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Sample records for carcinoembryonic antigen families

  1. Identification of a Carcinoembryonic Antigen Gene Family in the Rat

    OpenAIRE

    Kodelja, Vitam; Lucas, Kurt; Barnert, Sabine; Kleist, Sabine von; Thompson, John A.; Zimmermann, Wolfgang

    1989-01-01

    The existence of a carcinoembryonic antigen (CEA)-like gene family in rat has been demonstrated through isolation and sequencing of the N- terminal domain exons of presumably five discrete genes (rnCGM1-5). This finding will allow for the first time the study of functional and clinical aspects of the tumor marker CEA and related antigens in an animal model. Sequence comparison with the corresponding regions of members of the human CEA gene family revealed a relatively low similarity at the am...

  2. Carcino-Embryonic Antigen

    International Nuclear Information System (INIS)

    Tumour marker analysis has increased our understanding of the presence of tumours in the body. Carcino-embryonic antigen, CEA, is one of the best studied tumour markers and has proved an ideal diagnostic adjuvant. It has helped in quantifying the amount of disease present in a patient and thence to make accurate prognosis on the various diagnosed ailments. At UCH, it is observed that there is an increase in cancer related ailments and therefore the need for early diagnosis is more compelling in our environment to mitigate future cost of managing advanced manifestation

  3. COLONOSCOPY AND CARCINOEMBRYONIC ANTIGEN VARIATIONS

    Directory of Open Access Journals (Sweden)

    Rita G SOUSA

    2014-03-01

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

  4. A Carcinoembryonic Antigen-Secreting Adenocarcinoma Arising in Tailgut Cyst : Clinical Implications of Carcinoembryonic Antigen

    OpenAIRE

    Cho, Byoung Chul; Kim, Nam Kyu; Lim, Beom Jin; Kang, Sang Ook; Sohn, Ju Hyuk; Roh, Jae Kyung; Choi, Sang Tae; Kim, Sung Ai; Park, Se Eun

    2005-01-01

    Tailgut cysts (TGCs) are rare congenital cysts that occur in the retrorectal or presacral spaces. Although most tailgut cysts have been reported as benign, there have been at least 9 cases associated with malignant change. We report herein on an unusual case of a 40-year-old woman with a carcinoembryonic antigen (CEA)-producing adenocarcinoma arising within a TGC who underwent surgical resection and local radiation therapy. Despite the complete resection, metastatic adenocarcinoma developed f...

  5. A carcinoembryonic antigen-secreting adenocarcinoma arising in tailgut cyst: clinical implications of carcinoembryonic antigen.

    Science.gov (United States)

    Cho, Byoung Chul; Kim, Nam Kyu; Lim, Beom Jin; Kang, Sang Ook; Sohn, Ju Hyuk; Roh, Jae Kyung; Choi, Sang Tae; Kim, Sung Ai; Park, Se Eun

    2005-08-31

    Tailgut cysts (TGCs) are rare congenital cysts that occur in the retrorectal or presacral spaces. Although most tailgut cysts have been reported as benign, there have been at least 9 cases associated with malignant change. We report herein on an unusual case of a 40-year-old woman with a carcinoembryonic antigen (CEA)-producing adenocarcinoma arising within a TGC who underwent surgical resection and local radiation therapy. Despite the complete resection, metastatic adenocarcinoma developed five months after surgery. CEA-producing adenocarcinoma from a TGC is extremely rare and only two cases, including this case, have been reported in the English medical literature. Besides CEA, the serum levels of CA 19-9 became markedly elevated in this patient. Given that the serum CEA level decreased to the normal range after complete resection of tumor and that the tumor recurrence was associated with a rebound of the CEA serum level, our case shows that serial measurements of serum CEA can be used for treatment planning and for assessing the patient's treatment response for this rare disease. PMID:16127782

  6. Prognostic Effect of Pretreatment Serum Carcinoembryonic Antigen Level

    OpenAIRE

    Kim, Chang Hyun; Lee, Soo Young; Kim, Hyeong Rok; Kim, Young Jin

    2015-01-01

    Abstract Many studies have reported the prognostic value of pretreatment serum carcinoembryonic antigen (pre-CEA) levels on colorectal cancer outcomes. However, controversy remains concerning the significance of pre-CEA levels in patients with rectal cancer treated with neoadjuvant chemoradiotherapy (CRT). Our aim in this study was to investigate the prognostic role of the pre-CEA level in patients with locally advanced rectal cancer undergoing neoadjuvant CRT followed by total mesorectal exc...

  7. Reagents for radioimmunological determination of carcinoembryonic antigen (CEA)

    International Nuclear Information System (INIS)

    The work was undertaken to prepare the reagents for carcinoembryonic antigen (CEA) radioimmunoassay with double antibody method. The CEA standard of high immunoreactivity was prepared and purified. The purified CEA was used for immunozation of goats. The goat anti - CEA sera were received. IgG fraction from normal goat serum was purified and used for the production of horse anti-goat IgG serum which was then used in the radioimmunoassay of CEA. The labelling of CEA with iodine-125 has been carried out be means of the enzymatic method.(Z.R.)

  8. Carcinoembryonic antigen (CEA) dynamics in stomach cancer patients receiving cryotherapy

    International Nuclear Information System (INIS)

    Radioimmunologic assays of blood serum carcinoembryonic antigen (CEA) level were conducted at major stages of treatment of gastric cancer by subtotal stomach resection and gastrectomy with preliminary cryotreatment and thawing of tumor. A short-term rise in CEA level occurred in 53.9 % of cases 3-4 days after combined therapy. A decrease in CEA concentration at discharge from hospital as compared with preoperative level and that registered 3-4 days after operation was observed in 50 and 75 % of cases of combined therapy, respectively, and 47.5 and 37.5 % of controls (surgery without cryotreatment). There was nocorrelation between cryotreatment and changes in CEA level in gastric ulcer patients

  9. Carcinoembryonic antigen continuous epitopes determined by the spot method.

    Science.gov (United States)

    Solassol, I; Granier, C; Pèlegrin, A

    2001-01-01

    Carcinoembryonic antigen (CEA) is a heavily glycosylated tumor-associated protein with an N-A1-B1-A2-B2-A3-B3 domain structure. Circulating CEA immunoassays are used for monitoring digestive cancer patients, and radiolabeled anti-CEA monoclonal antibodies (MAb) are used for the diagnosis and therapy of CEA-positive tumors. The five major nonoverlapping epitopes (Gold 1-5) have been broadly correlated with the domain organization, but there is no precise localization of the epitopes at the sequence level. In an attempt to identify the peptide sequences corresponding to the five Gold epitopes on the CEA molecule, we prepared a set of 227 overlapping fifteen-mer peptides corresponding to the complete CEA sequence with the SPOT method. Using five high affinity MAbs directed against the five CEA Gold epitopes, we demonstrated that none of these epitopes could be mimicked by a fifteen-mer peptide sequence. However, using rabbit and goat anti-CEA sera, we identified six major continuous antigenic regions. All are included in the Ig-like domains of the CEA: two in the A1 domain (residues 120-134 and 153-164), one each in the A2 (329-337) and A3 domains (508-513), one at the junction between the A3 and B3 domains (553-561) and one in the B3 domain (565-573). A very homologous sequence (common residues VSPRL) was mapped in each of the three A domains. Thus, in terms of occurrence of continuous epitopes, the Ig-like domains A1, A2, A3 and B3 seem to be the most antigenic parts of CEA. These peptide sequences should be good candidates for the future development of site-specific anti-CEA MAbs. PMID:11275797

  10. Detection of Carcinoembryonic Antigens Using a Surface Plasmon Resonance Biosensor

    Directory of Open Access Journals (Sweden)

    Shin-Ichiro Nishimura

    2008-07-01

    Full Text Available Carcinoembryonic antigen (CEA is an oncofoetal cell-surface glycoprotein that serves as an important tumor marker for colorectal and some other carcinomas. In this work, a CEA immunoassay using a surface plasmon resonance (SPR biosensor has been developed. SPR could provide label-free, real-time detection with high sensitivity, though its ability to detect CEA in human serum was highly dependent on the analytical conditions employed. We investigated the influences of various analytical conditions including immobilization methods for anti-CEA antibody and composition of sensor surface on the selective and sensitive detection of CEA. The results show that anti-CEA antibody immobilized via Protein A or Protein G caused a large increase in the resonance signal upon injection of human serum due to the interactions with IgGs in serum, while direct covalent immobilization of anti-CEA antibody could substantially reduce it. An optimized protocol based on further kinetic analysis and the use of 2nd and 3rd antibodies for the sandwich assay allowed detecting spiked CEA in human serum as low as 25 ng/mL. Furthermore, a self-assembled monolayer of mixed ethylene-glycol terminated alkanethiols on gold was found to have a comparable ability in detecting CEA as CM5 with thick dextran matrix and C1 with short flat layer on gold.

  11. A recombinant vaccinia virus expressing human carcinoembryonic antigen (CEA).

    Science.gov (United States)

    Kaufman, H; Schlom, J; Kantor, J

    1991-07-30

    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.

  12. Carcinoma of the ureter with extensive squamous differentiation and positive immunoperoxidase staining for carcinoembryonic antigen: a case report.

    Science.gov (United States)

    Fulks, R M; Falace, P B

    1985-01-01

    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.

  13. Radionuclide-Based Cancer Imaging Targeting the Carcinoembryonic Antigen

    Directory of Open Access Journals (Sweden)

    Hao Hong

    2008-01-01

    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”.

  14. A rapid radioimmunoassay for determination of tumor antigens with reference to carcinoembryonic antigen

    International Nuclear Information System (INIS)

    A novel experimental procedure for the determination of carcinoembryonic antigen (CEA) by a solid phase microradioimmunoassay has been developed. Goat anti-CEA antibodies were immobilized by coupling to cyanogen bromide activated filter paper discs. The inhibition of binding of radioiodinated CEA to the discs was proportional to the amount of unlabelled CEA present in the test sample. The experimental procedure involved two steps: (i) the test material containing unlabelled CEA was allowed to react with the antibody coated discs at 37 deg C for 2 hrs., and (ii) a standard amount of 125I-CEA was added to the reaction mixture and incubated for 24 hours at 37 deg C or room temperature. The discs were then washed 4 times and the radioactivity of each disc was determined. The sensitivity of the test in its present state of development was 2.5 ng/ml. (author)

  15. Levels of estrogen, carcinoembryonic antigen and cancer antigen of breast in breast cancer patients

    International Nuclear Information System (INIS)

    This study was conducted during the period from february 2004 to July 2004; with the objective of measuring the levels of estrogen (E2), carcinoembryonic antigen (CEA) and cancer antigen of breast (CA-15.3) so as to facilitate the early diagnosis of breast cancer and determine the involvement of these parameters as risk factors for breast cancer. Ninety blood samples were collected from Sudanese females, divided into two groups; control group and patient groups. The patients group was sixty Sudanese females visiting the Radio Isotope Center, Khartoum (RICK) and they were confirmed as breast cancer patient by histopathology. The levels of the above mentioned parameters were determined by using radioimmunoassay technique. The results showed that, no significant (p=0.05) difference between the levels of the estrogen in patients compared to the control, on the other hand there was non significant (p>0.05) elevation in CEA levels in the patients with breast cancer compared to the control. The level of CA15.3 was significantly (p<0.0001) higher in the breast cancer patients compared to the control.(Author)

  16. Release of carcinoembryonic antigen from human colon cancer cells by phosphatidylinositol-specific phospholipase C.

    OpenAIRE

    Sack, T L; Gum, J R; Low, M G; Y. S. Kim

    1988-01-01

    Carcinoembryonic antigen (CEA) is released from colon cancer cells into the circulation where it is monitored clinically as an indicator of the recurrence or progression of cancer. We have studied the mechanism of CEA membrane attachment and release using the human colonic adenocarcinoma cell line LS-174T, specimens of human colon cancers, and serum from colon cancer patients. CEA release by cells in vitro and in vivo is associated with the conversion of CEA from a membrane-bound, hydrophobic...

  17. Serum and pancreatic juice carcinoembryonic antigen in pancreatic and biliary disease.

    OpenAIRE

    Carr-Locke, D L

    1980-01-01

    Serum and pancreatic juice carcinoembryonic antigen (CEA) concentrations were studied in a group of 144 patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) with a variety of benign and malignant pancreatic and biliary diseases. Serum CEA was found to be a poor diagnostic and discriminating marker for pancreatic disorders and was raised in obstructive jaundice from various causes correlating with serum alkaline phosphatase. A pancreatic juice CEA concentration of greater ...

  18. Design and cancer-targeting potential of antibody-based molecules directed against carcinoembryonic antigen.

    OpenAIRE

    Huhalov, A.

    2004-01-01

    This thesis examines the use of protein engineering to create antibody-based molecules for cancer treatment. The targeting unit used for these molecules was the single chain Fv antibody fragment MFE-23, which is directed against the tumour-associated marker carcinoembryonic antigen (CEA). It was hypothesised that implementation of molecular design features such as humanisation, high affinity, multivalency and mannose glycosylation to accelerate systemic clearance would result in the favourabl...

  19. An Ultrasensitive Chemiluminescence Biosensor for Carcinoembryonic Antigen Based on Autocatalytic Enlargement of Immunogold Nanoprobes

    OpenAIRE

    2012-01-01

    A sensitive flow injection chemiluminescence assay for carcinoembryonic antigen (CEA) detection based on signal amplification with gold nanoparticles (NPs) is reported in the present work. The sandwich system of CEA/anti-CEA/goat-anti-mouse IgG functionalized Au nanoparticles was used as the sensing platform. In order to improve detection sensitivity, a further gold enlargement step was developed based on the autocatalytic Au deposition of gold nanoprobes via the reduction of AuCl4 − to Au0 o...

  20. Use of radiolabeled antibodies to carcinoembryonic antigen for the detection and localization of diverse cancers by external photoscanning

    International Nuclear Information System (INIS)

    To determine whether tumors containing carcinoembryonic antigen could be detected by administration of a radiolabeled, affinity-purified, goat IgG having 70% immunoreactivity against carcinoembryonic antigen, 18 patients with a history of cancer of diverse histopathology received an average total dose of 1.0 mCi of 131I-labeled IgG. Total-body photoscans were performed with a gamma scintillation camera at various intervals after administration of the radioactive antibody. Ordinary photoscans proved difficult to interpret because of blood-pool background radioactivity, thus necessitating the computer subtraction of radioactive blood-pool agents from the antibody's 131I activity. Tumor location could be demonstrated at 48 hours after injection in almost all cases studied. The scans were negative in patients without demonstrable tumors or with tumors apparently devoid of carcinoembryonic antigen. Circulating antigen levels of up to 350 ng per milliliter did not prevent successful tumor imaging after injection of the radioantibody

  1. Experimental radioimmunotherapy of a xenografted human colonic tumor (GW-39) producing carcinoembryonic antigen

    International Nuclear Information System (INIS)

    Experiments were undertaken to evaluate the antitumor effects of 131I-labeled goat antibody immunoglobulin G prepared against carcinoembryonic antigen in hamsters bearing the carcinoembryonic antigen-producing GW-39 human colonic carcinoma. At a single injection of 1 mCi 131I and higher, a marked growth inhibition of GW-39 tumors, as well as a considerable increase in the survival time of the tumor-bearing hamsters, could be achieved. At a dose of 1 mCi, the radioactive affinity-purified antibody appeared to be superior to radioactive normal goat immunoglobulin G in influencing tumor growth and survival time, but no significant difference could be seen at the higher dose of 2 mCi given. Radiobiological calculations indicated that the tumors received, at up to 20 days after therapy, 1325 rads for the specific antibody and only 411 rads for the normal immunoglobulin G preparation. These findings encourage the further evaluation of antibodies to tumor markers for isotopic cancer therapy

  2. 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;

    2011-01-01

    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...

  3. Development of a PMMA Electrochemical Microfluidic Device for Carcinoembryonic Antigen Detection

    Science.gov (United States)

    Van Anh, Nguyen; Van Trung, Hoang; Tien, Bui Quang; Binh, Nguyen Hai; Ha, Cao Hong; Le Huy, Nguyen; Loc, Nguyen Thai; Thu, Vu Thi; Lam, Tran Dai

    2016-05-01

    In this study, a poly(methyl methacrylate) (PMMA) microfluidic device fabricated by an inexpensive CO2 laser etching system was developed for detection of carcino-embryonic antigens (CEA). The device was capable of working in continuous mode and was designed with the aid of numerical simulation. The detection of target CEA was based on immuno-assay via magnetic particles and electrochemical sensing. The as-prepared microfluidic can be used to detect CEA at the relatively low concentration of 150 pg mL-1. The device could be reused many times, since the capture and removal of magnetic particles in the assay could be manipulated by an external magnetic field. The proposed approach appears to be suitable for high-throughput and automated analysis of large biomolecules such as tumor markers and pathogens.

  4. Development of solid phase immunoradiometric assay for determination of carcinoembryonic antigen as a tumor marker

    International Nuclear Information System (INIS)

    Development of solid phase coated tube immunoradiometric assay for estimation of carcinoembryonic antigen (CEA) was the aim of the present study. Labeling of CEA was carried out using Ch-T and iodogen as oxidizing agents and 125I. The tracers were used to test the presence of antibodies produced by immunization. Production of polyclonal antibody was carried out through immunization of four mice. After purification step, the tubes were coated by purified polyclonal antibodies. Immunoradiometric that system was performed using the commercial IZOTOP 125I-anti hCEA tracer then the validity studies were carried out. The results show that the local coated tubes made the assay is more than sufficient to fulfill the clinical requirement of CEA as a tumor marker. (author)

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

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    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.

  6.  Human carcinoembryonic antygen family proteins, structure and function

    Directory of Open Access Journals (Sweden)

    Hanna Czepczyńska-Krężel

    2012-07-01

    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.

  7. Kinetics of anti-carcinoembryonic antigen antibody internalization: effects of affinity, bivalency, and stability

    Science.gov (United States)

    Schmidt, Michael M.; Thurber, Greg M.

    2010-01-01

    Theoretical analyses suggest that the cellular internalization and catabolism of bound antibodies contribute significantly to poor penetration into tumors. Here we quantitatively assess the internalization of antibodies and antibody fragments against the commonly targeted antigen carcinoembryonic antigen (CEA). Although CEA is often referred to as a non-internalizing or shed antigen, anti-CEA antibodies and antibody fragments are shown to be slowly endocytosed by LS174T cells with a half-time of 10–16 h, a time scale consistent with the metabolic turnover rate of CEA in the absence of antibody. Anti-CEA single chain variable fragments (scFvs) with significant differences in affinity, stability against protease digestion, and valency exhibit similar uptake rates of bound antibody. In contrast, one anti-CEA IgG exhibits unique binding and trafficking properties with twice as many molecules bound per cell at saturation and significantly faster cellular internalization after binding. The internalization rates measured herein can be used in simple computational models to predict the microdistribution of these antibodies in tumor spheroids. PMID:18408925

  8. A prospective study of serum tumour markers carcinoembryonic antigen, carbohydrate antigens 50 and 242, tissue polypeptide antigen and tissue polypeptide specific antigen in the diagnosis of pancreatic cancer with special reference to multivariate diagnostic score.

    OpenAIRE

    Pasanen, P. A.; Eskelinen, M.; Partanen, K.; Pikkarainen, P; Penttilä, I.; Alhava, E

    1994-01-01

    The aim of this study was to assess by a stepwise multivariate discriminant analysis the value of four current serum tumour markers - carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 50 and CA 242 and tissue polypeptide antigen (TPA) - and a new serum tumour marker, tissue polypeptide specific antigen (TPS), in the diagnosis of pancreatic cancer. The serum values were measured in a prospective series of patients with jaundice, with unjaundiced cholestasis and with a suspicion of chro...

  9. CHARACTERIZATION OF MONOCLONAL ANTIBODY CL58 AGAINST CARCINOEMBRYONIC ANTIGEN (CEA) AND STUDY OF ITS BIODISTRIBUTION

    Institute of Scientific and Technical Information of China (English)

    李振甫; 杨志; 张宏; 顾晋

    2002-01-01

    Objective: To study the preparation and characterization of monoclonal antibody (McAb) against carcinoembryonic antigen (CEA). Methods: CEA antigen was extracted from metastasized liver of patients with colorectal cancer and used for the preparation of McAb against CEA by hybridoma technique. Immunoreactivity of McAb to CEA antigen was evaluated using ELISA. Mouse ascites was purified by two steps, high performance liquid chromatography (HPLC) using protein A and high performance hydroxylapatite (HPHT). Normal adult tissues and tumor specimen were used for immunohistochemical evaluation of the McAb. Isotope 99mTc labeled CEA McAb was used for biodistribution in tumor-bearing mouse. Results: Purified CEA antigen was a glycoprotein of 180 kD. Anti-CEA McAb affinity constant was 7.4x109/M. The McAb showed positive staining in 54-88% of colorectal cancer, gastric cancer and lung cancer, while negative for normal tissues. 24 hours after injection of 99mTc labeled McAb, tumor ID%/g was higher than 15% and tumor/blood, tumor/kidney and tumor/liver were 1.82, 1.51 and 2.92 respectively. T/NT ratios of other viscera were over 3.0. Conclusion: Purified CEA antigen had very good immunogenicity. The anti-CEA McAb was highly specific. 99mTc labeled McAb was stabled both in vivo and in vitro. In vivo distribution result was satisfactory. McAb CL58 may be useful for RII and RIGS.

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

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    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.

  11. [Optical Analysis of the Interaction of Mercaptan Derivatives of Nanogold Particles with Carcinoembryonic Antigen].

    Science.gov (United States)

    Zeng, Hong-juan; Zhao, Ran-lin; Wang, De-shun; Li, Cai-xia; Liu, Yi-yao

    2016-02-01

    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 laboratory 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 surrounding a dielectric core, such as silica (gold nanoshells). their size range from 0.8 to 250 nm and are characterized by high absorption coefficients. AuNPs have some unique optical properties, such as enhanced absorption and scattering, where the absorption cross-section of AuNPs is 4~5 orders of magnitude greater than that of rhodamine 6G. When AuNPs aggregate, interaction 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 nanoparticles 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 needs to

  12. Carcinoembryonic antigen is anchored to membranes by covalent attachment to a glycosylphosphatidylinositol moiety: identification of the ethanolamine linkage site.

    OpenAIRE

    Hefta, S A; Hefta, L J; Lee, T.D. (Taunia D.); Paxton, R J; Shively, J. E.

    1988-01-01

    The COOH-terminal amino acid of carcinoembryonic antigen (CEA) is shown to covalently link with ethanolamine, evidence consistent with the anchorage of CEA to the plasma membrane through a phosphatidylinositol-glycan tail. Purified CEA was digested with trypsin, and the resulting peptides were isolated by reverse-phase HPLC. Tryptic hexapeptide T12, terminating atypically with alanine, corresponded in sequence (Ser-Ile-Thr-Val-Ser-Ala) with the last six residues (637-642) of the third repeati...

  13. Mesothelioma: profile of keratin proteins and carcinoembryonic antigen: an immunoperoxidase study of 20 cases and comparison with pulmonary adenocarcinomas.

    OpenAIRE

    Corson, J M; Pinkus, G. S.

    1982-01-01

    The distribution of keratin proteins and carcinoembryonic antigen (CEA) in 20 diffuse pleural malignant mesotheliomas and 20 adenocarcinomas of the lung was determined with the use of an indirect immunoperoxidase method. Keratin proteins were identified in all of the mesotheliomas, with strong staining observed in 17 of the cases. Tumor cells of various histologic types (tubular, papillary, solid, and spindle) revealed staining for keratin proteins. A variety of staining patterns were observe...

  14. 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

    2012-01-01

    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.

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

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    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.

  16. Aptasensor based on tripetalous cadmium sulfide-graphene electrochemiluminescence for the detection of carcinoembryonic antigen.

    Science.gov (United States)

    Shi, Gui-Fang; Cao, Jun-Tao; Zhang, Jing-Jing; Huang, Ke-Jing; Liu, Yan-Ming; Chen, Yong-Hong; Ren, Shu-Wei

    2014-11-21

    A facile label-free electrochemiluminescence (ECL) aptasensor, based on the ECL of cadmium sulfide-graphene (CdS-GR) nanocomposites with peroxydisulfate as the coreactant, was designed for the detection of carcinoembryonic antigen (CEA). Tripetalous CdS-GR nanocomposites were synthesized through a simple onepot solvothermal method and immobilized on the glassy carbon electrode surface. L-Cystine (L-cys) could largely promote the electron transfer and enhance the ECL intensity. Gold nanoparticles (AuNPs) were assembled onto the L-cys film modified electrode for aptamer immobilization and ECL signal amplification. The aptamer modified with thiol was adsorbed onto the surface of the AuNPs through a Au-S bond. Upon hybridization of the aptamer with the target protein, the sequence could conjugate CEA to form a Y architecture. With CEA as a model analyte, the decreased ECL intensity is proportional to the CEA concentration in the range of 0.01-10.0 ng mL(-1) with a detection limit of 3.8 pg mL(-1) (S/N = 3). The prepared aptasensor was applied to the determination of CEA in human serum samples. The recoveries of CEA in the human serum samples were between 85.0% and 109.5%, and the RSD values were no more than 3.4%. PMID:25209409

  17. 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

    2006-01-01

    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.

  18. 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

    2005-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Nasar Yousuf ALWAHAIBI

    2011-01-01

    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.

  20. 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

    2011-01-01

    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.

  1. 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

    2011-01-01

    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.

  2. Elevated Level of Serum Carcinoembryonic Antigen (CEA) and Search for a Malignancy: A Case Report.

    Science.gov (United States)

    Asad-Ur-Rahman, Fnu; Saif, Muhammad W

    2016-01-01

    Carcinoembryonic antigen (CEA) has been shown to be associated with tumor burden in patients with colorectal cancer. However, it is also elevated to a significant degree in a number of other malignant and non-malignant conditions. We report a case of reversible CEA elevation in a patient using lithium for bipolar disorder. A 58-year-old female with a longstanding smoking history and a past medical history of chronic obstructive pulmonary disease (COPD), bipolar illness, hypothyroidism, and obesity was found to have an elevated CEA level of 11.2 ng/ml (normal level lung cancer; however, it did not reveal any evidence of malignancy. Upon review of her medications, she reported that she had recently started lithium for her bipolar illness. We followed up her CEA level while her dose of lithium was reduced from 450 to 300 mg per day. Her CEA level decreased from 25 mg/dl to 6.1 mg/dl and remained stable over the course of the next eight months. Our case is the first case report that identifies lithium as a potential cause of reversible CEA elevation. The underlying mechanism is yet to be elucidated, but it underscores the importance of investigating the medications as part of the workup. PMID:27446768

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

    Directory of Open Access Journals (Sweden)

    Xing Xiaofang

    2010-07-01

    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.

  4. Electrochemical immunosensor based on nanoporpus gold loading thionine for carcinoembryonic antigen.

    Science.gov (United States)

    Sun, Xiaobin; Ma, Zhanfang

    2013-05-30

    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.

  5. Tumor localization of radiolabeled antibodies against carcinoembryonic antigen in patients with carcinoma

    International Nuclear Information System (INIS)

    Purified, [131I]-labeled goat antibodies against carcinoembryonic antigen, which have been shown to localize in human carcinoma in nude mice, were injected into 27 patients with carcinoma. Patients were scanned with a scintillation camera at various intervals. In 11 patients, radioactivity was detectable in the tumor 48 h after injection. Computerized subtraction of blood-pool radioactivity provided clearer pictures in positive cases, but in 16 patients the scans remained doubtful or negative. To study the specificity of [131]-antibody localization, we gave some patients simultaneous injections of [125]-labeled normal IgG. Both isotopes were measured by means of scintillation counting in tumors and normal tissues recovered after surgery. The results demonstrated that only the anti-CEA antibodies localized in tumors. However, the total antibody-derived radioactivity in the tumor was only about 0.001 of the injected dose. We conclude that, despite the present demonstration of specificity, this method of tumor detection is not yet clinically useful

  6. An ultrasensitive chemiluminescence biosensor for carcinoembryonic antigen based on autocatalytic enlargement of immunogold nanoprobes.

    Science.gov (United States)

    Hao, Minjia; Ma, Zhanfang

    2012-01-01

    A sensitive flow injection chemiluminescence assay for carcinoembryonic antigen (CEA) detection based on signal amplification with gold nanoparticles (NPs) is reported in the present work. The sandwich system of CEA/anti-CEA/goat-anti-mouse IgG functionalized Au nanoparticles was used as the sensing platform. In order to improve detection sensitivity, a further gold enlargement step was developed based on the autocatalytic Au deposition of gold nanoprobes via the reduction of AuCl(4)- to Au0 on their surface in the presence of NH(2)OH·HCl. AuCl(4)-, which is a soluble product of gold nanoprobes, served as an analyte in the CL reaction for the indirect measurement of CEA. Under optimized conditions, the CL intensity of the system was linearly related to the logarithm of CEA concentration in the range of 100 pg∙mL-1 to 1,000 ng∙mL-1, with a detection limit of 20 pg∙mL-1. PMID:23443399

  7. An Ultrasensitive Chemiluminescence Biosensor for Carcinoembryonic Antigen Based on Autocatalytic Enlargement of Immunogold Nanoprobes

    Directory of Open Access Journals (Sweden)

    Minjia Hao

    2012-12-01

    Full Text Available A sensitive flow injection chemiluminescence assay for carcinoembryonic antigen (CEA detection based on signal amplification with gold nanoparticles (NPs is reported in the present work. The sandwich system of CEA/anti-CEA/goat-anti-mouse IgG functionalized Au nanoparticles was used as the sensing platform. In order to improve detection sensitivity, a further gold enlargement step was developed based on the autocatalytic Au deposition of gold nanoprobes via the reduction of AuCl4− to Au0 on their surface in the presence of NH2OH·HCl. AuCl4−, which is a soluble product of gold nanoprobes, served as an analyte in the CL reaction for the indirect measurement of CEA. Under optimized conditions, the CL intensity of the system was linearly related to the logarithm of CEA concentration in the range of 100 pg∙mL−1 to 1,000 ng∙mL−1, with a detection limit of 20 pg∙mL−1.

  8. Carcinoembryonic antigen promotes colorectal cancer progression by targeting adherens junction complexes

    Energy Technology Data Exchange (ETDEWEB)

    Bajenova, Olga, E-mail: o.bazhenova@spbu.ru [Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg 199034 (Russian Federation); Department of Genetics and Biotechnology, St. Petersburg State University, St. Petersburg 199034 (Russian Federation); Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178 (United States); Chaika, Nina [Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178 (United States); Tolkunova, Elena; Davydov-Sinitsyn, Alexander [Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064 (Russian Federation); Gapon, Svetlana [Boston Children' s Hospital, Boston, MA 02115 (United States); Thomas, Peter [Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178 (United States); O’Brien, Stephen [Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg 199034 (Russian Federation)

    2014-06-10

    Oncomarkers play important roles in the detection and management of human malignancies. Carcinoembryonic antigen (CEA, CEACAM5) and epithelial cadherin (E-cadherin) are considered as independent tumor markers in monitoring metastatic colorectal cancer. They are both expressed by cancer cells and can be detected in the blood serum. We investigated the effect of CEA production by MIP101 colorectal carcinoma cell lines on E-cadherin adherens junction (AJ) protein complexes. No direct interaction between E-cadherin and CEA was detected; however, the functional relationships between E-cadherin and its AJ partners: α-, β- and p120 catenins were impaired. We discovered a novel interaction between CEA and beta-catenin protein in the CEA producing cells. It is shown in the current study that CEA overexpression alters the splicing of p120 catenin and triggers the release of soluble E-cadherin. The influence of CEA production by colorectal cancer cells on the function of E-cadherin junction complexes may explain the link between the elevated levels of CEA and the increase in soluble E-cadherin during the progression of colorectal cancer. - Highlights: • Elevated level of CEA increases the release of soluble E-cadherin during the progression of colorectal cancer. • CEA over-expression alters the binding preferences between E-cadherin and its partners: α-, β- and p120 catenins in adherens junction complexes. • CEA produced by colorectal cancer cells interacts with beta-catenin protein. • CEA over-expression triggers the increase in nuclear beta-catenin. • CEA over-expression alters the splicing of p120 catenin protein.

  9. 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

    2003-01-01

    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.

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

    Science.gov (United States)

    Eftekhar, Ebrahim; Jaberie, Hajar; Naghibalhossaini, Fakhraddin

    2016-01-01

    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. PMID:27478804

  11. Evaluation of tumor markers carcinoembryonic antigen, cytokeratin 19 fragment and cancer-associated antigen 72-4 in neoplastic and non-neoplastic canine effusions differentiation

    OpenAIRE

    L.V Teixeira; T.A. Guerra; F.O. Conrado; S.R. Terra; D.G. Gerardi; González, F.H.D.

    2014-01-01

    The concentration of tumor markers in body fluids can be used for diagnosis and prognosis of patients. This study aimed to investigate the performance of tumor markers cytokeratin 19 fragment (CYFRA 21-1), cancer-associated antigen 72-4 (CA 72-4) and carcinoembryonic antigen (CEA) in the neoplastic and non-neoplastic canine effusions. In thirty-two neoplastic (n=16) and non-neoplastic (n=16) samples of canine thoracic or abdominal effusions, tumor markers were measured. Significant statistica...

  12. Independent prognostic value of preoperative serum markers CA 242, specific tissue polypeptide antigen and human chorionic gonadotrophin beta, but not of carcinoembryonic antigen or tissue polypeptide antigen in colorectal cancer.

    OpenAIRE

    Carpelan-Holmström, M; Haglund, C.; Lundin, J; Alfthan, H.; Stenman, U H; Roberts, P. J.

    1996-01-01

    The prognostic value of preoperative serum concentrations of carcinoembryonic antigen (CEA), CA 242, tissue polypeptide antigen (TPA), specific tissue polypeptide antigen (TPS) and human chorionic gonadotrophin beta (hCG beta) in 251 patients with colorectal cancer (39 Dukes' A, 98 Dukes' B, 56 Dukes' C and 58 Dukes' D) was investigated. When using the cut-off levels recommended for diagnostic purposes, there was a significantly longer overall survival in patients with low tumour marker level...

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

    Directory of Open Access Journals (Sweden)

    Ning Gan

    2011-10-01

    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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  15. Intensified follow-up in colorectal cancer patients using frequent Carcino-Embryonic Antigen (CEA) measurements and CEA-triggered imaging : Results of the randomized "CEAwatch" trial

    NARCIS (Netherlands)

    Verberne, C. J.; Zhan, Z.; van den Heuvel, E.; Grossmann, I.; Doornbos, P. M.; Havenga, K.; Manusama, E.; Klaase, J.; van der Mijle, H. C. J.; Lamme, B.; Bosscha, K.; Baas, P.; van Ooijen, B.; Nieuwenhuijzen, G.; Marinelli, A.; van der Zaag, E.; Wasowicz, D.; de Bock, G. H.; Wiggers, T.

    2015-01-01

    Aim: The value of frequent Carcino-Embryonic Antigen (CEA) measurements and CEA-triggered imaging for detecting recurrent disease in colorectal cancer (CRC) patients was investigated in search for an evidence-based follow-up protocol. Methods: This is a randomized-controlled multicenter prospective

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

    Directory of Open Access Journals (Sweden)

    Rancés Blanco

    2013-01-01

    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.

  17. 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

    2016-05-01

    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

  18. A network signal amplification strategy of ultrasensitive photoelectrochemical immunosensing carcinoembryonic antigen based on CdSe/melamine network as label.

    Science.gov (United States)

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

    2016-11-15

    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. PMID:27281106

  19. Ultrasensitive non-enzymatic immunosensor for carcino-embryonic antigen based on palladium hybrid vanadium pentoxide/multiwalled carbon nanotubes.

    Science.gov (United States)

    Han, Jian; Jiang, Liping; Li, Faying; Wang, Ping; Liu, Qing; Dong, Yunhui; Li, Yueyun; Wei, Qin

    2016-03-15

    A novel and sensitive sandwich-type non-enzymatic electrochemical immunosensor was fabricated for quantitative monitoring of carcino-embryonic antigen (CEA). Nanocomposite of stannic oxide/reduced graphene oxide was used as substrate material to increase the specific surface area and enhance the conductivity of the glassy carbon electrode. Gold nanoparticles (Au NPs) were introduced to link substrate materials and primary antibodies (Ab1) and accelerate the electron transfer in this system. At the same time, the palladium nanoparticles (Pd NPs)-vanadium pentoxide (V2O5)/multiwalled carbon nanotubes (MWCNTs) were used as the label of secondary antibodies (Ab2). This composite label has shown excellent catalytic activity towards the reduction of H2O2. The nanomaterial-based signal amplification can improve the sensitivity and lower the limit of detection. The proposed immunosensor showed wide linear range from 0.5 pgmL(-1) to 25 ngmL(-1) with limit of detection of 0.17 pgmL(-1). This novel immunosensor was used to analyze serum sample. The results indicated that this immunosensor may find huge potential application for quantitative detection of CEA in the clinical diagnosis. PMID:26562331

  20. Adenovirus tumor targeting and hepatic untargeting by a coxsackie/adenovirus receptor ectodomain anti-carcinoembryonic antigen bispecific adapter.

