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Sample records for anti cd-20 c2b8

  1. Radioimmunotherapy in refractory b-cell nonhodgkins lymphoma with I-131-labeled chimeric anti cd-20 c2b8 (I-131 rituximab): preliminary result

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    Kang, Hye Jin; Park, Yeon Hee; Kim, Sung Eun and others [Korea University Medical School, Seoul (Korea, Republic of)

    2005-07-01

    Recently, the native chimeric human-mouse anti CD-20 antibody IDEC-C2B8 (Rituximab) has been widely applied in NHL. This ongoing phase study was to evaluate whether radioimmunotherapy (RIT) with I-131 rituximab is effective in refractory B-cell NHL. Inclusion criteria were as follows: B-cell NHL with relapsed or refractory to primary standard therapy, measurable disease, adequate hematologic, renal, and hepatic function, informed consent. The rituximab (Mabthera, Roach) was radiolabeled with iodine-131(I-131) using a modified chloramine T method with high radiochemical purity (95%) and preservation of immuno-reactivity. All patients received loading doses of unlabeled rituximab (median, 40 mg: range, 20{approx}70 mg) immediately prior to administration of therapeutic dose (51.4{approx}152.2 MBq/kg), and then underwent gamma camera scan. 11 patients were enrolled (4 low-grade B-cell NHL, 7 DLBCL, median age 63 years). Patients had received a median of three prior chemotherapy regimens. The objective response rate was 36.4% (1 CR, 3 PRs). These all responses were observed in low-grade B-cell NHL, except one with DLBCL. Adverse events were primarily hematologic toxicities; the incidence of grade 3/4 neutropenia, thrombocytopenia, and anemia was 27.3%, 45.5%, and 18.2%, respectively. The treatment-related mortality was observed in one patient, who had been previously treated with high-dose chemotherapy plus TBI with autologous stem cell transplantation. RIT with I-131 rituximab seems to be effective tolerable in refractory low-grade B-cell NHL, although modest activity in refractory DLBCL. Further studies to define the efficacy of I-131 rituximab in DLBCL are warranted.

  2. High-dose radioimmunotherapy in refractory b-celI non-Hodgikin's lymphoma with I-131-labeled chimeric anti CD-20 C2B8 (I-131 rituximab): pilot trial

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    Kim, Sung Eun; Park, Yeon Hee; Cheon, Gi Jeong; Ryoo, Baek Yeol; Lee, Seung Sook; Choi, Chang Woon; Lim, Sang Moo [Korea Institute of Radiological and Medical Science, Seoul (Korea, Republic of)

    2004-07-01

    The native chimeric human-mouse anti CD-20 antibody IDEC-C2B8 (rituximab) is therapeutically applied in relapsed or refractory NHL. This ongoing pilot study was to evaluate whether high-dose radioimmunotherapy (RIT) with I-131 rituximab is therapeutically effective in refractory B-cell NHL. 5 patients (5 male, aged 50.89{+-}16.89) with chemorefractory NHL of B-cell origin (2 diffuse large B cell, 1 burkitt's lymphoma, and 2 mantle cell Iymphoma) oe, with a life expectancy of at least 3 months, and with a Kamofsky performance score of 60 and above were studied. The chimeric IgG1 anti CD 20 monoclonal antibody rituximab (mabthera, Roche) was radiolabelled with iodine-131 (I-131) using a modified chloaramine T method with high radiochemical purity (95%{+-}0.9) and preservation of immunoreactivity. All patients received therapeutic loading doses of unlabelled rituximab (18.5 MBq/kg) immediately prior to administration of therapeutic dose (3.7 GBq-8.5 GBq), and then underwent gamma camera scan and pre-and post-RIT FDG PET (within 7 day and day 30). Blood cell nadirs were reached at 2-3 weeks after therapy infusion, but all patients recovered at 6 weeks after treatment. Non hematologic toxicity was restricted to mild-to moderate nausea, fever, transient bilirubin, or liver enzyme elevation. Two (8.5 GBq) with mantle cell lymphoma and one with burkitt's lymphoma experienced good partial remissions, and one (5.5 GBq, DLBL) with bulky disease had a partial remission, and one patient (3.7 GBq, DLBL) with bulky disease had a mixed response. High-dose RIT with I-131 labelled rituximab seems to be effective and moderate toxicity. Further follow-up to monitor the long-term outcome are indicated.

