Sample records for carcinoembryonic antigen families


    Directory of Open Access Journals (Sweden)

    Rita G SOUSA


    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.

  2. Differential recognition of members of the carcinoembryonic antigen family by Afa/Dr adhesins of diffusely adhering Escherichia coli (Afa/Dr DAEC). (United States)

    Berger, Cedric N; Billker, Oliver; Meyer, Thomas F; Servin, Alain L; Kansau, Imad


    Little is known about the molecular bases underlying the virulence of diffusely adhering Escherichia coli (DAEC) harbouring the Afa/Dr family of adhesins. These adhesins recognize as receptors the GPI-anchored proteins CD55 (decay-accelerating factor, DAF) and CD66e (carcinoembryonic antigen, CEA). CD66e is a member of the CEA-related cell adhesion molecules (CEACAM) family, comprising seven members. We analysed the interactions of Afa/Dr DAEC with the CEACAMs using CEACAM-expressing CHO and HeLa cells. The results demonstrate that only E. coli expressing a subfamily of Afa/Dr adhesins, named here Afa/Dr-I, including Dr, F1845 and AfaE-III adhesins, bound onto CHO cells expressing CEACAM1, CEA or CEACAM6. Whereas all the Afa/Dr adhesins elicit recruitment of CD55 around adhering bacteria, only the Afa/Dr-I subfamily elicits the recruitment of CEACAM1, CEA and CEACAM6. In addition, although CEACAM3 is not recognized as a receptor by the subfamily of Afa/Dr adhesins, it is recruited around bacteria in HeLa cells. The recruited CEACAM1, CEA and CEACAM6 around adhering bacteria resist totally or in part a detergent extraction, whereas the recruited CEACAM3 does not. Finally, the results show that recognition of CEA and CEACAM6, but not CEACAM1, is accompanied by tight attachment to bacteria of cell surface microvilli-like extensions, which are elongated. Moreover, recognition of CEA is accompanied by an activation of the Rho GTPase Cdc42 and by a phosphorylation of ERM, which in turn elicit the observed cell surface microvilli-like extensions.

  3. [The carcinoembryonic antigen: apropos of an old friend]. (United States)

    Téllez-Avila, Félix Ignacio; García-Osogobio, Sandra Minerva


    The carcinoembryonic antigen (CEA) is glycoprotein localized in the apical surface of mature enterocytes. The members of the CEA gene family are clustered on chromosome 19q13.2. It is formed by 29 genes, of which 18 are expressed. Many functions of CEA have been known in healthy indiuiduals, however its role as cell adhesion molecule is the most studied. Besides the colon, CEA is expressed in the stomach, tongue, oesophagus, cervix, and prostate. The most important clinical function is in colorectal, gastric and ovary cancer. It is used as prognosis marker, staging system, recurrence, treatment response and liver metastases. There are many non-neoplasic diseases that enhance CEA value. Actually, CEA is being studying as target of immunotherapy.

  4. Immunosensing procedures for carcinoembryonic antigen using graphene and nanocomposites. (United States)

    Luong, John H T; Vashist, Sandeep Kumar


    Two-dimensional (2D) graphene, sp(2)-hybridized carbon, and its two major derivatives, graphene oxide (GO) and reduced graphene oxide (rGO) have played an important role in immunoassays (IAs) and immunosensing (IMS) platforms for the detection of carcinoembryonic antigen (CEA), an implicated tumor biomarker found in several types of cancer. The graphene family with high surface area is functionalized to form stable nanocomposites with gold nanoparticles (AuNPs) and electron mediators. The capture anti-CEA antibody (Ab) with high density can be anchored on AuNPs of such composites to provide remarkable detection sensitivity, significantly below the level found in normal subjects and cancer patients. Electrochemical and fluorescence/chemiluminescence-quenching properties of graphene-based nanocomposites are exploited in various detection schemes. Future endeavors are envisioned for the development of an array platform with high-throughput for CEA together with other tumor biomarkers and C-reactive protein, a universal biomarker for infection and inflammation. The ongoing efforts dedicated to the replacement of a lab-based detector by a cellphone with smart applications will further enable cost-effective and frequent monitoring of CEA in order to establish its clinical relevance and provide tools for real-time monitoring of patients during chemotherapy.

  5. Phylogenetic discordance of human and canine carcinoembryonic antigen (CEA, CEACAM) families, but striking identity of the CEA receptors will impact comparative oncology studies. (United States)

    Weichselbaumer, Marlene; Willmann, Michael; Reifinger, Martin; Singer, Josef; Bajna, Erika; Sobanov, Yuriy; Mechtcherikova, Diana; Selzer, Edgar; Thalhammer, Johann G.; Kammerer, Robert; Jensen-Jarolim, Erika


    Comparative oncology aims at speeding up developments for both, human and companion animal cancer patients. Following this line, carcinoembryonic antigen (CEA, CEACAM5) could be a therapeutic target not only for human but also for canine (Canis lupus familiaris; dog) patients. CEACAM5 interacts with CEA-receptor (CEAR) in the cytoplasm of human cancer cells. Our aim was, therefore, to phylogenetically verify the antigenic relationship of CEACAM molecules and CEAR in human and canine cancer. Anti-human CEACAM5 antibody Col-1, previously being applied for cancer diagnosis in dogs, immunohistochemically reacted to 23 out of 30 canine mammary cancer samples. In immunoblot analyses Col-1 specifically detected human CEACAM5 at 180 kDa in human colon cancer cells HT29, and the canine antigen at 60, 120, or 180 kDa in CF33 and CF41 mammary carcinoma cells as well as in spontaneous mammary tumors. While according to phylogenicity canine CEACAM1 molecules should be most closely related to human CEACAM5, Col-1 did not react with canine CEACAM1, -23, -24, -25, -28 or -30 transfected to canine TLM-1 cells. By flow cytometry the Col-1 target molecule was localized intracellularly in canine CF33 and CF41 cells, in contrast to membranous and cytoplasmic expression of human CEACAM5 in HT29. Col-1 incubation had neither effect on canine nor human cancer cell proliferation. Yet, Col-1 treatment decreased AKT-phosphorylation in canine CF33 cells possibly suggestive of anti-apoptotic function, whereas Col-1 increased AKT-phosphorylation in human HT29 cells. We report further a 99% amino acid similarity of human and canine CEA receptor (CEAR) within the phylogenetic tree. CEAR could be detected in four canine cancer cell lines by immunoblot and intracellularly in 10 out of 10 mammary cancer specimens from dog by immunohistochemistry. Whether the specific canine Col-1 target molecule may as functional analogue to human CEACAM5 act as ligand to canine CEAR, remains to be defined. This

  6. A new Kupffer cell receptor mediating plasma clearance of carcinoembryonic antigen by the rat. (United States)

    Toth, C A; Thomas, P; Broitman, S A; Zamcheck, N


    Native human carcinoembryonic antigen is rapidly removed from the circulation by the rat liver Kupffer cell after intravenous injection. The molecule is subsequently transferred to the hepatocyte in an immunologically identifiable form. Carcinoembryonic antigen has a circulatory half-life of 3.7 (+/- 0.8) min, and cellular entry is by receptor-mediated endocytosis. Non-specific fluid pinocytosis and phagocytosis can be excluded as possible mechanisms by the kinetics of clearance and failure of colloidal carbon to inhibit uptake. Substances with known affinity for the hepatic receptors for mannose, N-acetylglucosamine, fucose and galactose all fail to inhibit carcinoembryonic antigen clearance. After two cycles of the Smith degradation, carcinoembryonic antigen is still able to inhibit clearance of the native molecule. Receptor specificity is apparently not dependent on those non-reducing terminal sugars of the native molecule. Performic acid-oxidized carcinoembryonic antigen also inhibits clearance of carcinoembryonic antigen in vivo. Receptor binding is not dependent on tertiary protein conformation. Non-specific cross-reacting antigen, a glycoprotein structurally similar to carcinoembryonic antigen, is cleared by the same mechanism.

  7. A recombinant vaccinia virus expressing human carcinoembryonic antigen (CEA). (United States)

    Kaufman, H; Schlom, J; Kantor, J


    Carcinoembryonic antigen (CEA) is a 180-kDa glycoprotein expressed on most gastrointestinal carcinomas. A 2.4-kb cDNA clone, containing the complete coding sequence, was isolated from a human colon tumor cell library and inserted into a vaccinia virus genome. This newly developed construct was characterized by Southern blotting, DNA hybridization studies, and polymerase chain reaction analysis. The CEA gene was stably integrated into the vaccinia virus thymidine kinase gene. The recombinant was efficiently replicated upon serial passages in cell cultures and in animals. The recombinant virus expresses on the surface of infected cells a protein product recognized by a monoclonal antibody (COL-I) directed against CEA. Immunization of mice with the vaccinia construct elicited a humoral immune response against CEA. Pilot studies also showed that administration of the recombinant CEA vaccinia construct was able to greatly reduce the growth in mice of a syngeneic murine colon adenocarcinoma which had been transduced with the human CEA gene. The use of this new recombinant CEA vaccinia construct may thus provide an approach in the specific active immunotherapy of human GI cancer and other CEA expressing carcinoma types.

  8. Carcinoma of the ureter with extensive squamous differentiation and positive immunoperoxidase staining for carcinoembryonic antigen: a case report. (United States)

    Fulks, R M; Falace, P B


    A case of ureteral carcinoma with extensive squamous differentiation and positive staining for carcinoembryonic antigen by the immunoperoxidase method is presented. Ureteral carcinoma should be added to the list of tumors that may produce carcinoembryonic antigen or antigen-like material.

  9. Radionuclide-Based Cancer Imaging Targeting the Carcinoembryonic Antigen

    Directory of Open Access Journals (Sweden)

    Hao Hong


    Full Text Available Carcinoembryonic antigen (CEA, highly expressed in many cancer types, is an important target for cancer diagnosis and therapy. Radionuclide-based imaging techniques (gamma camera, single photon emission computed tomography [SPECT] and positron emission tomography [PET] have been extensively explored for CEA-targeted cancer imaging both preclinically and clinically. Briefly, these studies can be divided into three major categories: antibody-based, antibody fragment-based and pretargeted imaging. Radiolabeled anti-CEA antibodies, reported the earliest among the three categories, typically gave suboptimal tumor contrast due to the prolonged circulation life time of intact antibodies. Subsequently, a number of engineered anti-CEA antibody fragments (e.g. Fab’, scFv, minibody, diabody and scFv-Fc have been labeled with a variety of radioisotopes for CEA imaging, many of which have entered clinical investigation. CEA-Scan (a 99mTc-labeled anti-CEA Fab’ fragment has already been approved by the United States Food and Drug Administration for cancer imaging. Meanwhile, pretargeting strategies have also been developed for CEA imaging which can give much better tumor contrast than the other two methods, if the system is designed properly. In this review article, we will summarize the current state-of-the-art of radionuclide-based cancer imaging targeting CEA. Generally, isotopes with short half-lives (e.g. 18F and 99mTc are more suitable for labeling small engineered antibody fragments while the isotopes with longer half-lives (e.g. 123I and 111In are needed for antibody labeling to match its relatively long circulation half-life. With further improvement in tumor targeting efficacy and radiolabeling strategies, novel CEA-targeted agents may play an important role in cancer patient management, paving the way to “personalized medicine”.

  10. Radionuclide-Based Cancer Imaging Targeting the Carcinoembryonic Antigen (United States)

    Hong, Hao; Sun, Jiangtao; Cai, Weibo


    Carcinoembryonic antigen (CEA), highly expressed in many cancer types, is an important target for cancer diagnosis and therapy. Radionuclide-based imaging techniques (gamma camera, single photon emission computed tomography [SPECT] and positron emission tomography [PET]) have been extensively explored for CEA-targeted cancer imaging both preclinically and clinically. Briefly, these studies can be divided into three major categories: antibody-based, antibody fragment-based and pretargeted imaging. Radiolabeled anti-CEA antibodies, reported the earliest among the three categories, typically gave suboptimal tumor contrast due to the prolonged circulation life time of intact antibodies. Subsequently, a number of engineered anti-CEA antibody fragments (e.g. Fab’, scFv, minibody, diabody and scFv-Fc) have been labeled with a variety of radioisotopes for CEA imaging, many of which have entered clinical investigation. CEA-Scan (a 99mTc-labeled anti-CEA Fab’ fragment) has already been approved by the United States Food and Drug Administration for cancer imaging. Meanwhile, pretargeting strategies have also been developed for CEA imaging which can give much better tumor contrast than the other two methods, if the system is designed properly. In this review article, we will summarize the current state-of-the-art of radionuclide-based cancer imaging targeting CEA. Generally, isotopes with short half-lives (e.g. 18F and 99mTc) are more suitable for labeling small engineered antibody fragments while the isotopes with longer half-lives (e.g. 123I and 111In) are needed for antibody labeling to match its relatively long circulation half-life. With further improvement in tumor targeting efficacy and radiolabeling strategies, novel CEA-targeted agents may play an important role in cancer patient management, paving the way to “personalized medicine”. PMID:19578524

  11. Elevated carcinoembryonic antigen tumour marker caused by head and neck cancer: a case report and literature study. (United States)

    Vingerhoedt, S I; Hauben, E; Hermans, R; Vander Poorten, V L; Nuyts, S


    Carcinoembryonic antigen is a tumour marker commonly increased in gastrointestinal and pulmonary cancers. We report a case of a 46-year-old man with a mucoepidermoid carcinoma of the base of tongue with an elevated and traceable serum carcinoembryonic antigen level. This antigen proved to be a valuable marker in the treatment follow-up. When a raised carcinoembryonic antigen level is found, salivary gland malignancies should be taken into the differential diagnosis and clinical examination of the head and neck region should not be overlooked.

  12. Significance of correlation between levels of carcinoembryonic antigen and carbohydrate antigen 19-9, carcinoembryonic antigen and C-reactive protein, carcinoembryonic antigen and alpha-1 antitrypsin in gastric and colon cancer patients

    Directory of Open Access Journals (Sweden)

    Bhawna Bagaria


    Full Text Available Aim: Recent progress in proteomics studies profiled that serum proteins of cancer patients and those of normal individuals have altered cancer antigen and acute phase protein expression for distinct types and stages of cancer. In our study, correlation between carcinoembryonic antigen (CEA and carbohydrate antigen (CA 19-9, CEA and C-reactive protein (CRP, CEA and alpha-1 antitrypsin (A1AT were evaluated in gastric and colon cancer patients. Materials and Methods: CEA was estimated by solid phase, two-site sequential chemiluminescent immunometric assay, CA19-9 by solid phase enzyme-linked immunosorbent assay, CRP by latex turbidimetry method and A1AT by turbidimetry method. Results: A significant correlation was seen in levels of CEA and CA19-9 in gastric (r = 0.457, P < 0.001 and colon cancer (r = 0.451, P < 0.001 patients. Correlation between CEA and CRP was significant in gastric (r = 0.462, P < 0.001 and colon cancer (r = 0.759, P < 0.001 patients and between CEA and A1AT also, correlation was found to be significant in gastric (r = 0.631, P < 0.001 and colon cancer patients (r = 0.516, P ≤ 0.001. Conclusion: Serum acute-phase protein concentrations, when combined with CEA increases the sensitivity of CEA and provide substantial information concerning the diagnosis of gastrointestinal cancers. They have a definite role as a significant prognostic indicator which undoubtedly correlates with progression of cancer. Combined CEA and CA19-9 positivity reflected more biologic malignant properties and were significantly correlated with lymph node metastasis, hepatic metastasis and lower rates of curative resection. Surgical outcomes of patients who were CEA and CA19-9 positive were poorer than those of patients with normal CEA and CA19-9 levels.

  13. Plasma lipid-bound sialic acid and carcinoembryonic antigen in cancer patients. (United States)

    Dnistrian, A M; Schwartz, M K


    We evaluated lipid-bound sialic acid as a "marker" in cancer patients and assessed the individual and combined value of lipid-bound sialic acid and carcinoembryonic antigen determinations in these patients. Plasma was sampled from 62 normal subjects and 125 cancer patients. Lipid-bound sialic acid was determined by the resorcinol method after total lipid extraction and isolation of the sialolipid fraction from plasma. Neither marker was increased in many breast cancer patients. Carcinoembryonic antigen was increased more commonly and to a greater degree in colon cancer patients and seems to be the preferred marker. Both markers were increased in lung cancer patients and their combined evaluation improved the rate of detection. Lipid-bound sialic acid was increased in more patients with leukemias, lymphomas, Hodgkin's disease, and melanomas, suggesting that it may be a useful biochemical marker in these types of cancer.

  14. Demonstration and immunochemical characterization of carcinoembryonic antigen in human pancreatic juice. (United States)

    McCabe, R P; Kupchik, H Z; Saravis, C A; Broitman, S A; Gregg, J A; Zamcheck, N


    Pancreatic juice collected from 10 patients without evidence of malignant disease of the pancreas or other organs was pooled, extracted, and fractionated by Sepharose 6-B and Sephadex G-200 gel filtration. The carcinoembryonic antigen (CEA) activity in the material was demonstrated and studied by: a) radioimmunoassay, b) competitive binding to antibodies against CEA, c) precipitin inhibition, and d) Ouchterlony analysis. The immunochemical identity of the active material to CEA purified from liver metastases of colon cancer was demonstrated.

  15. Carcinoembryonic antigens are targeted by diverse strains of typable and non-typable Haemophilus influenzae. (United States)

    Virji, M; Evans, D; Griffith, J; Hill, D; Serino, L; Hadfield, A; Watt, S M


    Haemophilus influenzae (Hi), a commensal of the human respiratory mucosa, is an important cause of localized and systemic infections. We show that distinct strains belonging to typable (THi) and non-typable (NTHi) H. influenzae target human carcinoembryonic antigens (the membrane associated CEA family of cell adhesion molecules, are now termed CEACAMs). All strains of H. influenzae biogroup aegyptius (Hi-aeg) and more than 70% of THi and NTHi strains tested specifically recognize CEACAMI-Fc soluble constructs. Furthermore, transfection of Chinese hamster ovary cells with human CEACAM1 cDNA alone was sufficient for promoting Hi interactions with the transfected cells. The majority of the Hi-aeg strains tested interacted with soluble constructs containing only the N-terminal domain. In contrast, several THi and NTHi strains reacted with soluble constructs only when additional extracellular A and B domains of the receptor were present. The use of monoclonal antibodies confirmed that THi and NTHi strains also interact primarily at the N-domain. We used site-directed mutants of CEACAM1 that contained substitutions at surface exposed amino acids and a molecular model of the N-domain to identify the residues involved in interactions with Hi ligands. The studies show that a common region exposed at the CFG face of the molecule is targeted by diverse Hi strains. However, mutation at distinct sites within this area affected the interactions of distinct strains signifying the potential for tissue tropism via this receptor. Analyses of the molecular basis of interaction with human cell lines and purified CEA show that Hi strains, especially those belonging to Hi-aeg, interact with multiple CEACAMs. Because Neisseria meningitidis (Nm) strains are also known to bind at the CFG face of the receptor, we used Nm and Hi strains in co-infection experiments and demonstrate competition between these mucosal pathogens in colonization of target cells via CEACAMs.

  16. Carcinoembryonic Antigen Expression and Resistance to Radiation and 5-Fluorouracil-Induced Apoptosis and Autophagy


    Eftekhar, Ebrahim; Jaberie, Hajar; Naghibalhossaini, Fakhraddin


    Understanding the mechanism of tumor resistance is critical for cancer therapy. In this study, we investigated the effect of carcinoembryonic antigen (CEA) overexpression on UV-and 5-fluorouracil (5-FU)-induced apoptosis and autophagy in colorectal cancer cells. We used histone deacetylase (HDAC) inhibitor, NaB and DNA demethylating agent, 5-azacytidine (5-AZA) to induce CEA expression in HT29/219 and SW742 colorectal cancer cell lines. MTT assay was used to measure IC50 value of the cells ex...

  17. A Rapid and Highly Selective Resonance Scattering Spectral Assay for Trace Carcinoembryonic Antigen

    Institute of Scientific and Technical Information of China (English)

    LI,Jian-Fu; JIANG,Zhi-Liang; DENG,An-Ping


    Gold nanoparticles, in size of 10 nm, were used to label monoclonal carcinoembryonic antigen antibody (CE-Aab) to obtain an immunonanogold resonance scattering (RS) spectral probe (AuCEAAb) for the measurement of trace carcinoembryonic antigen (CEA). In pH 6.8 Na2HPO4-NaH2PO4 buffer solution and the presence of polyeth-ylene glycol (PEG)-6000, the AuCEAAb combined with CEA to form the nanogold-labeled immunocomplex clus-ters in average size of 227 nm, which exhibited two scattering peaks at about 320 and 581 nm. The enhanced RS intensity at 581 nm (△I581 nm) is proportional to CEA concentration in the range of 1.0-50.0 ng/mL, with a detec-tion limit (DL) of 0.52 ng/mL. The immunonanogold RS assay was utilized to determine CEA in serum samples with high sensitivity, good selectivity and simplicity.

  18. Immunoradiometric assay for carcinoembryonic antigen using avidin—biotin separation technique

    Institute of Scientific and Technical Information of China (English)

    SONGShiping; TANGGuozhong; 等


    A sensitive,specific,noncompetitive,sandwich-type radioimmunoassay for carcinoembryonic antigen(CEA) has been developed in our laboratory,which can be performed conveniently.The assay involves two monoclonal antibodies,selected for high affinity and specificity and also for reaction against antigenic sites on CEA that are distal from each other.One of these antibodies was labeled with 125I and the other was conjugated covalently to biotin.Polystyrene tubes were conjugated covalently to avidin.These tubes represent a rapid,simple method for separating the CEA-bound antibody from the free antibody.The biotin-antibody-CEA-125I-labeled antibody complexes bind to the tubes and CEA concentration is driectly related to counts per minute.This assay can detect the CEA at a concentrastion of 0.22μg/L in serum.

  19. An electrochemical immunosensor for carcinoembryonic antigen enhanced by self-assembled nanogold coatings on magnetic particles. (United States)

    Li, Jianping; Gao, Huiling; Chen, Zhiqiang; Wei, Xiaoping; Yang, Catherine F


    A quick and reproducible electrochemical-based immunosensor technique, using magnetic core/shell particles that are coated with self-assembled multilayer of nanogold, has been developed. Magnetic particles that are structured from Au/Fe(3)O(4) core-shells were prepared and aminated after a reaction between gold and thiourea, and additional multilayered coatings of gold nanoparticles were assembled on the surface of the core/shell particles. The carcinoembryonic antibody (anti-CEA) was immobilized on the modified magnetic particles, which were then attached on the surface of solid paraffin carbon paste electrode (SPCE) by an external magnetic field. This is an assembly of a novel immuno biosensor for carcinoembryonic antigen (CEA). The sensitivity and response features of this immunoassay are significantly affected by the surface area and the biological compatibility of the multilayered nanogold. The linear range for the detection of CEA was from 0.005 to 50 ng mL(-1) and the limit of detection (LOD) was 0.001 ng mL(-1). The LOD is approximately 500 times more sensitive than that of the traditional enzyme-linked immunosorbent assay for CEA detection.

  20. A novel prognostic index in colorectal cancer defined by serum carcinoembryonic antigen and plasma tissue inhibitor of metalloproteinases-1

    DEFF Research Database (Denmark)

    Nielsen, Hans J.; Christensen, Ib J.; Brunner, Nils


    The introduction of stage-independent prognostic markers may play a significant role in future selection for adjuvant treatment for early-stage colorectal cancer (CRC). The purpose of this study was to assess the combination of preoperative serum carcinoembryonic antigen (CEA) and plasma tissue i...

  1. High expression of carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 6 and 8 in primary myelofibrosis

    DEFF Research Database (Denmark)

    Hasselbalch, Hans Carl; Skov, Vibe; Larsen, Thomas Stauffer;


    for the egress of CD34+ cells from the bone marrow. Carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 6 has been implicated in cell adhesion, cellular invasiveness, angiogenesis, and inflammation, which are all key processes in the pathophysiology of PMF. Accordingly, CEACAMs may play an important...

  2.  Human carcinoembryonic antygen family proteins, structure and function

    Directory of Open Access Journals (Sweden)

    Hanna Czepczyńska-Krężel


    Full Text Available  The CEA related cell adhesion molecules (CEACAM contain variable and constant immunoglobulin-like domains and are classified as a member of the immunoglobulin supergene family, IgSF. The seven CEACAM (CD66 antigens (CEACAM1, CEACAM3, CEACAM4, CEA, CEACAM6, CEACAM7 and CEACAM8 differ in the number of Ig-like domains, sugar content, presence of isoforms, tissue distribution and form of membrane attachment (transmembrane region or GPI anchor. CEACAMs with a transmembrane region possess a cytoplasmic domain with or without the immunoreceptor motifs. The structural diversity of CEACAMs results in their multifunctionality, especially displayed in calcium independent homo- and heterotypic adhesion interactions. The scientific data, collected mainly for CEA, strongly confirm involvement of this molecule in colorectal cancer. Recent research also indicates that CEACAMs play an important role in signal transduction, recognition and binding of pathogenic bacteria belonging to Neisseria and Escherichia genera.

  3. Selection of DMA aptamer that specific binding human carcinoembryonic antigen in vitro

    Institute of Scientific and Technical Information of China (English)


    Objective:To select the specific aptamer of carcinoembryonic antigen (CEA), one of the most attractive molecule for cancer target therapy and imaging. Methods: Seven rounds in vitro selection were performed against the purified CEA protein. Ligand-mediated target purification and Co-immunoprecipitation were adopted to verify the specific binding of the aptamer to the purified and native protein separately. Results:The CEA-specific aptamer which can bind both the purified and native protein with the high specificity was obtained. Conclusion:This is the first time the CEA specific apatmer was produced. The results in this study provides the preliminary evidence for further investigation and application of CEA-aptamer in the future.

  4. Micro-plate magnetic chemiluminescence immunoassay and its applications in carcinoembryonic antigen analysis

    Institute of Scientific and Technical Information of China (English)


    A micro-plate magnetic chemiluminescence immunoassay was developed for rapid and high throughput detection of carcinoembryonic antigens (CEA) in human sera. This method was based on a sandwich immunoreaction of fluorescein isothiocyanate (FITC)-labeled anti-CEA antibodies, CEA antigens, and horseradish peroxidase (HRP)-conjugated anti-CEA antibodies in mi- cro-plate. The immunomagnetic particles coated with anti-FITC antibodies were used as the solid phase for the immunoassay. The separation procedure was carried out by a magnetic plate adaptor and the luminol-hydrogen peroxide (H2O2)-HRP system was employed for the chemiluminescence detection. The proposed method combined the advantages of the micro-plate reactor and magnetic particle separation technology with the linear range of 5-250 ng mL·1. The detection limit of CEA was 0.61 ng mL·1. The coefficient of the variation was less than 7% and 13% for intra-assay and inter-assay precision, respectively. Compared with the commercial micro-plate chemiluminescent kit, the proposed method showed a good correlation.

  5. Receptor-mediated endocytosis of carcinoembryonic antigen by rat liver Kupffer cells. (United States)

    Toth, C A; Thomas, P; Broitman, S A; Zamcheck, N


    In vivo, carcinoembryonic antigen (CEA) is removed from the circulation by the liver Kupffer cells. Immunologically identifiable CEA is transferred from these macrophages to the hepatocytes, where degradation is completed. Circulatory clearance of CEA is specific, rapid [t1/2 = 3.7 +/- 0.9 (S.D.) min], and saturable. In vitro, Kupffer cells take up CEA by a saturable process which is time/temperature dependent and colchicine sensitive. Isolated Kupffer cells endocytose CEA with an apparent Km of 6 X 10(-8) M. There are approximately 16,000 CEA binding sites per cell. Nonspecific cross-reacting antigen (NCA), a glycoprotein structurally similar to CEA, is recognized with lower affinity by the same receptor. Endocytosis is independent of the nonreducing terminal sugars on the molecule: CEA modified by Smith degradation inhibits Kupffer cell recognition of native CEA. Since performic acid oxidized CEA also inhibits endocytosis, receptor binding is similarly independent of intact protein conformation. Isolated Kupffer cells have mannose and/or N-acetyl glucosamine receptor activity but do not internalize CEA by that mechanism. Galactose-terminated glycoproteins impede CEA and NCA clearance in vivo but not Kupffer cell endocytosis in vitro. Radiolabeled CEA released from isolated Kupffer cells following endocytosis shows no apparent molecular weight change. However, the released CEA contains species with higher isoelectric points, suggesting that perhaps the removal of sialic acid and the resulting exposure of galactose residues mediate the subsequent transfer to the hepatocyte.

  6. 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;


    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...

  7. Electrochemical immunosensor based on nanoporpus gold loading thionine for carcinoembryonic antigen. (United States)

    Sun, Xiaobin; Ma, Zhanfang


    Nanoporous gold (NPG) has recently received considerable attention in analytical electrochemistry because of its good conductivity and large specific surface area. A facile layer-by-layer assembly technique fabricated NPG was used to construct an electrochemical immunosensor for carcinoembryonic antigen (CEA). NPG was fabricated on glassy carbon (GC) electrode by alternatively assembling gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) using 1,4-benzenedimethanethiol as a cross-linker, and then AgNPs were dissolved with HNO3. The thionine was absorbed into the NPG and then gold nanostructure was electrodeposited on the surface through the electrochemical reduction of gold chloride tetrahydrate (HAuCl4). The anti-CEA was directly adsorbed on gold nanostructure fixed on the GC electrode. The linear range of the immunosensor was from 10 pg mL(-1) to 100 ng mL(-1) with a detection limit of 3 pg mL(-1) (S/N=3). The proposed immunosensor has high sensitivity, wide linear range, low detection limit, and good selectivity. The present method could be widely applied to construct other immunosensors.

  8. Peritoneal lavage cytology and carcinoembryonic antigen determination in predicting peritoneal metastasis and prognosis of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Ji-Kun Li; Miao Zheng; Chuan-Wen Miao; Jian-Hai Zhang; Guang-Han Ding; Wen-Shen Wu


    AIM: To evaluate the role of peritoneal lavage cytology (PLC) and carcinoembryonic antigen (CEA) determination of peritoneal washes (pCEA) in predicting the peritoneal metastasis and prognosis after curative resection of gastric cancer.METHODS: PLC and radioimmunoassay of CEA were performed in peritoneal washes from 64 patients with gastric cancer and 8 patients with benign diseases.RESULTS: The positive rate of pCEA (40.6%) was significantly higher than that of PLC (23.4%) (P<0.05).The positive rates of PLC and pCEA correlated with the depth of tumor invasion and lymph node metastasis (P<0.05). pCEA was found to have a higher sensitivity and a lower false-positive rate in predicting peritoneal metastasis after curative resection of gastric cancer as compared to PLC. The 1-, 3-, and 5-year survival rates of patients with positive cytologic findings or positive pCEA results were significantly lower than those of patients with negative cytologic findings or negative pCEA results (P<0.05). Multivariate analysis indicated that pCEA was an independent prognostic factor for the survival of patients with gastric cancer.CONCLUSION: Intraoperative pCEA is a more sensitive and reliable predictor of peritoneal metastasis as well as prognosis in patients with gastric cancer as compared to PLC method.

  9. Transcription Activity of Ectogenic Human Carcinoembryonic Antigen Promoter in Lung Adenocarcinoma Cells A549

    Institute of Scientific and Technical Information of China (English)

    XIONG Weining; FANG Huijuan; XU Yongjian; XIONG Shendao; CAO Yong; SONG Qingfeng; ZENG Daxiong; ZHANG Huilan


    The transcription activity of ectogenic human carcinoembryonic antigen (CEA) promoter in lung adenocarcinoma cells A549 was investigated for the further gene-targeting therapy. The reporter gene green fluorescent protein (GFP) driven by CEA promoter and human cytomegalovirus (CMV) promoter were relatively constructed and named plasmid pCEA-EGFP and pCMV-GFP respectively. The intensity of fluorescence was detected by fluorescence microscope and flow cytometry analysis after the pCEA-GFP and pSNAV-GFP plasmids were transfected into A549 cells through liposome respectively. The results showed (4.08±0.63) % of the A549 cells transfected with pCEA-AFP plasmid expressed, significantly lower than that of the A549 cells transfected with pCMV-GFP [(43.27±3.54) %]. It was suggested that ectogenic human CEA promoter in lung adenocarcinoma cells A549 was weakly expressed. The distinct specificity of CEA promoter in CEA high expression cells was regarded as a tool in selective gene therapy, but the transcription activity of ectogenic human CEA promoter was needed to increase in the future.

  10. Normal carcinoembryonic antigen indicates benefit from perioperative chemotherapy to gastric carcinoma patients

    Institute of Scientific and Technical Information of China (English)

    Shi Chen; Ying-Bo Chen; Yuan-Fang Li; Xing-Yu Feng; Zhi-Wei Zhou; Xiu-Hong Yuan; Chao-Nan Qian


    AIM:To evaluate pretreatment serum carcinoembryonic antigen (CEA) as a predictor of survival for patients with locally advanced gastric cancer receiving perioperative chemotherapy.METHODS:We retrospectively studied a cohort of 228gastric cancer patients who underwent D2 gastrectomy combined with chemotherapy at the Sun Yat-sen University Cancer Center between January 2005 and December 2009.Among them,168 patients received 6-12 cycles of oxaliplatin-based adjuvant (post-operative) chemotherapy,while 60 received perioperative chemotherapy (2 cycles of FOLFOX6 or XELOX before surgery and 4-10 cycles after surgery).Serum CEA was measured using an enzyme immunoassay.The followup lasted until December 2010.RESULTS:In the group that had elevated serum CEA,the difference in survival time between patients receiving perioperative chemotherapy and those receiving adjuvant chemotherapy had no statistical significance (P >0.05).However,in the group that had normal serum CEA,patients receiving perioperative chemotherapy had a longer survival time.In multivariate analysis,T staging and lymph node metastatic rate were independent prognostic factors for the patients.Perioperative chemotherapy improved the overall survival of patients who had a normal pretreatment CEA level (P =0.070).CONCLUSION:Normal pretreatment serum CEA is a predictor of survival for patients receiving perioperative chemotherapy.

  11. Carcinoembryonic antigen-producing adrenal adenoma resected using combined lateral and anterior transperitoneal laparoscopic surgery

    Institute of Scientific and Technical Information of China (English)


    A 74-year-old woman presented with symptoms consistent with hyperadrenocorticism and hyperca techolaminism. She had a cushingoid appearance and her cortisol level was elevated. Herserum dopamine and noradrenalin levels were also elevated.Computed tomography detected a left adrenal mass measuring 3.5 cm × 3.0 cm in diameter. Metaiodobenzylguanidine cintigraphy was negative. Unexpectedly, the serum Serum carcinoembryonic antigen (CEA) level was elevated.Fluorodeoxyglucose positron emission tomography showed increased uptake in the adrenal tumor only, with a maximum standardized uptake value of 2.8. Selective venography and blood sampling revealed that the concentrations of cortisol, catecholamines and CEA were significantly elevated in the vein draining the tumor. A diagnosis of CEA-produdng benign adenoma was made. After preoperative management, we performed a combined lateral and anterior transperitoneal laparoscopic adrenectomy. Her vital signs remained stable during surgery. Histopathological examination revealed a benign adenoma. Her cortisol, catecholamine and CEA levels normalized immediately after surgery. We present, to the best of our knowledge, the first case of CEA-roducin gadrenal adenoma, along with a review of the relevant literature, and discuss our laparoscopic surgery techniques.

  12. Tissue Carcinoembryonic Antigen, Calcium, Copper and Iron Levels in Cancerous Lung Patients

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    Nasar Yousuf ALWAHAIBI


    Full Text Available Background and objective The expression of various trace elements and markers in lung cancer is controversial. The aim of this study is to evaluate the presence of calcium (Ca, copper (Cu, iron (Fe and carcinoembryonic antigen (CEA in cancerous untreated lung tissues and to determine a possible association between these markers and lung cancer. Methods Fourty-eight cancerous lung tissue blocks, from Sultan Qaboos University Hospital, Sultanate of Oman, were studied. Fe, Ca, Cu, and CEA were demonstrated in the tissue blocks using Perl's Prussian blue, Von Kossa's, modified rhodanine and immunohistochemical staining methods, respectively. Results Twenty-three of 48 specimens showed positive Fe staining, 2 showed positive Ca staining and Cu was absent in all specimens. 93.7% expressed CEA in varying degree of positivity. 81.25% of these sections showed high expression of CEA. Conclusion Tissue concentrations of trace elements were not elevated in lung cancer and therefore cannot be considered as a potential marker. Despite the low sensitivity and specificity of CEA as previously reported, tissue CEA should be considered as a potential marker in the evaluation of lung cancer.

  13. Tissue Carcinoembryonic Antigen, Calcium, Copper and Iron Levels in Cancerous Lung Patients

    Institute of Scientific and Technical Information of China (English)

    Nasar Yousuf ALWAHAIBI; Jokha Sultan ALGHARIBI; Amna Salim ALSHUKAILI; Ahmed Khalifa ALSHUKAILI


    Background and objective The expression of various trace elements and markers in lung cancer is controversial. The aim of this study is to evaluate the presence of calcium (Ca), copper (Cu), iron (Fe) and carcinoembryonic antigen (CEA) in cancerous untreated lung tissues and to determine a possible association between these markers and lung cancer.Methods Fourty-eight cancerous lung tissue blocks, from Sultan Qaboos University Hospital, Sultanate of Oman, were studied. Fe, Ca, Cu, and CEA were demonstrated in the tissue blocks using Perl's Prussian blue, Von Kossa's, modified rhodanine and immunohistochemical staining methods, respectively.Results Twenty-three of 48 specimens showed positive Fe staining, 2 showed positive Ca staining and Cu was absent in all specimens. 93.7% expressed CEA in varying degree of positivity. 81.25% of these sections showed high expression of CEA. Conclusion Tissue concentrations of trace elements were not elevated in lung cancer and therefore cannot be considered as a potential marker. Despite the low sensitivity and specificity of CEA as previously reported, tissue CEA should be considered as a potential marker in the evaluation of lung cancer.

  14. Serum carcinoembryonic antigen as a tumour marker in patients with endometrial cancer (United States)

    Hashiguchi, Y.; Kasai, M.; Fukuda, T.; Ichimura, T.; Yasui, T.; Sumi, T.


    Background No potential tumour markers have been validated for prognosis in endometrial cancer. However, carcinoembryonic antigen (cea) is one of the most widely used tumour markers in various types of cancer. Although cea expression in endometrial cancer has been investigated, its prognostic value remains controversial, and no studies have investigated serum cea levels in large case series. In the present study, we investigated diagnostic and prognostic applications of serum cea for endometrial cancer. Methods This prospective study was approved by our Institutional Review Board. Between January 2006 and December 2012, serum cea was measured prospectively in 215 patients with endometrial cancer and was subsequently measured during treatment and at scheduled follow-up examinations in patients with elevated baseline serum cea. Results During the study period, 215 patients (142 stage i, 19 stage ii, 32 stage iii, 22 stage iv) were treated for endometrial cancer. By the time of last follow-up, 52 had relapsed (24.2%), and the median follow-up duration was 45 months (range: 1–95 months). Elevated serum cea was identified in 25 patients (11.6%) and was associated with histologic type (p = 0.04), histologic grade (p = 0.03), and myometrial invasion depth (p = 0.01). Elevated serum cea was not related to clinical stage, lymph node metastasis, distant metastasis, age, menopausal status, or body mass index. Relapse of disease was related to elevated serum cea (p = 0.006). Conclusions Serum cea is a potential prognostic indicator for endometrial cancer. PMID:27803603

  15. Synuclein gamma predicts poor clinical outcome in colon cancer with normal levels of carcinoembryonic antigen

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    Xing Xiaofang


    Full Text Available Abstract Background Synuclein gamma (SNCG, initially identified as a breast cancer specific gene, is aberrantly expressed in many different malignant tumors but rarely expressed in matched nonneoplastic adjacent tissues. In this study, we investigated the prognostic potential of SNCG in colon cancer particularly in the patients with normal carcinoembryonic antigen (CEA levels. Methods SNCG levels were assessed immunohistochemically in cancer tissues from 229 colon adenocarcinoma patients with a mean follow-up of 44 months. Correlations between SNCG levels and clinicopathologic features, preoperative serum CEA level, and clinical outcome were analyzed statistically using SPSS. Results SNCG levels in colon adenocarcinoma were closely associated with intravascular embolus and tumor recurrence but independent of preoperative serum CEA levels. SNCG expression was an independent prognostic factor of a shorter disease-free survival (DFS and overall survival (OS (P P = 0.001, P = 0.001, 0.002 for 97 patients with normal preoperative serum CEA level. Conclusions Our results suggest for the first time that SNCG is a new independent predicator for poor prognosis in patients with colon adenocarcinoma, including those with normal CEA levels. Combination of CEA with SNCG improves prognostic evaluation for patients with colon adenocarcinoma.

  16. Construction, Expression and Characterization of a Chimeric Protein Targeting Carcinoembryonic Antigen in Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    LI Yang; HUA Shu-cheng; MA Cheng-yuan; YU Zhen-xiang; XU Li-jun; LI Dan; SUN Li-li; LI Xiao; PENG Li-ping


    The carcinoembryonic antigen(CEA) is an oncofetal glycoprotein known as an important clinical tumor marker and is overexpressed in several types of tumors, including colorectal and lung carcinomas. We constructed a chimeric protein that exhibits both specific binding and immune stimulating activities, by fusing staphylococcal enterotoxin A(SEA) to the C-terminus of an anti-CEA single-chain disulfide-stabilized Fv(scdsFv) antibody (single-chain-C-terminus/SEA, SC-C/SEA). The SC-C/SEA protein was expressed in Escherichia coli(E. coli), refolded, and purified on an immobilized Ni2+ affinity chromatography column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE) and Western blot analysis reveal that the target protein was expressed sufficiently. We used immunofluorescence assays to demonstrate that SC-C/SEA could bind specifically to human lung carcinoma cells(A549), but almost human uterine cervix cells(HeLa). We also used the L-lactate dehydrogenase(LDH) release assay to show that SC-C/SEA elicits a strong A549 tumor-specific cytotoxic T lymphocyte(CTL) response in vitro. The results suggest that SC-C/SEA shows specific activity against CEA-positive cells and has potential application in CEA-targeted cancer immunotherapy.

  17. Carcinoembryonic Antigen Expression and Resistance to Radiation and 5-Fluorouracil-Induced Apoptosis and Autophagy. (United States)

    Eftekhar, Ebrahim; Jaberie, Hajar; Naghibalhossaini, Fakhraddin


    Understanding the mechanism of tumor resistance is critical for cancer therapy. In this study, we investigated the effect of carcinoembryonic antigen (CEA) overexpression on UV-and 5-fluorouracil (5-FU)-induced apoptosis and autophagy in colorectal cancer cells. We used histone deacetylase (HDAC) inhibitor, NaB and DNA demethylating agent, 5-azacytidine (5-AZA) to induce CEA expression in HT29/219 and SW742 colorectal cancer cell lines. MTT assay was used to measure IC50 value of the cells exposed to graded concentrations of 5- FU with either 0.1 mM NaB or 1 μM 5-AZA for 72 h . Using CHO- and SW742-CEA transfectants, we also investigated the effect of CEA expression on UV- and 5-FU-induced apoptosis and autophagy. Treatment of HT29/219 cell line with NaB and 5-AZA increased CEA expression by 29% and 31%, respectively. Compared with control cells, the IC50 value for 5-FU of NaB and 5-AZA-treated cells increased by 40% and 57%, respectively. Treatment of SW742 cells with NaB or 5-AZA increased neither CEA expression nor the IC50 value for 5-FU. In comparison to parental cells, CEA expression also significantly protected transfected cells against UV-induced apoptosis. Decreased proportions of autophagy and apoptosis were also observed in 5-FU treated SW742- and CHO-CEA transfectants. We conclude that CEA expression can effectively protect colorectal cancer cells against radiation and drug-induced apoptosis and autophagy.

  18. Biliary carcinoembryonic antigen levels in diagnosis of occult hepatic metastases from colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jaques Waisberg; Rog(e)rio T. Palma; Lu(i)s Contim Neto; Lourdes C. Martins; Maur(i)cio S. L. Oliveira; Carlos A. Nagashima; Antonio C. Godoy; Fabio S. Goffi


    AIM: To prospectively explore the role of carcinoembryonic antigen (CEA) in gallbladder bile in patients with colorectal carcinoma and the morphological and clinical features of neoplasia and the occurrence of hepatic metastases.METHODS: CEA levels in the gallbladder and peripheral blood were studied in 44 patients with colorectal carcinoma and 10 patients with uncomplicated cholelithiasis. CEA samples were collected from the gallbladder bile and peripheral blood during the operation, immediately before extirpating the colorectal neoplasia or cholecystectomy.Values of up to 5 ng/ml were considered normal for bile and serum CEA.RESULTS: In the 44 patients with colorectal carcinoma who underwent operation with curative intent, the average level of serum CEA was 8.5 ng/ml (range: 0.1 to 111.0 ng/ml) and for bile CEA it was 74.5 ng/ml (range: 0.2 to 571.0ng/ml). In the patients with uncomplicated cholelithiasis who underwent cholecystectomy, the average level of serum CEA was 1.9 ng/ml (range: 1.0 to 3.5 ng/ml) and for bile CEA it was 1.2 ng/ml (range: 0.3 to 2.9 ng/ml).The average duration of follow-up time was 16.5 months (range: 6 to 48 months). Four patients who underwent extirpation of the colorectal carcinoma without evidence of hepatic metastasis and with an average bile CEA value of 213.2 ng/ml presented hepatic metastases between three and seventeen months after removal of the primary colorectal neoplasia. Three of them successfully underwent extirpation of the hepatic lesions.CONCLUSION: High CEA levels in gallbladders of patients undergoing curative operation for colorectal carcinoma may indicate the presence of hepatic metastases. Such patients must be followed up with special attention to the diagnosis of such lesions.

  19. Construction of humanized carcinoembryonic antigen specific single chain variable fragment and mitomycin conjugate

    Institute of Scientific and Technical Information of China (English)


    AIM: To construct a new target-oriented conjugate of humanized carcinoembryonic antigen (CEA) specific single chain variable fragment (scFv) and mitomycin (MMC) against colorectal cancer, and to investigate its influence on the growth and apoptosis of colorectal cancer cells.METHODS: The primer was designed according to the gene sequence described in reference 16, which respectively contains restriction enzyme cleavage sites BamH Ⅰ and EcoR Ⅰ in its upstream and downstream.PCR was performed with the plasmid as template containing genes of humanized anti-CEA scFv. The product was digested by BamH Ⅰ and EcoR Ⅰ, and connected to an expression vector which also has the restriction enzyme cleavage sites BamH Ⅰ and EcoR.Expression of the reaction was induced by isopropy-β-D-thiogalactoside (IPTG). Then the expression product was covalently coupled with MMC by dextran T-40. The immunoreactivity of the conjugate against colorectal cancer cells as well as CEA was measured by enzyme linked immunosorbent assay (ELISA). The inhibiting ratio of conjugate on the growth of colorectal cancer cells was also measured by ELISA. The effect of conjugate on the apoptosis of colorectal cancer cells was determined by flow cytometry (FCM).RESULTS: Restriction endonuclease cleavage and gene sequencing confirmed that the expression vector was successfully constructed. Sodium dodecyl sulfate polyacrylamide gel electropheresis (SDS-VAGE) confirmed that this vector correctly expressed the fusion protein.ELISA confirmed that the conjugate had quite a strong immunoreactivity against colorectal cancer cells and CEA. The conjugate had inhibitory effects on colorectal cancer cells in a concentration-dependent manner and could induce apoptosis of colorectal cancer cells in a concentration-dependent manner.CONCLUSION: The CEA-scFv-MMC conjugate can be successfully constructed and is able to inhibit the growth and induce apoptosis of colorectal cancer cells.