    Science.gov (United States)

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

    2007-06-01

    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.

  1. Comparison between tissue and serum content of CA 125, CA 19-9, and carcinoembryonic antigen in ovarian tumors.

    Science.gov (United States)

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

    1989-01-01

    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.

  2. 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

    2006-01-01

    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.

  3. Regulation by gut commensal bacteria of carcinoembryonic antigen-related cell adhesion molecule expression in the intestinal epithelium.

    Science.gov (United States)

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

    2015-07-01

    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. PMID:25908210

  4. Immune-scintigraphy of recurrent colorectal tumors with Tc-99m-marked monoclonal carcinoembryonic antigen antibodies

    International Nuclear Information System (INIS)

    After surgery in 24 patients aged 39-80 years with colorectal tumors, immune-scintigraphic examinations with Tc-99m carcinoembryonic antigen (CEA) MAb were carried out. Prior to scintigraphy, the levels of CEA and Ca 19-9 tumor markers were determined. In the majority of cases there was firm clinical evidence of local recurrence or metastases. Twenty-two of the 24 cases were scintigraphically positive. Local recurrence and metastases of the liver were correctly identified in 12 and four cases, respectively. It was difficult to detect widespread metastases of the peritoneum or a growth at the helum of the lung. In three cases, metastases of lymph nodes were confirmed by both surgery and scintigraphy, although the computed tomographic (CT) examinations were negative. In 20 patients, CT and immune-scintigraphic findings correlated. Most positive scans were confirmed surgically and at biopsy. In two patients, none of the diagnostic procedures showed positive results, despite clinical grounds for suspecting a further spread of the disease. A false-positive immune-scintigram was observed in a histologically confirmed case of inflammation of the mucous membrane. In several cases Tc-99m enhancement was detected in almost all parts of the colon. This could be due to the antibody metabolism or to the deposit of free technetium in the bowel. There was no correlation between CEA serum levels and a positive immune-scan

  5. D-Dimer and Carcinoembryonic Antigen Levels: Useful Indicators for Predicting the Tumor Stage and Postoperative Survival.

    Science.gov (United States)

    Tekeşin, Kemal; Bayrak, Savaş; Esatoğlu, Varol; Özdemir, Ebru; Özel, Leyla; Melih Kara, Veli

    2016-01-01

    The purpose of this prospective study is to determine the preoperative plasma D-dimer and serum Carcinoembryonic Antigen (CEA) levels of patients scheduled for curative surgical resection for colorectal cancer and to evaluate the significance of these levels on the prognosis and postoperative survival rate. One hundred sixty-five patients with colorectal cancer, who were scheduled to have elective resection between January 2008 and January 2011, were included in the study. A significant increase was observed in the D-dimer levels, particularly in poorly differentiated tumors. The distance covered by the tumor inside the walls of the colon and rectum (T-stage) was significant for both D-dimer and CEA levels. As the T-stage increased, there was also a significant increase in the D-dimer and CEA levels. A high significance and correlation level was detected between the TNM staging and both D-dimer and CEA. A significant relationship was found between the advanced tumor stage and short postoperative survival rate of patients with colorectal cancer. Therefore, the analysis of preoperative D-dimer and CEA levels can be useful in predicting the stage and differentiation of the tumor and the postoperative survival rate. PMID:27651789

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Localization of 131Ilabeled goat and primate anti-carcinoembryonic antigen(CEA) antibodies in patients with cancer

    International Nuclear Information System (INIS)

    Thirty patients with anti-carcinoembryonic antigen (CEA)-producing cancers of the colon, breast, or thyroid were intected with 1 to 2 mCi of Iodine-131 (131I)-labeled, affinity-purified, goat or baboon anti-CEA antibodies. Images were obtained daily for four days. Computerized background subtraction using technetium 99m (99mTC)-labeled compounds was used. Images obtained with and without background subtraction were correlated with other evidence of disease. Activity levels in plasma, urine, and thyroid gland were monitored. Significant deiodination of antibody occurred within the first 24 hours. The mean plasma half-disappearance-time of baboon antibody was significantly longer than the mean half-disappearance-time of goat antibody. With exogenous blockade, total thyroid uptake was less than 0.1% of the injected dose. Without background subtraction, scintigraphic localization of known tumor was possible in one of two patients with colon carcinoma, in three of 20 patients with breast cancer, and in one of five patients with medullary carcinoma of the thyroid. With background subtraction, potential false-positive results could be generated for every patients, depending on the normalization site chosen and the degree of subtraction used. In contrast to results of previous reports, CEA-producing tumor was found to be infrequently localized using highly purified goat or primate radiolabeled anti-CEA. Furthermore, the subtraction technique described by previous investigators may lead to a high false-positive rate

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

    Science.gov (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

    2000-03-01

    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.

  9. Utility of endoscopic ultrasound, cytology and fluid carcinoembryonic antigen and CA 19-9 levels in pancreatic cystic lesions

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To assess the diagnostic accuracy of endoscopic ultrasound (EUS), fluid tumor markers and cytology in distinguishing benign from (pre)malignant pancreatic cystic lesions.METHODS: 46 consecutive patients, referred to a gastroenterologist and surgeon for a symptomatic or incidental pancreatic cyst, were reviewed. EUS, cytology,and carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) levels were compared with the final diagnosis, based on surgical pathology and/or imaging follow-up of at least 12 mo. Cysts were classified as benign (pseudocyst, serous cystadenoma) or malignant/pre-malignant (mucinous cystic neoplasm). Receiveroperator characteristics (ROC) curve analysis was performed.RESULTS: The mean age was 56 years; 29% were male and median cyst diameter was 3 cm. Final outcome was obtained in 41 (89%) patients. Twenty-three (56%) of these 41 had surgical pathology. Twenty-three (56%)had benign lesions and 18 (44%) had malignant/premalignant lesions. Sensitivity, specificity and positive and negative predictive value of EUS alone to distinguish benign from malignant/premalignant pancreatic cystic lesions were 50%, 56%, 36% and 54% and for cytology were 71%, 96%, 92% and 85%, respectively. The corresponding values for the ROC-derived ideal cutoffs were 75%, 90%, 75%, 90% for CA 19-9 (> 37 U/mL)and 70%, 85%, 79% and 78% for CEA (> 3.1 ng/mL).Subgroup analysis of those with surgical pathology yielded almost identical performance and cutoffs.CONCLUSION: Cytology and cyst fluid tumor marker analysis is a very useful tool in distinguishing benign from (pre)malignant pancreatic cystic lesions.

  10. 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

    Directory of Open Access Journals (Sweden)

    Bhawna Bagaria

    2015-01-01

    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.

  11. Evaluation of tumor markers carcinoembryonic antigen, cytokeratin 19 fragment and cancer-associated antigen 72-4 in neoplastic and non-neoplastic canine effusions differentiation

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    L.V. Teixeira

    2014-10-01

    Full Text Available The concentration of tumor markers in body fluids can be used for diagnosis and prognosis of patients. This study aimed to investigate the performance of tumor markers cytokeratin 19 fragment (CYFRA 21-1, cancer-associated antigen 72-4 (CA 72-4 and carcinoembryonic antigen (CEA in the neoplastic and non-neoplastic canine effusions. In thirty-two neoplastic (n=16 and non-neoplastic (n=16 samples of canine thoracic or abdominal effusions, tumor markers were measured. Significant statistical difference was found only for the CYFRA 21-1 marker. The levels were significantly higher for the neoplastic group. The lack of significance between groups for markers CA 72-4 and CEA can be explained by the presence of other diseases in the non-neoplastic group, causing elevated levels of these markers. This study concludes that CYFRA 21-1 performed well, showing good sensitivity, specificity and accuracy in the diagnosis of neoplastic effusions in dogs. However, further investigations are necessary in patients with malignancy as those with benign effusions.

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

    Science.gov (United States)

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

    2016-04-01

    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.

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

    Science.gov (United States)

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

    2016-01-01

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

  14. Murine carcinoma expressing carcinoembryonic antigen-like protein is restricted by antibody against neem leaf glycoprotein.

    Science.gov (United States)

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

    2014-11-01

    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.

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

    Science.gov (United States)

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

    2012-04-01

    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.

  16. Measurement of serum carcinoembryonic antigen, carbohydrate antigen 19-9, cytokeratin-19 fragment and matrix metalloproteinase-7 for detecting cholangiocarcinoma: a preliminary case-control study.

    Science.gov (United States)

    Lumachi, Franco; Lo Re, Giovanni; Tozzoli, Renato; D'Aurizio, Federica; Facomer, Flavio; Chiara, Giordano B; Basso, Stefano M M

    2014-11-01

    Cholangiocarcinoma is a malignant tumor of the liver arising from the bile duct epithelium, accounting for 10-25% of all primary hepatic cancers. The clinical presentation of this tumor is not specific and the diagnosis of early cholangiocarcinoma is difficult, especially in patients with other biliary diseases. Measurement of serum carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) are commonly used to monitor response to therapy, but are also useful for confirming the presence of a cholangiocarcinoma. In this setting, other biomarkers have been previously tested, including cytokeratin-19 fragment (CYFRA 21-1) and the matrix metalloproteinase-7 (MMP7). The purpose of this retrospective study was to determine the clinical usefulness of the assay of serum CEA, CA 19-9, CYFRA 21-1 and MMP7, individually and together, as tumor markers for the diagnosis of cholangiocarcinoma. Twenty-four patients (14 men, 10 women, 62.6±8.2 years of age) with histologically-confirmed cholangiocarcinoma (cases) and 25 age- and sex-matched patients with benign liver disease (controls) underwent measurement of these biomarkers. The mean values of all serum markers of patients with cholangiocarcinoma were significantly higher (pCYFRA 21-1: 76%, 79% and 78%; MMP7: 78%, 77% and 80%, respectively. The combination of all serum markers afforded 92.0% sensitivity and 96% specificity in detecting cholangiocarcinoma, showing the highest diagnostic accuracy (94%). In conclusion, our preliminary results suggest that the measurement of all four biomarkers together can help in the early detection of cholangiocarcinoma. PMID:25368272

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

    Directory of Open Access Journals (Sweden)

    Lee HC

    2013-06-01

    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

  18. Carcinoembryonic antigen (CEA) level, CEA ratio, and treatment outcome of rectal cancer patients receiving pre-operative chemoradiation and surgery

    International Nuclear Information System (INIS)

    To investigate serum carcinoembryonic antigen (CEA) as a prognostic factor for rectal cancer patients receiving pre-operative chemoradiotherapy (CRT). Between 2000 and 2009, 138 patients with advanced rectal cancer receiving CRT before surgery at our hospital were retrospectively classified into 3 groups: pre-CRT CEA <6 ng/ml (group L; n = 87); pre-CRT CEA ≥ 6 ng/ml and post-CRT CEA <6 ng/ml (group H-L; n = 32); and both pre- and post-CRT CEA ≥ 6 ng/ml (group H-H; n = 19). CEA ratio (defined as post-CRT CEA divided by pre-CRT CEA), post-CRT CEA level and other factors were reviewed for prediction of pathologic complete response (pCR). Five-year disease-free survival (DFS) was better in groups L (69.0%) and H-L (74.5%) than in group H-H (44.9%) (p = 0.024). Pathologic complete response was observed in 19.5%, 21.9% and 5.3% of groups L, H-L and H-H respectively (p = 0.281). Multivariate analysis showed that ypN stage and pCR were independent prognostic factors for DFS and that post-CRT CEA level was independently predictive of pCR. As a whole, post-CRT CEA <2.61 ng/ml predicted pCR (sensitivity 76.0%; specificity 58.4%). For those with pre-CRT CEA ≥6 ng/ml, post-CRT CEA and CEA ratio both predicted pCR (sensitivity 87.5%, specificity 76.7%). In patients with pre-CRT serum CEA ≥6 ng/ml, those with “normalized” CEA levels after CRT may have similar DFS to those with “normal” (<6 ng/ml) pre-CRT values. Post-CRT CEA level is a predictor for pCR, especially in those with pre-CRT CEA ≥6 ng/ml

  19. Sorafenib Decreases Tumor Exposure to an Anti-carcinoembryonic Antigen Monoclonal Antibody in a Mouse Model of Colorectal Cancer.

    Science.gov (United States)

    Thomas, Veena A; Balthasar, Joseph P

    2016-07-01

    In this investigation, we test the hypothesis that treatment with sorafenib, an anti-angiogenic agent, decreases tumor vascularization and, consequently, hinders the delivery of monoclonal antibodies (mAb) to xenograft tumors. Severe combined immunodeficiency mice bearing carcinoembryonic antigen (CEA) expressing tumor xenografts were divided into control and sorafenib-treated groups. Sorafenib was administered to the latter group at 50 mg/kg IP every 48 h, starting 4 days post-tumor implantation. When tumors attained a size of 200-300 mm(3), mice were evaluated for (a) tumor microvessel density (using immunohistochemical analysis), (b) tumor macromolecular extravasation (using Evans Blue Dye (EBD)), (c) pharmacokinetics of an anti-CEA mAb, T84.66, following an intravenous dose of 10 mg/kg, and (d) intra-tumoral spatial distribution of T84.66 (using autoradiography). Sorafenib treatment resulted in a substantial reduction in tumor growth rate, a visible reduction in tumor microvessel density, and in a 46.4% decrease in EBD extravasation in tumor tissue (p area under the mAb plasma concentration-time curve (AUC(0-7d): 1.67 × 10(3) ± 1.28 × 10(2) vs. 1.76 × 10(3) ± 1.75 × 10(2) nM × day, p = 0.51). However, tumor AUC(0-7d) was reduced by 40.8% in sorafenib-treated mice relative to that observed in control mice (5.61 × 10(2) ± 4.27 × 10(1) vs. 9.48 × 10(2) ± 5.61 × 10(1) nM × day, p < 0.001). Sorafenib therapy was also found to markedly alter mAb tumor spatial distribution. The results collectively suggest that sorafenib treatment causes a significant reduction in mAb delivery to, and distribution within, solid tumors. PMID:27029796

  20. Second antibody clearance of /sup 131/I-labeled anti-carcinoembryonic antigen for improved tumor imaging

    International Nuclear Information System (INIS)

    The authors have investigated the use of a second antibody (SA) directed against the radiolabeled primary anti-tumor antibody (PA) to enhance the clearance rate of the PA from the circulation and nontarget tissues. Administration of 50 or 250 μg of anti-goat IgG (SA) hr after the administration of 10 μg of /sup 131/I-goat anti-carcinoembryonic antigen antibody (PA) to hamsters bearing human colonic tumor xenografts resulted in a 5-fold reduction in the level of circulating PA after 4 hr in comparison to the control group only given /sup 131/I-PA. The percentage of PA in the blood decreased rapidly over 72 hr in animals given 250 μg of the SA, but at 50 μg of SA the level of activity in the blood after 24 hr was similar to the control. Tumor accretion was identical after 4 hr, but after 24 hr the animals given 250 μg of SA had 2-3 fold less PA in the tumor than either the control group or the 50 μg dose of SA. Tumor/nontumor ratios for all major organs but the spleen improved 6-8 fold within 48 hr after injection of 250 μg of the SA with tumor/blood ratios as high as 40:1. A SA dose of 50 μg resulted in a significantly higher tumor/blood ratio after only 4 hr; tumor/nontumor ratios at later times were similar to the control group. Tumors located in the hind legs were visible in all groups by imaging 24 hr after injection of the SA, but only the 250 μg dose of SA showed a significant reduction in total body activity. These results suggest that the SA approach may be used to reduce the total background radioactivity while maintaining tumor accretion of /sup 131/I-PA to allow for selective tumor imaging

  1. CEA (Carcinoembryonic Antigen) Test

    Science.gov (United States)

    ... may also be used as a marker for medullary thyroid cancer and cancers of the rectum, lung , ... ulcerative colitis , rectal polyps , emphysema , and benign breast disease. ^ Back to top Proudly sponsored by ... Learn more ...

  2. Utility of squamous cell carcinoma antigen, carcinoembryonic antigen, Cyfra 21-1 and neuron specific enolase in lung cancer diagnosis: a prospective study from China

    Institute of Scientific and Technical Information of China (English)

    SONG Wei-an; LIU Xi; TIAN Xiao-dong; WANG Wei; LIANG Chao-yang; ZHANG Tao; GUO Jun-tang; PENG Yang-hong; ZHOU Nai-kang

    2011-01-01

    Background Early detection and diagnosis is urgent for the sake of effective treatment strategy for lung cancer.However,a convenient,economical and relatively precise method is not available.We here report a prospective study to find the possible value of the combined use of four popular tumor markers in the early diagnosis of lung cancer among patients with suspicious nodules in the lung.Methods Six hundred and sixty inpatients with suspicious nodules in the lung were divided into a lung cancer group and a benign pulmonary tumor group according to post-operative histological examinations.Serum levels of four tumor markers including squamous cell carcinoma antigen (SCC),carcinoembryonic antigen (CEA),Cyfra 21-1 and neuron specific enolase (NSE) were assayed for each patient.Receiver operating characteristic (ROC) curves were constructed for each tumor marker.The power of lung cancer diagnosis of each tumor marker,as well as a combination of them were analyzed and compared.Results The serum levels (median,range) of SCC,CEA,Cyfra 21-1 and NSE were 0.44 (0.01-35.70) ng/ml,2.49(0.30-26.78) ng/ml,2.30 (0.82-73.33) ng/ml and 10.54 (0.10-56.41) ng/ml respectively in lung cancer group,and were 0.32 (0.01-0.90) ng/ml,1.60 (0.20-8.93) ng/ml,1.41 (0.72-4.82) ng/ml and 9.36 (6.56-24.24) ng/ml respectively in the benign pulmonary tumor group.The difference in each tumor marker between the two groups was significant (P <0.05).The ROCs of SCC,CEA,Cyfra 21-1 and NSE were 0.702 (95% CI,0.654-0.751),0.611 (95% CI,0.563-0.659),0.650(95% CI,0.601-0.700) and 0.598 (95% CI,0.542-0.654) respectively,indicating very low power of these four tumor markers.When a combination of SCC,CEA,Cyfra 21-1 and NSE were employed,the diagnosis power was strengthened.Conclusion SCC,CEA,Cyfra 21-1 and NSE are valuable in the early diagnosis of lung cancer among suspicious nodules in the lung,especially when they were assayed together for one patient.

  3. 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

    2008-01-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-04-15

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

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

    International Nuclear Information System (INIS)

    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.)

  6. 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

    2007-01-01

    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.

  7. Poly(o-phenylenediamine) nanosphere-conjugated capture antibody immobilized on a glassy carbon electrode for electrochemical immunoassay of carcinoembryonic antigen

    International Nuclear Information System (INIS)

    We report on a new electrochemical immunosensor for the carcinoembryonic antigen (CEA; a model analyte). First, poly(o-phenylenediamine) nanospheres (PPDNSs) were synthesized by using a wet-chemistry method. The nanospheres were utilized as the support for immobilizing horseradish peroxidase-labeled polyclonal rabbit anti-human CEA antibody (HRP-anti-CEA) on a pretreated glassy carbon electrode (GCE) using glutaraldehyde as a crosslinker. In the presence of target CEA, an antigen-antibody immunocomplex formed on the electrode. This results in a partial inhibition of the active center of HRP and decreases the activity of HRP in terms of H2O2 reduction. The performance and factors influencing the performance of the immunoelectrode were studied. Under optimal conditions, the reduction current obtained from the anti-CEA-conjugated HRP (best at a working voltage of −265 mV vs. Ag/AgCl) is proportional to the CEA concentration in the 0.01 to 60 ng mL−1 range, with a detection limit of 3.2 pg mL−1. Non-specific adsorption was not observed. Relative standard deviations for intra-assay and inter-assay are <8.3 % and <9.7 %, respectively. The method was applied to the analysis of nine human serum samples, and a good relationship was found between the electrochemical immunoassay and the commercialized ELISA kit for human CEA. (author)

  8. 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)

    2007-01-01

    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.

  9. 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

    2016-06-01

    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

  10. Comparing Prothrombin induced by vitamin K absence-II (PIVKA-II) with the oncofetal proteins Glypican-3, Alpha feto protein and Carcinoembryonic antigen in diagnosing hepatocellular carcinoma among Egyptian patients

    OpenAIRE

    Iman A. Abd El Gawad; Mossallam, Ghada I.; Noha H. Radwan; Elzawahry, Heba M; Niveen M. Elhifnawy

    2014-01-01

    Background: Hepatocellular carcinoma (HCC) is usually asymptomatic in the early stage and does not show elevated alpha-feto protein (AFP). AFP shows 60–80% sensitivity in diagnosing HCC. Glypican3 (GPC-3) is an oncofetal protein that is only detected in HCC cells but not in benign liver tissues, while Carcinoembryonic antigen (CEA) is expressed in various neoplasms including HCC. Although, it is not specific for HCC. Prothrombin induced by vitamin K absence-II (PIVKA-II) is an abnormal ...

  11. Immunohistochemical expression of carcinoembryonic antigen-related cell adhesion molecules 5, CEACAM6, and SLC7A5: Do they aid in predicting the response to neo-adjuvant chemotherapy in locally advanced breast cancer?

    OpenAIRE

    Anju Bansal; Mukesh Garg; Chintamani Chintamani; Sunita Saxena

    2014-01-01

    Context: Neo-adjuvant chemotherapy (NACT) has become an integral part of multimodality treatment for locally advanced breast cancer (LABC) worldwide. Predictors of therapeutic response to NACT are lacking. Whether carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) like CEACAM5 and CEACAM6 can act as a predictor of response to therapy is unclear. SLC7A5 gene in humans encodes a large neutral amino acid transporter protein, which has an essential role in tumor cell growth and su...

  12. Label-Free Electrochemiluminescent Immunosensor for Detection of Carcinoembryonic Antigen Based on Nanocomposites of GO/MWCNTs-COOH/Au@CeO₂.

    Science.gov (United States)

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

    2015-09-01

    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.

  13. 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

    Science.gov (United States)

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

    2013-12-01

    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.

  14. 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.

    1983-10-01

    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 ..mu..g 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.

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

    Science.gov (United States)

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

    1983-10-01

    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.

  16. Au-F127 strawberry-like nanospheres as an electrochemical interface for sensitive detection of carcinoembryonic antigen in real sample.

    Science.gov (United States)

    Li, Juan; Xie, Hangqing; Liu, Yuhong; Ren, Hang; Zhao, Wenbo; Huang, Xiaohua

    2015-11-01

    Nanomaterial-based signal-amplification strategies hold a great promise in realizing sensitive biological detection. A simple label-free electrochemical immunosensor for sensitive detection of carcinoembryonic antigen (CEA) was developed by immobilizing anti-CEA antibodies onto the Au-F127 strawberry-like nanospheres modified glassy carbon electrode (Au-F127/GCE). The Au-F127 strawberry-like nanospheres offered a large surface and multifunctional substrate for the effective immobilization of anti-CEA and the existence of Au could accelerate electron transfer and make the electrochemical signal amplified. The Au-F127 nanocomposites and anti-CEA were characterized by transmission electron microscopy (TEM), polycrystalline electron diffraction ring pattern, ultra-violet visible (UV-vis) spectra and attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectra. Electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) were employed to verify the stepwise assembly of the immunosensor and evaluated the analytical performance of the fabricated immunosensor, respectively. The immunosensor showed a wide liner response range between 0.01 and 80 ng mL(-1) with a low detection limit of 0.24 pg mL(-1) at a signal-to-noise (S/N) ratio of 3. Additionally, the proposed method was successfully applied to determine CEA in human serum samples with satisfactory results. PMID:26452840

  17. Label-Free Electrochemiluminescent Immunosensor for Detection of Carcinoembryonic Antigen Based on Nanocomposites of GO/MWCNTs-COOH/Au@CeO₂.

    Science.gov (United States)

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

    2015-09-01

    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. PMID:26271682

  18. 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

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    De Vecchis Liana

    2008-05-01

    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.

  19. 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

    2016-07-01

    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.

  20. Major Protein of Carcinoembryonic Antigen Gene Family - CD66c, A Novel Marker in Colon Carcinoma

    Science.gov (United States)

    Nataraj, Suma M; Prema, Chaitra Linganna; Vimalambike, Manjunath Gubbanna; Shivalingaiah, Sheeladevi Chandakavadi; Sundaram, Shivakumar; Kumar, Anjali Pradeep; Math, Ananda Kuruvatti

    2016-01-01

    Introduction In view of rising trend of the incidence of colorectal carcinoma in the Indian population due to adoption of western lifestyles and behaviours, we investigated the expression of the new emerging stem cell biomarker, CD66c in colorectal carcinoma of Indian origin. Aim To study the expression of CD66c in human colorectal carcinoma and to correlate level of marker expression with tumour staging. Materials and Methods This hospital based prospective study was conducted on 26 colorectal carcinoma patients in the age group of 20 years to 70 years. Surgically resected tumour specimens along with adjacent normal tissue were collected taking necessary precautions, paraffin embedded sections were prepared and used for histological and immunohistochemical analysis of CD66c. Statistical analysis Descriptive statistical measures like mean, standard deviation, percentage was applied. Other inferential statistical tests like Chi-square, Fisher’s-exact test and one-way ANOVA was applied to find out the association of CD66c with different stages. The difference were interpreted as statistically significant when p <0.05. Results CD66c showed differential expression with membrane positivity in normal colorectal epithelial cells and cytoplasmic expression in tumour cells. There was significant correlation between CD66c expression and tumour site (p=0.02) with colon carcinoma showing positive expression compared to the rectal carcinoma. There was no significant correlation between CD66c staining and tumour stage (p=0.947). No significant relationship was observed between CD66c expression and other clinicopathologic variables studied such as sex (p=0.552), age (p=0.713) and tumour grade (p=0.263). Conclusion CD66c can be specifically used for colon carcinoma and may be a novel marker in colon carcinoma stem cell isolation. The quantification of CD66c can be further verified by flow cytometry and RT-PCR. Further studies can be carried out using CD66c alone or in combination with other markers to develop cancer stem cell directed therapy. PMID:27042567

  1. 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: binhu@whu.edu.cn

    2015-04-01

    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.

  2. Photoelectrochemical Immunosensor for Detection of Carcinoembryonic Antigen Based on 2D TiO2 Nanosheets and Carboxylated Graphitic Carbon Nitride.

    Science.gov (United States)

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

    2016-06-06

    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.

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

    International Nuclear Information System (INIS)

    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−1 and 0.054 μg L−1 with the relative standard deviations (RSDs, n = 7, c = 5 μg L−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−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

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

    Science.gov (United States)

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

    2016-09-15

    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. PMID:27111123

  5. Expression of human carcinoembryonic antigen-related cell adhesion molecule 6 and alveolar progenitor cells in normal and injured lungs of transgenic mice.

    Science.gov (United States)

    Lin, Shin-E; Barrette, Anne Marie; Chapin, Cheryl; Gonzales, Linda W; Gonzalez, Robert F; Dobbs, Leland G; Ballard, Philip L

    2015-12-01

    Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is expressed in the epithelium of various primate tissues, including lung airway and alveoli. In human lung, CEACAM6 is developmentally and hormonally regulated, protects surfactant function, has anti-apoptotic activity and is dysregulated in cancers. We hypothesized that alveolar CEACAM6 expression increases in lung injury and promotes cell proliferation during repair. Studies were performed in CEABAC transgenic mice-containing human CEACAM genes. The level of CEACAM6 in adult CEABAC lung was comparable to that in human infants; expression occurred in epithelium of airways and of some alveoli but rarely co-localized with markers of type I or type II cells. Ten days after bleomycin instillation, both the number of CEACAM6(+) cells and immunostaining intensity were elevated in injured lung areas, and there was increased co-localization with type I and II cell markers. To specifically address type II cells, we crossed CEABAC mice with animals expressing EGFP driven by the SP-C promoter. After bleomycin injury, partially flattened, elongated epithelial cells were observed that expressed type I cell markers and were primarily either EGFP(+) or CEACAM6(+). In cell cycle studies, mitosis was greater in CEACAM6(+) non-type II cells versus CEACAM6(+)/EGFP(+) cells. CEACAM6 epithelial expression was also increased after hyperoxic exposure and LPS instillation, suggesting a generalized response to acute lung injuries. We conclude that CEACAM6 expression is comparable in human lung and the CEABAC mouse. CEACAM6 in this model appears to be a marker of a progenitor cell population that contributes to alveolar epithelial cell replenishment after lung injury. PMID:26702074

  6. Comparison Study of Cyfra 21-1, Carcinoembryonic Antigen and Telomerase Activity between Non Small Cell and Small Cell Lung Cancer Patients

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    B. Alani

    2008-10-01

    Full Text Available Introduction & Objective: The roles of tumor markers in the prognosis and diagnosis of lung cancer is under investigation. The aim of this study was to examine correlation between serum levels of Carcinoembryonic Antigen (CEA and Cyfra 21-1 with telomerase activity on biopsy samples in patients with lung cancer and controls.Materials & Methods: We studied 50 malignant lung cancer patients (mean age 68.3±13.8 years and 20 normal individuals (mean age 64.9±11.4 years. Serum levels of Cyfra21-1 and CEA were measured with available enzyme immunoassay kits. Telomerase activity was measured by TRAP assay based on PCR-ELISA in lung tumor biopsy. To compare quantitative means of the two groups, t-independent and Man-Whitney analysis were applied.Results: The mean serum levels of CEA and Cyfra21-1 concentration together telomerase activity of biopsy samples in lung cancer patients were significantly higher than controls. There were a strong correlation between Cyfra21-1 and CEA, Telomerase and CEA and Telomerase and Cyfra21-1 in patient group. In patients with small cell carcinoma, the mean serum levels of Cyfra21-1 and CEA were significantly higher than non small cell carcinoma patients. Telomerase activities in biopsy samples of small cell carcinoma were significantly lower than non small cell carcinoma patients.Conclusion: It is speculated that based on this findings, telomerase activity in biopsy samples for small cell carcinoma patients and serum levels of Cyfra 21-1 and CEA are the most useful tumor markers for diagnosis of squamous and adenocarcinoma of non small cell cancers respectively.

  7. 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: plasma@dankook.ac.kr [Department of Chemistry, NSBI, Dankook University, 126 Jukjeon-dong, Suji-gu, Yongin-si, Gyeonggi-do 448-701 (Korea, Republic of)

    2014-10-17

    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.

  8. Label-free electrochemical immunosensor for the carcinoembryonic antigen using a glassy carbon electrode modified with electrodeposited Prussian Blue, a graphene and carbon nanotube assembly and an antibody immobilized on gold nanoparticles

    International Nuclear Information System (INIS)

    We described a sensitive, label-free electrochemical immunosensor for the detection of carcinoembryonic antigen. It is based on the use of a glassy carbon electrode (GCE) modified with a multi-layer films made from Prussian Blue (PB), graphene and carbon nanotubes by electrodeposition and assembling techniques. Gold nanoparticles were electrostatically absorbed on the surface of the film and used for the immobilization of antibody, while PB acts as signaling molecule. The stepwise assembly process was investigated by differential pulse voltammetry and scanning electron microscopy. It is found that the formation of antibody-antigen complexes partially inhibits the electron transfer of PB and decreased its peak current. Under the optimal conditions, the decrease of intensity of the peak current of PB is linearly related to the concentration of carcinoembryonic antigen in two ranges (0.2–1.0, and 1.0–40.0 ng·mL−1), with a detection limit of 60 pg·mL−1 (S/N = 3). The immunosensor was applied to analyze five clinical samples, and the results obtained were in agreement with clinical data. In addition, the immunosensor exhibited good precision, acceptable stability and reproducibility. (author)

  9. 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.

    Science.gov (United States)

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

    2007-01-01

    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

  10. Prognostic Value of Pretreatment Carcinoembryonic Antigen After Definitive Radiotherapy With or Without Concurrent Chemotherapy for Squamous Cell Carcinoma of the Uterine Cervix

    International Nuclear Information System (INIS)

    Purpose: To evaluate whether pretreatment carcinoembryonic antigen (CEA) levels have a prognostic role in patients after definitive radiotherapy for squamous cell carcinoma (SCC) of the uterine cervix. Methods and Materials: A retrospective study of 550 patients was performed. The SCC antigen (SCC-Ag) and CEA levels were regarded as elevated when they were ≥2 and ≥5 ng/mL, respectively. A total of 208 patients underwent concurrent chemoradiotherapy (CCRT). The Kaplan-Meier method was used to calculate the distant metastasis (DM), local failure (LF), disease-free survival (DFS), and overall survival (OS) rates. Multivariate analysis was performed using the Cox proportional hazards model. The hazard ratio (HR) with 95% confidence interval (CI) was evaluated for the risk of a poor prognosis. Results: Compared with the patients with normal CEA/SCC-Ag levels, CEA levels ≥10 ng/mL but without elevated SCC-Ag levels was an independent factor for LF (HR, 51.81; 95% CI, 11.51–233.23; p < .001), DM (HR, 6.04; 95% CI, 1.58–23.01; p = .008), DFS (HR, 10.17; 95% CI, 3.18–32.56; p < .001), and OS (HR, 5.75; 95% CI, 1.82–18.18; p = .003) after RT alone. However, no significant role for CEA was noted in patients with SCC-Ag levels ≥2 ng/mL. In patients undergoing CCRT, a CEA level ≥10 ng/mL was an independent factor for LF (HR, 2.50; 95% CI, 1.01–6.21; p = .047), DM (HR, 3.41; 95% CI, 1.56–7.46; p = .002), DFS (HR, 2.73; 95% CI, 1.39–5.36; p = .003), and OS (HR, 3.93; 95% CI 1.99–7.75; p < .001). A SCC-Ag level of ≥40 ng/mL was another prognostic factor for DM, DFS, and OS in patients undergoing not only CCRT, but also RT alone. The 5-year OS rate for CCRT patients with CEA <10 ng/mL and ≥10 ng/mL was 75.3% and 35.8%, respectively (p < .001). CCRT was an independent factor for better OS (HR, 0.69; 95% CI, 0.50–0.97; p = .034). Conclusion: Pretreatment CEA levels in patients with SCC of the uterine cervix provide complementary information for

  11. 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

    2004-10-01

    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

  12. 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

    2013-01-01

      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.

  13. High preoperative and postoperative levels of carcinoembryonic antigen and CYFRA 21-1 indicate poor prognosis in patients with pathological Stage I nonsmall cell lung cancer

    Directory of Open Access Journals (Sweden)

    X Duan

    2015-01-01

    Full Text Available BACKGROUND: Serum carcinoembryonic antigen (CEA and the soluble fragment of cytokeratin 19 (CYFRA 21-1 are supposed to have a prognostic role in patients with nonsmall cell lung cancer (NSCLC after surgery, but it has not been used as an adjunct to the tumor-node-metastasis (TNM staging system to provide therapy options for patients with pathological Stage I NSCLC. This study was designed to investigate the effect of serum levels of CEA and CYFRA 21-1 before and after surgery on the prognosis of patients with Stage I NSCLC. MATERIALS AND METHODS: A retrospective review was performed regarding the medical records and follow-ups of 169 patients with Stage I NSCLC before and after surgery. The patients were divided into three groups based on levels of serum CEA and CYFRA 21-1 before and after surgery: (1 continuously normal-level groups (CEA [NN] and CYFRA 21-1 [NN] groups; (2 declined to normal-level groups (CEA [HN] and CYFRA 21-1 [HN] groups; and (3 continuously high-level groups (CEA [HH] and CYFRA 21-1 [HH] groups. Survival analysis was conducted using the Kaplan-Meier method for each group. The Chi-square or Fisher exact test was employed to compare clinical and pathologic factors at the level of P < 0.05. The prognostic factor was evaluated by the Cox proportional hazards model. RESULTS: Compared with the continuously normal-level groups, the CEA [HN] group was significantly correlated to tumor size (P = 0.011, and the CYFRA 21-1 [HN] group was significantly correlated to tumor type and pathological TNM in addition to tumor size. Five-year survivals were significantly lower (P = 0.004 in the CEA [HH] group (67.3% and the CEA [HN] group (86.5% than in the CEA [NN] group (85.7% and were significantly lower (P < 0.001 in the CYFRA 21-1 [HH] group (47.2% and the CYFRA 21-1 [HN] group (70.1% than in the CYFRA 21-1 [NN] group (90.1%. Multivariate analysis demonstrated that tumor size (21-50 mm, CEA [HH], and CYFRA 21-1 [HH] were independent

  14. 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)

    胡跃华

    2012-01-01

    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.