  3. Dosimetry and microdosimetry of 188 Re-anti-CD20 and 131 I-anti-CD20 for the treatment of No Hodgkin lymphomas

    International Nuclear Information System (INIS)

    The purpose of this investigation was to prepare 131I-anti-CD20 and 188Re-anti-CD20 and to estimate the radiation absorbed dose at macro- and micro- level during a NHL treatment. The work was divided in 4 general objectives: 1) preparation of 131I-anti-CD20 and 188Re-anti-CD20, 2) application in patients to obtain biokinetic parameters and estimate the organ absorbed doses 3) estimation of the cellular dosimetry using the MIRD methodology and the MCNP4C2 code and 4) estimation of the cellular microdosimetry using the NOREC code. 188Re-anti-CD20 was prepared by a direct labelling method using sodium tartrate as a weak ligand. To evaluate the biological recognition a comparative study of the in vitro binding of 188Re-anti-CD20, 125I-anti-CD20 (positive control) and 188Re-anti-CEA (negative control) to normal B Iymphocytes was performed. Biodistribution studies in normal mice were accomplished to assess the in vivo Re-anti-CD20 complex stability. The binding of ' Re-anti-CD20 to cells was in the same range as '251-anti-CD20 (>80%) considered as the positive control. 188Re-anti-CD20 and '3'1-anti-CD20 prepared were administered in patients diagnosed with B cell NHL at the Centro Medico Siglo XXI (IMSS). The protocol was approved by the hospital's Medical Ethics Committee. AJI patients signed a consent form after receiving detailed information on the aims of the study. N data were the input for the OLINDA/EXM software to calculate the radiation absorbed dose to organs and whole body. Dosimetric studies indicate that after administration of 6.4 GBq and 4.87 to 8.75 GBq of '3'1-anti-CD20 and 188Re-anti-CD20 respectively, the absorbed dose to total body would be 0.75 Gy which corresponds to the recommended dose for NHL therapies. The calculated organ absorbed doses indicate that 188Re-anti-CD20 may be used in radioimmunotherapy without the risk of toxicity to red marrow or healthy organs. The absorbed dose (D) into cellular nucleus was calculated by two different

  4. Dosimetry and microdosimetry of {sup 188} Re-anti-CD20 and {sup 131} I-anti-CD20 for the treatment of No Hodgkin lymphomas; Dosimetria y microdosimetria del {sup 188} Re-anti-CD20 y {sup 131} I-anti-CD20 para el tratamiento de linfomas No Hodgkin

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    Torres G, E

    2007-07-01

    The purpose of this investigation was to prepare {sup 131}I-anti-CD20 and {sup 188}Re-anti-CD20 and to estimate the radiation absorbed dose at macro- and micro- level during a NHL treatment. The work was divided in 4 general objectives: 1) preparation of {sup 131}I-anti-CD20 and {sup 188}Re-anti-CD20, 2) application in patients to obtain biokinetic parameters and estimate the organ absorbed doses 3) estimation of the cellular dosimetry using the MIRD methodology and the MCNP4C2 code and 4) estimation of the cellular microdosimetry using the NOREC code. {sup 188}Re-anti-CD20 was prepared by a direct labelling method using sodium tartrate as a weak ligand. To evaluate the biological recognition a comparative study of the in vitro binding of {sup 188}Re-anti-CD20, {sup 125}I-anti-CD20 (positive control) and {sup 188}Re-anti-CEA (negative control) to normal B Iymphocytes was performed. Biodistribution studies in normal mice were accomplished to assess the in vivo Re-anti-CD20 complex stability. The binding of ' Re-anti-CD20 to cells was in the same range as '251-anti-CD20 (>80%) considered as the positive control. {sup 188}Re-anti-CD20 and '3'1-anti-CD20 prepared were administered in patients diagnosed with B cell NHL at the Centro Medico Siglo XXI (IMSS). The protocol was approved by the hospital's Medical Ethics Committee. AJI patients signed a consent form after receiving detailed information on the aims of the study. N data were the input for the OLINDA/EXM software to calculate the radiation absorbed dose to organs and whole body. Dosimetric studies indicate that after administration of 6.4 GBq and 4.87 to 8.75 GBq of '3'1-anti-CD20 and {sup 188}Re-anti-CD20 respectively, the absorbed dose to total body would be 0.75 Gy which corresponds to the recommended dose for NHL therapies. The calculated organ absorbed doses indicate that {sup 188}Re-anti-CD20 may be used in radioimmunotherapy without the risk of toxicity to red marrow or