  20. Luminol/antibody labeled gold nanoparticles for chemiluminescence immunoassay of carcinoembryonic antigen

    Energy Technology Data Exchange (ETDEWEB)

    Yang Xiaoyan, E-mail: [Key Laboratory of Eco-chemical Engineering, Ministry of Education, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042 (China); Guo Yingshu; Wang Aiguo [Key Laboratory of Eco-chemical Engineering, Ministry of Education, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042 (China)


    A facile strategy by loading luminol and secondary antibody on gold nanoparticles (Au NPs) was described in the present work. The as-prepared luminol/antibody labeled Au NPs conjugates (LAAu NPs) were used as the chemiluminescent probe for the detection of carcinoembryonic antigen (CEA) in serum. The LAAu NPs were characterized by transmission electron microscopy (TEM), UV-vis spectrophotometry (UV-vis), and chemiluminescent method. Stable and efficient chemiluminescence (CL) was obtained when luminol molecules and secondary antibodies were coimmobilized on the Au NPs by using hydrogen peroxide (H{sub 2}O{sub 2}) as an oxidant, horseradish peroxidase (HRP) as a catalyst, and 4-(4'-iodo)phenylphenol (IPP) as an enhancer. The LAAu NPs were further evaluated via a sandwich-type CL immunoassay of CEA in serum. In this protocol, the CEA analyte was captured by the primary antibody immobilized on the surface of magnetic beads, and then was sandwiched by the secondary antibody loaded on luminol-labeled Au NPs. The chemiluminescent intensity was proportional to the concentration of CEA over the range of 5.0 x 10{sup -10} to 5.0 x 10{sup -8} g mL{sup -1} and 5.0 x 10{sup -9} to 2.0 x 10{sup -8} g mL{sup -1} by using HRP and Co{sup 2+} as catalysts, respectively. The present chemiluminescent immunoassay based on the luminol/antibody labeled Au NPs conjugates has offered great promise for simple, highly biocompatible, and cost-effective analysis of biological samples.

  1. A Sandwich Electrochemical Immunosensor Using Magnetic DNA Nanoprobes for Carcinoembryonic Antigen

    Directory of Open Access Journals (Sweden)

    Ning Gan


    Full Text Available A novel magnetic nanoparticle-based electrochemical immunoassay of carcinoembryonic antigen (CEA was designed as a model using CEA antibody-functionalized magnetic beads [DNA/Fe3O4/ZrO2; Fe3O4 (core/ZrO2 (shell nano particles (ZMPs] as immunosensing probes. To design the immunoassay, the CEA antibody and O-phenylenediamine (OPD were initially immobilized on a chitosan/nano gold composite membrane on a glassy carbon electrode (GCE/CS-nano Au, which was used for CEA recognition. Then, horseradish peroxidase (HRP-labeled anti-CEA antibodies (HRP-CEA Ab2 were bound to the surface of the synthesized magnetic ZMP nanoparticles as signal tag. Thus, the sandwich-type immune complex could be formed between secondary antibody (Ab2 modified DNA/ZMPs nanochains tagged by HRP and GCE/CS-nano Au. Unlike conventional nanoparticle-based electrochemical immunoassays, the recognition elements of this immunoassay included both electron mediators and enzyme labels, which obviously simplifies the electrochemical measurement process. The sandwich-type immunoassay format was used for online formation of the immunocomplex of CEA captured in the detection cell with an external magnet. The electrochemical signals derived from HRP during the reduction of H2O2 with OPD as electron mediator were measured. The method displayed a high sensitivity for CEA detection in the range of 0.008–200 ng/mL, with a detection limit of 5 pg/mL (estimated at a signal-to-noise ratio of 3. The precision, reproducibility, and stability of the immunoassay were good. The use of the assay was evaluated with clinical serum samples, and the results were in excellent accordance with those obtained using the standard enzyme-linked immunosorbent assay (ELISA method. Thus, the magnetic nanoparticle-based assay format is a promising approach for clinical applications, and it could be further developed for the detection of other biomarkers in cancer diagnosis.

  2. Association between carcinoembryonic antigen, carbohydrate antigen 19-9 and body mass index in colorectal cancer patients. (United States)

    Chen, Wei; Liu, Qin; Tan, Shu-Yun; Jiang, Yan-Hui


    Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been well recognized as tumor markers for colorectal cancer. Previous studies suggested that obesity is inversely associated with the screening of CEA and CA19-9 levels and may reduce screening sensitivity. This study was conducted to evaluate the association of body mass index (BMI) with serum CEA and CA19-9 concentration in colorectal cancer patients. A total of 300 patients were enrolled in the study, selected from 2,950 consecutive colorectal cancer patients who underwent surgical treatment between August, 1994 and December, 2005. The association of BMI with CEA concentration, total circulating CEA mass and plasma volume was assessed by determining P-values for trends. The multivariate linear regression analysis was used to adjust for clinicopathological confounding factors to analyze the main outcome measures when CEA and CA19-9 had been log-transformed. Increased BMI was linearly correlated with a higher plasma volume. Using the stepwise method, the multiple regression model including BMI categories was reconstructed as follows: loge[CEA]=0.208+0.241[liver metastasis]+0.051 [differentiation]+0.092[TNM]; loge[CA19-9]=0.969+0.233 [gender]+0.141[ascites]+0.09[TNM]. The mean survival time in CEA(+)/CA19-9(-), CEA(+)/CA19-9(+), CEA(-)/CA19-9(-) and CEA(-)/CA19-9(+) patients was 84.8, 58.2, 100.6 and 74.7 months, respectively. The 1-/3-year survival rates in each group was 76.0/59.8, 66.2/43.5, 96.3/87.6 and 71.7/41.0, respectively. In conclusion, the decreased concentration of CEA and CA19-9 in patients of higher BMIs may be the result of the hemodilution effect. The BMI factor should be considered during the surveillance of colorectal cancer. In addition, patients with simultaneous positive expression of CEA and CA19-9 exhibited shorter survival time.

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

    Institute of Scientific and Technical Information of China (English)

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


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

  4. Carcino-embryonic antigen in monitoring the growth of human colon adenocarcinoma tumour cells SK-CO-1 and HT-29 in vitro and in nude mice

    DEFF Research Database (Denmark)

    Sölétormos, G; Fogh, J M; Sehested-Hansen, B;


    A set of experimental model systems were designed to investigate (a) the inter-relationship between growth of two human cancer cell lines (SK-CO-1, HT-29) and carcino-embryonic antigen (CEA) kinetics; and (b) whether neoplastic growth or CEA concentration is modulated by human growth hormone (h...

  5. Tumor Expression of the Carcinoembryonic Antigen Correlates with High Mitotic Activity and Cell Pleomorphism Index in Lung Carcinoma

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    Rancés Blanco


    Full Text Available At present, some research efforts are focusing on the evaluation of a variety of tumor associated antigens (TAAs for a better understanding of tumor biology and genetics of lung tumors. For this reason, we evaluated the tissue expression of carcinoembryonic antigen (CEA and ior C2 (a cell surface O-linked glycoprotein carbohydrate chain TAA in lung carcinomas, as well as its correlation with a variety of clinicopathological features. The tissue expression of CEA was evidenced in 22/43 (51.16% lung carcinomas and it was correlated with mitotic activity, cell pleomorphism indexes, and age of patients. The expression of ior C2 was observed in 15/43 (34.88% tumors but no correlation with the clinicopathological features mentioned above was obtained. No correlation between both CEA and ior C2 antigens expression and the overall survival (OS of non-small-cell lung cancer patients was also observed. However, CEA-negative patients displayed higher OS rates as compared with positive ones (69.74 versus 58.26 months. Our results seem to be in agreement with the role of CEA expression in tumor cell proliferation, inhibition of cell polarizations and tissue architecture distortion. The significance of ior C2 antigen in these malignancies and it potential use in diagnosis, prognosis, and/or immunotherapy must be reevaluated.

  6. Anti-colorectal cancer effect of interleukin-2 and interferon-β fusion gene driven by carcinoembryonic antigen promoter

    Directory of Open Access Journals (Sweden)

    Wang Y


    Full Text Available Yan Wang, Mengchun Wang, Yan LiDepartment of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaAbstract: This study was designed to investigate the antitumor effects of combined interleukin-2/interferon-β-based gene therapy in colorectal cancer. Transfection of the fusion gene expression plasmid induced significant apoptosis of Lovo cells. Additionally, the fusion gene exhibited strong inhibitory activity against tumor growth and apoptosis when being injected into the nude mice implanted with human colon cancer cells. Furthermore, the tail-vein injection showed a more notable effect than direct injection into tumor. These results suggest that the combined interleukin-2/interferon-β-based gene therapy with the carcinoembryonic antigen promoter might be an effective antitumor strategy.Keywords: apoptosis, interferon-β, interleukin-2, antitumor, combined gene therapy

  7. A novel label-free microfluidic paper-based immunosensor for highly sensitive electrochemical detection of carcinoembryonic antigen. (United States)

    Wang, Yang; Xu, Huiren; Luo, Jinping; Liu, Juntao; Wang, Li; Fan, Yan; Yan, Shi; Yang, Yue; Cai, Xinxia


    In this work, a highly sensitive label-free paper-based electrochemical immunosensor employing screen-printed working electrode (SPWE) for detection of carcinoembryonic antigen (CEA) was fabricated. In order to raise the detection sensitivity and immobilize anti-CEA, amino functional graphene (NH2-G)/thionine (Thi)/gold nanoparticles (AuNPs) nanocomposites were synthesized and coated on SPWE. The principle of the immunosensor determination was based on the fact that the decreased response currents of Thi were proportional to the concentrations of corresponding antigens due to the formation of antibody-antigen immunocomplex. Experimental results revealed that the immunoassay enabled the determination of standard CEA solutions with linear working ranges of 50pgmL(-1) to 500ngmL(-1), the limit of detections for CEA is 10pgmL(-1) (S/N=3) and its corresponding correlation coefficients were 0.996. Furthermore, the proposed immunosensor could be used for the determination of clinical serum samples. A large number of clinical serum samples were detected and the relative errors between measured values and reference concentrations were calculated. Results showed that this novel paper-based electrochemical immunosensor could provide a new platform for low cost, sensitive, specific, and point-of-care diagnosis in cancer detection.

  8. Carcinoembryonic antigen (CEA)-based cancer vaccines: recent patents and antitumor effects from experimental models to clinical trials. (United States)

    Turriziani, Mario; Fantini, Massimo; Benvenuto, Monica; Izzi, Valerio; Masuelli, Laura; Sacchetti, Pamela; Modesti, Andrea; Bei, Roberto


    Carcinoembryonic antigen (CEA), a glycosylated protein of MW 180 kDa, is overexpressed in a wide range of human carcinomas, including colorectal, gastric, pancreatic, non-small cell lung and breast carcinomas. Accordingly, CEA is one of several oncofetal antigens that may serve as a target for active anti-cancer specific immunotherapy. Experimental results obtained by employing animal models have supported the design of clinical trials using a CEA-based vaccine for the treatment of different types of human cancers. This review reports findings from experimental models and clinical evidence on the use of a CEA-based vaccine for the treatment of cancer patients. Among the diverse CEA-based cancer vaccines, DCs- and recombinant viruses-based vaccines seem the most valid. However, although vaccination was shown to induce a strong immune response to CEA, resulting in a delay in tumor progression and prolonged survival in some cancer patients, it failed to eradicate the tumor in most cases, owing partly to the negative effect exerted by the tumor microenvironment on immune response. Thus, in order to develop more efficient and effective cancer vaccines, it is necessary to design new clinical trials combining cancer vaccines with chemotherapy, radiotherapy and drugs which target those factors responsible for immunosuppression of immune cells. This review also discusses relevant patents relating to the use of CEA as a cancer vaccine.

  9. A network signal amplification strategy of ultrasensitive photoelectrochemical immunosensing carcinoembryonic antigen based on CdSe/melamine network as label. (United States)

    Li, Jiaojiao; Zhang, Yong; Kuang, Xuan; Wang, Zhiling; Wei, Qin


    Taking advantage of CdSe/melamine network as label and Au-TiO2 as substrate, this work developed a novel kind of signal amplification strategy for fabricating photoelectrochemical (PEC) immunoassay. The melamine, a star-shaped triamino molecule, was firstly used for readily capturing CdSe QDs and forming a CdSe/melamine network, which was formed through strong interactions between the carboxyl groups of TGA-stabilized CdSe QDs and the three amino groups of each melamine molecule. In this strategy, the primary antibody (Ab1) was immobilized onto Au-TiO2 substrate, which made the photoelectric conversion efficiency increase significantly. After the formed Ab2-CdSe/melamine network labels were captured onto the electrode surface via the specific antibody-antigen interaction, the photoelectric activity could be further enhanced via the interaction between the Au-TiO2 substrate and CdSe/melamine network. Due to this amplification of PEC signals and the special structure of the label, the fabricated PEC immunosensor was applied for sensitive and specific detection of cancer biomarker carcinoembryonic antigen (CEA), and displayed a wide linear range (0.005-1000ngmL(-1)) and low detection limit (5pgmL(-1)). In addition, the immunosensor was performed with good stability and reproducibility, and the results to analyze human serum samples were satisfactory.

  10. Carcinoembryonic antigen-related cell adhesion molecules (CEACAM 1, 5 and 6 as biomarkers in pancreatic cancer.

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    Florian Gebauer

    Full Text Available BACKGROUND: Aim of this study was to assess the biological function in tumor progression and metastatic process carcinoembryonic antigen-related cell adhesion molecules (CEACAM 1, 5 and 6 in pancreatic adenocarcinoma (PDAC. EXPERIMENTAL DESIGN: CEACAM knock down cells were established and assessed in vitro and in a subcutaneous and intraperitoneal mouse xenograft model. Tissue and serum expression of patients with PDAC were assessed by immunohistochemistry (IHC and by enzyme linked immunosorbent assays. RESULTS: Presence of lymph node metastasis was correlated with CEACAM 5 and 6 expression (determined by IHC and tumor recurrence exclusively with CEACAM 6. Patients with CEACAM 5 and 6 expression showed a significantly shortened OS in Kaplan-Meier survival analyses. Elevated CEACAM6 serum values showed a correlation with distant metastasis and. Survival analysis revealed a prolonged OS for patients with low serum CEACAM 1 values. In vitro proliferation and migration capacity was increased in CEACAM knock down PDAC cells, however, mice inoculated with CEACAM knock down cells showed a prolonged overall-survival (OS. The number of spontaneous pulmonary metastasis was increased in the CEACAM knock down group. CONCLUSION: The effects mediated by CEACAM expression in PDAC are complex, though overexpression is correlated with loco-regional aggressive tumor growth. However, loss of CEACAM can be considered as a part of epithelial-mesenchymal transition and is therefore of rather importance in the process of distant metastasis.

  11. Comparison between tissue and serum content of CA 125, CA 19-9, and carcinoembryonic antigen in ovarian tumors. (United States)

    Breitenecker, G; Neunteufel, W; Bieglmayer, C; Kölbl, H; Schieder, K


    Tumor markers CA 125, CA 19-9, and carcinoembryonic antigen (CEA) were detected by immunohistochemistry in paraffin embedded tissue samples obtained from two different locations in 35 ovarian tumors. In addition, serum concentrations of these tumor markers were measured before cytoreductive surgery. The staining reaction was heterogeneous in different parts of the tumor as well as within the parenchyma. Of the marker positive tumors, a staining reaction was observed in both tissue samples in only 10 of 22 cases for CA 125, in eight of 13 cases for CEA, and in three of eight cases for CA 19-9. Eighty-one percent of the patients whose tumor was positive for CA 125 also showed elevated serum levels of this marker. A poor correlation was found between tissue and circulating CA 19-9 levels. CEA was detected in 28% of the tumors and seemed to be valuable only for monitoring in rare cases of ovarian cancer. For purposes of selecting a marker for monitoring of patients with ovarian carcinoma, immunohistochemistry has a predictive value for CA 125 only. In order to better define the marker expressed in a tumor, it is necessary to examine at least two samples of different parts of the malignant tissue.

  12. A novel sandwiched electrochemiluminescence immunosensor for the detection of carcinoembryonic antigen based on carbon quantum dots and signal amplification. (United States)

    Li, Nian-Lu; Jia, Li-Ping; Ma, Rong-Na; Jia, Wen-Li; Lu, Yi-Yang; Shi, Sha-Shan; Wang, Huai-Sheng


    In this study, a novel sandwiched electrochemiluminescence (ECL) immunosensor for the detection of carcinoembryonic antigen (CEA) was developed. The nanocomposite of polydopamine and Ag nanoparticles (PDA-AgNPs) was prepared by the redox reaction between Ag(+) and dopamine. This nanocomposite not only provided an effective matrix for the immobilization of primary antibody (Ab1) but also enhanced the conductivity of the electrode. Carbon quantum dots (CQDs) were immobilized on the poly(ethylenimine) functionalized graphene oxide (PEI-GO) through amido-bond. Then Au nanoparticles were decorated on the CQDs modified PEI-GO matrix, and the resulted complex AuNPs/CQDs-PEI-GO was introduced to link secondary antibody (Ab2). The CQDs can be connected to the electrode surface through the combination of CEA with Ab1 and Ab2, and then the amplified electrochemiluminescence signal of CQDs was obtained with the synergistic effect of AgNPs, polydopamine, AuNPs and PEI-GO. Under the optimal conditions, the ECL intensity was proportional to the logarithm value of CEA concentration in the linear range from 5pgmL(-1) to 500ngmL(-1) with a detection limit of 1.67pgmL(-1) for CEA detection. The immunosensor was applied for the CEA detection in real samples with satisfactory results. The proposed ECL immunosensor showed good performance with high sensitivity, specificity, reproducibility, stability and will be potential in clinical detection.

  13. Regulation by gut commensal bacteria of carcinoembryonic antigen-related cell adhesion molecule expression in the intestinal epithelium. (United States)

    Kitamura, Yasuaki; Murata, Yoji; Park, Jung-Ha; Kotani, Takenori; Imada, Shinya; Saito, Yasuyuki; Okazawa, Hideki; Azuma, Takeshi; Matozaki, Takashi


    Carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 1 and CEACAM20, immunoglobulin superfamily members, are predominantly expressed in intestinal epithelial cells (IECs) and co-localized at the apical surface of these cells. We here showed that the expression of mouse CEACAM1 and CEACAM20 at both mRNA and protein levels was markedly reduced in IECs of the small intestine by the treatment of mice with antibiotics against Gram-positive bacteria. The expression of both proteins was also decreased in IECs of the small intestine from germ-free mice, compared with that from control specific-pathogen-free mice. Exposure of intestinal organoids to IFN-γ markedly increased the expression of either CEACAM1 or CEACAM20, whereas the exposure to TNF-α increased the expression of the former protein, but not that of the latter. In contrast, the expression of CEACAM20, but not of CEACAM1, in intestinal organoids was markedly increased by exposure to butyrate, a short-chain fatty acid produced by bacterial fermentation in the intestine. Collectively, our results suggest that Gram-positive bacteria promote the mRNA expression of CEACAM1 or CEACAM20 in the small intestine. Inflammatory cytokines or butyrate likely participates in such effects of commensal bacteria.

  14. Detection of carcinoembryonic antigen mRNA in peritoneal washes from gastric cancer patients and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    Yan-Song Zhang; Jun Xu; Guang-Hua Luo; Rong-Chao Wang; Jiang Zhu; Xiao-Ying Zhang; Peter Nilsson-Ehle; Ning Xu


    AIM: To establish a more sensitive method for detection of free cancer cells in peritoneal washes from gastric cancer patients during surgery and to evaluate its clinical significance.METHODS: The carcinoembryonic antigen (CEA) mRNA levels in peritoneal washes from 65 cases of gastric cancer were detected by real-time RT-PCR. Peritoneal lavage cytology (PLC) was applied simultaneously to detection of free cancer cells. Negative controls included peritoneal washes from 5 cases of benign gastric disease and blood samples from 5 adult healthy volunteers.RESULTS: There was no CEA mRNA in peritoneal washes from benign gastric disease patients and in blood of adult healthy volunteers. The positive percentage of free cancer cells detected by real-time RT-PCR was 47.7% and only 12.3% by PLC. The positive rate of CEA mRNA was significantly related with serosa invasion between peritoneal metastasis and stage of gastric cancer.CONCLUSION: Real-time RT-PCR is a sensitive and rapid method for the detection of free cancer cells in peritoneal washes. The presence of free cancer cells in peritoneal washes is related to the pathologic stage of gastric cancer.

  15. Combined measurement and significance of lipid-bound sialic acid and carcinoembryonic antigen in detection of human cancer. (United States)

    Munjal, D D; Picken, J; Pritchard, J


    We evaluated the clinical usefulness of lipid-bound sialic acid (LSA) as a "tumor marker" and assessed individual and carcinoembryonic antigen (CEA) in cancer patients. Serum LSA and CEA concentrations were measured by the resorcinol method after total lipid extraction and isolation of the sialolipid fraction, and by Abbott enzyme immunoassay procedures, respectively. Results indicate that the frequency of elevation and mean LSA values were highest in patients with lung cancer (318 mg/liter), intermediate in miscellaneous (210 mg/liter) and colorectal cancers (200 mg/liter), and lowest in breast cancer (175 mg/liter); while mean CEA values were highest in colorectal cancer (162.5 micrograms/liter), followed by lung (33.8 micrograms/liter), miscellaneous (30.3 micrograms/liter), and breast cancers (11.6 micrograms/liter). Statistically, LSA and CEA values for cancer patients were significantly (P less than 0.001) higher than for normal subjects. The combined measurement of LSA and CEA in serum provides better detection potential for cancer patients than either of the two markers alone.

  16. Adenovirus tumor targeting and hepatic untargeting by a coxsackie/adenovirus receptor ectodomain anti-carcinoembryonic antigen bispecific adapter. (United States)

    Li, Hua-Jung; Everts, Maaike; Pereboeva, Larisa; Komarova, Svetlana; Idan, Anat; Curiel, David T; Herschman, Harvey R


    Adenovirus vectors have a number of advantages for gene therapy. However, because of their lack of tumor tropism and their preference for liver infection following systemic administration, they cannot be used for systemic attack on metastatic disease. Many epithelial tumors (e.g., colon, lung, and breast) express carcinoembryonic antigen (CEA). To block the natural hepatic tropism of adenovirus and to "retarget" the virus to CEA-expressing tumors, we used a bispecific adapter protein (sCAR-MFE), which fuses the ectodomain of the coxsackie/adenovirus receptor (sCAR) with a single-chain anti-CEA antibody (MFE-23). sCAR-MFE untargets adenovirus-directed luciferase transgene expression in the liver by >90% following systemic vector administration. Moreover, sCAR-MFE can "retarget" adenovirus to CEA-positive epithelial tumor cells in cell culture, in s.c. tumor grafts, and in hepatic tumor grafts. The sCAR-MFE bispecific adapter should, therefore, be a powerful agent to retarget adenovirus vectors to epithelial tumor metastases.

  17. Cost/effectiveness ratio of carcinoembryonic antigen--importance of adequacy of routine requests of tumor markers. (United States)

    Gion, M; Rampazzo, A; Mione, R; Bruscagnin, G


    Since 1987 we have been evaluating the cost/effectiveness ratio of tumor markers using carcinoembryonic antigen (CEA) as a leading indicator. Preliminary to the evaluation of cost/effectiveness ratio we verified the fitness of CEA requests to the proper clinical problems in order to identify any bias of cost due to inadequate CEA use. 2677 CEA orders were evaluated in 1987. The percentage of inadequate requests was very high (43%). Therefore, it seemed not advisable to carry out the evaluation of cost/effectiveness ratio, while educational actions (divulgation of informative material, service of telephone consultation) were addressed to the physicians of the geographic area of laboratory users. In 1991 the adequacy of CEA requests was reevaluated. The percentage of inadequate requests on 2647 orders was 29.4%. This result, although not yet satisfactory, suggests that proper educational programs may probably improve the fitness of tumor marker requests to correct clinical problems. Additional educational actions are mandatory to further reduce the rate of inadequate tumor marker orders.

  18. Crystal structure of the anti-(carcinoembryonic antigen) single-chain Fv antibody MFE-23 and a model for antigen binding based on intermolecular contacts. (United States)

    Boehm, M K; Corper, A L; Wan, T; Sohi, M K; Sutton, B J; Thornton, J D; Keep, P A; Chester, K A; Begent, R H; Perkins, S J


    MFE-23 is the first single-chain Fv antibody molecule to be used in patients and is used to target colorectal cancer through its high affinity for carcinoembryonic antigen (CEA), a cell-surface member of the immunoglobulin superfamily. MFE-23 contains an N-terminal variable heavy-chain domain joined by a (Gly(4)Ser)(3) linker to a variable light-chain (V(L)) domain (kappa chain) with an 11-residue C-terminal Myc-tag. Its crystal structure was determined at 2.4 A resolution by molecular replacement with an R(cryst) of 19.0%. Five of the six antigen-binding loops, L1, L2, L3, H1 and H2, conformed to known canonical structures. The sixth loop, H3, displayed a unique structure, with a beta-hairpin loop and a bifurcated apex characterized by a buried Thr residue. In the crystal lattice, two MFE-23 molecules were associated back-to-back in a manner not seen before. The antigen-binding site displayed a large acidic region located mainly within the H2 loop and a large hydrophobic region within the H3 loop. Even though this structure is unliganded within the crystal, there is an unusually large region of contact between the H1, H2 and H3 loops and the beta-sheet of the V(L) domain of an adjacent molecule (strands DEBA) as a result of intermolecular packing. These interactions exhibited remarkably high surface and electrostatic complementarity. Of seven MFE-23 residues predicted to make contact with antigen, five participated in these lattice contacts, and this model for antigen binding is consistent with previously reported site-specific mutagenesis of MFE-23 and its effect on CEA binding.

  19. Diagnostic sensitivity of serum carcinoembryonic antigen, carbohydrate antigen 19-9, alpha-fetoprotein, and beta-human chorionic gonadotropin in esophageal carcinoma (receiver operating characteristic curve analysis

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    Bhawna Bagaria


    Full Text Available Background: Esophageal carcinomas are very lethal disease relatively unresponsive to therapy. The continued development of new and more effective chemotherapeutic agents and regimens offers hope that in the future, this carcinoma may be amenable to either more effective palliative treatment or possibly increased cure. We, therefore, aimed to evaluate the marker with best diagnostic sensitivity in esophageal carcinoma. Materials and Methods: Serum carcinoembryonic antigen (CEA, carbohydrate antigen 19-9 (CA19-9, alpha-fetoprotein (AFP, and beta-human chorionic gonadotropin (β-HCG levels were assessed in healthy subjects (n = 50 and patients (n = 50 initially diagnosed of esophageal carcinoma by endoscopic examination and biopsy before receiving any therapy. The data were analyzed using SPSS software version 10.0 (SPSS Inc. USA and MedCalc to estimate mean ± standard deviation, the significance of the observed differences (P value, for calculating sensitivity and for plotting receiver operating characteristic curves. Results: Sensitivity of CEA, CA19-9, AFP, and β-HCG detected in esophagus cancer was 38%, 18%, 10%, and 26% respectively. Conclusion: From the above studied markers, CEA has the highest sensitivity followed by β-HCG, CA19-9 and AFP. Although the sensitivity of tumor markers in esophagus cancer is low, they may be useful additional parameter in the prediction of neoplasms involved at the early stage of tumor growth.

  20. Association of pretreatment serum carcinoembryonic antigen levels with chemoradiation-induced downstaging and downsizing of rectal cancer. (United States)

    Yeo, Seung-Gu


    The aim of this study was to identify pretreatment clinical parameters associated with preoperative chemoradiotherapy (CRT)-induced downstaging and downsizing of locally advanced rectal cancer (LARC T3-4 or N+). Data from 51 LARC patients, who received preoperative CRT and radical surgery between 2010 and 2013, were retrospectively analyzed. Rectal adenocarcinoma was histologically confirmed in all patients, who ranged in age between 41 and 81 years (median, 64 years). CRT consisted of 50.4 Gy pelvic radiotherapy with concurrent chemotherapy using 5-fluorouracil and leucovorin. After a median interval of 7 weeks post-CRT, the patients underwent total mesorectal excision. Downstaging was defined as the transition from cStage II-III to ypStage 0-I. The longest tumor diameter was measured pre- and post-CRT using computed tomography or magnetic resonance imaging, and based on the surgical specimen, respectively. Downstaging was observed in 16 (31.4%) patients, including 5 (9.8%) with a pathological complete response. The median downsizing rate was 60%. The serum carcinoembryonic antigen (CEA) levels were 0.8-153.9 ng/ml (median, 4.4 ng/ml). The maximum standardized uptake value was 4.7-33.9 (median, 10.8). On univariate analysis, cT stage, tumor size and CEA level were associated with downstaging. On multivariate analysis, only CEA level (≤5 ng/ml) was a significant predictor of downstaging (odds ratio = 16.0; 95% confidence interval: 1.8-146.7; P=0.014). CEA level was the only factor significantly associated with downsizing (>60%) in the univariate analysis. These results demonstrated that pretreatment serum CEA levels are significantly associated with downstaging as well as downsizing of LARC following preoperative CRT. Therefore, this parameter may be useful in personalizing the management of LARC patients.

  1. Computed tomography of pulmonary changes in rheumatoid arthritis: carcinoembryonic antigen (CEA) as a marker of airway disease. (United States)

    Koch, Milene Caroline; Pereira, Ivânio Alves; Nobre, Luiz Felipe Souza; Neves, Fabricio Souza


    Rheumatoid arthritis (RA) classically affects the joints, but can present extra-articular manifestations, including pulmonary disease. The present study aimed to identify possible risk factors or laboratory markers for lung involvement in RA, particularly the presence of rheumatoid factor (RF), anti-citrullinated peptide antibodies (ACPA), and tumor markers, by correlating them with changes observed on chest high-resolution computerized tomography (HRCT). This cross-sectional study involved RA patients who were examined and questioned by a specialist physician and later subjected to chest HRCT and blood collection for measurement of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), ACPA (anti-vimentin and/or anti-CCP3), and the tumor markers carcinoembryonic antigen (CEA), CA 125, CA 15-3, and CA 19-9. A total of 96 patients underwent chest HRCT. The most frequent findings were bronchial thickening (27/28.1 %) and bronchiectasis (25/26 %). RF was present in 63.2 % of patients (55/87), and ACPA (anti-vimentin or anti-CCP3) was present in 72.7 % of patients (64/88). CEA levels were high in 14 non-smokers (37.8 %) and 23 smokers (62.2 %). CA-19-9 levels were high in 6 of 86 patients (7.0 %), CA 15-3 levels were high in 3 of 85 patients (3.5 %), and CA 125 levels were high in 4 of 75 patients (5.3 %). Multivariate analysis indicated a statistically significant association between high CEA levels and the presence of airway changes in patients with RA (p = 0.048). CEA can serve as a predictor of lung disease in RA and can help identify individuals who require more detailed examination for the presence of respiratory disorders.

  2. Correlation of the Serum Level of Carcinoembryonic Antigen and Prolactin with Different Stages of Colorectal Carcinoma According to Dukes' Staging. (United States)

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


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

  3. Clinical significance of preoperative carcinoembryonic antigen level in patients with clinical stage IA non-small cell lung cancer (United States)

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


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

  4. Development of an FPW Biosensor with Low Insertion Loss and High Fabrication Yield for Detection of Carcinoembryonic Antigen

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    Je-Wei Lan


    Full Text Available In the last two decades, various flexural plate-wave (FPW-based biosensors with low phase velocity, low operation frequency, high sensitivity, and short response time, have been developed. However, conventional FPW transducers have low fabrication yield because controlling the thickness of silicon/isolation/metal/piezoelectric multilayer floating thin-plate is difficult. Additionally, conventional FPW devices usually have high insertion loss because of wave energy dissipation to the silicon substrate or outside area of the output interdigital transducers (IDTs. These two disadvantages hinder the application of FPW devices. To reduce the high insertion loss of FPW devices, we designed two focus-type IDTs (fan-shaped and circular, respectively that can effectively confine the launched wave energy, and adopted a focus-type silicon-grooved reflective grating structure (RGS that can reduce the wave propagation loss. To accurately control the thickness of the silicon thin-plate and substantially improve the fabrication yield of FPW transducers, a 60 °C/27 °C two-step anisotropic wet etching process was developed. Compared with conventional FPW devices (with parallel-type IDTs and without RGS, the proposed FPW devices have lower insertion loss (36.04 dB and higher fabrication yield (63.88%. Furthermore, by using cystamine-based self-assembled monolayer (SAM nanotechnology, we used the improved FPW device to develop a novel FPW-based carcinoembryonic antigen (CEA biosensor for detection of colorectal cancer, and this FPW-CEA biosensor has a low detection limit (5 ng/mL, short response time (<10 min, high sensitivity (60.16–70.06 cm2/g, and high sensing linearity (R-square = 0.859–0.980.

  5. Targeting Carcinoembryonic Antigen with DNA Vaccination: On-Target Adverse Events Link with Immunological and Clinical Outcomes (United States)

    Chudley, Lindsey; Stasakova, Jana; Thirdborough, Stephen; King, Andrew; Lloyd-Evans, Paul; Buxton, Emily; Edwards, Ceri; Halford, Sarah; Bateman, Andrew; O’Callaghan, Ann; Clive, Sally; Anthoney, Alan; Jodrell, Duncan I.; Weinschenk, Toni; Simon, Petra; Sahin, Ugur; Thomas, Gareth J.; Stevenson, Freda K.; Ottensmeier, Christian H.


    Purpose We have clinically evaluated a DNA fusion vaccine to target the HLA-A*0201 binding peptide CAP-1 from carcinoembryonic antigen (CEA605–613) linked to an immunostimulatory domain (DOM) from fragment C of tetanus toxin. Experimental Design Twenty-seven patients with CEA-expressing carcinomas were recruited: 15 patients with measurable disease (Arm-I) and 12 patients without radiological evidence of disease (Arm-II). Six intramuscular vaccinations of naked DNA (1mg/dose) were administered up to week 12. Clinical and immunological follow-up was to week 64 or clinical/radiological disease. Results DOM-specific immune responses demonstrated successful vaccine delivery. All patients without measurable disease compared to 60% with advanced disease responded immunologically, while 58% and 20% expanded anti-CAP-1 CD8+ T-cells, respectively. CAP-1-specific T-cells were only detectable in the blood post-vaccination, but could also be identified in previously resected cancer tissue. The gastrointestinal adverse event diarrhea was reported by 48% of patients and linked to more frequent decreases in CEA (pdiarrhea. In advanced disease patients, decreases in CEA were associated with better overall survival (HR=0.14, p=0.017). CAP-1 peptide was detectable on MHC class I of normal bowel mucosa and primary colorectal cancer tissue by mass-spectrometry, offering a mechanistic explanation for diarrhea through CD8+ T-cell attack. Conclusions Our data suggest that DNA vaccination is able to overcome peripheral tolerance in normal and tumor tissue and warrants testing in combination studies, for example, by vaccinating in parallel to treatment with an anti-PD1 antibody. PMID:27091407

  6. Murine carcinoma expressing carcinoembryonic antigen-like protein is restricted by antibody against neem leaf glycoprotein. (United States)

    Das, Arnab; Barik, Subhasis; Bose, Anamika; Roy, Soumyabrata; Biswas, Jaydip; Baral, Rathindranath; Pal, Smarajit


    We have generated a polyclonal antibody against a novel immunomodulator, neem leaf glycoprotein (NLGP) that can react to a specific 47 kDa subunit of NLGP. Generated anti-NLGP antibody (primarily IgG2a) was tested for its anti-tumor activity in murine carcinoma (EC, CT-26), sarcoma (S180) and melanoma (B16Mel) tumor models. Surprisingly, tumor growth restriction was only observed in CT-26 carcinoma models, without any alteration in other tumor systems. Comparative examination of antigenicity between four different tumor models revealed high expression of CEA-like protein on the surface of CT-26 tumors. Subsequent examination of the cross-reactivity of anti-NLGP antibody with purified or cell bound CEA revealed prominent recognition of CEA by anti-NLGP antibody, as detected by ELISA, Western Blotting and immunohistochemistry. This recognition seems to be responsible for anti-tumor function of anti-NLGP antibody only on CEA-like protein expressing CT-26 tumor models, as confirmed by ADCC reaction in CEA(+) tumor systems where dependency to anti-NLGP antibody is equivalent to anti-CEA antibody. Obtained result with enormous therapeutic potential for CEA(+) tumors may be explained in view of the epitope spreading concept, however, further investigation is crucial.

  7. Value of carcinoembryonic antigen and cytokeratins for the detection of recurrent disease following curative resection of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Luís C Fernandes; Su B Kim; Sarhan S Saad; Delcio Matos


    AIM: To evaluate the efficacy of postoperative serial assay of carcinoembryonic antigen (CEA) and cytokeratins for the detection of recurrent disease in patients with colorectal adenocarcinoma after radical surgery.METHODS: Between 1993 and 2000, 120 patients with colorectal adenocarcinoma underwent radical surgery in the Department of Surgical Gastroenterology, Federal University of Sao Paulo-Escola Paulista de Medicina,Sao Paulo, Brazil. Periodic postoperative evaluation was performed by assaying markers in peripheral serum,colonoscopy and imaging examination. Presence of CEA was detected using the Delfia(R) method with 5 μg/L threshold, and cytokeratins using the LIA-mat(R) TPA-M Prolifigen(R) method with 72 U/L threshold.RESULTS: In the first postoperative year, patients without recurrent disease had normal levels of CEA (1.5 ± 0.9 μg/L) and monoclonal tissue polypeptide antigen-M (TPA-M, 64.4 ± 47.8 U/L), while patients with recurrences had high levels of CEA (6.9 ± 9.8 μg/L,P < 0.01) and TPA-M (192.2 ± 328.8 U/L, P < 0.05).During the second postoperative year, patients without tumor recurrence had normal levels of CEA (2.0 ± 1.8μg/L) and TPA-M (50.8 ± 38.4 U/L), while patients with recurrence had high levels of CEA (66.3 ± 130.8 μg/L, P < 0.01) and TPA-M (442.7 ± 652.8 U/L, P < 0.05). The mean follow-up time was 22.3 mo. There was recurrence in 23 cases. Five reoperations were performed without achieving radical excision. Rises in tumor marker levels preceded identification of recurrences: CEA in seven (30%) and TPA-M in eleven individuals (48%).CONCLUSION: Intensive follow-up by serial assay of CEA and cytokeratins allows early detection of colorectal neoplasm recurrence.

  8. Higher importance of interleukin 6 than classic tumor markers (carcinoembryonic antigen and squamous cell cancer antigen) in the diagnosis of esophageal cancer patients. (United States)

    Łukaszewicz-Zając, M; Mroczko, B; Kozłowski, M; Nikliński, J; Laudański, J; Szmitkowski, M


    It has been suggested that interleukin 6 (IL-6) plays a potential role in the growth and progression of tumors, including esophageal cancer (EC). The aim of the study was to compare clinical significance of serum IL-6 with classic tumor markers - carcinoembryonic antigen (CEA) and squamous cell cancer antigen (SCC-Ag) - in EC patients in relation to its histological types - squamous cell carcinoma of esophagus (ESCC) and adenocarcinoma (AD) of esophagus. The study included 53 EC patients and 90 healthy subjects. Serum IL-6 and CEA levels were determined using immunoenzyme assays, while SCC-Ag - chemiluminescent assay. The diagnostic criteria and prognostic values for markers were defined. The levels of all proteins tested in EC, ESCC, and AD were higher than in healthy subjects. The percentage of elevated results was substantially higher for IL-6 (86%) than for CEA (30%) and SCC-Ag (24%) in EC, similarly as in ESCC (87%, 23%, and 33%) and AD (87%, 39%, and 13%, respectively) patients. Concentrations of IL-6 depended on distant metastases and patients' survival in EC and were significantly higher in ESCC patients with more advanced tumor stage and nodal metastases. The IL-6 area under receiver operating characteristic curve (0.92) was larger than for CEA (0.84) and SCC-Ag (0.62) in EC, likewise in ESCC (0.92, 0.87, 0.77) and AD (0.91, 0.79, 0.57, respectively). Our findings indicate better usefulness of IL-6 than classic tumor markers in the diagnosis of EC, especially in patients with ESCC.

  9. Drug-resistant colon cancer cells produce high carcinoembryonic antigen and might not be cancer-initiating cells

    Directory of Open Access Journals (Sweden)

    Lee HC


    Full Text Available Hsin-chung Lee,1,2 Qing-Dong Ling,1,3 Wan-Chun Yu,4 Chunh-Ming Hung,4 Ta-Chun Kao,4 Yi-Wei Huang,4 Akon Higuchi3–51Graduate Institute of Systems Biology and Bioinformatics, National Central University, Jhongli, Taoyuan, 2Department of Surgery, Cathay General Hospital, Da'an District, Taipei, 3Cathay Medical Research Institute, Cathay General Hospital, Hsi-Chi City, Taipei, 4Department of Chemical and Materials Engineering, National Central University, Jhongli, Taoyuan, Taiwan; 5Department of Reproduction, National Research Institute for Child Health and Development, Okura, Tokyo, JapanPurpose: We evaluated the higher levels of carcinoembryonic antigen (CEA secreted by the LoVo human colon carcinoma cells in a medium containing anticancer drugs. Drug-resistant LoVo cells were analyzed by subcutaneously xenotransplanting them into mice. The aim of this study was to evaluate whether the drug-resistant cells isolated in this study were cancer-initiating cells, known also as cancer stem cells (CSCs.Methods: The production of CEA was investigated in LoVo cells that were cultured with 0–10 mM of anticancer drugs, and we evaluated the increase in CEA production by the LoVo cells that were stimulated by anticancer drug treatment. The expression of several CSC markers in LoVo cells treated with anticancer drugs was also evaluated. Following anticancer drug treatment, LoVo cells were injected subcutaneously into the flanks of severe combined immunodeficiency mice in order to evaluate the CSC fraction.Results: Production of CEA by LoVo cells was stimulated by the addition of anticancer drugs. Drug-resistant LoVo cells expressed lower levels of CSC markers, and LoVo cells treated with any of the anticancer drugs tested did not generate tumors within 8 weeks from when the cells were injected subcutaneously into severe combined immunodeficiency mice. These results suggest that the drug-resistant LoVo cells have a smaller population of CSCs than the

  10. Development of a streptavidin-anti-carcinoembryonic antigen antibody, radiolabeled biotin pretargeting method for radioimmunotherapy of colorectal cancer. Reagent development. (United States)

    Karacay, H; Sharkey, R M; Govindan, S V; McBride, W J; Goldenberg, D M; Hansen, H J; Griffiths, G L


    With pretargeting, radioisotope delivery to tumor is decoupled from the long antibody localization process, and this can increase tumor:blood ratios dramatically. Several reagents were prepared for each step of a "two-step" pretargeting method, and their properties were investigated. For pretargeting tumor, streptavidin-monoclonal antibody (StAv-mab) conjugates were prepared by cross-linking sulfo-SMCC-derivatized streptavidin to a free thiol (SH) group on MN-14 [a high-affinity anti-carcinoembryonic antigen (CEA) mab]. Thiolated mabs were generated either by reaction of 2-iminothiolane (2-IT) with mab lysine residues or by reduction of mab disulfide bonds with (2-mercaptoethyl)amine (MEA). Both procedures gave protein-protein conjugates isolated in relatively low yields (20-25%) after preparative size-exclusion (SE) chromatography purification with conservative peak collection. Both StAv-MN-14 conjugates retained their ability to bind to CEA, to an anti-idiotypic antibody to MN-14 (WI2), and to biotin, as demonstrated by SE-HPLC. Two clearing agents, WI2 mab and a biotin-human serum albumin (biotin-HSA) conjugate, were developed to remove excess circulating StAv-MN-14 conjugates in animals. Both clearing proteins were also modified with galactose residues, introduced using an activated thioimidate derivative, to produce clearing agents which would clear rapidly and clear primary mab rapidly. At least 14 galactose residues on WI2 were required to reduce blood levels to 5.9 +/- 0.7% ID/g in 1 h. Faster blood clearance (0.7 +/- 0.2% ID/g) was observed in 1 h using 44 galactose units per WI2. For the delivery of radioisotope to tumor, several biotinylated conjugates consisting of biotin, a linker, and a chelate were prepared. Conjugates showed good in vitro and in vivo stability when D-amino acid peptides were used as linkers, biotin-peptide-DOTA-indium-111 had a slightly longer blood circulation time (0.09 +/- 0.02% ID/g in 1 h) than biotin-peptide-DTPA-indium-111 (0

  11. Carcinoembryonic antigen (CEA) measurement during follow-up for rectal carcinoma is useful even if normal levels exist before surgery. A retrospective study of CEA values in the TME trial

    NARCIS (Netherlands)

    Grossmann, I.; de Bock, G. H.; Kranenbarg, W. M. Meershoek-Klein; de Velde, C. J. H. van; Wiggers, T.


    Background: Carcinoembryonic antigen (CEA) as a marker in the follow-up after curative resection of colorectal carcinoma (CRC) is often omitted from follow-up despite guideline recommendations. One reason is the assumption that when a normal CEA value exists before curative resection of CRC, it will

  12. The relevance of serum carcinoembryonic antigen as an indicator of brain metastasis detection in advanced non-small cell lung cancer. (United States)

    Lee, Dong-Soo; Kim, Yeon-Sil; Jung, So-Lyoung; Lee, Kyo-Young; Kang, Jin-Hyoung; Park, Sarah; Kim, Young-Kyoon; Yoo, Ie-Ryung; Choi, Byung-Ock; Jang, Hong-Seok; Yoon, Sei-Chul


    Although many biomarkers have emerged in non-small cell lung cancer (NSCLC), the predictive value of site-specific spread is not fully defined. We designed this study to determine if there is an association between serum biomarkers and brain metastasis in advanced NSCLC. We evaluated 227 eligible advanced NSCLC patients between May 2005 and March 2010. Patients who had been newly diagnosed with stage IV NSCLC but had not received treatment previously, and had available information on at least one of the following pretreatment serum biomarkers were enrolled: carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CYFRA 21-1), cancer antigen 125 (CA 125), cancer antigen 19-9, and squamous cancer cell antigen. Whole body imaging studies and magnetic resonance imaging of the brain were reviewed, and the total number of metastatic regions was scored. Brain metastasis was detected in 66 (29.1%) patients. Although serum CEA, CYFRA 21-1, and CA 125 levels were significantly different between low total metastatic score group (score 1-3) and high total metastatic score group (score 4-7), only CEA level was significantly different between patients with brain metastasis and those without brain metastasis (p present study demonstrated that the pretreatment serum CEA level was significantly correlated with brain metastasis in advanced NSCLC. These findings suggested the possible role of CEA in the pathogenesis of brain invasion. More vigilant surveillance would be warranted in the high-risk group of patients with high serum CEA level and multiple synchronous metastasis.

  13. Increased basolateral sorting of carcinoembryonic antigen in a polarized colon carcinoma cell line after cholesterol depletion-Implications for treatment of inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Robert Ehehalt; Markus Krautter; Martin Zorn; Richard Sparla; Joachim Fūllekrug; Hasan Kulaksiz; Wolfgang Stremmel


    AIM:To investigate a possible increase of basolateral expression of carcinoembryonic antigen(CEA)by interfering with the apical transport machinery,we studied the effect of cholesterol depletion on CEA sorting and secretion.METHODS:Cholesterol depletion was performed in polarized Caco-2 cells using Iovastatin and methyl-βcyclodextrin.RESULTS:We show that CEA is predominantly expressed and secreted at the apical surface.Reduction of the cholesterol level of the cell by 40%-50% with Iovastatin and methyl-β-cyclodextrin led to a significant change of the apical-to-basolateral transport ratio towards the basolateral membrane.CONCLUSION:As basolateral expression of CEA has been suggested to have anti-inflamatory properties,Cholesterol depletion of enterocytes might be a potential approach to influence the course of inflammatory bowel disease.