  15. Pericyte antigens in angiomyolipoma and PEComa family tumors.

    Science.gov (United States)

    Shen, Jia; Shrestha, Swati; Yen, Yu-Hsin; Scott, Michelle A; Asatrian, Greg; Barnhill, Raymond; Lugassy, Claire; Soo, Chia; Ting, Kang; Peault, Bruno; Dry, Sarah M; James, Aaron W

    2015-08-01

    Perivascular epithelioid cell tumors (PEComas) are an uncommon family of soft tissue tumors with dual myoid-melanocytic differentiation. Although PEComa family tumors commonly demonstrate a perivascular growth pattern, pericyte antigen expression has not yet been examined among this unique tumor group. Previously, we demonstrated that a subset of perivascular soft tissue tumors exhibit a striking pericytic immunophenotype, with diffuse expression of αSMA, CD146, and PDGFRβ. Here, we describe the presence of pericyte antigens across a diverse group of PEComa family tumors (n = 19 specimens). Results showed that pericyte antigens differed extensively by histological appearance. Typical angiomyolipoma (AML) specimens showed variable expression of pericyte antigens among both perivascular and myoid-appearing cells. In contrast, AML specimens with a predominant spindled morphology showed diffuse expression of pericyte markers, including αSMA, CD146, and PDGFRβ. AML samples with predominant epithelioid morphology showed a marked reduction in or the absence of immunoreactivity for pericyte markers. Lymphangiomyoma samples showed more variable and partial pericyte marker expression. In summary, pericyte antigen expression is variable among PEComa family tumors and largely varies by tumor morphology. Pericytic marker expression in PEComa may represent a true pericytic cell of origin, or alternatively aberrant pericyte marker adoption. Markers of pericytic differentiation may be of future diagnostic utility for the evaluation of mesenchymal tumors, or identify actionable signaling pathways for future therapeutic intervention. PMID:26123600

  16. 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.

    Science.gov (United States)

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

    2014-01-01

    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.

  17. 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.

  18. 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

    Science.gov (United States)

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

    2014-10-01

    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 pdyes). Human pancreatic tumors subcutaneously implanted into nude mice were labeled with antibody-dye conjugates and serially imaged. Labeling with conjugated PEGylated dyes resulted in significantly brighter tumors compared to the non-PEGylated dyes (pdyes; p=0.01 for 750 dyes). PEGylation of the NIR dyes also decreased 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.

  19. Family distances and human-lymphocyte antigens

    NARCIS (Netherlands)

    Nauta, M J; van Treuren, R; ten Kate, L P; te Meerman, G J; D'Amaro, J

    1987-01-01

    We compared family distances of homozygotes and heterozygotes for HLA-A and -B. When matched on number of inhabitants per birthplace, no significant differences were found. However, when homozygotes were compared with heterozygotes from larger birthplaces, homozygotes showed significantly smaller fa

  20. Comparing Prothrombin induced by vitamin K absence-II (PIVKA-II) with the oncofetal proteins Glypican-3, Alpha feto protein and Carcinoembryonic antigen in diagnosing hepatocellular carcinoma among Egyptian patients

    International Nuclear Information System (INIS)

    Background: Hepatocellular carcinoma (HCC) is usually asymptomatic in the early stage and does not show elevated alpha-feto protein (AFP). AFP shows 60-80% sensitivity in diagnosing HCC. Glypican3 (GPC-3) is an oncofetal protein that is only detected in HCC cells but not in benign liver tissues, while Carcinoembryonic antigen (CEA) is expressed in various neoplasms including HCC. Although, it is not specific for HCC. Prothrombin induced by vitamin K absence-II (PIVKA-II) is an abnormal prothrombin protein that is increased in the serum of HCC patients. It has higher sensitivity and specificity compared to AFP. The aim of this study is to compare the clinical utility of PIVKA-II with GPC-3, AFP and CEA in diagnosing HCC. Prothrombin induced by vitamin K absence-II Patients and methods: This study included 40 patients with HCC, 10 patients with cirrhosis as a benign control group, and 10 apparently healthy volunteers as normal controls. Serum samples were subjected to routine laboratory investigations, measurement of CEA, AFP using MEIA technique (Axsym), glypican3, and PIVKA-II using ELISA technique in the sera of all patients and controls. Results: All markers showed the highest results in the HCC group. Higher concentrations of PIVKA- II were detected in patients with splenomegaly, and in tumors with size (>3 cm). Combination of Glypican-3 and PIVKA-II showed the highest sensitivity, while GPC-3 alone and combination of GPC-3 and AFP showed the highest specificity to differentiate HCC from liver cirrhosis and normal controls. GPC-3, PIVKAII, and combination of both showed the highest sensitivity, while GPC-3 alone showed the highest specificity to differentiate HCC from liver cirrhosis. Conclusion: Glypican-3 is the only oncofetal antigen that showed comparable high diagnostic accuracy as PIVKA-II in diagnosing HCC among Egyptian patients.

  1. Distribution of HLA antigens in families of patients with leukaemias

    Directory of Open Access Journals (Sweden)

    Vojvodić Svetlana

    2008-01-01

    Full Text Available Introduction. Since the discovery of major histocompatihility complex influence on manse leukaemia in 1964, an HLA association with leukaemia in humans has been considered as a possible genetic risk factor that contributes to development of leukaemia. In addition to associations of several IILA antigens with leukaemias, it has been observed that patients with leukaemia have an increase in the frequency of HLA identical siblings, higher degree of HLA compatibility with their parents as well as higher parental HLA sharing rate in comparison to the families without patients suffering from leukaemia. Material and methods. To test hypothesis that susceptibility to leukaemia can be caused bv influence of a recessive genes associated with the major histocompatibilily complex in man, we analyzed the distribution of I class HLA antigens in 77 families of patients suffering from different types of leukaemia. In the affected families and in 72 families of healthy controls, we investigated HLA identical sibling frequency, parental sharing of one, two or three HLA antigens and degree of compatibility of parents and off springs: existence of haploidentity, compatibility in l' and 4/4 HLA antigens of A and B loci. Results We have found that in families with affected persons there is a statistically significant difference in number of HLA identical siblings in comparison to the group of healthy controls (t=2,63. Also the results have shown that among the parents of affected persons there is a statistically significant difference in mutual compatibility in one (t=3,012 and two ft= 2,4 HLA antigens. In addition, we observed an increase in the frequency of higher rate of compatibility between patients and their parents (t=3,88 in l' HLA antigens, to their mothers (t=2,83 and to their fathers (t=2,55, respectively, in comparison to the healthy control group. Conclusion The results of this study show that in families with persons suffering from leukaemia there are

  2. Immunohistochemical expression of carcinoembryonic antigen-related cell adhesion molecules 5, CEACAM6, and SLC7A5: Do they aid in predicting the response to neo-adjuvant chemotherapy in locally advanced breast cancer?

    Directory of Open Access Journals (Sweden)

    Anju Bansal

    2014-01-01

    Full Text Available Context: Neo-adjuvant chemotherapy (NACT has become an integral part of multimodality treatment for locally advanced breast cancer (LABC worldwide. Predictors of therapeutic response to NACT are lacking. Whether carcinoembryonic antigen-related cell adhesion molecules (CEACAMs like CEACAM5 and CEACAM6 can act as a predictor of response to therapy is unclear. SLC7A5 gene in humans encodes a large neutral amino acid transporter protein, which has an essential role in tumor cell growth and survival. Materials and Methods: Thirty histopathologically proven cases of LABC, being given NACT, were included in the study. Immunohistochemical examination of the tumor sections was performed for CEACAM5, CEACAM6, and SLC7A5. Response to chemotherapy was assessed using "Response Evaluation Criteria in Solid Tumors" (RECIST 1.1 criteria. A total of three cycles were given at 3 weekly intervals. After 3 weeks of the last cycle of NACT, the patients were taken up for modified radical mastectomy. The specimen was subjected to histopathological examination. The immunohistochemical results were correlated with response to NACT based on RECIST criteria and histopathology. Results: 12/30 (40% of the patients had objective clinical response of which 4 (13.33% patients had pathological complete response. The relationship between CEACAM5 and CEACAM6 and response to NACT was found to be statistically significant, P = 0.004 and P = 0.020, respectively. Furthermore, relationship between response to NACT and node-positive tumors with SLC7A5 immunoreactivity was found to be highly significant (P = 0.009. Conclusion: Biomarkers (CEACAM5, CEACAM6, and SLC7A5 showed promise as predictors of poor response to NACT and can help plan an alternative regime in likely nonresponders to prevent the toxicity of chemotherapy and also in tailoring the therapy in a patient with LABC.

  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

    2009-02-01

    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

    2016-01-01

    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. Establishment of Immunoradiometric Assay for Carcinoembryonic Antigen

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Two anti-CEA monoclonal antibodies are used, one is coated on the microtiter plate, the other is labeled to make 125I-CEAMcAb. The one-step assay is established based on immunoradiometric assay(IRMA). The sensitivity of the assay is 0.5 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 97.4% to 107.8%. The reference cut-out value of 35 normal serum is lower than

  6. 一种新型免疫传感器阵列检测癌胚抗原和糖类抗原199技术%A New Type of Sensor Array Detection of Carcinoembryonic Antigen and Carbohydrate Antigen 199 Technology

    Institute of Scientific and Technical Information of China (English)

    周靖; 胡富陶; 余红卫

    2015-01-01

    制备了一种新型的含2个包覆分子印迹聚合物的丝网印刷碳工作电极的电化学发光夹心免疫传感器阵列,通过该阵列实现了肿瘤标志物癌胚抗原(CEA)和糖类抗原199(CA199)的近同时免疫分析。该新型的电化学发光免疫方法将空间分辨技术与分子印迹技术相结合,为 CEA 和CA199的复合免疫分析提供了一条简单、低成本、快速和灵敏的途径。该方法对临床实验中多种蛋白质的近同时测定也显示了较大的潜力。%In this study, a novel electrochemiluminescence (ECL) immunosensor array is engineered consisting of two screen-printed carbon working electrodes coated with molecular imprinting polymer (MIPs). The array is formed to perform multiplexed immunoassay of tumor markers (carcinoembryonic antigen (CEA) and carbohydrate antigen-199 (CA199)). Based on spatial-resolved technique, and coupled with molecularly imprinted technique, this novel ECL strategy provides a simple, low-cost, fast and sensitive approach for multiplexed immunoassay of CEA and CA199. This approach may render promising potential for protein detection in the circumstances of clinical laboratory setting.

  7. Research on immunosensor for the determination of carcinoembryonic antigen and its application%免疫传感器在癌胚抗原检测中的构建与应用研究

    Institute of Scientific and Technical Information of China (English)

    马霄; 莫利明; 虞成; 逯岭松; 杨攀

    2014-01-01

    目的:设计一种新型的基于丝网印刷技术的癌胚抗原(CEA)免疫传感器,用于癌胚抗原浓度的床边检测。方法:在丝网印刷电极(SPE)上层层修饰上多壁碳纳米管(MWNTs)N,N-二甲基甲酰胺(DMF)分散液与壳聚糖纳米二氧化铈(Chitosan-Nano CeO2)溶液两种纳米材料,利用纳米铈固载癌胚抗原抗体(anti-CEA),最后用牛血清白蛋白(BSA)封闭纳米铈上非特异位点,构建一种新型的癌胚抗原免疫传感器。采用透射电镜(TEM)及循环伏安法(CV)对修饰过程进行表征。结果:探讨不同pH、孵育温度及孵育时间对该免疫传感器性能的影响,该传感器在最适条件下对CEA响应良好,其线性范围为0~80 ng/ml,线性相关系数r=0.99825,检出限为0.08 ng/ml。结论:CEA免疫传感器具有稳定性好、灵敏度高、特异性好、结果准确可靠和可再生等优点,可应用于临床检测。%Objective: To design immunosensor for the determination of Carcinoembryonic Antigen(CEA) and be used in the piont-of-care test of the concentration of CEA. Methods:The immunosensor was developed by modifying multi-wall carbon nanotubes(MWNTs)which dispersed in N, N-dimethyl-formamide(DMF)on the Screen-Printed Electrodes (SPE), then Chitosan-NanoCeO2 were immobilized self-assembly. And then the antibody of CEA (anti-CEA) was absorbed on the surface of NanoCeO2 monolayer. Finally, Albumin from bovine serum (BSA) blocked the non-specific adsorption site.The modification process was characterized by transmisCeOn electronmicroscope(TEM)and cyclic voltammetry(CV). The factors possibly influenced the performance of the proposed immunosensor were studied in detail. Results:Under optimal conditions,the obtained immunosensor exhibited good electrochemical behavior to CEA in a linear range of 0 to 80 ng/ml (r=0.99825), with a detection limit of 0.08 ng/ml. Conclusion: The immunosensor prepared using this method has advantages of good

  8. 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

    2013-01-01

    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、

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

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    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.

  10. Noninherited maternal antigens do not increase the susceptibility for familial rheumatoid arthritis. European Consortium on Rheumatoid Arthritis Families (ECRAF).

    NARCIS (Netherlands)

    Barrera Rico, P.; Balsa, A.; Alves, H.; Westhovens, R.; Maenaut, K.; Cornelis, F.; Fritz, P.; Bardin, T.; Ceu Maia, M.; Lopes-Vaz, A.; Pascual-Salcedo, D.; Concha, E. de la; Radstake, T.R.D.J.; Putte, L.B.A. van de; Migliorini, P.; Prudhomme, J.F.; Charron, D.; Spyropoulou, M.; Mendes, A.; Spaepen, M.; Martinez, M.; Stavropoulos, C.

    2001-01-01

    OBJECTIVE: It has been proposed that noninherited maternal HLA-DR antigens (NIMA) might play a role in the susceptibility for rheumatoid arthritis (RA). This hypothesis has not been thoroughly tested in patients with familial RA, in whom genetic factors, either inherited or not, might have stronger

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

    DEFF Research Database (Denmark)

    Straten, Per thor; Andersen, Mads Hald

    2010-01-01

    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......, spontaneous cellular immune responses against the Bcl-2 family proteins have been identified as frequent features in cancer patients underscoring that these proteins are natural targets for the immune system. Thus, Bcl-2 family may serve as an important and widely applicable target for anti......-cancer immunotherapeutic strategies, alone or in the combination with conventional therapy. Here, we summarize the current knowledge of Bcl-2 family proteins as T-cell antigens, which has set the stage for the first explorative trial using these antigens in therapeutic vaccinations against cancer, and discuss future...

  12. Evolutionary origin and human-specific expansion of a cancer/testis antigen gene family.

    Science.gov (United States)

    Zhang, Qu; Su, Bing

    2014-09-01

    Cancer/testis (CT) antigens are encoded by germline genes and are aberrantly expressed in a number of human cancers. Interestingly, CT antigens are frequently involved in gene families that are highly expressed in germ cells. Here, we presented an evolutionary analysis of the CTAGE (cutaneous T-cell-lymphoma-associated antigen) gene family to delineate its molecular history and functional significance during primate evolution. Comparisons among human, chimpanzee, gorilla, orangutan, macaque, marmoset, and other mammals show a rapid and primate specific expansion of CTAGE family, which starts with an ancestral retroposition in the haplorhini ancestor. Subsequent DNA-based duplications lead to the prosperity of single-exon CTAGE copies in catarrhines, especially in humans. Positive selection was identified on the single-exon copies in comparison with functional constraint on the multiexon copies. Further sequence analysis suggests that the newly derived CTAGE genes may obtain regulatory elements from long terminal repeats. Our result indicates the dynamic evolution of primate genomes, and the recent expansion of this CT antigen family in humans may confer advantageous phenotypic traits during early human evolution. PMID:24916032

  13. 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

    2009-01-01

    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.

  14. The serum carbohydrate antigen 125 and carcinoembryonic antigen comparsion for the han and uyghur patients of terminal gallbladder cancer in xinjiang uygur autonomous region%新疆地区汉族与维吾尔族晚期胆囊癌患者血清糖类抗原125、癌胚抗原水平比较

    Institute of Scientific and Technical Information of China (English)

    毛拉艾沙·买买提; 薛峰; 依马木买买提江·阿不拉

    2013-01-01

    目的 比较新疆地区汉族与维吾尔族晚期胆囊癌患者血清糖类抗原125(CA125)、癌胚抗原(CEA)水平是否存在差异.方法 原发性晚期胆囊癌患者80例,其中维吾尔族40例,汉族40例;随机选取同期住院的胆囊炎患者60例作为对照组,其中维吾尔族34例,汉族26例;均进行血清CA125、CEA检测.结果 胆囊癌组的汉族、维吾尔族患者与对照组同民族患者CA125、CEA水平差异均有统计学意义(t=27.01、28.06、10.68、11.25,均P<0.05);而两组内汉族、维吾尔族患者间的CA125、CEA水平差异均无统计学意义(t=0.47、0.34、0.11、1.23,均P>0.05);胆囊癌Ⅳ期汉族、维吾尔族患者与Ⅴ期同民族患者CA125、CEA水平差异均有统计学意义(t=26.92、25.01、16.58、14.54,均P<0.05);汉族、维吾尔族的胆囊癌Ⅳ期患者之间、Ⅴ期患者之间的CA125、CEA水平差异均无统计学意义(t=1.13、0.11、0.38、0.07,均P>0.05).结论 新疆地区汉族与维吾尔族晚期胆囊癌患者血清CA125、CEA水平无差异,晚期胆囊癌患者进行CA125、CEA检测有助于病情诊断.%Objective To compare the differences on the serum carbohydrate antigen 125 and carcinoembryonic antigen for the Han and Uyghur patients of terminal gallbladder cancer in Xinjiang Uygur Autonomous Region.Methods 80 cases of patients with primary advanced gallbladder,including 40 cases of Uighur,Han 40 cases,The cholecystitis patients randomly selected from the same period of hospitalization of 60 cases as the control group.Including 34 cases of Uighur and Han 26 cases,Levels of serum CA125,CEA were detected.Results The gallbladder group of Han,Uygur patients and the control group with ethnic patients CA125,CEA level differences were statistically significant(t =27.01,28.06,10.68,11.25,all P < 0.05) ; CA125,CEA level differences between the two groups within the Han,Uygur patients were not statistically significant(t =0.47,0.34,0.1 l,1.23,all P > 0

  15. Proposta para estadiamento do câncer colorretal baseada em critérios morfofuncionais: correlação com níveis séricos do antígeno carcinoembrionário Proposal for colorectal cancer stages based on morphofunctional criteria: correlation with carcinoembryonic antigen levels

    Directory of Open Access Journals (Sweden)

    Denise Gonçalves Priolli

    2007-12-01

    tempo de sobrevida, a classificação morfofuncional e o nível sérico de antígeno carcinoembrionário. CONCLUSÃO: O estadiamento morfofuncional é válido para a avaliação prognóstica dos pacientes com adenocarcinoma colorretal, e relaciona-se com os níveis séricos do CEA.The analysis of morphofunctions characteristics can be useful in the colorectal cancer evolution, especially if related to the serum carcinoembryonic antigen levels. The research of chromosomes and genes instability, as well as the alterations of tissue protein codified, makes attractive the possibility to use potentially valid functional factors as variables for the understanding of colorectal carcinoma prognosis. OBJECTIVE: To consider classes based on morphologic and functional colorectal carcinoma characteristics, valuing serum carcinoembryonic antigen levels prognostic power. METHOD: Third-five patients in different stages of colorectal carcinoma underwent operations from 2001 to 2007. Serum CEA levels, histological grade, tissue CEA cell polarization capacity were analyzed. Colorectal carcinoma was classified according to TNM stages. The morphofunctional classification was determined by the combination between histological grade and antigen polarization, morphofunctional stages have been based in association between morphofunctional classification and stages TNM, by punctuation attributed to each one classification. The results had been analyzed by variance analysis, correlation test and survival analysis (Kaplan-Meier and Cox Model Regression, adopting p<0.05. RESULTS: Morphofunctional stages survival curve resulted similar to the joined ones in stages TNM. It had relation between new classification proposed and patient survival time. They had observed relation among survival time, morphofunctional classification and serum carcinoembryonic antigen. CONCLUSION: Morphofunctional classification is valid for colorectal cancer patient's prognostic evaluation and is related with the serum CEA

  16. 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

    2013-01-01

    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.

  17. 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;

    2014-01-01

    -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....

  18. Advances in Biomarkers: Going Beyond the Carcinoembryonic Antigen.

    Science.gov (United States)

    Lopez, Nicole E; Peterson, Carrie Y

    2016-09-01

    Using biologically available markers to guide treatment decisions in colorectal cancer care is becoming increasingly common, though our understanding of these biomarkers is in its infancy. In this article, we will discuss how this area is rapidly changing, review important biomarkers being used currently, and explain how the results influence clinical decision-making. We will also briefly discuss the possibility of a liquid biopsy and explore several exciting and new options. PMID:27582644

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

    DEFF Research Database (Denmark)

    Knudsen, Mie Grunnet; Sorensen, J B

    2012-01-01

    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...

  20. The DnaJ domain of polyomavirus large T antigen is required to regulate Rb family tumor suppressor function.

    OpenAIRE

    Sheng, Q.; Denis, D; Ratnofsky, M; Roberts, T.M.; DeCaprio, J A; Schaffhausen, B

    1997-01-01

    Tumor suppressors of the retinoblastoma susceptibility gene family regulate cell growth and differentiation. Polyomavirus large T antigens (large T) bind Rb family members and block their function. Mutations of large T sequences conserved with the DnaJ family affect large T binding to a cellular DnaK, heat shock protein 70. The same mutations abolish large T activation of E2F-containing promoters and Rb binding-dependent large T activation of cell cycle progression. Cotransfection of a cellul...

  1. Sarcocystis neurona Merozoites Express a Family of Immunogenic Surface Antigens That Are Orthologues of the Toxoplasma gondii Surface Antigens (SAGs) and SAG-Related Sequences†

    OpenAIRE

    Howe, Daniel K.; Rajshekhar Y Gaji; Mroz-Barrett, Meaghan; Gubbels, Marc-Jan; Striepen, Boris; Stamper, Shelby

    2005-01-01

    Sarcocystis neurona is a member of the Apicomplexa that causes myelitis and encephalitis in horses but normally cycles between the opossum and small mammals. Analysis of an S. neurona expressed sequence tag (EST) database revealed four paralogous proteins that exhibit clear homology to the family of surface antigens (SAGs) and SAG-related sequences of Toxoplasma gondii. The primary peptide sequences of the S. neurona proteins are consistent with the two-domain structure that has been describe...

  2. A New Gene Family (ariel) Encodes Asparagine-Rich Entamoeba histolytica Antigens, Which Resemble the Amebic Vaccine Candidate Serine-Rich E. histolytica Protein

    OpenAIRE

    Mai, Zhiming; Samuelson, John

    1998-01-01

    A family of genes, called ariel, are named for and encode asparagine-rich Entamoeba histolytica antigens containing 2 to 16 octapeptide repeats. Ariel proteins, which are constitutively expressed by trophozoites, belong to a large antigen family that includes the serine-rich E. histolytica protein (SREHP), an amebic vaccine candidate.

  3. Mitotic evolution of Plasmodium falciparum shows a stable core genome but recombination in antigen families.

    Directory of Open Access Journals (Sweden)

    Selina E R Bopp

    Full Text Available Malaria parasites elude eradication attempts both within the human host and across nations. At the individual level, parasites evade the host immune responses through antigenic variation. At the global level, parasites escape drug pressure through single nucleotide variants and gene copy amplification events conferring drug resistance. Despite their importance to global health, the rates at which these genomic alterations emerge have not been determined. We studied the complete genomes of different Plasmodium falciparum clones that had been propagated asexually over one year in the presence and absence of drug pressure. A combination of whole-genome microarray analysis and next-generation deep resequencing (totaling 14 terabases revealed a stable core genome with only 38 novel single nucleotide variants appearing in seventeen evolved clones (avg. 5.4 per clone. In clones exposed to atovaquone, we found cytochrome b mutations as well as an amplification event encompassing the P. falciparum multidrug resistance associated protein (mrp1 on chromosome 1. We observed 18 large-scale (>1 kb on average deletions of telomere-proximal regions encoding multigene families, involved in immune evasion (9.5×10(-6 structural variants per base pair per generation. Six of these deletions were associated with chromosomal crossovers generated during mitosis. We found only minor differences in rates between genetically distinct strains and between parasites cultured in the presence or absence of drug. Using these derived mutation rates for P. falciparum (1.0-9.7×10(-9 mutations per base pair per generation, we can now model the frequency at which drug or immune resistance alleles will emerge under a well-defined set of assumptions. Further, the detection of mitotic recombination events in var gene families illustrates how multigene families can arise and change over time in P. falciparum. These results will help improve our understanding of how P. falciparum

  4. 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

    2002-01-01

    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.

  5. 晚期非小细胞肺癌患者血清癌胚抗原水平和全身转移能力的风险评估%Serum Level of Carcinoembryonic Antigen and Whole-body Metastasis Ability Risk Assessment in Patients with Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    李捷; 李付广; 常保萍; 焦江琴

    2015-01-01

    Objective: To study the serum level of carcinoembryonic antigen and whole-body metastasis ability risk in patients with advanced non-small cell lung cancer,and provide the reference for clinical.Method: 160 patients with stage IV NSCLC in our hospital from March 2012 to January 2014 were selected. Research indicators included age, height,weight,age,sex,histological classification,tumor differentiation ,CEA level,smoking status,bone metastases,lymphatic metastasis,obstinate/transfer, transfer, soft tissue of neck metastases, brain metastases, systemic metastasis score and systemic metastasis LN-adjustment score, and the statistical analysis was performed.Result: The sex,bone metastases,histological classification lymph node metastasis and brain metastasis of different CEA level patients had statistical significance (P0.05).Serum CEA level increased from 2.7 ng/mL in LN-adjusted whole-body metastatic score 1 to 374.1 ng/mL in LN-adjusted whole-body metastatic score 7,the difference was statistically significant (P=0.003).Similarly, the low LN-adjusted whole-body metastatic score (rating 1-3) showed CEA level significantly reduced when compared with adjustment of high LN-adjusted whole-body metastatic score (rating 4-7),the difference was statistically significant(P0.05)。血清CEA水平从LN-调整全身转移得分1分中的2.7 ng/mL上升至LN-调整全身转移得分7分中的374.1 ng/mL(P=0.003)。低LN-调整全身转移得分(评分1~3分)与高LN-调整全身转移得分(评分4~7分)比较表现出CEA水平显著降低,两组比较差异具有统计学意义(P<0.001)。血清高CEA水平的比例从全身转移得分1分中占37.5%(15/40)上升至全身转移得分6中的100%(1/1),两组比较差异具有统计学意义(P<0.001)。血清高CEA水平的比例从LN-调整全身转移得分1分中占25.0%(2/8)上升至LN-调整全身转移得分7分中的100%(1/1)(P<0.001)。单因素分析结果表明,

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

    Directory of Open Access Journals (Sweden)

    Misri Rachita

    2009-01-01

    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.

  7. Nephritogenic antigen determinants in epidermal and renal basement membranes of kindreds with Alport-type familial nephritis.

    OpenAIRE

    Kashtan, C; Fish, A. J.; Kleppel, M; Yoshioka, K; Michael, A. F.

    1986-01-01

    We probed epidermal basement membranes (EBM) of acid-urea denatured skin from members of kindreds with Alport-type familial nephritis (FN) for the presence of antigens reactive with Goodpasture sera (GPS) and serum (FNS) from an Alport patient who developed anti-glomerular basement membrane (GBM) nephritis in a renal allograft. By immunoblotting, GPS reacted primarily with the 28,000 molecular weight (mol wt) monomer but also the 24,000 mol wt and 26,000 mol wt monomers of the noncollagenous ...

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

    NARCIS (Netherlands)

    Kramer, AB; Roozendaal, C; Dullaart, RPF

    2004-01-01

    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

  9. The Echinococcus granulosus antigen B gene family comprises at least 10 unique genes in five subclasses which are differentially expressed.

    Directory of Open Access Journals (Sweden)

    Wenbao Zhang

    Full Text Available BACKGROUND: Antigen B (EgAgB is a major protein produced by the metacestode cyst of Echinococcus granulosus, the causative agent of cystic hydatid disease. This protein has been shown to play an important role in modulating host immune responses, although its precise biological function still remains unknown. It is generally accepted that EgAgB is comprised of a gene family of five subfamilies which are highly polymorphic, but the actual number of genes present is unknown. METHODOLOGY/PRINCIPAL FINDINGS: Based on published sequences for the family, we designed specific primers for each subfamily and used PCR to amplify them from genomic DNA isolated from individual mature adult worms (MAW taken from an experimentally infected dog in China and individual larval protoscoleces (PSC excised from a single hydatid cyst taken from an Australian kangaroo. We then used real-time PCR to measure expression of each of the genes comprising the five EgAgB subfamilies in all life-cycle stages including the oncosphere (ONC. CONCLUSIONS/SIGNIFICANCE: Based on sequence alignment analysis, we found that the EgAgB gene family comprises at least ten unique genes. Each of the genes was identical in both larval and adult E. granulosus isolates collected from two geographical areas (different continents. DNA alignment comparisons with EgAgB sequences deposited in GenBank databases showed that each gene in the gene family is highly conserved within E. granulosus, which contradicts previous studies claiming significant variation and polymorphism in EgAgB. Quantitative PCR analysis revealed that the genes were differentially expressed in different life-cycle stages of E. granulosus with EgAgB3 expressed predominantly in all stages. These findings are fundamental for determining the expression and the biological function of antigen B.

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

    Science.gov (United States)

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

    2011-06-01

    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.

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

    Science.gov (United States)

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

    2014-09-01

    The prognosis of head and neck squamous cell carcinoma (HNSCC) patients remains poor. The identification of high-risk subgroups is needed for the development of custom-tailored therapies. The expression of cancer-testis antigens (CTAs) has been linked to a worse prognosis in other cancer types; however, their prognostic value in HNSCC is unclear because only few patients have been examined and data on CTA protein expression are sparse. A tissue microarray consisting of tumor samples from 453 HNSCC patients was evaluated for the expression of CTA proteins using immunohistochemistry. Frequency of expression and the subcellular expression pattern (nuclear, cytoplasmic, or both) was recorded. Protein expression of melanoma antigen (MAGE)-A family CTA, MAGE-C family CTA and NY-ESO-1 was found in approximately 30, 7 and 4% of tumors, respectively. The subcellular expression pattern in particular had a marked impact on the patients' prognosis. Median overall survival (OS) of patients with (i) simultaneous cytoplasmic and nuclear expression compared to (ii) either cytoplasmic or nuclear expression and (iii) negative patients was 23.0 versus 109.0 versus 102.5 months, for pan-MAGE (p 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.

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

    OpenAIRE

    Chaouachi Kamal; Sajid Khan; Mahmood Rubaida

    2008-01-01

    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 b...

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

    Directory of Open Access Journals (Sweden)

    Chaouachi Kamal

    2008-05-01

    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.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...

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

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    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.

  16. Utility of a stool antigen test to detect the incidence of helicobacter pylori infection and familial and community enviromental risk factors for this infection in pediatric age

    Directory of Open Access Journals (Sweden)

    T. Sabbi

    2012-04-01

    Full Text Available Background: helicobacter pylori (hp infection is mainly acquired during childhood; it is recognised as a cause of gastritis and peptic ulcer and it has been classified as a group A carcinogen by World health organization. the exact mode of transmission is as yet, not known. Aim of our study has been to identify risk factors associated with helicobacter pylori infection in a preschool and school population and to confirm if hp antigen in faeces is useful as screening in epidemiological studies. Methods: We interviewed, with questionnaire, 400 children (203 male; age range 3-10 years; mean age 6 years of 3 different schools and stool samples were collected of all children too. 35 of 400 (8% children underwent to upper gastrointestinal endoscopy because of a suspect of upper gastrointestinal disease. Results: stool were collected from 400 school children and 35 of them shown positivity of hp antigen test. A questionnaire about presence of nausea, vomit, recurrent abdominal pain, family size, parent’s occupations and education, use of antibiotics, country of birth of child and parents, personal hygiene, breast feeding, presence of the animals was completed. 35 children with positive hp stool antigen test and a suspicious of upper gastrointestinal disease (recurrent abdominal pain, diurnal or nocturnal abdominal pain, nausea, vomiting, iron deficiency underwent to esophagogastroduodenoscopy (egdS that demonstrated antral gastritis and positive histology and urease rapid test. Conclusions: the results of this study suggest that risk factors for hp infection are low socioeconomics factors, hygiene and living conditions and that hp antigen in faeces is useful as screening test.

  17. The J Domain of Simian Virus 40 Large T Antigen Is Required To Functionally Inactivate RB Family Proteins

    OpenAIRE

    Zalvide, Juan; Stubdal, Hilde; DeCaprio, James A.

    1998-01-01

    Transformation by simian virus 40 large T antigen (TAg) is dependent on the inactivation of cellular tumor suppressors. Transformation minimally requires the following three domains: (i) a C-terminal domain that mediates binding to p53; (ii) the LXCXE domain (residues 103 to 107), necessary for binding to the retinoblastoma tumor suppressor protein, pRB, and the related p107 and p130; and (iii) an N-terminal domain that is homologous to the J domain of DnaJ molecular chaperone proteins. We ha...

  18. Antigenicity and protective efficacy of a Leishmania amastigote-specific protein, member of the super-oxygenase family, against visceral leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Vivian T Martins

    Full Text Available BACKGROUND: The present study aimed to evaluate a hypothetical Leishmania amastigote-specific protein (LiHyp1, previously identified by an immunoproteomic approach performed in Leishmania infantum, which showed homology to the super-oxygenase gene family, attempting to select a new candidate antigen for specific serodiagnosis, as well as to compose a vaccine against VL. METHODOLOGY/PRINCIPAL FINDINGS: The LiHyp1 DNA sequence was cloned; the recombinant protein (rLiHyp1 was purified and evaluated for its antigenicity and immunogenicity. The rLiHyp1 protein was recognized by antibodies from sera of asymptomatic and symptomatic animals with canine visceral leishmaniasis (CVL, but presented no cross-reactivity with sera of dogs vaccinated with Leish-Tec, a Brazilian commercial vaccine; with Chagas' disease or healthy animals. In addition, the immunogenicity and protective efficacy of rLiHyp1 plus saponin was evaluated in BALB/c mice challenged subcutaneously with virulent L. infantum promastigotes. rLiHyp1 plus saponin vaccinated mice showed a high and specific production of IFN-γ, IL-12, and GM-CSF after in vitro stimulation with the recombinant protein. Immunized and infected mice, as compared to the control groups (saline and saponin, showed significant reductions in the number of parasites found in the liver, spleen, bone marrow, and in the paws' draining lymph nodes. Protection was associated with an IL-12-dependent production of IFN-γ, produced mainly by CD4 T cells. In these mice, a decrease in the parasite-mediated IL-4 and IL-10 response could also be observed. CONCLUSIONS/SIGNIFICANCE: The present study showed that this Leishmania oxygenase amastigote-specific protein can be used for a more sensitive and specific serodiagnosis of asymptomatic and symptomatic CVL and, when combined with a Th1-type adjuvant, can also be employ as a candidate antigen to develop vaccines against VL.

  19. 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)

    2011-09-28

    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

  20. Cancer testis antigen and immunotherapy

    Directory of Open Access Journals (Sweden)

    Krishnadas DK

    2013-04-01

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

  1. Identification of antigens specific to non-tuberculous mycobacteria: the Mce family of proteins as a target of T cell immune responses.