  5. Anti-CD20 multivalent HPMA copolymer-Fab′ conjugates for the direct induction of apoptosis

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    Chu, Te-Wei; Yang, Jiyuan; Kopeček, Jindřich

    2012-01-01

    A hybrid biomimetic system comprising high-molecular-weight, linear copolymer of N-(2-hydroxypropyl)methacrylamide (HPMA) grafted with multiple Fab′ fragments of anti-CD20 monoclonal antibody (mAb) was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization followed by attachment of Fab′ fragments via thioether bonds. Exposure of human non-Hodgkin’s lymphoma (NHL) Raji B cells to the multivalent conjugates resulted in crosslinking of CD20 receptors and commenceme...

  6. Improving therapeutic activity of anti-CD20 antibody therapy through immunomodulation in lymphoid malignancies.

    Science.gov (United States)

    Lipowska-Bhalla, Grazyna; Fagnano, Ester; Illidge, Timothy M; Cheadle, Eleanor J

    2016-06-01

    Nearly two decades ago rituximab heralded a new era in management of B cell malignancies significantly increasing response rates and survival. However, despite clear therapeutic advantage, significant numbers of patients become refractory to anti-CD20 mAb therapy, suggesting urgent improvements are required. It is now well recognized that the suppressive tumor microenvironment plays an important role in the outcome of anti-CD20 mAb therapy and that manipulation of this environment may improve the efficacy and produce long-term tumor control. The past few years have seen a surge of interest in immunomodulatory agents capable of overwriting immune suppressive networks into favorable clinical outcome. Currently, a number of such combinations with anti-CD20 mAb is under evaluation and some have produced encouraging outcomes in rituximab refractory disease. In this review, we give an outline of anti-CD20 mAbs and explore the combinations with immunomodulatory agents that enhance antitumor immunity through targeting stimulatory or inhibitory pathways and have proven potential to synergize with anti-CD20 mAb therapy. These agents, primarily mAbs, target CTLA-4, PD-1/PD-L1, and CD40. PMID:27050042

  7. Dosimetric studies of anti-CD20 labeled with therapeutic radionuclides at IPEN/CNEN-SP

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    Barrio, G.; Dias, C.R.B.R.; Osso Junior, J.A., E-mail: gracielabarrio@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2012-07-01

    Radioimmunotherapy (RIT) makes use of monoclonal antibodies (MAb) labeled with alpha/beta radionuclides for therapeutical purposes, leading to tumor irradiation and destruction, preserving the normal organs on the radiation excess. The therapeutic activity to be injected in a specific patient is based on information obtained in dosimetric studies. Beta emitting radionuclides such as {sup 131}I, {sup 188}Re, {sup 90}Y, {sup 177}Lu and {sup 166}Ho are useful for the development of therapeutic radiopharmaceuticals. Anti-CD20 (Rituximab) is a chimeric MAb directed against antigen surface CD20 on B-lymphocytes, used in non-Hodgkin lymphoma treatment (NHL). The association with beta radionuclides have shown greater therapeutic efficacy. Currently, two radiopharmaceuticals with Anti-CD20 for radioimmunotherapy have FDA approval for NHL treatment: {sup 131}I-AntiCD20 (Bexar) and {sup 90}Y-AntiCD20 (Zevalin). Techniques for the radiolabeling of {sup 188}Re-antiCD20 have been recently developed by IPEN-CNEN/SP in order to evaluate the clinical use of this radionuclide in particular. The use of {sup 188}Re (T{sub 1/2} 17h) produced by the decay of {sup 188}W (T{sub 1/2} 69d), from an {sup 188}W/{sup 188}Re generator system, has represented an alternative to RIT. Beyond high energy beta emission for therapy, {sup 188}Re also emits gamma rays (155keV) suitable for image. The aim of this new project is to compare the labeling of anti-CD20 with {sup 188}Re with the same MAb labeled with {sup 131}I, {sup 177}Lu, {sup 90}Y and even {sup 99m}Tc. The first step in this project is the review of the published data available concerning the labeling of this MAb with different radionuclides, along with data obtained at IPEN, taking into account labeling procedures, labeling yields, reaction time, level and kind of impurities and biodistribution studies. The pharmacokinetic code will be developed in Visual Studio.NET platform through VB.NET and C{sup ++} for biodistribution and dosimetric