  14. Self-assembled polymeric nanoparticles film stabilizing gold nanoparticles as a versatile platform for ultrasensitive detection of carcino-embryonic antigen. (United States)

    Xu, Sheng; Zhang, Rongli; Zhao, Wei; Zhu, Ye; Wei, Wei; Liu, Xiaoya; Luo, Jing


    In this work, a novel impedimetric immunosensor was developed based on electrophoretic deposition of polymeric self-assembled nanoparticles for the sensitive determination of carcino-embryonic antigen (CEA). Biocompatible polymeric nanoparticles γ-PGA-DA@CS were prepared by self-assembly of chitosan (CS) and dopamine modified poly(γ-glutamic acid) (γ-PGA-DA) under mild conditions. A dense and nanostructured nanoparticles film was obtained on the electrode surface by electrophoretic deposition of γ-PGA-DA@CS nanoparticles. Gold nanoparticles (Au NPs) were then tightly anchored on γ-PGA-DA@CS film with homogeneous dispersion due to numerous exposed dopamine adhesive dots present on the surface of γ-PGA-DA@CS. The obtained Au/γ-PGA-DA@CS nanocomposite film not only increases the electrode surface area in nanoscale dimension, but also provides a highly stable and biocompatible matrix for the convenient conjugation of antibody, thus providing a high-efficiency immunoassay platform. Monoclonal antibodies to carcinoembryonic antigen (CEA-Ab) were effectively immobilized on the Au/γ-PGA-DA@CS film and a label-free impedimetric immunosensor was fabricated successfully as the ultimate goal. Under optimal conditions, the resultant immunosensor exhibited a wide linear range from 2.0×10(-14)gmL(-1) to 2.0×10(-8)gmL(-1) for the detection of CEA with a low detection limit of 10fgmL(-1). To the best of our knowledge, this was the lowest detection limit compared with other counterparts of label-free impedimetric immunosensors. Moreover, the immunosensor showed high specificity, good stability and satisfactory reproducibility. As a proof of concept, the proposed strategy provided a promising and versatile platform for clinical immunoassay of other tumor markers and biomolecules.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  16. Determination of carcinoembryonic antigen using a novel amperometric enzyme-electrode based on layer-by-layer assembly of gold nanoparticles and thionine

    Institute of Scientific and Technical Information of China (English)


    Electrochemical sensing of carcinoembryonic antigen(CEA)on a gold electrode modified by the se- quential incorporation of the mediator,thionine(Thi),and gold nanoparticles(nano-Au),through co- valent linkage and electrostatic interactions onto a self-assembled monolayer configuration is de- scribed in this paper.The enzyme,horseradish peroxidase(HRP),was employed to block the possible remaining active sites of the nano-Au monolayer,avoid the non-specific adsorption,instead of bovine serum albumin(BSA),and amplify the response of the antigen-antibody reaction.Electrochemical ex- periments indicated highly efficient electron transfer by the imbedded Thi mediator and adsorbed nano-Au.The HRP kept its activity after immobilization,and the studied electrode showed sensitive response to CEA and high stability during a long period of storage.The working range for the system was 2.5 to 80.0 ng/mL with a detection limit of 0.90 ng/mL.The model membrane system in this work is a potential biosensor for mimicking the other immunosensor and enzyme sensor.

  17. Determination of carcinoembryonic antigen using a novel amperometric enzyme-electrode based on layer-by-layer assembly of gold nanoparticles and thionine

    Institute of Scientific and Technical Information of China (English)

    YUAN Ruo; ZHUO Ying; CHAI YaQin; ZHANG Ying; SUN AiLi


    Electrochemical sensing of carcinoembryonic antigen (CEA) on a gold electrode modified by the sequential incorporation of the mediator, thionine (Thi), and gold nanoparticles (nano-Au), through covalent linkage and electrostatic interactions onto a self-assembled monolayer configuration is described in this paper. The enzyme, horseradish peroxidase (HRP), was employed to block the possible remaining active sites of the nano-Au monolayer, avoid the non-specific adsorption, instead of bovine serum albumin (BSA), and amplify the response of the antigen-antibody reaction. Electrochemical experiments indicated highly efficient electron transfer by the imbedded Thi mediator and adsorbed nano-Au. The HRP kept its activity after immobilization, and the studied electrode showed sensitive response to CEA and high stability during a long period of storage. The working range for the system was 2.5 to 80.0 ng/mL with a detection limit of 0.90 ng/mL. The model membrane system in this work is a potential biosensor for mimicking the other immunosensor and enzyme sensor.

  18. Relationship between serum carcinoembryonic antigen level and epidermal growth factor receptor mutations with the influence on the prognosis of non-small-cell lung cancer patients

    Directory of Open Access Journals (Sweden)

    Cai ZX


    Full Text Available Zuxun Cai Department of Thoracic Surgery, Henan Provincial Chest Hospital, Zhengzhou City, People’s Republic of China Objective: To investigate the relationship between serum carcinoembryonic antigen (CEA level and epidermal growth factor receptor (EGFR gene mutations in non-small-cell lung cancer (NSCLC patients and to analyze the influence of CEA level on postoperative survival time in lung cancer patients. Methods: A total of 296 patients who were treated in Thoracic Surgery Department of Henan Provincial Chest Hospital from September 2011 to September 2013 were recruited. The level of tumor markers, such as CEA, was determined before the surgery, and EGFR gene mutations were detected after surgery. Thereby, the relationship between tumor makers, including CEA, and EGFR mutation and its influence on prognosis could be investigated. Results: Among 296 patients, the positive rate of EGFR gene mutation was 37.84% (112/296; the mutation occurred more frequently in nonsmokers, adenocarcinoma patients, women, and patients aged <60 years (P<0.05. Both tumor markers and chemosensitivity indicators were related to the profile of EGFR mutations. Elevated squamous cell carcinoma and Cyfra21-1 as well as positively expressed ERCC1 were more common in patients with wild-type EGFR (P<0.05, whereas increased CEA level was observed more frequently in patients with EGFR gene mutation (P=0.012. The positive rate of EGFR gene mutations was higher as the serum CEA level increased, that is, the positive rate in patients with serum CEA level <5, 5–20, and >20 µg/L was 39.81%, 45.32%, and 65.47%, respectively (P=0.004. Logistic regression analysis showed that CEA level was an independent factor in predicting EGFR gene mutations, and serum CEA level was also an independent factor in affecting the prognosis of NSCLC patients, as the overall 2-year survival rate was 73.86% in elevated CEA group and 86.43% in normal group (P<0.01. Conclusion: The prognosis of

  19. Neisserial outer membrane vesicles bind the coinhibitory receptor carcinoembryonic antigen-related cellular adhesion molecule 1 and suppress CD4+ T lymphocyte function. (United States)

    Lee, Hannah S W; Boulton, Ian C; Reddin, Karen; Wong, Henry; Halliwell, Denise; Mandelboim, Ofer; Gorringe, Andrew R; Gray-Owen, Scott D


    Pathogenic Neisseria bacteria naturally liberate outer membrane "blebs," which are presumed to contribute to pathology, and the detergent-extracted outer membrane vesicles (OMVs) from Neisseria meningitidis are currently employed as meningococcal vaccines in humans. While the composition of these vesicles reflects the bacteria from which they are derived, the functions of many of their constituent proteins remain unexplored. The neisserial colony opacity-associated Opa proteins function as adhesins, the majority of which mediate bacterial attachment to human carcinoembryonic antigen-related cellular adhesion molecules (CEACAMs). Herein, we demonstrate that the Opa proteins within OMV preparations retain the capacity to bind the immunoreceptor tyrosine-based inhibitory motif-containing coinhibitory receptor CEACAM1. When CD4(+) T lymphocytes were exposed to OMVs from Opa-expressing bacteria, their activation and proliferation in response to a variety of stimuli were effectively halted. This potent immunosuppressive effect suggests that localized infection will generate a "zone of inhibition" resulting from the diffusion of membrane blebs into the surrounding tissues. Moreover, it demonstrates that OMV-based vaccines must be developed from strains that lack CEACAM1-binding Opa variants.

  20. Label-Free Electrochemiluminescent Immunosensor for Detection of Carcinoembryonic Antigen Based on Nanocomposites of GO/MWCNTs-COOH/Au@CeO₂. (United States)

    Pang, Xuehui; Li, Jianxiu; Zhao, Yongbei; Wu, Dan; Zhang, Yong; Du, Bin; Ma, Hongmin; Wei, Qin


    A high-sensitivity electrochemiluminescence (ECL) sensor was conducted to detect carcinoembryonic antigen (CEA). Nanocomposites of graphene oxide/carboxylated multiwall carbon nanotubes/gold/cerium oxide nanoparticles (GO/MWCNTs-COOH/Au@CeO2) were used as antibody carriers and sensing platforms to modify on glassy carbon electrodes (GCE). CeO2 nanoparticles were first exploited as an ECL luminescent material and the possible ECL mechanism was proposed in this work. GO/MWCNTs-COOH was used as a loading matrix for CeO2 nanoparticles because of the superior conductivity and large specific surface area. Au nanoparticles were further deposited on this matrix to attach anti-CEA and enhance the sensitivity of immunosensor. The proposed sensing platform showed excellent cathodic ECL performance and sensitive response to CEA. The effects of experimental conditions on the ECL performance were investigated. The proposed immunosensor showed the broad linear range (0.05-100 ng/mL) and the low detection limit (LOD, 0.02 ng/mL, signal-to-noise ratio = 3) according to the selected experimental conditions. The excellent analysis performance for determination of CEA in the human serum samples simplied this immunosensor displayed high sensitivity and excellent repeatability. More importantly, this conducted immunosensor broadens the use scope of CeO2 nanoparticles.

  1. Evaluation of the use of decision-support software in carcino-embryonic antigen (CEA-based follow-up of patients with colorectal cancer

    Directory of Open Access Journals (Sweden)

    Verberne Charlotte J


    Full Text Available Abstract Background The present paper is a first evaluation of the use of "CEAwatch", a clinical support software system for surgeons for the follow-up of colorectal cancer (CRC patients. This system gathers Carcino-Embryonic Antigen (CEA values and automatically returns a recommendation based on the latest values. Methods Consecutive patients receiving follow-up care for CRC fulfilling our in- and exclusion criteria were identified to participate in this study. From August 2008, when the software was introduced, patients were asked to undergo the software-supported follow-up. Safety of the follow-up, experiences of working with the software, and technical issues were analyzed. Results 245 patients were identified. The software-supported group contained 184 patients; the control group contained 61 patients. The software was safe in finding the same amount of recurrent disease with fewer outpatient visits, and revealed few technical problems. Clinicians experienced a decrease in follow-up workload of up to 50% with high adherence to the follow-up scheme. Conclusion CEAwatch is an efficient software tool helping clinicians working with large numbers of follow-up patients. The number of outpatient visits can safely be reduced, thus significantly decreasing workload for clinicians.

  2. Comparison of a chimeric anti-carcinoembryonic antigen antibody conjugated with visible or near-infrared fluorescent dyes for imaging pancreatic cancer in orthotopic nude mouse models (United States)

    Maawy, Ali A.; Hiroshima, Yukihiko; Kaushal, Sharmeela; Luiken, George A.; Hoffman, Robert M.; Bouvet, Michael


    The aim of this study was to evaluate a set of visible and near-infrared dyes conjugated to a tumor-specific chimeric antibody for high-resolution tumor imaging in orthotopic models of pancreatic cancer. BxPC-3 human pancreatic cancer was orthotopically implanted into pancreata of nude mice. Mice received a single intravenous injection of a chimeric anti-carcinoembryonic antigen antibody conjugated to one of the following fluorophores: 488-nm group (Alexa Fluor 488 or DyLight 488); 550-nm group (Alexa Fluor 555 or DyLight 550); 650-nm group (Alexa Fluor 660 or DyLight 650), or the 750-nm group (Alexa Fluor 750 or DyLight 755). After 24 h, the Olympus OV100 small-animal imaging system was used for noninvasive and intravital fluorescence imaging of mice. Dyes were compared with respect to depth of imaging, resolution, tumor-to-background ratio (TBR), photobleaching, and hemoglobin quenching. The longer wavelength dyes had increased depth of penetration and ability to detect the smallest tumor deposits and provided the highest TBRs, resistance to hemoglobin quenching, and specificity. The shorter wavelength dyes were more photostable. This study showed unique advantages of each dye for specific cancer imaging in a clinically relevant orthotopic model.

  3. Combined effects of 5-Fluorouracil, Folinic acid and Oxaliplatin on the expression of carcinoembryonic antigen in human colon cancer cells: pharmacological basis to develop an active antitumor immunochemotherapy

    Directory of Open Access Journals (Sweden)

    De Vecchis Liana


    Full Text Available Abstract Background Five-fluorouracil (FU, mainly associated with leucovorin (L, plays an essential role in chemotherapy of colorectal carcinoma. Moreover, FU ± L has been found to increase the expression of tumor-associated carcinoembryonic antigen (CEA, that may be an important target in therapeutic protocols of active specific immunotherapy. FU + L (FUL are frequently combined with oxaliplatin (OXA in advanced colon cancer patients. Thus, we investigated whether FUL in combination with OXA according to 2 different schedules may influence CEA expression in human colon cancer cells in vitro. Methods CEA protein expression was evaluated by cytofluorimetric and western blot analysis. Relative quantification of CEA mRNA was assessed by real time RT-PCR analysis. Results Levels of CEA protein and transcript were found to be higher in FUL-treated cells than in controls. However, when target cells were exposed to OXA before but not after FUL treatment, the up-regulation of CEA was partially inhibited. Conclusion These results suggest that target cells must be exposed to OXA after but not before treatment with the fluoropyrimidine in order to exploit drug-induced up-regulation of CEA. This finding appears to provide useful information to design chemo-immunotherapy protocols based on FUL + OXA, combined with host's immunity against CEA directed cancer vaccines.

  4. Carcinoembryonic antigen: assay following heat compared with perchloric acid extraction in patients with colon cancer, non-neoplastic gastrointestinal diseases, or chronic renal failure

    Energy Technology Data Exchange (ETDEWEB)

    Witherspoon, L.R.; Shuler, S.E.; Alyea, K.; Husserl, F.E.


    Heat inactivation has been proposed as an alternative to perchloric acid (PCA) precipitation for the extraction of carcinoembryonic antigen (CEA) from human plasma. A commercial RIA kit using heat inactivation was examined and results compared with those obtained with PCA precipitation. Adequate sensitivity (1.5 CEA/I plasma), satisfactory analytical recovery of CEA added to plasma, and dilutional linearity of samples found to have elevated CEA concentrations, were demonstrated for the heat-inactivation assay. Between-assay precision was better with the heat inactivation than with the PCA assay. Although the absolute concentration of CEA estimated after heat inactivation was consistently lower than that estimated after PCA extraction of plasma specimens, there was excellent correlation between results obtained with the two methods in colon cancer patients free of disease, colon cancer patients with residual or recurrent disease, patients with benign gastrointestinal disease, and in patients with chronic renal failure. The heat-inactivation assay is an excellent alternative to the PCA assay.

  5. Carcinoembryonic antigen: assay following heat compared with perchloric acid extraction in patients with colon cancer, non-neoplastic gastrointestinal diseases, or chronic renal failure. (United States)

    Witherspoon, L R; Shuler, S E; Alyea, K; Husserl, F E


    Heat inactivation has been proposed as an alternative to perchloric acid (PCA) precipitation for the extraction of carcinoembryonic antigen (CEA) from human plasma. We examined a commercial RIA kit using heat inactivation, and compared results with those obtained with PCA precipitation. Adequate sensitivity (1.5 micrograms CEA/l plasma), satisfactory analytical recovery of CEA added to plasma, and dilutional linearity of samples found to have elevated CEA concentrations, were demonstrated for the heat-inactivation assay. Between-assay precision was better with the heat inactivation than with the PCA assay. Although the absolute concentration of CEA estimated after heat inactivation was consistently lower than that estimated after PCA extraction of plasma specimens, there was excellent correlation between results obtained with the two methods in colon cancer patients free of disease, colon cancer patients with residual or recurrent disease, patients with benign gastrointestinal disease, and in patients with chronic renal failure. We conclude that the heat-inactivation assay is an excellent alternative to the PCA assay.

  6. A Label-Free Microelectrode Array Based on One-Step Synthesis of Chitosan–Multi-Walled Carbon Nanotube–Thionine for Ultrasensitive Detection of Carcinoembryonic Antigen

    Directory of Open Access Journals (Sweden)

    Huiren Xu


    Full Text Available Carcinoembryonic antigen (CEA has been an extensively used tumor marker responsible for clinical early diagnosis of cervical carcinomas, and pancreatic, colorectal, gastric and lung cancer. Combined with micro-electro mechanical system (MEMS technology, it is important to develop a novel immune microelectrode array (MEA not only for rapid analysis of serum samples, but also for cell detection in vitro and in vivo. In this work, we depict a simple approach to modify chitosan–multi-walled carbon nanotubes–thionine (CS–MWCNTs–THI hybrid film through one-step electrochemical deposition and the CS-MWCNTs-THI hybrid films are successfully employed to immobilize anti-CEA for fabricating simple, label-free, and highly sensitive electro-chemical immune MEAs. The detection principle of immune MEA was based on the fact that the increasing formation of the antigen-antibody immunocomplex resulted in the decreased response currents and the relationship between the current reductions with the corresponding CEA concentrations was directly proportional. Experimental results indicated that the label-free MEA had good selectivity and the limit of detection for CEA is 0.5 pg/mL signal to noise ratio (SNR = 3. A linear calibration plot for the detection of CEA was obtained in a wide concentration range from 1 pg/mL to 100 ng/mL (r = 0.996. This novel MEA has potential applications for detecting CEA for the research on cancer cells and cancer tissue slices as well as for effective early diagnosis.

  7. Magnetic immunoassay coupled with inductively coupled plasma mass spectrometry for simultaneous quantification of alpha-fetoprotein and carcinoembryonic antigen in human serum

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xing; Chen, Beibei; He, Man; Zhang, Yiwen; Xiao, Guangyang; Hu, Bin, E-mail:


    The absolute quantification of glycoproteins in complex biological samples is a challenge and of great significance. Herein, 4-mercaptophenylboronic acid functionalized magnetic beads were prepared to selectively capture glycoproteins, while antibody conjugated gold and silver nanoparticles were synthesized as element tags to label two different glycoproteins. Based on that, a new approach of magnetic immunoassay-inductively coupled plasma mass spectrometry (ICP-MS) was established for simultaneous quantitative analysis of glycoproteins. Taking biomarkers of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) as two model glycoproteins, experimental parameters involved in the immunoassay procedure were carefully optimized and analytical performance of the proposed method was evaluated. The limits of detection (LODs) for AFP and CEA were 0.086 μg L{sup −1} and 0.054 μg L{sup −1} with the relative standard deviations (RSDs, n = 7, c = 5 μg L{sup −1}) of 6.5% and 6.2% for AFP and CEA, respectively. Linear range for both AFP and CEA was 0.2–50 μg L{sup −1}. To validate the applicability of the proposed method, human serum samples were analyzed, and the obtained results were in good agreement with that obtained by the clinical chemiluminescence immunoassay. The developed method exhibited good selectivity and sensitivity for the simultaneous determination of AFP and CEA, and extended the applicability of metal nanoparticle tags based on ICP-MS methodology in multiple glycoprotein quantifications. - Highlights: • 4-Mercaptophenylboronic acid functionalized magnetic beads were prepared and characterized. • ICP-MS based magnetic immunoassay approach was developed for quantification of glycoproteins. • AFP and CEA were quantified simultaneously with Au and Ag NPs as element tags. • The developed method exhibited good selectivity and sensitivity for target glycoproteins.

  8. Increased electrocatalyzed performance through hairpin oligonucleotide aptamer-functionalized gold nanorods labels and graphene-streptavidin nanomatrix: Highly selective and sensitive electrochemical biosensor of carcinoembryonic antigen. (United States)

    Wen, Wei; Huang, Jing-Yi; Bao, Ting; Zhou, Jun; Xia, Hong-Xing; Zhang, Xiu-Hua; Wang, Sheng-Fu; Zhao, Yuan-Di


    We report a triplex signal amplification strategy for sensitive biosensing of cancer biomarker by taking advantage of hairpin-shaped oligonucleotide-functionalized gold nanorods (HO-GNRs), graphene and the avidin-biotin reation. The strategy expands electrochemical detection of carcinoembryonic antigen (CEA) by using an aptamer as biosensor's recognition element and HO-GNRs as signal enhancer. To construct this biosensor, the GNR was used as a carrier of horseradish peroxidase (HRP) and HO aptamer with a biotin at the 3'-end and a thiol at the 5'-end, which amplified the electrochemical response because of a large molar ratio of HRP to HO. In the presence of target CEA, the binding reactions of CEA with the loop portions of the HOs caused HOs' loop-stem structure opened and exposed the biotins, and then HRP-GNRs-HO conjugates were captured on graphene and streptavidin modified electrodes via the reaction between the exposed biotins and preimmobilized streptavidins. The accumulation of HRP effectively catalyzed the hydrogen peroxide-mediated oxidation of o-phenylenediamine to generate an electrochemical reduction current for CEA detection. Under optimal conditions, the electrochemical biosensor exhibited a wide dynamic range of 5pgmL(-1) and 50ngmL(-1) toward CEA standards with a low detection limit of 1.5pgmL(-1) (signal-to-noise ratio of 3). The proposed biosensor accurately detected CEA concentration in 8 human serum samples from patients with lung diseases, showing excellent correlations with standard chemiluminescence immunoassay. Furthermore, these results of target DNA detection made it abundantly clear that the proposed strategy can also be extended for detection of other relative biomarkers using different functional DNA structures, which shows great prospects in single-nucleotide polymorphisms analysis, biomedical sensing and application for accurate clinical diseases diagnostic.

  9. Photoelectrochemical Immunosensor for Detection of Carcinoembryonic Antigen Based on 2D TiO2 Nanosheets and Carboxylated Graphitic Carbon Nitride. (United States)

    Wang, Huan; Wang, Yaoguang; Zhang, Yong; Wang, Qi; Ren, Xiang; Wu, Dan; Wei, Qin


    Carcinoembryonic antigen (CEA) was used as the model, an ultrasensitive label-free photoelectrochemical immunosensor was developed using 2D TiO2 nanosheets and carboxylated graphitic carbon nitride (g-C3N4) as photoactive materials and ascorbic acid as an efficient electron donor. 2D TiO2 nanosheets was sythsized by surfactant self-assembly method and proved to have higher photoelectrochemical signals than TiO2 nanoparticles. Firstly, carboxylated g-C3N4 could be attached to 2D TiO2 nanosheets through the bond formed between carboxyl group of carboxylated g-C3N4 and TiO2. And the photocurrent of g-C3N4/TiO2 drastically enhances compared to carboxylated g-C3N4 and TiO2. Then, antibody of CEA was bonded to TiO2 through the dentate bond formed between carboxyl group of anti-CEA and TiO2, leading to the decrease of the photocurrents. As proven by PEC experiments and electrochemical impedance spectroscopy (EIS) analysis, the fabrication process of the immunosensor is successful. Under the optimal conditions, the intensity decreased linearly with CEA concentration in the range of 0.01~10 ng/mL. The detection limit is 2.1 pg/mL. The work provides an effective method for the detection of tumor markers and can be extended for the application in food safety and environmental monitoring analysis.

  10. Macroporous graphene capped Fe3O4 for amplified electrochemiluminescence immunosensing of carcinoembryonic antigen detection based on CeO2@TiO2. (United States)

    Yang, Lei; Zhu, Wenjuan; Ren, Xiang; Khan, Malik Saddam; Zhang, Yong; Du, Bin; Wei, Qin


    A novel electrochemiluminescence (ECL) signal-amplified immunosensing strategy was proposed by using gold nanoparticles (Au NPs) functionalized reduced graphene oxide (rGO) capped Fe3O4 (Au-FrGO). In this work, CeO2@TiO2 was prepared by a sol-gel method to wrap CeO2 with TiO2. In the presence of CeO2, CeO2@TiO2 exhibited better ECL activity than TiO2 with peroxydisulfate as coreactant. In addition, FrGO with macroporous structure was synthesized by self-assembly of rGO sheets capped cationic Fe3O4 nanoparticles, exhibiting larger specific surface area than rGO. Due to the low toxicity and magnetism of Fe3O4, FrGO owned more favorable biocompatibility and the application of magnetic-separation simplified the preparation procedure. After hybridizing with Au NPs, FrGO exhibited more excellent electrical conductivity and could immobilize more CeO2@TiO2 and antibodies. Therefore, a novel label-free ECL immunosensor based on Au-FrGO-CeO2@TiO2 was constructed which generated higher ECL response. To investigate the performance of the immunosensor, carcinoembryonic antigen (CEA) was chosen as a model target analyte. Under optimal conditions, the immunosensor had sensitive response to CEA in a wide linear range of 0.01pgmL(-1) to 10ngmL(-1) with a detection limit of 3.28 fg mL(-1). The proposed ECL immunosensor exhibited excellent stability, repeatability and selectivity, which opened another promising avenue for CEA determination in real serum samples.

  11. Ultrasensitive electrochemical immunoassay for carcinoembryonic antigen based on three-dimensional macroporous gold nanoparticles/graphene composite platform and multienzyme functionalized nanoporous silver label

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Guoqiang; Lu, Juanjuan [Key Laboratory of Chemical Sensing and Analysis in Universities of Shandong, School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022 (China); Ge, Shenguang [Shandong Provincial Key Laboratory of Fluorine Chemistry and Chemical Materials, School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022 (China); Song, Xianrang [Cancer Research Center, Shandong Tumor Hospital, Jinan 250012 (China); Yu, Jinghua, E-mail: [Key Laboratory of Chemical Sensing and Analysis in Universities of Shandong, School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022 (China); Yan, Mei; Huang, Jiadong [Key Laboratory of Chemical Sensing and Analysis in Universities of Shandong, School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022 (China)


    Graphical abstract: Three-dimensional macroporous AuNPs/graphene complex (3D-AuNPs/GN) and functionalized NPS were prepared to immobilize Ab{sub 1} and Ab{sub 2} respectively and combined to fabricate a sandwich-type ultrasensitive electro-chemical immunosensor for detecting CEA. -- Highlights: •Ultrasensitive electrochemical immunoassay for detecting CEA was developed. •3D-AuNPs/GN was employed as the carrier of primary antibodies. •Multienzyme functionalized nanoporous silver was used as signal enhancer. -- Abstract: Three-dimensional macroporous gold nanoparticles/graphene composites (3D-AuNPs/GN) were synthesized through a simple two-step process, and were used to modify working electrode sensing platform, based on which a facile electrochemical immunoassay for sensitive detection of carcinoembryonic antigen (CEA) in human serum was developed. In the proposed 3D-AuNPs/GN, AuNPs were distributed not just on the surface, but also on the inside of graphene. And this distribution property increased the area of sensing surface, resulting in capturing more primary antibodies as well as improving the electronic transmission rate. In the presence of CEA, a sandwich-type immune composite was formed on the sensing platform, and the horseradish peroxidase-labeled anti-CEA antibody (HRP-Ab{sub 2})/thionine/nanoporous silver (HRP-Ab{sub 2}/TH/NPS) signal label was captured. Under optimal conditions, the electrochemical immunosensor exhibited excellent analytical performance: the detection range of CEA is from 0.001 to 10 ng mL{sup −1} with low detection limit of 0.35 pg mL{sup −1} and low limit of quantitation (LOQ) of 0.85 pg mL{sup −1}. The electrochemical immunosensor showed good precision, acceptable stability and reproducibility, and could be used for the detection of CEA in real samples. The proposed method provides a promising platform of clinical immunoassay for other biomolecules.

  12. Cerium oxide-deposited mesoporous silica nanoparticles for the determination of carcinoembryonic antigen in serum using inductively coupled plasma-mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Choi, H.W. [Department of Chemistry, NSBI, Dankook University, 126 Jukjeon-dong, Suji-gu, Yongin-si, Gyeonggi-do 448-701 (Korea, Republic of); Lee, K.H.; Hur, N.H. [Department of Chemistry, Sogang University, Shinsu-dong, Mapo-gu, Seoul (Korea, Republic of); Lim, H.B., E-mail: [Department of Chemistry, NSBI, Dankook University, 126 Jukjeon-dong, Suji-gu, Yongin-si, Gyeonggi-do 448-701 (Korea, Republic of)


    Highlights: • Sandwich-type immunoassay using ICP-MS and nanoparticles to determine biomarkers. • CeO{sub 2}-deposited mesoporous silica nanoparticles were synthesized as a probe. • Ratiometric measurement significantly improved the calibration linearity. • Excellent detection limit was achieved by signal amplification. - Abstract: CeO{sub 2}-deposited mesoporous silica nanoparticles were synthesized as a probe to determine carcinoembryonic antigen (CEA) in serum by inductively coupled plasma-mass spectrometry (ICP-MS). The prepared mesoporous nanoparticles were modified and tagged to the target for sandwich-type immunoassay. Fe{sub 3}O{sub 4} magnetic nanoparticles (MNPs) were also synthesized and immobilized with antibody to extract the target biomarker. The calibration curve of the synthesized CeO{sub 2}-deposited silica nanoparticles, which was plotted by the signal ratio of {sup 140}Ce/{sup 57}Fe measured by ICP-MS vs. the concentration of CEA, showed excellent linearity and sensitivity owing to the signal amplification and low spectral interference. Under optimal conditions, the sandwich-type analytical method was applied to determine CEA in serum spiked in the range of 0.001–5 ng mL{sup −1} and showed a limit of detection of 0.36 ng mL{sup −1}. Since the deposited CeO{sub 2} in the mesoporous silica layer can be substituted by other metal compounds, various kinds of metal-deposited nanoparticles can be prepared as probe materials for multiplex detection in bioanalysis.

  13. Co-ordinate action of bacterial adhesins and human carcinoembryonic antigen receptors in enhanced cellular invasion by capsulate serum resistant Neisseria meningitidis. (United States)

    Rowe, Helen A; Griffiths, Natalie J; Hill, Darryl J; Virji, Mumtaz


    Neisseria meningitidis (Nm) is a human specific opportunistic pathogen that occasionally penetrates mucosal barriers via the action of adhesins and invasins and evades host immune mechanisms during further dissemination via capsule expression. From in vitro studies, the primary adhesion of capsulate bacteria is believed to be mediated by polymeric pili, followed by invasion via outer membrane adhesins such as Opa proteins. As the latter requires the surface capsule to be down-modulated, invading bacteria would be serum sensitive and thus avirulent. However, there is recent evidence that capsulate bacteria may interact via Opa proteins when host cells express high levels of carcinoembryonic antigen-related cell adhesion molecules (CEACAMs), their target receptors. Such a situation may arise following increased circulation of inflammatory cytokines that upregulate certain adhesion molecules on host cells. In this study, using a tetracycline controlled expression system, we have developed cell lines with inducible CEACAM expression to mimic post-inflammation state of target tissues and analysed the interplay between the three surface components capsule, pili and Opa proteins in cellular interactions. With two distinct cell lines, not only the level but also the rate of adhesion of capsulate Opa-expressing Nm increased concurrently with CEACAM density. Moreover, when threshold levels of receptor were reached, cellular invasion ensued in an Opa-dependent manner. In studies with cell lines intrinsically expressing pilus receptors, notable synergism in cellular interactions between pili and Opa of several meningococcal strains was observed and was independent of capsule type. A number of internalized bacteria were shown to express capsule and when directly isolated from host cells, these bacteria were as serum resistant as the inoculated phenotype. Furthermore, we observed that agents that block Opa-CEACAM binding substantially reduced cellular invasion, while maintaining

  14. Utility of slot-blot-ELISA as a new, fast, and sensitive immunoassay for detection of carcinoembryonic antigen in the urine samples of patients with various gastrointestinal malignancies. (United States)

    El-Masry, Samir; El-Sayed, Ibrahim H; Lotfy, Mahmoud; Mahmoud, Lamiaa; El-Naggar, Mohamed


    Carcinoembryonic antigen (CEA) is the most widely used clinical tumor marker. CEA immunoassay has found acceptance as a diagnostic adjunct in clinical diagnosis of gastrointestinal tumors (GIT). Several immunoassays have been established for detection of CEA in plasma, serum, tissue, feces, and urine of cancer patients using polyclonal or monoclonal antibodies raised against CEA. Some of these assays display both high sensitivity and specificity for the detection of CEA. However, these assays require special and highly expensive equipment and the procedures require long periods for their completion. In the present study, we established a Slot-Blot Enzyme Linked Immunosorbent Assay (SB-ELISA), based on anti-CEA monoclonal antibody (CEA-mAb), as a new, simple, fast, cheap, and non-invasive immunodiagnostic technique for detection of CEA in the urine of GIT patients. Urine and serum samples were collected from 248 GIT patients (58 with pancreatic cancer, 20 with hepatoma, 23 with ampullary carcinoma, 15 with hilar cholangiocarcinoma, 28 with gastric cancer, 14 with esophageal cancer, and 90 with colorectal cancer). Moreover, urine and serum samples were collected from 50 healthy individuals to serve as negative controls. The traditional ELISA technique was used for determination of CEA in the sera of GIT patients using anti-CEA monoclonal antibody. A comparison between the results of both techniques (ELISA and SB-ELISA) was carried out. The traditional ELISA detected CEA in the sera of 154 out of 248 GIT patients with a sensitivity of 59.8%, 51.7% positive predictive value (PPV) and 75.37% negative predictive value (NPV). In addition, it identified 15 false positive cases out of 50 healthy individuals with a specificity of 70%. The urinary CEA was identified by a Western blotting technique and CEA-mAb at a molecular mass of 180 Kda. The developed SB-ELISA showed higher sensitivity, specificity, PPV, and NPV (70.1%, 78%, 62.4%, and 82.13%, respectively) for detection

  15. Fully human IgG and IgM antibodies directed against the carcinoembryonic antigen (CEA Gold 4 epitope and designed for radioimmunotherapy (RIT of colorectal cancers

    Directory of Open Access Journals (Sweden)

    Pugnière Martine


    Full Text Available Abstract Background Human monoclonal antibodies (MAbs are needed for colon cancer radioimmunotherapy (RIT to allow for repeated injections. Carcinoembryonic antigen (CEA being the reference antigen for immunotargeting of these tumors, we developed human anti-CEA MAbs. Methods XenoMouse®-G2 animals were immunized with CEA. Among all the antibodies produced, two of them, VG-IgG2κ and VG-IgM, were selected for characterization in vitro in comparison with the human-mouse chimeric anti-CEA MAb X4 using flow cytometry, surface plasmon resonance, and binding to radiolabeled soluble CEA and in vivo in human colon carcinoma LS174T bearing nude mice. Results Flow cytometry analysis demonstrated binding of MAbs on CEA-expressing cells without any binding on NCA-expressing human granulocytes. In a competitive binding assay using five reference MAbs, directed against the five Gold CEA epitopes, VG-IgG2κ and VG-IgM were shown to be directed against the Gold 4 epitope. The affinities of purified VG-IgG2κ and VG-IgM were determined to be 0.19 ± 0.06 × 108 M-1 and 1.30 ± 0.06 × 108 M-1, respectively, as compared with 0.61 ± 0.05 × 108 M-1 for the reference MAb X4. In a soluble phase assay, the binding capacities of VG-IgG2κ and VG-IgM to soluble CEA were clearly lower than that of the control chimeric MAb X4. A human MAb concentration of about 10-7 M was needed to precipitate approximatively 1 ng 125I-rhCEA as compared with 10-9 M for MAb X4, suggesting a preferential binding of the human MAbs to solid phase CEA. In vivo, 24 h post-injection, 125I-VG-IgG2κ demonstrated a high tumor uptake (25.4 ± 7.3%ID/g, close to that of 131I-X4 (21.7 ± 7.2%ID/g. At 72 h post-injection, 125I-VG-IgG2κ was still concentrated in the tumor (28.4 ± 11.0%ID/g whereas the tumor concentration of 131I-X4 was significantly reduced (12.5 ± 4.8%ID/g. At no time after injection was there any accumulation of the radiolabeled MAbs in normal tissues. A pertinent analysis of

  16. The Comparison of ELISA And ICA in Carcinoembryonic Antigen Detection%ELISA与ICA对癌胚抗原检测的比较

    Institute of Scientific and Technical Information of China (English)

    彭文忠; 余高冰


      目的:比较磁粒子捕获免疫发光法(ICA)和酶联免疫吸附分析法(ELISA)测定血癌胚抗原(CEA)的结果,了解这两种方法的优劣,探讨ICA和ELISA检测CEA的灵敏性和准确性。方法:ICA和ELISA作对比试验、回收试验和精密度试验。结果:对比试验,ICA法所测CEA含量为Y值, ELISA所测CEA含量为X值,则回归方程:Y=1.32X+8.23,相关系数r=0.991;回收试验,用ICA和ELSIA平均回收率分别为97.64%和96.73%;精密度试验,ELISA和ICA的批内精密度分别为11.74%和1.92%,批间精密度分别15.41%和3.68%。结论:ICA与ELISA线性相关性较好,批内、批间精密度均优于ELISA法,ICA的检测精度高,稳定性强,回收率高于ELISA,ICA法在检测准确度和稳定性上,较之ELISA具有很强的优越性。%Objective:To compare magnetic particle capture immune luminescence(ICA) method and enzyme linked immunosorbent assay(ELISA) in determination of serum carcinoembryonic antigen (CEA) results,and understanding these two methods advantages and disadvantages and discuss ICA and ELISA detection of CEA sensitivity and accuracy.Methods:ICA and ELISA contrast test,recovery test and precision test.Results:Contrast test,Y was ICA method measured CEA content,X was ELISA measured CEA content,the regression equation:Y=1.32X+8.23,correlation coefficient r=0.991.Recovery test,with the ICA and ELSIA average recovery rate was 97.64%and 96.73%.The accuracy test,ELISA and the group of ICA in precision were 11.74%and 1.92%respectively. Batch precision was between 15.41%and 3.68%respectively.Conclusion:ICA and ELISA linear correlation is better,in the group,and group were superior to that of ELISA method between precision,ICA has high accuracy,stability is strong,ICA recovery than ELISA is high,the ICA in detection accuracy and stability compared with ELISA has a strong advantage.

  17. Establishment of Carcinoembryonic Antigen Working Standard for Immunoassay%癌胚抗原工作标准品的制备

    Institute of Scientific and Technical Information of China (English)

    徐立根; 孙有香; 焦岩


    The article is to prepare the working standard of carcinoembryonic antigen (CEA) for immunoassay and determine its potency.CEA solution of 320 μg/L was prepared from purified CEA solution of 4.6mg/L and 1% human albumin solution buffered with 50mmol/L sodium phosphate,pH7.4.This solution was distributed in an aliquot of0.5mL(160 ng per ampoule) and lyophilized.The potency of CEA working standard,in terms of present standard of CEA RIA and IRMA kits made by Chinese manufacturers and in terms of 1st IRP CEA HUMAN 73/601 supplied by WHO,has been determined.Mean immunological potency of the working standard is 163 ng per ampoule with confident limit of 159-168 ng per ampoule at 95% probability level.Test of parallelism of dose-response curve for the working standard to that for 1st IRP CEA HUMAN 73/601 has been passed.CEA working standard is suitable to the kits standard for CEA radioimmunoassay and immunoradiometric assay.%制备供免疫分析用的癌胚抗原工作标准品并标定其免疫效价。用4.6mg/L CEA纯品溶液和pH7.4的1%人白蛋白-50mmol Na2HPO4-NaH2PO4溶液配制浓度为320μg/L的工作标准品溶液。将该溶液按每安瓿(amp.)0.5mL(160ng/amp.)分装、冻干。以国产CEA RIA和CEA IRMA药盒现行标准品为对照品,标定工作标准品效价,并与国际参考制剂1st IRP CEA HUMAN 73/601进行对照实验。以药盒标准品为对照品,工作标准品平均免疫效价为163ng/amp.,95%可信限为159-168ng/amp.,工作标准品与国际参考制剂的剂量-反应曲线不显著偏离平行。CEA工作标准品与国际参考制剂1st IRP CEA 73/601在免疫学反应中是同质的,可以作为实验室间对照品使用。

  18. 血清CA125、CEA水平与宫颈癌相关性分析%Association of serum carcinoembryonic antigen and carbohydrate antigen 125 with cervical cancer

    Institute of Scientific and Technical Information of China (English)



    Objective To analyze the association of serum carcinoembryonic antigen ( CEA )and carbohydrate antigen 125 ( CA125 ) with cervical cancer.Methods 100 patients with cervical cancer who had been treated in our hospital during the period of February 2007 to March 2011 were enrolled into a study group.Serum levels of CEA and CA125 were detected and their assoication with cervical cancer was analyzed; and the levels of these markers were compared with those from 60 non-cervical cancer patients ( control group ).Results Serum levels of CEA and CA125 were higher in the study group than in the control group,with a significant difference between 2 groups ( P< 0.05 ) except for stage Ⅰ cervical cancer.The correlation between CA125 and stages of cervical cancer was greater than that between CEA and cervical cancer ( P< 0.05 ).Conclusions Serum levels of CEA and CA125 are associated with cervical cancer at some degree.CA125 has more diagnostic values than CEA.%目的 分析研究血清CA125(糖链抗原125)、CEA(癌胚抗原)水平与宫颈癌的相关性.方法 将我院从2007年2月至2011年3月收治的100例宫颈癌病患设为实验组,进行血清CA125、CEA水平检测,并与宫颈癌分期相分析,将同期收治的60例非宫颈癌病患设为对照组,对比两组血清CA125、CEA水平.结果 实验组血清CA125、CEA水平均高于对照组,除Ⅰ期宫颈癌数据外,差异有统计学意义(P<0.05);血清CA125与宫颈癌分期的相关性高于血清CEA,差异有统计学意义(P<0.05 ).结论 血清CA125、CEA水平与宫颈癌有一定相关性,检测简单方便,且血清CA125比血清CEA更具诊断价值.

  19. Polyethylene glycol (PEG) linked to near infrared (NIR) dyes conjugated to chimeric anti-carcinoembryonic antigen (CEA) antibody enhances imaging of liver metastases in a nude-mouse model of human colon cancer. (United States)

    Maawy, Ali A; Hiroshima, Yukihiko; Zhang, Yong; Luiken, George A; Hoffman, Robert M; Bouvet, Michael


    We report here that polyethylene glycol (PEG) linked to near infrared dyes conjugated to chimeric mouse-human anti-carcinoembryonic antigen (CEA) antibody greatly improves imaging of liver metastases in a nude mouse model of colon-cancer experimental metastases. PEGylated and non-PEGylated DyLight 650 and 750 dyes were conjugated to the chimeric anti-CEA antibody. The dyes were initially injected intravenously into nude mice without tumors. Tissue biodistribution was determined by tissue sonication and analyzing tissue dye concentration profiles over time. PEGylated dyes had significantly lower accumulation in the liver (p = 0.03 for the 650 dyes; p = 0.002 for the 750 dyes) compared to non-PEGylated dyes. In an experimental liver metastasis model of HT-29 colon cancer, PEGylated dyes conjugated to the anti-CEA antibody showed good labeling of metastatic tumors with high contrast between normal and malignant tissue which was not possible with the non-PEGylated dyes since there was so much non-specific accumulation in the liver. PEGylation of the DyLight 650 and 750 NIR dyes significantly altered tissue biodistribution, allowing brighter tissue labeling, decreased accumulation in normal organs, particularly the liver. This enabled high fidelity and high contrast imaging of liver metastases.

  20. Polyethylene glycol (PEG linked to near infrared (NIR dyes conjugated to chimeric anti-carcinoembryonic antigen (CEA antibody enhances imaging of liver metastases in a nude-mouse model of human colon cancer.

    Directory of Open Access Journals (Sweden)

    Ali A Maawy

    Full Text Available We report here that polyethylene glycol (PEG linked to near infrared dyes conjugated to chimeric mouse-human anti-carcinoembryonic antigen (CEA antibody greatly improves imaging of liver metastases in a nude mouse model of colon-cancer experimental metastases. PEGylated and non-PEGylated DyLight 650 and 750 dyes were conjugated to the chimeric anti-CEA antibody. The dyes were initially injected intravenously into nude mice without tumors. Tissue biodistribution was determined by tissue sonication and analyzing tissue dye concentration profiles over time. PEGylated dyes had significantly lower accumulation in the liver (p = 0.03 for the 650 dyes; p = 0.002 for the 750 dyes compared to non-PEGylated dyes. In an experimental liver metastasis model of HT-29 colon cancer, PEGylated dyes conjugated to the anti-CEA antibody showed good labeling of metastatic tumors with high contrast between normal and malignant tissue which was not possible with the non-PEGylated dyes since there was so much non-specific accumulation in the liver. PEGylation of the DyLight 650 and 750 NIR dyes significantly altered tissue biodistribution, allowing brighter tissue labeling, decreased accumulation in normal organs, particularly the liver. This enabled high fidelity and high contrast imaging of liver metastases.

  1. Specific tumor labeling enhanced by polyethylene glycol linkage of near infrared dyes conjugated to a chimeric anti-carcinoembryonic antigen antibody in a nude mouse model of human pancreatic cancer (United States)

    Maawy, Ali A.; Hiroshima, Yukihiko; Zhang, Yong; Luiken, George A.; Hoffman, Robert M.; Bouvet, Michael


    Labeling of metastatic tumors can aid in their staging and resection of cancer. Near infrared (NIR) dyes have been used in the clinic for tumor labeling. However, there can be a nonspecific uptake of dye by the liver, lungs, and lymph nodes, which hinders detection of metastasis. In order to overcome these problems, we have used two NIR dyes (DyLight 650 and 750) conjugated to a chimeric anti-carcinoembryonic antigen antibody to evaluate how polyethylene glycol linkage (PEGylation) can improve specific tumor labeling in a nude mouse model of human pancreatic cancer. The conjugated PEGylated and non-PEGylated DyLight 650 and 750 dyes were injected intravenously into non-tumor-bearing nude mice. Serum samples were collected at various time points in order to determine serum concentrations and elimination kinetics. Conjugated PEGylated dyes had significantly higher serum dye concentrations than non-PEGylated dyes (p=0.005 for the 650 dyes and pdecreased their accumulation in lymph nodes, liver, and lung. These results demonstrate enhanced selective tumor labeling by PEGylation of dyes conjugated to a tumor-specific antibody, suggesting their future clinical use in fluorescence-guided surgery.

  2. Structure and Function of Human Carcinoembryonic Antigen-related Cellular Adhesion Molecule 1%人体癌胚抗原相关细胞黏附分子1的结构与功能

    Institute of Scientific and Technical Information of China (English)



    人癌胚抗原相关细胞黏附分子1(CEACAMl)是广泛表达于中性粒细胞、巨噬细胞、内皮细胞、上皮细胞及淋巴细胞表面的Ⅰ型跨膜糖蛋白,属癌胚抗原家族免疫球蛋白超家族分子,胞膜外区有Ig样结构域,CEACAM1-L型具有两个免疫受体酪氨酸抑制性基序,其生物学功能包括免疫调节、促进血管形成、调节血管重构、参与细胞凋亡调控、促进腺体管腔形成及调控胰岛素的清除,同时CEACAM1也是致病微生物的黏着受体.%Human carcinoembryonic antigen-related cellular adhesion molenile l( CEACAM1 )is a member of the carcinoembryonir antigen iamily(CEA )whirh is a type I-transmembrane glycoprotein broadly expressed on the surface oi cells including: macrophages, neutrophilic granulocyte, lymphocyte, epithelial, and endothelial cells. It is an adhesion molecule oi immunoglobulin superfamily. The extiacellulai' domain oi CEACAM 1 contains IgG-like stmctuie. The long form oi CEACAM1 protein has two immunoieceptoi tinosine-based inhibitoiy motiis( ITIMs )that have crucial roles in immu no-regulation, vascular neogenesis, vascular remolding, cell apoptosis regulation, gland lumen formation and insulin clearance. CEACAM1 is also a receptor for pathogenic bacteria and viruses.

  3. Randomised Phase I/II trial assessing the safety and efficacy of radiolabelled anti-carcinoembryonic antigen I131 KAb201 antibodies given intra-arterially or intravenously in patients with unresectable pancreatic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Bosonnet Lorraine


    Full Text Available Abstract Background Advanced pancreatic cancer has a poor prognosis, and the current standard of care (gemcitabine based chemotherapy provides a small survival advantage. However the drawback is the accompanying systemic toxicity, which targeted treatments may overcome. This study aimed to evaluate the safety and tolerability of KAb201, an anti-carcinoembryonic antigen monoclonal antibody, labelled with I131 in pancreatic cancer (ISRCTN 16857581. Methods Patients with histological/cytological proven inoperable adenocarcinoma of the head of pancreas were randomised to receive KAb 201 via either the intra-arterial or intravenous delivery route. The dose limiting toxicities within each group were determined. Patients were assessed for safety and efficacy and followed up until death. Results Between February 2003 and July 2005, 25 patients were enrolled. Nineteen patients were randomised, 9 to the intravenous and 10 to the intra-arterial arms. In the intra-arterial arm, dose limiting toxicity was seen in 2/6 (33% patients at 50 mCi whereas in the intravenous arm, dose limiting toxicity was noted in 1/6 patients at 50 mCi, but did not occur at 75 mCi (0/3. The overall response rate was 6% (1/18. Median overall survival was 5.2 months (95% confidence interval = 3.3 to 9 months, with no significant difference between the intravenous and intra-arterial arms (log rank test p = 0.79. One patient was still alive at the time of this analysis. Conclusion Dose limiting toxicity for KAb201 with I131 by the intra-arterial route was 50 mCi, while dose limiting toxicity was not reached in the intravenous arm.