    Directory of Open Access Journals (Sweden)

    Anna M Checkley

    Full Text Available The lack of an effective TB vaccine hinders current efforts in combating the TB pandemic. One theory as to why BCG is less protective in tropical countries is that exposure to non-tuberculous mycobacteria (NTM reduces BCG efficacy. There are currently several new TB vaccines in clinical trials, and NTM exposure may also be relevant in this context. NTM exposure cannot be accurately evaluated in the absence of specific antigens; those which are known to be present in NTM and absent from M. tuberculosis and BCG. We therefore used a bioinformatic pipeline to define proteins which are present in common NTM and absent from the M. tuberculosis complex, using protein BLAST, TBLASTN and a short sequence protein BLAST to ensure the specificity of this process. We then assessed immune responses to these proteins, in healthy South Africans and in patients from the United Kingdom and United States with documented exposure to NTM. Low level responses were detected to a cluster of proteins from the mammalian cell entry family, and to a cluster of hypothetical proteins, using ex vivo ELISpot and a 6 day proliferation assay. These early findings may provide a basis for characterising exposure to NTM at a population level, which has applications in the field of TB vaccine design as well as in the development of diagnostic tests.

  2. Distribution and surfactant association of carcinoembryonic cell adhesion molecule 6 in human lung

    OpenAIRE

    Chapin, Cheryl; Bailey, Nicole A.; Gonzales, Linda W.; Lee, Jae-Woo; Gonzalez, Robert F.; Ballard, Philip L.

    2011-01-01

    Carcinoembryonic cell adhesion molecule 6 (CEACAM6) is a glycosylated, glycophosphatidylinositol-anchored protein expressed in epithelial cells of various primate tissues. It binds gram-negative bacteria and is overexpressed in human cancers. CEACAM6 is associated with lamellar bodies of cultured type II cells of human fetal lung and protects surfactant function in vitro. In this study, we characterized CEACAM6 expression in vivo in human lung. CEACAM6 was present in lung lavage of premature ...

  3. 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.

  4. THE EFFECTS OF GAMMA-INTERFERON COMBINED WITH 5-FLUOROURACIL OR 5-FLUORO-2'-DEOXYURIDINE ON PROLIFERATION AND ANTIGEN EXPRESSION IN A PANEL OF HUMAN COLORECTAL-CANCER CELL-LINES

    NARCIS (Netherlands)

    MAAS, IWHM; BOVEN, E; PINEDO, HM; SCHLUPER, HMM; Haisma, Hidde

    1991-01-01

    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

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

    Institute of Scientific and Technical Information of China (English)

    丁春艳; 桑梅香

    2010-01-01

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

  6. 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

    2005-01-01

    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.

  7. Combination of Circulating Tumor Cells with Serum Carcinoembryonic Antigen Enhances Clinical Prediction of Non-Small Cell Lung Cancer

    OpenAIRE

    Xi Chen; Xu Wang; Hua He; Ziling Liu; Ji-Fan Hu; Wei Li

    2015-01-01

    Circulating tumor cells (CTCs) have emerged as a potential biomarker in the diagnosis, prognosis, treatment, and surveillance of lung cancer. However, CTC detection is not only costly, but its sensitivity is also low, thus limiting its usage and the collection of robust data regarding the significance of CTCs in lung cancer. We aimed to seek clinical variables that enhance the prediction of CTCs in patients with non-small cell lung cancer (NSCLC). Clinical samples and pathological data were c...

  8. P48 Major Surface Antigen of Mycoplasma agalactiae Is Homologous to a malp Product of Mycoplasma fermentans and Belongs to a Selected Family of Bacterial Lipoproteins

    OpenAIRE

    Rosati, Sergio; Pozzi, Sarah; Robino, Patrizia; Montinaro, Barbara; Conti, Amedeo; Fadda, Manlio; Pittau, Marco

    1999-01-01

    A major surface antigenic lipoprotein of Mycoplasma agalactiae, promptly recognized by the host's immune system, was characterized. The mature product, P48, showed significant similarity and shared conserved amino acid motifs with lipoproteins or predicted lipoproteins from Mycoplasma fermentans, Mycoplasma hyorhinis, relapsing fever Borrelia spp., Bacillus subtilis, and Treponema pallidum.

  9. Characterization of a common antigen of colorectal and mucinous ovarian tumors, COTA.

    Science.gov (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

    1984-01-01

    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.

  10. 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

    2013-01-01

    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.

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

    Science.gov (United States)

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

    2011-01-15

    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. Study of the structure and impact of human leukocyte antigen (HLA)-G-A, HLA-G-B, and HLA-G-DRB1 haplotypes in families with recurrent miscarriage

    DEFF Research Database (Denmark)

    Kolte, Astrid Marie; Steffensen, Rudi Nora; Nielsen, Henriette S;

    2010-01-01

    A 14-base pair (bp) long insertion (ins)/deletion (del) polymorphism in exon 8 in the 3'-untranslated region of the human leukocyte antigen (HLA)-G gene is suggested to affect transcription of the gene. Carriage of the G14bp ins is associated with low levels of soluble HLA-G and increases the risk...... of recurrent miscarriage (RM). Due to existence of strong linkage disequilibrium (LD) in the HLA region, the primary susceptibility genes for RM in the HLA-G region have not yet been identified. HLA-A, -B, -DRB1, and -G14bp polymorphisms were investigated in 29 Caucasian families with two or more...... siblings suffering unexplained RM. Strong positive LD was detected between the G14bp ins and HLA-A*01, -A*11, -A*31, -B*08, and DRB1*03, whereas strong negative LD was found between G14bp ins and HLA-A*02, -A*03, and -A*24. The frequency of haplotypes with HLA-G14bp ins inherited from the mother was...

  13. Study of the structure and impact of human leukocyte antigen (HLA)-G-A, HLA-G-B, and HLA-G-DRB1 haplotypes in families with recurrent miscarriage

    DEFF Research Database (Denmark)

    Kolte, Astrid Marie; Steffensen, Rudi Nora; Nielsen, Henriette S;

    2010-01-01

    siblings suffering unexplained RM. Strong positive LD was detected between the G14bp ins and HLA-A*01, -A*11, -A*31, -B*08, and DRB1*03, whereas strong negative LD was found between G14bp ins and HLA-A*02, -A*03, and -A*24. The frequency of haplotypes with HLA-G14bp ins inherited from the mother was......A 14-base pair (bp) long insertion (ins)/deletion (del) polymorphism in exon 8 in the 3'-untranslated region of the human leukocyte antigen (HLA)-G gene is suggested to affect transcription of the gene. Carriage of the G14bp ins is associated with low levels of soluble HLA-G and increases the risk...... of recurrent miscarriage (RM). Due to existence of strong linkage disequilibrium (LD) in the HLA region, the primary susceptibility genes for RM in the HLA-G region have not yet been identified. HLA-A, -B, -DRB1, and -G14bp polymorphisms were investigated in 29 Caucasian families with two or more...

  14. Histocompatibility antigen test

    Science.gov (United States)

    ... more common in certain autoimmune diseases . For example, HLA-B27 antigen is found in many people (but not ... More Ankylosing spondylitis Autoimmune disorders Bone marrow transplant HLA-B27 antigen Kidney transplant Reactive arthritis Update Date 2/ ...

  15. Characterization of Ewing sarcoma associated cancer/testis antigens

    OpenAIRE

    Mahlendorf, Dorothea E.; Staege, Martin Sebastian

    2013-01-01

    The prognosis of patients suffering from tumors of the Ewing family (EFT) is still poor. Immunotherapy strategies are pursued and EFT-specific antigens have to be identified as targets for cytotoxic T-lymphocytes (CTL). Due to the lack of expression of cancer/testis antigens (CTA) in normal tissues, these antigens are partially able to induce immune responses in cancer patients. Therefore, they are promising targets for immunotherapy. EFT are characterized by chromosomal rearrangements involv...

  16. Cyst Fluid Carcinoembryonic Antigen Level Is not Predictive of Invasive Cancer in Patients with Intraductal Papillary Mucinous Neoplasm of the Pancreas

    Directory of Open Access Journals (Sweden)

    Stephen Kucera

    2012-07-01

    Full Text Available Context Cyst fluid CEA concentration >192ng/mL has proven accurate to differentiate mucinous from non-mucinous pancreatic cystic neoplasms. It is unclear whether the degree of cyst fluid CEA elevation is predictive of malignant behavior in IPMNs. Objectives To determine whether elevated cyst fluid CEA concentrations were predictive of invasive cancer. Design Cross sectional study. Setting Single National Cancer Institute comprehensive cancer care center experience. Patients Forty-seven patients underwent preoperative EUS-FNA with cyst fluid analysis and surgical resection of an IPMN over a 9 year period. Main outcome measurements Cyst fluid CEA concentrations among the four grades associated with IPMN (low grade dysplasia, moderate dysplasia, high grade dysplasia, and invasive cancer. Results The mean±standard deviation cyst fluid CEA concentration increased as the pathology progressed from low grade dysplasia (1,261±1,679 ng/mL to moderate dysplasia (7,171±22,210 ng/mL to high grade dysplasia (10,807±36,203 ng/mL. However, the mean CEA level decreased (462±631 ng/mL once invasive cancer developed (P=0.869. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of a cyst fluid CEA concentration greater than 200 ng/mL for the diagnosis of malignant IPMN (cases of high grade dysplasia and invasive IPMN was 52.4%, 42.3%, 42.3%, 52.4% and 46.8%, respectively. Limitations Single center experience, small patient numbers, retr ospective data collection. Conclusion The degree of cyst fluid CEA elevation is a poor predictor of malignant degeneration within IPMNs. Clinical management decisions regarding surgical resection should not be based upon degree of cyst fluid CEA elevation.

  17. Diagnostic utility of serum and pleural fluid carcinoembryonic antigen, and cytokeratin 19 fragments in patients with effusion from nonsmall cell lung cancer

    OpenAIRE

    Sushil Kumar Sharma; Sanjay Bhat; Vikas Chandel; Mayank Sharma; Pulkit Sharma; Sakul Gupta; Sashank Sharma; Aijaz Ahmed Bhat

    2015-01-01

    Aims: To assess the diagnostic value of CEA and CYFRA 21-1 (cytokeratin 19 fragments) in serum and pleural fluid in non small cell lung cancer with malignant pleural effusion (MPE). Settings and Design: Two subsets of patients were recruited with lymphocytic exudative effusion, one subset constituted diagnosed patients of NSCLC with malignant pleural effusion and the other subset of constituted with Tubercular pleural effusion. Methods and Material : CYFRA 21-1 and CEA levels were measured us...

  18. Comparison of a new tumour marker CA 242 with CA 19-9, CA 50 and carcinoembryonic antigen (CEA) in digestive tract diseases.

    OpenAIRE

    Kuusela, P.; Haglund, C.; Roberts, P. J.

    1991-01-01

    The levels of CA 242, a new tumour marker of carbohydrate nature, were measured in sera of 185 patients with malignancies of the digestive tract and of 123 patients with benign digestive tract diseases. High percentages of elevated CA 242 levels (greater than 20 U ml-1) were recorded in patients with pancreatic and biliary cancers (68%). The sensitivity was somewhat lower than that of CA 19-9 (76%) and CA 50 (73%). On the other hand, in benign pancreatic and biliary tract diseases the CA 242 ...

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

    Science.gov (United States)

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

    2010-01-01

    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

  20. 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

    2005-02-01

    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.

  1. Diagnostic utility of serum and pleural fluid carcinoembryonic antigen, and cytokeratin 19 fragments in patients with effusion from nonsmall cell lung cancer

    Directory of Open Access Journals (Sweden)

    Sushil Kumar Sharma

    2015-01-01

    Full Text Available Aims: To assess the diagnostic value of CEA and CYFRA 21-1 (cytokeratin 19 fragments in serum and pleural fluid in non small cell lung cancer with malignant pleural effusion (MPE. Settings and Design: Two subsets of patients were recruited with lymphocytic exudative effusion, one subset constituted diagnosed patients of NSCLC with malignant pleural effusion and the other subset of constituted with Tubercular pleural effusion. Methods and Material : CYFRA 21-1 and CEA levels were measured using Electrochemilumiscence Immunoassay (ECLIA. The test principle used the Sandwich method. For both the tests, results are determined via a calibration curve which is instrument specifically generated by 2 - point calibration and a master curve provided via reagent barcode. Statistical Analysis Used: All data are expressed as means ± SD and percentage. All the parametric variables were analysed by student-t test where as non parametric variables were compared by Mann-Whitney U-test Statistical significance was accepted for P values < 0.05. Software used were SPSS 11.5, and MS excel 2007. In order to compare the performance of the tumor markers, receiver operating characteristic (ROC curves were constructed and compared with area under the curve (AUC. The threshold for each marker was selected based on the best diagnostic efficacy having achieved equilibrium between sensitivity and specificity. Results: In cases serum CYFRA21-1 levels had mean value of 34.1 ± 29.9 with a range of 1.6-128.3 where as in controls serum CYFRA21-1 levels had mean value of 1.9 ± 1.0 with a range of 0.5-4.7. In cases serum CEA levels had mean value of 24.9 ± 47.3 with a range of 1.0, 267.9 where as in controls serum CEA levels had mean value of 1.9 ± 1.4 with a range of 0.2-6.8. The difference in the means of serum CYFRA 21-l (P = 0.000 and CEA (P = 0.046 were statistically significant. In cases pleural fluid CYFRA21-1 levels had mean value of 160.1 ± 177.1 with a range of 5.4-517.2 where as in controls pleural fluid CYFRA21-1 levels had mean value of 15.9 ± 5.7 with a range of 7.2-29.6. In cases CEA pleural fluid levels had mean value of 89.8 ± 207.4 with a range of 1.0-861.2 where as in controls CEA levels had mean value of 2.5 ± 2.3 with a range of 1-8.9. The difference in the means of CYERA 21-1 (P = 0.001 between cases and controls is statistically significant. Conclusions: CYFRA21-1 (serum - pleural fluid is a sensitive marker for NSCLC with sensitivity of 96.7%, highest of any combination [Serum (CYFRA 21-1 - CEA. CEA (Serum + Pleural Fluid, Pleural Fluid (CYFRA 21-1 + CEA] and specificity of 77.8%. Levels of CYFRA21-l (serum + pleural fluid are increased in malignant pleural effusion, so it is better to be used in suspicious malignant pleural effusion showing negative cytology, particularly in the absence of a visible tumor and or unsuitability for invasive procedure.

  2. Development of a double-antibody radioimmunoassay for detecting ovarian tumor-associated antigen fraction OCA in plasma

    International Nuclear Information System (INIS)

    Ovarian tumor-associated antigen isolated from human tumor tissue was shown to have a different mobility from that of carcinoembryonic antigen (CEA) in both acrylamide gel electrophoresis and immunoelectrophoresis in agarose. The ovarian tumor antigen is composed of six species with different electrophoretic mobility in acrylamide gel electrophoresis. Three of these species were detected in Sephadex G-100 ovarian fraction OCA (from the void volume peak) and the other three species of lower apparent molecular weight were detected in fraction OCD (from the second peak). Fractions OCA and OCD did not share common antigenic determinants as determined by immunodiffusion. CEA was shown to share antigenic determinants with both OCA and OCD. A double-antibody radioimmunoassay capable of detecting nanogram quantities of plasma OCA was developed. In a preliminary study of ovarian cancer patients, OCA appeared to be a more sensitive marker for ovarian cancer than CEA. There was virtually no correlation (r2 = 0.1) between OCA and CEA levels in these patients, as determined by radioimmunoassay

  3. Intramolecular trimerization, a novel strategy for making multispecific antibodies with controlled orientation of the antigen binding domains.

    Science.gov (United States)

    Alvarez-Cienfuegos, Ana; Nuñez-Prado, Natalia; Compte, Marta; Cuesta, Angel M; Blanco-Toribio, Ana; Harwood, Seandean Lykke; Villate, Maider; Merino, Nekane; Bonet, Jaume; Navarro, Rocio; Muñoz-Briones, Clara; Sørensen, Karen Marie Juul; Mølgaard, Kasper; Oliva, Baldo; Sanz, Laura; Blanco, Francisco J; Alvarez-Vallina, Luis

    2016-01-01

    Here, we describe a new strategy that allows the rapid and efficient engineering of mono and multispecific trivalent antibodies. By fusing single-domain antibodies from camelid heavy-chain-only immunoglobulins (VHHs) to the N-terminus of a human collagen XVIII trimerization domain (TIE(XVIII)) we produced monospecific trimerbodies that were efficiently secreted as soluble functional proteins by mammalian cells. The purified VHH-TIE(XVIII) trimerbodies were trimeric in solution and exhibited excellent antigen binding capacity. Furthermore, by connecting with two additional glycine-serine-based linkers three VHH-TIE(XVIII) modules on a single polypeptide chain, we present an approach for the rational design of multispecific tandem trimerbodies with defined stoichiometry and controlled orientation. Using this technology we report here the construction and characterization of a tandem VHH-based trimerbody capable of simultaneously binding to three different antigens: carcinoembryonic antigen (CEA), epidermal growth factor receptor (EGFR) and green fluorescence protein (GFP). Multispecific tandem VHH-based trimerbodies were well expressed in mammalian cells, had good biophysical properties and were capable of simultaneously binding their targeted antigens. Importantly, these antibodies were very effective in inhibiting the proliferation of human epidermoid carcinoma A431 cells. Multispecific VHH-based trimerbodies are therefore ideal candidates for future applications in various therapeutic areas. PMID:27345490

  4. Molecular cloning of cDNA for the human tumor-associated antigen CO-029 and identification of related transmembrane antigens

    Energy Technology Data Exchange (ETDEWEB)

    Szala, S.; Kasai, Yasushi; Steplewski, Z.; Rodeck, U.; Koprowski, H.; Linnenbach, A.J. (Wistar Inst. of Anatomy and Biology, Philadelphia, PA (USA))

    1990-09-01

    The human tumor-associated antigen CO-029 is a monoclonal antibody-defined cell surface glycoprotein of 27-34 kDa. By using the high-efficiency COS cell expression system, a full-length cDNA clone for CO-029 was isolated. When transiently expressed in COS cells, the cDNA clone directed the synthesis of an antigen reactive to monoclonal antibody CO-029 in mixed hemadsorption and immunoblot assays. Sequence analysis revealed that CO-029 belongs to a family of cell surface antigens that includes the melanoma-associated antigen ME491, the leukocyte cell surface antigen CD37, and the Sm23 antigen of the parasitic helminth Schistosoma mansoni. CO-029 and ME491 antigen expression and the effect of their corresponding monoclonal antibodies on cell growth were compared in human tumor cell lines of various histologic origins.

  5. Murine antigen-induced arthritis.

    NARCIS (Netherlands)

    Berg, W.B. van den; Joosten, L.A.B.; Lent, P.L.E.M. van

    2007-01-01

    Antigen induced arthritis is a unilateral T-cell driven model caused by direct injection of an antigen into the knee joint of a FCA preimmunized animal. The chronicity is determined by antigen retention in avascular structures of the joint through charge mediated binding or antibody mediated trappin

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

    Science.gov (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

    2007-12-15

    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.

  7. The effects of Nigella sativa (Ns), Anthemis hyalina (Ah) and Citrus sinensis (Cs) extracts on the replication of coronavirus and the expression of TRP genes family

    OpenAIRE

    Ulasli, Mustafa; Gurses, Serdar A.; Bayraktar, Recep; Yumrutas, Onder; Oztuzcu, Serdar; Igci, Mehri; Igci, Yusuf Ziya; Cakmak, Ecir Ali; Arslan, Ahmet

    2014-01-01

    Extracts of Anthemis hyalina (Ah), Nigella sativa (Ns) and peels of Citrus sinensis (Cs) have been used as folk medicine to fight antimicrobial diseases. To evaluate the effect of extracts of Ah, Ns and Cs on the replication of coronavirus (CoV) and on the expression of TRP genes during coronavirus infection, HeLa-CEACAM1a (HeLa-epithelial carcinoembryonic antigen-related cell adhesion molecule 1a) cells were inoculated with MHV-A59 (mouse hepatitis virus–A59) at moi of 30. 1/50 dilution of t...

  8. A "new" primed lymphocyte typing (PLT) defined DP-antigen associated with a private HLA--DR antigen

    DEFF Research Database (Denmark)

    Morling, N; Jakobsen, B K; Platz, P;

    1980-01-01

    We have recently described a "new" private HLA-DR antigen, DR"LTM", which has a frequency of approximately 0.6% in Danes. Primed Lymphocyte Typing (PLT) cells directed towards DR"LTM"-associated determinants were generated in vitro by haplotype primings in two unrelated families with DR...... total agreement between the results obtained by HLA-DR typing with the antiserum "LTM" and by PLT-typing with these two haplotype primed PLT-cells. None of the DP"LTM"-positive individuals carried more than one of the antigens HLA-Dw/-DRw/DP1-8 and the local specificity D/DP"H". Accordingly, this "new......" PLT-defined antigen, DP"LTM", most probably belongs to the series of HLA-D/DR-associated DP-antigens previously described....

  9. 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.

    Science.gov (United States)

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

    1995-01-01

    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.

  10. Application of In Vivo Induced Antigen Technology (IVIAT) to Bacillus anthracis

    OpenAIRE

    Peppercorn, Amanda; Young, John S; Drysdale, Melissa; Baresch, Andrea; Bikowski, Margaret V.; Ashford, David A.; Quinn, Conrad P.; Handfield, Martin; Hillman, Jeffrey D.; Lyons, C. Rick; Koehler, Theresa M.; Sonenshein, Abraham L.; Rollins, Sean McKenzie; Calderwood, Stephen Beaven; Ryan, Edward Thomas

    2008-01-01

    In vivo induced antigen technology (IVIAT) is an immuno-screening technique that identifies bacterial antigens expressed during infection and not during standard in vitro culturing conditions. We applied IVIAT to Bacillus anthracis and identified PagA, seven members of a N-acetylmuramoyl-L-alanine amidase autolysin family, three P60 family lipoproteins, two transporters, spore cortex lytic protein SleB, a penicillin binding protein, a putative prophage holin, respiratory nitrate reductase Nar...

  11. Human leucocyte antigens in tympanosclerosis.

    Science.gov (United States)

    Dursun, G; Acar, A; Turgay, M; Calgüner, M

    1997-02-01

    This study was designed to evaluate the association between certain HLA antigens and tympanosclerosis. The serum concentrations of HLA antigens were measured by a microlymphocytotoxicity technique in patients with tympanosclerosis and compared with a healthy control group. The serum levels of HLA-B35 and -DR3 were significantly higher in the patients with tympanosclerosis. This result suggests that certain types of HLA antigens may play an important role as an indicator or mediator in the pathogenesis of tympanosclerosis. PMID:9088683

  12. Antigen antibody interactions

    CERN Document Server

    DeLisi, Charles

    1976-01-01

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

  13. 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

    2005-04-01

    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.

  14. HLA antigens in Japanese patients with myasthenia gravis.

    OpenAIRE

    Matsuki, K; Juji, T.; Tokunaga, K.; Takamizawa, M; Maeda, H.; Soda, M; Nomura, Y; Segawa, M.

    1990-01-01

    HLA antigens in 104 Japanese patients and 41 families with myasthenia gravis (MG) were investigated. The frequencies of DR9 and DRw13 were significantly increased in the patients who developed MG before 3 yr of age. The DQw3 antigen was positive for all the patients that developed MG before 15 yr with only one exception. All the examined cases that developed MG before 3 yr (including this DQw3 negative patient) had the same DQA and DQB DNA restriction fragments. These HLA frequencies decrease...

  15. [Immunoglobulin genes encoding antibodies directed to oncodevelopmental carbohydrate antigens].

    Science.gov (United States)

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

    1990-07-01

    We investigated the immunoglobulin genes which encode the variable region of the monoclonal antibodies directed to the onco-developmental carbohydrate antigens such SSEA-1, fucosyl SSEA-1, SSEA-3 and SSEA-4. The VH region of these antibodies was preferentially encoded by the gene members of the X24, VH7183 and Q52 families, the families which are known to be located at the 3'-end region of the murine germ line VH gene. This result is interesting particularly when considering that the members of the 3'-end VH families are known to be preferentially expressed in embryonic B lymphocytes by an intrinsic genetic program. The comparative study of the nucleic acid sequences of mRNAs encoding these antibodies and the sequences of the corresponding germ line VH genes disclosed that the sequences encoding the antibodies contain no mutation from the germ line VH genes, or contain only a few somatic mutations, which are thought to be insignificant for the reactivity of the antibodies to the nominal antigens. These results imply that some of the embryonic B lymphocytes that express the unmutated germ line VH genes of the 3'-end families can be reactive with embryonic carbohydrate antigens, albeit rearranged with appropriate D-JH gene segments, and coupled with proper light chains. The VH region of the syngenic monoclonal anti-idiotypic antibodies directed to these anti-carbohydrate antibodies were also encoded preferentially by the members of the 3'-end VH families. We propose here that a part of the virgin embryonic B lymphocytes, which express the antibody encoded by the gene members of the 3'-end VH families at the cell surface, will be stimulated by the embryonic carbohydrate antigens which are abundantly present in the internal milieu of the embryo. The clonally expanded B lymphocytes, in turn, will facilitate the proliferation of other populations of embryonic B lymphocytes expressing the corresponding anti-idiotypic antibodies, which are also encoded by the gene members

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

    Science.gov (United States)

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

    2011-12-01

    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.

  17. [Antigenic response against PPD and antigen 60 in tubercular patients: single antigen versus the combined test].

    Science.gov (United States)

    Máttar, S; Broquetas, J M; Gea, J; Aran, X; el-Banna, N; Sauleda, J; Torres, J M

    1992-05-01

    We analyze serum samples from 70 patients with pulmonary tuberculosis and 50 healthy individuals. The antigenic activity (IgG) against protein purified antigen (PPD) and antigen 60 (A60) from M. tuberculosis. Thirteen patients were also HIV infected, and three patients had AIDS defined by the presence of disseminated tuberculosis. The test using antigen alone showed a 77% sensitivity and 74% specificity when PPD is used. When A60 was used, both values improved (81% sensitivity, 94% specificity). The use of a combined test (PPD and A60) improves the sensitivity (89%) but reduces the specificity (82%). The HIV infected patients showed similar responses to those of other patients. The combined use of different antigens might be useful for diagnosing tuberculosis. PMID:1390996

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

    Directory of Open Access Journals (Sweden)

    Claudia Schlimper

    2012-01-01

    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.

  19. Role of tumor-associated antigen expression in radioimmunoguided surgery for colorectal and breast cancer.

    Science.gov (United States)

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

    1998-12-01

    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.

  20. Increased serum carbohydrate antigen 19-9 in relapsed ductal breast carcinoma.

    Science.gov (United States)

    Papantoniou, Vassilios; Tsiouris, Spyridon; Koutsikos, John; Ptohis, Nikolaos; Lazaris, Dimitrios; Zerva, Cherry

    2006-01-01

    Increased serum carbohydrate antigen (CA) 19-9 is a quite uncommon manifestation of breast cancer both on early disease and on relapse. A 53-year-old woman with invasive ductal breast carcinoma underwent left-sided mastectomy. Two years later she palpated a subcutaneous mass at the mastectomy scar, arousing suspicion of local relapse. Surgery and histopathology revealed infiltration by breast adenocarcinoma and she was treated with chemotherapy. At that time serum tumor markers, carcinoembryonic antigen (CEA) and CA 15-3 were within normal range. Over the next six months she displayed an increase of serum CEA while serum CA 15-3 remained within normal range. In an attempt to search for a second neoplasm possibly of gastrointestinal (GI) origin, abdominal computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangio-pancreatography (MRCP), endoscopy of the upper GI tract and colonoscopy were performed, as well as measurement of serum CA 19-9. While no indication of a GI neoplasm was detected, she displayed an over 10-fold increase of serum CA 19-9. The patient had also an X-ray mammography and technetium-99m hexakis-2-methoxyisobutylisonitrile ((99m)Tc-MIBI) scintimammography (SM). Whilst mammography was negative for contralateral disease recurrence, SM was suggestive of axillary lymph node involvement. Axillary lymph node dissection confirmed an extensive metastatic infiltration of these nodes by breast adenocarcinoma. Three months later serum CA 19-9 and CEA became normal. The interest of this case lies on the unexpected high serum CA 19-9 values found in a breast relapsed adenocarcinoma and in the important contribution of SM in diagnosing the axillary lymph node metastatic infiltration. PMID:16617392

  1. 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.

    2007-01-01

    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

  2. Family Life

    Science.gov (United States)

    ... Family and Friends > Family Life Request Permissions Family Life Approved by the Cancer.Net Editorial Board , 07/ ... treatment become as overwhelming for others in your life as they are for you. Understanding the potential ...

  3. Familial hypertriglyceridemia

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000397.htm Familial hypertriglyceridemia To use the sharing features on this page, please enable JavaScript. Familial hypertriglyceridemia is a common disorder passed down through families. ...

  4. Family Disruptions

    Science.gov (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 ...

  5. Family Arguments

    Science.gov (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 ...

  6. Family Meals

    Science.gov (United States)

    ... Story" 5 Things to Know About Zika & Pregnancy Family Meals KidsHealth > For Parents > Family Meals Print A ... even more important as kids get older. Making Family Meals Happen It can be a big challenge ...

  7. [Farmer's lung antigens in Germany].

    Science.gov (United States)

    Sennekamp, J; Joest, M; Sander, I; Engelhart, S; Raulf-Heimsoth, M

    2012-05-01

    Recent studies suggest that besides the long-known farmer's lung antigen sources Saccharopolyspora rectivirgula (Micropolyspora faeni), Thermoactinomyces vulgaris, and Aspergillus fumigatus, additionally the mold Absidia (Lichtheimia) corymbifera as well as the bacteria Erwinia herbicola (Pantoea agglomerans) and Streptomyces albus may cause farmer's lung in Germany. In this study the sera of 64 farmers with a suspicion of farmer's lung were examined for the following further antigens: Wallemia sebi, Cladosporium herbarum, Aspergillus versicolor, and Eurotium amstelodami. Our results indicate that these molds are not frequent causes of farmer's lung in Germany. PMID:22477566

  8. Family Privilege

    Science.gov (United States)

    Seita, John R.

    2014-01-01

    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…

  9. Rationally designed inhibitor targeting antigen-trimming aminopeptidases enhances antigen presentation and cytotoxic T-cell responses.

    Science.gov (United States)

    Zervoudi, Efthalia; Saridakis, Emmanuel; Birtley, James R; Seregin, Sergey S; Reeves, Emma; Kokkala, Paraskevi; Aldhamen, Yasser A; Amalfitano, Andrea; Mavridis, Irene M; James, Edward; Georgiadis, Dimitris; Stratikos, Efstratios

    2013-12-01

    Intracellular aminopeptidases endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and ERAP2), and as well as insulin-regulated aminopeptidase (IRAP) process antigenic epitope precursors for loading onto MHC class I molecules and regulate the adaptive immune response. Their activity greatly affects the antigenic peptide repertoire presented to cytotoxic T lymphocytes and as a result can regulate cytotoxic cellular responses contributing to autoimmunity or immune evasion by viruses and cancer cells. Therefore, pharmacological regulation of their activity is a promising avenue for modulating the adaptive immune response with possible applications in controlling autoimmunity, in boosting immune responses to pathogens, and in cancer immunotherapy. In this study we exploited recent structural and biochemical analysis of ERAP1 and ERAP2 to design and develop phosphinic pseudopeptide transition state analogs that can inhibit this family of enzymes with nM affinity. X-ray crystallographic analysis of one such inhibitor in complex with ERAP2 validated our design, revealing a canonical mode of binding in the active site of the enzyme, and highlighted the importance of the S2' pocket for achieving inhibitor potency. Antigen processing and presentation assays in HeLa and murine colon carcinoma (CT26) cells showed that these inhibitors induce increased cell-surface antigen presentation of transfected and endogenous antigens and enhance cytotoxic T-cell responses, indicating that these enzymes primarily destroy epitopes in those systems. This class of inhibitors constitutes a promising tool for controlling the cellular adaptive immune response in humans by modulating the antigen processing and presentation pathway. PMID:24248368

  10. Natural selection promotes antigenic evolvability

    NARCIS (Netherlands)

    Graves, C.J.; Ros, V.I.D.; Stevenson, B.; Sniegowski, P.D.; Brisson, D.

    2013-01-01

    The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide

  11. Oncogenic cancer/testis antigens

    DEFF Research Database (Denmark)

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

    2015-01-01

    /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...

  12. Proteomic selection of immunodiagnostic antigens for Trypanosoma congolense.

    Directory of Open Access Journals (Sweden)

    Jennifer R Fleming

    2014-06-01

    Full Text Available Animal African Trypanosomosis (AAT presents a severe problem for agricultural development in sub-Saharan Africa. It is caused by several trypanosome species and current means of diagnosis are expensive and impractical for field use. Our aim was to discover antigens for the detection of antibodies to Trypanosoma congolense, one of the main causative agents of AAT. We took a proteomic approach to identify potential immunodiagnostic parasite protein antigens. One hundred and thirteen proteins were identified which were selectively recognized by infected cattle sera. These were assessed for likelihood of recombinant protein expression in E. coli and fifteen were successfully expressed and assessed for their immunodiagnostic potential by ELISA using pooled pre- and post-infection cattle sera. Three proteins, members of the invariant surface glycoprotein (ISG family, performed favorably and were then assessed using individual cattle sera. One antigen, Tc38630, evaluated blind with 77 randomized cattle sera in an ELISA assay gave sensitivity and specificity performances of 87.2% and 97.4%, respectively. Cattle immunoreactivity to this antigen diminished significantly following drug-cure, a feature helpful for monitoring the efficacy of drug treatment.

  13. Localization of tumors by radiolabelled antibodies

    International Nuclear Information System (INIS)

    A method of utilizing radiolabelled antibodies to carcinoembryonic antigens for determining the site of tumors which produce or are associated with carcinoembryonic antigen is disclosed. 3 claims, no drawings

  14. Concepts and applications for influenza antigenic cartography

    Science.gov (United States)

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

    2011-01-01

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

  15. Muslim Families and Family Therapy.

    Science.gov (United States)

    Daneshpour, Manijeh

    1998-01-01

    Examines the applicability of the Anglo-American models of family therapy to Muslim immigrant families. The differences in value systems are the Muslim families' preferences for greater connectedness, a less flexible and more hierarchical family structure, and an implicit communication style. Suggests that directions for change for Muslims need to…

  16. Genome Scale Identification of Treponema pallidum Antigens

    OpenAIRE

    McKevitt, Matthew; Brinkman, Mary Beth; McLoughlin, Melanie; Perez, Carla; Howell, Jerrilyn K.; Weinstock, George M.; Norris, Steven J; Palzkill, Timothy

    2005-01-01

    Antibody responses for 882 of the 1,039 proteins in the proteome of Treponema pallidum were examined. Sera collected from infected rabbits were used to systematically identify 106 antigenic proteins, including 22 previously identified antigens and 84 novel antigens. Additionally, sera collected from rabbits throughout the course of infection demonstrated a progression in the breadth and intensity of humoral immunoreactivity against a representative panel of T. pallidum antigens.

  17. Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition

    Energy Technology Data Exchange (ETDEWEB)

    Archbold, Julia K.; Macdonald, Whitney A.; Gras, Stephanie; Ely, Lauren K.; Miles, John J.; Bell, Melissa J.; Brennan, Rebekah M.; Beddoe, Travis; Wilce, Matthew C.J.; Clements, Craig S.; Purcell, Anthony W.; McCluskey, James; Burrows, Scott R.; Rossjohn, Jamie; (Monash); (Queensland Inst. of Med. Rsrch.); (Melbourne)

    2009-07-10

    Human leukocyte antigen (HLA) gene polymorphism plays a critical role in protective immunity, disease susceptibility, autoimmunity, and drug hypersensitivity, yet the basis of how HLA polymorphism influences T cell receptor (TCR) recognition is unclear. We examined how a natural micropolymorphism in HLA-B44, an important and large HLA allelic family, affected antigen recognition. T cell-mediated immunity to an Epstein-Barr virus determinant (EENLLDFVRF) is enhanced when HLA-B*4405 was the presenting allotype compared with HLA-B*4402 or HLA-B*4403, each of which differ by just one amino acid. The micropolymorphism in these HLA-B44 allotypes altered the mode of binding and dynamics of the bound viral epitope. The structure of the TCR-HLA-B*4405EENLLDFVRF complex revealed that peptide flexibility was a critical parameter in enabling preferential engagement with HLA-B*4405 in comparison to HLA-B*4402/03. Accordingly, major histocompatibility complex (MHC) polymorphism can alter the dynamics of the peptide-MHC landscape, resulting in fine-tuning of T cell responses between closely related allotypes.

