional inflammatory responses, according to the type of pathogen and the circumstances of infection. Here we aim to give a simplified conceptual understanding of virus infection and original antigenic sin by comparing and contrasting the two examples of recurring infections such as influenza and dengue viruses in humans. PMID:27799871

  19. Herpesvirus glycoproteins undergo multiple antigenic changes before membrane fusion.

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    Daniel L Glauser

    Full Text Available Herpesvirus entry is a complicated process involving multiple virion glycoproteins and culminating in membrane fusion. Glycoprotein conformation changes are likely to play key roles. Studies of recombinant glycoproteins have revealed some structural features of the virion fusion machinery. However, how the virion glycoproteins change during infection remains unclear. Here using conformation-specific monoclonal antibodies we show in situ that each component of the Murid Herpesvirus-4 (MuHV-4 entry machinery--gB, gH/gL and gp150--changes in antigenicity before tegument protein release begins. Further changes then occurred upon actual membrane fusion. Thus virions revealed their final fusogenic form only in late endosomes. The substantial antigenic differences between this form and that of extracellular virions suggested that antibodies have only a limited opportunity to block virion membrane fusion.

  20. Detection and Measurement of Antigen-Antibody Reactions

    Science.gov (United States)

    1963-09-30

    kaolin . With low titer serum, much of the antibody also is removed, so that high titer antibody is made even more necessary. The use of immunodiffusion...increase the antibody titer significantly. In addition, a series of animals has been started on injections of bovine serum albumin with Freund’s... bovine serum albumin (BSA) has been obtained. With this available, a comparison can be made with normal antibody to the same antigen. Since the