  4. 硫醇衍生化的纳米金与癌胚抗原相互作用的光学分析%Optical Analysis of the Interaction of Mercaptan Derivatives of Nanogold Particles with Carcinoembryonic Antigen

    Institute of Scientific and Technical Information of China (English)

    曾红娟; 赵然琳; 王德舜; 李彩霞; 刘贻尧


    Gold nanoparticles (AuNPs) have been the subject of intense research for use in biomedicine over the past couple of decades .AuNPs ,also referred to as colloidal gold ,possess some astounding optical and physical properties that have earned them a prime spot among the new promising tools for medical applications .Today ,AuNPs are offered to provide the clinical la-boratory with more sensitive ,faster ,and simpler assays ,which are also cost-effective .AuNPs can be used to develop point-of-care tests and novel testing strategies such as in drug targeting ,disease detection ,molecular recognition ,and biological labels . The typical structure of AuNPs is spherical nano-sized gold particles ,but they can also be composed of a thin gold shell sur-rounding a dielectric core ,such as silica (gold nanoshells) .their size range from 0.8 to 250 nm and are characterized by high ab-sorption coefficients .AuNPs have some unique optical properties ,such as enhanced absorption and scattering ,where the ab-sorption cross-section of AuNPs is 4~5 orders of magnitude greater than that of rhodamine 6G .When AuNPs aggregate ,inter-action of locally adjacent AuNPs (plasmon-plasmon interaction) shifts their color to blue .Thus ,the binding of AuNP-labeled entities to their respective target would lead to aggregation of the nanoparticles and a detectable shift in the optical signal .The strong absorption of AuNPs can also be used in colorimetric detection of analytes by measuring changes in the refractive index of the AuNP's environment caused by adsorption of the target analytes .However ,a large number of surface atoms of nanoparticles have huge surplus bonding ability ,because of surface effect of gold nanoparticles ,result in reuniting and sinking among the nan-oparticles which make them unstable .In order to detect traces of carcinoembryonic antigen ,one of the tumor targets ,a new kind of gold nanoparticle with hyperchormic effect and fluorescence sensitization effect material

  5. Radioimmunotherapy of small cell lung carcinoma with the two-step method using a bispecific anti-carcinoembryonic antigen/anti-diethylenetriaminepentaacetic acid (DTPA) antibody and iodine-131 Di-DTPA hapten: results of a phase I/II trial. (United States)

    Vuillez, J P; Kraeber-Bodéré, F; Moro, D; Bardiès, M; Douillard, J Y; Gautherot, E; Rouvier, E; Barbet, J; Garban, F; Moreau, P; Chatal, J F


    As small cell lung carcinoma (SCLC) is frequently a widespread disease at diagnosis, highly radiosensitive and often only partially responsive to chemotherapy, radioimmunotherapy (RIT) would appear to be a promising technique for treatment. We report the preliminary results of a Phase I/II trial of RIT in SCLC using a two-step method and a myeloablative protocol with circulating stem cells transplantation. Fourteen patients with proved SCLC relapse after chemotherapy were treated with RIT. They were first injected i.v. with a bispecific (anti-carcinoembryonic antigen/anti-diethylenetriaminepentaacetic acid) monoclonal antibody (20-80 mg in 100 ml of saline solution) and then 4 days later with di-(In-diethylenetriaminepentaacetic acid)-tyrosyl-lysine hapten labeled with 1.48-6.66 GBq (40-180 mCi) of I-131 and diluted in 100 ml of saline solution. In patients receiving 150 mCi or more, circulating stem cells were harvested before treatment and reinfused 10-15 days later. Treatment response was evaluated by CT and biochemical data during the month before and 1, 3, 6, and 12 months after treatment. All patients received the scheduled dose without immediate adverse reactions to bispecific antibody or 1-131 hapten. Toxicity was mainly hematological, with two cases of grade 2 leukopenia and three cases of grade 3 or 4 thrombopenia. Body scanning 8 days after injection of the radiolabeled hapten generally showed good uptake at the tumor sites. Estimated tumor dose was 2.6-32.2 cGy/mCi. Among the 12 patients evaluated to date, we have observed 9 progressions, 2 partial responses (one almost complete for 3 months), and 1 stabilization of more than 24 months. Efficiency and toxicity were dose-related. The maximal tolerable dose without hematological rescue was 150 mCi. These preliminary results are encouraging, and dose escalation is currently continuing to reach 300 mCi. RIT should prove to be an interesting therapeutic method for SCLC, although repeated injections and

  6. 血清AFP、CEA、AFU、GGT-Ⅱ联合检测诊断原发性肝癌的临床价值%Clinical value of combined measurement of serum alpha-fetoprotein, carcinoembryonic antigen, alpha-L-fucosidase, gamma-glutamyltransferase isoenzymes for diagnosis of primary liver cancer

    Institute of Scientific and Technical Information of China (English)

    宁珠; 殷芳; 刘海; 尤丽英; 杨晋辉; 郑盛


    Objective To evaluate the clinical value of combined measurement of four serum tumor markers (alpha-fe-toprotein, carcinoembryonic antigen, alpha-L-fucosidase, gamma-glutamyltransferase isoenzymes) for diagnosis of primary liver cancer. Methods 160 patients with primary liver cancer and 120 healthy subjects were measured the serum levels of alpha-fetoprotein, carcinoembryonic antigen, alpha-L-fucosidase, gamma-glutamyltransferase isoenzymes was detected by using not continuous PAGE. The results were analyzed by SPSS 15.0 software. Results The serum levels of alpha-fetoprotein, carcinoembryonic antigen, alpha-L-fucosidase were significantly higher in the primary liver cancer patients than those in the control group (P < 0.01). The positive rate of single marker of alpha-fetoprotein, carcinoembryonic antigen, alpha-L-fucosidase, gamma-glutamyltransferase isoenzymes was 68.00%, 28.00%, 84.00% and 77.00% respectively, and there were statistical significances during carcinoembryonic antigen, alpha-L-fucosidase, gamma-glutamyltransferase isoenzymes (all P < 0.05). The positive rate of the combined measured of two markers: alpha-fe-toprotein/carcinoembryonic antigen, alpha-fetoprotein/alpha-L-fucosidase and alpha-fetoprotein/gamma-glutamyltrans-ferase isoenzymes were 75.00%, 84.00% and 89.00% respectively, and there were statistical significances during the positive rates of the combined measured of alpha-fetoprotein/alpha-L-fucosidase, alpha-fetoprotein/gamma-glutamyl-transferase isoenzymes compared with alpha-fetoprotein (all P < 0.05). But the positive rate of combined measurement of four markers was 96.00% and there was evidently statistical significance compared with the alpha-fetoprotein result (P < 0.01). Conclusion The combined measurement of alpha-fetoprotein, carcinoembryonic antigen, alpha-L-fucosidase, gamma-glutamyltransferase isoenzymes can be used as an accessory tool in diagnosis of primary liver cancer.%目的 探讨血清甲胎蛋白、癌胚抗原、

  7. Immunoradiometric assay for carcinoembryonic antigenusing avidin-biotin separation technique

    Institute of Scientific and Technical Information of China (English)


    A sensitive, specific, noncompetitive, sandwich-typeradioimmunoassay for carcinoembryonic antigen (CEA) has been developedin our laboratory, which can be performedconveniently. The assay involves two monoclonal antibodies, selected for highaffinity and specificity and also for reaction against antigenic sites on CEA that aredistal from each other. One of these antibodies was labeled with125I and the other wasconjugated covalently to biotin. Polystyrene tubes were conjugated covalently toavidin. These tubes represent a rapid, simple method for separating the CEA-boundantibody from the free antibody. The biotin-antibody-CEA-125I-labeled antibodycomplexes bind to the tubes and CEA concentration is directly related to counts perminute. This assay can detect the CEA at a concentration of 0.22 μg/L in serum.

  8. 乳腺癌患者血清乳脂球表皮生长因子8、糖类抗原125及癌胚抗原的表达及其意义%Expression and significance of serum milk fat globule epidermal growth factor 8,carbohydrate antigen 125,carcinoembryonic antigen in patients with breast cancer

    Institute of Scientific and Technical Information of China (English)

    张超; 姜炜


    目的:探讨乳腺癌患者血清乳脂球表皮生长因子8(MFG⁃E8)、糖类抗原125(CA125)、CEA的表达及其临床意义。方法测定108例乳腺癌患者(乳腺癌组)、108例乳腺良性肿瘤患者(乳腺良性肿瘤组)的血清MFG⁃E8、CA125、CEA浓度,比较良恶性患者、转移与否患者各肿瘤标志物的浓度,分析单独及联合检测对乳腺癌的诊断价值。结果与乳腺良性肿瘤组[(207.2±47.1) ng/L、(8.64±2.86) U/ml、(1.38±0.37)μg/L]比较,乳腺癌组血清 MFG⁃E8[(5182.1±564.5) ng/L]、CA125[(34.22±7.20) U/ml]、CEA[(4.41±1.22)μg/L]均显著升高(t 值分别为91.27、34.31、24.70,P 均<0.05);与乳腺癌未转移者[(4814.4±351.1) ng/L、(24.13±5.71) U/ml]比较,转移者血清MFG⁃E8[(6362.8±678.4) ng/L]、CA125[(37.45±10.40) U/ml]浓度显著升高(t 值分别为15.47、8.53,P 均<0.05),转移者、未转移者血清CEA浓度差异无统计学意义( P>0.05);3项指标联合检测的敏感性为82.4%,均明显高于血清 MFG⁃E8、CA125、CEA 任一指标单独检测,诊断准确率为85.2%,显著高于CA125、CEA单独检测,差异均有统计学意义( P均<0.05)。结论血清MFGE8、CA125、CEA在乳腺癌患者中呈高表达状态,联合检测对于明确诊断以及治疗方案的选择具有一定指导意义。%Objective To explore the expression and clinical significance of serum milk fat globule epi⁃dermal growth factor 8(MFG⁃E8),carbohydrate antigen 125(CA125),carcinoembryonic antigen(CEA) in pa⁃tients with breast cancer. Methods The levels of serum MFG⁃E8,CA125,CEA were detected in 108 cases pa⁃tients with breast cancer(breast cancer group) and 108 cases patient with benign breast tumors(benign breast tumor group). The level of each indicators between malignant and non

  9. 乳脂肪球表面生长因子8、糖类抗原153和癌胚抗原在乳腺癌中的表达及意义%Expression and significance of milk fat globule epidermal growth factor 8 and carbohydrate antigen 153, carcinoembryonic antigen in breast cancer

    Institute of Scientific and Technical Information of China (English)

    张家衡; 杨泳; 李杰宝; 崔天盆; 冯先华


    目的 探讨乳脂肪球表面生长因子8(MFGE8)、糖类抗原153(CA153)和癌胚抗原(CEA)在乳腺癌中的表达及其意义.方法 选取乳腺癌患者、乳腺纤维瘤患者和健康体检者各30例,采用酶联免疫吸附试验(ELISA)检测MFGE8水平,采用电化学发光法检测CA153、CEA水平.结果 乳腺癌患者血清中MFGE8、CA153、CEA分别为(6032.3±3043.7) ng/L、(58.72±28.80) U/ml、(4.35 ± 3.20) μg,/L,明显高于良性组和对照组,与两组间差异有统计学意义(P<0.01).MFGE8、CA153、CEA诊断乳腺癌的敏感性分别为68.4%、55.9%、33.5%,良性组分别为8.1%、5.7%、3.1%,对照组分别为1.1%、0.7%、0.3%,各组间两两比较,差异有统计学意义(P<0.05).三者联合检测的敏感性为86.3%;准确性分别为88.3%、63.3%、55.6%,三者联合检测为92.2%.结论 MFGE8、CA153、CEA联合检测可做为乳腺癌的预测指标.%Objective To discuss the expression and significance of milk fat globule epidermal growth factor 8 (MFGE8) and carbohydrate antigen 153 (CA153),carcinoembryonic antigen (CEA) in breast cancer.Methods 30 patients with breast cancer,30 patients with mammary gland fibroma and 30 healthy volunteers were selected.Eenzyme-linked immunosorbent assay was used to detect serum level of MFGES,and electrochemiluminescence immunoassay to detect serum level of CA153 and CEA.Results The serum levels of MFGE8,CA153 and CEA in patients with breast cancer were (6032.3 ±3043.7) ng/L,(58.72 ± 28.8) U/ml and (4.35 ± 3.2) μg/L respectively,which were significantly higher than others (P < 0.01 for all).The positive rate of MFGES,CA153 and CEA in patients with breast cancer was 68.4%,55.9% and 33.5%,that was 8.1%,5.7% and 3.1% in patients with mammary gland fibroma,and that was 1.1%,0.7% and 0.3% in control group,respectively.There was significant difference between each two groups (P < 0.05).By combined detection of MFGE8,CA153 and CEA

  10. Differential Recognition and Hydrolysis of Host Carbohydrate Antigens by Streptococcus pneumoniae Family 98 Glycoside Hydrolases

    Energy Technology Data Exchange (ETDEWEB)

    Higgins, M.; Whitworth, G; El Warry, N; Randriantsoa, M; Samain, E; Burke, R; Vocadlo, D; Boraston, A


    The presence of a fucose utilization operon in the Streptococcus pneumoniae genome and its established importance in virulence indicates a reliance of this bacterium on the harvesting of host fucose-containing glycans. The identities of these glycans, however, and how they are harvested is presently unknown. The biochemical and high resolution x-ray crystallographic analysis of two family 98 glycoside hydrolases (GH98s) from distinctive forms of the fucose utilization operon that originate from different S. pneumoniae strains reveal that one enzyme, the predominant type among pneumococcal isolates, has a unique endo-{beta}-galactosidase activity on the LewisY antigen. Altered active site topography in the other species of GH98 enzyme tune its endo-{beta}-galactosidase activity to the blood group A and B antigens. Despite their different specificities, these enzymes, and by extension all family 98 glycoside hydrolases, use an inverting catalytic mechanism. Many bacterial and viral pathogens exploit host carbohydrate antigens for adherence as a precursor to colonization or infection. However, this is the first evidence of bacterial endoglycosidase enzymes that are known to play a role in virulence and are specific for distinct host carbohydrate antigens. The strain-specific distribution of two distinct types of GH98 enzymes further suggests that S. pneumoniae strains may specialize to exploit host-specific antigens that vary from host to host, a factor that may feature in whether a strain is capable of colonizing a host or establishing an invasive infection.

  11. Immunohistology of carcinoembryonic antigen (CEA)-expressing tumors grafted in nude mice after radioimmunotherapy with 131I-labeled bivalent hapten and anti-CEA x antihapten bispecific antibody. (United States)

    Gautherot, E; Kraeber-Bodéré, F; Daniel, L; Fiche, M; Rouvier, E; Saï-Maurel, C; Thedrez, P; Chatal, J F; Barbet, J


    We have developed a pretargeting strategy, called the Affinity Enhancement System (AES), which uses bispecific antibodies (BsF(ab')2) to target radiolabeled bivalent haptens to tumor cells. We performed several radioimmunotherapy (RIT) experiments in nude mice grafted with LS174T colon carcinoma or TT medullary thyroid cancer. Mice were treated with 131I-labeled di-DTPA-indium-tyrosyl-lysine bivalent hapten (75-112 MBq) administered 15-48 h after anti-CEA x anti-DTPA-indium BsF(ab')2. Immunohistological studies were performed on tumors at their minimal relative volume (TT), on stabilized tumor nodules (LS174T), and on regrowing tumors (TT and LS174T). Untreated tumors were used as controls. On microscopic examination, regrowing tumors (2 months posttherapy) were similar to untreated tumors with cells showing their respective typical morphology (large cells with a high nucleocytoplasmic ratio for TT, small and very undifferentiated cells for LS174T). However, regrowing tumors showed larger necrotic areas and a higher mitotic index correlated with Ki-67 antigen staining. Immunostaining for CEA was as strong as for controls. By contrast, the immunohistology of TT tumors at their minimal relative volume (1 month posttherapy) or of LS174T residual nodules (8 months posttherapy) showed decreased mitotic indices correlated with poor Ki-67 antigen staining. Some clusters of LS174T presented with features of glandular lumen, which suggested a more differentiated and less aggressive status. In TT tumors, CEA expression remained unchanged (80-100% membrane and cytoplasmic staining), whereas only 70% of the LS174T tumors were stained, with 58% loss of the membrane expression. Repeated treatment early after the tumor has reached its minimal relative volume should thus be efficient and improve the overall efficacy of AES RIT.

  12. Expression and evolution of members of the Trypanosoma cruzi trypomastigote surface antigen multigene family. (United States)

    Ruef, B J; Dawson, B D; Tewari, D; Fouts, D L; Manning, J E


    The trypomastigote specific surface antigens of Trypanosoma cruzi are encoded by a supergene family which includes the TSA family. The TSA family is characterized by the presence of a 27-bp tandem repeat array in the coding region. Here, we report the characterization and analysis of the three TSA family members in the Esmeraldo strain of the parasite. In this strain 2 distinct telomeric members are expressed abundantly as 3.7-kb mRNAs, while the remaining member is located at an internal chromosomal site and is expressed at less than 2% of the level seen for the telomeric members. Based on hybridization to DNA separated by PFGE, 3 chromosomes of sizes 1.8 Mb, 0.98 Mb, and 0.90 Mb each contain one of the telomeric members. In addition, the two smaller chromosomes also contain the single internal member. Since both chromosomes contain similar TSA family members, and vary only slightly in size, we suggest that they are homologues. Comparisons of the nucleotide sequences of the different members of the family show that the internal gene differs from the telomeric genes primarily in sequences found 3' of the repeat array. These comparisons also reveal that the three genes are analogous, supporting the hypothesis that short segments between the family members are exchanged by gene conversion events. We propose that similar conversion events between members of different gene families may generate some of the diversity found within the supergene family.

  13. Human carcinoembryonic antigen-related cellular adhesion molecules 1 mediated susceptibility of Neisseria gonorrhoeae to mouse%人癌胚抗原相关细胞黏附分子1介导的小鼠淋病奈瑟菌易感性

    Institute of Scientific and Technical Information of China (English)

    李国才; 季明春; 杜庆辉; 王晓红; 王劲松; 于峰; 刘双喜; 解如山; 焦红梅; 严华


    Objective To develop a transgenic mouse model for N.gonorrhoeae researches.Methods Human carcinoembryonic antigen-related cellular adhesion molecules 1 (hCEACAM1) eukaryotic expression vector,pCDPGICAM1,was used to generate transgenic mice by microinjection.The funder mice were screened by PCR,sequence analysis,Western blot and fluorescence-activated cell sorting analysis,respectively.The transgenic mice expressing hCEACAM1 were inoculated with N.gonorrhoeae intravaginally.Adhesion and infection of gonococci to mice were analyzed by bacteria culture and microscopy.Results Four (lines 50,53,54,and 59) of the 22 F0 generation transgenic mice were found to carry the transgene.The hCEACAM1 protein was expressed on the cell membrane of various tissues in the line 53 transgenic mouse.Compared with normal mice,N.gonorrhoeae can successfully infect and cause inflammation in the transgenic mice.Conclusion The hCEACAM1 transgenic mouse can be used as an animal model for gonococcal infections.%目的 研究制备淋病奈瑟菌感染人癌胚抗原相关细胞黏附分子1(hCEACAM1)转基因小鼠模型的可行性.方法 用hCEACAM1真核表达载体pCDPGICEA1,通过显微注射法制备转基因小鼠,PCR及序列分析法检测目的基因在小鼠基因组中的整合,Western blot及FACS技术检测目的基因的表达,镜检及培养法检查淋病奈瑟菌对转基因小鼠的感染.结果 产生的22只F0代小鼠中4只为转基因整合阳性,其中1只可表达hCEACAM1蛋白,且目的蛋白表达在细胞膜上.淋病奈瑟菌可在转基因小鼠中形成感染.结论 hCEACAM1转基因小鼠可作为淋病奈瑟菌感染研究的转基因动物模型.

  14. Effect of Quercetin on proliferation and invasion of colon carcinoma LOVO cells and the expression level of carcinoembryonic antigen%槲皮素对结肠癌LOVO细胞增殖侵袭能力及癌胚抗原CEA表达的影响

    Institute of Scientific and Technical Information of China (English)

    安昌勇; 谢刚; 汤为学; 杨小丁; 张才全


    目的:研究槲皮素对结肠癌LOVO细胞增殖侵袭能力及癌胚抗原(CEA)表达的影响.方法:采用MTT法检测不同浓度的槲皮素对LOVO细胞增殖能力的影响;内皮细胞粘附实验和小室侵袭实验检测槲皮素对LOVO细胞侵袭能力的影响;细胞免疫荧光、WB及RT-PCR检测槲皮素对LOVO细胞癌胚抗原CEA表达的影响.结果:槲皮素能显著抑制LOVO细胞的增殖,呈浓度剂量依赖关系,IC50约为40 μmol/L;增强LOVO细胞与内皮细胞间的粘附能力,减弱其侵袭能力;并能显著抑制 CEA蛋白及mRNA的表达水平,且呈浓度剂量依赖关系.结论:槲皮素对LOVO细胞的增殖侵袭能力具有抑制作用,并能抑制CEA的表达.%AIM: To investigate the effect of Quercetin on proliferation and invasion of colon carcinoma LOVO cells as well as the expression level of carcinoembryonic antigen. METHODS: LOVO cells were treated with Quercetin at various concentrations,then determined for prolifer ation level by MTT assay, for cell adhesion and invasion of LOVO cell by tumor cell adhere to the vascular endothelial cell assay and transwell chamber invasion assay, and for the expression level of CEA by Immunocellulerchemistry (ICC), Western Blot and RT-PCR. RESULTS: Significantly, Quercetin showed dose-dependent inhibitory effect on proliferation of LOVO cells with an IC50 of about 40 μmol/L, also improved the ability of LOVO cells adhere to the vascular endothelial cells and reduced the invasion ability of LOVO cells. Meanwhile, Quercetin signifi cantly inhibited the protein and mRNA expres sion levels of CEA in LOVO cells. CONCLU SION: Quercetin has inhibition effect on the proliferation invasion ability of LOVO cells,also inhibit the protein and mRNA expression levels of CEA in LOVO cells.

  15. Analysis of Urinary Catecholamine Metabolites, Serum Carcinoembryonic Antigen and Neural Enolase in Neuroblastoma Patients%神经母细胞瘤患者尿液儿茶酚胺代谢物及血清癌胚抗原、神经烯醇化酶水平变化分析

    Institute of Scientific and Technical Information of China (English)

    杜同信; 方群; 王自正; 俞杨; 傅雷; 赵飞浪; 周俊山; 周峰


    Objective To investigate the value of detection of urinary catecholamine metabolites, serum carcino-embryonic antigen (CEA) and neural enolase (NSE) in the diagnosis and differential diagnosis of neuroblasto-ma (NB). Method The urinary catecholamine metabolites including vanillylmandelic acid (VMA) and ho-movanillic acid (HVA), and serum CEA and NSE levels in 36 neuroblastoma patients and 30 controls were detected by high-performance liquid chromatography and chemiluminescence assay respectively. Results The urinary catecholamine metabolites VMA, HVA, serum CEA and NSE in NB patients were significant higher than those in the control group (P%目的 探讨尿中儿茶酚胺代谢物及血清癌胚抗原(CEA)、神经烯醇化酶(NSE)在神经母细胞瘤(NB)诊断和鉴别诊断中的应用价值.方法 用高效液相色谱和化学发光免疫分析技术,分别对36例NB患者和30名正常对照者尿液儿茶酚胺代谢产物香草扁桃酸(VMA)、高香草酸(HVA)和血清CEA、NSE含量进行检测分析.结果 NB患者尿液VMA、HVA和血清CEA、NSE均显著高于正常对照组(P<0.01),VMA、HVA单项检测的阳性率分别为86.1%、75.0%,两项同时检测可提高到91.7%,结合NSE、CEA进行三项或四项联合检测,其阳性率可分别提高至94.4%和97.2%.结论 尿液儿茶酚胺代谢物VMA、HVA和血清肿瘤标志物CEA、NSE水平变化对NB的诊断和鉴别诊断具有重要意义,这些指标的联合检测可大大提高检测的阳性率.

  16. Carcinoembryonic antigen (CEA) as tumor marker in lung cancer

    DEFF Research Database (Denmark)

    Knudsen, Mie Grunnet; Sorensen, J B


    The use of CEA as a prognostic and predictive marker in patients with lung cancer is widely debated. The aim of this review was to evaluate the results from studies made on this subject. Using the search words "CEA", "tumor markers in lung cancer", "prognostic significance", "diagnostic...... significance" and "predictive significance", a search was carried out on PubMed. Exclusion criteria was articles never published in English, articles before 1981 and articles evaluating tumor markers in lung cancer not involving CEA. Initially 217 articles were found, and 34 were left after selecting those...... relevant for the present study. Four of these included both Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC) patients, and 31 dealt solely with NSCLC patients. Regarding SCLC no studies showed that serum level of CEA was a prognostic marker for overall survival (OS). The use of CEA...

  17. Positive and negative regulation of antigen receptor signaling by the Shc family of protein adapters. (United States)

    Finetti, Francesca; Savino, Maria Teresa; Baldari, Cosima T


    The Shc adapter family includes four members that are expressed as multiple isoforms and participate in signaling by a variety of cell-surface receptors. The biological relevance of Shc proteins as well as their variegated function, which relies on their highly conserved modular structure, is underscored by the distinct and dramatic phenotypic alterations resulting from deletion of individual Shc isoforms both in the mouse and in two model organisms, Drosophila melanogaster and Caenorhabditis elegans. The p52 isoform of ShcA couples antigen and cytokine receptors to Ras activation in both lymphoid and myeloid cells. However, the recognition of the spectrum of activities of p52ShcA in the immune system has been steadily expanding in recent years to other fundamental processes both at the cell and organism levels. Two other Shc family members, p66ShcA and p52ShcC/Rai, have been identified recently in T and B lymphocytes, where they antagonize survival and attenuate antigen receptor signaling. These developments reveal an unexpected and complex interplay of multiple Shc proteins in lymphocytes.

  18. 瘦素、脂联素联合癌胚抗原在恶性胸腔积液中的诊断价值%Diagnostic value of leptin, adiponectin and carcino-embryonic antigen in patients with malignant pleural effusion

    Institute of Scientific and Technical Information of China (English)

    朱述阳; 何军; 陈亮


    目的 探讨瘦素(Lp)、脂联素(Adipo)和癌胚抗原(CEA)对恶性胸腔积液诊断的临床意义。方法 42例良性和36例恶性胸腔积液患者的胸水和血清标本中Lp、Adipo含量采用双抗体夹心酶联免疫吸附法测定,CEA含量采用放射免疫分析法来测定。结果恶性组胸水与血清Lp、CEA含量高于良性组(P值均<0.01);恶性组胸水与血清Adipo含量低于良性组(P值均<0.01);Lp、Adipo和CEA对诊断恶性胸腔积液的敏感性分别是81.0%、76.2%和64.7%,特异性分别是74.0%、77.8%和88.1%,阳性似然比分别是3.12、3.43和5.44;指标联合诊断中以Lp和Adipo分别与CEA联合诊断功效较好,其敏感性和特异性分别是52.4%、96.9%和49.3%、97.4%,阳性似然比分别是16.90和18.96。结论 恶性胸腔积液患者的血清与胸水中Lp、Adipo与CEA浓度对诊断恶性胸腔积液有临床价值,其中以胸水中Lp和Adipo分别与CEA联合诊断功效较好。%Objective To study the clinical value of combined determination of leptin (Lp),adiponectin (Adipo) and carcino-embryonic antigen (CEA) in diagnosis of malignant pleural effusion.Methods The levels of Lp and Adipo were measured by enzyme linked immunosorbent assay and CEA was detected by radioimmunoassay in serum and pleural effusion of 36 patients with malignant pleural effusion and 42 patients with benign disease. Results The concentrations of Lp and CEA in the pleural effusion and serum of patients with malignant pleural effusion were higher than those in patients with benign pleural effusion (all P <0.01). The concentration of Adipo in the pleural effusion and serum of patients with malignant pleural effusion was lower than that in patients with benign pleural effusion (all P <0. 01). The sensitivities of Lp, Adipo,and CEA in pleural effusion were 81.0% ,76.2% ,and 64.7%,the specificities were 74.0%, 77.8%, and 88. 1%, and positive likelihood ratio were 3.12, 3

  19. DNA secondary structures are associated with recombination in major Plasmodium falciparum variable surface antigen gene families

    DEFF Research Database (Denmark)

    Sander, Adam F.; Lavstsen, Thomas; Rask, Thomas Salhøj


    -wide recombination hotspots in var genes, we show that during the parasite’s sexual stages, ectopic recombination between isogenous var paralogs occurs near low folding free energy DNA 50-mers and that these sequences are heavily concentrated at the boundaries of regions encoding individual Plasmodium falciparum......-erythrocyte membrane protein 1 structural domains. The recombinogenic potential of these 50-mers is not parasite-specific because these sequences also induce recombination when transferred to the yeast Saccharomyces cerevisiae. Genetic cross data suggest that DNA secondary structures (DSS) act as inducers...... of recombination during DNA replication in P. falciparum sexual stages, and that these DSS-regulated genetic exchanges generate functional and diverse P. falciparum adhesion antigens. DSS-induced recombination may represent a common mechanism for optimizing the evolvability of virulence gene families in pathogens....

  20. Identification of a New Member of the Ep-CAM (17-1A)Tumor-Associated Antigen Family

    Institute of Scientific and Technical Information of China (English)

    秦莉; 陈应华


    The tumor-associated antigen Ep-CAM (17-1A antigen), defined by the murine monoclonal antibody (mAb) 17-1A, has been identified as a 42-kD glycoprotein. The mAb 17-1A has been used for immunotherapy of colorectal cancer. We obtained mAb 19F4 using a synthetic peptide containing antigen determinants of 17-1A antigen. The mAb 19F4 can bind the corresponding dominants of the 17-1A antigen in ELISA. Western-blot analysis demonstrated that mAb 19F4 recognized a 50-kD protein from cell lysates of MCF-7 (breast cancer cell line). Both mAb 19F4 and 17-1A detected a 42-kD protein in the cell lysates of HT-29 (colorectal cancer cell line). The results suggest that new members of the tumor-associated antigen family 17-1A may exist.

  1. Change of level of high liquid carcinoembryonic antigen 125 in peritoneal dialysis patients with peritoneal infections and distribution of pathogens%透出液癌胚抗原125在腹膜透析患者腹膜感染时的变化与病原菌分布

    Institute of Scientific and Technical Information of China (English)

    申新宏; 陶瑾; 王焕


    OBJECTIVE To observe the change of level of the high liquid carcinoembryonic antigen 125 (CA125) in the peritoneal dialysis patients with peritoneal infections and explore the distribution of pathogens so as to provide guidance for prevention and treatment of peritoneal infections in the peritoneal dialysis patients .METHODS A total of 230 patients who underwent the peritoneal dialysis were enrolled in the study and were grouped according to the status of peritoneal infections during the peritoneal dialysis :26 patients with peritoneal infections were assigned as the infection group ,and 204 patients without peritoneal infections were set as the non‐infection group .The levels of CA125 in the dialysates and serum were determined by using electrochemiluminescence assay ,the C‐reactive protein (CRP) was detected with the use of automatic biochemical analyzer ,and the dialysates were collected from the patients with peritoneal infections for the bacterial culture .RESULTS The level of CA125 in the dialysates was (68 .44 ± 10 .78)U/ml in the infection group ,significantly higher than (29 .09 ± 9 .77)U/ml in the non‐infection group;the level of serum CRP of the infection group was (58 .95 ± 14 .63)mg/L ,significantly higher than (1 .12 ± 0 .57)mg/L of the non‐infection group(P<0 .05) .The level of CA125 in the dialysates of the patients with peri‐toneal infections was (68 .44 ± 10 .78)U/ml before the treatment of infections ,significantly higher than (29 .87 ± 9 .89)U/ml after the control of infections ;the level of serum CRP of the patients with peritoneal infections was (58 .95 ± 14 .63)mg/L before the treatment of infections ,significantly higher than (5 .27 ± 2 .03)mg/L after the control of infections(P<0 .05) .The positive rate of culture of pathogens from the dialysates was 100 .00% for the 26 patients with the peritoneal infections .Totally 41 strains of pathogens have been isolated , including 17(41 .46% ) strains of gram‐negative bacteria

  2. Relationship of levels of serum carcinoembryonic antigen and pathological imaging changes of lungs in patients with acquired immune deficiency syndrome (AIDS)%AIDS患者血清CEA水平与胸部影像学关系的临床观察

    Institute of Scientific and Technical Information of China (English)

    王家驷; 王廷杰; 王平飞; 张雪漫; 冉梅


    目的:探讨AIDS患者血清癌胚抗原(CEA)增高与胸部病变的关系。方法观察2008年1月至2011年12月间因胸部疾病入住四川省达州市中心医院呼吸内科且确诊为AIDS感染者,选取同时有胸部CT检查及血清CEA检测资料的病例68例,包括男性54例,女性14例,年龄26~78岁,平均年龄51.10岁,分析临床病史、症状、胸部CT影像学变化与血清CEA水平之间的关系。结果68例AIDS患者中,CEA增高者占44.12%,平均年龄较CEA正常组偏大3.22岁;发热、咳嗽症状患者两组间比例接近,主诉气促及合并真菌感染者是CEA正常者的1倍,而乏力盗汗、胸部不适等其他主诉则约是CEA正常者的1/2(47.83%)。CEA正常组的均值是(2.04±1.34)ng/ml,CEA增高组为(8.28±4.54)ng/ml;组间差异有显著统计学意义(P <0.001),CEA增高组发生胸部磨玻璃影(GGO)的几率是CEA正常者的4倍,而CEA正常组斑片影则约为CEA增高组的1倍;AIDS患者胸部GGO影像的密度和范围不同,其CEA的平均水平出现相应的水平差异;而未合并GGO的胸部团块影、纵膈增大及纤维索条影者CEA水平在0.00~10.93 ng/ml,与GGO者比较差异有显著统计学意义(P <0.001)。结论 AIDS患者血CEA增高可能与胸部磨玻璃影的形成相关,是CEA的一种非肿瘤性特性,可能与PCP感染相关。%Objective To approach relative of increased levels of serum carcinoembryonic antigen (CEA) to pathological changes of lunges in patients with acquired immune deficiency syndrome (AIDS). Methods The patients with diagnosed AIDS admitted on the basis of illness in department of respiratory medicine of our hospital (general hospital) from Jan 2008 to Dec 2011 were prospectively observed, in which 68 cases of patients (male 54, female 14, age range 26-78 years old, means 51.10 years old) with serum CEA data and CT detections of thorax were selected, and the relevance

  3. 基于氧化石墨烯信号放大的化学发光法联合检测甲胎蛋白和癌胚抗原%A New Dual Immunoassay for the Determination of α-Fetoprotein and Carcinoembryonic Antigen Based on Chemiluminescence Signal Amplification by Functional Graphite Oxide

    Institute of Scientific and Technical Information of China (English)

    林洁华; 张慧慧; 楚鹏飞


    A sensitive dual immunoassay was proposed for the determination of carcinoembryonic antigen(CEA) and α-fetoprotein(AFP) based on signal amplification.Monoclonal antibodies of AFP and CEA were immobilized on magnetic mesoporous silica particles(Fe3O4/SiO2) respectively and prepared as the primary probe(AFP-Ab1/Fe3O4/SiO2 and CEA-Ab1/Fe3O4/SiO2).In order to improve the detection sensitivity,the current work was focused on the signal amplification by using increased amount of horseradish peroxidase(HRP).Graphite oxide(GO) with functioned carboxyl groups were used to immobilize the HRP labeled antibodies to prepare the secondary probes(AFP-HRP-Ab2/GO and CEA-HRP-Ab2/GO).The enhanced signals were attributed to a high HRP-tag molar ratio on the surface of GO.Two subminiature quartz flow cells were set upon the photomultiplier(PMT) in parallel.As soon as CEA-Ab1/Fe3O4/SiO2 and AFP-Ab1/Fe3O4/SiO2 were injected into the corresponding flow cell,they were adsorbed on the inside walls by the bar magnet.Then,the mixed solutions of CEA,AFP,AFP-HRP-Ab2/GO and CEA-HRP-Ab2/GO were injected into the two flow cells and stopped for 30 min.Based on a sandwich immunoassay format,the HRP tags were retained in the flow cells.Finally,the CL substrates of luminol and H2O2 were controlled to the two parallel flow cells,so the sequential determination of two tumor markers was achieved.Due to the increased amount of HRP on the surface of GO and the increased amount of monoclonal antibodies on Fe3O4/SiO2,the signals were largely amplified.The effects on the dual immunoassay,such as the concentrations of luminol and H2O2,the incubation time,and the pH value of the buffer solution,were investigated in the current work.Under the optimal conditions,typical flow injection CL signals have been obtained with the sandwich multiplexed immunoassay for CEA and AFP.AFP could be detected in the linear ranges 0.005~0.5 and 0.5~100 ng/mL.CEA could be detected in the linear ranges of 0.0025~1.0 and 1.0~80 ng

  4. 子宫内膜癌患者血清CP2、CA125、唾液酸和癌胚抗原检测的临床意义%Clinical significance of serum CP2, CA125, salicylic acid and carcinoembryonic antigen in endometrial carcinoma

    Institute of Scientific and Technical Information of China (English)

    王志启; 王建六; 杨静华; 魏丽惠


    Objective To explore the clinical significance of CP2,CA125,salicylic acid(SA)and carcinoembryonic antigen(CEA)in endometrial carcinoma patients. Methods A retrospective study was carried out on 154 cases of endometrial carcinoma with tumor markers test results who were admitted to our department from Aug 1992 to Nov 2004.Results The patients were followed up for(38±28)months.23.4%,36.8%,19.0%and 30.3%of cases were with abnormal values of CP2,SA,CA125 and CEA.CP2 abnormal level was related with the stage,cell differentiation,adnexa metastasis,positive peritoneal cytology and pelvic lymph node metastasis(P=0.002,P=0.040,P=0.019,P=0.019,P:0.005).SA abnormal level was related with the adnexa metastasis and positive peritoneal eytology(P=0.021,P=0.000). CA125 abnormal level was related with the cell differentiation,cervical metastasis and pelvic lymph node metastasis(P=0.014,P=0.006,P=0.018).The survival was related with CP2,CA125 and CEA (P=0.016,P=0.000,P=0.016),especially CA125. Conclusions Among the commonly used tumor markers,CP2 is related with many clinical pathological parameters.CA125 elevation may strongly suggest worse prognosis.%目的 探讨肿瘤标志物CP2、CA125唾液酸(SA)和癌胚抗原(CEA)检测对子宫内膜癌患者的临床意义.方法 选取154例具有肿瘤标志物检测结果 的子宫内膜癌患者的临床病理资料进行回顾性分析.结果 子宫内膜癌患者血清CP2、SA、CA125和CEA水平升高的百分率分别为23.4%、36.8%、19.0%和30.3%.血清CP2水平升高与手术病理分期、病理分化程度、附件受累、腹腔细胞学检查阳性及盆腔淋巴结转移相关(P值分别为0.002、0.040、0.019、0.019、0.005);血清SA水平升高与附件受累、腹腔细胞学检查阳性相关(P值分别为0.021、0.000);血清CA125水平升高与病理分化程度、宫颈受累和盆腔淋巴结转移相关(P值分别为0.014、0.006、0.018);CEA与各临床病理特征间均无相关性(P均>0.05).血清CP2

  5. Levels of carcinoembryonic antigen and CA 19-9 in the sera and peritoneal washing of patients undergoing surgical treatment for gastric carcinoma Níveis do antígeno carcinoembriônico e do CA 19-9 no soro e no lavado peritonial em doentes submetidos ao tratamento cirúrgico do carcinoma gástrico

    Directory of Open Access Journals (Sweden)

    René Crepaldi-Filho


    Full Text Available BACKGROUND: Early peritoneal recurrence of gastric carcinoma following curative resection remains a great challenge in the treatment and prevention of this disease. AIM: To analyze the relationship between levels of tumor markers, carcinoembryonic antigen (CEA and CA 19-9 in the sera and peritoneal washing, and anatomopathological aspects of the gastric carcinoma. METHODS: Of the 46 patients in the study, 29 (63.0% were males and 17 (37.0% females. Mean age was 63.6 ± 11.7 years (31 to 91 years. Peripheral venous blood samples were collected from the upper limb vein from both patient groups after anesthetic induction, in order to determine serum levels of CEA and CA 19-9. After the end of the procedure, 50 mL of physiologic solution was introduced into the bottom of the Douglas sack and a portion aspirated to determine CEA and CA 19-9 levels in the peritoneal washing. Levels of CEA and CA 19-9 in the sera and peritoneal washing were compared to the following variables: lesion diameter ≤4 cm or >4 cm, lymph node involvement, angiolymphatic invasion, depth of invasion into gastric wall, and initial or late stage. RESULTS: Sera CEA levels were significantly higher in patients with lesions >5 cm. CEA levels in the sera and peritoneal washing were significantly greater in patients with signet ring cell gastric carcinoma. In addition, levels of CEA in peripheral blood and peritoneal washing showed significant association with the degree of carcinoma penetration into the gastric wall, while sera CEA was significantly higher in patients at more advanced stages. There was no significant difference between sera and peritoneal CEA values regarding grade of differentiation. Patients with gastric lesions measuring > 5cm and more differentiated lesions had significantly higher sera CA 19-9 values. In patients with lymph nodes invasion by gastric carcinoma, CA 19-9 levels in peritoneal washing were significantly higher than in peripheral blood. Levels of CA

  6. Determination of carcinoembryonic antigen levels in peripheral and draining venous blood in patients with colorectal carcinoma Determinação dos níveis do antígeno carcinoembriônico no sangue periférico e no efluente venoso em doentes com carcinoma colorretal

    Directory of Open Access Journals (Sweden)

    Jaques Waisberg


    Full Text Available BACKGROUND: The problem of the relationship between blood carcinoembryonic antigen (CEA levels and tissue CEA content in colorectal carcinoma, and the mechanisms for CEA release from tumor cells in tissue adjacent to the neoplasm is important to understanding the biology of colorectal carcinoma. It has not been adequately explained whether CEA in the peripheral blood is drained mainly by portal system blood or by the lymphatic system, or indeed by both systems. AIM: To study the behavior of CEA levels in peripheral blood (CEA-p and venous effluent blood (CEA-d among patients with colorectal tumors, who underwent curative operation. METHOD: A total of 28 patients were studied (12 male [42.9%] and 16 female [57.1%], mean age 66.1 years [range: 43 - 84]. Immediately after laparotomy, peripheral venous blood was extracted by antecubital venous puncture and venous effluent blood was collected from the main drainage vein of the lesions. Values of CEA-p, CEA-d and the gradient between CEA-d and CEA-p that were less than 5.0 ng/mL were considered normal. RESULTS: Eight (28.6% patients were stage A in Duke's classification, nine (32.1% stage B and 11 (39.3% stage C. The neoplasm was located in the rectum of 14 patients (50.0%, in the transverse colon in five (17.9%, in the sigmoid in four (14.3%, in the cecum and/or ascending colon in three (10.7%, and in the descending colon in two (7.1%. The histopathological examination revealed well-differentiated adenocarcinoma in all the patients. Only one patient (3.6%, Duke's classification stage C, presented neoplasm with venous invasion. The gradient between the CEA-p and CEA-d levels were normal in 25 patients (88.3% and high in three (10.7%. The mean value for CEA-p was 3.8 ± 4.1 ng/mL (0.1-21.1 ng/mL and for the drained CEA (CEA-d it was 4.5 ± 4.3 ng/mL (0.3-20.2 ng/mL, without significant difference between these values. There was a significant difference between the mean value for CEA-p and CEA-d levels

  7. 单核细胞趋化蛋白-1、癌胚抗原和C-反应蛋白在平阳霉素胸膜固定术中的变化及意义%Changes and significance of monocyte chemoattractant protein-1, carcinoembryonic antigen and C-reactive protein in pingyangmycin pleurodesis

    Institute of Scientific and Technical Information of China (English)

    张鹏; 孙耕耘; 周群


    Objective To investigate the mechanism of pingyangmycin (PYM) pleurodesis by detecting the changes of the levels of monocyte chemoattractant protein-1 (MCP-1), carcinoembryonic antigen (CEA), and C-reactive protein (CRP) in malignant pleural effusion (MPE) before and after intrapleural injection with PYM. Methods Thirty-one patients with MPE were intrapleurally injected with PYM. The levels of MCP-1, CEA,CRP and white blood cell count in pleural fluid were detected before and at 6th, 24th, 48th hour after injection. According to therapeutic effect, the patients were divided into effective group and ineffective group. The indexes were compared between groups and before and after treatment. Results Four weeks after PYM administration, the effective rate of MPE control was 58.1% (18/31). The levels of MCP-1 and CEA at 48th hour after treatment were lower than those before treatment (all P<0.05). In effective group, the levels of MCP-1 and CEA began to decrease at 6th hour after treatment (all P <0.05). In ineffective group, MCP-1 level decreased from 48th hour after injection ( P <0.05), there was no statistical significance on CEA level among different time points. The CRP level and white blood cell count in pleural fluid gradually increased after injection, there was statistical significance in effectively group and ineffective group at 24th hour after injection (all P <0.05). CRP level at 6th hour after injection and MCP-1 level at 48th hour after injection in effective group were higher than those in ineffective group (all P <0.05). There was no statistical significance on CEA level and white blood cell count between the two groups at the same time ( )t. Conclusions The intrapleural injection with PYM induces pleurodesis by inflammation and anti-tumor effect.%目的 观察胸膜腔内注射平阳霉素(PYM)后胸腔积液(胸水)中单核细胞趋化蛋白-1(MCP-1)-1、癌胚抗原(CEA)和C-反应蛋白(CRP)水平的变化,探讨PYM

  8. Inhibition of the function of the FcgammaRIIB by a monoclonal antibody to thymic shared antigen-1, a Ly-6 family antigen. (United States)

    Ding, L; Shevach, E M


    Thymic shared antigen-1 (TSA-1) is a member of the Ly-6 family of glycosyl-phosphatidylinositol (GPI)-linked proteins. While it has been proposed that TSA-1 may play a role in thymic development, a physiological ligand for this antigen has not been identified. Here we report that a monoclonal antibody (mAb) to TSA-1, generated by immunizing a hamster with CD40 ligand (CD40L)-activated B cells, interferes with the function of FcgammaRIIB on splenic B cells and the B-cell lymphoma cell line, M12, by binding to TSA on the same cells. The interaction of anti-TSA with FcgammaRIIB resulted in an inhibition of the ability of the FcgammaRIIB to cross-link and/or aggregate soluble anti-CD3 or soluble anti-Cbeta T-cell receptor (TCR), leading to an inhibition of induction of expression of CD25 and CD69, interleukin (IL)-2 production and proliferation of naive T cells. Cross-blocking studies with mAbs strongly suggested that a physical association exists between TSA-1 and the FcgammaRIIB on the surface of activated B cells and favour the view that a functional intermolecular association exists between these two distinct membrane antigens.