  18. 肺鳞癌CEA及CYFRA 21-1和NSE检测的临床意义%Clinical significance of detection of carcinoembryonic antigen, CYFRA 21-1, and neuron-specific enolase in lung squamous cell cancer patients

    Institute of Scientific and Technical Information of China (English)

    崔永; 龚民; 常栋; 吕可洁; 王天佑

    2008-01-01

    目的 研究癌胚抗原(CEA)、细胞角质蛋白(CYFRA21-1)和神经元特异性烯醇化酶(NSE)在肺鳞状细胞癌(SQC)患者血清中的水平与患者TNM分期、可否行手术治疗及预后之间的关系.方法 检测210例SQC患者的血清标本(Ⅰ期20例、Ⅱ期27例、ⅢA期55例、ⅢB期80例、Ⅳ期28例)CEA、CYFRA 21-1和NSE的血清水平.NSE和CYFRA21-1采用放免测定,CEA采用化学发光法测定.结果 CYFRA 21-1升高最为常见.CEA和CYFRA 21-1与TNM分期相关,而NSE与TNM分期无关.CEA和CYFRA 21-1血清水平均值与可手术(1、Ⅱ、ⅢA)和不可手术(ⅢB、Ⅳ期)有相关性(P<0.001).NSE血清水平均值与可否手术差异无显著性.结论 治疗前CYFRA 21-1和NSE的血清浓度与预后有关,可作为SQC患者可否手术的参考指标,并可为SQC预后判断提供重要信息.

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

    Science.gov (United States)

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

    2016-01-13

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

  20. Antigenic Variation in Plasmodium falciparum.

    Science.gov (United States)

    Petter, Michaela; Duffy, Michael F

    2015-01-01

    Plasmodium falciparum is the protozoan parasite that causes most malaria-associated morbidity and mortality in humans with over 500,000 deaths annually. The disease symptoms are associated with repeated cycles of invasion and asexual multiplication inside red blood cells of the parasite. Partial, non-sterile immunity to P. falciparum malaria develops only after repeated infections and continuous exposure. The successful evasion of the human immune system relies on the large repertoire of antigenically diverse parasite proteins displayed on the red blood cell surface and on the merozoite membrane where they are exposed to the human immune system. Expression switching of these polymorphic proteins between asexual parasite generations provides an efficient mechanism to adapt to the changing environment in the host and to maintain chronic infection. This chapter discusses antigenic diversity and variation in the malaria parasite and our current understanding of the molecular mechanisms that direct the expression of these proteins. PMID:26537377

  1. Familial gigantism

    Directory of Open Access Journals (Sweden)

    Wouter W. de Herder

    2012-01-01

    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.

  2. [HLA antigens in juvenile rheumatoid arthritis].

    Science.gov (United States)

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

    1990-01-01

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

  3. Stable solid-phase Rh antigen.

    Science.gov (United States)

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

    1997-12-01

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

  4. 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: shan.lu@umassmed.edu [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)

    2012-04-20

    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.

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

    International Nuclear Information System (INIS)

    Highlights: ► EV71 is a major emerging infectious disease in many Asian countries. ► Inactivated EV71 vaccines are in clinical studies but their safety and efficacy are unknown. ► Developing subunit based EV71 vaccines is significant and novel antigen design is needed. ► DNA immunization is an efficient tool to test the immunogenicity of VP1 based EV71 vaccines. ► 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.

  6. ANTIGENICITY OF COW'S MILK PROTEINS IN TWO ANIMAL MODELS

    Directory of Open Access Journals (Sweden)

    T.R. Neyestani

    2000-08-01

    Full Text Available Antigenicity of proteins found in cow's milk is age dependent. This is primarily due to infants possessing a more permeable intestinal wall than that in adults. Thus infants may acquire cow's milk allergy during their first year of life. While milk antigen specific IgE may cause allergy in susceptible subjects, there is some evidence indicating that milk antigen specific IgG may play some role in chronic disease development. The puropose of this study was to determine the antigenicity of cow's milk proteins in two animal models and to recommend the more sensitivie one, as an evaluation tool, to assess the antigenicity of a poteintial hypoallergenic formula. A crude extract of cow's milk was injected either to young male rabbits or BALB/C mice in four doses. Pure standard proteins of cow's milk were also injected to separate groups of animals to use their anti sera in later stages. The polyclonal pooled serum was then used to evaluate the antigenicity of the extract by indirect enzyme-linked immunossorbeni assay (LEISA. and Western blotting. Both the rabbit and BALB/C murine mode! demonstrated strong ELISA titres against casein and BSA proteins. However, the rabbit model also had a high antibody response against beta-lactoglobulin (/Mg. The lowest antibody response was found against alpha-kictalbumin («-la in both animal models and no response against immunoglobulins (Igs in either model. In Western blotting, rabbit antiserum showed four bands («-la, /Mg, caseins and BSA compared to two bands (caseins and BSA for mouse antiserum. Considering the allergenicity of these proteins in genetically prone subjects, it may be wise to exclude food sources of caseins as well as major whey proteins (BSA, from the diet of infants with a family history of atopy during the first year of life. The rabbit hyperimmunization model was more sensitive than the murine mode! in detecting antibodies against milk proteins. Thus, the rabbii model should be employed when

  7. 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

    2012-01-01

    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.

  8. 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.

    2007-01-01

    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

  9. Family therapy

    Directory of Open Access Journals (Sweden)

    Shaikh Altamash

    2013-01-01

    Full Text Available Another major force not letting us succeed in the treatment of diabetes remains right inside the patients home, their family members. Hence, it is important to know the perception of the close family members about this simple and strong tool in diabetes, ′insulin′. The drug is nearing its century, it has not fully being accepted gracefully even in todays electronic savvy society. So, we need to strongly discover the reason for its non-acceptance, while trials are out inventing new drugs. One vital thing that can change this attitude is increasing the understanding of this drug, insulin in depth to close people around the patient, the ′family′. Underestimating family′s perception about disease and treatment for diabetes is detrimental to both diseased and the doctor. This consists of a biopsychosocial model; biological, psychological and social factors. Family forms the most important part of it. The strategies in family therapy include psychodynamic, structural, strategic, and cognitive-behavioral component. Diabetes has and will continue to rise, so will be the treatment options. From the clinicians side its to fix fasting first but from patients its fix family first. Family therapy demonstrates the importance of insulin initiation and maintenance in insulin naive patients, and continuation for others. The specific needs of such patients and their impact on family life are met with family therapy. Who needs family therapy? Benefits of family therapy and a case based approach is covered.

  10. Family Finance

    OpenAIRE

    Christopher Kobrak

    2008-01-01

    As Mira Wilkins has argued, there is a curious disconnect between business and financial history. (Wilkins, 2003) Whereas business history literature has rediscovered the importance of family business in many countries and in many sectors of contemporary commercial life, for example, little has been written about family banking as an alternative to joint-stock, management-run financial institutions. This lacuna is odd for many reasons. First, family banking is one of the best-known examples o...

  11. My Family

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    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. Screening and characterization of early diagnostic antigens in excretory-secretory proteins from Trichinella spiralis intestinal infective larvae by immunoproteomics.

    Science.gov (United States)

    Liu, Ruo Dan; Jiang, Peng; Wen, Hui; Duan, Jiang Yang; Wang, Li Ang; Li, Jie Feng; Liu, Chun Ying; Sun, Ge Ge; Wang, Zhong Quan; Cui, Jing

    2016-02-01

    The excretory-secretory (ES) antigens from Trichinella spiralis muscle larvae are the most commonly used diagnostic antigens for trichinellosis, but specific IgG antibodies were not detected in early stage of infection. The aim of this study was to identify early diagnostic antigens from ES proteins of intestinal infective larvae (IIL), the first invasive stage of T. spiralis. Six bands (92, 52, 45, 35, 32, and 29 kDa) of IIL ES proteins were recognized by infection sera in Western blotting as early as 10 days post infection. Total of 54 T. spiralis proteins in six bands were identified by shotgun LC-MS/MS, 30 proteins were annotated, and 27 had hydrolase activity. Several proteins (serine protease, putative trypsin, deoxyribonuclease II family protein, etc.) could be considered as the potential early diagnostic antigens for trichinellosis. Our study provides new insights for screening early diagnostic antigens from intestinal worms of T. spiralis. PMID:26468148

  13. Family literacy

    DEFF Research Database (Denmark)

    Sehested, Caroline

    2012-01-01

    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....

  14. Antigen Incorporation on Cryptosporidium parvum Oocyst Walls

    OpenAIRE

    Entrala Emilio; Sbihi Younes; Sánchez-Moreno Manuel; Mascaró Carmen

    2001-01-01

    Cryptosporidium parvum oocysts are the infective stages responsible for transmission and survival of the organism in the environment. In the present work we show that the oocyst wall, far from being a static structure, is able to incorporate antigens by a mechanism involving vesicle fusion with the wall, and the incorporation of the antigen to the outer oocyst wall. Using immunoelectron microscopy we show that the antigen recognized by a monoclonal antibody used for diagnosis of cryptosporidi...

  15. Histocompatibility antigens in coal miners with pneumoconiosis.

    OpenAIRE

    Soutar, C A; Coutts, I.; Parkes, W R; Dodi, I. A.; Gauld, S; Castro, J E; Turner-Warwick, M

    1983-01-01

    Twenty-five histocompatibility antigens have been measured in 100 coal miners with pneumoconiosis attending a pneumoconiosis medical panel and the results compared with a panel of 200 normal volunteers not exposed to dust. Chest radiographs were read independently by three readers according to the ILO U/C classification. On a combined score, 40 men were thought to have simple pneumoconiosis and 60 men complicated pneumoconiosis. The number of antigens tested and associations between antigens ...

  16. Merozoite Surface Antigen 2 Proteins of Babesia bovis Vaccine Breakthrough Isolates Contain a Unique Hypervariable Region Composed of Degenerate Repeats

    OpenAIRE

    Berens, Shawn J.; Brayton, Kelly A.; Molloy, John B.; Bock, Russell E.; Lew, Ala E.; McElwain, Terry F.

    2005-01-01

    The merozoite surface antigen 2 (MSA-2) proteins of Babesia bovis are members of the variable merozoite surface antigen (VMSA) family that have been implicated in erythrocyte invasion and are important targets for antibody-mediated blocking of invasion. Extensive sequence variation in another VMSA member, MSA-1, has been shown in all vaccine breakthrough isolates. To test the hypothesis that the msa-2 genes of vaccine breakthrough isolates would also encode a diverse set of proteins, the comp...

  17. 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.

  18. Family matters

    DEFF Research Database (Denmark)

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

    2013-01-01

    scores for the children. For the adjusted associations, we again found the family stress variables in the healthy spouse to be related to the risk of emotional and behavioral problems in the children. CONCLUSIONS: The present results suggest that in ABI families, the children’s emotional functioning......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...

  19. HLA II class antigens and susceptibility to coeliac disease

    Directory of Open Access Journals (Sweden)

    Vojvodić Svetlana

    2011-01-01

    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 http://sysbio.cvm.msstate.edu/AntigenMap.

  1. A computational framework for influenza antigenic cartography.

    Science.gov (United States)

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

    2010-10-07

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

  2. HLA antigens in Japanese patients with myasthenia gravis.

    Science.gov (United States)

    Matsuki, K; Juji, T; Tokunaga, K; Takamizawa, M; Maeda, H; Soda, M; Nomura, Y; Segawa, M

    1990-01-01

    HLA antigens in 104 Japanese patients and 41 families with myasthenia gravis (MG) were investigated. The frequencies of DR9 and DRw13 were significantly increased in the patients who developed MG before 3 yr of age. The DQw3 antigen was positive for all the patients that developed MG before 15 yr with only one exception. All the examined cases that developed MG before 3 yr (including this DQw3 negative patient) had the same DQA and DQB DNA restriction fragments. These HLA frequencies decreased as the age of onset increased, and no significant association was observed in adult-onset MG. No patients had B8, DR3, and DQw2. The relative risk was higher for the DR9/DRw13 heterozygotes (37.4) than for DR9 (16.4) or DRw13 (7.1) in the childhood-onset MG. Statistical analysis suggested that DR9 and DRw13 (or DQw1 and DQw3) act synergistically in the disease development. Family study revealed diverse DR9 haplotypes. The most frequent DRw13 haplotype was Bw44-BFF-C4A3B1-DRw13-DQw1, which may be evolutionarily related to the caucasian B8-DR3-DQw2 haplotype. These results showed that MG in early childhood in Japanese individuals is genetically different from that in adulthood and that in caucasians. Images PMID:1974553

  3. Development of an algorithm for production of inactivated arbovirus antigens in cell culture.

    Science.gov (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

    2014-11-01

    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.

  4. Antibodies to new beta cell antigen ICA12 in Latvian diabetes patients.

    Science.gov (United States)

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

    2002-04-01

    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.

  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

    1998-04-01

    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. Virosomes for antigen and DNA delivery

    NARCIS (Netherlands)

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

    2005-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2015-10-01

    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.

  9. Editing of CD1d-Bound Lipid Antigens by Endosomal Lipid Transfer Proteins

    OpenAIRE

    Zhou, Dapeng; Cantu, Carlos; Sagiv, Yuval; Schrantz, Nicolas; Kulkarni, Ashok B.; Qi, Xiaoyang; Mahuran, Don J.; Carlos R Morales; Grabowski, Gregory A.; Benlagha, Kamel; Savage, Paul; Bendelac, Albert; Teyton, Luc

    2003-01-01

    It is now established that CD1 molecules present lipid antigens to T cells, although it is not clear how the exchange of lipids between membrane compartments and the CD1 binding groove is assisted. We report that mice deficient in prosaposin, the precursor to a family of endosomal lipid transfer proteins (LTP), exhibit specific defects in CD1d-mediated antigen presentation and lack Vα14 NKT cells. In vitro, saposins extracted monomeric lipids from membranes and from CD1, thereby promoting the...

  10. FAMILY RHAGIONIDAE.

    Science.gov (United States)

    Santos, Charles Morphy D; Carmo, Daniel D D

    2016-01-01

    The family Rhagionidae is one of the oldest Brachyeran lineages. Its monophyly is still uncertain. There are four rhagionid genera distributed in Neotropical Region but only three species of Chrysopilus are found in Colombia. PMID:27395270

  11. FAMILY PIOPHILIDAE.

    Science.gov (United States)

    Wolff, Marta; Pérez, Sandra; Grisales, Diana

    2016-01-01

    Piophilidae is a little family poorly known in Colombia, with only Piophila casei (L.) and Stearibia nigriceps Meigen reported so far. This catalogue expands the distribution of these species to other localities in the country. PMID:27395294

  12. Family History

    Science.gov (United States)

    ... to your relatives about their health. Draw a family tree and add the health information. Having copies of medical records and death certificates is also helpful. Centers for Disease Control and Prevention

  13. Familial hypercholesterolemia

    Science.gov (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 ...

  14. Family Business

    OpenAIRE

    UNAI ARTECHE

    2003-01-01

    Family Business, Pitzhanger Manor. Curated by Danielle Arnaud and Matthew Poole. The artists in the exhibition explore how their 'authorship' or 'individuality' is expressed as images. Here, artworks are produced that deal with the public face of the personal, private or local. In brief, the thematic of this exhibition is interested in the consequence and legitimacy of 'individual choice' as a genre or style. Hence, Family Business looks to artworks that claim, utilise and reflect upon lan...

  15. Expression, biosynthesis and release of preadipocyte factor-1/ delta-like protein/fetal antigen-1 in pancreatic -cells

    DEFF Research Database (Denmark)

    Friedrichsen, B N; Carlsson, C; Møldrup, A;

    2003-01-01

    Preadipocyte factor-1 (Pref-1)/delta-like protein/fetal antigen-1 (FA1) is a member of the epidermal growth factor-like family. It is widely expressed in embryonic tissues, whereas in adults it is confined to the adrenal gland, the anterior pituitary, the endocrine pancreas, the testis and the ov......Preadipocyte factor-1 (Pref-1)/delta-like protein/fetal antigen-1 (FA1) is a member of the epidermal growth factor-like family. It is widely expressed in embryonic tissues, whereas in adults it is confined to the adrenal gland, the anterior pituitary, the endocrine pancreas, the testis...

  16. Further characterization of filarial antigens by SDS polyacrylamide gel electrophoresis

    OpenAIRE

    Dissanayake, S.; Galahitiyawa, S. C.; Ismail, M. M.

    1983-01-01

    SDS (sodium dodecyl sulfate)-polyacrylamide gel electrophoresis of an antigen isolated from sera of Wuchereria bancrofti-infected patients and Setaria digitata antigen SD2-4 is reported. Both antigens showed carbohydrate (glycoprotein) staining. The W. bancrofti antigen had an apparent relative molecular mass of 35 000 while the S. digitata antigen SD2-4 migrated at the marker dye position on SDS-polyacrylamide gel electrophoresis. SDS treatment of these antigens did not abolish the precipita...

  17. Meningococcal vaccine antigen diversity in global databases.

    Science.gov (United States)

    Brehony, Carina; Hill, Dorothea M; Lucidarme, Jay; Borrow, Ray; Maiden, Martin C

    2015-01-01

    The lack of an anti-capsular vaccine against serogroup B meningococcal disease has necessitated the exploration of alternative vaccine candidates, mostly proteins exhibiting varying degrees of antigenic variation. Analysis of variants of antigen-encoding genes is facilitated by publicly accessible online sequence repositories, such as the Neisseria PubMLST database and the associated Meningitis Research Foundation Meningococcus Genome Library (MRF-MGL). We investigated six proposed meningococcal vaccine formulations by deducing the prevalence of their components in the isolates represented in these repositories. Despite high diversity, a limited number of antigenic variants of each of the vaccine antigens were prevalent, with strong associations of particular variant combinations with given serogroups and genotypes. In the MRF-MGL and globally, the highest levels of identical sequences were observed with multicomponent/multivariant vaccines. Our analyses further demonstrated that certain combinations of antigen variants were prevalent over periods of decades in widely differing locations, indicating that vaccine formulations containing a judicious choice of antigen variants have potential for long-term protection across geographic regions. The data further indicated that formulations with multiple variants would be especially relevant at times of low disease incidence, as relative diversity was higher. Continued surveillance is required to monitor the changing prevalence of these vaccine antigens. PMID:26676305

  18. Antigen incorporation on Cryptosporidium parvum oocyst walls

    Directory of Open Access Journals (Sweden)

    Entrala Emilio

    2001-01-01

    Full Text Available Cryptosporidium parvum oocysts are the infective stages responsible for transmission and survival of the organism in the environment. In the present work we show that the oocyst wall, far from being a static structure, is able to incorporate antigens by a mechanism involving vesicle fusion with the wall, and the incorporation of the antigen to the outer oocyst wall. Using immunoelectron microscopy we show that the antigen recognized by a monoclonal antibody used for diagnosis of cryptosporidiosis (Merifluor®, Meridian Diagnostic Inc. could be found associated with vesicles in the space between the sporozoites and the oocysts wall, and incorporated to the outer oocyst wall by an unknown mechanism.

  19. Family business

    OpenAIRE

    KLUZÁKOVÁ, Lucie

    2009-01-01

    This thesis focuses on family business companies and above all on their problem of succession planning. For the purposes of this work, I have chosen a family business company that is owned by two shareholders. Both shareholders are going to leave the company within next 5 to 10 years. The thesis deals with the succession plan of both shareholders and this concerning the rate of preparedness as well as the rate of coordination of both plans. Prior to the research, two hypotheses were fixed. Th...

  20. Family therapy.

    OpenAIRE

    Shaikh Altamash

    1987-01-01

    Another major force not letting us succeed in the treatment of diabetes remains right inside the patients home, their family members. Hence, it is important to know the perception of the close family members about this simple and strong tool in diabetes, ′insulin′. The drug is nearing its century, it has not fully being accepted gracefully even in todays electronic savvy society. So, we need to strongly discover the reason for its non-acceptance, while trials are out inventing new drugs. One ...

  1. Prostate-specific antigen (PSA) blood test

    Science.gov (United States)

    Prostate-specific antigen; Prostate cancer screening test; PSA ... PSA testing is an important tool for detecting prostate cancer, but it is not foolproof. Other conditions can cause a rise in PSA, including: A larger prostate ...

  2. Mapping Epitopes on a Protein Antigen by the Proteolysis of Antigen-Antibody Complexes

    Science.gov (United States)

    Jemmerson, Ronald; Paterson, Yvonne

    1986-05-01

    A monoclonal antibody bound to a protein antigen decreases the rate of proteolytic cleavage of the antigen, having the greatest effect on those regions involved in antibody contact. Thus, an epitope can be identified by the ability of the antibody to protect one region of the antigen more than others from proteolysis. By means of this approach, two distinct epitopes, both conformationally well-ordered, were characterized on horse cytochrome c.

  3. Tales of Antigen Evasion from CAR Therapy.

    Science.gov (United States)

    Sadelain, Michel

    2016-06-01

    Both T cells bearing chimeric antigen receptors and tumor-specific antibodies can successfully target some malignancies, but antigen escape can lead to relapse. Two articles in this issue of Cancer Immunology Research explore what effective countermeasures may prevent it. Cancer Immunol Res; 4(6); 473-473. ©2016 AACRSee articles by Zah et al., p. 498, and Rufener et al., p. 509. PMID:27252092

  4. Characterization of an antigenically distinct porcine rotavirus.

    OpenAIRE

    Bridger, J C; Clarke, I. N.; McCrae, M A

    1982-01-01

    A porcine virus with rotavirus morphology, which was antigenically unrelated to previously described rotaviruses, is described. Particles with an outer capsid layer measured 75 nm and those lacking the outer layer were 63 nm in diameter. Particles which resembled cores were also identified. The virus was shown to be antigenically distinct from other rotaviruses as judged by immunofluorescence and immune electron microscopy, and it failed to protect piglets from challenge with porcine rotaviru...

  5. FAMILY ROPALOMERIDAE.

    Science.gov (United States)

    Ale-Rocha, Rosaly

    2016-01-01

    Ropalomeridae is a small family with most species distributed in the Neotropical Region, from Mexico to Argentina, and only one Nearctic species. In Colombia, eight species distributed in four genera have been found. This catalogue, based on the study of specimens and available literature records, summarizes and updates the information on the Colombian fauna. PMID:27395300

  6. Familial hyperamylasemia

    Directory of Open Access Journals (Sweden)

    Koda Yu Kar Ling

    2002-01-01

    Full Text Available A 7-year-old white boy was referred to us with a history of 3 attacks of hypogastric pain over the previous 2 years and persistently elevated serum amylase concentrations. At physical examination, he was well with no evidence of clinical abnormalities. His weight and height were normal. Laboratory diagnostic investigations were all normal except for the presence of Ascaris lumbricoides in the feces and persistently elevated serum amylase levels. Serum amylase determinations in the family members were normal in his father and maternal grandmother but elevated in his mother, sister, maternal aunt, and uncle, all of whom asymptomatic. Macroamylasemia was excluded in the child and in the mother. The finding of persistently elevated amylasemia in the child and in the other family members spanning 3 generations, and the exclusion of diseases that lead to hyperamilasemia are consistent with the diagnosis of familial hyperamylasemia. Until now, only 1 similar case has been reported. Familial hyperamylasemia must be considered in the differential diagnosis of hyperamylasemias in childhood.

  7. Familial hyperamylasemia.

    Science.gov (United States)

    Koda, Yu Kar Ling; Vidolin, Eliana

    2002-01-01

    A 7-year-old white boy was referred to us with a history of 3 attacks of hypogastric pain over the previous 2 years and persistently elevated serum amylase concentrations. At physical examination, he was well with no evidence of clinical abnormalities. His weight and height were normal. Laboratory diagnostic investigations were all normal except for the presence of Ascaris lumbricoides in the feces and persistently elevated serum amylase levels. Serum amylase determinations in the family members were normal in his father and maternal grandmother but elevated in his mother, sister, maternal aunt, and uncle, all of whom asymptomatic. Macroamylasemia was excluded in the child and in the mother. The finding of persistently elevated amylasemia in the child and in the other family members spanning 3 generations, and the exclusion of diseases that lead to hyperamilasemia are consistent with the diagnosis of familial hyperamylasemia. Until now, only 1 similar case has been reported. Familial hyperamylasemia must be considered in the differential diagnosis of hyperamylasemias in childhood. PMID:11981589

  8. Family Circle

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    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.

  9. Finding Family

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    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

  10. Family Hypnotherapy.

    Science.gov (United States)

    Araoz, Daniel L.; Negley-Parker, Esther

    1985-01-01

    A therapeutic model to help families activate experiential and right hemispheric functioning through hypnosis is presented in detail, together with a clinical illustration. Different situations in which this model is effective are mentioned and one such set of circumstances is described. (Author)

  11. Familial hyperaldosteronism.

    Science.gov (United States)

    Stowasser, M; Gordon, R D

    2001-09-01

    Primary aldosteronism (PAL) may be as much as ten times more common than has been traditionally thought, with most patients normokalemic. The study of familial varieties has facilitated a fuller appreciation of the nature and diversity of its clinical, biochemical, morphological and molecular aspects. In familial hyperaldosteronism type I (FH-I), glucocorticoid-remediable PAL is caused by inheritance of an ACTH-regulated, hybrid CYP11B1/CYP11B2 gene. Genetic testing has greatly facilitated diagnosis. Hypertension severity varies widely, demonstrating relationships with gender, affected parent's gender, urinary kallikrein level, degree of biochemical disturbance and hybrid gene crossover point position. Analyses of aldosterone/PRA/cortisol 'day-curves' have revealed that (1) the hybrid gene dominates over wild type CYP11B2 in terms of aldosterone regulation and (2) correction of hypertension in FH-I requires only partial suppression of ACTH, and much smaller glucocorticoid doses than those previously recommended. Familial hyperaldosteronism type II is not glucocorticoid-remediable, and is clinically, biochemically and morphologically indistinguishable from apparently sporadic PAL. In one informative family available for linkage analysis, FH-II does not segregate with either the CYP11B2, AT1 or MEN1 genes, but a genome-wide search has revealed linkage with a locus in chromosome 7. As has already occurred in FH-I, elucidation of causative mutations is likely to facilitate earlier detection of PAL and other curable or specifically treatable forms of hypertension. PMID:11595502

  12. MYCN: From Oncoprotein To Tumor-Associated Antigen

    Directory of Open Access Journals (Sweden)

    Vito ePistoia

    2012-11-01

    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

  13. Antigen delivery to macrophages using liposomal nanoparticles targeting sialoadhesin/CD169.

    Directory of Open Access Journals (Sweden)

    Weihsu C Chen

    Full Text Available Sialoadhesin (Sn, Siglec-1, CD169 is a member of the sialic acid binding Ig-like lectin (siglec family expressed on macrophages. Its macrophage specific expression makes it an attractive target for delivering antigens to tissue macrophages via Sn-mediated endocytosis. Here we describe a novel approach for delivering antigens to macrophages using liposomal nanoparticles displaying high affinity glycan ligands of Sn. The Sn-targeted liposomes selectively bind to and are internalized by Sn-expressing cells, and accumulate intracellularly over time. Our results show that ligand decorated liposomes are specific for Sn, since they are taken up by bone marrow derived macrophages that are derived from wild type but not Sn(-/- mice. Importantly, the Sn-targeted liposomes dramatically enhance the delivery of antigens to macrophages for presentation to and proliferation of antigen-specific T cells. Together, these data provide insights into the potential of cell-specific targeting and delivery of antigens to intracellular organelles of macrophages using Sn-ligand decorated liposomal nanoparticles.

  14. Usefulness of cancer-testis antigens as biomarkers for the diagnosis and treatment of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Frezza Eldo E

    2007-01-01

    Full Text Available Abstract Despite advances in our cellular and molecular knowledge, hepatocellular carcinoma (HCC remains one of the major public health problems throughout the world. It is now known to be highly heterogeneous: it encompasses various pathological entities and a wide range of clinical behaviors, and is underpinned by a complex array of gene alterations that affect supra-molecular processes. Four families of HCC tumour markers have been recently proposed: a onco-fetal and glycoprotein antigens; b enzymes and iso-enzymes; c cytokines and d genes. A category of tumour-associated antigens called cancer-testis (CT antigens has been identified and their encoding genes have been extensively investigated. CT antigens are expressed in a limited number of normal tissues as well as in malignant tumors of unrelated histological origin, including the liver. Given that cancers are being recognized as increasingly complex, we here review the role of CT antigens as liver tumour biomarkers and their validation process, and discuss why they may improve the effectiveness of screening HCC patients and help in determining the risk of developing HCC.

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

    Directory of Open Access Journals (Sweden)

    Bruschi F.

    2001-06-01

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

    Science.gov (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

    2013-10-01

    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.

  17. Antigen detection of rabies virus in brain smear using direct Rapid Immunohistochemistry Test

    OpenAIRE

    Damayanti R; Rahmadani I; Fitria Y

    2014-01-01

    Rabies is zoonotic disease caused by a fatal, neurotropic virus. Rabies virus is classified into the Genus of Lyssavirus under the yang family of Rhabdoviridae. Rabies affecting hot- blooded animals, as well as human. Dogs, cats, monkeys are the vectors or reservoirs for rabies and the virus was transmitted through the saliva after infected animal’s bites. The aim of this study was to conduct rapid diagnosis to detect rabies viral antigen in brain smear using immunohistochemical (IHC) method ...

  18. Architecture of the DNA polymerase B-proliferating cell nuclear antigen (PCNA)-DNA ternary complex

    OpenAIRE

    Mayanagi, Kouta; Kiyonari, Shinichi; Nishida, Hirokazu; Saito, Mihoko; Kohda, Daisuke; Ishino, Yoshizumi; Shirai, Tsuyoshi; Morikawa, Kosuke

    2011-01-01

    DNA replication in archaea and eukaryotes is executed by family B DNA polymerases, which exhibit full activity when complexed with the DNA clamp, proliferating cell nuclear antigen (PCNA). This replication enzyme consists of the polymerase and exonuclease moieties responsible for DNA synthesis and editing (proofreading), respectively. Because of the editing activity, this enzyme ensures the high fidelity of DNA replication. However, it remains unclear how the PCNA-complexed enzyme temporally ...

  19. Murine Pregnancy-Specific Glycoprotein 23 Induces the Proangiogenic Factors Transforming-Growth Factor Beta 1 and Vascular Endothelial Growth Factor A in Cell Types Involved in Vascular Remodeling in Pregnancy1

    OpenAIRE

    Wu, Julie A.; Johnson, Briana L.; Chen, Yongqing; Ha, Cam T.; Dveksler, Gabriela S.

    2008-01-01

    Haemochorial placentation is a unique physiological process in which the fetal trophoblast cells remodel the maternal decidual spiral arteries to establish the fetoplacental blood supply. Pregnancy-specific glycoproteins (PSGs) are members of the carcinoembryonic antigen family. PSGs are produced by the placenta of rodents and primates and are secreted into the bloodstream. PSG23 is one of 17 members of the murine PSG family (designated PSG16 to PSG32). Previous studies determined that PSGs h...

  20. FAMILY BOMBYLIIDAE.

    Science.gov (United States)

    Lamas, Carlos José Einicker; Evenhuis, Neal L

    2016-01-01

    Bombyliidae is one of the largest Diptera families with more than 4,500 recognized species worldwide. Their species vary from robust to thin, and may be small to large (2-20mm) and looks like bees or wasps. They also present great variation in color. Adults can often be seen either resting and sunning themselves on trails, rocks or twigs or feeding on flowering plants as they are nectar feeders. All reared bee flies are predators or parasitoids of arthropods. The Colombian fauna of bombyliids comprises at the moment 22 species, and 12 genera, of which, six are endemic species. Nonetheless, this number may be much higher, as Colombia is a megadiverse country and there are not many specimens of this family deposited in collections all over the world. PMID:27395279

  1. Family Polymorphism

    DEFF Research Database (Denmark)

    Ernst, Erik

    2001-01-01

    This paper takes polymorphism to the multi-object level. Traditional inheritance, polymorphism, and late binding interact nicely to provide both flexibility and safety — when a method is invoked on an object via a polymorphic reference, late binding ensures that we get the appropriate...... implementation of that method for the actual object. We are granted the flexibility of using different kinds of objects and different method implementations, and we are guaranteed the safety of the combination. Nested classes, polymorphism, and late binding of nested classes interact similarly to provide both...... 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...

  2. Familial hypercholesterolemia

    OpenAIRE

    Lahiri Koushik; Lahiri Bhabesh Chandra

    2001-01-01

    Familial hypercholesterolemia is a common, inherited disorder of cholesterol metabolism that leads to early cardiovascular morbidity and mortality. It is underdiagnosed and undertreated. Statins, ezetimibe, bile acid sequestrants, niacin, lomitapide, mipomersen and LDL apheresis are treatments that can lower LDL cholesterol levels. Early treatment can lead to substantial reduction of cardiovascular events and death in patients with FH. It is important to increase awareness of this disorder in...

  3. Familial Hypercholesterolemia

    Science.gov (United States)

    Bouhairie, Victoria Enchia; Goldberg, Anne Carol

    2015-01-01

    Familial hypercholesterolemia is a common, inherited disorder of cholesterol metabolism that leads to early cardiovascular morbidity and mortality. It is underdiagnosed and undertreated. Statins, ezetimibe, bile acid sequestrants, niacin, lomitapide, mipomersen and LDL apheresis are treatments that can lower LDL cholesterol levels. Early treatment can lead to substantial reduction of cardiovascular events and death in patients with FH. It is important to increase awareness of this disorder in physicians and patients in order to reduce the burden of this disorder. PMID:25939291

  4. Familial hyperamylasemia

    OpenAIRE

    Koda Yu Kar Ling; Vidolin Eliana

    2002-01-01

    A 7-year-old white boy was referred to us with a history of 3 attacks of hypogastric pain over the previous 2 years and persistently elevated serum amylase concentrations. At physical examination, he was well with no evidence of clinical abnormalities. His weight and height were normal. Laboratory diagnostic investigations were all normal except for the presence of Ascaris lumbricoides in the feces and persistently elevated serum amylase levels. Serum amylase determinations in the family memb...

  5. Impact of antigenic diversity on laboratory diagnosis of Avian bornavirus infections in birds.

    Science.gov (United States)

    Zimmermann, Vanessa; Rinder, Monika; Kaspers, Bernd; Staeheli, Peter; Rubbenstroth, Dennis

    2014-11-01

    Avian bornaviruses (ABVs) are a group of genetically diverse viruses within the Bornaviridae family that can infect numerous avian species and represent the causative agents of proventricular dilatation disease, an often fatal disease that is widely distributed in captive populations of parrots and related species. The current study was designed to assess the antigenic variability of the family Bornaviridae and to determine its impact on ABV diagnosis by employing fluorescent antibody assays. It was shown that polyclonal rabbit sera directed against recombinant bornavirus nucleoprotein, X protein, phosphoprotein, and matrix protein provided sufficient cross-reactivity for the detection of viral antigen from a broad range of bornavirus genotypes grown in cell culture. In contrast, a rabbit anti-glycoprotein serum and 2 monoclonal antibodies directed against nucleoprotein and phosphoprotein proteins reacted more specifically. Antibodies were readily detected in sera from avian patients infected with known ABV genotypes if cells persistently infected with a variety of different bornavirus genotypes were used for analysis. For all sera, calculated antibody titers were highest when the homologous or a closely related target virus was used for the assay. Cross-reactivity with more distantly related genotypes of other phylogenetic groups was usually reduced, resulting in titer reduction of up to 3 log units. The presented results contribute to a better understanding of the antigenic diversity of family Bornaviridae and further emphasize the importance of choosing appropriate diagnostic tools for sensitive detection of ABV infections. PMID:25135010

  6. PLAP efficiently generates mature antigenic peptides in vitro but in patterns distinct from ERAP11

    OpenAIRE

    Georgiadou, Dimitra; Hearn, Arron; Evnouchidou, Irini; Chroni, Angeliki; Leondiadis, Leondios; Ian A York; Rock, Kenneth L.; Stratikos, Efstratios

    2010-01-01

    All three members of the oxytocinase sub-family of M1 aminopeptidases, ERAP1 (ERAAP), ERAP2 and PLAP (IRAP), have been implicated in the generation of MHC class I-presented peptides. ERAP1 and 2 trim peptides in the endoplasmic reticulum for direct presentation whereas PLAP has been recently implicated in cross presentation. The best characterized member of the family, ERAP1, has unique enzymatic properties that fit well with its role in antigen processing. ERAP1 can trim a large variety of l...

  7. Tresyl-Based Conjugation of Protein Antigen to Lipid Nanoparticles Increases Antigen Immunogencity

    Science.gov (United States)

    Jain, Anekant; Yan, Weili; Miller, Keith R.; O'Carra, Ronan; Woodward, Jerold G.; Mumper, Russell J.