  8. Labelling and biological valuation of anti-CD-20 for treatment of non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Full text: Anti-CD20 monoclonal chimeric humanized murine antibodies (Rituximab), have been successfully applied for the treatment of Non Hodgkin's Lymphoma. However, upon labelling of the mab-CD20 with β-emitters as 90Y, the therapeutic efficacy has significantly increased due to radiological effects of ionizing radiation. Our objective was to develop reliable and efficient methods for labelling anti-CD20 with β-emitters of therapeutic interest and simple and rugged quality control methods to evaluate radiochemical purity, biological performance and immunoreactivity assessment. 131I and 188Re have been used for the labelling of anti-CD20 as two attractive alternatives due to decay properties and availability (188Re: Eβmax: 2.2MeV, Eγ 0,155MeV, T=17h, generator produced; 131I: Eβmax: 0,63MeV, Eγ 0,364MeV, T=8d). Labelling of anti-CD20 was optimized following the oxidation procedure of chloramine-T in the case of 131I and the synthesis of 188Re(IV) complex with the previously reduced monoclonal antibody. Quality control of the species obtained were done by physicochemical methods, including ITLC-SG and HPLC, non specific protein precipitation, biological distribution in normal mice and immunoreactivity studies with membrane antigens extracted from isolated leucocytes. 131I- (more than 3.7 GBq/mL) was introduced on tyrosyl residues of the protein chain by adding 28 MBq to 20μg of anti CD20 (Mab Thera, 10mg/mL) at pH 7.4 and 1.3μg of Choramine-T. Purification was done by gel-permeation with sephadex G-25 (PD-10, Pharmacia). For labelling with 188Re, anti CD20 was first reduced by incubation with 2- mercaptoethanol and purified over a PD10 column. Fractions of reduced antibody were pooled and formulated as kit for instant labelling. Each kit contained 1mg anti-CD20; 82.8mg of sodium tartrate; 1.67 mg of stannous fluoride and 0.25 mg gentisic acid. For the labelling, sodium perrhenate (1.5-1.9 GBq) was acidified, added to the kit and then incubated for 1 hour at

  9. The γ-radiation induced CD20 expression and anti-CD20 antibodies mediated cell death on hematopoietic cancer cell

    International Nuclear Information System (INIS)

    Daudi cells were exposed to sub lethal doses of γ-radiation (0.5 Gy and 1.5 Gy; dose rate 1.8Gy/min, 60CO) and followed by incubation at 37℃. Changes in CD20 expression was measured at different time intervals. In other experiment cells with over expression of CD20 were further treated with either RTX or TST following by incubation at 37℃. Anti-CD20 mediated changes in ROS, MMP and cell death were studied after 24hrs. Exposure of cells to γ-radiation showed increase in CD20 level maximally at 20h. Cells treated with both radiation and AntiCD20 antibodies showed differential responses. Combination of radiation with either RTX or TST showed significant increase in ROS generation. 0.5Gy+TST and 1.5Gy+TST showed sudden decrease in MMP with respect to TST or radiation alone, whereas Rad+RTX was shown to increase of MMP (at 24h) which was reduced with time. Percentage of cell death was significantly high in all combination group with respect to corresponding control groups. However, 1.5Gy+TST have shown high cell death levels as compared to 1.5Gy+RTX. All combination groups have shown increased PARP cleavage with respect to control groups. The combination of anti-CD20 with radiation significantly increased cell death in CD20 over expressing cells. However in vivo studies need to be done to confirm hypothesis

  10. Expression and biological characterization of an anti-CD20 biosimilar candidate antibody: a case study.

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    Dorvignit, Denise; Palacios, Julio L; Merino, Maylin; Hernández, Tays; Sosa, Katya; Casaco, Angel; López-Requena, Alejandro; Mateo de Acosta, Cristina