  9. The clinical value of tissue polypeptide specific antigen,neuron-specific enolase,carcinoembryonic antigen and CA125 level in small cell lung cancer%四项肿瘤标志联合检测在小细胞肺癌中的临床价值

    Institute of Scientific and Technical Information of China (English)

    李学祥; 周善良; 王慜杰; 韩彬彬; 齐军


    目的 探讨小细胞肺癌(SCLG)患者血清中组织多肽特异性抗原(TPS)、神经元特异烯醇化酶(NSE)、癌抗原125(CA125)和癌胚抗原(CEA)水平,对SCLC临床诊断、病情监测的临床意义.方法 用ELISA法检测271例SCLC和80例肺良性疾病患者及224名健康对照者血清TPS水平;同时用电化学发光法检测血清NSE、CA125和CEA水平;并用约登指数和受试者工作特征曲线(ROC曲线)分析4项肿瘤标志及其各项肿瘤标志联合检测SCLC患者的效能.结果 SCLC组的TPS、NSE、CA125和CEA血清水平明显高于肺良性疾病组和健康对照组(Z均>1.90,P均<0.01);广泛期SCLC患者的血清TPS和NSE明显高于局限期患者(Z分别为2.69、2.27,P分别为0.009、0.02).治疗后不同预后患者的TPS和NSE浓度差异有统计学意义(Z分别为4.06、3.11,P分别为0.001、0.007).多指标联合检测时,以TPS+NSE组合的敏感度最高(86.7%),其特异度、阳性预测值(PPV)和阴性预测值(NPV)分别为75.0%、81.0%和82.2%.结论 血清TPS、NSE、CA125和CEA均可作为SCLC的诊断指标,以TPS+NSE联合检测的临床价值最好.%Objective To investigate the clinical value of tissue polypeptide specific antigen(TPS),neuron-specific enolase(NSE),carcinoembryonie antigen(CEA)and CA125 in serum of small cell lung cancer(SCLC)patients and its significance in diagnosis and disease monitoring.Methods Serum leveh of TPS was detected using ELISA and serum levels of NSE,CA125 and CEA was detected using ECLin 27 1 SCLC patients.80 pulmonary benign disease patients and 224 normal healthy people.Diagnostic values of these tumor markers were analyzed by receiver operative characteristic(ROC)curve.Results The levels of TPS,NSE,CA125 and CEA iu the serum of SCLC group were signifieanfly higher than those in pulmonary benign disease and healthy group(Z>1.90,P<0.01).The levels of TPS and NSE in the serum of extensive stage small cell lung cancer(ESCLC)patients were significantly

  10. Prognostic value of carcinoembryonic antigen distribution in tumor tissue of colorectal carcinoma Valor prognóstico da distribuição do antígeno carcinoembriônico (CEA no tecido neoplásico do carcinoma colorretal

    Directory of Open Access Journals (Sweden)

    Débora Maria Nazato


    Full Text Available CONTEXT: Carcinoembryonic antigen (CEA can be detected in colorectal tumor tissue but its role in the survival of patients remains controversial. OBJECTIVE: To characterize the expression of tissue CEA using immunohistochemical staining in colorectal tumors and to analyze the relationship between this finding and preoperative plasmatic level of CEA, morphologic features and survival of patients operated with curative intent for colorectal carcinoma. METHOD: Forty-seven patients were included in the study: 18 (38.3% males and 29 (61.7% females, with a mean age of 67.8 ± 9.7 years (37 to 84 years. Immediately before laparotomy, pre-operative serum levels of CEA were obtained where normal levels were considered CONTEXTO: O antígeno carcinoembrionário (CEA pode ser detectado no tecido do carcinoma colorretal, mas seu papel na sobrevivência dos doentes permanece controverso. OBJETIVO: Caracterizar a expressão do CEA tecidual com coloração imunoistoquímica na neoplasia colorretal e analisar a relação entre esse achado e os níveis plasmáticos pré-operatórios do CEA, aspectos morfológicos e a sobrevivência dos doentes operados com intenção curativa de carcinoma colorretal. MÉTODO: Quarenta e sete doentes foram incluídos neste estudo: 18 (38,3% homens e 29 (61,7% mulheres, com média de idade de 67,8 ± 9,7 anos (37 to 84 anos. Imediatamente antes da laparotomia, foram obtidos os níveis plasmáticos pré-operatórios do CEA. Níveis séricos pré-operatórios normais de CEA foram considerados < 2,5 ng/mL para não-fumantes e <5,0 ng/mL para fumantes. O estudo imunoistoquímico do CEA foi realizado utilizando anticorpo monoclonal de rato anti-CEA humano. A expressão da imunocoloração de cada neoplasia foi classificada de acordo com o padrão de distribuição tecidual do CEA em apical ou citoplasmática. As variáveis consideradas para a análise estatística foram os níveis plasmáticos pré-operatórios do CEA, localização da

  11. Stage and strain specific expression of the tandemly repeated 90 kDa surface antigen gene family in Trypanosoma cruzi. (United States)

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


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

  12. Surface proteome analysis and characterization of surface cell antigen (Sca or autotransporter family of Rickettsia typhi.

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    Khandra T Sears

    Full Text Available Surface proteins of the obligate intracellular bacterium Rickettsia typhi, the agent of murine or endemic typhus fever, comprise an important interface for host-pathogen interactions including adherence, invasion and survival in the host cytoplasm. In this report, we present analyses of the surface exposed proteins of R. typhi based on a suite of predictive algorithms complemented by experimental surface-labeling with thiol-cleavable sulfo-NHS-SS-biotin and identification of labeled peptides by LC MS/MS. Further, we focus on proteins belonging to the surface cell antigen (Sca autotransporter (AT family which are known to be involved in rickettsial infection of mammalian cells. Each species of Rickettsia has a different complement of sca genes in various states; R. typhi, has genes sca1 thru sca5. In silico analyses indicate divergence of the Sca paralogs across the four Rickettsia groups and concur with previous evidence of positive selection. Transcripts for each sca were detected during infection of L929 cells and four of the five Sca proteins were detected in the surface proteome analysis. We observed that each R. typhi Sca protein is expressed during in vitro infections and selected Sca proteins were expressed during in vivo infections. Using biotin-affinity pull down assays, negative staining electron microscopy, and flow cytometry, we demonstrate that the Sca proteins in R. typhi are localized to the surface of the bacteria. All Scas were detected during infection of L929 cells by immunogold electron microscopy. Immunofluorescence assays demonstrate that Scas 1-3 and 5 are expressed in the spleens of infected Sprague-Dawley rats and Scas 3, 4 and 5 are expressed in cat fleas (Ctenocephalides felis. Sca proteins may be crucial in the recognition and invasion of different host cell types. In short, continuous expression of all Scas may ensure that rickettsiae are primed i to infect mammalian cells should the flea bite a host, ii to remain

  13. 癌胚抗原启动子驱动双自杀基因对裸鼠大肠癌移植瘤的作用%Cytosine deaminase and thymidine kinase double suicide gene system driven by carcinoembryonic antigen promoter for the treatment of colorectal carcinoma xenograft in nude mice

    Institute of Scientific and Technical Information of China (English)

    黄正接; 冯庆钊; 尤俊; 许林; 罗维远; 易文城; 曾岳岳; 罗琪


    Objective To explore the therapeutic efficacy of double suicide gene system driven by carcinoembryonic antigen (CEA) promoter (Cp-CDglyTK) on colorectal carcinoma xenograft in nude mice.Methods The plasmid pcDNA3.1 (-) Cp-CDglyTK was transfected into the CEA-positive SW480 and CEA-negative HeLa cells respectively.The expression of suicide gene was detected by RT-PCR.And the transfected cells were treated with 5-fluorocytosine (5-FC) and ganciclovir (GCV) at different concentrations and the cell-killing and bystander effects assayed by methyl thiazolyl tetrazolium (MTT).By a transplantation of cultivated cells,SW480 or HeLa cell lines were injected subcutaneously into right axillary of nude mice to establish 96 SW480 and 72 HeLa tumor animal models.Nude mice were completely randomized with statistical software according to tumor volume.For prodrug therapy,48 SW480-bearing mice were divided equally into 4 groups of Ⅰ-Ⅳ.At the same time,48 HeLa-bearing mice were divided equally into 4 groups of Ⅴ-Ⅷ.Groups Ⅰ & Ⅴreceived an intratumoral injection of PBS,groups Ⅱ & ⅥGCV and 5-FC intratumorally,groups Ⅲ & Ⅶ PBS intraperitoneally and groups Ⅳ & Ⅷ GCV and 5-FC intraperitoneally.Forty-eight SW480-bearing mice were divided equally into 4 groups of Ⅸ ~ Ⅻ and 24 Hela-bearing ones into groups of ⅩⅢ & ⅩⅣ in therapy experiment by suicide gene plus prodrug.Six groups received an intratumoral injection of liposome Lipofectamine (R) and plasmid CP-CDglyTK and then an intraperitoneal injection of drug.The groups of Ⅸ and ⅩⅢ received an injection of PBS,group Ⅹ GCV,group Ⅺ 5-FC and groups Ⅻ & ⅩⅣ GCV and 5-FC.The observation parameters included tumor bulk,tumor weight,survival time and treatment effect in each group.Results SW480 cells transfected by plasmid pcDNA3.1 (-) Cp-CDglyTK expressed CDglyTK gene.The inhibition rates of GCV and 5-FC were significantly higher than those of HeLa cells (59.87% ± 0.21% vs 9.90% ± 0.09

  14. Comparative case control study of clinical features and human leukocyte antigen susceptibility between familial and nonfamilial vitiligo

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    Misri Rachita


    Full Text Available Background: Various studies worldwide suggest that human leukocyte antigen (HLA region may be involved in the genetic susceptibility of vitiligo but little information is available from India. Aim: To find the HLA associated susceptibility to develop vitiligo in Indian patients and to detect role of HLA in familial vitiligo. Methods: This was a case controlled study which included all patients suffering from vitiligo over a period of one and half years. Clinical details were noted and sera collected from these patients were screened for the presence of HLA class I antibodies. The clinical features and HLA antigens were assessed and comparison was made between patients with familial and nonfamilial vitiligo. Results: Out of 114 patients studied, 84 had family history and 30 had no family history. Patients with family history of vitiligo have higher chances of acquiring vitiligo if first degree relatives are affected compared to if second degree relatives are affected. Family history of vitiligo is associated with an early onset of vitiligo (< 20 years. There was no statistically significant difference in the type, stability, and severity of vitiligo in both the groups. HLA results in both the groups revealed increase in HLA A2, A11, A31, A33, B17, B35, B40, and B44 alleles while HLA A9, B13, and B53 alleles were decreased. Family history was associated with HLA A2, A28, A31, and B44 alleles. Early onset of vitiligo (< 20 years was significantly associated with HLA A2, A11, B17, B35, and B44 alleles. The patients with severe affection (> 10% area showed in significant association with HLA A10 and B8. Conclusion: Family history of vitiligo is associated with an early onset of vitiligo. There is no correlation of family history with the type of vitiligo, stability of lesions, and areas involved. Severity is not associated with family history. Apart from other alleles, alleles A2, and B44 play a significant role in vitiligo in the Indian patients.

  15. Familial occurrence of subacute thyroiditis associated with human leukocyte antigen-B35

    NARCIS (Netherlands)

    Kramer, AB; Roozendaal, C; Dullaart, RPF


    Subacute thyroiditis (SAT) is a spontaneously remitting inflammatory disorder of the thyroid, associated with human leukocyte antigen (HLA)-B35, and may be virally induced in genetically predisposed individuals. A 57-year-old Caucasian man presented with symptoms of hyperthyroidism as well as enlarg

  16. The MASP family of Trypanosoma cruzi: changes in gene expression and antigenic profile during the acute phase of experimental infection.

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    Sara Lopes dos Santos

    Full Text Available BACKGROUND: Trypanosoma cruzi is the etiological agent of Chagas disease, a debilitating illness that affects millions of people in the Americas. A major finding of the T. cruzi genome project was the discovery of a novel multigene family composed of approximately 1,300 genes that encode mucin-associated surface proteins (MASPs. The high level of polymorphism of the MASP family associated with its localization at the surface of infective forms of the parasite suggests that MASP participates in host-parasite interactions. We speculate that the large repertoire of MASP sequences may contribute to the ability of T. cruzi to infect several host cell types and/or participate in host immune evasion mechanisms. METHODS: By sequencing seven cDNA libraries, we analyzed the MASP expression profile in trypomastigotes derived from distinct host cells and after sequential passages in acutely infected mice. Additionally, to investigate the MASP antigenic profile, we performed B-cell epitope prediction on MASP proteins and designed a MASP-specific peptide array with 110 putative epitopes, which was screened with sera from acutely infected mice. FINDINGS AND CONCLUSIONS: We observed differential expression of a few MASP genes between trypomastigotes derived from epithelial and myoblast cell lines. The more pronounced MASP expression changes were observed between bloodstream and tissue-culture trypomastigotes and between bloodstream forms from sequential passages in acutely infected mice. Moreover, we demonstrated that different MASP members were expressed during the acute T. cruzi infection and constitute parasite antigens that are recognized by IgG and IgM antibodies. We also found that distinct MASP peptides could trigger different antibody responses and that the antibody level against a given peptide may vary after sequential passages in mice. We speculate that changes in the large repertoire of MASP antigenic peptides during an infection may contribute to

  17. Aguacate virus, a new antigenic complex of the genus Phlebovirus (family Bunyaviridae). (United States)

    Palacios, Gustavo; da Rosa, Amelia Travassos; Savji, Nazir; Sze, Wilson; Wick, Ivan; Guzman, Hilda; Hutchison, Stephen; Tesh, Robert; Lipkin, W Ian


    Genomic and antigenic characterization of Aguacate virus, a tentative species of the genus Phlebovirus, and three other unclassified viruses, Armero virus, Durania virus and Ixcanal virus, demonstrate a close relationship to one another. They are distinct from the other nine recognized species within the genus Phlebovirus. We propose to designate them as a new (tenth) serogroup or species (Aguacate virus) within the genus. The four viruses were all isolated from phlebotomine sandflies (Lutzomyia sp.) collected in Central and South America. Aguacate virus appears to be a natural reassortant and serves as one more example of the high frequency of reassortment in this genus.

  18. 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


    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....

  19. The anti-apoptotic members of the Bcl-2 family are attractive tumor-associated antigens

    DEFF Research Database (Denmark)

    Straten, Per thor; Andersen, Mads Hald


    Anti-apoptotic members of the Bcl-2 family (Bcl-2, Bcl-X(L) and Mcl-2) are pivotal regulators of apoptotic cell death. They are all highly overexpressed in cancers of different origin in which they enhance the survival of the cancer cells. Consequently, they represent prime candidates for anti-ca...

  20. The extended family of CD1d-restricted T cells: sifting through a mixed bag of TCRs, antigens and functions

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    Elodie eMacho-Fernandez


    Full Text Available Natural killer T (NKT cells comprise a family of specialized T cells that recognize lipid antigens presented by CD1d. Based on their T cell receptor (TCR usage and antigen-specificities, CD1d-restricted NKT cells have been divided into two main subsets: type I NKT cells that use a canonical invariant TCR α-chain and recognize α-galactosylceramide (α-GalCer, and type II NKT cells that use a more diverse αβ TCR repertoire and do not recognize α-GalCer. In addition, α-GalCer-reactive NKT cells that use non-canonical αβ TCRs and CD1d-restricted T cells that use γδ or δ/αβ TCRs have recently been identified, revealing further diversity among CD1d-restricted T cells. Importantly, in addition to their distinct antigen specificities, functional differences are beginning to emerge between the different members of the CD1d-restricted T cell family. In this review, while using type I NKT cells as comparison, we will focus on type II NKT cells and the other non-invariant CD1d-restricted T cell subsets, and discuss our current understanding of the antigens they recognize, the formation of stimulatory CD1d/antigen complexes, the modes of TCR-mediated antigen recognition, and the mechanisms and consequences of their activation that underlie their function in antimicrobial responses, antitumor immunity, and autoimmunity.

  1. A method of identifying and isolating a unique member of a multigene family: application to a trypanosome surface antigen gene. (United States)

    Ruef, B J; Hecht, J H; Manning, J E


    A chimeric oligonucleotide was constructed using DNA sequences from two distal regions of a cDNA which encodes a major surface antigen (TSA-1) of Trypanosoma cruzi. Conditions were found that allowed the chimeric oligonucleotide to hybridize only to a 5.4 kb EcoRI fragment in a Southern blot of total genomic DNA. The 5.4 kb EcoRI genomic DNA fragment has previously been shown to be located at a telomeric site, thus the studies described here directly demonstrate that the TSA-1 gene is telomeric in location. It is also shown that the chimeric oligonucleotide can be used to selectively identify recombinant lambda phage which harbor the TSA-1 gene using standard library screening procedures. Since these studies demonstrate that a chimeric oligonucleotide can be used to identify in both Southern blots and library screens a single member among the more than sixty members of the TSA-1 gene family, it seems likely that chimeric oligonucleotides may be of general use in studies involving repetitive DNA sequence families.

  2. The development of laboratory tests for cancer in Japan with special reference to carcinoembryonic proteins. (United States)

    Hirai, H


    The present paper describes the present status of clinical tests for cancer in Japan. Since no cancer-specific substance has been found so far the clinical tests for cancer at present are always quantitative but not qualitative. Among these substances, alpha-fetoprotein is one of the most specific substances for cancer and its test is essential for diagnosis of hepatoma beins used worldwide. AFP is a specific product of liver cancer cells. The measurement of carcinoembryonic antigen in patient blood is a hopeful method for cancer diagnosis. This substance is not specifically produced by cancer cells, but the phenomenon of appearance in bloodstream appears to be cancer-specific. This may reflect the invasion of blood vessels in tissues such as colorectum, lung, etc., by infiltration of cancer cell. This is the reason for the appearance of CEA in a wide variety of cancers. There are many other clinical tests at present but these are only secondary aids for the diagnosis of cancer. This is the reason why the description concentrates mostly on AFP and CEA. The companies manufacturing the kits for these tests in Japan are also listed in this paper.

  3. The Shc family protein adaptor, Rai, negatively regulates T cell antigen receptor signaling by inhibiting ZAP-70 recruitment and activation.

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    Micol Ferro

    Full Text Available Rai/ShcC is a member of the Shc family of protein adaptors expressed with the highest abundance in the central nervous system, where it exerts a protective function by coupling neurotrophic receptors to the PI3K/Akt survival pathway. Rai is also expressed, albeit at lower levels, in other cell types, including T and B lymphocytes. We have previously reported that in these cells Rai attenuates antigen receptor signaling, thereby impairing not only cell proliferation but also, opposite to neurons, cell survival. Here we have addressed the mechanism underlying the inhibitory activity of Rai on TCR signaling. We show that Rai interferes with the TCR signaling cascade one of the earliest steps--recruitment of the initiating kinase ZAP-70 to the phosphorylated subunit of the TCR/CD3 complex, which results in a generalized dampening of the downstream signaling events. The inhibitory activity of Rai is associated to its inducible recruitment to phosphorylated CD3, which occurs in the physiological signaling context of the immune synapse. Rai is moreover found as a pre-assembled complex with ZAP-70 and also constitutively interacts with the regulatory p85 subunit of PI3K, similar to neuronal cells, notwithstanding the opposite biological outcome, i.e. impairment of PI-3K/Akt activation. The data highlight the ability of Rai to establish interactions with the TCR and key signaling mediators which, either directly (e.g. by inhibiting ZAP-70 recruitment to the TCR or sequestering ZAP-70/PI3K in the cytosol or indirectly (e.g. by promoting the recruitment of effectors responsible for signal extinction prevent full triggering of the TCR signaling cascade.

  4. Transcription analysis of the major antigenic protein 1 multigene family of three in vitro-cultured Ehrlichia ruminantium isolates. (United States)

    Bekker, Cornelis P J; Postigo, Milagros; Taoufik, Amar; Bell-Sakyi, Lesley; Ferraz, Conchita; Martinez, Dominique; Jongejan, Frans


    Ehrlichia ruminantium, an obligate intracellular bacterium transmitted by ticks of the genus Amblyomma, causes heartwater disease in ruminants. The gene coding for the major antigenic protein MAP1 is part of a multigene family consisting of a cluster containing 16 paralogs. In the search for differentially regulated genes between E. ruminantium grown in endothelial and tick cell lines that could be used in vaccine development and to determine if differences in the map1 gene cluster exist between different isolates of E. ruminantium, we analyzed the map1 gene cluster of the Senegal and Gardel isolates of E. ruminantium. Both isolates contained the same number of genes, and the same organization as found in the genome sequence of the Welgevonden isolate (H. Van Heerden, N. E. Collins, K. A. Brayton, C. Rademeyer, and B. A. Allsopp, Gene 330:159-168, 2004). However, comparison of two subpopulations of the Gardel isolate maintained in different laboratories demonstrated that recombination between map1-3 and map1-2 had occurred in one subpopulation with deletion of one entire gene. Reverse transcription-PCR on E. ruminantium derived mRNA from infected cells using gene-specific primers revealed that all 16 map1 paralogs were transcribed in endothelial cells. In one vector (Amblyomma variegatum) and several nonvector tick cell lines infected with E. ruminantium, transcripts were found for between 4 and 11 paralogs. In all these cases the transcript for the map1-1 gene was detected and was predominant. Our results indicate that the map1 gene cluster is relatively conserved but can be subject to recombination, and differences in the transcription of map1 multigenes in host and vector cell environments exist.

  5. The promastigote surface antigen gene family of the Leishmania parasite: differential evolution by positive selection and recombination

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    Bañuls Anne-Laure


    Full Text Available Abstract Background PSA (promastigote surface antigen is one of the major classes of membrane proteins present at the surface of the parasitic protozoan Leishmania. While it harbours leucine rich repeats, which are suggestive of its involvement in parasite-to-host physical interactions, its exact role is largely unknown. Furthermore, the extent of diversity of this gene family, both in copy number and sequence has not been established. Results From the newly available complete genome sequences of L. major, L. infantum and L. braziliensis, we have established the complete list of PSA genes, based on the conservation of specific domain architecture. The latter includes an array of leucine rich repeats of unique signature flanked by conserved cysteine-rich domains. All PSA genes code either for secreted or membrane-anchored surface proteins. Besides the few previously identified PSA genes, which are shown here to be part of a relatively large subclass of PSA genes located on chromosome 12, this study identifies seven other PSA subtypes. The latter, whose genes lie on chromosomes 5, 9, 21 and 31 in all three species, form single gene (two genes in one instance subfamilies, which phylogenetically cluster as highly related orthologs. On the other hand, genes found on chromosome 12 generally show high diversification, as reflected in greater sequence divergence between species, and in an extended set of divergent paralogs. Moreover, we show that the latter genes are submitted to strong positive selection. We also provide evidence that evolution of these genes is driven by intra- and intergenic recombination, thereby modulating the number of LRRs in protein and generating chimeric genes. Conclusion PSA is a Leishmania family of membrane-bound or secreted proteins, whose main signature consists in a specific LRR sequence. All PSA genes found in the genomes of three sequenced Leishmania species unambiguously distribute into eight subfamilies of orthologs

  6. The diagnostic accuracy of carcinoembryonic antigen to detect colorectal cancer recurrence

    DEFF Research Database (Denmark)

    Sørensen, Caspar G; Karlsson, William K; Pommergaard, Hans-Christian;


    was to assess the diagnostic accuracy of CEA in detecting recurrence after intended curative surgery for primary colorectal cancer. METHODS: Systematic literature searches were performed in PubMed, EMBASE and Cochrane databases, and articles were chosen based on predefined inclusion criteria. Reference lists...... from included articles were manually searched for additional publications of relevance. RESULTS: Forty-two original studies with generally representative populations and long follow-up were included. Data were reported on outcomes from 9,834 CEA tests during follow-up. Reporting on the reference...

  7. Hookah smoking and cancer: carcinoembryonic antigen (CEA levels in exclusive/ever hookah smokers

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    Chaouachi Kamal


    Full Text Available Abstract Background We have recently published some work on CEA levels in hookah (also called narghile, shisha elsewhere and cigarette smokers. Hookah smokers had higher levels of CEA than non-smokers although mean levels were low compared to cigarette smokers. However some of them were also users of other tobacco products (cigarettes, bidis, etc.. Objectives To find serum CEA levels in ever/exclusive hookah smokers, i.e. those who smoked only hookah (no cigarettes, bidis, etc., prepared between 1 and 4 times a day with a quantity of up to 120 g of a tobacco-molasses mixture each (i.e. the tobacco weight equivalent of up to 60 cigarettes of 1 g each and consumed in 1 to 8 sessions. Methods Enhanced chemiluminescent immunometric technique was applied to measure CEA levels in serum samples from 59 exclusive male smokers with age ranging from 20–80 years (mean = 58.8 ± 14.7 years and 8–65 years of smoking (mean = 37.7 ± 16.8. 36 non-smokers served as controls. Subjects were divided into 3 groups according to the number of preparations; the number of sessions and the total daily smoking time: Light (1; 1; ≤ 20 minutes; Medium (1–3; 1–3; >20 min to ≤ 2 hrs and Heavy smokers (2–4; 3–8; >2 hrs to ≤ 6 hrs. Because of the nature of distribution of CEA levels among our individuals, Wilcoxon's rank sum two-sample test was applied to compare the variables. Results The overall CEA levels in exclusive hookah smokers (mean: 3.58 ± 2.61 ng/ml; n = 59 were not significantly different (p ≤ 0.0937 from the levels in non-smokers (2.35 ± 0.71 ng/ml. Mean levels in light, medium and heavy smokers were: 1.06 ± 0.492 ng/ml (n = 5; 2.52 ± 1.15 ng/ml (n = 28 and 5.11 ± 3.08 ng/ml (n = 26 respectively. The levels in medium smokers and non-smokers were also not significantly different (p ≤ 0.9138. In heavy smokers, the CEA levels were significantly higher than in non-smokers (p ≤ 0.0001567. Conclusion Overall CEA levels in exclusive hookah smokers were low compared to cigarette smokers. However, heavy hookah smoking substantially raises CEA levels. Low-nitrosamines smokeless tobacco of the SNUS Swedish type could be envisaged as an alternative to smoking for this category of users and also, in a broad harm reduction perspective, to the prevalent low-quality moist snuff called naswar.

  8. Pretargeted 177Lu radioimmunotherapy of carcinoembryonic antigen-expressing human colonic tumors in mice.

    NARCIS (Netherlands)

    Schoffelen, R.; Graaf, W.T.A. van der; Franssen, G.M.; Sharkey, R.M.; Goldenberg, D.M.; McBride, W.J.; Rossi, E.A.; Eek, A.; Oyen, W.J.G.; Boerman, O.C.


    Pretargeted radioimmunotherapy (PRIT) with bispecific antibodies in combination with a radiolabeled peptide reduces the radiation dose to normal tissues, especially the bone marrow. In this study, the optimization, therapeutic efficacy, and toxicity of PRIT of colon cancer with a (177)Lu-labeled pep

  9. The Establishment of an Enzyme-linked Immunosorbent Assay for Carcinoembryonic Antigen

    Institute of Scientific and Technical Information of China (English)


    Two anti-CEA monoclonal antibodies are used, one is coated on the microtiter plate, the other is labeled with horseradish peroxidase(HRP). The two-step assay is established based on enzyme-linked immunosorbent assay(ELISA). TMB-H2O2 solution is used as the substrate of HRP. The sensitivity of the assay is 0.4 μ g/L. The intra-assay CVs and the inter-assay CVs are lower than 10.0% and 15.0%, respectively. The analytical recoveries are ranged from 99.4% to 108.7%. The reference cut-off value of normal serum (n= 100 ) is 10.0 ng/L.

  10. 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. (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


    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.

  11. Comparative evaluation of low-molecular-mass proteins from Mycobacterium tuberculosis identifies members of the ESAT-6 family as immunodominant T-cell antigens

    DEFF Research Database (Denmark)

    Skjøt, R L; Oettinger, T; Rosenkrands, I;


    Culture filtrate from Mycobacterium tuberculosis contains protective antigens of relevance for the generation of a new antituberculosis vaccine. We have identified two previously uncharacterized M. tuberculosis proteins (TB7.3 and TB10.4) from the highly active low-mass fraction of culture filtrate...... in cultures of peripheral blood mononuclear cells from human tuberculosis (TB) patients, Mycobacterium bovis BCG-vaccinated donors, and nonvaccinated donors. The two ESAT-6 family members, TB10.4 and CFP10, were very strongly recognized and induced gamma interferon release at the same level (CFP10...

  12. A method of identifying and isolating a unique member of a multigene family: application to a trypanosome surface antigen gene.



    A chimeric oligonucleotide was constructed using DNA sequences from two distal regions of a cDNA which encodes a major surface antigen (TSA-1) of Trypanosoma cruzi. Conditions were found that allowed the chimeric oligonucleotide to hybridize only to a 5.4 kb EcoRI fragment in a Southern blot of total genomic DNA. The 5.4 kb EcoRI genomic DNA fragment has previously been shown to be located at a telomeric site, thus the studies described here directly demonstrate that the TSA-1 gene is telomer...

  13. The impact of human leukocyte antigen (HLA) micropolymorphism on ligand specificity within the HLA-B*41 allotypic family

    Energy Technology Data Exchange (ETDEWEB)

    Bade-Döding, Christina; Theodossis, Alex; Gras, Stephanie; Kjer-Nielsen, Lars; Eiz-Vesper, Britta; Seltsam, Axel; Huyton, Trevor; Rossjohn, Jamie; McCluskey, James; Blasczyk, Rainer (Springe); (Hannover-MED); (Monash); (Melbourne)


    Polymorphic differences between human leukocyte antigen (HLA) molecules affect the specificity and conformation of their bound peptides and lead to differential selection of the T-cell repertoire. Mismatching during allogeneic transplantation can, therefore, lead to immunological reactions. We investigated the structure-function relationships of six members of the HLA-B*41 allelic group that differ by six polymorphic amino acids, including positions 80, 95, 97 and 114 within the antigen-binding cleft. Peptide-binding motifs for B*41:01, *41:02, *41:03, *41:04, *41:05 and *41:06 were determined by sequencing self-peptides from recombinant B*41 molecules by electrospray ionization tandem mass spectrometry. The crystal structures of HLA-B*41:03 bound to a natural 16-mer self-ligand (AEMYGSVTEHPSPSPL) and HLA-B*41:04 bound to a natural 11-mer self-ligand (HEEAVSVDRVL) were solved. Peptide analysis revealed that all B*41 alleles have an identical anchor motif at peptide position 2 (glutamic acid), but differ in their choice of C-terminal p{Omega} anchor (proline, valine, leucine). Additionally, B*41:04 displayed a greater preference for long peptides (>10 residues) when compared to the other B*41 allomorphs, while the longest peptide to be eluted from the allelic group (a 16mer) was obtained from B*41:03. The crystal structures of HLA-B*41:03 and HLA-B*41:04 revealed that both alleles interact in a highly conserved manner with the terminal regions of their respective ligands, while micropolymorphism-induced changes in the steric and electrostatic properties of the antigen-binding cleft account for differences in peptide repertoire and auxiliary anchoring. Differences in peptide repertoire, and peptide length specificity reflect the significant functional evolution of these closely related allotypes and signal their importance in allogeneic transplantation, especially B*41:03 and B*41:04, which accommodate longer peptides, creating structurally distinct peptide

  14. Differential transcription of the major antigenic protein 1 multigene family of Ehrlichia ruminantium in Amblyomma variegatum ticks. (United States)

    Postigo, M; Taoufik, A; Bell-Sakyi, L; de Vries, E; Morrison, W I; Jongejan, F


    The rickettsial pathogen Ehrlichia ruminantium causes heartwater in ruminants and is transmitted by ticks of the genus Amblyomma. The map1 gene, encoding the major surface protein MAP1, is a member of a multigene family containing 16 paralogs. In order to investigate differential transcription of genes of the map1 multigene family in vivo in unfed and feeding ticks, RNA was extracted from midguts and salivary glands of E. ruminantium-infected adult female Amblyomma variegatum ticks and analysed by RT-PCR using MAP1 paralog-specific primers. In unfed ticks, only transcripts from the map1-1 gene were observed in midguts and no transcripts were detected in salivary glands. In feeding ticks, map1-1 transcripts were more abundant in midguts whereas high levels of map1 transcripts were observed in salivary glands. Our results show that differential transcription of genes of the E. ruminantium map1 cluster occurs in vivo in different tissues of infected ticks before and during transmission feeding, indicating that this multigene family may be involved in functions of biological relevance in different stages of the life cycle of E. ruminantium.


    NARCIS (Netherlands)



    The selective targeting of tumours by enzymes conjugated to monoclonal antibodies (mAb) may be an ideal approach to convert relatively nontoxic prodrugs into active agents at the tumour site. We used the anti-carcinoembryonic antigen mAb BW431/26 conjugated to alkaline phosphatase (AP) and phosphory

  16. Cancer testis antigen and immunotherapy

    Directory of Open Access Journals (Sweden)

    Krishnadas DK


    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

  17. Description of a computer program to assess cancer antigen 15.3, carcinoembryonic antigen, and tissue polypeptide antigen information during monitoring of metastatic breast cancer

    DEFF Research Database (Denmark)

    Sölétormos, G; Schiøler, V


    It is time-consuming to process and compare the clinical and marker information registered during monitoring of breast cancer patients. To facilitate the assessment, we developed a computer program for interpreting consecutive measurements. The intraindividual biological variation, the analytical...

  18. JC virus small T antigen binds phosphatase PP2A and Rb family proteins and is required for efficient viral DNA replication activity.

    Directory of Open Access Journals (Sweden)

    Brigitte Bollag

    Full Text Available BACKGROUND: The human polyomavirus, JC virus (JCV produces five tumor proteins encoded by transcripts alternatively spliced from one precursor messenger RNA. Significant attention has been given to replication and transforming activities of JCV's large tumor antigen (TAg and three T' proteins, but little is known about small tumor antigen (tAg functions. Amino-terminal sequences of tAg overlap with those of the other tumor proteins, but the carboxy half of tAg is unique. These latter sequences are the least conserved among the early coding regions of primate polyomaviruses. METHODOLOGY AND FINDINGS: We investigated the ability of wild type and mutant forms of JCV tAg to interact with cellular proteins involved in regulating cell proliferation and survival. The JCV P99A tAg is mutated at a conserved proline, which in the SV40 tAg is required for efficient interaction with protein phosphatase 2A (PP2A, and the C157A mutant tAg is altered at one of two newly recognized LxCxE motifs. Relative to wild type and C157A tAgs, P99A tAg interacts inefficiently with PP2A in vivo. Unlike SV40 tAg, JCV tAg binds to the Rb family of tumor suppressor proteins. Viral DNAs expressing mutant t proteins replicated less efficiently than did the intact JCV genome. A JCV construct incapable of expressing tAg was replication-incompetent, a defect not complemented in trans using a tAg-expressing vector. CONCLUSIONS: JCV tAg possesses unique properties among the polyomavirus small t proteins. It contributes significantly to viral DNA replication in vivo; a tAg null mutant failed to display detectable DNA replication activity, and a tAg substitution mutant, reduced in PP2A binding, was replication-defective. Our observation that JCV tAg binds Rb proteins, indicates all five JCV tumor proteins have the potential to influence cell cycle progression in infected and transformed cells. It remains unclear how these proteins coordinate their unique and overlapping functions.


    NARCIS (Netherlands)



    Gamma-Interferon (IFN-gamma) and the antimetabolites 5-fluorouracil (5-FU) and S-fluoro-2'-deoxyuridine (FUdR) were investigated as individual agents and in combination for their in vitro antiproliferative capacity and for their effect on the expression of HLA class-I antigen, carcinoembryonic antig

  20. The Bartonella vinsonii subsp. arupensis Immunodominant Surface Antigen BrpA Gene, Encoding a 382-Kilodalton Protein Composed of Repetitive Sequences, Is a Member of a Multigene Family Conserved among Bartonella Species


    Gilmore, Robert D.; Bellville, Travis M.; Sviat, Steven L.; Frace, Michael


    Bartonella proteins that elicit an antibody response during an infection are poorly defined; therefore, to characterize antigens recognized by the host, a Bartonella genomic expression library was screened with serum from an infected mouse. This process led to the discovery of a Bartonella vinsonii subsp. arupensis gene encoding a 382-kDa protein, part of a gene family encoding large proteins, each containing multiple regions of repetitive segments. The genes were termed brpA to -C (bartonell...

  1. Familial clustering of juvenile thyroid autoimmunity: higher risk is conferred by human leukocyte antigen DR3-DQ2 and thyroid peroxidase antibody status in fathers. (United States)

    Segni, Maria; Pani, Michael A; Pasquino, Anna Maria; Badenhoop, Klaus


    Thyroid autoimmunity is one of the most common immune disorders in females, and its polygenic background remains to be elucidated. The human leukocyte antigen (HLA) DQ region of chromosome 6 has been shown to confer susceptibility to thyroid autoimmune disease. The aim of our present investigation was to determine whether the transmission of high risk HLA DQ to patients with thyroid autoimmunity differs when transmission is from fathers as opposed to when transmission is from mothers. We studied 91 juvenile patients with chronic lymphocytic thyroiditis (68 females and 23 males; mean age, 10.5 +/- 3.9 yr), 12 patients with Graves' disease (all females; mean age, 8.8 +/- 4.0 yr), 53 healthy siblings, and their parents for thyroid function, antibodies, ultrasound, and DNA typing for HLA DQ susceptibility alleles. We observed an increased rate of transmission for the DQA1*0501-DQB1*0201 (DQ2) haplotype [35 of 53 transmitted (66%); P = 0.02]. This allele was preferentially transmitted by fathers [21 of 27 (78%); P < 0.004], whereas the maternal DQ2 haplotypes were not transmitted more often than expected. Subsequently, families were stratified as follows according to the parental thyroid peroxidase antibody (TPOAb) status: no parent, only mothers, only fathers, and both parents positive. There was no significant maternal transmission disequilibrium in any subset, but the paternal HLA DQ2 was preferentially transmitted [11 of 14 cases (79%); P = 0.03] in the group of TPOAb-positive mothers, and we observed a similar trend in the group of TPOAb- positive fathers (P = 0.08). Also, the portion of offspring affected by Graves' disease was significantly higher in TPOAb-positive than in TPOAb-negative fathers (P < 0.02). In conclusion, our findings demonstrate a significant effect of paternal HLA DQ alleles as well as antibody status on susceptibility to thyroid autoimmune disease in juvenile patients.

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

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


    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.

  3. Radioimmunotherapy of carcinoma of colon with [131I]-labeled recombinant chimeric monoclonal antibodies to carcinoembryonic antigen

    Institute of Scientific and Technical Information of China (English)

    Qiu-jun LU; Guang-xing BIAN; Yuan-yuan CHEN; Min ZHANG; Shao-ming GUO; Li-qing WEN


    Aim: To study the distribution of [131I]-labeled anti-CEA MoAbs and its therapeutic effect on the human colonic cancer model in nude mice. Methods: A nude mice model of human colonic cancer was established. [131I]-labeled anti-CEA MoAbs were injected intravenously into mice. The distribution of the MoAbs was then determined and the effect of RIT on human colonic cancer was observed. Results:The [131I]-labeled anti-CEA MoAbs had a specific distribution after injection.Tumor/non-tumor ratios for [131I]-labeled anti-CEA MoAbs were 10-20 times higher than [131I]-labeled IgG 96 h after injection. Thirty days after injection, significant inhibition of the volume and weight of tumor was observed in the treated mice compared with the control. The tumor growth inhibition rate of 3.1 mCi/kg CEA MoAbs group (LS 180, LS 174T, SW1116) was 47.8%-64.0%. This was 69.6%-78.6%in the 6.25 mCi/kg CEA MoAbs group, and 81.8%-86.2% in the 12.5 mCi/kg [131I]-labeled anti-CEA MoAbs group. The plasma CEA level was also lower in treated mice. Conclusion: The results indicate that [131I]-labeled anti-CEA MoAbs can be effective in RIT on colonic cancers.

  4. 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


    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.

  5. Opa+ Neisseria gonorrhoeae exhibits reduced survival in human neutrophils via Src family kinase-mediated bacterial trafficking into mature phagolysosomes. (United States)

    Johnson, M Brittany; Ball, Louise M; Daily, Kylene P; Martin, Jennifer N; Columbus, Linda; Criss, Alison K


    During gonorrhoeal infection, there is a heterogeneous population of Neisseria gonorrhoeae (Gc) varied in their expression of opacity-associated (Opa) proteins. While Opa proteins are important for bacterial attachment and invasion of epithelial cells, Opa+ Gc has a survival defect after exposure to neutrophils. Here, we use constitutively Opa- and OpaD+ Gc in strain background FA1090 to show that Opa+ Gc is more sensitive to killing inside adherent, chemokine-treated primary human neutrophils due to increased bacterial residence in mature, degradative phagolysosomes that contain primary and secondary granule antimicrobial contents. Although Opa+ Gc stimulates a potent oxidative burst, neutrophil killing of Opa+ Gc was instead attributable to non-oxidative components, particularly neutrophil proteases and the bactericidal/permeability-increasing protein. Blocking interaction of Opa+ Gc with carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) or inhibiting Src family kinase signalling, which is downstream of CEACAM activation, enhanced the survival of Opa+ Gc in neutrophils. Src family kinase signalling was required for fusion of Gc phagosomes with primary granules to generate mature phagolysosomes. Conversely, ectopic activation of Src family kinases or coinfection with Opa+ Gc resulted in decreased survival of Opa- Gc in neutrophils. From these results, we conclude that Opa protein expression is an important modulator of Gc survival characteristics in neutrophils by influencing phagosome dynamics and thus bacterial exposure to neutrophils' full antimicrobial arsenal.

  6. Characterization of a common antigen of colorectal and mucinous ovarian tumors, COTA. (United States)

    Pant, K D; Zamora, P O; Rhodes, B A; Sachatello, C R; Hagihara, P F; Griffen, W O; van Nagell, J R; Fulks, R; Ram, M D


    A new colon cancer antigen is reported. It is designated as COTA, Colon-Ovarian Tumor Antigen, because it is found in mucins produced by both tissues during malignancy. The new antigen was identified by making antibodies against human colon cancer tissue in goats. The antisera were exhaustively absorbed with lyophilized extracts of normal colon, lung, liver, spleen, kidney, plasma, and the well-known colon tumor antigen, carcinoembryonic antigen (CEA). The new antigen was identified by immunodiffusion. Studies of 28 malignant tissue extracts, 10 ovarian adenocarcinoma cyst fluids, 43 normal tissues, and 5 plasma samples revealed that this antigen is found only in colon tumors and mucinous ovarian adenocarcinomas. The antigen was not detected in serous adenocarcinoma of the ovaries, extracts of adenocarcinoma of lung, breast, kidney or stomach nor in the extracts of normal tissues. Other tests show that this antigen is not CEA, Ca 19-9, or CSAp. It is stable to heating at 65 degrees for 5 minutes; it elutes from an ion exchange matrix (DEAE) with 0.3-0.5M NaCl; it migrates to the alpha-2 region on immunoelectrophoresis; and its size, by exclusion chromatography on Sepharose 4B, is 3-15 million daltons. Anti-COTA stains colon cancer tissue sections indicating that COTA is present in goblet-cell mucin.

  7. Cloning and molecular characterization of cDNA encoding a mouse male-enhanced antigen-2 (Mea-2): a putative family of the Golgi autoantigen. (United States)

    Kondo, M; Sutou, S


    The male-enhanced antigen-2 (Mea-2) gene was originally identified with a monoclonal histocompatibility Y (H-Y) antibody (mAb4VII). There is no report of the full length cDNA encode for Mea-2 product until this report. In this study, we isolated the full length mouse Mea-2 cDNA by screening a testis cDNA library with a PCR-amplified Mea-2 product, and direct PCR amplification of its upstream sequences from the cDNA library. The primary structure of the Mea-2 peptide, deduced from this nucleotide sequence, shows that it encode a 150 kDa protein, of 1325 amino acid residues, which contained five putative N-glycosylation sites and four leucine zipper motifs. A data bank search indicated that it has high homology with a human Golgi autoantigen (golgin-160) both in its nucleotides (78%) and amino acids sequence (83%). This suggests that Mea-2 gene product may encode a golgi structural protein. In situ hybridization analysis suggested that the Mea-2 gene is expressed in spermatids during spermatogenesis as already shown by Mea-1, suggesting that Mea-2 gene product as well as Mea-1 have also some role for spermatogenesis.

  8. Characterization of a single b-type heme, FAD, and metal binding sites in the transmembrane domain of six-transmembrane epithelial antigen of the prostate (STEAP) family proteins. (United States)

    Kleven, Mark D; Dlakić, Mensur; Lawrence, C Martin


    Six-transmembrane epithelial antigen of the prostate 3 (Steap3) is the major ferric reductase in developing erythrocytes. Steap family proteins are defined by a shared transmembrane domain that in Steap3 has been shown to function as a transmembrane electron shuttle, moving cytoplasmic electrons derived from NADPH across the lipid bilayer to the extracellular face where they are used to reduce Fe(3+) to Fe(2+) and potentially Cu(2+) to Cu(1+). Although the cytoplasmic N-terminal oxidoreductase domain of Steap3 and Steap4 are relatively well characterized, little work has been done to characterize the transmembrane domain of any member of the Steap family. Here we identify high affinity FAD and iron biding sites and characterize a single b-type heme binding site in the Steap3 transmembrane domain. Furthermore, we show that Steap3 is functional as a homodimer and that it utilizes an intrasubunit electron transfer pathway through the single heme moiety rather than an intersubunit electron pathway through a potential domain-swapped dimer. Importantly, the sequence motifs in the transmembrane domain that are associated with the FAD and metal binding sites are not only present in Steap2 and Steap4 but also in Steap1, which lacks the N-terminal oxidoreductase domain. This strongly suggests that Steap1 harbors latent oxidoreductase activity.

  9. Skewed Helper T-Cell Responses to IL-12 Family Cytokines Produced by Antigen-Presenting Cells and the Genetic Background in Behcet’s Disease

    Directory of Open Access Journals (Sweden)

    Jun Shimizu


    Full Text Available Behcet’s disease (BD is a multisystemic inflammatory disease and is characterized by recurrent attacks on eyes, brain, skin, and gut. There is evidence that skewed T-cell responses contributed to its pathophysiology in patients with BD. Recently, we found that Th17 cells, a new helper T (Th cell subset, were increased in patients with BD, and both Th type 1 (Th1 and Th17 cell differentiation signaling pathways were overactivated. Several researches revealed that genetic polymorphisms in Th1/Th17 cell differentiation signaling pathways were associated with the onset of BD. Here, we summarize current findings on the Th cell subsets, their contribution to the pathogenesis of BD and the genetic backgrounds, especially in view of IL-12 family cytokine production and pattern recognition receptors of macrophages/monocytes.

  10. Isolation of a cDNA encoding thymic shared antigen-1. A new member of the Ly6 family with a possible role in T cell development. (United States)

    MacNeil, I; Kennedy, J; Godfrey, D I; Jenkins, N A; Masciantonio, M; Mineo, C; Gilbert, D J; Copeland, N G; Boyd, R L; Zlotnik, A


    We have previously characterized a novel mouse thymocyte marker, defined as thymic shared Ag-1 (TSA-1), present on both immature thymocytes and a subset of thymic medullary epithelial cells. MTS 35, a mAb specific for TSA-1, alters T cell differentiation when added to fetal thymic organ cultures, suggesting TSA-1 may be important for T cell development in the thymus. In this study, we describe the isolation of a cDNA encoding TSA-1 using transient expression of COS-7 cells and selection with MTS 35. The predicted amino acid sequence of this cDNA encodes a 15 to 17-kDa protein and the expressed protein is linked to the membrane via a phosphatidylinositol moiety. TSA-1 is transcriptionally active at various levels in all organs examined, suggesting that its role is not solely intrathymic. TSA-1 shares amino acid sequence homology to the mouse Ly6 multigene family, epidermal growth factor-like receptors, and to cobra venom neurotoxin. The Tsa-1 locus is located on chromosome 15 linked to Ly6 on the mouse genome. We also examined the effects of MTS 35 in fetal thymic organ cultures repopulated with two subsets of thymocytes representing defined stages of T cell development. Our results suggest that TSA-1 may play a role during positive selection and the transition from CD4+CD8+ thymocytes to the mature CD4+CD8- and CD4-CD8+ subsets.

  11. Expression of the SLAM family of receptors adapter EAT-2 as a novel strategy for enhancing beneficial immune responses to vaccine antigens. (United States)

    Aldhamen, Yasser A; Appledorn, Daniel M; Seregin, Sergey S; Liu, Chyong-jy J; Schuldt, Nathaniel J; Godbehere, Sarah; Amalfitano, Andrea


    Recent studies have shown that activation of the signaling lymphocytic activation molecule (SLAM) family of receptors plays an important role in several aspects of immune regulation. However, translation of this knowledge into a useful clinical application has not been undertaken. One important area where SLAM-mediated immune regulation may have keen importance is in the field of vaccinology. Because SLAM signaling plays such a critical role in the innate and adaptive immunity, we endeavored to develop a strategy to improve the efficacy of vaccines by incorporation of proteins known to be important in SLAM-mediated signaling. In this study, we hypothesized that coexpression of the SLAM adapter EWS-FLI1-activated transcript 2 (EAT-2) along with a pathogen-derived Ag would facilitate induction of beneficial innate immune responses, resulting in improved induction of Ag-specific adaptive immune responses. To test this hypothesis, we used rAd5 vector-based vaccines expressing murine EAT-2, or the HIV-1-derived Ag Gag. Compared with appropriate controls, rAd5 vectors expressing EAT-2 facilitated bystander activation of NK, NKT, B, and T cells early after their administration into animals. EAT-2 overexpression also augments the expression of APC (macrophages and dendritic cells) surface markers. Indeed, this multitiered activation of the innate immune system by vaccine-mediated EAT-2 expression enhanced the induction of Ag-specific cellular immune responses. Because both mice and humans express highly conserved EAT-2 adapters, our results suggest that human vaccination strategies that specifically facilitate SLAM signaling may improve vaccine potency when targeting HIV Ags specifically, as well as numerous other vaccine targets in general.

  12. Interpretation of sequential measurements of cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) based on analytical imprecision and biological variation in the monitoring of ovarian cancer

    DEFF Research Database (Denmark)

    Tuxen, Malgorzata K.; Sölétormos, G; Petersen, P H


    patients with serological tumor markers should take into account the stochastic variation, i.e. the probability that observed increases and decreases may solely be due to analytical imprecision and normal intra-individual biological variation. The aim of this study was to provide a detailed characteristic...... that it is necessary to adjust the assessment criteria to the type of marker, and that assessment may be facilitated if based on natural logarithmic transformed concentrations....

  13. Synthetic antigens reveal dynamics of BCR endocytosis during inhibitory signaling. (United States)

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


    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.