    2010-01-01

    The present studies were aimed at investigating the engineering of NPs with protein-conjugated-surfactant at their surface. In order to increase the immunogenicity of a protein antigen, Brij 78 was functionalized by tresyl chloride and then further reacted with the primary amine of the model proteins ovalbumin (OVA) or horseradish peroxide (HRP). The reaction yielded Brij 78-OVA and Brij 78-HRP conjugates which were then used directly to form NP-OVA or NP-HRP using a one-step warm oil-in-water microemulsion precursor method with emulsifying wax as the oil phase, and Brij 78 and the Brij 78-OVA or Brij 78-HRP conjugate as surfactants. Similarly, Brij 700 was conjugated to HIV p24 antigen to yield Brij 700-p24 conjugate. The utility of these NPs for enhancing the immune responses to protein-based vaccines was evaluated in vivo using ovalbumin (OVA) as model protein and p24 as a relevant HIV antigen. In separate in vivo studies, female BALB/c mice were immunized by subcutaneous (s.c.) injection with NP-OVA and NP-p24 formulations along with several control formulations. These results suggested that with multiple antigens, covalent attachment of the antigen to the NP significantly enhanced antigen-specific immune responses. This facile covalent conjugation and incorporation method may be utilized to further incorporate other protein antigens, even multiple antigens, into an enhanced vaccine delivery system. PMID:20837122

  8. Tresyl-based conjugation of protein antigen to lipid nanoparticles increases antigen immunogenicity.

    Science.gov (United States)

    Jain, Anekant; Yan, Weili; Miller, Keith R; O'Carra, Ronan; Woodward, Jerold G; Mumper, Russell J

    2010-11-30

    The present studies were aimed at investigating the engineering of NPs with protein-conjugated-surfactant at their surface. In order to increase the immunogenicity of a protein antigen, Brij 78 was functionalized by tresyl chloride and then further reacted with the primary amine of the model proteins ovalbumin (OVA) or horseradish peroxide (HRP). The reaction yielded Brij 78-OVA and Brij 78-HRP conjugates which were then used directly to form NP-OVA or NP-HRP using a one-step warm oil-in-water microemulsion precursor method with emulsifying wax as the oil phase, and Brij 78 and the Brij 78-OVA or Brij 78-HRP conjugate as surfactants. Similarly, Brij 700 was conjugated to HIV p24 antigen to yield Brij 700-p24 conjugate. The utility of these NPs for enhancing the immune responses to protein-based vaccines was evaluated in vivo using ovalbumin (OVA) as model protein and p24 as a relevant HIV antigen. In separate in vivo studies, female BALB/c mice were immunized by subcutaneous (s.c.) injection with NP-OVA and NP-p24 formulations along with several control formulations. These results suggested that with multiple antigens, covalent attachment of the antigen to the NP significantly enhanced antigen-specific immune responses. This facile covalent conjugation and incorporation method may be utilized to further incorporate other protein antigens, even multiple antigens, into an enhanced vaccine delivery system. PMID:20837122

  9. Characteristics of family firms with family management

    OpenAIRE

    Søndergaard, Kathrine Lærke; Almli, Line Floan

    2012-01-01

    In this paper we examine what characterizes family firms’ decisions when it comes to having a family member being the CEO or the chairman of the board of the company. We define this as family management, which is the dependent variable in our research. This variable has four non-ordered mutually exclusive values; family CEO, family chairman of the board, family CEO and family chairman of the board, and neither family CEO nor family chairman of the board. Using data from the Center for Corpora...

  10. Family Genericity

    DEFF Research Database (Denmark)

    Ernst, Erik

    2006-01-01

    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...... abstraction, yielding more precise knowledge about the outcome. The prime example is type parameterized classes. This paper argues that these techniques should be clearly separated to work optimally, and also that current languages fail to do this. We have applied this design philosophy to a language based...... the result as family genericity. The presented language design has been implemented....

  11. Antigenic typing Polish isolates of canine parvovirus

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-12-31

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

  12. Antigen sampling in the fish intestine.

    Science.gov (United States)

    Løkka, Guro; Koppang, Erling Olaf

    2016-11-01

    Antigen uptake in the gastrointestinal tract may induce tolerance, lead to an immune response and also to infection. In mammals, most pathogens gain access to the host though the gastrointestinal tract, and in fish as well, this route seems to be of significant importance. The epithelial surface faces a considerable challenge, functioning both as a barrier towards the external milieu but simultaneously being the site of absorption of nutrients and fluids. The mechanisms allowing antigen uptake over the epithelial barrier play a central role for maintaining the intestinal homeostasis and regulate appropriate immune responses. Such uptake has been widely studied in mammals, but also in fish, a number of experiments have been reported, seeking to reveal cells and mechanisms involved in antigen sampling. In this paper, we review these studies in addition to addressing our current knowledge of the intestinal barrier in fish and its anatomical construction. PMID:26872546

  13. Idiopathic focal segmental glomerulosclerosis and HLA antigens.

    Science.gov (United States)

    Gerbase-DeLima, M; Pereira-Santos, A; Sesso, R; Temin, J; Aragão, E S; Ajzen, H

    1998-03-01

    The objective of the present study was to investigate a possible association between HLA class II antigens and idiopathic focal segmental glomerulosclerosis (FSGS). HLA-A, -B, -DR and -DQ antigens were determined in 19 Brazilian patients (16 white subjects and three subjects of Japanese origin) with biopsy-proven FSGS. Comparison of the HLA antigen frequencies between white patients and white local controls showed a significant increase in HLA-DR4 frequency among FSGS patients (37.7 vs 17.2%, P < 0.05). In addition, the three patients of Japanese extraction, not included in the statistical analysis, also presented HLA-DR4. In conclusion, our data confirm the association of FSGS with HLA-DR4 previously reported by others, thus providing further evidence for a role of genes of the HLA complex in the susceptibility to this disease. PMID:9698788

  14. Idiopathic focal segmental glomerulosclerosis and HLA antigens

    Directory of Open Access Journals (Sweden)

    M. Gerbase-DeLima

    1998-03-01

    Full Text Available The objective of the present study was to investigate a possible association between HLA class II antigens and idiopathic focal segmental glomerulosclerosis (FSGS. HLA-A, -B, -DR and -DQ antigens were determined in 19 Brazilian patients (16 white subjects and three subjects of Japanese origin with biopsy-proven FSGS. Comparison of the HLA antigen frequencies between white patients and white local controls showed a significant increase in HLA-DR4 frequency among FSGS patients (37.7 vs 17.2%, P<0.05. In addition, the three patients of Japanese extraction, not included in the statistical analysis, also presented HLA-DR4. In conclusion, our data confirm the association of FSGS with HLA-DR4 previously reported by others, thus providing further evidence for a role of genes of the HLA complex in the susceptibility to this disease

  15. Temporal differences in the activation of three classes of non-transmembrane protein tyrosine kinases following B-cell antigen receptor surface engagement.

    OpenAIRE

    Saouaf, S J; Mahajan, S.; Rowley, R B; Kut, S A; Fargnoli, J.; Burkhardt, A L; Tsukada, S; Witte, O. N.; Bolen, J B

    1994-01-01

    We evaluated in WEHI 231 B cells the time-dependent responses of Lyn, Blk, Btk, Syk, and three members of the Jak family of protein tyrosine kinases following antibody-mediated surface engagement of the B-cell antigen receptor. Our results show that the enzyme activities of Lyn and Blk were stimulated within seconds of antigen receptor engagement and correlated with the initial tyrosine phosphorylation of the Ig alpha and Ig beta subunits of the B-cell antigen receptor. Btk enzyme activity wa...

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

    Science.gov (United States)

    Rodgers, William; Smith, Kenneth

    2005-01-01

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

  17. Identification and Analysis of Immunodominant Antigens for ELISA-Based Detection of Theileria annulata

    Science.gov (United States)

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

    2016-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    Ewoud Bernardus Compeer

    2012-03-01

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

  19. Antigen-Antibody Interaction Database (AgAbDb): a compendium of antigen-antibody interactions.

    Science.gov (United States)

    Kulkarni-Kale, Urmila; Raskar-Renuse, Snehal; Natekar-Kalantre, Girija; Saxena, Smita A

    2014-01-01

    Antigen-Antibody Interaction Database (AgAbDb) is an immunoinformatics resource developed at the Bioinformatics Centre, University of Pune, and is available online at http://bioinfo.net.in/AgAbDb.htm. Antigen-antibody interactions are a special class of protein-protein interactions that are characterized by high affinity and strict specificity of antibodies towards their antigens. Several co-crystal structures of antigen-antibody complexes have been solved and are available in the Protein Data Bank (PDB). AgAbDb is a derived knowledgebase developed with an objective to compile, curate, and analyze determinants of interactions between the respective antigen-antibody molecules. AgAbDb lists not only the residues of binding sites of antigens and antibodies, but also interacting residue pairs. It also helps in the identification of interacting residues and buried residues that constitute antibody-binding sites of protein and peptide antigens. The Antigen-Antibody Interaction Finder (AAIF), a program developed in-house, is used to compile the molecular interactions, viz. van der Waals interactions, salt bridges, and hydrogen bonds. A module for curating water-mediated interactions has also been developed. In addition, various residue-level features, viz. accessible surface area, data on epitope segment, and secondary structural state of binding site residues, are also compiled. Apart from the PDB numbering, Wu-Kabat numbering and explicit definitions of complementarity-determining regions are provided for residues of antibodies. The molecular interactions can be visualized using the program Jmol. AgAbDb can be used as a benchmark dataset to validate algorithms for prediction of B-cell epitopes. It can as well be used to improve accuracy of existing algorithms and to design new algorithms. AgAbDb can also be used to design mimotopes representing antigens as well as aid in designing processes leading to humanization of antibodies. PMID:25048123

  20. IDENTIFICATION OF ACROSOME AS THE MAIN ANTIGEN OF THE SPERM CELLS PROVOKING AUTOANTIBODIES IN VASECTOMIZED IRANIAN MEN

    Directory of Open Access Journals (Sweden)

    M R Nowroozi

    2008-12-01

    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.

  1. Roles within the Family

    Science.gov (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. ...

  2. Multivalent TB vaccines targeting the esx gene family generate potent and broad cell-mediated immune responses superior to BCG.

    Science.gov (United States)

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

    2014-01-01

    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.

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

    Science.gov (United States)

    Gota, F

    1980-01-01

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

  4. HLA antigens and asthma in Greeks.

    Science.gov (United States)

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

    1996-04-01

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

  5. Antigen dynamics of follicular dendritic cells

    NARCIS (Netherlands)

    Heesters, B.A.

    2015-01-01

    Stromal-derived follicular dendritic cells (FDCs) are a major depot for antigen that are essential for formation of germinal centers, the site where memory and effector B cells differentiate and high-affinity antibody production takes place. Historically, FDCs have been characterized as ‘accessory’

  6. Circulating filarial antigen detection in brugian filariasis.

    Science.gov (United States)

    Tripathi, Praveen Kumar; Mahajan, Ramesh Chander; Malla, Nancy; Mewara, Abhishek; Bhattacharya, Shailja Misra; Shenoy, Ranganatha Krishna; Sehgal, Rakesh

    2016-03-01

    Human lymphatic filariasis (LF) is a major cause of disability globally. The success of global elimination programmes for LF depends upon effectiveness of tools for diagnosis and treatment. In this study on stage-specific antigen detection in brugian filariasis, L3, adult worm (AW) and microfilarial antigenaemia were detected in around 90-95% of microfilariae carriers (MF group), 50-70% of adenolymphangitis (ADL) patients, 10-25% of chronic pathology (CP) patients and 10-15% of endemic normal (EN) controls. The sensitivity of the circulating filarial antigen (CFA) detection in serum samples from MF group was up to 95%. In sera from ADL patients, unexpectedly, less antigen reactivity was observed. In CP group all the CFA positive individuals were from CP grade I and II only and none from grade III or IV, suggesting that with chronicity the AWs lose fecundity and start to disintegrate and die. Amongst EN subject, 10-15% had CFA indicating that few of them harbour filarial AWs, thus they might not be truly immune as has been conventionally believed. The specificity for antigen detection was 100% when tested with sera from various other protozoan and non-filarial helminthic infections.

  7. Wegener's granulomatosis and autoantibodies to neutrophil antigens

    OpenAIRE

    McCluskey, D R; Maxwell, A. P.; Watt, L

    1988-01-01

    We report five cases of Wegener's granulomatosis all of whom had clinical and histological evidence of disease activity at presentation and in whom autoantibodies to neutrophil antigens were detected. This test may prove useful for the diagnosis of this serious condition and help to monitor disease activity during treatment.

  8. Antigenic characterisation of lyssaviruses in South Africa

    Directory of Open Access Journals (Sweden)

    Ernest Ngoepe

    2014-02-01

    Full Text Available There are at least six Lyssavirus species that have been isolated in Africa, which include classical rabies virus, Lagos bat virus, Mokola virus, Duvenhage virus, Shimoni bat virus and Ikoma lyssavirus. In this retrospective study, an analysis of the antigenic reactivity patterns of lyssaviruses in South Africa against a panel of 15 anti-nucleoprotein monoclonal antibodies was undertaken. A total of 624 brain specimens, collected between 2005 and 2009, confirmed as containing lyssavirus antigen by direct fluorescent antibody test, were subjected to antigenic differentiation. The lyssaviruses were differentiated into two species, namely rabies virus (99.5% and Mokola virus (0.5%. Furthermore, rabies virus was further delineated into two common rabies biotypes in South Africa: canid and mongoose. Initially, it was found that the canid rabies biotype had two reactivity patterns; differential staining was observed with just one monoclonal antibody. This difference was likely to have been an artefact related to sample quality, as passage in cell culture restored staining. Mongoose rabies viruses were more heterogeneous, with seven antigenic reactivity patterns detected. Although Mokola viruses were identified in this study, prevalence and reservoir host species are yet to be established. These data demonstrate the usefulness of monoclonal antibody typing panels in lyssavirus surveillance with reference to emergence of new species or spread of rabies biotypes to new geographic zones.

  9. Lea blood group antigen on human platelets

    International Nuclear Information System (INIS)

    One- and two-stage radioligand assays were used to determine if human platelets possess the Lea antigen. Goat IgG anti-Lea antibody was purified by multiple adsorptions with Le(a-b-) human red blood cells, followed by affinity chromatography with synthetic Lea substance and labeling with 125I. Human IgG anti-Lea antibody was used either in a two stage radioassay with 125I-labeled mouse monoclonal IgG anti-human IgG as the second antibody or, alternatively, purified by Staph protein A chromatography, labeled with 125I, and used in a one-stage radioassay. Platelets from donors of appropriate red blood cell phenotypes were incubated with the antisera, centrifuged through phthalate esters, and assayed in a gamma scintillation counter. Dose response and saturation curve analysis demonstrate the presence of Lewis a antigen on platelets from Lea+ donors. Furthermore, platelets from an Le(a-b-) donor incubated in Le (a+b-) plasma adsorb Lea antigen in a similar manner to red blood cells. The clinical significance of these antigens in platelet transfusion remains undefined

  10. Integrating Family Resilience and Family Stress Theory.

    Science.gov (United States)

    Patterson, Joan M.

    2002-01-01

    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)

  11. Family Psychology and Family Therapy in Japan.

    Science.gov (United States)

    Kameguchi, Kenji; Murphy-Shigematsu, Stephen

    2001-01-01

    Reviews the development of family psychology and family therapy in Japan, tracing the origins of these movements, explaining how these fields were activated by the problem of school refusal, and describing an approach to family therapy that has been developed to work with families confronting this problem, as well as preventive programs of family…

  12. Credentialing Caregivers. Families Matter.

    Science.gov (United States)

    Dean, Christiana

    The Families Matter series of papers from the Harvard Family Research Project advances the concept of family-centered child care, advocating an approach to early childhood education that addresses the development of the child and family together. Grounded in family support principles, which build on family strengths and work from a community's…

  13. Reclaiming Family Privilege

    Science.gov (United States)

    Seita, John

    2012-01-01

    The pull for family is strong, almost primeval, most likely it is evolutionary, and for those lacking the benefit of family or Family Privilege, the loss of family is painful and profoundly sad. Young people who struggle to cope without stable family connections are profoundly aware of their lack of "Family Privilege." In this article, the author…

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

    Directory of Open Access Journals (Sweden)

    Mario Recker

    2011-03-01

    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.

  15. Cysteine proteases as potential antigens in antiparasitic DNA vaccines

    DEFF Research Database (Denmark)

    Jørgensen, Louise von Gersdorff; Buchmann, Kurt

    2011-01-01

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

  16. 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.R. Smith (Derek Richard)

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Day-Yu Chao

    2015-01-01

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

  18. [Identification of serological antigens in excretory-secretory antigens of Trichinella spiralis muscle larvae].

    Science.gov (United States)

    Huang, Xuegui; He, Lifang; Yuan, Shishan; Liu, Hui; Wang, Xin

    2016-05-01

    Objective To isolate and identify serological antigens in the excretory-secretory antigens of Trichinella spiralis muscle larvae by the combination of co-immunoprecipitation and mass spectrometric technology. Methods The serum IgG of New Zealand rabbits infected with Trichinella spiralis was isolated by ammonium sulfate precipitation. Muscle larvaes were isolated from the infected muscle, and then purified and cultured to collect excretory-secretory antigens. Serological antigens in excretory-secretory antigens were isolated by co-immunoprecipitation and SDS-PAGE, and analyzed by Western blotting. Moreover, the protein bands in New Zealand rabbit sera infected with Trichinella spiralis were identified by mass spectrometric technology. Results Indirect ELISA showed that the titer of serum antibody of New Zealand rabbits infected with Trichinella spiralis was 1:6400. The rabbit serum IgG was effectively isolated by ammonium sulfate precipitation. A total of four clear protein bands of the excretory-secretory antigens of Trichinella spiralis were obtained by electrophoresis. Among them, three clear protein bands with relative molecular mass (Mr) being 40 kDa, 50 kDa and 83 kDa were recognized by the rabbit sera infected with Trichinella spiralis but not recognized by the normal rabbit sera. The obtained four protein molecules were confirmed as serine protease, specific serine protease of muscle larvae, 43 kDa secreted glycoprotein and 53 kDa excretory-secretory antigen. Conclusion Four proteins were obtained from the excretory-secretory antigens of Trichinella spiralis muscle larvae by combination of co-immunoprecipitation and mass spectrometric technique analysis, which provided new sources and insights for the diagnosis and vaccine candidates of Trichinellosis. PMID:27126943

  19. [Immunodiffusion analysis of plasma proteins in the canine family].

    Science.gov (United States)

    Baranov, O K; Iurishina, N A; Savina, M A

    1976-01-01

    Immunodiffusion studies have been made on the plasma of 9 species (Vulpes vulpes, V. corsak, Alopex lagopus, Canis aureus, C. lupus, C. familiaris, C. dingo, Nyctereutes procynoides, Fennecus zerde) from the family of Canidae using milk antisera. Unlike rabbit antisera used earlier, milk antisera make it possible to detect more significant antigenic divergency with respect to 5 alpha- and beta-globulins. These globulins seem to have a higher evolution rate of antigenic mosaics as compared to other plasma proteins in the family investigated. The family Canidae serologically may be divided into two main groups: 1) the genus Canis which includes the wolf, domestic dog, dingo, jackal and 2) species which significantly differ from the former (the fox, polar fox, dog fox, fennec). In relation to these two groups, the raccoon dog occupies special position. PMID:62473

  20. Carbohydrate-functionalized nanovaccines preserve HIV-1 antigen stability and activate antigen presenting cells.

    Science.gov (United States)

    Vela Ramirez, J E; Roychoudhury, R; Habte, H H; Cho, M W; Pohl, N L B; Narasimhan, B

    2014-01-01

    The functionalization of polymeric nanoparticles with ligands that target specific receptors on immune cells offers the opportunity to tailor adjuvant properties by conferring pathogen mimicking attributes to the particles. Polyanhydride nanoparticles are promising vaccine adjuvants with desirable characteristics such as immunomodulation, sustained antigen release, activation of antigen presenting cells (APCs), and stabilization of protein antigens. These capabilities can be exploited to design nanovaccines against viral pathogens, such as HIV-1, due to the important role of dendritic cells (DCs) and macrophages in viral spread. In this work, an optimized process was developed for carbohydrate functionalization of HIV-1 antigen-loaded polyanhydride nanoparticles. The carbohydrate-functionalized nanoparticles preserved antigenic properties upon release and also enabled sustained antigen release kinetics. Particle internalization was observed to be chemistry-dependent with positively charged nanoparticles being taken up more efficiently by DCs. Up-regulation of the activation makers CD40 and CD206 was demonstrated with carboxymethyl-α-d-mannopyranosyl-(1,2)-d-mannopyranoside functionalized nanoparticles. The secretion of the cytokines IL-6 and TNF-α was shown to be chemistry-dependent upon stimulation with carbohydrate-functionalized nanoparticles. These results offer important new insights upon the interactions between carbohydrate-functionalized nanoparticles and APCs and provide foundational information for the rational design of targeted nanovaccines against HIV-1. PMID:25068589

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

    Directory of Open Access Journals (Sweden)

    N Chacón

    2002-10-01

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

  2. Characterization of gastric adenocarcinoma cell lines established from CEA424/SV40 T antigen-transgenic mice with or without a human CEA transgene

    International Nuclear Information System (INIS)

    Gastric carcinoma is one of the most frequent cancers worldwide. Patients with gastric cancer at an advanced disease stage have a poor prognosis, due to the limited efficacy of available therapies. Therefore, the development of new therapies, like immunotherapy for the treatment of gastric cancer is of utmost importance. Since the usability of existing preclinical models for the evaluation of immunotherapies for gastric adenocarcinomas is limited, the goal of the present study was to establish murine in vivo models which allow the stepwise improvement of immunotherapies for gastric cancer. Since no murine gastric adenocarcinoma cell lines are available we established four cell lines (424GC, mGC3, mGC5, mGC8) from spontaneously developing tumors of CEA424/SV40 T antigen (CEA424/Tag) mice and three cell lines derived from double-transgenic offsprings of CEA424/Tag mice mated with human carcinoembryonic antigen (CEA)-transgenic (CEA424/Tag-CEA) mice (mGC2CEA, mGC4CEA, mGC11CEA). CEA424/Tag is a transgenic C57BL/6 mouse strain harboring the Tag under the control of a -424/-8 bp CEA gene promoter which leads to the development of invasive adenocarcinoma in the glandular stomach. Tumor cell lines established from CEA424/Tag-CEA mice express the well defined tumor antigen CEA under the control of its natural regulatory elements. The epithelial origin of the tumor cells was proven by morphological criteria including the presence of mucin within the cells and the expression of the cell adhesion molecules EpCAM and CEACAM1. All cell lines consistently express the transgenes CEA and/or Tag and MHC class I molecules leading to their susceptibility to lysis by Tag-specific CTL in vitro. Despite the presentation of CTL-epitopes derived from the transgene products the tumor cell lines were tumorigenic when grafted into C57BL/6, CEA424/Tag or CEA424/Tag-CEA-transgenic hosts and no significant differences in tumor take and tumor growth were observed in the different hosts. Although

  3. 21 CFR 866.3402 - Plasmodium species antigen detection assays.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Plasmodium species antigen detection assays. 866... Plasmodium species antigen detection assays. (a) Identification. A Plasmodium species antigen detection assay... malaria caused by the four malaria species capable of infecting humans: Plasmodium falciparum,...

  4. Antigen-specific active immunotherapy for ovarian cancer

    NARCIS (Netherlands)

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

    2010-01-01

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

  5. 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.

  6. 21 CFR 660.40 - Hepatitis B Surface Antigen.

    Science.gov (United States)

    2010-04-01

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

  7. Mapping epitopes and antigenicity by site-directed masking

    Science.gov (United States)

    Paus, Didrik; Winter, Greg

    2006-06-01

    Here we describe a method for mapping the binding of antibodies to the surface of a folded antigen. We first created a panel of mutant antigens (-lactamase) in which single surface-exposed residues were mutated to cysteine. We then chemically tethered the cysteine residues to a solid phase, thereby masking a surface patch centered on each cysteine residue and blocking the binding of antibodies to this region of the surface. By these means we mapped the epitopes of several mAbs directed to -lactamase. Furthermore, by depleting samples of polyclonal antisera to the masked antigens and measuring the binding of each depleted sample of antisera to unmasked antigen, we mapped the antigenicity of 23 different epitopes. After immunization of mice and rabbits with -lactamase in Freund's adjuvant, we found that the antisera reacted with both native and denatured antigen and that the antibody response was mainly directed to an exposed and flexible loop region of the native antigen. By contrast, after immunization in PBS, we found that the antisera reacted only weakly with denatured antigen and that the antibody response was more evenly distributed over the antigenic surface. We suggest that denatured antigen (created during emulsification in Freund's adjuvant) elicits antibodies that bind mainly to the flexible regions of the native protein and that this explains the correlation between antigenicity and backbone flexibility. Denaturation of antigen during vaccination or natural infections would therefore be expected to focus the antibody response to the flexible loops. backbone flexibility | Freund's adjuvant | conformational epitope | antisera

  8. Echinococcus granulosus antigen B: a Hydrophobic Ligand Binding Protein at the host-parasite interface.

    Science.gov (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

    2015-02-01

    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.

  9. Analysis of subtelomeric virulence gene families in Plasmodium falciparum by comparative transcriptional profiling

    OpenAIRE

    Witmer, Kathrin; Schmid, Christoph D.; Brancucci, Nicolas M. B.; Luah, Yen-Hoon; Preiser, Peter R.; Bozdech, Zbynek; Voss, Till S.

    2012-01-01

    Summary The Plasmodium falciparum genome is equipped with several subtelomeric gene families that are implicated in parasite virulence and immune evasion. Members of these families are uniformly positioned within heterochromatic domains and are thus subject to variegated expression. The best-studied example is that of the var family encoding the major parasite virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1). PfEMP1 undergoes antigenic variation through switches in mutua...

  10. 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;

    2006-01-01

    immune responses by catalyzing the peptide loading of human class II MHC molecules HLA-DR. Here we show now that they achieve this by interacting with a defined binding site of the HLA-DR peptide receptor. Screening of a compound library revealed a set of adamantane derivatives that strongly accelerated......, transient occupation of this pocket by the organic compound stabilizes the peptide-receptive conformation permitting rapid antigen loading. This interaction appeared restricted to the larger Gly(beta86) pocket and allowed striking enhancements of T cell responses for antigens presented by these "adamantyl......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...

  11. Classification of human leukocyte antigen (HLA) supertypes

    DEFF Research Database (Denmark)

    Wang, Mingjun; Claesson, Mogens H

    2014-01-01

    Identification of new antigenic peptides, derived from infectious agents or cancer cells, which bind to human leukocyte antigen (HLA) class I and II molecules, is of importance for the development of new effective vaccines capable of activating the cellular arm of the immune response. However, the...... barrier to the development of peptide-based vaccines with maximum population coverage is that the restricting HLA genes are extremely polymorphic resulting in a vast diversity of peptide-binding HLA specificities and a low population coverage for any given peptide-HLA specificity. One way to reduce 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...

  12. Radionuclide-labelled antigens in serological epidemiology

    International Nuclear Information System (INIS)

    The feasibility of tests using radionuclide-labelled antigens in serological surveys was studied, with particular attention to the likely availability of facilities and personnel in the tropics and arctics, where measurements may be disturbed by climatic influences. The methodology required was to be simple, rapid and suitable for examining large numbers of sera, as for epidemological surveys. In the introduction, limitations of labelled antigen tests are discussed, the choice of radionuclide and measurement methods, test procedures and evaluation of results. Collection, preservation and shipment of speciments (serum, faeces, cerebrospinal fluid, sputum, etc.) are described. Experiments with bacteria and bacterial toxins (Enterobacteriaceae, vibrios, staphylococci, meningococci, etc.), with protozoa and metazoa (Entamoeba hystolytica, Schistosoma mansoni, Trypanosoma cruzi, Plasmodia and other parasites), with viruses (vaccinia, adeno-, polio-, and influenza viruses, etc.), and with fungi are discussed

  13. A competitive-inhibiton radioimmunoassay for influenza virus envelope antigens

    International Nuclear Information System (INIS)

    A double-antibody competitive-inhibition radioimmunoassay for influenza virus envelope antigens is described. A viral antigen preparation from influenza A virus recombinant MRC11 [antigenically identical to A/Port Chalmers/1/73 (H3N2)] consisting of haemagglutinin and neuraminidase was labelled with radioiodine. Rabbit antisera were allowed to react with the labelled antigen and the resultant antigen-antibody complexes were precipitated with the appropriate antiglobulin. The competitive-inhibition radioimmunoassay very sensitively elucidated differences even among closely related influenza virus strains. Attempts have been made to eliminate neuraminidase from radioimmunoprecipitation to obtain a competitive-inhibition radioimmunoassay system for haemagglutinin alone. (author)

  14. Class II HLA antigens in multiple sclerosis.

    Science.gov (United States)

    Miller, D H; Hornabrook, R W; Dagger, J; Fong, R

    1989-01-01

    HLA typing in Wellington revealed a stronger association of multiple sclerosis with DR2 than with DQw1. The association with DQw1 appeared to be due to linkage disequilibrium of this antigen with DR2. These results, when considered in conjunction with other studies, are most easily explained by the hypothesis that susceptibility to multiple sclerosis is influenced by multiple risk factors, with DR2 being an important risk factor in Caucasoid populations. PMID:2732726

  15. Yeast retrotransposon particles as antigen delivery systems.

    Science.gov (United States)

    Kingsman, A J; Burns, N R; Layton, G T; Adams, S E

    1995-05-31

    The development of technologies to produce recombinant proteins for use in the pharmaceutical industry has made substantial advances, in particular in the area of generating antigens containing multiple copies of important immunological regions. One such antigen-carrier system is based on the ability of a protein encoded by the yeast retrotransposon, Ty, to self-assemble into virus-like particles. Ty-fusion proteins retain this ability to form particles, and a range of hybrid VLPs carrying a variety of heterologous antigens have been produced and shown to induce potent immune responses. In particular, hybrid VLPs carrying the core protein p24 of HIV (p24-VLPs) have been shown to induce antibody and T-cell proliferative responses in both experimental animals and human volunteers, and immunization of rabbits with VLPs carrying the principal neutralizing determinant of HIV (V3-VLPs) resulted in the induction of neutralizing antibody responses and T-cell proliferation. Further studies with V3-VLPs have shown that this particulate antigen stimulates enhanced V3-specific lymphoproliferative responses as compared to whole recombinant gp120 or to V3 peptide conjugated to albumin. The V3-VLPs also induce potent CTL responses following immunization of mice in the absence of adjuvant. These responses are MHC class I restricted and are mediated by CD8-positive cells. These observations therefore demonstrate that hybrid Ty-VLPs induce both humoral and cellular immune responses against HIV and suggest that these immunogens may be important in combatting AIDS and other infections. PMID:7625653

  16. Antigenicity of low molecular weight surfactant species.

    OpenAIRE

    Strayer, D. S.; Merritt, T A; Makunike, C.; Hallman, M

    1989-01-01

    The authors tested the antigenicity of human lung surfactant isolated from amniotic fluid. Mice and rabbits were immunized. Rabbit polyclonal antisera to these surfactant preparations were absorbed with normal human plasma proteins. Polyclonal antisera reacted with both high molecular weight (35 kd) surfactant apoprotein and to lower molecular weight species, both 18 kd and 9 kd. Mice were used to generate monoclonal antibodies to surfactant. Enzyme-linked immunosorbant assay was used to iden...

  17. Rationalisation of Legionella Urinary Antigen Testing.

    OpenAIRE

    Lynch, Breda

    2014-01-01

    Introduction: Legionnaires’ is a severe pneumonia, the diagnosis of which can be confirmed by a positive Legionella Urinary Antigen (LUA) test. The British Thoracic Society has specific guidelines for its use. Incorrect LUA test requests can result in false-positive results while accumulating costs. Aims and Objectives: The aim is the rationalisation of LUA testing. The first objective is to educate clinicians on indications for testing reducing unnecessary orders. The second is to develop...

  18. Family Reading Night

    Science.gov (United States)

    Hutchins, Darcy; Greenfeld, Marsha; Epstein, Joyce

    2007-01-01

    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…

  19. Study of serum Helicobacter pylori soluble antigen

    Institute of Scientific and Technical Information of China (English)

    吴勤动; 朱永良

    2002-01-01

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

  20. Study of serum Helicobacter pylori soluble antigen

    Institute of Scientific and Technical Information of China (English)

    吴勤动; 朱永良

    2002-01-01

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

  1. 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.

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

    Science.gov (United States)

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

    2015-01-01

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

  3. Family Capital: Implications for Interventions with Families

    Science.gov (United States)

    Belcher, John R.; Peckuonis, Edward V.; Deforge, Bruce R.

    2011-01-01

    Social capital has been extensively discussed in the literature as building blocks that individuals and communities utilize to leverage system resources. Similarly, some families also create capital, which can enable members of the family, such as children, to successfully negotiate the outside world. Families in poverty confront serious…

  4. 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

    2006-01-01

    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

  5. PSYCHOLOGY OF FAMILY BUSINESS

    OpenAIRE

    Taylyakova, Feruzahon

    2014-01-01

    This article analyzes the basic psychological characteristics of family businesses. The author describes the psychological properties that contribute to improve individual and family businesses. The article also discusses mental properties adversely affect the development of a family business.

  6. Learning about Familial Hypercholesterolemia

    Science.gov (United States)

    ... genetic terms used on this page Learning About Familial Hypercholesterolemia What is familial hypercholesterolemia? What are the symptoms ... Hypercholesterolemia Additional Resources About Familial Hypercholesterolemia What is ... hypercholesterolemia is an inherited condition that causes ...

  7. Family Reunion Health Guide

    Science.gov (United States)

    ... can post this message as a note on Facebook, tagging family members and loved ones. You also may include ... gov . Planning Tip 2. | Develop a Family Reunion Facebook page and help family members stay in touch throughout the year. Share ...

  8. Normal Functioning Family

    Science.gov (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 ...

  9. Family Adjustment to Aphasia

    Science.gov (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 ...

  10. Family Activities for Fitness

    Science.gov (United States)

    Grosse, Susan J.

    2009-01-01

    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.

  11. Surface antigen expression in chronic lymphocytic leukemia: clustering analysis, interrelationships and effects of chromosomal abnormalities.