  14. Neutron-capture therapy of human cancer: in vitro results on the preparation of boron-labeled antibodies to carcinoembryonic antigen.


    Mizusawa, E; Dahlman, H L; Bennett, S. J.; Goldenberg, D M; Hawthorne, M F


    Two samples of 2-phenyl-1,2-dicarba-closo-[1-3H]dodecaborane(12) were prepared by treating 1-lithio-2-phenyl-1,2-dicarba-closo-dodecaborane(12) with 3H2O (0.1 and 5.0 Ci/ml, respectively). These tritiated phenylcarborane samples were subsequently converted to corresponding samples of p-[1,2-dicarba-closo-[1-3H]dodecaboran(12)-2-yl]benzenediazonium ion ([3H]DBD) suitable for azo-coupling reactions. Reaction of the two tritiated diazonium ion samples with 2-napthol resulted in the formation of ...

  15. Antígeno carcinoembrionário no diagnóstico diferencial dos derrames pleurais Carcinoembryonic antigen in differential diagnosis of pleural effusion

    Directory of Open Access Journals (Sweden)

    Miguel Angelo Martins de Castro Junior


    Full Text Available OBJETIVO: Analisar a sensibilidade e a especificidade da dosagem do CEA no diagnóstico diferencial do derrame pleural de pacientes portadores de doenças benígnas e malígnas. MÉTODO: Estudo contemporâneo de série de casos, realizado do Serviço de Cirurgia Torácica do Hospital Nossa Senhora da Conceição, Porto Alegre, Rio Grande do Sul. Entre julho de 2000 e julho de 2001, 64 pacientes foram submetidos à investigação etiológica de efusão pleural,e submetidos aos seguintes exames: pH, LDH, dosagem protêica, densidade, glicose, citologia diferencial, pesquisa de fungos e BAAR, gram e cultura com antibiograma, citopatologia, dosagem de CEA e biópsia pleural. RESULTADOS: Pacientes com derrames de etiologia maligna (n=26 tiveram resultado do CEA variando de zero a 5000ng/ml, enquanto nos de etiologia benígna os valores variaram de zero a 4,8ng/ml. Nível médio de CEA na efusão carcinomatosa foi de 431 ± 1237 ng/ml (média ± desvio padrão, significativamente maior que nos benignos (1,1 ± 1,0 ng/ml; pBACKGROUND: To analyze patients with diagnosis of benign or malignant diseases, in whose evolution develop pleural effusion, in which CEA measurement was questioned in relation to sensitivity and specificity in the differentiation of these two groups. METHODS: Prospective consecutive case series of the Department of Thoracic Surgery, Conceição Hospital, Porto Alegre, Brazil. From July 2000 to December 2001, 64 patients were subjected to clinical investigation in search for a pleural effusion aetiology. All patients underwent the following laboratory evaluation of pleural fluid: pH, LDH, proteins, density, glucose, differential cytology, bacterial culture, search for fungus and acid-fast bacilli, cytology, CEA determination and pleural biopsy. RESULTS: Patients with malignant etiologic diagnosis (n=26, had CEA results ranging from zero to 5000 ng/ ml, while benign cases results were from zero to 4.8 ng/ml. CEA level in malignant fluids was of 431 ± 1237 ng/ml (mean ± SE, significantly higher than benign fluids (1.1 ± 1.0 ng/ml; p< 0.001. Sensitivity, for a cut-off of 5 ng/ml, was 61.5% and specificity of 100%. CONCLUSION: We conclude that for patients with pleural effusion, CEA concentrations may represent an useful criteria to diagnosis.

  16. Half-Antibody Functionalized Lipid-Polymer Hybrid Nanoparticles for Targeted Drug Delivery to Carcinoembryonic Antigen (CEA) Presenting Pancreatic Cancer Cells (United States)

    Hu, Che-Ming Jack; Kaushal, Sharmeela; Tran Cao, Hop S.; Aryal, Santosh; Sartor, Marta; Esener, Sadik; Bouvet, Michael; Zhang, Liangfang


    Current chemotherapy regimens against pancreatic cancer are met with little success as poor tumor vascularization significantly limits the delivery of oncological drugs. High-dose targeted drug delivery, through which a drug delivery vehicle releases a large payload upon tumor localization, is thus a promising alternative strategy against this lethal disease. Herein, we synthesize anti-CEA half-antibody conjugated lipid-polymer hybrid nanoparticles and characterize their ligand conjugation yields, physicochemical properties, and targeting ability against pancreatic cancer cells. Under the same drug loading, the half-antibody targeted nanoparticles show enhanced cancer killing effect compared to the corresponding non-targeted nanoparticles. PMID:20394436

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

    Directory of Open Access Journals (Sweden)

    Kuo Chao-Hung


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

  18. Eosinofil Sel Penyaji Antigen

    Directory of Open Access Journals (Sweden)

    Safari Wahyu Jatmiko


    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

  19. Pars planitis in a family. (United States)

    Tejada, P; Sanz, A; Criado, D


    The familial occurrence of pars planitis is rare. We have found ten cases reported previously. We describe a new case of pars planitis in a family. The affected members included a mother and two of her four children. The family was tested for HLA antigens in order to establish a comparison with others HLA types by different authors. We have not identified any cause for the familial occurrence of this disease. We discuss the role of genetic and ambiental factors.

  20. Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and antitumor effects. (United States)

    Osada, Takuya; Berglund, Peter; Morse, Michael A; Hubby, Bolyn; Lewis, Whitney; Niedzwiecki, Donna; Yang, Xiao Yi; Hobeika, Amy; Burnett, Bruce; Devi, Gayathri R; Clay, Timothy M; Smith, Jonathan; Kim Lyerly, H


    We recently demonstrated that Venezuelan equine encephalitis virus-based replicon particle (VRPs) encoding tumor antigens could break tolerance in the immunomodulatory environment of advanced cancer. We hypothesized that local injection of VRP-expressing interleukin-12 (IL-12) at the site of injections of VRP-based cancer vaccines would enhance the tumor-antigen-specific T cell and antibody responses and antitumor efficacy. Mice were immunized with VRP encoding the human tumor-associated antigen, carcinoembryonic antigen (CEA) (VRP-CEA(6D)), and VRP-IL-12 was also administered at the same site or at a distant location. CEA-specific T cell and antibody responses were measured. To determine antitumor activity, mice were implanted with MC38-CEA-2 cells and immunized with VRP-CEA with and without VRP-IL-12, and tumor growth and mouse survival were measured. VRP-IL-12 greatly enhanced CEA-specific T cell and antibody responses when combined with VRP-CEA(6D) vaccination. VRP-IL-12 was superior to IL-12 protein at enhancing immune responses. Vaccination with VRP-CEA(6D) plus VRP-IL-12 was superior to VRP-CEA(6D) or VRP-IL-12 alone in inducing antitumor activity and prolonging survival in tumor-bearing mice. Importantly, local injection of VRP-IL-12 at the VRP-CEA(6D) injection site provided more potent activation of CEA-specific immune responses than that of VRP-IL-12 injected at a distant site from the VRP-CEA injections. Together, this study shows that VRP-IL-12 enhances vaccination with VRP-CEA(6D) and was more effective at activating CEA-specific T cell responses when locally expressed at the vaccine site. Clinical trials evaluating the adjuvant effect of VRP-IL-12 at enhancing the immunogenicity of cancer vaccines are warranted.

  1. 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))


    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.

  2. A new human cholangiocellular carcinoma cell line (HuCC-T1) producing carbohydrate antigen 19/9 in serum-free medium. (United States)

    Miyagiwa, M; Ichida, T; Tokiwa, T; Sato, J; Sasaki, H


    A human cholangiocellular carcinoma cell line, HuCC-T1, was established in vitro from the malignant cells of ascites of a 56-yr-old patient. Histologic findings of the primary liver tumor revealed a moderately differentiated adenocarcinoma. Tumor cells from the ascites have been cultured with RPMI 1640 medium containing 0.2% lactalbumin hydrolysate and the cultured cells grew as monolayers with a population doubling time of 74 h during exponential growth at Passage 25. They had an epithelial-like morphology and were positive for mucine staining. Ultrastructural studies revealed the presence of microvilli on the cell surface and poorly developed organelles in the cytoplasm. The HuCC-T1 cell was tumorigenic in nude mice. The number of chromosomes in HuCC-T1 ranged from 61 to 80. These human cholangiocellular carcinoma cells in serum-free medium secreted several tumor markers, including carbohydrate antigen 19/9, carbohydrate antigen 125, carcinoembryonic antigen, and tissue polypeptide antigen. The carbohydrate antigen 19/9 secretion level of HuCC-T1 cells cultured in RPMI 1640 medium with 1% fetal bovine serum was sixfold higher than that with 0.2% lactalbumin hydrolysate. These findings suggest that HuCC-T1 will provide useful information to clarify the mechanism of tumor marker secretion and tumor cell growth in the human cholangiocellular carcinoma.

  3. Immunochemical analysis of Taenia taeniaeformis antigens expressed in Escherichia coli. (United States)

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


    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.

  4. Immunoliposome-PCR: a generic ultrasensitive quantitative antigen detection system

    Directory of Open Access Journals (Sweden)

    He Junkun


    Full Text Available Abstract Background The accurate quantification of antigens at low concentrations over a wide dynamic range is needed for identifying biomarkers associated with disease and detecting protein interactions in high-throughput microarrays used in proteomics. Here we report the development of an ultrasensitive quantitative assay format called immunoliposome polymerase chain reaction (ILPCR that fulfills these requirements. This method uses a liposome, with reporter DNA encapsulated inside and biotin-labeled polyethylene glycol (PEG phospholipid conjugates incorporated into the outer surface of the liposome, as a detection reagent. The antigenic target is immobilized in the well of a microplate by a capture antibody and the liposome detection reagent is then coupled to a biotin-labeled second antibody through a NeutrAvidin bridge. The liposome is ruptured to release the reporter DNA, which serves as a surrogate to quantify the protein target using real-time PCR. Results A liposome detection reagent was prepared, which consisted of a population of liposomes ~120 nm in diameter with each liposome possessing ~800 accessible biotin receptors and ~220 encapsulated reporters. This liposome detection reagent was used in an assay to quantify the concentration of carcinoembryonic antigen (CEA in human serum. This ILPCR assay exhibited a linear dose–response curve from 10-10 M to 10-16 M CEA. Within this range the assay coefficient of variance was Conclusions The ILPCR assay has several advantages over other immuno-PCR methods. The reporter DNA and biotin-labeled PEG phospholipids spontaneously incorporate into the liposomes as they form, simplifying preparation of the detection reagent. Encapsulation of the reporter inside the liposomes allows nonspecific DNA in the assay medium to be degraded with DNase I prior to quantification of the encapsulated reporter by PCR, which reduces false-positive results and improves quantitative accuracy. The ability to

  5. Cancer-testis antigen lymphocyte antigen 6 complex locus K is a serologic biomarker and a therapeutic target for lung and esophageal carcinomas. (United States)

    Ishikawa, Nobuhisa; Takano, Atsushi; Yasui, Wataru; Inai, Kouki; Nishimura, Hitoshi; Ito, Hiroyuki; Miyagi, Yohei; Nakayama, Haruhiko; Fujita, Masahiro; Hosokawa, Masao; Tsuchiya, Eiju; Kohno, Nobuoki; Nakamura, Yusuke; Daigo, Yataro


    Gene expression profile analyses of non-small cell lung carcinomas (NSCLC) and esophageal squamous cell carcinomas (ESCC) revealed that lymphocyte antigen 6 complex locus K (LY6K) was specifically expressed in testis and transactivated in a majority of NSCLCs and ESCCs. Immunohistochemical staining using 406 NSCLC and 265 ESCC specimens confirmed that LY6K overexpression was associated with poor prognosis for patients with NSCLC (P = 0.0003), as well as ESCC (P = 0.0278), and multivariate analysis confirmed its independent prognostic value for NSCLC (P = 0.0035). We established an ELISA to measure serum LY6K and found that the proportion of the serum LY6K-positive cases was 38 of 112 (33.9%) NSCLC and 26 of 81 (32.1%) ESCC, whereas only 3 of 74 (4.1%) healthy volunteers were falsely diagnosed. In most cases, there was no correlation between serum LY6K and conventional tumor markers of carcinoembryonic antigen (CEA) and cytokeratin 19-fragment (CYFRA 21-1) values. A combined ELISA for both LY6K and CEA classified 64.7% of lung adenocarcinoma patients as positive, and the use of both LY6K and CYFRA 21-1 increased sensitivity in the detection of lung squamous cell carcinomas and ESCCs up to 70.4% and 52.5%, respectively, whereas the false positive rate was 6.8% to 9.5%. In addition, knocked down of LY6K expression with small interfering RNAs resulted in growth suppression of the lung and esophageal cancer cells. Our data imply that a cancer-testis antigen, LY6K, should be useful as a new type of tumor biomarker and probably as a target for the development of new molecular therapies for cancer treatment.

  6. 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


    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...

  7. Umbilical cord blood regulatory T-cell expansion and functional effects of tumor necrosis factor receptor family members OX40 and 4-1BB expressed on artificial antigen-presenting cells. (United States)

    Hippen, Keli L; Harker-Murray, Paul; Porter, Stephen B; Merkel, Sarah C; Londer, Aryel; Taylor, Dawn K; Bina, Megan; Panoskaltsis-Mortari, Angela; Rubinstein, Pablo; Van Rooijen, Nico; Golovina, Tatiana N; Suhoski, Megan M; Miller, Jeffrey S; Wagner, John E; June, Carl H; Riley, James L; Blazar, Bruce R


    Previously, we showed that human umbilical cord blood (UCB) regulatory T cells (Tregs) could be expanded approximately 100-fold using anti-CD3/28 monoclonal antibody (mAb)-coated beads to provide T-cell receptor and costimulatory signals. Because Treg numbers from a single UCB unit are limited, we explored the use of cell-based artificial antigen-presenting cells (aAPCs) preloaded with anti-CD3/28 mAbs to achieve higher levels of Treg expansion. Compared with beads, aAPCs had similar expansion properties while significantly increasing transforming growth factor beta (TGF-beta) secretion and the potency of Treg suppressor function. aAPCs modified to coexpress OX40L or 4-1BBL expanded UCB Tregs to a significantly greater extent than bead- or nonmodified aAPC cultures, reaching mean expansion levels exceeding 1250-fold. Despite the high expansion and in contrast to studies using other Treg sources, neither OX40 nor 4-1BB signaling of UCB Tregs reduced in vitro suppression. UCB Tregs expanded with 4-1BBL expressing aAPCs had decreased levels of proapoptotic bim. UCB Tregs expanded with nonmodified or modified aAPCs versus beads resulted in higher survival associated with increased Treg persistence in a xeno-geneic graft-versus-host disease lethality model. These data offer a novel approach for UCB Treg expansion using aAPCs, including those coexpressing OX40L or 4-1BBL.

  8. New mucin-like cancer-associated antigens (CA M 26, CA M 29 and CA 549) and a new proliferation marker (TPS) in patients with primary or advanced breast cancer. (United States)

    Locker, G J; Mader, R M; Braun, J; Sieder, A E; Marosi, C; Rainer, H; Jakesz, R; Steger, G G


    In patients with breast cancer no tumor markers giving satisfactory results have been found yet. The aim of our investigation was to compare the usefulness of newly developed tumor markers with the most common used carcinoembryonic antigen and cancer antigen (CA) 15-3. We evaluated the concentrations of carcinoma-associated antigen (CA) 549, carcinoma-associated mucin antigen (CA M) 26 and CA M 29, and the proliferation markers tissue polypeptide antigen (TPA) and tissue polypeptide-specific antigen (TPS) in 84 breast cancer patients with disease progression and in 69 patients with no evidence of disease after surgery for breast cancer. Using receiver-operating characteristic curves (ROC curves) we were able to demonstrate increased sensitivity and specificity of all tested tumor markers in patients with metastatic disease compared with local disease. In our investigation TPA is superior to TPS in all disease states. In local disease, none of the tested markers shows satisfying results. In metastatic disease, the new mucin markers CA M 26 and CA M 29 show slightly better results than CA 15-3 although their ROC curves are nearly congruent. CA 549 is exceeded by the other mucin markers. The best results in this investigation were obtained with CA M 29. The overall results concerning the detection of small tumor masses (i.e. local disease) were unsatisfactory.

  9. Myeloid antigens in childhood lymphoblastic leukemia:clinical data point to regulation of CD66c distinct from other myeloid antigens

    Directory of Open Access Journals (Sweden)

    Madzo Jozef


    Full Text Available Abstract Background Aberrant expression of myeloid antigens (MyAgs on acute lymphoblastic leukemia (ALL cells is a well-documented phenomenon, although its regulating mechanisms are unclear. MyAgs in ALL are interpreted e.g. as hallmarks of early differentiation stage and/or lineage indecisiveness. Granulocytic marker CD66c – Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6 is aberrantly expressed on ALL with strong correlation to genotype (negative in TEL/AML1 and MLL/AF4, positive in BCR/ABL and hyperdiploid cases. Methods In a cohort of 365 consecutively diagnosed Czech B-precursor ALL patients, we analyze distribution of MyAg+ cases and mutual relationship among CD13, CD15, CD33, CD65 and CD66c. The most frequent MyAg (CD66c is studied further regarding its stability from diagnosis to relapse, prognostic significance and regulation of surface expression. For the latter, flow cytometry, Western blot and quantitative RT-PCR on sorted cells is used. Results We show CD66c is expressed in 43% patients, which is more frequent than other MyAgs studied. In addition, CD66c expression negatively correlates with CD13 (p Conclusion In contrast to general notion we show that different MyAgs in lymphoblastic leukemia represent different biological circumstances. We chose the most frequent and tightly genotype-associated MyAg CD66c to show its stabile expression in patients from diagnosis to relapse, which differs from what is known on the other MyAgs. Surface expression of CD66c is regulated at the gene transcription level, in contrast to previous reports.

  10. Dd-antigen-antibody system in five caste groups in north India. (United States)

    Berry, V; Kaur, H


    Antigen Dd, a polymorphic antigen found in extracts of certain human dandruff specimens, was investigated in five caste groups of north India. The incidence of antigen Dd-positive type varied from 21.21 per cent in Brahmins to 29.08 per cent in the Jat Sikhs of Punjab. However, a high frequency (45%) was observed in the Sunni Muslims of Kashmir, which differed significantly, when compared with different caste groups of Punjab. Family studies on 44 families indicated its inherited nature, the mode of inheritance being autosomal dominant.

  11. Antigen antibody interactions

    CERN Document Server

    DeLisi, Charles


    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...

  12. [Immunoglobulin genes encoding antibodies directed to oncodevelopmental carbohydrate antigens]. (United States)

    Zenita, K; Yago, K; Fujimoto, E; Kannagi, R


    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

  13. Antigenic Variation in Bacterial Pathogens. (United States)

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


    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.

  14. 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.


    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.

  15. Radioimmunoassays of hidden viral antigens. (United States)

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


    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

  16. Improved Activation toward Primary Colorectal Cancer Cells by Antigen-Specific Targeting Autologous Cytokine-Induced Killer Cells

    Directory of Open Access Journals (Sweden)

    Claudia Schlimper


    Full Text Available Adoptive therapy of malignant diseases with cytokine-induced killer (CIK cells showed promise in a number of trials; the activation of CIK cells from cancer patients towards their autologous cancer cells still needs to be improved. Here, we generated CIK cells ex vivo from blood lymphocytes of colorectal cancer patients and engineered those cells with a chimeric antigen receptor (CAR with an antibody-defined specificity for carcinoembryonic antigen (CEA. CIK cells thereby gained a new specificity as defined by the CAR and showed increase in activation towards CEA+ colon carcinoma cells, but less in presence of CEA− cells, indicated by increased secretion of proinflammatory cytokines. Redirected CIK activation was superior by CAR-mediated CD28-CD3ζ than CD3ζ signaling only. CAR-engineered CIK cells from colon carcinoma patients showed improved activation against their autologous, primary carcinoma cells from biopsies resulting in more efficient tumour cell lysis. We assume that adoptive therapy with CAR-modified CIK cells shows improved selectivity in targeting autologous tumour lesions.

  17. Trypanosoma cruzi as an effective cancer antigen delivery vector. (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


    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.

  18. Family Life (United States)

    ... With Family and Friends > Family Life Request Permissions Family Life Approved by the Cancer.Net Editorial Board , ... your outlook on the future. Friends and adult family members The effects of cancer on your relationships ...

  19. Dissolved families

    DEFF Research Database (Denmark)

    Christoffersen, Mogens

    The situation in the family preceding a family separation is studied here, to identify risk factors for family dissolution. Information registers covering prospective statistics about health aspects, demographic variables, family violence, self-destructive behaviour, unemployment, and the spousal...

  20. Stem cell antigen 2 expression in adult and developing mice. (United States)

    Antica, M; Wu, L; Scollay, R


    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.

  1. An iron-binding Trypanosoma cruzi urinary antigen. (United States)

    Corral, R S; Bertot, G M; Petray, P B; Altcheh, J M; Singh, M; Orn, A; Rapoport, M F; Grinstein, S


    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.

  2. Role of tumor-associated antigen expression in radioimmunoguided surgery for colorectal and breast cancer. (United States)

    Bertoglio, S; Percivale, P; Schenone, F; Peressini, A; Murolo, C; Badellino, F


    One hundred thirty-six patients with colorectal and breast cancer were enrolled in a retrospective study using radioimmunoguided surgery (RIGS) with Iodine-125 (I125) radiolabeled B72.3 (Group A, 73 patients) and F023C5 (Group B, 63 patients) monoclonal antibodies (MAbs). The correlation between intraoperative tumor-to-normal tissue (T/NT) gamma-detecting probe (GDP) counts ratio and the expression of tumor-associated glycoprotein (TAG)-72 (GroupA patients) and carcinoembryonic antigen (CEA; Group B patients) tumor-associated antigens (TAA) expression of 209 resected or biopsy tumor specimens was assessed. Ex vivo radioimmunolocalization index (R.I.) was carried out on the same specimens as a control of intraoperative GDP ratio values. RIGS positive definition of tumor occurred in 80/113 (70.8%) tumor sites of Group A patients and in 84/96 (87.5%) tumor sites of Group B patients. Mean percent B72.3 TAA expression of 113 tumor sites of Group A patients was 62.74 +/- 28.79% vs. 73.00 +/- 26.28% of 96 tumor sites of Group B patients (P < 0.05). The higher incidence of positive RIGS results was observed in tumor sites with the higher expression of the relative TAA. A statistically significant correlation between RIGS ratios and B72.3 and CEA expression was observed in the 113 tumor sites of Group A (P < 0.05) and in the 96 tumor sites of Group B (P < 0.01), respectively. The role of a preoperative evaluation of TAA expression in patients undergoing RIGS is discussed. Its assessment, whenever possible, may help to select those patients who will benefit more from this immunodiagnostic technique.

  3. Oncogenic cancer/testis antigens

    DEFF Research Database (Denmark)

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


    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...

  4. Molecular cloning of Taenia taeniaeformis oncosphere antigen genes. (United States)

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


    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.

  5. Intermolecular forces and enthalpies in the adhesion of Streptococcus mutans and antigen I/II deficient mutant to laminin films

    NARCIS (Netherlands)

    Busscher, H.J.; Belt-Gritter, van de B.; Dijkstra, R.J.B.; Norde, W.; Mei, van der H.C.


    The antigen I/II family of surface proteins is expressed by most oral streptococci, including Streptococcus mutans, and mediates specific adhesion to, among other things, salivary films and extracellular matrix proteins. In this study we showed that antigen I/II-deficient S. mutans isogenic mutant I

  6. Antigen, allele, and haplotype frequencies report of the ASHI minority antigens workshops: part 1, African-Americans. (United States)

    Zachary, A A; Bias, W B; Johnson, A; Rose, S M; Leffell, M S


    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.

  7. Family History (United States)

    Your family history includes health information about you and your close relatives. Families have many factors in common, including their genes, ... as heart disease, stroke, and cancer. Having a family member with a disease raises your risk, but ...

  8. Family Disruptions (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Life Listen Español Text Size Email Print Share Family Disruptions Page Content Article Body No matter how ...

  9. Family Arguments (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Life Listen Español Text Size Email Print Share Family Arguments Page Content Article Body We seem to ...

  10. Family Therapy (United States)

    ... may be credentialed by the American Association for Marriage and Family Therapy (AAMFT). Family therapy is often short term. ... challenging situations in a more effective way. References Marriage and family therapists: The friendly mental health professionals. American Association ...

  11. Structural and Functional Variation within the Alanine-Rich Repetitive Domain of Streptococcal Antigen I/II


    Demuth, Donald R; Irvine, Douglas C.


    Members of the antigen I/II family of cell surface proteins are highly conserved, multifunctional adhesins that mediate interactions of oral streptococci with other oral bacteria, with cell matrix proteins (e.g., type I collagen), and with salivary glycoproteins, e.g., gp340. The interaction of gp340 (formerly designated salivary agglutinin) with Streptococcus mutans requires an alanine-rich repetitive domain (A region) of antigen I/II that is highly conserved in all members of this family of...

  12. [An avian strain of Escherichia coli with antigens common to the genus Salmonella]. (United States)

    Terzolo, H R; Zoratti de Verona, A; d'Empaire, M; Furowicz, A J


    On a commercial poultry farm, a large percentage (9%) of clinically healthy fowls had positive reaction to the plate test, with commercial polyvalent pullorum antigens. We could not isolate Salmonella from the positive birds. An strain, of Escherichia coli Balcarce (E. coli B) was isolated from the feces of one of the birds. The isolate was identified biochemically and the antigenic study showed correlation with E. coli 044 and the somatic fraction 1, 2, 8, 14 and 23 of the Salmonella genus. The common antigens were studied by agglutination, absorption and crossed immunodiffusion tests, comparing the isolated strain and the different Salmonella serotypes. Four pullorum polyvalent commercial antigens reacted with sera containing somatic agglutinins 1, and with the E. coli B antiserum. These observations confirm the high antigenic correlation between the genus of the Enterobacteriaceae family. It is indicated that for the diagnosis of avian salmonelosis rather than using a single serological tests, the isolation and identification of the etiological agent is required.

  13. Family Privilege (United States)

    Seita, John R.


    Family privilege is defined as "strengths and supports gained through primary caring relationships." A generation ago, the typical family included two parents and a bevy of kids living under one roof. Now, every variation of blended caregiving qualifies as family. But over the long arc of human history, a real family was a…

  14. Proteomic selection of immunodiagnostic antigens for Trypanosoma congolense.

    Directory of Open Access Journals (Sweden)

    Jennifer R Fleming


    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.

  15. Identification of a macromolecule containing an anticarcinoembryonic antigen-reactive substance and immunoglobulin M in human pancreatic cancer. (United States)

    Harvey, S R; Van Dusen, L R; Douglass, H O; Holyoke, E D; Chu, T M


    Ascitic fluid from a patient with carcinoma of the pancreas was fractionated by ammonium sulfate precipitation. The fraction precipitated between 25 and 50% saturation of ammonium sulfate was sequentially chromatographed on Sephadex G-200 and Sepharose 6B. A macromolecular fraction (greater than 10(6) daltons) obtained was found to react with both antihuman IgM and antiserum to carcinoembryonic antigen (CEA). This fraction was further purified by adsorption with protein A-Sepharose CL-4B and chromatography on DEAE-Sephacel. The purified macromolecular fraction had a sedimentation value of 28S as determined by ultracentrifugation. Upon dissociation of the purified macromolecule at pH 2.3 and purification of the dissociated components on Sepharose CL-2B and BioGel A 1.5M, a 19S protein and a 5S protein were recovered. The 19S protein showed a complete line of identity with a reference human IgM when reacted with antihuman IgM in gel diffusion, whereas the 5S protein showed a partial immunologic identity with colon CEA against anti-CEA. These results indicated the existence of an IgM-containing macromolecular complex with an anti-CEA cross-reactive substance in the extracellular fluid of human pancreatic cancer.

  16. Concepts and applications for influenza antigenic cartography (United States)

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


    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 PMID:21761589

  17. Familial gigantism

    Directory of Open Access Journals (Sweden)

    Wouter W. de Herder


    Full Text Available Familial GH-secreting tumors are seen in association with three separate hereditary clinical syndromes: multiple endocrine neoplasia type 1, Carney complex, and familial isolated pituitary adenomas.

  18. Familial dermographism. (United States)

    Jedele, K B; Michels, V V


    Urticaria in response to various physical stimuli has been reported in sporadic and familial patterns. The most common of these physical urticarias, dermographism, is a localized urticarial response to stroking or scratching of the skin and has not been reported previously to be familial. A four-generation family with dermographism, probably inherited as an autosomal dominant trait, is presented along with a discussion of sporadic dermographism and other types of familial physical urticarias.

  19. Antigen Export Reduces Antigen Presentation and Limits T Cell Control of M. tuberculosis. (United States)

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


    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.


    Directory of Open Access Journals (Sweden)

    Laura eSantambrogio


    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.

  1. Bacterial phospholipide antigens and their taxonomic significance. (United States)

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


    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.

  2. [HLA antigens in juvenile rheumatoid arthritis]. (United States)

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


    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.

  3. Cytokeratin 19 fragment antigen 21-1 as an independent predictor for definitive chemoradiotherapy sensitivity in esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    YAN Hong-jiang; WANG Ren-ben; ZHU Kun-li; JIANG Shu-mei; ZHAO Wei; XU Xiao-qing; FENG Rui


    Background Patients with esophageal squamous cell carcinoma (ESCC) undergoing definitive chemoradiotherapy (CRT) seem to have a disparity in therapeutic response.The identification of CRT sensitivity-related clinicopathological factors would be helpful for selecting patients most likely to benefit from CRT.Cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and carcinoembryonic antigen (CEA) have been reported as useful tumor markers for esophageal cancer.The aim of this study was to examine the predictive value of CYFRA21-1 in comparison with CEA and other clinicopathological factors in patients with ESCC treated with definitive CRT.Methods Pretreatment serum CYFRA21-1 and CEA levels were measured by immunoradiometric assays.The relationships between pretreatment clinicopathological factors and the efficacy of CRT were analyzed.Overall survival (OS) was estimated by univariate and multivariate analysis.Results The results from a univariate analysis indicated that the efficacy of CRT was significantly associated with the serum levels of CYFRA21-1 and CEA before treatment (P=0.001 and P=0.023,respectively).It also indicated that the efficacy of CRT was significantly associated with the pretreatment tumor location (P=0.041).By Logistic regression analysis,the independent predictive factor associated with efficacy of CRT was CYFRA21-1 (P=0.002).The OS of the patients with high CYFRA 21-1 levels was worse than that of those with low CYFRA21-1 levels (P=0.001).In multivariate analysis,a low level of CYFRA21-1 was the most significant independent predictor of good OS (P=0.007).Conclusions CEA and tumor location may be useful in predicting the sensitivity of ESCC to CRT.CYFRA21-1 may be an independent predictor for definitive CRT sensitivity in ESCC.

  4. Stable solid-phase Rh antigen. (United States)

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


    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.

  5. Common antigens between hydatid cyst and cancers

    Directory of Open Access Journals (Sweden)

    Shima Daneshpour


    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.

  6. Common antigens between hydatid cyst and cancers (United States)

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


    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

  7. Expression and immunogenicity of novel subunit enterovirus 71 VP1 antigens

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Juan [China-US Vaccine Research Center, The First Affiliated Hospital, Nanjing Medical University (China); Department of Microbiology and Immunology, Nanjing Medical University (China); Wang, Shixia [China-US Vaccine Research Center, The First Affiliated Hospital, Nanjing Medical University (China); Department of Medicine, University of Massachusetts Medical School (United States); Gan, Weihua [Department of Pediatrics, The Second Affiliated Hospital, Nanjing Medical University (China); Zhang, Wenhong [Department of Infectious Diseases, Huashan Hospital, Fudan University (China); Ju, Liwen [School of Public Health, Fudan University (China); Huang, Zuhu [Department of Infectious Diseases, The First Affiliated Hospital, Nanjing Medical University (China); China-US Vaccine Research Center, The First Affiliated Hospital, Nanjing Medical University (China); Lu, Shan, E-mail: [Department of Infectious Diseases, The First Affiliated Hospital, Nanjing Medical University (China); China-US Vaccine Research Center, The First Affiliated Hospital, Nanjing Medical University (China); Department of Medicine, University of Massachusetts Medical School (United States)


    Highlights: Black-Right-Pointing-Pointer EV71 is a major emerging infectious disease in many Asian countries. Black-Right-Pointing-Pointer Inactivated EV71 vaccines are in clinical studies but their safety and efficacy are unknown. Black-Right-Pointing-Pointer Developing subunit based EV71 vaccines is significant and novel antigen design is needed. Black-Right-Pointing-Pointer DNA immunization is an efficient tool to test the immunogenicity of VP1 based EV71 vaccines. Black-Right-Pointing-Pointer Multiple VP1 antigens are developed showing immunogenic potential. -- Abstract: Hand, foot, and mouth disease (HFMD) is a common viral illness in young children. HFMD is caused by viruses belonging to the enterovirus genus of the picornavirus family. Recently, enterovirus 71 (EV71) has emerged as a virulent agent for HFMD with severe clinical outcomes. In the current report, we conducted a pilot antigen engineering study to optimize the expression and immunogenicity of subunit VP1 antigen for the design of EV71 vaccines. DNA immunization was adopted as a simple technical approach to test different designs of VP1 antigens without the need to express VP1 protein in vitro first. Our studies indicated that the expression and immunogenicity of VP1 protein can be improved with alternated VP1 antigen designs. Data presented in the current report revealed novel pathways to optimize the design of VP1 antigen-based EV71 vaccines.


    Directory of Open Access Journals (Sweden)

    T.R. Neyestani


    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

  9. Intermolecular forces and enthalpies in the adhesion of Streptococcus mutans and an antigen I/II-deficient mutant to laminin films

    NARCIS (Netherlands)

    Busscher, Henk J.; van de Belt-Gritter, Betsy; Dijkstra, Rene J. B.; Norde, Willem; Petersen, Fernanda C.; Scheie, Anne A.; van der Mei, Henny C.


    The antigen I/II family of surface proteins is expressed by most oral streptococci, including Streptococcus mutans, and mediates specific adhesion to, among other things, salivary films and extracellular matrix proteins. In this study we showed that antigen I/II-deficient S. mutans isogenic mutant I

  10. Family Polymorphism

    DEFF Research Database (Denmark)

    Ernst, Erik


    safety and flexibility at the level of multi-object systems. We are granted the flexibility of using different families of kinds of objects, and we are guaranteed the safety of the combination. This paper highlights the inability of traditional polymorphism to handle multiple objects, and presents family...... polymorphism as a way to overcome this problem. Family polymorphism has been implemented in the programming language gbeta, a generalized version of Beta, and the source code of this implementation is available under GPL....

  11. My Family

    Institute of Scientific and Technical Information of China (English)


    Everyone has a family.We live in it and feel very warm.There are three persons in my family,my mother,father and I.We live together very happily and there are many interesting stories about my family. My father is a hard-working man.He works as a doctor.He always tries his best to help every,patient and make patients comfortable.But sonetimes he works so hard

  12. Family literacy

    DEFF Research Database (Denmark)

    Sehested, Caroline


    I Projekt familielæsning, der er et samarbejde mellem Nationalt Videncenter for Læsning og Hillerød Bibliotek, arbejder vi med at få kontakt til de familier, som biblioteket ellers aldrig ser som brugere og dermed også de børn, der vokser op i familier, for hvem bøger og oplæsningssituationer ikke...... er en selvfølgelig del af barndommen. Det, vi vil undersøge og ønsker at være med til at udvikle hos disse familier, er det, man kan kalde family literacy....

  13. Interaction forces between salivary proteins and Streptococcus mutans with and without antigen I/II

    NARCIS (Netherlands)

    Xu, C.P.; Belt-Gritter, van de B.; Dijkstra, R.J.B.; Norde, W.; Mei, van der H.C.; Busscher, H.J.


    The antigen I/II family of surface proteins is expressed by oral streptococci, including Streptococcus mutans, and mediates specific binding to, among others, salivary films. The aim of this study was to investigate the interaction forces between salivary proteins and S. mutans with (LT11) and witho

  14. Stool Test: H. Pylori Antigen (United States)

    ... Development Infections Diseases & Conditions Pregnancy & Baby Nutrition & Fitness Emotions & Behavior School & Family Life First Aid & Safety Doctors & ... placed in tiny vials. Specific chemicals and a color developer are added. At the end of the ...

  15. Specificity of mimotope-induced anti-high molecular weight-melanoma associated antigen (HMW-MAA antibodies does not ensure biological activity.

    Directory of Open Access Journals (Sweden)

    Julia Latzka

    Full Text Available Vaccines based on peptide mimics (mimotopes of conformational tumor antigen epitopes have been investigated for a variety of human tumors including breast cancer, tumors expressing the carcinoembryonic antigen, B cell lymphoma, neuroblastoma, and melanoma. In our previous work, we designed a vaccine based on a mimotope of the high molecular weight-melanoma associated antigen (HMW-MAA that elicited HMW-MAA-specific antibodies (Abs with anti-tumor activity in vitro and in vivo. In this study, we aimed to identify mimotopes of additional distinct HMW-MAA epitopes, since they could be used to construct a polymimotope melanoma vaccine. For this purpose, random peptide phage libraries were screened with the anti-HMW-MAA monoclonal antibodies (mAbs VT80.12 and VF1-TP43 yielding one peptide ligand for each mAb. Both peptides inhibited the binding of the corresponding mAb to the HMW-MAA. Furthermore, when coupled to the carrier protein keyhole limpet hemocyanin (KLH, both HMW-MAA mimotopes elicited peptide-specific Abs in rabbits or BALB/c mice, but only the mimotope isolated with the mAb VT80.12 elicited HMW-MAA-specific Abs and only in mice. However, the latter Abs had no detectable effect on HMW-MAA expressing human melanoma cells in vitro. These results describe limitations related to the phage display technique and emphasize the need to characterize the functional properties of the mAb utilized to isolate mimotopes of the corresponding epitopes.


    Wendt, Lisiane Dilli


    Platystomatidae (Signal Flies) are one of the largest families of Tephritoidea, with about 1200 species and four subfamilies, worldwide distributed. However, Platystomatidae are not well represented in the New World, and in the Neotropical Region only four genera and 26 species, belonging to Platystomatinae, are recorded. The family is a group understudied in Colombia and only one species is recorded to the country.

  17. [Antigenic relationships between Debaryomyces strains (author's transl)]. (United States)

    Aksoycan, N


    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.

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


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


    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 ...

  19. HLA II class antigens and susceptibility to coeliac disease

    Directory of Open Access Journals (Sweden)

    Vojvodić Svetlana


    Full Text Available Coeliac disease (CD is a systemic autoimmune, complex and multifactorial disorder, which is caused by interactions between genetic and environmental factors. The only established genetic risk factors so far are the human leucocyte antigens. The aim of this study was to assess the distribution of II class human leukocyte antigens (HLA in patients with coeliac disease and to investigate the susceptibility to coeliac disease in family members. We typed HLA DR and DQ antigens in 37 patients from Vojvodina with coeliac disease, 23 first-degree relatives, and 210 controls, serologically using standard lymphocytotoxicity technique. HLA DQ5(1, DQ6(1, DR11(5, DQ7(3, DQ2 and DR15(2 were the most common antigens in the control group. Frequency of HLA DQ2, DR3 and DR7 was higher in CD patients than in the control group. The relative risks for HLA DQ2, DR3 and DR7 were 4.846, 6.986 and 2.106, respectively, while positive association was found between HLA DQ2 and DR3 and CD. Frequency of HLA DQ2, DR3 and DR16(2 was higher in first-degree relatives than in the control group while a positive association was found between HLA DQ2 and DR3. A negative association was found between HLA DQ5(1 and DQ6(1 in coeliac patients from Vojvodina and their relatives, in addition to HLA DR11(5 in the group of relatives (RR=0.363,PF=0.232. These findings indicate the impact of the HLA testing for CD in clinical practice in order to rule out the possibility to CD in doubtful cases or in at-risk subjects.

  20. 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

  1. A computational framework for influenza antigenic cartography. (United States)

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


    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

  2. Family matters

    DEFF Research Database (Denmark)

    Kieffer-Kristensen, Rikke; Siersma, Volkert Dirk; Teasdale, Thomas William


    OBJECTIVES: To relate illness and family factors to emotional and behavioural problems in school-age children (7–14 years old) of parents with acquired brain injury and their healthy spouses. PARTICIPANTS, MATERIALS/METHODS: Members of 35 families in which a parent had been diagnosed with acquired...... brain injury participated. Family and brain injury characteristics were reported by the ill and healthy parents. Children self-reported post-traumatic stress symptoms (PSS) using the Child Impact of Events revised (CRIES). Emotional and behavioural problems among the children were also identified...... by the parents using the Achenbach’s Child Behaviour Checklist (CBCL). RESULTS: The family stress variables relating to the healthy spouse in all six comparisons were significant (p

  3. Small Families (United States)

    ... neighborhood activity centers also can fulfill these needs. Even if your relatives are scattered, try to strengthen your child's sense of family by keeping in touch by phone and letters. Encourage your child to draw pictures for relatives, ...

  4. Familial hypercholesterolemia (United States)

    ... hypercholesterolemia or early heart attacks High level of LDL cholesterol in either or both parents People from families ... called fibroblasts to see how the body absorbs LDL cholesterol Genetic test for the defect associated with this ...

  5. Association of Alport's syndrome with HLA-DR2 antigen in a group of unrelated patients

    Directory of Open Access Journals (Sweden)

    E.A. Donadi


    Full Text Available A few family studies have evaluated HLA antigens in Alport's syndrome; however, there are no large population studies. In the present report, we studied 40 unrelated white patients with Alport's syndrome seen at the Unit of Renal Transplantation, Faculty of Medicine of Ribeirão Preto, São Paulo, Brazil. HLA-A, -B, -DR and -DQ antigens were typed using a complement-dependent microlymphocytotoxicity assay. A control white population (N = 403 from the same geographical area was also typed for HLA antigens. Although the frequencies of HLA-A and -B antigens of patients were not statistically different from controls, the frequency of HLA-DR2 antigen observed in patients (65% was significantly increased in relation to controls (26%; P<0.001. The relative risk and etiologic fraction for HLA-DR2 antigen were 5.2 and 0.525, respectively. Although few immunological abnormalities have been shown in Alport's syndrome, in this report we emphasize the association of HLA molecules and Alport's syndrome. Besides the well-known inherited molecular defects encoded by type IV collagen genes in Alport's syndrome, the major histocompatibility alleles may be in linkage disequilibrium with these defective collagen genes

  6. Isolation and partial characterization of an immunogenic antigen of Giardia lamblia. (United States)

    Quintero, Jael; Valdez, Alejandra; Samaniego, Brenda; Lopez-Romero, Gloria; Astiazaran-Garcia, Humberto; Rascon, Lucila; Breci, Linda; Garibay-Escobar, Adriana; Robles-Zepeda, Ramón; Velazquez, Carlos


    Humoral and cellular immune responses play an important role during Giardia lamblia infection. Several Giardia proteins have been identified as immunogenic antigens based on their elicited humoral immune response. Poorly is known about Giardia antigens that stimulate a cellular immune response. The main purpose of this study was to isolate and partial characterize an immunogenic antigen (5G8) of G. lamblia. The 5G8 protein was isolated from G. lamblia trophozoite lysates by affinity chromatography using moAb 5G8-coupled CNBr-Sepharose. The isolated protein was analysed by electrospray tandem mass spectrometry (ESI-MS/MS), and by diverse bioinformatics tools (GiardiaDB, BLASTn, BLASTp and ExPASy). Additionally, several biochemical and immunological characteristics of the isolated protein were analysed. By ESI-MS/MS the amino acidic 5G8 sequence was deduced. The 5G8 antigen belongs to the VSP family proteins of G. lamblia. This protein is composed by one polypeptide chain (±71kDa). Using the algorithm SYFPHEITI, we identified candidate CD4(+) T-cell epitopes from the 5G8 antigen, which can elicit cell-mediated immune responses. In this study, we have identified a G. lamblia protein that induces a strong immune response in infected mice. The biochemical and immunological characterization of the immunogenic 5G8 antigen may contribute to the rational design of a Giardia vaccine.

  7. Development of an algorithm for production of inactivated arbovirus antigens in cell culture. (United States)

    Goodman, C H; Russell, B J; Velez, J O; Laven, J J; Nicholson, W L; Bagarozzi, D A; Moon, J L; Bedi, K; Johnson, B W


    Arboviruses are medically important pathogens that cause human disease ranging from a mild fever to encephalitis. Laboratory diagnosis is essential to differentiate arbovirus infections from other pathogens with similar clinical manifestations. The Arboviral Diseases Branch (ADB) reference laboratory at the CDC Division of Vector-Borne Diseases (DVBD) produces reference antigens used in serological assays such as the virus-specific immunoglobulin M antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA). Antigen production in cell culture has largely replaced the use of suckling mice; however, the methods are not directly transferable. The development of a cell culture antigen production algorithm for nine arboviruses from the three main arbovirus families, Flaviviridae, Togaviridae, and Bunyaviridae, is described here. Virus cell culture growth and harvest conditions were optimized, inactivation methods were evaluated, and concentration procedures were compared for each virus. Antigen performance was evaluated by the MAC-ELISA at each step of the procedure. The antigen production algorithm is a framework for standardization of methodology and quality control; however, a single antigen production protocol was not applicable to all arboviruses and needed to be optimized for each virus.

  8. Antibodies to new beta cell antigen ICA12 in Latvian diabetes patients. (United States)

    Shtauvere-Brameus, A; Hagopian, W; Rumba, I; Sanjeevi, C B


    In Latvia diabetes mellitus is diagnosed using the WHO's clinical criteria, and assays for the detection of autoantibodies are not available. In consequence, slowly progressive autoimmune diabetes or LADA is likely to be missed. Antibodies to GAD65 and IA-2 are the major immunological markers in autoimmune diabetes. Recently, a new beta cell antigen, called ICA12, has been identified, which has a homology to the SOX family of transcription factors. The aim of the study was to analyze the prevalence of ICA12 antibodies in diabetes mellitus patients and controls from Latvia and to see whether this antigen is important in revealing autoimmunity when antibodies against major antigens are not present. We studied 88 IDDM patients and 100 NIDDM patients as well as controls for the prevalence of GAD65, IA-2, and ICA12 antibodies by radioligand binding assay (RIA) using (35)S-labeled islet antigens. We found ICA12Abs in 26 of 88 IDDM patients (30%) vs. 4% in healthy controls (4/100) and in 9 of 100 NIDDM patients (9%) vs. 2% controls (2/100). ICA12Abs alone are present in only 3% (3/88) of the patients with IDDM and 1% (1/100) of the NIDDM patients. We conclude that ICA12 represents the minor antigens in autoimmune diabetes and that, as a minor antigen, ICA12 alone does not contribute significantly in revealing new cases of autoimmunity.

  9. Blood Group Antigen Recognition via the Group A Streptococcal M Protein Mediates Host Colonization (United States)

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


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

  10. Antigen/Antibody Analyses in Leishmaniasis. (United States)


    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

  11. Virosomes for antigen and DNA delivery

    NARCIS (Netherlands)

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


    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

  12. Pseudomonas aeruginosa Cif protein enhances the ubiquitination and proteasomal degradation of the transporter associated with antigen processing (TAP) and reduces major histocompatibility complex (MHC) class I antigen presentation. (United States)

    Bomberger, Jennifer M; Ely, Kenneth H; Bangia, Naveen; Ye, Siying; Green, Kathy A; Green, William R; Enelow, Richard I; Stanton, Bruce A


    Cif (PA2934), a bacterial virulence factor secreted in outer membrane vesicles by Pseudomonas aeruginosa, increases the ubiquitination and lysosomal degradation of some, but not all, plasma membrane ATP-binding cassette transporters (ABC), including the cystic fibrosis transmembrane conductance regulator and P-glycoprotein. The goal of this study was to determine whether Cif enhances the ubiquitination and degradation of the transporter associated with antigen processing (TAP1 and TAP2), members of the ABC transporter family that play an essential role in antigen presentation and intracellular pathogen clearance. Cif selectively increased the amount of ubiquitinated TAP1 and increased its degradation in the proteasome of human airway epithelial cells. This effect of Cif was mediated by reducing USP10 deubiquitinating activity, resulting in increased polyubiquitination and proteasomal degradation of TAP1. The reduction in TAP1 abundance decreased peptide antigen translocation into the endoplasmic reticulum, an effect that resulted in reduced antigen available to MHC class I molecules for presentation at the plasma membrane of airway epithelial cells and recognition by CD8(+) T cells. Cif is the first bacterial factor identified that inhibits TAP function and MHC class I antigen presentation.

  13. Protein antigen delivery by gene gun-mediated epidermal antigen incorporation (EAI). (United States)

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


    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.

  14. Tumor antigens as related to pancreatic cancer. (United States)

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


    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.

  15. A putative, novel coli surface antigen 8B (CS8B) of enterotoxigenic Escherichia coli. (United States)

    Njoroge, Samuel M; Boinett, Christine J; Madé, Laure F; Ouko, Tom T; Fèvre, Eric M; Thomson, Nicholas R; Kariuki, Samuel


    Enterotoxigenic Escherichia coli (ETEC) strains harbor multiple fimbriae and pili to mediate host colonization, including the type IVb pilus, colonization factor antigen III (CFA/III). Not all colonization factors are well characterized or known in toxin positive ETEC isolates, which may have an impact identifying ETEC isolates based on molecular screening of these biomarkers. We describe a novel coli surface antigen (CS) 8 subtype B (CS8B), a family of CFA/III pilus, in a toxin producing ETEC isolate from a Kenyan collection. In highlighting the existence of this putative CS, we provide the sequence and specific primers, which can be used alongside other ETEC primers previously described.

  16. Family Structure and Family Processes in Mexican American Families


    Zeiders, Katharine H.; Roosa, Mark W.; Tein, Jenn-Yun


    Despite increases in single-parent families among Mexican Americans (MA), few studies have examined the association of family structure and family adjustment. Utilizing a diverse sample of 738 Mexican American families (21.7% single parent), the current study examined differences across family structure on early adolescent outcomes, family functioning, and parent-child relationship variables. Results revealed that early adolescents in single parent families reported greater school misconduct,...

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


    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

  18. Finding Family

    Institute of Scientific and Technical Information of China (English)



    @@ It took 14 years--and just two min-utes-for an adopted Chinese girl to find her biological family. July 21 this year marked the first anniversary of Haley Butler's finding of her biological parents in Maanshan in east China's Anhui Province.

  19. Finding Family

    Institute of Scientific and Technical Information of China (English)


    Discovering her birth parents was an exciting adventure for a 15-year-old girl It took 14 years-and just two minutes-for an adopted Chinese girl to find her biological family.July 21 this year marked the first

  20. Family Genericity

    DEFF Research Database (Denmark)

    Ernst, Erik


    Type abstraction in object-oriented languages embody two techniques, each with its own strenghts and weaknesses. The first technique is extension, yielding abstraction mechanisms with good support for gradual specification. The prime example is inheritance. The second technique is functional abst...... the result as family genericity. The presented language design has been implemented....

  1. My Family

    Institute of Scientific and Technical Information of China (English)



    There are four people in my family. They are grandma, father,mother and I. Now we all live in Wuhan. They are from different places. My grandma comes from Sichuan. She likes hot(辣4的) meat very much. She doesn't like bread or noodles at all. She likes vegetables a little. My father is from Guang Zhou.

  2. Family Circle

    Institute of Scientific and Technical Information of China (English)


    Foster care is conducive to giving orphaned children a better life For most children living in orphanages, having a real home is just a pipe dream. Although they may be well looked after, receive a good education and proper nutrition, the love and care that come from being part of a real family just aren't there.

  3. FAMILY RICHARDIIDAE. (United States)

    Wendt, Lisiane Dilli; Ale-Rocha, Rosaly


    Richardiidae are a family of "acalyptrate" Diptera represented by ca. 180 species distributed in the New World, mostly in the Neotropical region. The species that occur in Colombia have received little attention from taxonomists, and the great majority of them are known only from their type localities. Currently, 14 genera and 23 species are known to occur in the country.

  4. My Family

    Institute of Scientific and Technical Information of China (English)



    There are four people in my family--my parents, my brother and I. My name is Li Mei. I'm fifteen years old. I am of medium height and build. I like English very much. It's very interesting. I can play the piano very well. It makes me feel very happy.

  5. Improved cytotoxic T-lymphocyte immune responses to a tumor antigen by vaccines co-expressing the SLAM-associated adaptor EAT-2. (United States)

    Aldhamen, Y A; Seregin, S S; Kousa, Y A; Rastall, D P W; Appledorn, D M; Godbehere, S; Schutte, B C; Amalfitano, A


    The signaling lymphocytic activation molecule-associated adaptor Ewing's sarcoma's-activated transcript 2 (EAT-2) is primarily expressed in dendritic cells, macrophages and natural killer cells. Including EAT-2 in a vaccination regimen enhanced innate and adaptive immune responses toward pathogen-derived antigens, even in the face of pre-existing vaccine immunity. Herein, we investigate whether co-vaccinations with two recombinant Ad5 (rAd5) vectors, one expressing the carcinoembryonic antigen (CEA) and one expressing EAT-2, can induce more potent CEA-specific cytotoxic T lymphocyte (CTL) and antitumor activity in the therapeutic CEA-expressing MC-38 tumor model. Our results suggest that inclusion of EAT-2 significantly alters the kinetics of Th1-biasing proinflammatory cytokine and chemokine responses, and enhances anti-CEA-specific CTL responses. As a result, rAd5-EAT2-augmented rAd5-CEA vaccinations are more efficient in eliminating CEA-expressing target cells as measured by an in vivo CTL assay. Administration of rAd5-EAT2 vaccines also reduced the rate of growth of MC-38 tumor growth in vivo. Also, an increase in MC-38 tumor cell apoptosis (as measured by hematoxylin and eosin staining, active caspase-3 and granzyme B levels within the tumors) was observed. These data provide evidence that more efficient, CEA-specific effector T cells are generated by rAd5 vaccines expressing CEA, when augmented by rAd5 vaccines expressing EAT-2, and this regimen may be a promising approach for cancer immunotherapy in general.

  6. Antigen-specific memory B cell development. (United States)

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


    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.

  7. Platelet antigens and antibodies. Literature review

    Directory of Open Access Journals (Sweden)

    N. V. Mineeva


    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.

  8. Platelet antigens and antibodies. Literature review

    Directory of Open Access Journals (Sweden)

    N. V. Mineeva


    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.

  9. Natural Family Planning (United States)

    ... Sex and Birth Control Birth Control Natural Family Planning Natural Family Planning Birth ControlPrevention and WellnessSex and Birth Control Share Natural Family Planning Natural Family PlanningWhat is natural family planning?Natural ...

  10. MAGE-A Antigens and Cancer Immunotherapy (United States)

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


    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

  11. MYCN: From Oncoprotein To Tumor-Associated Antigen

    Directory of Open Access Journals (Sweden)

    Vito ePistoia


    Full Text Available MYCN is a well known oncogene overexpressed in different human malignancies including neuroblastoma, rhabdomyosarcoma, medulloblastoma, astrocytoma, Wilms’ tumor and small cell lung cancer. In the case of neuroblastoma (NB, MYCN amplification is an established biomarker of poor prognosis. MYCN belongs to a family of transcription factors (the most important of which is CMYC that show a high degree of homology. Downregulation of MYC protein expression leads to tumor regression in animal models, indicating that MYC proteins represent interesting therapeutic targets.Pre-requisites for a candidate tumor-associated antigen (TAA to be targeted by immunotherapeutic approaches are the following, i expression should be tumor-restricted, ii the putative TAA should be up-regulated in cancer cells and iii protein should be processed into immunogenic peptides capable of associating to MHC molecules with high affinity. Indeed, the MYCN protein is not expressed in human adult tissues and upregulated variably in NB cells, and MYCN peptides capable of associating to HLA-A1 or –A2 molecules with high affinity have been identified. Thus the MYCN protein qualifies as putative TAA in NB.Additional issues that determine the feasibility of targeting a putative TAA with cytotoxic T lymphocytes (CTL and will be here discussed are the following, i the inadequacy of tumor cells per se to act as antigen-presenting cells witnessed, in the case of NB cells, by the low to absent expression of HLA- class I molecules, the lack of costimulatory molecules and multiple defects in the HLA class I related antigen processing machinery, and ii the immune evasion mechanisms operated by cancer cells to fool the host immune system, such as up-regulation of soluble immunosuppressive molecules (e.g. soluble MICA and HLA-G in the case of NB or generation of immunosuppressive cells in the tumor microenvironment. A final issue that deserves consideration is the strategy used to generate

  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


    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. Outer membrane proteome and antigens of Tannerella forsythia. (United States)

    Veith, Paul D; O'Brien-Simpson, Neil M; Tan, Yan; Djatmiko, Deasy C; Dashper, Stuart G; Reynolds, Eric C


    Tannerella forsythia is a Gram-negative, anaerobic, fusiform bacterium implicated as a periodontal pathogen. With use of 2D PAGE, SDS PAGE, and LC-MALDI-TOF/TOF MS, 221 proteins of T. forsythia outer membrane preparations were identified, of which 197 were predicted to be localized to the cell envelope. Fifty-six proteins were reproducibly mapped by 2D PAGE and included several highly abundant proteins in the MW range 140-250 kDa that exhibited C-terminal sequence similarity to the CTD family of Porphyromonas gingivalis. Two-dimensional Western blot analyses revealed that these CTD family proteins together with several other outer membrane proteins were antigenic. The CTD family proteins exhibited a higher than expected MW, and were strongly reactive with the fluorescent glycoprotein stain, ProQ Emerald. This group included BspA and surface layer proteins A and B. TonB-dependent receptors (TDRs) (46) were identified together with 28 putative lipoproteins whose genes are immediately downstream of a TDR gene. The major OmpA-like protein was found to be TF1331. Uniquely, it was found to exist as a homodimer held together by up to three disulfide bridges as demonstrated by MS/MS of a tryptic peptide derived from unreduced TF1331.

  14. Epitope selection to male specific antigens for sex selection in swine. (United States)

    Mohammadi, Azarm Akhavien; Tetro, Jason A; Filion, Lionel G


    Immunological approaches to gender selection have been contemplated since the discovery of the family of male-specific H-Y antigens found only on the surface of male cells. H-Y antigens are able to elicit an immune reaction when cells or tissues from a male donor are grafted to a female recipient. We describe here the development and testing of an inexpensive approach using polyclonal antibodies against four specific H-Y outer membrane proteins male enhanced antigen 1 (MEA 1), male enhanced antigen 2 (MEA 2), sex determining region Y (SRY) and testis determining factor (TDF). Epitopes based on hydrophilic primary sequences of the proteins were synthesized, N-terminal biotin-labeled, linked to streptavidin and mixed with a Ribi adjuvant prior to immunization in rabbits. The antiserum was tested to determine affinity to swine spermatozoa using anti-motility, flow cytometry and motility and sedimentation chambers. Fluorescent microscopy and fluorescent in situ hybridization (FISH) was used to identify the percentage of motile spermatozoa that contained the Y chromosome. We found that the polyclonal antibodies had high affinity to the spermatozoa leading to a cessation of motility. Furthermore, the majority of these non-motile spermatozoa contained the Y chromosome. We conclude that the use of polyclonal antiserum against synthetic H-Y peptide antigens may be an inexpensive and simple means to inhibit the motility of swine spermatozoa bearing the Y chromosome.

  15. The use of a synthetic antigen for the serological diagnosis of human trichinellosis

    Directory of Open Access Journals (Sweden)

    Bruschi F.


    Full Text Available Hosts infected with Trichinella produce antibodies specific for an epitope common to the TSL-1 family antigens. This epitope contained uncommon terminal 3, 6-dideoxy-D-arabinohexose (so called tyvelose residues. The disaccharide moiety was synthesized and an immunodiagnostic assay was developed, which was specific and sensitive in swine trichinellosis. We aimed to verify the specificity and sensitivity of this immunodiagnostic test in human trichinellosis. 15 sera from normal subjects, 12 from patients with other parasitic diseases and 50 from trichinellosis patients were tested. Indirect enzyme linked immunosorbent assay (ELISA for specific IgG and an amplified ELISA for specific IgE were performed using β-tyvelose-GalNAc-bovine serum albumin (BSA disaccharide conjugate or T. spiralis muscle larvae excretory/secretory (E/S products, as antigens. Neither control sera nor other parasitic infection sera resulted positive both for IgG and IgE when synthetic or E/S antigens were used. In trichinellosis patient sera, specific IgG were present in 100 % of cases, irrespective of the antigen used, but whereas specific IgE were detected in 78 % using E/S antigens, a 100% positivity rate was obtained, using the β-tyvelose- BSA conjugate.

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

    Directory of Open Access Journals (Sweden)

    Leila Hasanzadeh


    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. 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 .

  17. Small organic compounds enhance antigen loading of class II major histocompatibility complex proteins by targeting the polymorphic P1 pocket

    DEFF Research Database (Denmark)

    Höpner, Sabine; Dickhaut, Katharina; Hofstätter, Maria;


    Major histocompatibility complex (MHC) molecules are a key element of the cellular immune response. Encoded by the MHC they are a family of highly polymorphic peptide receptors presenting peptide antigens for the surveillance by T cells. We have shown that certain organic compounds can amplify im...

  18. Antigen cross-presentation of immune complexes. (United States)

    Platzer, Barbara; Stout, Madeleine; Fiebiger, Edda


    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.

  19. 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.


    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...

  20. The antigenic relationship between Brettanomyces-Debaryomyces strains and the Salmonella cholerae-suis O antigen. (United States)

    Aksoycan, N; Sağanak, I; Wells, G


    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.

  1. Superexpression of tuberculosis antigens in plant leaves. (United States)

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


    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.

  2. Antigen presentation by MHC-dressed cells

    Directory of Open Access Journals (Sweden)

    Masafumi eNakayama


    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.

  3. 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)


    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.

  4. 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: [Division of Molecular Immunology, Cincinnati Children' s Hospital Research Foundation, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229 (United States)


    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.

  5. Roles within the Family (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Text Size Email Print Share Roles Within the Family Page Content Article Body Families are not democracies. ...

  6. Antigenic variation of Streptococcus mutans colonizing gnotobiotic rats. (United States)

    Bratthall, D; Gibbons, R J


    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.

  7. Properties of glycolipid-enriched membrane rafts in antigen presentation. (United States)

    Rodgers, William; Smith, Kenneth


    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.

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


    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.

  9. Classification of human leukocyte antigen (HLA) supertypes

    DEFF Research Database (Denmark)

    Wang, Mingjun; Claesson, Mogens H


    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...

  10. Identification and Analysis of Immunodominant Antigens for ELISA-Based Detection of Theileria annulata (United States)

    Bakırcı, Serkan; Tait, Andrew; Kinnaird, Jane; Eren, Hasan


    Tropical or Mediterranean theileriosis, caused by the protozoan parasite Theileria annulata, remains an economically important bovine disease in North Africa, Southern Europe, India, the Middle East and Asia. The disease affects mainly exotic cattle and imposes serious constraints upon livestock production and breed improvement programmes. While microscopic and molecular methods exist which are capable of detecting T. annulata during acute infection, the identification of animals in the carrier state is more challenging. Serological tests, which detect antibodies that react against parasite-encoded antigens, should ideally have the potential to identify carrier animals with very high levels of sensitivity and specificity. However, assays developed to date have suffered from a lack of sensitivity and/or specificity and it is, therefore, necessary to identify novel parasite antigens, which can be developed for this purpose. In the present study, genes encoding predicted antigens were bioinformatically identified in the T. annulata genome. These proteins, together with a panel of previously described antigens, were assessed by western blot analysis for immunoreactivity, and this revealed that four novel candidates and five previously described antigens were recognised by immune bovine serum. Using a combination of immunoprecipitation and mass spectrophotometric analysis, an immunodominant protein (encoded by TA15705) was identified as Ta9, a previously defined T cell antigen. Western blotting revealed another of the five proteins in the Ta9 family, TA15710, also to be an immunodominant protein. However, validation by Enzyme-Linked Immunosorbent Assay indicated that due to either allelic polymorphism or differential immune responses of individual hosts, none of the novel candidates can be considered ideal for routine detection of T. annulata-infected/carrier animals. PMID:27270235

  11. Integrating Family Resilience and Family Stress Theory. (United States)

    Patterson, Joan M.


    The construct, family resilience, is defined differently by practitioners and researchers. This study tries to clarify the concept of family resilience. The foundation is family stress and coping theory, particularly the stress models that emphasize adaptation processes in families exposed to major adversities. (JDM)


    Directory of Open Access Journals (Sweden)

    M R Nowroozi


    Full Text Available "nVasectomy is one of the extensively used methods of contraception in family planning programs. Antisperm antibodies (ASA develop after vasectomy which can result in auto-immune male infertility. The precise sperm antigens involved in the autoimmune response are still poorly defined, therefore we determined the circulating ASA and identified relevant sperm antigens based on localization of binding sites of ASA to sperm cell antigens, using a rapid, inexpensive and clinically relevant assay in vasectomized men. Results showed that 2.5% of men had ASA at the time of vasectomy, whereas 53.5% of the study population subsequently developed ASA. The numbers of men with circulating ASA increased significantly for the first three months after vasectomy. These antibodies were distinguishable into three groups based on their bindings to different sites of sperm cell antigens including against acrosome and tail in 67.56% and 10.8%, respectively; 21.6% of subjects had antibody to the other parts of the sperm cell antigens. The results of this study are discussed in terms of an autoimmune response against sperm antigens and development of ASA.

  13. Multivalent TB vaccines targeting the esx gene family generate potent and broad cell-mediated immune responses superior to BCG. (United States)

    Villarreal, Daniel O; Walters, Jewell; Laddy, Dominick J; Yan, Jian; Weiner, David B


    Development of a broad-spectrum synthetic vaccine against TB would represent an important advance to the limited vaccine armamentarium against TB. It is believed that the esx family of TB antigens may represent important vaccine candidates. However, only 4 esx antigens have been studied as potential vaccine antigens. The challenge remains to develop a vaccine that simultaneously targets all 23 members of the esx family to induce enhanced broad-spectrum cell-mediated immunity. We sought to investigate if broader cellular immune responses could be induced using a multivalent DNA vaccine representing the esx family protein members delivered via electroporation. In this study, 15 designed esx antigens were created to cross target all members of the esx family. They were distributed into groups of 3 self-processing antigens each, resulting in 5 trivalent highly optimized DNA plasmids. Vaccination with all 5 constructs elicited robust antigen-specific IFN-γ responses to all encoded esx antigens and induced multifunctional CD4 Th1 and CD8 T cell responses. Importantly, we show that when all constructs are combined into a cocktail, the RSQ-15 vaccine, elicited substantial broad Ag-specific T cell responses to all esx antigens as compared with vaccination with BCG. Moreover, these vaccine-induced responses were highly cross-reactive with BCG encoded esx family members and were highly immune effective in a BCG DNA prime-boost format. Furthermore, we demonstrate the vaccine potential and immunopotent profile of several novel esx antigens never previously studied. These data highlight the likely importance of these novel immunogens for study as preventative or therapeutic synthetic TB vaccines in combination or as stand alone antigens.

  14. [Presence of Australia antigen in blood donors]. (United States)

    Gota, F


    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.

  15. HLA antigens and asthma in Greeks. (United States)

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


    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.

  16. Prostate-specific antigen (PSA) blood test (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 ...


    NARCIS (Netherlands)



    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


    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

  19. Antigenic variation in Plasmodium falciparum malaria involves a highly structured switching pattern.

    Directory of Open Access Journals (Sweden)

    Mario Recker


    Full Text Available Many pathogenic bacteria, fungi, and protozoa achieve chronic infection through an immune evasion strategy known as antigenic variation. In the human malaria parasite Plasmodium falciparum, this involves transcriptional switching among members of the var gene family, causing parasites with different antigenic and phenotypic characteristics to appear at different times within a population. Here we use a genome-wide approach to explore this process in vitro within a set of cloned parasite populations. Our analyses reveal a non-random, highly structured switch pathway where an initially dominant transcript switches via a set of switch-intermediates either to a new dominant transcript, or back to the original. We show that this specific pathway can arise through an evolutionary conflict in which the pathogen has to optimise between safeguarding its limited antigenic repertoire and remaining capable of establishing infections in non-naïve individuals. Our results thus demonstrate a crucial role for structured switching during the early phases of infections and provide a unifying theory of antigenic variation in P. falciparum malaria as a balanced process of parasite-intrinsic switching and immune-mediated selection.

  20. CLIC1 regulates dendritic cell antigen processing and presentation by modulating phagosome acidification and proteolysis

    Directory of Open Access Journals (Sweden)

    Kanin Salao


    Full Text Available Intracellular chloride channel protein 1 (CLIC1 participates in inflammatory processes by regulating macrophage phagosomal functions such as pH and proteolysis. Here, we sought to determine if CLIC1 can regulate adaptive immunity by actions on dendritic cells (DCs, the key professional antigen presenting cells. To do this, we first generated bone marrow-derived DCs (BMDCs from germline CLIC1 gene-deleted (CLIC1−/− and wild-type (CLIC1+/+ mice, then studied them in vitro and in vivo. We found phagocytosis triggered cytoplasmic CLIC1 translocation to the phagosomal membrane where it regulated phagosomal pH and proteolysis. Phagosomes from CLIC1−/− BMDCs displayed impaired acidification and proteolysis, which could be reproduced if CLIC1+/+, but not CLIC1−/− cells, were treated with IAA94, a CLIC family ion channel blocker. CLIC1−/− BMDC displayed reduced in vitro antigen processing and presentation of full-length myelin oligodendrocyte glycoprotein (MOG and reduced MOG-induced experimental autoimmune encephalomyelitis. These data suggest that CLIC1 regulates DC phagosomal pH to ensure optimal processing of antigen for presentation to antigen-specific T-cells. Further, they indicate that CLIC1 is a novel therapeutic target to help reduce the adaptive immune response in autoimmune diseases.

  1. Rational antigen modification as a strategy to upregulate or downregulate antigen recognition. (United States)

    Abrams, S I; Schlom, J


    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.

  2. 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)


    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

  3. Cysteine proteases as potential antigens in antiparasitic DNA vaccines

    DEFF Research Database (Denmark)

    Jørgensen, Louise von Gersdorff; Buchmann, Kurt


    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....

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

    Directory of Open Access Journals (Sweden)

    Day-Yu Chao


    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.

  5. Intrarectal vaccination with recombinant vaccinia virus expressing carcinoembronic antigen induces mucosal and systemic immunity and prevents progression of colorectal cancer. (United States)

    Kim-Schulze, Seunghee; Kim, Hong Sung; Wainstein, Alberto; Kim, Dae Won; Yang, Wein Cui; Moroziewicz, Dorota; Mong, Phyllus Y; Bereta, Michal; Taback, Bret; Wang, Qin; Kaufman, Howard L


    The gastrointestinal mucosa contains an intact immune system that protects the host from pathogens and communicates with the systemic immune system. Absorptive epithelial cells in the mucosa give rise to malignant tumors although the interaction between tumor cells and the mucosal immune system is not well defined. The pathophysiology of colorectal cancer has been elucidated through studies of hereditary syndromes, such as familial adenomatous polyposis, a cancer predisposition syndrome caused by germline mutations in the adenomatous polyposis coli tumor suppressor gene. Patients with FAP develop adenomas and inevitably progress to invasive carcinomas by the age of 40. To better delineate the role of mucosal immunity in colorectal cancer, we evaluated the efficacy of intrarectal recombinant vaccinia virus expressing the human carcinoembryonic Ag (CEA) in a murine FAP model in which mice are predisposed to colorectal cancer and also express human CEA in the gut. Mucosal vaccination reduced the incidence of spontaneous adenomas and completely prevented progression to invasive carcinoma. The therapeutic effects were associated with induction of mucosal CEA-specific IgA Ab titers and CD8(+) CTLs. Mucosal vaccination was also associated with an increase in systemic CEA-specific IgG Ab titers, CD4(+) and CD8(+) T cell responses and resulted in growth inhibition of s.c. implanted CEA-expressing tumors suggesting communication between mucosal and systemic immune compartments. Thus, intrarectal vaccination induces mucosal and systemic antitumor immunity and prevents progression of spontaneous colorectal cancer. These results have implications for the prevention of colorectal cancer in high-risk individuals.

  6. 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.

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


    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.

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

    Directory of Open Access Journals (Sweden)

    N Chacón


    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.

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


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


    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 ...

  10. 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.

  11. 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.


    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

  12. 21 CFR 660.40 - Hepatitis B Surface Antigen. (United States)


    ... 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...

  13. Family and family therapy in Russia. (United States)

    Bebtschuk, Marina; Smirnova, Daria; Khayretdinov, Oleg


    This article represents the information about family and family therapy in the context of culture, traditions and contemporary changes of social situations in Russia. The legislation of family rights are mentioned within items about marriage and family in the Constitution, Civil Code and Family Code of the Russian Federation which has changed during recent years. The definition of family and description of family structure are given through the prism of the current demographic situation, dynamics of statistics of marriage and divorce rates, mental disorders, disabilities and such phenomena as social abandonment. The actual curriculum, teaching of family therapy and its disadvantages, system of continuous education, supervision and initiatives of the Institute of Integrative Family Therapy in improvement of preparing of specialists who can provide qualified psychosocial assistance for the family according to the actual needs of society are noted. The directions of state and private practice of family counselling and therapy both for psychiatric patients and medical patients, for adults and children in a family systemic approach are highlighted with an indication of the spectrum of techniques and methods used by Russian professionals. The main obstacles and perspectives of development of family therapy in Russia are summarized.

  14. Echinococcus granulosus antigen B: a Hydrophobic Ligand Binding Protein at the host-parasite interface. (United States)

    Silva-Álvarez, Valeria; Folle, Ana Maite; Ramos, Ana Lía; Zamarreño, Fernando; Costabel, Marcelo D; García-Zepeda, Eduardo; Salinas, Gustavo; Córsico, Betina; Ferreira, Ana María


    Lipids are mainly solubilized by various families of lipid binding proteins which participate in their transport between tissues as well as cell compartments. Among these families, Hydrophobic Ligand Binding Proteins (HLBPs) deserve special consideration since they comprise intracellular and extracellular members, are able to bind a variety of fatty acids, retinoids and some sterols, and are present exclusively in cestodes. Since these parasites have lost catabolic and biosynthetic pathways for fatty acids and cholesterol, HLBPs are likely relevant for lipid uptake and transportation between parasite and host cells. Echinococcus granulosus antigen B (EgAgB) is a lipoprotein belonging to the HLBP family, which is very abundant in the larval stage of this parasite. Herein, we review the literature on EgAgB composition, structural organization and biological properties, and propose an integrated scenario in which this parasite HLBP contributes to adaptation to mammalian hosts by meeting both metabolic and immunomodulatory parasite demands.

  15. Family Reading Night (United States)

    Hutchins, Darcy; Greenfeld, Marsha; Epstein, Joyce


    This book offers clear and practical guidelines to help engage families in student success. It shows families how to conduct a successful Family Reading Night at their school. Family Night themes include Scary Stories, Books We Love, Reading Olympics, Dr. Seuss, and other themes. Family reading nights invite parents to come to school with their…

  16. 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;


    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...

  17. Recovery of antigenically reactive HIV-2 cores. (United States)

    Chrystie, I L; Almeida, J D


    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).

  18. Tumor Immunity by Hydrophobic Bearing Antigens (United States)


    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

  19. Family Adjustment to Aphasia (United States)

    ... Public / Speech, Language and Swallowing / Disorders and Diseases Family Adjustment to Aphasia Richard S. was a senior manager ... It also presents a great challenge to the family. There may be tension among family members and ...

  20. Improving Family Communications (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Listen Español Text Size Email Print Share Improving Family Communications Page Content Article Body How can I ...

  1. Normal Functioning Family (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Español Text Size Email Print Share Normal Functioning Family Page Content Article Body Is there any way ...

  2. Families in the Military (United States)

    ... Families Guide - Search Spanish Facts for Families Guide Military Families No. 88; updated March 2017 Global conflict ... have led to deployment of large numbers of military personnel (active duty, Reserves, National Guard). As a ...

  3. Family Activities for Fitness (United States)

    Grosse, Susan J.


    This article discusses how families can increase family togetherness and improve physical fitness. The author provides easy ways to implement family friendly activities for improving and maintaining physical health. These activities include: walking, backyard games, and fitness challenges.

  4. Study of serum Helicobacter pylori soluble antigen

    Institute of Scientific and Technical Information of China (English)

    吴勤动; 朱永良


    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.

  5. Study of serum Helicobacter pylori soluble antigen

    Institute of Scientific and Technical Information of China (English)

    吴勤动; 朱永良


    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.

  6. Branding a family business


    Pohjola, Matti


    This master’s thesis main object was to understand better the very little researched topic: branding a family business. The main aim was to seek the values used behind family business that are the family values used in the brand and how the branding has been implemented in a family company. A qualitative method was chosen for this research for an interpretative analysis of the subject. Five family companies were chosen for the interviews. All these family companies are known Fi...

  7. Limited antigenic variation in the Trypanosoma cruzi candidate vaccine antigen TSA-1. (United States)

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


    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.

  8. 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.

  9. Conformational Dynamics and Antigenicity in the Disordered Malaria Antigen Merozoite Surface Protein 2 (United States)

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


    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

  10. Expression, purification and antigenicity of Neospora caninum-antigens using silkworm larvae targeting for subunit vaccines. (United States)

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


    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.

  11. Families and family therapy in Hong Kong. (United States)

    Tse, Samson; Ng, Roger M K; Tonsing, Kareen N; Ran, Maosheng


    Family therapy views humans not as separate entities, but as embedded in a network of relationships, highlighting the reciprocal influences of one's behaviours on one another. This article gives an overview of family demographics and the implementation of family therapy in Hong Kong. We start with a review of the family demographics in Hong Kong and brief notes on families in mainland China. Demographics show that the landscape has changed markedly in the past decade, with more cross-border marriages, an increased divorce rate, and an ageing overall population - all of which could mean that there is increasing demand for professional family therapy interventions. However, only a limited number of professionals are practising the systems-based approach in Hong Kong. Some possible reasons as to why family therapy is not well disseminated and practised are discussed. These reasons include a lack of mental health policy to support family therapy, a lack of systematic family therapy training, and a shortage of skilled professionals. Furthermore, challenges in applying the western model in Chinese culture are also outlined. We conclude that more future research is warranted to investigate how family therapy can be adapted for Chinese families.

  12. Identification of a novel PROS1 c.1113T -> GG frameshift mutation in a family with mixed type I/type III protein S deficiency

    NARCIS (Netherlands)

    ten Kate, Min Ki; Mulder, Rene; Platteel, Mathieu; Brouwer, Jan-Leendert P.; van der Steege, Gerrit; van der Meer, Jan


    We report a family with type I and type III protein S (PS) deficiency, which showed to be phenotypic variants of the same genetic disease. Direct sequencing analysis of the PROS1 gene was performed to establish the genotype. The ratio of protein C antigen and total PS antigen levels (protein C/S rat

  13. Family doctors' involvement with families in Estonia

    Directory of Open Access Journals (Sweden)

    Lember Margus


    Full Text Available Abstract Background Family doctors should care for individuals in the context of their family. Family has a powerful influence on health and illness and family interventions have been shown to improve health outcomes for a variety of health problems. The aim of the study was to investigate the Estonian family doctors' (FD attitudes to the patients' family-related issues in their work: to explore the degree of FDs involvement in family matters, their preparedness for management of family-related issues and their self-assessment of the ability to manage different family-related problems. Methods A random sample (n = 236 of all FDs in Estonia was investigated using a postal questionnaire. Altogether 151 FDs responded to the questionnaire (response rate 64%, while five of them were excluded as they did not actually work as FDs. Results Of the respondents, 90% thought that in managing the health problems of patients FDs should communicate and cooperate with family members. Although most of the family doctors agreed that modifying of the health damaging risk factors (smoking, alcohol and drug abuse of their patients and families is their task, one third of them felt that dealing with these problems is ineffective, or perceived themselves as poorly prepared or having too little time for such activities. Of the respondents, 58% (n = 83 were of the opinion that they could modify also relationship problems. Conclusions Estonian family doctors are favourably disposed to involvement in family-related problems, however, they need some additional training, especially in the field of relationship management.

  14. Nucleotide sequence and transcription of a trypomastigote surface antigen gene of Trypanosoma cruzi. (United States)

    Fouts, D L; Ruef, B J; Ridley, P T; Wrightsman, R A; Peterson, D S; Manning, J E


    In previous studies we identified a 500-bp segment of the gene, TSA-1, which encodes an 85-kDa trypomastigote-specific surface antigen of the Peru strain of Trypanosoma cruzi. TSA-1 was shown to be located at a telomeric site and to contain a 27-bp tandem repeat unit within the coding region. This repeat unit defines a discrete subset of a multigene family and places the TSA-1 gene within this subset. In this study, we present the complete nucleotide sequence of the TSA-1 gene from the Peru strain. By homology matrix analysis, fragments of two other trypomastigote specific surface antigen genes, pTt34 and SA85-1.1, are shown to have extensive sequence homology with TSA-1 indicating that these genes are members of the same gene family as TSA-1. The TSA-1 subfamily was also found to be active in two other strains of T. cruzi, one of which contains multiple telomeric members and one of which contains a single non-telomeric member, suggesting that transcription is not necessarily dependent on the gene being located at a telomeric site. Also, while some of the sequences found in this gene family are present in 2 size classes of poly(A)+ RNA, others appear to be restricted to only 1 of the 2 RNA classes.

  15. Targeted delivery of lipid antigen to macrophages via the CD169/sialoadhesin endocytic pathway induces robust invariant natural killer T cell activation (United States)

    Kawasaki, Norihito; Vela, Jose Luis; Nycholat, Corwin M.; Rademacher, Christoph; Khurana, Archana; van Rooijen, Nico; Crocker, Paul R.; Kronenberg, Mitchell; Paulson, James C.


    Invariant natural killer T (iNKT) cells induce a protective immune response triggered by foreign glycolipid antigens bound to CD1d on antigen-presenting cells (APCs). A limitation of using glycolipid antigens to stimulate immune responses in human patients has been the inability to target them to the most effective APCs. Recent studies have implicated phagocytic CD169+ macrophages as major APCs in lymph nodes for priming iNKT cells in mice immunized with glycolipid antigen in particulate form. CD169 is known as sialoadhesin (Sn), a macrophage-specific adhesion and endocytic receptor of the siglec family that recognizes sialic acid containing glycans as ligands. We have recently developed liposomes decorated with glycan ligands for CD169/Sn suitable for targeted delivery to macrophages via CD169/Sn-mediated endocytosis. Here we show that targeted delivery of a lipid antigen to CD169+ macrophages in vivo results in robust iNKT cell activation in liver and spleen using nanogram amounts of antigen. Activation of iNKT cells is abrogated in Cd169−/− mice and is macrophage-dependent, demonstrating that targeting CD169+ macrophages is sufficient for systemic activation of iNKT cells. When pulsed with targeted liposomes, human monocyte–derived dendritic cells expressing CD169/Sn activated human iNKT cells, demonstrating the conservation of the CD169/Sn endocytic pathway capable of presenting lipid antigens to iNKT cells. PMID:23610394

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

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


    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).

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

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


    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.

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


    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.

  19. 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;


    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...

  20. Regulation of antigenic variation in Plasmodium falciparum: censoring freedom of expression? (United States)

    Duffy, Michael F; Reeder, John C; Brown, Graham V


    Plasmodium falciparum employs a strategy of clonal antigenic variation to evade the host immune response during the intraerythrocytic stage of its life cycle. The major variant parasite molecule is the P. falciparum erythrocyte membrane protein (PfEMP)1, which is encoded by the var multigene family. The parasite switches between different PfEMP1 molecules through regulation of var transcription. Recent studies have shed considerable light on this process, but much remains unknown. However, striking parallels between transcriptional control of var and genes in other organisms provide direction for future studies.

  1. Protamine-based nanoparticles as new antigen delivery systems. (United States)

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


    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.

  2. Competitiveness of Family Businesses

    NARCIS (Netherlands)

    M.A.A.M. Leenders (Mark); E. Waarts (Eric)


    textabstractThe purpose of this study is to systematically examine the advantages and disadvantages of different types of family businesses. We distinguish four different types of family businesses based on their family and business orientation: (1) House of Business, (2) Family Money Machine, (3) F

  3. Families in Transition . (United States)

    Bundy, Michael L., Ed.; Gumaer, James, Ed.


    Focuses on disrupted families and the role of the school counselor in helping children adjust. Describes characteristics of healthy families, and discusses the transition to the blended family, effects of divorce groups on children's classroom behavior, counseling children in stepfamilies, single-parent families, and parenting strengths of single…

  4. Genetic Immunization Elicits Antigen-Specific Protective Immune Responses and Decreases Disease Severity in Trypanosoma cruzi Infection



    Immunity to Trypanosoma cruzi requires elicitation of humoral and cell-mediated immune responses to extracellular trypomastigotes and intracellular amastigotes. In this study, the effectiveness of the T. cruzi trans-sialidase family (ts) genes ASP-1, ASP-2, and TSA-1 as genetic vaccines was assessed. Immunization of mice with plasmids encoding ASP-1, ASP-2, or TSA-1 elicited poor antigen-specific cytotoxic-T-lymphocyte (CTL) activity and T. cruzi-specific antibody responses. Codelivery of int...

  5. Goodpasture Antigen-binding Protein/Ceramide Transporter Binds to Human Serum Amyloid P-Component and Is Present in Brain Amyloid Plaques

    NARCIS (Netherlands)

    Mencarelli, Chiara; Bode, Gerard H.; Losen, Mario; Kulharia, Mahesh; Molenaar, Peter C.; Veerhuis, Robert; Steinbusch, Harry W. M.; De Baets, Marc H.; Nicolaes, Gerry A. F.; Martinez-Martinez, Pilar


    Serum amyloid P component (SAP) is a non-fibrillar glycoprotein belonging to the pentraxin family of the innate immune system. SAP is present in plasma, basement membranes, and amyloid deposits. This study demonstrates, for the first time, that the Goodpasture antigen-binding protein (GPBP) binds to

  6. Tissue polypeptide antigen activity in cerebrospinal fluid

    DEFF Research Database (Denmark)

    Bach, F; Söletormos, Georg; Dombernowsky, P


    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...

  7. Biofunctionalizing nanofibers with carbohydrate blood group antigens. (United States)

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


    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.

  8. Studies on the Antigenic Relationship among Phleboviruses (United States)


    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

  9. Protective antibody titres and antigenic competition in multivalent Dichelobacter nodosus fimbrial vaccines using characterised rDNA antigens. (United States)

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


    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

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

    Directory of Open Access Journals (Sweden)



    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.

  11. Antigen presentation for priming T cells in central system. (United States)

    Dasgupta, Shaoni; Dasgupta, Subhajit


    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.

  12. Human Ia-like antigens in non-lymphoid organs. (United States)

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


    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

  13. Tissue distribution of histo-blood group antigens

    DEFF Research Database (Denmark)

    Ravn, V; Dabelsteen, Erik


    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...

  14. 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


    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

  15. 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.


    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.

  16. HLA Bw35 antigen and mesangial IgA glomerulo-nephritis: a poor prognosis marker? (United States)

    Berthoux, F C; Genin, C; Gagne, A; Le Petit, J C; Sabatier, J C


    Familial cases of mesangial IgA glomerulonephritis (MGN) have raised the possibility of a genetic control in this disease. In 50 patients with MGN, diagnosed on renal biopsy, and in 105 controls, we have compared the distribution of HLA antigens (A and B loci). We found a significant increase in the frequency of HLA Bw35 antigen in the patient group compared with controls (36% versus 13%: p less than 0.02). There was no significant difference between the Bw35 positive and negative MGN subgroups, in clinical, serological, and pathological data. Both subgroups had elevated mean serum IgA levels (154% of normal), and also mean serum IgM levels (146%). However, the follow-up data exhibited a significantly worse prognosis (p less than 0.01) in the Bw35 positive subgroup: 9 out of 18 patients versus 4 out of 32 progressed to chronic renal failure (serum creatinine greater than 1.5 mg/dl). We have established a genetic linkage between the HLA complex and the occurrence of MGN. The Bw35 antigen may serve as a marker (risk of disease = 4), in particular for poor prognosis cases.

  17. Shark Variable New Antigen Receptor (VNAR Single Domain Antibody Fragments: Stability and Diagnostic Applications

    Directory of Open Access Journals (Sweden)

    Stewart Nuttall


    Full Text Available The single variable new antigen receptor domain antibody fragments (VNARs derived from shark immunoglobulin new antigen receptor antibodies (IgNARs represent some of the smallest known immunoglobulin-based protein scaffolds. As single domains, they demonstrate favorable size and cryptic epitope recognition properties, making them attractive in diagnosis and therapy of numerous disease states. Here, we examine the stability of VNAR domains with a focus on a family of VNARs specific for apical membrane antigen 1 (AMA-1 from Plasmodium falciparum. The VNARs are compared to traditional monoclonal antibodies (mAbs in liquid, lyophilized and immobilized nitrocellulose formats. When maintained in various formats at 45 °C, VNARs have improved stability compared to mAbs for periods of up to four weeks. Using circular dichroism spectroscopy we demonstrate that VNAR domains are able to refold following heating to 80 °C. We also demonstrate that VNAR domains are stable during incubation under potential in vivo conditions such as stomach acid, but not to the protease rich environment of murine stomach scrapings. Taken together, our results demonstrate the suitability of shark VNAR domains for various diagnostic platforms and related applications.

  18. Glycoconjugates as target antigens in peripheral neuropathies

    Directory of Open Access Journals (Sweden)

    Ljubica Suturkova


    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.

  19. 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


    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.

  20. Immunoregulation by Taenia crassiceps and Its Antigens

    Directory of Open Access Journals (Sweden)

    Alberto N. Peón


    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.

  1. Detection of peste des petits ruminants virus antigen using immunofiltration and antigen-competition ELISA methods. (United States)

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


    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.


    Directory of Open Access Journals (Sweden)

    L. A. Kadnikova


    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

  3. Strengthening Family Practices for Latino Families (United States)

    Chartier, Karen G.; Negroni, Lirio K.; Hesselbrock, Michie N.


    This study examined the effectiveness of a culturally adapted Strengthening Families Program (SFP) for Latinos to reduce risks for alcohol and drug use in children. Latino families, predominantly Puerto Rican, with a 9- to 12-year-old child and a parent(s) with a substance abuse problem participated in the study. Pre- and post-tests were conducted…

  4. Identification of protective antigens for vaccination against systemic salmonellosis

    Directory of Open Access Journals (Sweden)

    Dirk eBumann


    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.

  5. Cancer-germline antigen vaccines and epigenetic enhancers

    DEFF Research Database (Denmark)

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


    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...

  6. Bayesian nonparametric clustering in phylogenetics: modeling antigenic evolution in influenza. (United States)

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


    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.

  7. MHC structure and function – antigen presentation. Part 1 (United States)

    Goldberg, Anna Carla; Rizzo, Luiz Vicente


    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

  8. Screening of Epstein—Barr Virus Early Antigen Expression Inducers from Chinese Medicinal Herbs and Plants

    Institute of Scientific and Technical Information of China (English)

    ZENGY; ZHONGJian-Ming; 等


    Ethern extracts of 1693 Chinese medicinal herbs and plants from 268 families were studied for the induction of Epstein-Barr viral(EVB)early antigen(EA)expression in the Raji cell line.Fifty-two from 18 families were found to have inducing activity.Twenty-five and seven of them were from Euphorbiaceae and Thymelaeaceae,respactively.Some of them,such as Croton tiglium,Euphorbia kansui,Daphne genkwa,Wikstroemia chamaedaphen,Wikstroemia indica,Prunus mandshurica Koehne and Achyranthes bidentata are commonly used drugs.The significance of these herbs in the activation of EBV in vivo and their relation to the development of nasopharyngeal carcinoma were discussed.

  9. 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? (United States)

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


    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.

  10. Use of a molecular decoy to segregate transport from antigenicity in the FrpB iron transporter from Neisseria meningitidis.

    Directory of Open Access Journals (Sweden)

    Muhammad Saleem

    Full Text Available FrpB is an outer membrane transporter from Neisseria meningitidis, the causative agent of meningococcal meningitis. It is a member of the TonB-dependent transporter (TBDT family and is responsible for iron uptake into the periplasm. FrpB is subject to a high degree of antigenic variation, principally through a region of hypervariable sequence exposed at the cell surface. From the crystal structures of two FrpB antigenic variants, we identify a bound ferric ion within the structure which induces structural changes on binding which are consistent with it being the transported substrate. Binding experiments, followed by elemental analysis, verified that FrpB binds Fe(3+ with high affinity. EPR spectra of the bound Fe(3+ ion confirmed that its chemical environment was consistent with that observed in the crystal structure. Fe(3+ binding was reduced or abolished on mutation of the Fe(3+-chelating residues. FrpB orthologs were identified in other Gram-negative bacteria which showed absolute conservation of the coordinating residues, suggesting the existence of a specific TBDT sub-family dedicated to the transport of Fe(3+. The region of antigenic hypervariability lies in a separate, external sub-domain, whose structure is conserved in both the F3-3 and F5-1 variants, despite their sequence divergence. We conclude that the antigenic sub-domain has arisen separately as a result of immune selection pressure to distract the immune response from the primary transport function. This would enable FrpB to function as a transporter independently of antibody binding, by using the antigenic sub-domain as a 'molecular decoy' to distract immune surveillance.

  11. 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;


    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 ...

  12. A universal computational model for predicting antigenic variants of influenza A virus based on conserved antigenic structures (United States)

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


    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

  13. Familial aggregation in inflammatory bowel disease: Is it genes or environment?

    Institute of Scientific and Technical Information of China (English)

    Tiago Nunes; Gionata Fiorino; Silvio Danese; Miquel Sans


    Inflammatory bowel disease (IBD) develops in genetically susceptible individuals due to the influence of environmental factors, leading to an abnormal recognition of microbiota antigens by the innate immune system which triggers an exaggerated immune response and subsequent bowel tissue damage. IBD has been more frequently found in families, an observation that could be due to either genetic, environmental or both types of factors present in these families. In addition to expanding our knowledge on IBD pathogenesis, defining the specific contribution to familial IBD of each one of these factors might have also clinical usefulness. We review the available evidence on familial IBD pathogenesis.

  14. A Role For Mitochondria In Antigen Processing And Presentation. (United States)

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


    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.

  15. NLRC5 regulates MHC class Ⅰ antigen presentation in host defense against intracellular pathogens

    Institute of Scientific and Technical Information of China (English)

    Yikun Yao; Yalong Wang; Fuxiang Chen; Yin Huang; Shu Zhu; Qibin Leng; Hongyan Wang; Yufang Shi; Youcun Qian


    NOD-like receptors (NLRs) are a family of intracellular proteins that play critical roles in innate immunity against microbial infection.NLRC5,the largest member of the NLR family,has recently attracted much attention.However,in vitro studies have reported inconsistent results about the roles of NLRC5 in host defense and in regulating immune signaling pathways.The in vivo function of NLRC5 remains unknown.Here,we report that NLRC5 is a critical regulator of host defense against intraeellular pathogens in vivo.NLRC5 was specifically required for the expression of genes involved in MHC class Ⅰ antigen presentation.NLRC5-deficient mice showed a profound defect in the expression of MHC class Ⅰ genes and a concomitant failure to activate L.monocytogenes-specific CD8+ T cell responses,including activation,proliferation and cytotoxicity,and the mutant mice were more susceptible to the pathogen infection.NLRP3-mediated inflammasome activation was also partially impaired in NLRC5-deficient mice.However,NLRC5 was dispensable for pathogen-induced expression of NF-KB-dependent pro-inflammatory genes as well as type I interferon genes.Thus,NLRC5 critically regulates MHC class Ⅰ antigen presentation to control intracellular pathogen infection.

  16. The biology of cancer testis antigens: putative function, regulation and therapeutic potential. (United States)

    Fratta, Elisabetta; Coral, Sandra; Covre, Alessia; Parisi, Giulia; Colizzi, Francesca; Danielli, Riccardo; Nicolay, Hugues Jean Marie; Sigalotti, Luca; Maio, Michele


    Cancer testis antigens (CTA) are a large family of tumor-associated antigens expressed in human tumors of different histological origin, but not in normal tissues except for testis and placenta. This tumor-restricted pattern of expression, together with their strong in vivo immunogenicity, identified CTA as ideal targets for tumor-specific immunotherapeutic approaches, and prompted the development of several clinical trials of CTA-based vaccine therapy. Driven by this practical clinical interest, a more detailed characterization of CTA biology has been recently undertaken. So far, at least 70 families of CTA, globally accounting for about 140 members, have been identified. Most of these CTA are expressed during spermatogenesis, but their function is still largely unknown. Epigenetic events, particularly DNA methylation, appear to be the primary mechanism regulating CTA expression in both normal and transformed cells, as well as in cancer stem cells. In view of the growing interest in CTA biology, the aim of this review is to provide the most recent information on their expression, regulation and function, together with a brief summary of the major clinical trials involving CTA as therapeutic agents. The pharmacologic modulation of CTA expression profiles on neoplastic cells by DNA hypomethylating drugs will also be discussed as a feasible approach to design new combination therapies potentially able to improve the clinical efficacy of currently adopted CTA-based immunotherapeutic regimens in cancer patients.