    Science.gov (United States)

    Hulkkonen, J; Vilpo, L; Hurme, M; Vilpo, J

    2002-02-01

    Chronic lymphocytic leukemia (CLL) is a phenotypically distinguishable form of B-lymphoid leukemias. The regularity of surface membrane antigen expression patterns, their interrelationships as well as the effects of the three frequent chromosomal aberrations, ie 11q deletion, 13q deletion and trisomy 12, were investigated in 35 classic CLL cases by flow cytometry. The two-way cluster analysis of 31 individual antigens revealed three expression patterns: (1) most cells in most cases positive (CD5, CD19, CD20, CD23, CD27, CD40, CD45, CD45RA); (2) most cells in most cases negative (CD10, CD14, CD34, CD122, CD154, mIgG); and (3) a mixed pattern with a variable number of positive cases and a variable percentage of positive cells in individual cases (CD11c, CD21, CD22, CD25, CD38, CD45RO, CD79b, CD80, CD95, CD124, CD126, CD130, FMC7, mIgD, mIgkappa, mIglambda, mIgM). The expressions of several antigens were strongly interdependent, even when antigens belonged to entirely different gene families. Such antigen pairs were: CD11c/CD21; CD19/CD45; CD19/CD79b; CD22/CD45RA; CD23/Igkappa; CD25/mIgM; CD27/CD45; CD45/CD79b; CD45RA/Igkappa. In contrast, the expression of some antigens was mutually exclusive, the best examples being CD45RA/CD45RO, CD38/CD80 and CD45RA/CD80. Deletion of chromosome arm 11q attenuated expression of splicing variant CD45RA, but enhanced CD45RO expression. In contrast, cases of trisomy 12 were associated with enhanced CD45RA and attenuated CD45RO expression. Similarly, trisomy 12 was associated with enhanced CD27 and mIgkappa expression. The variable levels of signaling surface membrane antigens, their interactions and interference by genetic aberrations are likely to affect the clinical progression and drug response of CLL. PMID:11840283

  12. Typing of HLA class II and class I antigens using PHA-activated, IL-2-propagated T lymphocytes.

    Science.gov (United States)

    Leshem, B; Cohen, I; Sherman, L; Brautbar, C; Kedar, E

    1988-06-28

    We describe here a simple procedure, by which HLA class II antigens can be accurately and reliably identified in those patients where there is minimal or absent expression of HLA-DR,DQw antigens on B cells, or when the total number of leukocytes recovered from the patients do not permit reliable typing. Ficoll-Hypaque-separated peripheral blood mononuclear leukocytes, fresh or cryopreserved, were activated by PHA and then propagated in IL-2-containing medium until enough cells for typing were obtained (usually 7-14 days). At this stage, the cultured cells were shown to be primarily T cells (greater than 90% CD3+). Since the activated T cells propagate in the presence of IL-2, even a small number (10(4] of fresh or cryopreserved patients' cells suffice for this protocol. To date we have been able to successfully HLA-DR,DQw type 34/34 bone marrow transplantation candidates and 12/12 long-term dialysis patients, who were untypable using fresh cells. HLA-DR,DQw antigens on activated T cells from normal individuals were identical to those found on their uncultured B cells. In addition, class I antigens that were undetectable on the uncultured cells of one patient could be identified on activated T cells. The HLA antigens identified on the patients' activated T cells were confirmed by phenotypic analysis of cells from family members. PMID:3260612

  13. An Ultrasensitive Electrochemiluminescence Immunoassay for Carbohydrate Antigen 19-9 in Serum Based on Antibody Labeled Fe3O4 Nanoparticles as Capture Probes and Graphene/CdTe Quantum Dot Bionanoconjugates as Signal Amplifiers

    Science.gov (United States)

    Gan, Ning; Zhou, Jing; Xiong, Ping; Li, Tianhua; Jiang, Shan; Cao, Yuting; Jiang, Qianli

    2013-01-01

    The CdTe quantum dots (QDs), graphene nanocomposite (CdTe-G) and dextran–Fe3O4 magnetic nanoparticles have been synthesized for developing an ultrasensitive electrochemiluminescence (ECL) immunoassay for Carcinoembryonic antigen 19-9 (CA 19-9) in serums. Firstly, the capture probes (CA 19-9 Ab1/Fe3O4) for enriching CA 19-9 were synthesized by immobilizing the CA 19-9’s first antibody (CA 19-9 Ab1) on magnetic nanoparticles (dextran-Fe3O4). Secondly, the signal probes (CA 19-9 Ab2/CdTe-G), which can emit an ECL signal, were formed by attaching the secondary CA 19-9 antibody (CA 19-9 Ab2) to the surface of the CdTe-G. Thirdly, the above two probes were used for conjugating with a serial of CA 19-9 concentrations. Graphene can immobilize dozens of CdTe QDs on their surface, which can emit stronger ECL intensity than CdTe QDs. Based on the amplified signal, ultrasensitive antigen detection can be realized. Under the optimal conditions, the ECL signal depended linearly on the logarithm of CA 19-9 concentration from 0.005 to 100 pg/mL, and the detection limit was 0.002 pg/mL. Finally, five samples of human serum were tested, and the results were compared with a time-resolved fluorescence assay (TRFA). The novel immunoassay provides a stable, specific and highly sensitive immunoassay protocol for tumor marker detection at very low levels, which can be applied in early diagnosis of tumor. PMID:23685872

  14. An Ultrasensitive Electrochemiluminescence Immunoassay for Carbohydrate Antigen 19-9 in Serum Based on Antibody Labeled Fe3O4 Nanoparticles as Capture Probes and Graphene/CdTe Quantum Dot Bionanoconjugates as Signal Amplifiers

    Directory of Open Access Journals (Sweden)

    Ning Gan

    2013-05-01

    Full Text Available The CdTe quantum dots (QDs, graphene nanocomposite (CdTe-G and dextran–Fe3O4 magnetic nanoparticles have been synthesized for developing an ultrasensitive electrochemiluminescence (ECL immunoassay for Carcinoembryonic antigen 19-9 (CA 19-9 in serums. Firstly, the capture probes (CA 19-9 Ab1/Fe3O4 for enriching CA 19-9 were synthesized by immobilizing the CA 19-9’s first antibody (CA 19-9 Ab1 on magnetic nanoparticles (dextran-Fe3O4. Secondly, the signal probes (CA 19-9 Ab2/CdTe-G, which can emit an ECL signal, were formed by attaching the secondary CA 19-9 antibody (CA 19-9 Ab2 to the surface of the CdTe-G. Thirdly, the above two probes were used for conjugating with a serial of CA 19-9 concentrations. Graphene can immobilize dozens of CdTe QDs on their surface, which can emit stronger ECL intensity than CdTe QDs. Based on the amplified signal, ultrasensitive antigen detection can be realized. Under the optimal conditions, the ECL signal depended linearly on the logarithm of CA 19-9 concentration from 0.005 to 100 pg/mL, and the detection limit was 0.002 pg/mL. Finally, five samples of human serum were tested, and the results were compared with a time-resolved fluorescence assay (TRFA. The novel immunoassay provides a stable, specific and highly sensitive immunoassay protocol for tumor marker detection at very low levels, which can be applied in early diagnosis of tumor.

  15. Branding a family business

    OpenAIRE

    Pohjola, Matti

    2016-01-01

    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...

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

    Science.gov (United States)

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

    2000-05-01

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

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

    Science.gov (United States)

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

    2015-12-01

    The excretory-secretory (ES) antigens from Trichinella spiralis muscle larvae (ML) are the most commonly used diagnostic antigens for trichinellosis, but anti-Trichinella IgG antibodies cannot be detected until 2-3 weeks after infection; there is an obvious window period between Trichinella infection and antibody positivity. Intestinal infective larvae (IIL) are the first invasive stage during Trichinella infection, and their ES antigens are firstly exposed to the immune system and might be the early diagnostic markers of trichinellosis. The aim of this study was to evaluate the early diagnostic values of IIL ES antigens for trichinellosis. The IIL were collected from intestines of infected mice at 6 h postinfection (hpi), and IIL ES antigens were prepared by incubation for 18 h. Anti-Trichinella IgG antibodies in mice infected with 100 ML were detectable by ELISA with IIL ES antigens as soon as 10 days postinfection (dpi), but ELISA with ML ES antigens did not permit detection of infected mice before 12 dpi. When the sera of patients with trichinellosis at 19 dpi were assayed, the sensitivity (100 %) of ELISA with IIL ES antigens was evidently higher than 75 % of ELISA with ML ES antigens (P < 0.05) The specificity (96.86 %) of ELISA with IIL ES antigens was also higher than 89.31 % of ELISA with ML ES antigens (P < 0.05). The IIL ES antigens provided a new source of diagnostic antigens and could be considered as a potential early diagnostic antigen for trichinellosis. PMID:26342828

  18. Entrepreneurial Families : From a Family Enterprise to an Entrepreneurial Family

    OpenAIRE

    Sieger, Philipp; Zellweger, Thomas

    2013-01-01

    How do family firms succeed from generation to generation? While this is likely the most important question for the members of a family business, little is known about the central success factors in creating value across the generations. For this reason, our study aims to explore the secrets of family firms with a long, successful track record and to expand the current state of knowledge. In so doing, we want to look not only at «the family firm» but also broaden our scope to the entire entre...

  19. Families and family therapy in Hong Kong.

    Science.gov (United States)

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

    2012-04-01

    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. PMID:22515459

  20. Families and family therapy in Hong Kong.

    Science.gov (United States)

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

    2012-04-01

    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.

  1. Abnormal antigens in breast cancer tissues and production of monoclonal antibodies against one of these antigens

    International Nuclear Information System (INIS)

    Breast cancer is associated with up regulation, down regulation of normal antigens or abnormal antigens. These antigens are very useful candidates as targets for the different breast cancer therapies and for vaccination trials. This study was done to characterize abnormal antigens, extract one of them and to produce monoclonal antibodies against the extracted antigen. One hundred and twenty Sudanese female patients were included in this study after informed consent. The mean age was 47. 2 years (16-80). Two tissue samples were obtained from each patient and they were confirmed as normal and cancerous breast tissues microscopically. 2D PAGE was used to analyze the protein content of samples. LC/MS and nr. fast a database search were used for separation and indentification of the abnormal proteins. Three different patterns of 2D Page results were obtained, the first pattern involved detection of four abnormal proteins in 26.7% of the patient cancerous tissues while they were undetected in the normal tissues of the same patients. In the second 2D PAGE result pattern the cancerous and the normal tissues of 67.5% patients were identical and they did not contain the four abnormal proteins while the third 2D PAGE pattern involved the presence of two abnormal antigens (from the four) in the cancerous tissues of 5.8% of the patients and they were absent from the normal tissues of the same patients. The four abnormal proteins were identified as, human Thioredoxin (D60nmutant), x-ray crystal structure of human galectin-1, retrocopy of tropomyosin 3(rc TPM3) and beta-tropomyosin (isoform 2). The primary and the secondary structures were obtained from the SWISSPROT and the PDB databases. Beta tropomyosin spot was extracted and used as antigen for monoclonal antibody production. Monoclonal antibody against beta- tropomyosin with a concentration of 0.35 mg/ml and a G11 anti beta-tropomyosin hybridoma cell line were produced. The monoclonal antibody was with single bad and

  2. The pericyte antigen RGS5 in perivascular soft tissue tumors.

    Science.gov (United States)

    Shen, Jia; Shrestha, Swati; Yen, Yu-Hsin; Scott, Michelle A; Soo, Chia; Ting, Kang; Peault, Bruno; Dry, Sarah M; James, Aaron W

    2016-01-01

    Perivascular soft tissue tumors are relatively uncommon neoplasms of unclear lineage of differentiation, although most are presumed to originate from or differentiate to pericytes or a modified perivascular cell. Among these, glomus tumor, myopericytoma, and angioleiomyoma share a spectrum of histologic findings and a perivascular growth pattern. In contrast, solitary fibrous tumor was once hypothesized to have pericytic differentiation--although little bona fide evidence of pericytic differentiation exists. Likewise the perivascular epithelioid cell tumor (PEComa) family shares a perivascular growth pattern, but with distinctive dual myoid-melanocytic differentiation. RGS5, regulator of G-protein signaling 5, is a novel pericyte antigen with increasing use in animal models. Here, we describe the immunohistochemical expression patterns of RGS5 across perivascular soft tissue tumors, including glomus tumor (n = 6), malignant glomus tumor (n = 4), myopericytoma (n = 3), angioleiomyoma (n = 9), myofibroma (n = 4), solitary fibrous tumor (n = 10), and PEComa (n = 19). Immunohistochemical staining and semi-quantification was performed, and compared to αSMA (smooth muscle actin) expression. Results showed that glomus tumor (including malignant glomus tumor), myopericytoma, and angioleiomyoma shared a similar diffuse immunoreactivity for RGS5 and αSMA across all tumors examined. In contrast, myofibroma, solitary fibrous tumor and PEComa showed predominantly focal to absent RGS5 immunoreactivity. These findings further support a common pericytic lineage of differentiation in glomus tumors, myopericytoma and angioleiomyoma. The pericyte marker RGS5 may be of future clinical utility for the evaluation of pericytic differentiation in soft tissue tumors. PMID:26558691

  3. Antigenic characterization of dimorphic surface protein in Mycobacterium tuberculosis.

    Science.gov (United States)

    Matsuba, Takashi; Siddiqi, Umme Ruman; Hattori, Toshio; Nakajima, Chie; Fujii, Jun; Suzuki, Yasuhiko

    2016-05-01

    The Mycobacterium tuberculosis Rv0679c protein is a surface protein that contributes to host cell invasion. We previously showed that a single nucleotide transition of the Rv0679c gene leads to a single amino acid substitution from asparagine to lysine at codon 142 in the Beijing genotype family. In this study, we examined the immunological effect of this substitution. Several recombinant proteins were expressed in Escherichia coli and Mycobacterium smegmatis and characterized with antisera and two monoclonal antibodies named 5D4-C2 and 8G10-H2. A significant reduction of antibody binding was detected by enzyme-linked immunosorbent assay (ELISA) and western blot analysis in the Lys142-type protein. This reduction of 8G10-H2 binding was more significant, with the disappearance of a signal in the proteins expressed by recombinant mycobacteria in western blot analysis. In addition, epitope mapping analysis of the recombinant proteins showed a linear epitope by 5D4-C2 and a discontinuous epitope by 8G10-H2. The antibody recognizing the conformational epitope detected only mycobacterial Asn142-type recombinant protein. Our results suggest that a single amino acid substitution of Rv0679c has potency for antigenic change in Beijing genotype strains. PMID:27190237

  4. Raman spectroscopy of HIV-1 antigen and antibody

    Science.gov (United States)

    Zinin, Pavel V.; Hu, Ningjie; Kamemoto, Lori E.; Yu, Qigui; Misra, Anupam K.; Sharma, Shiv K.

    2011-05-01

    Raman spectra of anti-HIV-1 antibody, HIV-1 antigen (p24), and HIV-1 antibody-antigen complex have been measured in near-infrared and UV regions: 785 nm; 830 nm; and 244 nm laser excitations. The spectrum of the HIV-1 antigen was excited with an infrared laser and contains numerous Raman peaks. The most prominent peaks are broad bands at 1343, 1449, 1609 and 1655 cm-1, which are characteristic of the Raman spectra of biological cells. The UV Raman spectrum of the HIV-1 antigen has a completely different structure. It has two strong peaks at 1613 cm-1 and 1173 cm-1. The peak at 1613 cm-1 is associated with vibrations of the aromatic amino acids tyrosine (Tyr) and tryptophan (Try). The second strongest peak at 1173 cm-1 is associated with the vibration of Tyr. The Raman peak pattern of the HIV-1 antigen-antibody complex is very similar to that of the HIV-1 antigen. The only difference is that the peak at 1007 cm-1 of the Raman spectrum of the HIV-1 antigen-antibody complex is slightly enhanced compared to that of the HIV-1 antigen. This indicates that the peaks of the HIV-1 antigen dominate the Raman spectrum of the HIV-1 antigen-antibody complex.

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

    Science.gov (United States)

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

    2015-11-01

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

  6. Regulation of antigenic variation in Plasmodium falciparum: censoring freedom of expression?

    Science.gov (United States)

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

    2003-03-01

    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.

  7. A family outbreak of Chlamydia pneumoniae infection.

    Science.gov (United States)

    Ghosh, K; Frew, C E; Carrington, D

    1992-07-01

    Chlamydia pneumoniae, a newly described Chlamydia species, has been shown to be a cause of acute respiratory tract infection in both adults and children, but its role in human infection is still under investigation. Here we present a family outbreak of C. pneumoniae infection where three members of a family presented with a 'flu-like illness' and acute upper respiratory tract infection which did not improve despite penicillin or septrin therapy. No history of exposure to birds, pets or animals was obtained. As C. pneumoniae isolation from respiratory secretions is not without difficulty, diagnosis usually relies currently on serum-based tests. In this study C. pneumoniae specific IgM determined by the micro-immunofluorescence test was detected in the three clinical cases. All three cases had an elevated complement-fixing antibody titre to Psittacosis-LGV antigen, which may have suggested psittacosis, if type-specific tests had not been performed. In addition, three other members of the family had C. pneumoniae-specific IgG antibody although specific IgM was absent. These three younger members of the family had been symptomatic in the month preceding symptoms in their older sibling and their parents. All the symptomatic members of the family made a complete recovery on tetracycline therapy. PMID:1522345

  8. Human leukocyte antigen-DO regulates surface presentation of human leukocyte antigen class II-restricted antigens on B cell malignancies

    NARCIS (Netherlands)

    Kremer, A.N.; Meijden, E.D. van der; Honders, M.W.; Pont, M.J.; Goeman, J.J.; Falkenburg, J.H.F.; Griffioen, M.

    2014-01-01

    Hematological malignancies often express surface HLA class II, making them attractive targets for CD4+ T cell therapy. We previously demonstrated that HLA class II ligands can be divided into DM-resistant and DM-sensitive antigens. In contrast to presentation of DM-resistant antigens, presentation o

  9. Enhancing the recognition of tumor associated antigens

    OpenAIRE

    Restifo, Nicholas P; Irvine, Kari R.; Minev, Boris R.; Taggarse, Akash S.; McFariand, Barbra J.; Wang, Michael

    1994-01-01

    Activated CD8+ T cells (TCD8+) can directly recognize malignant cells because processed fragments of tumor associated antigens (TAA), 8-10 amino acids in length and complexed with MHC class I molecules, are displayed on tumor cell surfaces. Tumor cells have been genetically modified in a variety of ways in efforts to enhance the immune recognition of TAA. An alternative strategy is the expression of TAA in recombinant or synthetic form. This has been made possible by the recent cloning of TAA...

  10. Simian Virus 40 Large T Antigen's Association with the CUL7 SCF Complex Contributes to Cellular Transformation

    OpenAIRE

    Kasper, Jocelyn S.; Kuwabara, Hiroshi; Arai, Takehiro; Ali, Syed Hamid; DeCaprio, James A.

    2005-01-01

    Simian virus 40 large T antigen (T Ag) is capable of immortalizing and transforming rodent cells. The transforming activity of T Ag is due in large part to perturbation of the tumor suppressor proteins p53 and the retinoblastoma (pRB) family members. Inactivation of these tumor suppressors may not be sufficient for T Ag-mediated cellular transformation. It has been shown that T Ag associates with an SCF-like complex that contains a member of the cullin family of E3 ubiquitin ligases, CUL7, as...

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

    Directory of Open Access Journals (Sweden)

    Kurose,Masao

    1981-10-01

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

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

    DEFF Research Database (Denmark)

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

    1994-01-01

    , on the other hand, expressed A, H, and inconstantly sialosyl-T, Tn, and sialosyl-Tn antigens in major salivary glands, whereas serous cells of minor (labial) salivary glands expressed H exclusively, Tn and sialosyl-T antigens inconstantly, but never sialosyl-Tn and A antigens. The difference may be related...... to a more simple cytodifferentiation of serous cells of minor (labial) salivary glands as compared with major salivary glands. Duct cells in major salivary glands expressed A, H, and inconstantly T, sialosyl-T, and Tn antigens, whereas minor (labial) salivary glands ducts exclusively expressed H, T...... and sialosyl-T antigens, differences that may be related to dissimilarities in the duct system. Myoepithelial cells and basal cells exclusively expressed T and sialosyl-T antigens, which may prove useful in studies of salivary gland tumors, since these cells are known to play a key role in the histological...

  13. Tissue distribution of histo-blood group antigens

    DEFF Research Database (Denmark)

    Ravn, V; Dabelsteen, Erik

    2000-01-01

    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...... 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...

  14. Monoclonal antibody-defined human pancreatic cancer-associated antigens.

    Science.gov (United States)

    Schmiegel, W H; Kalthoff, H; Arndt, R; Gieseking, J; Greten, H; Klöppel, G; Kreiker, C; Ladak, A; Lampe, V; Ulrich, S

    1985-03-01

    Three pancreatic cancer-associated antigens were characterized by use of monoclonal antibodies in immunobinding studies with various cellular and soluble target antigens, in immunoprecipitation, and in immunoperoxidase staining. C54-0 represents a tumor-associated Mr 122,000 antigen, which appears to be widely distributed on various epithelial tumors and to a lower extent on normal tissue. C1-N3 antigen exhibited a more restricted distribution, reacting with pancreatic and various gastrointestinal tract tumors as well as with chronically inflamed pancreatic tissue. The most specific antigen expression was observed for C1-P83 antigen, found on all exocrine tumors of the pancreas, but not on normal or chronically inflamed pancreatic tissue.

  15. Families in Transition .

    Science.gov (United States)

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

    1984-01-01

    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…

  16. Competitiveness of Family Businesses

    NARCIS (Netherlands)

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

    2001-01-01

    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

  17. Identification and characterization of profilin antigen among Babesia species as a common vaccine candidate against babesiosis.

    Science.gov (United States)

    Munkhjargal, Tserendorj; Aboge, Gabriel Oluga; Ueno, Akio; Aboulaila, Mahmoud; Yokoyama, Naoaki; Igarashi, Ikuo

    2016-07-01

    We have characterized a member of the profilin (PROF) family protein as a common antigen in three pathogens-Babesia bovis (B. bovis), Babesia bigemina (B. bigemina), and Babesia microti (B. microti)-and evaluated its immunogenic and cross-protective properties against a challenge infection with B. microti in BALB/c mice. The recombinant PROF proteins of B. bovis, B. bigemina, and B. microti were successfully expressed in Escherichia coli (E. coli) as soluble GST fusion proteins (rBboPROF, rBbigPROF, and rBmPROF, respectively), and they were found to be antigenic. On probing with mouse anti-rPROF serum, green fluorescence was observed on the parasites' cytosols by confocal laser microscopy. Immunization regimes in BALB/c mice using rPROFs induced cross-protective immunity against B. microti infection based on high levels of cytokines and immunoglobulin (IgG) titers, a reduction in peak parasitemia levels, and earlier clearance of the parasite as compared with control mice. The findings of the present study indicate that PROF is a common antigen among bovine and murine Babesia parasites, and it might be used as a common vaccine candidate against babesiosis. PMID:27003460

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

    Directory of Open Access Journals (Sweden)

    Stewart Nuttall

    2013-01-01

    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.

  19. HLA Bw35 antigen and mesangial IgA glomerulo-nephritis: a poor prognosis marker?

    Science.gov (United States)

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

    1979-01-01

    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.

  20. Antigenic cross-reactivity and species-specific identification of Pseudocerastes persicus fieldi snake venom.

    Science.gov (United States)

    Ibrahim, Nihal M; El-Kady, Ebtsam M

    2016-09-01

    In the present study, we recognized progressively high immunological cross-reactivity between Pseudocerastes persicus fieldi (Pf) venom and six other medically important Egyptian snake venoms belonging to families Viperidae and Elapidae. Antibodies with a range of bonding strengths were shown to be involved in such cross-reactivity. Two strategies have been tried to access specificity; (i) using affinity purified species-specific anti-Pf antivenom antibodies, (ii) conducting the assay in the presence of ammonium thiocyanate (NH4SCN). The discrimination power of the prepared species-specific antivenom was demonstrated by its ability to detect Pf venom over a range of Pf concentrations (2.5 ng-2.5 μg) in a variety of body fluids. The assay could distinguish circulating Pf antigens from other viper antigens in the whole blood of experimentally envenomed mice. What seems promising in our work is the use of the chaotrope, NH4SCN, which renders the reaction medium more favorable for the specific homologous antigen-antibody interactions, primarily via preventing lower avid antibodies to share and, to a bit lesser extent, by decreasing non-specific absorbance signals frequently encountered with ELISA assays. The ELISA described herein may be useful for clinicians for identification of snake bites inflicted by Pf snake species. Balancing between specificity and sensitivity has to be considered for best results. PMID:27319296

  1. Formaldehyde scavengers function as novel antigen retrieval agents

    OpenAIRE

    Craig T. Vollert; Moree, Wilna J; Steven Gregory; Bark, Steven J.; Eriksen, Jason L.

    2015-01-01

    Antigen retrieval agents improve the detection of formaldehyde-fixed proteins, but how they work is not well understood. We demonstrate that formaldehyde scavenging represents a key characteristic associated with effective antigen retrieval; under controlled temperature and pH conditions, scavenging improves the typical antigen retrieval process through reversal of formaldehyde-protein adduct formation. This approach provides a rational framework for the identification and development of more...

  2. T-cell recognition of a cross-reactive antigen(s) in erythrocyte stages of Plasmodium falciparum and Plasmodium yoelii: inhibition of parasitemia by this antigen(s).

    OpenAIRE

    Lucas, B.; Engels, A; Camus, D; Haque, A.

    1993-01-01

    In the current study, we investigated the presence of a cross-reactive antigen(s) in the erythrocyte stage from Plasmodium yoelii (265 BY strain) and Plasmodium falciparum through recognition by T cells primed in vivo with antigens from each of these parasites. BALB/c mice are naturally resistant to P. falciparum but are susceptible to P. yoelii infection. Mice that had recovered from P. yoelii primary infection became resistant to a second infection. A higher in vitro proliferative response ...

  3. Novel selective inhibitors of aminopeptidases that generate antigenic peptides.

    Science.gov (United States)

    Papakyriakou, Athanasios; Zervoudi, Efthalia; Theodorakis, Emmanuel A; Saveanu, Loredana; Stratikos, Efstratios; Vourloumis, Dionisios

    2013-09-01

    Endoplasmic reticulum aminopeptidases, ERAP1 and ERAP2, as well as Insulin regulated aminopeptidase (IRAP) play key roles in antigen processing, and have recently emerged as biologically important targets for manipulation of antigen presentation. Taking advantage of the available structural and substrate-selectivity data for these enzymes, we have rationally designed a new series of inhibitors that display low micromolar activity. The selectivity profile for these three highly homologous aminopeptidases provides a promising avenue for modulating intracellular antigen processing. PMID:23916253

  4. Pneumocystis carinii antigen detection in rat serum and lung lavage.

    OpenAIRE

    McNabb, S J; Graves, D C; Kosanke, S.D.; Moyer, M J; Ivey, M H

    1988-01-01

    We developed a modified double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) that detected relatively low concentrations of known Pneumocystis carinii antigen added to buffer or rat sera. Artificial immunization-derived polyclonal rabbit anti-P. carinii antibody was used on the solid phase to capture the antigen. Infection-derived (after P. carinii pneumonia) polyclonal rat anti-P. carinii antibody or a mixture of five murine monoclonal antibodies was used as the antigen detecto...

  5. Antigen epitope of Helicobacter pylorivacuolating cytotoxin A

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

  6. Immunoregulation by Taenia crassiceps and Its Antigens

    Directory of Open Access Journals (Sweden)

    Alberto N. Peón

    2013-01-01

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

  7. [Mucose associated lymphoid tissue. Antigen presenting cells].

    Science.gov (United States)

    Luzardo-Baptista, Mario J; Luzardo, José Rafael

    2013-12-01

    We studied samples of normal and abnormal human mucosae, including oral tissue and uterine cervix, using electron microscopy. Special attention was given to the functions and mechanisms of defense carried out by the epithelial (EC) and dendritic cells (DC). Activated epithelial cells posses the capacity to uptake and process antigens, in order to present them, subsequently, to the dendritic cells. The structures and elements of the cells intervening on this function are: micropinocytic vesicles, multivesicular bodies, lysosomes, phagosomes, clathrin-covered vesicles, dense granules covered by a unit membrane, granules with onion likes leaves, microbodies, and dense granules with acid phosphatase activity. When they first arrive within the epithelial layers, the DC are clear with long cytoplasmic projections, which later become short, and the density of their cytoplasm increases. They possess mycropinocytic vesicles, some clathrine-covered vesicles, lysososmes and Birbeck granules. At this moment, they are known as Langerhans cells. EC and DC present many surface folds rich in micropynocytic vesicles. Between EC and DC there are many contacts (close junctions or tight junctions), through which antigens, phagocitized and processed by the EC, are given to the DC. These cells join them to major histocompatibility complex molecules or to other molecules with similar functions (CD1). Then the Langerhans cells travel to the lymphatic node to activate T cells and continue the immunologic task. So, in this way, both the EC and the DC are a link between the natural and the acquired immunological mechanisms. PMID:24502183

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

    Science.gov (United States)

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

    2008-06-22

    Peste des petits ruminants (PPR) is one of the most economically important diseases affecting sheep and goats in India. An immunofiltration-based test has been developed using either mono-specific serum/monoclonal antibodies (mAb) prepared against a recombinant truncated nucleocapsid protein of rinderpest virus (RPV) cross-reactive with PPR virus. This method consists of coating ocular swab eluate from suspected animals onto a nitrocellulose membrane housed in a plastic module, which is allowed to react with suitable dilutions of a mAb or a mono-specific polyclonal antibody. The antigen-antibody complex formed on the membrane is then detected by protein A-colloidal gold conjugate, which forms a pink colour. In the immunofiltration test, concordant results were obtained using either PPRV mAb or mono-specific serum. Another test, an antigen-competition ELISA which relies on the competition between plate-coated recombinant truncated 'N' protein of RPV and the PPRV 'N' protein present in ocular swab eluates (sample) for binding to the mono-specific antibody against N protein of RPV (in liquid phase) was developed. The cut-off value for this test was established using reverse transcription polymerase chain reaction (RT-PCR) positive and negative oculo-nasal swab samples. Linear correlation between percent inhibition (PI) values in antigen-competition ELISA and virus infectivity titres was 0.992. Comparison of the immunofiltration test with the antigen-competition ELISA yielded a sensitivity of 80% and specificity of 100%. These two tests can serve as a screening (immunofiltration) and confirmatory (antigen-competition ELISA) test, respectively, in the diagnosis of PPR in sheep or goats. PMID:18182256

  9. Antigen-Specific versus Non-Antigen-Specific Immunoadsorption in ABO-Incompatible Renal Transplantation.

    Directory of Open Access Journals (Sweden)

    Gerold Thölking

    Full Text Available ABO-incompatible (ABOi renal transplantation (RTx from living donors is an established procedure to expand the donor pool for patients with end stage renal disease. Immunoadsorption (IA is a standard procedure for the removal of preformed antibodies against the allograft. In this study, antigen-specific and non-antigen-specific IA in ABOi RTx were compared.10 patients underwent antigen-specific IA (Glycosorb group and 13 patients non-antigen-specific IA (Immunosorba group. The effects of both procedures regarding antibody reduction, number of treatments, complications, costs, as well as the allograft function and patient survival were compared between both groups.Although the IgG levels were reduced equally by both procedures (p=0.82, the reduction of the IgM level was more effective in the Glycosorb group (p=0.0172. Patients in both groups required a median number of 6 IA before ABOi RTx. Allograft function at one year after AB0i RTx was similar in both groups (estimated glomerular filtration rate: 66 vs. 64 ml/min/1.73m² respectively, with a death-censored graft survival of 90.0% and 92.3% respectively. Complication rates did not differ between procedures. Due to the reuse of non-antigen-specific Immunosorba columns, costs were considerably lower in this group; however, the use of the Immunosorba-based IA was less time-efficient.Considering upcoming alternatives as simultaneous performance of dialysis and IA or a possible reuse of Glycosorb columns, this might become less relevant in the future.

  10. Inside the Family Firm

    OpenAIRE

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

    2005-01-01

    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...

  11. Familial breast cancer.

    OpenAIRE

    Phipps, R. F.; Perry, P M

    1988-01-01

    Familial breast cancer is important because of all the known risk factors associated with developing the disease. The one with the most predictability is a positive family history. It is also important because a family history causes anxiety in the families concerned, and young women will often ask their chance of developing the disease. This form of breast cancer accounts for 10% of causes and has factors that distinguish it from the sporadic variety. Relatives of familial breast cancer pati...

  12. FAMILIES AND HEALTH INTERACTIONS

    OpenAIRE

    Zdanowicz, Nicolas; Lepièce, Brice; Tordeurs, David; Jacques, Denis; Janne, Pascal; Reynaert, Christine

    2011-01-01

    Background: In recent years, psychologists of health have attempted to understand the relations between family dynamics and health. The aim of our study is not only to study relations inside families and couples (relations between family of origin, nuclear and ideal family, current and ideal couple) but also outside between families and couples and different health indicator (physical and mental health, consumption of medications, and frequency of medical consultations). Subjects and methods:...

  13. Breed differences in the frequency of bovine lymphocyte antigens.

    Science.gov (United States)

    Stear, M J; Brown, S C; Dimmock, C K; Dufty, J H; Hetzel, D J; Mackie, J T; Nicholas, F W; Tierney, T J; Wetherall, J D

    1987-01-01

    Lymphocytes from 1,564 cattle of 18 breeds and cross-bred groups in Australia were tested for major histocompatibility system class 1 antigens. Gene frequencies were calculated for the Angus, Belmont Red, Brahman, Hereford and Holstein-Friesian breeds. There were substantial differences among these breeds in antigen and gene frequency. There were striking differences among all 18 breeds in the presence or absence of certain antigens. Two antigens, CA13 and CA36, were strongly associated in Hereford cattle but occurred independently of each other in the other breeds. PMID:3273412

  14. Identification of protective antigens for vaccination against systemic salmonellosis

    Directory of Open Access Journals (Sweden)

    Dirk eBumann

    2014-08-01

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

  15. Cancer-germline antigen vaccines and epigenetic enhancers

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  16. СAPSULAR ANTIGEN OF YERSINIA PESTIS

    Directory of Open Access Journals (Sweden)

    L. A. Kadnikova

    2015-01-01

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

  17. 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

    1994-01-01

    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.

  18. Antigen-Specific CD4+ T Cells Recognize Epitopes of Protective Antigen following Vaccination with an Anthrax Vaccine

    OpenAIRE

    Laughlin, Elsa M.; Miller, Joseph D.; James, Eddie; Fillos, Dimitri; Ibegbu, Chris C.; Mittler, Robert S.; Akondy, Rama; Kwok, William; Ahmed, Rafi; Nepom, Gerald,

    2007-01-01

    Detection of antigen-specific CD4+ T cells is facilitated by the use of fluorescently labeled soluble peptide-major histocompatibility complex (MHC) multimers which mirror the antigen specificity of T-cell receptor recognition. We have used soluble peptide-MHC class II tetramers containing peptides from the protective antigen (PA) of Bacillus anthracis to detect circulating T cells in peripheral blood of subjects vaccinated with an anthrax vaccine. PA-specific HLA class II-restricted T lympho...

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

    DEFF Research Database (Denmark)

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

    1988-01-01

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

  20. Use of antigenic cartography in vaccine seed strain selection.

    Science.gov (United States)

    Fouchier, Ron A M; Smith, Derek J

    2010-03-01

    Human influenza A viruses are classic examples of antigenically variable pathogens that have a seemingly endless capacity to evade the host's immune response. The viral hemagglutinin (HA) and neuraminidase (NA) proteins are the main targets of our antibody response to combat infections. HA and NA continuously change to escape from humoral immunity, a process known as antigenic drift. As a result of antigenic drift, the human influenza vaccine is updated frequently. The World Health Organization (WHO) coordinates a global influenza surveillance network that, by the hemagglutination inhibition (HI) assay, routinely characterizes the antigenic properties of circulating strains in order to select new seed viruses for such vaccine updates. To facilitate a quantitative interpretation and easy visualization of HI data, a new computational technique called "antigenic cartography" was developed. Since its development, antigenic cartography has been applied routinely to assist the WHO with influenza surveillance activities. Until recently, antigenic variation was not considered a serious issue with influenza vaccines for poultry. However, because of the diversification of the Asian H5N1 lineage since 1996 into multiple genetic clades and subclades, and because of the long-term use of poultry vaccines against H5 in some parts of the world, this issue needs to be re-addressed. The antigenic properties of panels of avian H5N1 viruses were characterized by HI assay, using mammalian or avian antisera, and analyzed using antigenic cartography methods. These analyses revealed antigenic differences between circulating H5N1 viruses and the H5 viruses used in poultry vaccines. Considerable antigenic variation was also observed within and between H5N1 clades. These observations have important implications for the efficacy and long-term use of poultry vaccines.

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

    Science.gov (United States)

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

    2014-09-23

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

  2. Family Therapy for the "Truncated" Nuclear Family.

    Science.gov (United States)

    Zuk, Gerald H.

    1980-01-01

    The truncated nuclear family consists of a two-generation group in which conflict has produced a polarization of values. The single-parent family is at special risk. Go-between process enables the therapist to depolarize sharply conflicted values and reduce pathogenic relating. (Author)

  3. Strengthening Family Practices for Latino Families

    Science.gov (United States)

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

    2010-01-01

    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. The biology of cancer testis antigens: putative function, regulation and therapeutic potential.

    Science.gov (United States)

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

    2011-04-01

    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.

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

    Science.gov (United States)

    Parker, Jennifer Janell

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

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

    Science.gov (United States)

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

    2013-01-01

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

  7. 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

    2011-01-01

    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.

  8. Loosely coupled class families

    DEFF Research Database (Denmark)

    Ernst, Erik

    2001-01-01

    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...... 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....

  9. Engineering antigen-specific immunological tolerance.

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-01

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

  10. Pneumocystis carinii from pigs and humans are antigenically distinct

    DEFF Research Database (Denmark)

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

    1996-01-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  12. 9 CFR 113.408 - Avian mycoplasma antigen.

    Science.gov (United States)

    2010-01-01

    ... requirements. A 2.5 ml sample of completed antigen shall be diluted with 2.5 ml of buffer solution formulated... with 9 CFR 114.8. If phenol is used, a direct titration with a standardized bromide-bromate solution... tested against the antigens diluted 1:4 in buffer solution formulated in the same manner as the...