  17. Assessing postpartum family functioning. (United States)

    Midmer, D; Talbot, Y


    The birth of a child requires adaptation and reorganization within the family system in order to accommodate the new family member and to allow the family to continue in its psychosocial development. Knowledge of the normative and transitional changes required at this stage of family life will enhance family practitioners' understanding of some of the common concerns and complaints related to them by various family members during the postpartum period. The Family FIRO model represents a helpful conceptual framework to increase the family physician's understanding of the issues of inclusion, control, and intimacy that are highlighted during the transition to parenthood. The authors briefly present this model and discuss its application to postpartum adjustment and its implications for health-care professionals.

  18. Family Caregiver Alliance (United States)

    ... on your schedule. Look for our launch soon! FAMILY CARE NAVIGATOR ─ Click on Your State AL AK ... Group) Smart Patients Caregivers Community In partnership with Family Caregiver Alliance Learn more Caregiver Research Caregivers exhibit ...

  19. IGSF9 Family Proteins

    DEFF Research Database (Denmark)

    Hansen, Maria; Walmod, Peter Schledermann


    The Drosophila protein Turtle and the vertebrate proteins immunoglobulin superfamily (IgSF), member 9 (IGSF9/Dasm1) and IGSF9B are members of an evolutionarily ancient protein family. A bioinformatics analysis of the protein family revealed that invertebrates contain only a single IGSF9 family gene......, the longest isoforms of the proteins have the same general organization as the neural cell adhesion molecule family of cell adhesion molecule proteins, and like this family of proteins, IGSF9 family members are expressed in the nervous system. A review of the literature revealed that Drosophila Turtle...... facilitates homophilic cell adhesion. Moreover, IGSF9 family proteins have been implicated in the outgrowth and branching of neurites, axon guidance, synapse maturation, self-avoidance, and tiling. However, despite the few published studies on IGSF9 family proteins, reports on the functions of both Turtle...

  20. National Military Family Association (United States)

    ... 931.6632 © 2016 - National Military Family Association Twitter Facebook Pinterest Instagram Charity Navigator Four Star Charity GuideStar Exchange Better Business Bureau Charity Watch Independent Charity of America nonprofit ...

  1. Importance of Family Routines (United States)

    ... Structure Your Child's Nighttime Routine . Weekends: Weekends are good times for family togetherness. You might go grocery shopping as a family, visit museums and zoos, do chores​ that everyone participates in, go on ...

  2. MSUD Family Support Group (United States)

    ... Group The MSUD Family Support Group is a non-profit 501 (c)(3) organization for those with MSUD ... Family Support Group is a 501(c)(3) non-profit organization with no paid staff. Funds are needed ...

  3. Loosely coupled class families

    DEFF Research Database (Denmark)

    Ernst, Erik


    are expressed using virtual classes seem to be very tightly coupled internally. While clients have achieved the freedom to dynamically use one or the other family, it seems that any given family contains a xed set of classes and we will need to create an entire family of its own just in order to replace one......Families of mutually dependent classes that may be accessed polymor- phically provide an advanced tool for separation of concerns, in that it enables client code to use a group of instances of related classes safely without depending on the exact classes involved. However, class families which...... of the members with another class. This paper shows how to express class families in such a manner that the classes in these families can be used in many dierent combinations, still enabling family polymorphism and ensuring type safety....

  4. Family Obligations in Denmark

    DEFF Research Database (Denmark)

    Koch-Nielsen, Inger

    How is the balance in obligations between the Family and the Danish Welfare State? Can we observe a trend to shift the responsibility back to the family? This booklet intends to sketch the legal framework around the division of responsibilities between the Family and the state and to analyse...... to what extent and where the unit of rights and obliagations is the individual and where it is the family or household....

  5. Family and Enterprise


    Fletcher, Denise Elaine


    This chapter provides a review of the different approaches that have been utilised to examine the link between family and enterprise. Definitional issues are addressed, as are rationalist and ‘systems’ ways of evaluating the relationship between family and enterprise. Criticism is made of the effects of rationalist thinking on studies of family businesses which have tended to create duality and polarity in our understanding of the family-enterprise relationship. It is argued that a developm...

  6. Engineering antigen-specific immunological tolerance.

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

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

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


    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.

  8. Family systems and fertility

    NARCIS (Netherlands)

    Moenkediek, Bastian


    This thesis studies the role of regional family organization principles, so called family systems, for explaining fertility behaviours in different parts of Europe. Studying family systems and its impact on fertility is important, because many aspects of societal life, such as the organization of we

  9. Families in Transition. (United States)

    Britton, Patti O., Ed.; McGee, Michael, Ed.


    This issue of "Emphasis" deals with families in transition, providing some model programs for the new family and some historical perspectives on how families have developed over time. Articles include: (1) "Nostalgia on the Right" (Nancy Theriot); (2) "Heart to Heart" (Nancy Harrington-MacLennan); (3) "The Media Get the Message" (Janet Alyn); (4)…

  10. Books in the Family. (United States)

    Swinger, Alice K.


    Opportunities for parents to encourage reading in the family are noted and ways to enhance the reading experience are discussed, including writing letters to book characters, singing combined with reading aloud, supplementing school subjects with enjoyable reading, sharing books at family gatherings, and using family experiences for book…

  11. Strengths of Remarried Families. (United States)

    Knaub, Patricia Kain; And Others


    Focuses on remarried families' (N=80) perceptions of family strengths, marital satisfaction, and adjustment to the remarried situation. Results indicated that although most would like to make some changes, scores on the measurements used were high. A supportive environment was the most important predictor of family strength and success. (JAC)

  12. Germinal center reaction: antigen affinity and presentation explain it all. (United States)

    Oropallo, Michael A; Cerutti, Andrea


    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.

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

    DEFF Research Database (Denmark)

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


    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...

  14. 21 CFR 866.3402 - Plasmodium species antigen detection assays. (United States)


    ... 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...

  15. Pneumocystis carinii from pigs and humans are antigenically distinct

    DEFF Research Database (Denmark)

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


    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...

  16. Expression of Treponema pallidum Antigens in Escherichia coli (United States)

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


    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.

  17. Antigen Loss Variants: Catching Hold of Escaping Foes (United States)

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


    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

  18. Acid test: lipid antigens get into the groove. (United States)

    Kronenberg, Mitchell; Sullivan, Barbara A


    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.

  19. Complex Antigens Drive Permissive Clonal Selection in Germinal Centers. (United States)

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


    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.

  20. 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.

  1. The global antigenic diversity of swine influenza A viruses

    DEFF Research Database (Denmark)

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


    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...

  2. Tumor Antigen-Derived Peptides Delivery for Cancer Immunotherapy. (United States)

    Wenxue, Ma


    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.

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

    Directory of Open Access Journals (Sweden)

    A. Montanelli


    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.

  4. Family traditions and generations. (United States)

    Schneiderman, Gerald; Barrera, Maru


    Currently, traditional family values that have been passed down through generations appear to be at risk. This has significant implications for the stability and health of individuals, families, and communities. This article explores selected issues related to intergenerational transmission of family values and cultural beliefs, with particular reference to Western culture and values that are rooted in Jewish and Christian traditions. It also examines family values and parenting styles as they influence the developing perspective of children and the family's adaptation to a changing world.

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

    Directory of Open Access Journals (Sweden)

    Sarah L James


    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.

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

    Directory of Open Access Journals (Sweden)

    Alyssa E Barry


    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

  7. Antigenic Relationships among Human Pathogenic Orientia tsutsugamushi Isolates from Thailand (United States)

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


    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

  8. Structural characterization and MHCII-dependent immunological properties of the zwitterionic O-chain antigen of Morganella morganii. (United States)

    Young, N Martin; Kreisman, Lori S C; Stupak, Jacek; MacLean, Leann L; Cobb, Brian A; Richards, James C


    Morganella morganii is a commensal Gram-negative bacterium that has long been known to produce an antigen bearing phosphocholine groups. We determined the structure of this O-chain antigen and found that its repeating unit also contains a free amino group and a second phosphate: This alternating charge character places the M. morganii O-chain polysaccharide into a small family of zwitterionic polysaccharides (ZPSs) known to induce T-cell-dependent immune responses via presentation by class II major histocompatibility complex (MHCII) molecules. In vitro binding assays demonstrate that this O-chain interacts with MHCII in a manner that competes with binding of the prototypical ZPS antigen PSA from Bacteroides fragilis, despite its lack of a helical structure. Cellular studies also showed that the M. morganii polysaccharide induces activation of CD4(+) T-cells. Antibody binding experiments using acid hydrolyzed fragments representing the monomer and higher oligomers of the repeating unit showed that the phosphocholine group was the dominant element of the epitope with an overall affinity (K(D)) of about 5 × 10(-5) M, a typical value for an IgM anti-carbohydrate antibody but much lower than the affinity for phosphocholine itself. These data show that the structure of the M. morganii polysaccharide contains a unique zwitterionic repeating unit which allows for immune recognition by T-cells, making it the first identified T-cell-dependent O-chain antigen.

  9. Asteroid family ages

    CERN Document Server

    Spoto, Federica; Knezevic, Zoran


    A new family classification, based on a catalog of proper elements with $\\sim 384,000$ numbered asteroids and on new methods is available. For the $45$ dynamical families with $>250$ members identified in this classification, we present an attempt to obtain statistically significant ages: we succeeded in computing ages for $37$ collisional families. We used a rigorous method, including a least squares fit of the two sides of a V-shape plot in the proper semimajor axis, inverse diameter plane to determine the corresponding slopes, an advanced error model for the uncertainties of asteroid diameters, an iterative outlier rejection scheme and quality control. The best available Yarkovsky measurement was used to estimate a calibration of the Yarkovsky effect for each family. The results are presented separately for the families originated in fragmentation or cratering events, for the young, compact families and for the truncated, one-sided families. For all the computed ages the corresponding uncertainties are pro...

  10. Inside the Family Firm

    DEFF Research Database (Denmark)

    Bennedsen, Morten; Nielsen, Kasper; Pérez-González, Francisco


    This paper uses a unique dataset from Denmark to investigate (1) the role of family characteristics in corporate decision making, and (2) the consequences of these decisions on firm performance. We focus on the decision to appoint either a family or an external chief executive officer (CEO). We...... show that a departing CEO's family characteristics have a strong predictive power in explaining CEO succession decisions: family CEOs are more frequently selected the larger the size of the family, the higher the ratio of male children and when the departing CEOs had only had one spouse. We...... then analyze the impact of family successions on performance. We overcome endogeneity and omitted variables problems of previous papers in the literature by using the gender of a departing CEO's first-born child as an instrumental variable (IV) for family successions. This is a plausible IV as male first...

  11. A family with extrinsic allergic alveolitis caused by wild city pigeons: A case report

    NARCIS (Netherlands)

    G.J. du Marchie Sarvaas; P.J.F.M. Merkus (Peter); J.C. de Jongste (Johan)


    textabstractWe describe a family in which the mother died of unresolved lung disease and whose 5 children, some of whom had previous signs of asthma, were subsequently affected by extrinsic allergic alveolitis caused by contact with wild city pigeon antigens. The children received

  12. The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interaction

    KAUST Repository

    Jackson, Andrew P.


    Babesia spp. are tick-borne, intraerythrocytic hemoparasites that use antigenic variation to resist host immunity, through sequential modification of the parasite-derived variant erythrocyte surface antigen (VESA) expressed on the infected red blood cell surface. We identified the genomic processes driving antigenic diversity in genes encoding VESA (ves1) through comparative analysis within and between three Babesia species, (B. bigemina, B. divergens and B. bovis). Ves1 structure diverges rapidly after speciation, notably through the evolution of shortened forms (ves2) from 5? ends of canonical ves1 genes. Phylogenetic analyses show that ves1 genes are transposed between loci routinely, whereas ves2 genes are not. Similarly, analysis of sequence mosaicism shows that recombination drives variation in ves1 sequences, but less so for ves2, indicating the adoption of different mechanisms for variation of the two families. Proteomic analysis of the B. bigemina PR isolate shows that two dominant VESA1 proteins are expressed in the population, whereas numerous VESA2 proteins are co-expressed, consistent with differential transcriptional regulation of each family. Hence, VESA2 proteins are abundant and previously unrecognized elements of Babesia biology, with evolutionary dynamics consistently different to those of VESA1, suggesting that their functions are distinct. 2014 The Author(s) 2014.

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

    Directory of Open Access Journals (Sweden)

    L. L. Golovkina


    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.

  14. Recognition of antigen-specific B-cell receptors from chronic lymphocytic leukemia patients by synthetic antigen surrogates. (United States)

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


    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.

  15. Identification and molecular cloning of tactile: A novel human T cell activation antigen that is a member of the Ig gene superfamily

    Energy Technology Data Exchange (ETDEWEB)

    Wang, P.L.; O' Farrell, S.; Clayberger, C. (Stanford Univ. School of Medicine, Stanford, CA (United States)); Krensky, A.M. (Stanford Univ. Medical Center, Stanford, CA (United States) Stanford Univ. School of Medicine, Stanford, CA (United States))


    The authors have identified and cloned cDNA for a novel cell-surface protein named Tactile for T cell activation, increased late expression. It is expressed on normal T cell lines and clones, and some transformed T cells, but no other cultured cell lines tested. It is expressed at low levels on peripheral T cells and is strongly up-regulated after activation, peaking 6 to 9 days after the activating stimulus. It is also up-regulated on NK cells activated in allogeneic cultures. It is not found on peripheral B cells but is expressed at very low levels on activated B cells. Tactile-specific mAb immuno-precipitates a band of 160 kDa when reduced and bands of 240, 180, and 160 kDa nonreduced. Using an antiserum produced with affinity-purified Tactile protein to screen a [lambda]gt11 library, the authors have identified Tactile cDNA. Northern blot analysis shows an expression pattern similar to that of the protein and transfection of COS cells with the full-length 5.2-kb cDNA results in cell-surface expression. Comparison with the sequence databanks show that Tactile is a member of the immunoglobulin gene superfamily, with similarity to Drosophila amalgam, the melanoma Ag MUC-18, members of the carcinoembryonic Ag family, the poliovirus receptor, and the neural cell adhesion molecule. The deduced primary sequence encodes a protein with three Ig domains, a long serine/threonine/proline-rich region typical of an extensively O-glycosylated domain, a transmembrane domain, and a 45 residue cytoplasmic domain. These data suggest that Tactile may be involved in adhesive interactions of activated T and NK cells during the late phase of the immune response.

  16. Opening Doors: Understanding School and Family Influences on Family Involvement (United States)

    Carlisle, Erin; Stanley, Lindsey; Kemple, Kristen Mary


    Family involvement in schooling can benefit young children, teachers, and families. Family involvement in schools can be influenced by both school-related and family-related factors. School-related factors include teachers' attitudes toward families, and school and teacher expectations. Family-related factors include ethnicity, prior school…

  17. Family governance practices and teambuilding : Paradox of the enterprising family

    NARCIS (Netherlands)

    Berent-Braun, M.M.; Uhlaner, L.M.


    This paper explores the relationship between family governance practices and financial performance of the business and family assets of business-owning families. A business-owning family that shares a focus on preserving and growing wealth as a family is defined as the enterprising family. Results o

  18. Family dynamics and family psychotherapy of psychosomatic. (United States)

    Wirsching, M; Stierlin, H


    Family therapy of psychosomatic disorders is oftern difficult and comparable to the therapy of psychotic patients. Nonetheless, the results published today by authors such as Minuchin and Selvini and our own experiences are promising indeed. We have found that what seemed to be a deep-rooted psychic structure changed rapidly and enduringly if the relationship field changed. Amelioration of symptoms is in many cases easily attained if they are understood in their function within a relational system. Also, we regard the system or family approach as a chance for medical practice. The general practioner who usually deals with family systems has, in our view, an ideal position to bring about change if he uses his authority and trust properly. He has to obtain a positive, not pathology-oriented view and should use family and social resources in spite of engaging in an often fruitless and endless contact with the designated patient, which only serves to maintain and even to increase the homeostatic lock of the family system.

  19. Atomic structure of anthrax protective antigen pore elucidates toxin translocation. (United States)

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


    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.

  20. Standardization and characterization of antigens for the diagnosis of aspergillosis. (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


    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.

  1. Molecular mimics of the tumour antigen MUC1.

    Directory of Open Access Journals (Sweden)

    Tharappel C James

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

  2. Antigenic variation with a twist--the Borrelia story. (United States)

    Norris, Steven J


    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.

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

    DEFF Research Database (Denmark)

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


    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...

  4. 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


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

  5. Monocytic HLA DR antigens in schizophrenic patients. (United States)

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


    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.

  6. Immunofluorescence antigen mapping for hereditary epidermolysis bullosa

    Directory of Open Access Journals (Sweden)

    Raghavendra Rao


    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.

  7. Engineering less immunogenic and antigenic FVIII proteins (United States)

    Pratt, Kathleen P.


    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

  8. Hepatitis B Virus e Antigen Variants

    Directory of Open Access Journals (Sweden)


    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.

  9. Advancing family psychology. (United States)

    Fiese, Barbara H


    To realize the broad and complex nature of the field of family psychology, I have slightly revised the mission statement of the Journal of Family Psychology (JFP) to capture contemporary scholarship in family psychology and to advance systems perspectives in this top-tier scientific journal. Over the next 6 years, I hope that authors will consider JFP as an outlet for their best work in the following areas: (1) JFP addresses societal challenges faced by families today; (2) JFP publishes important studies on what makes couple and family relationships work; (3) JFP is a leader in publishing reports that use cutting-edge sophisticated approaches to research design and data analysis; and (4) JFP imparts knowledge about effective therapy and prevention programs relevant to couples and families. The journal is also expanding its publication rate to eight issues per year.

  10. Internationalization of Family Businesses

    DEFF Research Database (Denmark)

    Boyd, Britta; Hollensen, Svend; Goto, Toshio


    This article focuses on the international joint venture formation process of family businesses. The reasoning behind Danfoss’ decision to cooperate with two competing family businesses in Japan and China as well as two nonfamily businesses in Canada and Britain will be analysed. In......-depth qualitative interviews reveal the driving forces on both sides and show how the psychic distance can be reduced between the different parent firms including the joint venture (JV) child. The purpose of this study is to compare equal split or equity joint ventures of non-family and family firms regarding...... the formation process including competences and cultures. The study indicates what core competences of a family business matter when cooperating in equal split joint ventures. Implications for family business owners and ideas for future research are discussed....

  11. Familial pituitary tumor syndromes. (United States)

    Elston, Marianne S; McDonald, Kerrie L; Clifton-Bligh, Roderick J; Robinson, Bruce G


    The vast majority of pituitary tumors are benign and occur sporadically; however, they can still result in significant morbidity and even premature mortality through mass effects and hormone dysfunction. The etiology of sporadic tumors is still poorly understood; by contrast, advances have been made in our understanding of familial pituitary adenoma syndromes in the past decade. Currently, four genes are known to be associated with familial pituitary tumor syndromes: MEN1, CDKN1B, PRKAR1A and AIP. The first three genes are associated with a variety of extrapituitary pathologies, for example, primary hyperparathyroidism with multiple endocrine neoplasia type 1, which might aid identification of these syndromes. By contrast, AIP mutations seem to occur in the setting of isolated familial pituitary adenomas, particularly of the growth-hormone-secreting subtype. Awareness and identification of familial pituitary tumor syndromes is important because of potential associated pathologies and important implications for family members. Here, we review the current knowledge of familial pituitary tumor syndromes.

  12. Isolation and purification of antigenic components of Cryptococcus. (United States)

    Wozniak, Karen L; Levitz, Stuart M


    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


    -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. KSF of family business


    Boroš, Petr


    Family business is a business in which family members have a large stake in ownership and also a deciding vote on business operation. This thesis deals with what makes the family businesses thriving. The research is conducted using the Good to Great framework by Jim Collins. Based mainly on quantitative and qualitative survey of 8 Czech companies of various fields and sizes, it was discovered that there are some links between the companies' success. These findings yield a set of recommendatio...

  15. Family in contemporary society


    Rabije Murati


    The family is part of social change and, as such changes and transform into steps with modern trends of society. Family function in a given society is structured according to the overall changes that occur in all areas of social life, not neglecting family life. The contemporary conditions impose requirements that must be met to move forward with the times that follow. In particular, should highlight the social changes that are related to the growth and advancement of the educational and prof...

  16. Serum α-L-fucosidase in the diagnosis of primary hepatic carcinoma -compared with α -fetoprotein and carcinoembryonic antigen by Receiver Operating Characteristic Curves%绘制ROC曲线评价血清α-L-岩藻糖苷酶(AFu)在原发性肝癌中的诊断价值

    Institute of Scientific and Technical Information of China (English)

    席云; 肖刚; 陈国强


    目的:确定血清α-L-岩藻糖苷酶(AFu)用于诊断原发性肝癌的临界值,比较AFU,AFP及CEA的筛查价值,为制定原发性肝癌的癌查方案提供依据.方法:对43例PHC、180例其他良性肝病及144例体检者,联合检测AFP、AFu和CEA,绘制ROC曲线,比较这三种诊断试验的ROC曲线下的面积.结果:ROC曲线下面积:AFU为0.927,AFP为0.966,CEA为0.415.结论:AFP的筛查价值略高于AFU,CEA没有价值,据ROC曲线确定AFU临界值为35.5 U/L.

  17. Diagnostic value of combinative detection of serum carcinoembryonic antigen(CEA),adenosine deaminase(ADA),lactate dehydrogenase(LDH) and ESR in differential diagnosis of pleural effusion%联合检测CEA、ADA、LDH及血沉对胸腔积液性质判断的临床意义

    Institute of Scientific and Technical Information of China (English)

    夏静; 闫雪波; 刘荣玉


    Objective To establish the diagnostic value of combinative detection of serum CEA,serum and pleural fluid LDH,pleural fluid ADA and ESR in different pleural effusion patients. Methods From December 2011 to June 2012 ,89 cases of in-patients with pleural effusion in the First Affiliated Hospital of Anhui Medical University were chosen,including 25 cases of tuberculous effusion( TE ),42 patients with malignant pleural effusion( MPE ) and 22 cases of inflammatory patients with pleural effusion( IPE ). The levels of serum CEA were examined by electrochemilumin-escence immunoassay method, serum LDH by the enzymatic( L method ), pleural fluid LDH and ADA by rating method and ESR by Westergren. Results The serum CEA of malignant pleural effusion patients is higher than that of TE and IPE patients;The serum and pleural fluid LDH levels in TE,MPE,IPE patients showed no significant difference,but the three pleural effusion LDH levels were significantly higher than the normal range, and the ratio of pleural effusion and serum LDH in patients with TE was significantly higher than that of patients with MPE; The pleural fluid ADA levels of TE were significantly higher than those of the MPE and IPE; The IPE patients ESR levels were significantly higher than those of TE and MPE patients, and ESR levels of TE patients were significantly higher than those of MPE patients. Conclusion Combined detection of serum CEA, pleural fluid and serum LDH, pleural fluid ADA and ESR has great significance in judging the nature of pleural fluid.%目的 探讨联合检测血清癌胚抗原(CEA)、血清及胸水乳酸脱氢酶(LDH)、胸水腺苷脱氨酶(ADA)及血沉对胸腔积液性质判断的临床意义.方法 以安徽医科大学第一附属医院2011年12月至2012年6月89例住院胸腔积液患者为研究对象,其中25例结核性胸腔积液患者,42例恶性胸腔积液患者,22例炎性胸腔积液患者;采用电化学发光免疫分析法测定血清CEA,酶法(L法)测定血清LDH,速率法测定胸水LDH及ADA,魏氏法测定血沉.结果 恶性胸腔积液患者血清CEA含量明显高于结核性及炎性胸腔积液患者;胸水及血清LDH含量在结核性、恶性、炎性胸腔积液患者中比较无显著性差异,但三者胸水LDH含量均明显高于正常范围,结核性胸腔积液患者胸水与血清LDH比值明显高于恶性胸腔积液患者;结核性胸腔积液患者胸水ADA含量明显高于恶性及炎性胸腔积液患者;炎性胸腔积液患者血沉明显高于结核性及恶性胸腔积液患者,结核性胸腔积液患者血沉明显高于恶性胸腔积液患者.结论 联合检测胸腔积液患者血清CEA、胸水及血清LDH,胸水ADA及血沉对辅助判断胸腔积液的性质具有重要价值.

  18. Alanine mutagenesis of the primary antigenic escape residue cluster, c1, of apical membrane antigen 1. (United States)

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


    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.

  19. Saturating Sperner families

    CERN Document Server

    Gerbner, Dániel; Lemons, Nathan; Pálvölgyi, Dömötör; Palmer, Cory; Patkós, Balázs


    A family $\\cF \\subseteq 2^{[n]}$ saturates the monotone decreasing property $\\cP$ if $\\cF$ satisfies $\\cP$ and one cannot add any set to $\\cF$ such that property $\\cP$ is still satisfied by the resulting family. We address the problem of finding the minimum size of a family saturating the $k$-Sperner property and the minimum size of a family that saturates the Sperner property and that consists only of $l$-sets and $(l+1)$-sets.

  20. Family in contemporary society

    Directory of Open Access Journals (Sweden)

    Rabije Murati


    Full Text Available The family is part of social change and, as such changes and transform into steps with modern trends of society. Family function in a given society is structured according to the overall changes that occur in all areas of social life, not neglecting family life. The contemporary conditions impose requirements that must be met to move forward with the times that follow. In particular, should highlight the social changes that are related to the growth and advancement of the educational and professional standards, which will increase the overall impact on the family and its function. If you're looking for full responsibility of parents in the upbringing of children then it is necessary to see the conditions in which the family lives. For normal education and the rights of children with special meaning the number of members in the (quantity family. The tendency to a higher standard of economic life, a small number of children in the family and it is more than obvious that fewer family members or less have greater opportunity for parents to pay more attention to their children. One of the main roles of family, no matter where they are located in the city, village, developed or developing countries, by all means participate, intermediates and transfers the moral, social and other values in modern life.

  1. The Hoffmeister asteroid family (United States)

    Carruba, V.; Novaković, B.; Aljbaae, S.


    The Hoffmeister family is a C-type group located in the central main belt. Dynamically, it is important because of its interaction with the ν1C nodal secular resonance with Ceres, which significantly increases the dispersion in inclination of family members at a lower semimajor axis. As an effect, the distribution of inclination values of the Hoffmeister family at a semimajor axis lower than its centre is significantly leptokurtic, and this can be used to set constraints on the terminal ejection velocity field of the family at the time it was produced. By performing an analysis of the time behaviour of the kurtosis of the vW component of the ejection velocity field [γ2(vW)], as obtained from Gauss' equations, for different fictitious Hoffmeister families with different values of the ejection velocity field, we were able to exclude that the Hoffmeister family should be older than 335 Myr. Constraints from the currently observed inclination distribution of the Hoffmeister family suggest that its terminal ejection velocity parameter VEJ should be lower than 25 m s-1. Results of a Yarko-YORP Monte Carlo method to family dating, combined with other constraints from inclinations and γ2(vW), indicate that the Hoffmeister family should be 220^{+60}_{-40} Myr old, with an ejection parameter VEJ = 20 ± 5 m s-1.

  2. Responses of synovial fluid and peripheral blood mononuclear cells to bacterial antigens and autologous antigen presenting cells. (United States)

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


    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

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

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


    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.

  4. Communication in family businesses : Relationships between family and non-family managers


    Grytsaieva, Tetiana; Strandberg, Johan


    Problem: Family firms often comprise of a complex web of relationships between family and non-family managers that are active within the business. Family enterprises are also known for their closed communication and decision-making practices. It often occurs that families do not include non-family managers into important business-related discussions and do not consult their decisions with managers from outside of the family. At the same time, research in the area of family business defines th...

  5. A Bangladeshi family with three sisters 'Bombay' or Oh phenotype. (United States)

    Rahman, M; Abdullah, A Z; Husain, M; Hague, K M; Hossain, M M


    Three sisters in a same family (MIAH FAMILY) are of 'Bombay' phenotype. These being the first known female examples of 'Bombay' blood group have been detected in Bangladesh. As predicted by current theory their red cells are Le(a+b-) and their saliva do not contain any of the antigens A, B and H except Lea substance. Family studies showed that individuals with 'Bombay' or Oh phenotype may have A or B gene which are not expressed. This very particular type of blood is one of the rarest in any other parts of world except in India. Due to the presence of anti-H antibody in the plasma of Oh phenotype, when considering such patients for transfusion only blood of identical Bombay type can be safely transfused.

  6. Genetic immunization elicits antigen-specific protective immune responses and decreases disease severity in Trypanosoma cruzi infection. (United States)

    Garg, Nisha; Tarleton, Rick L


    Immunity to Trypanosoma cruzi requires elicitation of humoral and cell-mediated immune responses to extracellular trypomastigotes and intracellular amastigotes. In this study, the effectiveness of the T. cruzi trans-sialidase family (ts) genes ASP-1, ASP-2, and TSA-1 as genetic vaccines was assessed. Immunization of mice with plasmids encoding ASP-1, ASP-2, or TSA-1 elicited poor antigen-specific cytotoxic-T-lymphocyte (CTL) activity and T. cruzi-specific antibody responses. Codelivery of interleukin-12 and granulocyte-macrophage colony-stimulating factor plasmids with antigen-encoding plasmids resulted in a substantial increase in CTL activity and antibody production and in increased resistance to T. cruzi infection. In pooled results from two to four experiments, 30 to 60% of mice immunized with antigen-encoding plasmids and 60 to 80% of mice immunized with antigen-encoding plasmids plus cytokine adjuvants survived a lethal challenge with T. cruzi. In comparison, 90% of control mice injected with empty plasmid DNA died during the acute phase of infection. However, the pool of three ts genes provided no greater protection than the most effective single gene (ASP-2) either with or without coadministration of cytokine plasmids. Importantly, the extent of tissue parasitism, inflammation, and associated tissue damage in skeletal muscles during the chronic phase of T. cruzi infection in mice immunized with antigen-encoding plasmids plus cytokine adjuvants was remarkably reduced compared to mice immunized with only cytokine adjuvants or empty plasmid DNA. These results identify new vaccine candidates and establish some of the methodologies that might be needed to develop effective vaccine-mediated control of T. cruzi infection. In addition, this work provides the first evidence that prophylactic genetic immunization can prevent the development of Chagas' disease.

  7. The use of high-throughput DNA sequencing in the investigation of antigenic variation: application to Neisseria species.

    Directory of Open Access Journals (Sweden)

    John K Davies

    Full Text Available Antigenic variation occurs in a broad range of species. This process resembles gene conversion in that variant DNA is unidirectionally transferred from partial gene copies (or silent loci into an expression locus. Previous studies of antigenic variation have involved the amplification and sequencing of individual genes from hundreds of colonies. Using the pilE gene from Neisseria gonorrhoeae we have demonstrated that it is possible to use PCR amplification, followed by high-throughput DNA sequencing and a novel assembly process, to detect individual antigenic variation events. The ability to detect these events was much greater than has previously been possible. In N. gonorrhoeae most silent loci contain multiple partial gene copies. Here we show that there is a bias towards using the copy at the 3' end of the silent loci (copy 1 as the donor sequence. The pilE gene of N. gonorrhoeae and some strains of Neisseria meningitidis encode class I pilin, but strains of N. meningitidis from clonal complexes 8 and 11 encode a class II pilin. We have confirmed that the class II pili of meningococcal strain FAM18 (clonal complex 11 are non-variable, and this is also true for the class II pili of strain NMB from clonal complex 8. In addition when a gene encoding class I pilin was moved into the meningococcal strain NMB background there was no evidence of antigenic variation. Finally we investigated several members of the opa gene family of N. gonorrhoeae, where it has been suggested that limited variation occurs. Variation was detected in the opaK gene that is located close to pilE, but not at the opaJ gene located elsewhere on the genome. The approach described here promises to dramatically improve studies of the extent and nature of antigenic variation systems in a variety of species.

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

    Directory of Open Access Journals (Sweden)

    Mayu Suzuki


    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.

  9. The Rafita asteroid family (United States)

    Aljbaae, S.; Carruba, V.; Masiero, J. R.; Domingos, R. C.; Huaman, M.


    The Rafita asteroid family is an S-type group located in the middle main belt, on the right side of the 3J:-1A mean-motion resonance. The proximity of this resonance to the family left side in semi-major axis caused many former family members to be lost. As a consequence, the family shape in the (a, 1/D) domain is quite asymmetrical, with a preponderance of objects on the right side of the distribution. The Rafita family is also characterized by a leptokurtic distribution in inclination, which allows the use of methods of family age estimation recently introduced for other leptokurtic families such as Astrid, Hansa, Gallia, and Barcelona. In this work we propose a new method based on the behavior of an asymmetry coefficient function of the distribution in the (a, 1/D) plane to date incomplete asteroid families such as Rafita. By monitoring the time behavior of this coefficient for asteroids simulating the initial conditions at the time of the family formation, we were able to estimate that the Rafita family should have an age of 490 ± 200 Myr, in good agreement with results from independent methods such as Monte Carlo simulations of Yarkovsky and Yorp dynamical induced evolution and the time behaviour of the kurtosis of the sin (i) distribution. Asteroids from the Rafita family can reach orbits similar to 8% of the currently known near Earth objects. ≃1% of the simulated objects are present in NEO-space during the final 10 Myr of the simulation, and thus would be comparable to objects in the present-day NEO population.

  10. Sub-grouping and sub-functionalization of the RIFIN multi-copy protein family

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    Sonnhammer Erik L


    Full Text Available Abstract Background Parasitic protozoans possess many multicopy gene families which have central roles in parasite survival and virulence. The number and variability of members of these gene families often make it difficult to predict possible functions of the encoded proteins. The families of extra-cellular proteins that are exposed to a host immune response have been driven via immune selection to become antigenically variant, and thereby avoid immune recognition while maintaining protein function to establish a chronic infection. Results We have combined phylogenetic and function shift analyses to study the evolution of the RIFIN proteins, which are antigenically variant and are encoded by the largest multicopy gene family in Plasmodium falciparum. We show that this family can be subdivided into two major groups that we named A- and B-RIFIN proteins. This suggested sub-grouping is supported by a recently published study that showed that, despite the presence of the Plasmodium export (PEXEL motif in all RIFIN variants, proteins from each group have different cellular localizations during the intraerythrocytic life cycle of the parasite. In the present study we show that function shift analysis, a novel technique to predict functional divergence between sub-groups of a protein family, indicates that RIFINs have undergone neo- or sub-functionalization. Conclusion These results question the general trend of clustering large antigenically variant protein groups into homogenous families. Assigning functions to protein families requires their subdivision into meaningful groups such as we have shown for the RIFIN protein family. Using phylogenetic and function shift analysis methods, we identify new directions for the investigation of this broad and complex group of proteins.

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

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    Ana Laín


    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.

  12. The Antigen Presenting Cells Instruct Plasma Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Wei eXu


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

  13. 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.


    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

  14. The Synthesis of a Novel Phosphorus Containing Antigen

    Institute of Scientific and Technical Information of China (English)


    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.

  15. Antigen-specific lymphocyte transformation in patients with recent yersiniosis. (United States)

    Vuento, R


    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.

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

    DEFF Research Database (Denmark)

    Dabelsteen, Erik


    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...

  17. Chlamydia trachomatis antigen in female genital tract infection

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    Badrinath S


    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.

  18. Instability of induction cooker (electromagnetic stove) antigen retrieval in immunohistochemistry. (United States)

    Ding, Wei; Zheng, Xiang-Yi


    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.

  19. Photoaffinity antigens for human γδ T cells1 (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.


    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

  20. Melanocyte antigen triggers autoimmunity in human psoriasis. (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


    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.

  1. Clinical characteristics and HLA alleles of a family with simultaneously occurring alopecia areata. (United States)

    Emre, Selma; Metin, Ahmet; Caykoylu, Ali; Akoglu, Gulsen; Ceylan, Gülay G; Oztekin, Aynure; Col, Esra S


    Alopecia areata (AA) is a T-cell-mediated autoimmune disease resulting in partial or total noncicatricial hair loss. HLA class II antigens are the most important markers that constitute genetic predisposition to AA. Various life events and intense psychological stress may play an important role in triggering AA attacks. We report an unusual case series of 4 family members who had simultaneously occurring active AA lesions. Our aim was to evaluate the clinical and psychiatric features of 4 cases of active AA lesions occurring simultaneously in a family and determine HLA alleles. The clinical and psychological features of all patients were examined. HLA antigen DNA typing was performed by polymerase chain reaction with sequence-specific primers. All patients had typical AA lesions over the scalp and/or beard area. Psychological examinations revealed obsessive-compulsive personality disorder in the proband's parents as well as anxiety and lack of self-confidence in both the proband and his sister. HLA antigen types were not commonly shared with family members. These findings suggest that AA presenting concurrently in members of the same family was not associated with genetic predisposition. Shared psychological disorders and stressful life events might be the major key points in the concurrent presentation of these familial AA cases and development of resistance against treatments.

  2. Partial purification of protective antigens from Nippostrongylus brasiliensis in mice. (United States)

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


    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.

  3. Dynamic quantification of antigen molecules with flow cytometry (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.


    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

  4. Microbial antigenic variation mediated by homologous DNA recombination



    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...

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

    Directory of Open Access Journals (Sweden)

    Baert K


    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

  6. Serological diagnosis with recombinant N antigen for hantavirus infection. (United States)

    Yoshimatsu, Kumiko; Arikawa, Jiro


    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.

  7. Surface antigens of metacyclic trypomastigotes of Trypanosoma cruzi.



    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.

  8. Prostate Tumor Antigen Discovery: Development of a Novel Genetic Approach (United States)


    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

  9. Antigen-specific immune reactions to ischemic stroke

    Directory of Open Access Journals (Sweden)

    Xabier eUrra


    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.

  10. Conservation of Meningococcal Antigens in the Genus Neisseria


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


    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...

  11. Fibroblasts as Efficient Antigen-Presenting Cells in Lymphoid Organs (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.


    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.

  12. Prevalence of Weak D Antigen In Western Indian Population

    Directory of Open Access Journals (Sweden)

    Tanvi Sadaria


    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.

  13. Regulator T cells: specific for antigen and/or antigen receptors? (United States)

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


    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?

  14. Assessment of Troubled Families. (United States)

    Combs-Orme, Terri; Thomas, Katherine H.


    Tests the utility of four standardized instruments used in assessing 105 families that sought services in a juvenile corrections setting for their teenage children. Results demonstrate that parents and adolescents can complete standardized assessment instruments and that the information provided can help in understanding distressed families. (RJM)

  15. The Family Victivallaceae

    NARCIS (Netherlands)

    Plugge, C.M.; Zoetendal, E.G.


    The family Victivallaceae is a member of the order Victivallales and holds only two cultured representatives: Victivallis vadensis strain CelloT and the uncharacterized strain NML 080035. They are Gram-negative, nonmotile, and anaerobic. Within the family as well as the order, cloned 16S rRNA gene s

  16. Golden Matrix Families (United States)

    Fontaine, Anne; Hurley, Susan


    This student research project explores the properties of a family of matrices of zeros and ones that arises from the study of the diagonal lengths in a regular polygon. There is one family for each n greater than 2. A series of exercises guides the student to discover the eigenvalues and eigenvectors of the matrices, which leads in turn to…

  17. Helping Friends and Family (United States)

    ... chapter Join our online community Helping Friends and Family Part of living well with Alzheimer’s is adjusting to your “new normal” and helping family and friends do the same. Knowing what to ...

  18. America's Family Time Famine. (United States)

    Mattox, Jr., William R.


    Parents spend increasingly less time with their children because of the pressures of dual careers and single parenthood. Economic pressures and social values have affected sharing of family time. Studies show both parents and children consider spending time together the most important element in improving family life. (BC)

  19. Marriage or Family Therapy. (United States)

    Haley, Jay


    Reviews the differences between family therapy and marriage counseling in terms of professional organization, theory, and practice. Suggests that training in marriage therapy does not appear adequate for family therapy. The goal of the therapy field should be more consensus in theory and a single profession of therapists. (JAC)

  20. Narrative Family Therapy. (United States)

    Walsh, William M.; Keenan, Robert


    States that narrative family therapy is informed by social constructionism and postmodern worldviews, and is a relatively significant departure from mainstream psychotherapy. Discusses the use of narrative family therapy. Uses the story of Adam and Eve in the Garden of Eden as an example. (MKA)

  1. Closure Issues with Families. (United States)

    Craig, Steven E.; Bischof, Gary H.

    Closure of the counseling relationship constitutes both an ending and a beginning. Although closure signifies the ending of the present counseling relationship, many family counselors conceptualize closure as the start of a working relationship between counselor and family that may be summoned in future times of crisis or during a difficult life…

  2. Selecting Family Interventions. (United States)

    Watts, Richard E.

    Just as counseling approaches designed for individuals have their theory-specific techniques, family counseling approaches also have theory-specific interventions and strategies. Whatever presenting problem the family brings to counseling, one or more of four essential components (communication, problem solving, roles and boundaries) is typically…

  3. Family Report 2011

    NARCIS (Netherlands)

    Freek Bucx


    Original title: Gezinsrapport 2011. Between 2007 and 2010 the Netherlands had its first ever Minister for Youth and Family. The position of the family in modern society is a subject of considerable debate, not just at political and policy level, but also in society itself. Voices are frequently hea

  4. Privacy in the family

    NARCIS (Netherlands)

    Newell, Bryce; Metoyer, Cheryl A.; Moore, Adam D.


    Popular access to increasingly sophisticated forms of electronic surveillance technologies has altered the dynamics of family relationships. Monitoring, mediated and facilitated by practices of both covert and overt electronic surveillance, has changed the nature of privacy within the family. In thi

  5. Changing Families, Changing Workplaces (United States)

    Bianchi, Suzanne M.


    American families and workplaces have both changed dramatically over the past half-century. Paid work by women has increased sharply, as has family instability. Education-related inequality in work hours and income has grown. These changes, says Suzanne Bianchi, pose differing work-life issues for parents at different points along the income…

  6. Isolation and characterization of human rhinovirus antigenic variants

    Energy Technology Data Exchange (ETDEWEB)

    Watson, D.G.


    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.

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

    Directory of Open Access Journals (Sweden)

    Murat Akkus


    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.

  8. Urine antigen detection for the diagnosis of human neurocysticercosis. (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


    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.

  9. T Cells as Antigen Carriers for Anti-tumor Vaccination. (United States)

    Traversari, Catia; Russo, Vincenzo


    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.

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

    Directory of Open Access Journals (Sweden)

    Nathan P Croft


    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.

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

    Directory of Open Access Journals (Sweden)

    A Halajian


    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.

  12. Antigen specificity of invariant natural killer T-cells

    Directory of Open Access Journals (Sweden)

    Alysia M. Birkholz


    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.

  13. Antigen specificity of invariant natural killer T-cells. (United States)

    Birkholz, Alysia M; Kronenberg, Mitchell


    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.

  14. 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.

  15. Fighting for the family

    DEFF Research Database (Denmark)

    Heiselberg, Maj Hedegaard


    The article explores how military deployment affects the everyday lives of Danish soldiers’ families. By approaching the challenges faced by soldiers and their partners from an anthropological perspective of the family, the article provides new insights into the social consequences of military...... deployment and the processes of militarization at home. Drawing on ethnographic examples from recent fieldwork among women, children, and soldiers at different stages of deployment, the article demonstrates how soldiers and their families attempt to live up to ideals about parenthood and family by creating...... ‘relational spaces’ that allow them to preserve intimate relationships despite geographical distances. Besides dealing with the practical responsibilities of everyday life, soldiers’ partners also fight to maintain the sense of closeness associated with normative ideals about family relations and a ‘good...

  16. Maintenance of family networks

    DEFF Research Database (Denmark)

    marsico, giuseppina; Chaudhary, N; Valsiner, Jaan


    Families are social units that expand in time (across generations) and space (as a geographically distributed sub-structures of wider kinship networks). Understanding of intergenerational family relations thus requires conceptualization of communication processes that take place within a small...... collective of persons linked with one another by a flexible social network. Within such networks, Peripheral Communication Patterns set the stage for direct everyday life activities within the family context. Peripheral Communication Patterns are conditions where one family network member (A) communicates...... manifestly with another member (B) with the aim of bringing the communicative message to the third member (C) who is present but is not explicitly designated as the manifest addressee of the intended message. Inclusion of physically non-present members of the family network (elders living elsewhere, deceased...

  17. Genetics of familial melanoma

    DEFF Research Database (Denmark)

    Aoude, Lauren G; Wadt, Karin A W; Pritchard, Antonia L


    Twenty years ago, the first familial melanoma susceptibility gene, CDKN2A, was identified. Two years later, another high-penetrance gene, CDK4, was found to be responsible for melanoma development in some families. Progress in identifying new familial melanoma genes was subsequently slow; however......, with the advent of next-generation sequencing, a small number of new high-penetrance genes have recently been uncovered. This approach has identified the lineage-specific oncogene MITF as a susceptibility gene both in melanoma families and in the general population, as well as the discovery of telomere...... maintenance as a key pathway underlying melanoma predisposition. Given these rapid recent advances, this approach seems likely to continue to pay dividends. Here, we review the currently known familial melanoma genes, providing evidence that most additionally confer risk to other cancers, indicating...

  18. Familial malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Kopf, A.W.; Hellman, L.J.; Rogers, G.S.; Gross, D.F.; Rigel, D.S.; Friedman, R.J.; Levenstein, M.; Brown, J.; Golomb, F.M.; Roses, D.F.; Gumport, S.L.


    Characteristics associated with familial compared with nonfamilial malignant melanoma were assessed. These data were obtained from consecutive prospectively completed questionnaires on 1169 cases of cutaneous malignant melanoma. Of these, 69 patients indicated a positive family history for this cancer. Among the various clinical and histological variables compared, those that significantly correlated with the familial occurrence of malignant melanoma include younger age at first diagnosis, smaller diameter of the lesion, lower Clark level, decreased frequency of nonmelanoma skin cancer, and reduced prevalence of noncutaneous cancer. Increased awareness of malignant melanoma among family members could account for some of these observations. Identification of the familial variety of malignant melanoma has practical implications concerning early detection and prompt intervention.

  19. Human-leukocyte antigen typing in Javanese patients with recurrent aphthous stomatitis

    Directory of Open Access Journals (Sweden)

    Diah Savitri Ernawati


    Full Text Available Background: Recurrent aphthous stomatitis (RAS is a common oral disorder that despite extensive researches, the etiology of this phenomenon is still unknown. Because this phenomenon has been observed more often in families than in individual cases, genetic influence has been investigated in most researches. Purpose: The aim of study was to evaluate the association between human leukocyte antigen (HLA and RAS in Javanese more precisely. Method: The analysis of HLA-A, and HLA-B in 85 Javanese RAS patients and 71 healthy control subjects, were performed by using the standard NIH microlymhocytotoxicity technique. Immunohistochemistry was performed for identification of HLA-DR and HLA- DQ antigen using monoclonal antibodies anti HLA-DR and DQ. Result: Our result revealed a close association between HLA-A9 and HLA-B35 RAS subject. A significant increase in the frequency of some antigens such as HLA-A9 (72,94%, p < 0,05;RR = 2,21, HLA-A24 (65,82%; RR = 1,24 and HLA-B35 in subjects with RAS was observed. Analysis with Immunohistochemistry HLA-DR, HLA-DQ is expressed on the surface of epithelial cells membrane of oral mucosa and macrophages in both major and minor RAS patients. Conclusion: HLA antigens are involved in susceptibility to RAS and the phenotypes were difference with other previous studies. HLA- linked genetic factors may play a role in the development of RAS.Latar belakang: Stomatitis aftosa rekuren (SAR merupakan salah satu gangguan di rongga mulut yang paling sering terjadi. Fenomenapenyakit ini masih belum jelas dan masih membutuhkanpenelitian yang lebih lanjut. Faktor keturunan lebih sering daripada kasus individual. Pengaruh faktor genetik telah diteliti oleh beberapapeneliti. Tujuan: Tujuan penelitian ini untuk mengetahui adanya kaitan HLA dengan SARpada suku jawa secara lebih tepat. Metode: Analisis HLA-A, HLA-Bpada 85penderita RAS dan 71 penderita kontrol yang berasal dari suku Jawa dihitung dengan menggunakan teknik NIH Micro

  20. 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


    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...