  13. Expression and immunoactivity of chimeric particulate antigens of receptor binding site-core antigen of hepatitis B virus

    Institute of Scientific and Technical Information of China (English)

    Hai-Jie Yang; Ning-Shao Xia; Min Chen; Tong Cheng; Shui-Zhen He; Shao-Wei Li; Bao-Quan Guan; Zi-Heng Zhu; Ying Gu; Jun Zhang

    2005-01-01

    AIM: To improve the immunogenicity of receptor binding site of hepatitis B virus (HBV) on preS1 antigen using HBV core antigen as an immuno-carrier.METHODS: One to 6 tandem copies of HBV preS1 (21-47)fragment were inserted into HBcAg at the sites of aa 78 and 82, and expressed in E. coli. ELISA, Western blot and animal immunization were used to analyze the antigenicity and immmunogenicity of purified particulate antigens. The ability to capture HBV by antibodies elicited by chimeric partides was detected with immuno-capture PCR.RESULTS: Recombinant antigens CⅠ, CⅡ, CⅢ carrying 1-3 copies of HBV preS1 (21-47) individually could form viruslike particles (VLPs), similar to HBcAg in morphology. But recombinant antigens carrying 4-6 copies of HBV preS1 (21-47) were poorly expressed in E.coli. Chimeric antigens were lacking of immunoreactivity with anti-HBc monoclonal antibodies (McAbs), but still reserved good immunoreactivity with anti-HBe McAbs. CⅠ, CⅡ, CⅢ could strongly react with anti-preS1 McAb, suggesting that preS1 (21-47) fragment was well exposed on the surface of chimeric VLPs. Three chimeric VLP antigens (CⅠ, CⅡ and CⅢ) could stimulate mice to produce high-level antibody responses, and their immunogenicity was stronger than non-particulate antigen 21-47*6, containing 6 copies of preS1 (21-47). Mouse antibodies to CⅠ, CⅡ and CⅢ were able to capture HBV virions in immuno-capture PCR assay in vitro.CONCLUSION: Chimeric particulate antigens of receptor binding site-core antigen of HBV can elicit strong antibody responses to preS1. They have a potential to be developed into prophylactic or therapeutic vaccines against HBV infection.

  14. [HLA and keloids: antigenic frequency and therapeutic response].

    Science.gov (United States)

    Rossi, A; Bozzi, M

    1989-01-01

    Twenty keloid subjects were typed for class 1 (HLA-A, B and C) and class 2 (HLA-DR and DQ) histocompatibility antigens. Their frequencies were compared to those found in control populations. Of all the antigens belonging to class 1, B 21 was more prevalent in patients. The findings regarding class 2 antigens were noteworthy: in keloid patients there was a significant prevalence of DR 5 (RR = 3.54 and 7.93 respectively for the two control groups) and DQw 3 (RR = 16.8). The patients typed for HLA-antigens were treated with corticosteroid infiltrations. The responses to the treatments were no related to the histocompatibility antigens. PMID:2628278

  15. 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.

  16. Methods for examination of antigenicity of heterogeneous polymerized hemoglobin

    International Nuclear Information System (INIS)

    Objective: To choose and establish the methods for examination of heterogeneous polymerized hemoglobin in order to offer the reference for evaluating the antigenicity of heterogeneous polymerized hemoglobin against human. Methods: Antigenicity of heterogeneous polymerized hemoglobin was examined for hypersensitivity, cell-mediated immunity reaction, humoral immunity reaction and cross-reaction of antigen. Results: The rabbit and guinea pig did not give rise to hypersensitivity. In immunized rabbits, the level of serum total IgG was normal, but the level of serum specific IgG was high. The examination of B lymphocytes showed that there was no significant difference (P>0.05) in comparison with control. Cross-reaction of antigen proved that bovine hemoglobin had cross-reaction with human hemoglobin. Suggesting that they may be homologous, the level of the serum specific antibody is high in the immunized animal. According to the immunology theories, the polymerized hemoglobin has antigenicity. (authors)

  17. The global antigenic diversity of swine influenza A viruses

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Science.gov (United States)

    Wenxue, Ma

    2014-02-05

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

  19. Family Theory and Family Health Research: Understanding the family health and illness cycle

    OpenAIRE

    Doherty, William J.

    1991-01-01

    Different family theories can be applied to different aspects of how families experience health and illness. The family health and illness cycle describes the phases of a family's experience, beginning with health promotion and risk reduction, then family vulnerability and disease onset or relapse, family illness appraisal, family acute response, and finally family adaptation to illness and recovery. For each phase, specific family theories that are most appropriate for guiding family and hea...

  20. Xeroderma Pigmentosum - A Family

    Directory of Open Access Journals (Sweden)

    Garg Anush

    2000-01-01

    Full Text Available A family of xeroderma pigmentosum is reported. Four children of different ages were afflicted with varying clinical presentation. Sequential development and progression of the disease from freckling to malignancy within the family are discussed.

  1. Xeroderma Pigmentosum - A Family

    OpenAIRE

    Garg Anush; Singhi M.K

    2000-01-01

    A family of xeroderma pigmentosum is reported. Four children of different ages were afflicted with varying clinical presentation. Sequential development and progression of the disease from freckling to malignancy within the family are discussed.

  2. Importance of Family Routines

    Science.gov (United States)

    ... Listen Español Text Size Email Print Share The Importance of Family Routines Page Content ​Every family needs ... child to sleep. These rituals can include storytelling, reading aloud, conversation, and songs. Try to avoid exciting ...

  3. Resilience of refugee families

    Directory of Open Access Journals (Sweden)

    Batić Dragana

    2012-01-01

    Full Text Available This study attempted to find a correlation between the trauma of family members of war and exile, and the characteristics of family functioning and lasted from 1992-1995. The term “family resilience” refers to the processes of adaptation and coping in the family as a functional unit. This paper presents a study of refugee families from Bosnia, who lived in refugee camps in Macedonia during the war of 1992- 1995. Data were obtained by interviews, observations, and a number of psychological instruments especially for children and parents, which measured the effects of psychological stress and family relationships. Based on the results obtained by quantitative and qualitative analysis, and application of theoretical models of systemic theory and family therapy, existence for four types of refugee families has been found and described, depending on the structure and the level of functionality.

  4. Family Caregiver Alliance

    Science.gov (United States)

    ... path forward. Discover ways to survive, post-caregiving. >> FAMILY CARE NAVIGATOR ─ Click on Your State AL AK ... our Advanced Search FCA Blog A Complex Web: Family Caregiving and Healthcare [Editor's note: This blog was ...

  5. Assessing postpartum family functioning.

    Science.gov (United States)

    Midmer, D; Talbot, Y

    1988-09-01

    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.

  6. Family Patterns in Dogmatism

    Science.gov (United States)

    Lesser, Harvey; Steininger, Marion

    1975-01-01

    Explored Rokeach's theory that dogmatism develops within the family. Subjects were college students and their parents who took the 40-item Dogmatism Scale. Results indicated that family experiences are one source of children's dogmatism but not the only source. (SDH)

  7. Familial lipoprotein lipase deficiency

    Science.gov (United States)

    ... medlineplus.gov/ency/article/000408.htm Familial lipoprotein lipase deficiency To use the sharing features on this page, please enable JavaScript. Familial lipoprotein lipase deficiency is a group of rare genetic disorders ...

  8. National Military Family Association

    Science.gov (United States)

    ... 931.6632 info@MilitaryFamily.org © 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 ...

  9. IGSF9 Family Proteins

    DEFF Research Database (Denmark)

    Hansen, Maria; Walmod, Peter Schledermann

    2013-01-01

    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...

  10. MSUD Family Support Group

    Science.gov (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 ...

  11. Structural characterization and MHCII-dependent immunological properties of the zwitterionic O-chain antigen of Morganella morganii.

    Science.gov (United States)

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

    2011-10-01

    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.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sarah L James

    2016-06-01

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

  14. Succession in Family Business

    OpenAIRE

    Zheng, Ting

    2009-01-01

    Abstract In the development of the world’s enterprises, family enterprises always have a very important role. And the succession problem is also related with the development of the family business deeply. So the succession problem is always the hot topic among the management scholars. How to deal with succession in family business issues will be directly related to the continuing operations of enterprises. Nowadays, Chinese family businesses enter the peak time of succession. Analysis of ...

  15. Internationalization of Family Businesses

    DEFF Research Database (Denmark)

    Boyd, Britta; Hollensen, Svend; Goto, Toshio

    2010-01-01

    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...... 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....

  16. Family Policy in France

    OpenAIRE

    Fagnani, Jeanne

    2006-01-01

    Over the last two decades, contrary to the pension system, the family policy branch of the Social security system has been immune to cutbacks in provision and no retrenchment measures have been implemented. This mirrors the salience of family-related issues in the social and political agenda. This also reflects the fact that the family branch and its large network of Local Allowance Funds (CAFs) are responsible for the management of welfare state provisions. The family branch is a transfer-he...

  17. Genetics of familial melanoma

    DEFF Research Database (Denmark)

    Aoude, Lauren G; Wadt, Karin A W; Pritchard, Antonia L;

    2015-01-01

    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...

  18. Family systems and fertility

    NARCIS (Netherlands)

    Moenkediek, Bastian

    2016-01-01

    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

  19. Families in Transition.

    Science.gov (United States)

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

    1987-01-01

    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)…

  20. Strengths of Remarried Families.

    Science.gov (United States)

    Knaub, Patricia Kain; And Others

    1984-01-01

    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)

  1. Single Mothers "Do" Family

    Science.gov (United States)

    Nelson, Margaret K.

    2006-01-01

    This paper explores how single mothers both incorporate others into family life (e.g., when they ask others to care for their children) and simultaneously "do families" in a manner that holds out a vision of a "traditional" family structure. Drawing on research with White, rural single mothers, the author explores the manner in which these women…

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

    Directory of Open Access Journals (Sweden)

    L. L. Golovkina

    2015-01-01

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

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

    KAUST Repository

    Jackson, Andrew P.

    2014-05-05

    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.

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

    DEFF Research Database (Denmark)

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

    1998-01-01

    We have screened peripheral blood mononuclear cells (PBMC) from tuberculosis (TB) patients for proliferative reactivity and interferon-gamma (IFN-gamma) secretion against a panel of purified recombinant (r) and natural (n) culture filtrate (rESAT-6, nMPT59, nMPT64 and nMPB70) and somatic-derived (r....... tuberculosis, MT-CF and M. bovis BCG. We also observed that most of the high responders to complex antigens recognized all of the antigens tested (covariation), demonstrating that the repertoire of human T-cell specificities induced by natural infection is directed towards several unrelated culture filtrate...... as well as somatic-derived protein antigens. In conclusion, the results obtained suggest that the cellular immune response in humans is directed against several important target antigens of M. tuberculosis and that some antigens, such as ESAT-6, are recognized by a high number of individuals...

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

    Science.gov (United States)

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

    2014-12-18

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

  6. Expression of an antigen homologous to the human CO17-1A/GA733 colon cancer antigen in animal tissues.

    OpenAIRE

    Zaloudik, J; Basak, S.; Nesbit, M.; Speicher, D W; Wunner, W H; Miller, E.; Ernst-Grotkowski, C.; Kennedy, R; Bergsagel, L. P.; Koido, T.; Herlyn, D

    1997-01-01

    The CO17-1A/GA733 antigen is associated with human carcinomas and some normal epithelial tissues. This antigen has shown promise as a target in approaches to passive and active immunotherapy of colorectal cancer. The relevance of animal models for studies of immunotherapy targeting this antigen in patients is dependent on the expression of the antigen on normal animal tissues. Immunohistoperoxidase staining with polyclonal rabbit antibodies to the human antigen revealed the human homologue on...

  7. 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)

    2000-01-01

    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

  8. Asteroid family ages

    CERN Document Server

    Spoto, Federica; Knezevic, Zoran

    2015-01-01

    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...

  9. [Familial pituitary tumors].

    Science.gov (United States)

    Yoshimoto, K; Saito, S

    1995-11-01

    Familial pituitary tumors are relatively rare. Most commonly, they occur as a part of multiple endocrine neoplasia type 1 (MEN 1). However, familial pituitary adenomas unrelated MEN 1 (familial pituitary adenomas) are extremely rare. In review of MEN 1 in Japan, 60% of the patients with MEN 1 had pituitary tumors. Only 45 cases of familial pituitary adenomas have been reported from 20 families. In our review of familial pituitary adenomas, 30 (67%) of 45 reported cases are acromegaly or gigantism. This incidence is much higher than 28% in MEN 1 patients with pituitary tumors. Allelic deletions at 11q13 were identified in MEN 1 associated pituitary adenomas and familial pituitary adenomas in two gigantism brothers. PMID:8538028

  10. Inside the Family Firm

    DEFF Research Database (Denmark)

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

    2005-01-01

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

    Science.gov (United States)

    Norris, Steven J

    2006-06-01

    A common mechanism of immune evasion in pathogenic bacteria and protozoa is antigenic variation, in which genetic or epigenetic changes result in rapid, sequential shifts in a surface-exposed antigen. In this issue of Molecular Microbiology, Dai et al. provide the most complete description to date of the vlp/vsp antigenic variation system of the relapsing fever spirochaete, Borrelia hermsii. This elaborate, plasmid-encoded system involves an expression site that can acquire either variable large protein (vlp) or variable small protein (vsp) surface lipoprotein genes from 59 different archival copies. The archival vlp and vsp genes are arranged in clusters on at least five different plasmids. Gene conversion occurs through recombination events at upstream homology sequences (UHS) found in each gene copy, and at downstream homology sequences (DHS) found periodically among the vlp/vsp archival genes. Previous studies have shown that antigenic variation in relapsing fever Borrelia not only permits the evasion of host antibody responses, but can also result in changes in neurotropism and other pathogenic properties. The vlsE antigenic variation locus of Lyme disease spirochaetes, although similar in sequence to the relapsing fever vlp genes, has evolved a completely different antigenic variation mechanism involving segmental recombination from a contiguous array of vls silent cassettes. These two systems thus appear to represent divergence from a common precursor followed by functional convergence to create two distinct antigenic variation processes. PMID:16796669

  12. A 2-Step Laemmli and Antigen Retrieval Method Improves Immunodetection.

    Science.gov (United States)

    Scalia, Carla R; Gendusa, Rossella; Cattoretti, Giorgio

    2016-07-01

    Detection by immunohistochemistry of antigens relies on reproducibly optimal preanalytical and analytical variables such as fixation conditions, antigen retrieval (AR), and the resolutive power of the detection system. There is a need to improve immunodetection on routinely fixed and embedded material, particularly for scarcely represented but relevant antigens. We devised a 2-step method and applied it to a panel of antigens of common use for diagnosis, prognosis, individualized therapy use, or research. The first step consists of a 10 minutes. Incubation at 95°C with a modified Laemmli extraction buffer. This was followed by a traditional AR method. Detection of the vast majority of antigens was improved over a simple AR with preservation of tissue integrity, as shown by quantitative image analysis. The mechanism underlying the improved detection may be controlled denaturation followed by heat-mediated retrieval, a method we dubbed "antigen relaxing" and which will improve routine detection of scarce antigens in formalin-fixed, paraffin-embedded material. PMID:26067142

  13. 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.

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

    DEFF Research Database (Denmark)

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

    1987-01-01

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

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

    DEFF Research Database (Denmark)

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

    1993-01-01

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

  16. NKT cell stimulation with glycolipid antigen in vivo: co-stimulation-dependent expansion, Bim-dependent contraction, and hypo-responsiveness to further antigenic challenge1

    Science.gov (United States)

    Kyparissoudis, Konstantinos; Pellicci, Daniel G.; Zhan, Yifan; Lew, Andrew M.; Bouillet, Philippe; Strasser, Andreas; Smyth, Mark J.; Godfrey, Dale I.

    2005-01-01

    Activation of NKT cells using the glycolipid α-galactosylceramide (α-GalCer4) has availed many investigations into their immunoregulatory and therapeutic potential. However, it remains unclear how NKT cells respond to stimulation in vivo, which co-stimulatory pathways are important, and what factors (eg. antigen availability and activation-induced cell death) limit their response. We have explored these questions in the context of anin vivo model of NKT cell dynamics spanning activation, population expansion and subsequent contraction. Neither the B7/CD28 nor the CD40/CD40-L co-stimulatory pathways were necessary for cytokine production by activated NKT cells, either early (2 hours) or late (3 days) following initial stimulation, but both pathways were necessary for normal proliferative expansion of NKT cells in vivo. The pro-apoptotic Bcl-2 family member Bim was necessary for normal contraction of the NKT cell population between days 3-9 after stimulation, suggesting the pool size is regulated by apoptotic cell death in a manner similar to that of conventional T cells. Antigen availability was not the limiting factor for NKT cell expansion in vivo, and a second injection of α-GalCer induced a very blunted response, whereby cytokine production was reduced and further expansion did not occur. This appeared to be a form of anergy that was intrinsic to the NKT cells and not associated with up-regulation of inhibitory NK cell receptors such as NKG2A or Ly49 family members. Furthermore, NKT cells from mice pre-challenged with α-GalCer in vivoshowed little cytokine production and reduced proliferation in vitro. In summary, this study significantly enhances our understanding of how NKT cells respond to α-GalCer in vivo, revealing that the full primary response depends on costimulation via the CD28 and CD40 pathways, with subsequent Bim-dependent contraction. After contraction, the NKT cells are hypo-responsive to further antigenic induced expansion. PMID:16116198

  17. Antigen receptor signaling: integration of protein tyrosine kinase functions.

    Science.gov (United States)

    Tamir, I; Cambier, J C

    1998-09-17

    Antigen receptors on T and B cells function to transduce signals leading to a variety of biologic responses minimally including antigen receptor editing, apoptotic death, developmental progression, cell activation, proliferation and survival. The response to antigen depends upon antigen affinity and valence, involvement of coreceptors in signaling and differentiative stage of the responding cell. The requirement that these receptors integrate signals that drive an array of responses may explain their evolved structural complexity. Antigen receptors are composed of multiple subunits compartmentalized to provide antigen recognition and signal transduction function. In lieu of on-board enzymatic activity these receptors rely on associated Protein Tyrosine Kinases (PTKs) for their signaling function. By aggregating the receptors, and hence their appended PTKs, antigens induce PTK transphosphorylation, activating them to phosphorylate the receptor within conserved motifs termed Immunoreceptor Tyrosine-based Activation Motifs (ITAMs) found in transducer subunits. The tyrosyl phosphorylated ITAMs then interact with Src Homology 2 (SH2) domains within the PTKs leading to their further activation. As receptor phosphorylation is amplified, other effectors, such as Shc, dock by virtue of SH2 binding, and serve, in-turn, as substrates for these PTKs. This sequence of events not only provides a signal amplification mechanism by combining multiple consecutive steps with positive feedback, but also allows for signal diversification by differential recruitment of effectors that provide access to distinct parallel downstream signaling pathways. The subject of antigen receptor signaling has been recently reviewed in depth (DeFranco, 1997; Kurosaki, 1997). Here we discuss the biochemical basis of antigen receptor signal transduction, using the B cell receptor (BCR) as a paradigm, with specific emphasis on the involved PTKs. We review several specific mechanisms by which responses

  18. Proliferating cell nuclear antigen in neutrophil fate.

    Science.gov (United States)

    Witko-Sarsat, Véronique; Ohayon, Delphine

    2016-09-01

    The life span of a neutrophil is a tightly regulated process as extended survival is beneficial for pathogen elimination and cell death necessary to prevent cytotoxic content release from activated neutrophils at the inflammatory site. Therefore, the control between survival and death must be a dynamic process. We have previously described that proliferating cell nuclear antigen (PCNA) which is known as a nuclear protein pivotal in DNA synthesis, is a key element in controlling neutrophil survival through its association with procaspases. Contrary to the dogma which asserted that PCNA has a strictly nuclear function, in mature neutrophils, PCNA is present exclusively within the cytosol due to its nuclear export at the end of the granulocytic differentiation. More recent studies are consistent with the notion that the cytosolic scaffold of PCNA is aimed at modulating neutrophil fate rather than simply preventing death. Ultimately, targeting neutrophil survival might have important applications not just in the field of immunology and inflammation, but also in hematology and transfusion. The neutrophil emerges as a unique and powerful cellular model to unravel the basic mechanisms governing the cell cycle-independent functions of PCNA and should be considered as a leader of the pack. PMID:27558345

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

    NARCIS (Netherlands)

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

    2012-01-01

    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

  20. Myth of the Perfect Family

    Science.gov (United States)

    ... together fulfill the multiple responsibilities of family life. MYTH: The "Nuclear Family" Is A Universal Phenomenon The ... members and in progressive fragmentation of the family. MYTH: Family Harmony Is The Rule, Not The Exception ...

  1. Administration for Children and Families

    Science.gov (United States)

    ... Releases RSS Feeds Speeches Videos What is the Administration for Children & Families? The Administration for Children and Families (ACF) is a division ... more about the 100-day challenge Visit the Administration on Children, Youth and Families Website The Family ...

  2. Radiolabelled parasite antigens as tools for diagnosis and identification of protective antigens

    International Nuclear Information System (INIS)

    Radiolabelling specific compartments and molecules of parasites provides a valuable tool for establishing parasite antigen-host response systems with utility and/or importance in protection, diagnosis and pathology. The combined immunological, biochemical and molecular biological expertise currently available forms a sufficient basis for a relatively logical and effective programme directed towards the ultimate eradication of tropical diseases. The organization of carefully selected and clinically well characterized sera and patients, representing the range of commonly occurring parasitic infections, would be of great practical value in the pursuance of this goal. (author)

  3. Tresyl-Based Conjugation of Protein Antigen to Lipid Nanoparticles Increases Antigen Immunogencity

    OpenAIRE

    Jain, Anekant; Yan, Weili; Keith R Miller; O'Carra, Ronan; Woodward, Jerold G.; Russell J Mumper

    2010-01-01

    The present studies were aimed at investigating the engineering of NPs with protein-conjugated-surfactant at their surface. In order to increase the immunogenicity of a protein antigen, Brij 78 was functionalized by tresyl chloride and then further reacted with the primary amine of the model proteins ovalbumin (OVA) or horseradish peroxide (HRP). The reaction yielded Brij 78-OVA and Brij 78-HRP conjugates which were then used directly to form NP-OVA or NP-HRP using a one-step warm oil-in-wate...

  4. 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.

  5. Familial germ cell tumor

    Directory of Open Access Journals (Sweden)

    Sanju Cyriac

    2012-01-01

    Full Text Available Familial testicular germ cell tumors are well known in literature. Only few cases are reported where both brother and sister of the same family suffered from germ cell malignancies. We present a family where the proband is a survivor of ovarian dysgerminoma stage IA. Her elder male sibling became acutely ill and was detected to have disseminated testicular malignancy with grossly elevated markers and vegetations in the mitral valve leaflets. Despite all measures he could not be saved. Presence of germ cell malignancies in the siblings of different sex in the same family points toward a genetic susceptibility. Literature review revealed only six similar cases. A discussion regarding the rare occurrence of familial germ cell malignancies with the affected family members may be worthwhile.

  6. Aspergillus antigen testing in bone marrow transplant recipients

    OpenAIRE

    Williamson, E; Oliver, D.; Johnson, E.; Foot, A.; D. Marks; Warnock, D.

    2000-01-01

    Aims—To assess the clinical usefulness of a commercial aspergillus antigen enzyme linked immunosorbent assay (ELISA) in the diagnosis of invasive aspergillosis (IA) in bone marrow transplant recipients, and to compare it with a commercial latex agglutination (LA) test.

  7. The Synthesis of a Novel Phosphorus Containing Antigen

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

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

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

    DEFF Research Database (Denmark)

    Dabelsteen, Erik

    2002-01-01

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

  9. Immune activation by casein dietary antigens in bipolar disorder

    NARCIS (Netherlands)

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

    2010-01-01

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

  10. Control of T cell antigen reactivity via programmed TCR downregulation.

    Science.gov (United States)

    Gallegos, Alena M; Xiong, Huizhong; Leiner, Ingrid M; Sušac, Bože; Glickman, Michael S; Pamer, Eric G; van Heijst, Jeroen W J

    2016-04-01

    The T cell antigen receptor (TCR) is unique in that its affinity for ligand is unknown before encounter and can vary by orders of magnitude. How the immune system regulates individual T cells that display very different reactivity to antigen remains unclear. Here we found that activated CD4(+) T cells, at the peak of clonal expansion, persistently downregulated their TCR expression in proportion to the strength of the initial antigen recognition. This programmed response increased the threshold for cytokine production and recall proliferation in a clone-specific manner and ultimately excluded clones with the highest antigen reactivity. Thus, programmed downregulation of TCR expression represents a negative feedback mechanism for constraining T cell effector function with a suitable time delay to thereby allow pathogen control while avoiding excess inflammatory damage. PMID:26901151

  11. Fragrance - The Commonest Antigen Testing Positive In Chronic Hand Dermatitis

    OpenAIRE

    Dixit Alok; Srinivas C R; Balachandran C; Shenoi S D

    1995-01-01

    Fifty cases of chronic hand dermatitis were patch tested with standard series using antigens from Chemotechnique. Cases with positive reaction to fragrance mix were tested with fragrance series. Results are reported here.

  12. Fragrance - The Commonest Antigen Testing Positive In Chronic Hand Dermatitis

    Directory of Open Access Journals (Sweden)

    Dixit Alok

    1995-01-01

    Full Text Available Fifty cases of chronic hand dermatitis were patch tested with standard series using antigens from Chemotechnique. Cases with positive reaction to fragrance mix were tested with fragrance series. Results are reported here.

  13. The Antigen Presenting Cells Instruct Plasma Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Wei eXu

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ana Laín

    2008-01-01

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

  15. Chlamydia trachomatis antigen in female genital tract infection

    Directory of Open Access Journals (Sweden)

    Badrinath S

    1996-01-01

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

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

    Science.gov (United States)

    Ding, Wei; Zheng, Xiang-Yi

    2012-03-01

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

  17. Family business entrepreneurship

    OpenAIRE

    Wright, Mike; De Massis, Alfredo; Scholes, Louise; Hughes, Mat; Kotlar, Josip

    2016-01-01

    This report investigates the depth and nature of entrepreneurship and innovation in family firms. It sets out the findings and recommendations from new research into the entrepreneurial orientation of private family firms in the UK, the drivers of this orientation, and the impact this has on innovation activity and financial performance. The project has been funded by the Institute for Family Business Research Foundation and conducted by researchers from three UK business schools – Imperial C...

  18. The family lecture.

    Science.gov (United States)

    Rose, Nancy E

    2002-10-01

    SUMMARY This paper describes a lecture about my extended family, in which I discuss a variety of configurations consisting of lesbian, gay, and bisexual adults, and our children. It raises an array of issues, including alternative insemination, biological and nonbiological parentage, donors and birthmothers, adoption, co-parenting and blended families, significant others, and gay marriage and domestic partnership. It helps many students obtain both a more expansive sense of family and adeeper understanding of homophobia. PMID:24804601

  19. Familial germ cell tumor

    OpenAIRE

    Sanju Cyriac; Rejeev Rajendranath; A. Robert Louis; Sagar, T. G.

    2012-01-01

    Familial testicular germ cell tumors are well known in literature. Only few cases are reported where both brother and sister of the same family suffered from germ cell malignancies. We present a family where the proband is a survivor of ovarian dysgerminoma stage IA. Her elder male sibling became acutely ill and was detected to have disseminated testicular malignancy with grossly elevated markers and vegetations in the mitral valve leaflets. Despite all measures he could not be saved. Presenc...

  20. Immigrant Families in Australia

    OpenAIRE

    Jock Collins

    1992-01-01

    Australia has a larger and more diverse immigrant population than most Western societies. Australia's immigration history is linked to the story of family migration as Australia sought immigrants for permanent settlement. However, it is important to aviod over-generalisation when studying immigrant families in Australia today. The main hypothesis is that in order to understand the immigrant family in Australia today it is necessary to study the intersection of factors such as ethnicity, class...

  1. KSF of family business

    OpenAIRE

    Boroš, Petr

    2014-01-01

    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...

  2. Continuous family groupoids

    OpenAIRE

    Paterson, Alan L. T.

    2007-01-01

    In this paper, we define and investigate the properties of continuous family groupoids. This class of groupoids is necessary for investigating the groupoid index theory arising from the equivariant Atiyah-Singer index theorem for families, and is also required in noncommutative geometry. The class includes that of Lie groupoids, and the paper shows that, like Lie groupoids, continuous family groupoids always admit (an essentially unique) continuous left Haar system of smooth...

  3. A Bangladeshi family with three sisters 'Bombay' or Oh phenotype.

    Science.gov (United States)

    Rahman, M; Abdullah, A Z; Husain, M; Hague, K M; Hossain, M M

    1990-12-01

    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.

  4. Antigenic Challenge in the Etiology of Autoimmune Disease in Women

    OpenAIRE

    Mary A M Rogers; Levine, Deborah A.; Blumberg, Neil; Fisher, Gwenith G.; Kabeto, Mohammed; Kenneth M. Langa

    2011-01-01

    Infection has long been implicated as a trigger for autoimmune disease. Other antigenic challenges include receipt of allogeneic tissue or blood resulting in immunomodulation. We investigated antigenic challenges as possible risk factors for autoimmune disease in women using the Health and Retirement Study, a nationally representative longitudinal study, linked to Medicare files, years 1991–2007. The prevalence of autoimmune disease (rheumatoid arthritis, Hashimoto’s disease, Graves’ disease,...

  5. Immunogenicity of transgenic plant-derived hepatitis B surface antigen.

    OpenAIRE

    Thanavala, Y; Yang, Y. F.; Lyons, P; Mason, H S; Arntzen, C

    1995-01-01

    The focus of the Children's Vaccine Initiative is to encourage the discovery of technology that will make vaccines more readily available to developing countries. Our strategy has been to genetically engineer plants so that they can be used as inexpensive alternatives to fermentation systems for production of subunit antigens. In this paper we report on the immunological response elicited in vivo by using recombinant hepatitis B surface antigen (rHBsAg) purified from transgenic tobacco leaves...

  6. Typing of murine cell-surface antigens by cellular radioimmunoassay

    International Nuclear Information System (INIS)

    A cellular radioimmunoassay utilizing 125I-labelled Protein A was used for detecting antigen-antibody complexes on gultaraldehyde fixed cells attached to microtiter plates. This method is rapid, sensitive and specific for revealing H-2 private and public specificities as well as Ia and Lyt antigens. As plates may be kept for months, several reactivities can be tested in one step on a large panel rendering a regular supply of animals unnecessary. (Auth.)

  7. Modeling Influenza Antigenic Shift and Drift with LEGO Bricks

    OpenAIRE

    Boriana Marintcheva

    2016-01-01

    The concepts of antigenic shift and drift could be found in almost every microbiology and virology syllabus, usually taught in the context of Influenza virus biology. They are central to understanding viral diversity and evolution and have direct application to anti-flu vaccine design and effectiveness. To aid student understanding of the concepts, I have developed an exercise to visualize the mechanistic aspects of antigenic shift and drift using LEGO bricks. This hands-on/minds-on exercise ...

  8. Antibody avidity in swine lymphocyte antigen-defined miniature pigs.

    OpenAIRE

    Appleyard, G D; Mallard, B A; Kennedy, B. W.; Wilkie, B. N.

    1992-01-01

    Antibody avidity to hen egg white lysozyme (HEWL) was measured by thiocyanate ion elution enzyme-linked immunosorbent assay (ELISA) in swine lymphocyte antigen (SLA) defined miniature pigs. Serum antibody avidity was evaluated on day 14 and 30 after primary (day 0) and secondary (day 14) immunizations in eight to ten week old miniature pigs previously typed for swine lymphocyte antigen genotype. The effect of SLA genotype, litter, and gender on anti-HEWL antibody avidity was determined by lea...

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

    OpenAIRE

    Ewa Łukasik; Kazimiera Waśniowska

    2016-01-01

    Duffy (Fy) blood group antigens are located on seven-transmembrane glycoprotein expressed on erythrocytes and endothelial cells, which acts as atypical chemokine receptor (ACKR1) and malarial receptor. The biological role of the Duffy glycoprotein has not been explained yet. It is suggested that Duffy protein modulate the intensity of the inflammatory response. The Duffy blood group system consists of two major antigens, Fya and Fyb, encoded by two codominant alleles designated FY*A and FY*B ...

  10. Antigen-specific immune reactions to ischemic stroke

    Directory of Open Access Journals (Sweden)

    Xabier eUrra

    2014-09-01

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

  11. Antigenicity and Immunogenicity of Plasmodium vivax Merozoite Surface Protein-3

    OpenAIRE

    Amanda R Bitencourt; Elaine C Vicentin; Jimenez, Maria C.; Ricardo Ricci; Leite, Juliana A.; Fabio T Costa; Luis C Ferreira; Bruce Russell; François Nosten; Laurent Rénia; Galinski, Mary R.; Barnwell, John W.; Rodrigues, Mauricio M; Soares, Irene S

    2013-01-01

    A recent clinical trial in African children demonstrated the potential utility of merozoite surface protein (MSP)-3 as a vaccine against Plasmodium falciparum malaria. The present study evaluated the use of Plasmodium vivax MSP-3 (PvMSP-3) as a target antigen in vaccine formulations against malaria caused by P. vivax. Recombinant proteins representing MSP-3α and MSP-3β of P. vivax were expressed as soluble histidine-tagged bacterial fusions. Antigenicity during natural infection was evaluated...

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

    Science.gov (United States)

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

    1988-01-01

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

  13. Prevalence of Weak D Antigen In Western Indian Population

    Directory of Open Access Journals (Sweden)

    Tanvi Sadaria

    2015-12-01

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

  14. Antigenic distinctiveness, heterogeneity, and relationships of Methanothrix spp.

    OpenAIRE

    Macario, A J; Conway de Macario, E

    1987-01-01

    A detailed immunologic analysis of Methanothrix soehngenii Opfikon (the type species of the genus), Methanothrix sp. strain CALS-1, and Methanothrix concilii GP6 was performed. A variety of poly- and monoclonal antibody probes for a comprehensive panel of reference organisms were used to determine immunogenicity, antigenicity, and relationships. The three organisms are antigenically distinct but interrelated, forming an immunologically cohesive group, weakly related to methanosarcinae. A prom...

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

    Science.gov (United States)

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

    1995-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Baert K

    2016-05-01

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

  17. Nonprostatic sources of prostate-specific antigen.

    Science.gov (United States)

    Diamandis, E P; Yu, H

    1997-05-01

    The name prostate-specific antigen has been given to a protein that now is known not to be prostate-specific; however, prostatic tissue does produces extremely high levels of PSA and secrets it into the seminal plasma. Seminal plasma contains about 1 million micrograms/L of PSA and is the richest source of PSA reported. The biologic fluid with the second highest PSA concentration, however, is nipple aspirate fluid from the female breast (up to about 5000 micrograms/L), and the third is milk from lactating women (up to 300 micrograms/L). Male serum PSA is usually less than 4 micrograms/L. In nonprostatic tissues, PSA exists mainly in its free molecular form, but PSA-ACT complex is also present in most of the fluids that contain PSA, such as breast secretions and amniotic fluid. The gene expression and protein production of PSA in nonprostatic tissues are under the regulation of steroid hormones via their receptors. Androgens, glucocorticoids, and progestins up-regulate the PSA gene expression, resulting in an increase of protein production. Estrogen by itself seems to have no effect on PSA regulation, but it can impair PSA production induced by androgen. It remains unknown whether PSA is enzymatically active and what is the physiologic role of PSA in nonprostatic tissues. It is speculated that PSA may be involved in the regulation of growth factors. Measuring PSA in breast cancer cytosol, breast-nipple aspirate fluid, and female serum may have potential clinical utilities, including breast cancer prognosis, breast cancer risk assessment, and evaluation of androgen excess. Further studies are needed to identify the exact function and regulation of PSA in nonprostatic tissues and to explore the clinical application of this protein. PMID:9126224

  18. Melanocyte antigen triggers autoimmunity in human psoriasis.

    Science.gov (United States)

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

    2015-12-14

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

  19. Familial combined hyperlipidemia

    Science.gov (United States)

    Multiple lipoprotein-type hyperlipidemia ... Familial combined hyperlipidemia is the most common genetic disorder that increases blood fats. It can cause early heart attacks. Diabetes , alcoholism, ...

  20. Family in contemporary society

    Directory of Open Access Journals (Sweden)

    Rabije Murati

    2016-01-01

    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.