    2012-01-01

    The CD20 molecule is a non-glycosylated protein expressed mainly on the surface of B lymphocytes. In some pathogenic B cells, it shows an increased expression, thus becoming an attractive target for diagnosis and therapy. Rituximab is a chimeric antibody that specifically recognizes the human CD20 molecule. This antibody is indicated for the treatment of non-Hodgkin lymphomas and autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. In this work, we describe the stable expression and biological evaluation of an anti-CD20 biosimilar antibody. While rituximab is produced in fed-batch culture of recombinant Chinese hamster ovary (CHO) cells, our biosimilar antibody expression process consists of continuous culture of recombinant murine NS0 myeloma cells. The ability of the purified biosimilar antibody to recognize the CD20 molecule on human tumor cell lines, as well as on peripheral blood mononuclear cells from humans and primates, was demonstrated by flow cytometry. The biosimilar antibody induced complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity and apoptosis on human cell lines with high expression of CD20. In addition, this antibody depleted CD20-positive B lymphocytes from peripheral blood in monkeys. These results indicate that the biological properties of the biosimilar antibody compare favorably with those of the innovator product, and that it should be evaluated in future clinical trials. PMID:22647435

  11. Expression and biological characterization of an anti-CD20 biosimilar candidate antibody

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    Dorvignit, Denise; Palacios, Julio L.; Merino, Maylin; Hernández, Tays; Sosa, Katya; Casacó, Angel; López-Requena, Alejandro; Mateo de Acosta, Cristina

    2012-01-01

    The CD20 molecule is a non-glycosylated protein expressed mainly on the surface of B lymphocytes. In some pathogenic B cells, it shows an increased expression, thus becoming an attractive target for diagnosis and therapy. Rituximab is a chimeric antibody that specifically recognizes the human CD20 molecule. This antibody is indicated for the treatment of non-Hodgkin lymphomas and autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. In this work, we describe the stable expression and biological evaluation of an anti-CD20 biosimilar antibody. While rituximab is produced in fed-batch culture of recombinant Chinese hamster ovary (CHO) cells, our biosimilar antibody expression process consists of continuous culture of recombinant murine NS0 myeloma cells. The ability of the purified biosimilar antibody to recognize the CD20 molecule on human tumor cell lines, as well as on peripheral blood mononuclear cells from humans and primates, was demonstrated by flow cytometry. The biosimilar antibody induced complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity and apoptosis on human cell lines with high expression of CD20. In addition, this antibody depleted CD20-positive B lymphocytes from peripheral blood in monkeys. These results indicate that the biological properties of the biosimilar antibody compare favorably with those of the innovator product, and that it should be evaluated in future clinical trials. PMID:22647435

  12. Anti-CD20 antibody promotes cancer escape via enrichment of tumor-evoked regulatory B cells expressing low levels of CD20 and CD137L.

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    Bodogai, Monica; Lee Chang, Catalina; Wejksza, Katarzyna; Lai, Jinping; Merino, Maria; Wersto, Robert P; Gress, Ronald E; Chan, Andrew C; Hesdorffer, Charles; Biragyn, Arya

    2013-04-01

    The possible therapeutic benefits of B-cell depletion in combating tumoral immune escape have been debated. In support of this concept, metastasis of highly aggressive 4T1 breast cancer cells in mice can be abrogated by inactivation of tumor-evoked regulatory B cells (tBreg). Here, we report the unexpected finding that B-cell depletion by CD20 antibody will greatly enhance cancer progression and metastasis. Both murine and human tBregs express low levels of CD20 and, as such, anti-CD20 mostly enriches for these cells. In the 4T1 model of murine breast cancer, this effect of enriching for tBregs suggests that B-cell depletion by anti-CD20 may not be beneficial at all in some cancers. In contrast, we show that in vivo-targeted stimulation of B cells with CXCL13-coupled CpG oligonucleotides (CpG-ODN) can block cancer metastasis by inhibiting CD20(Low) tBregs. Mechanistic investigations suggested that CpG-ODN upregulates low surface levels of 4-1BBL on tBregs to elicit granzyme B-expressing cytolytic CD8(+) T cells, offering some explanative power for the effect. These findings underscore the immunotherapeutic importance of tBreg inactivation as a strategy to enhance cancer therapy by targeting both the regulatory and activating arms of the immune system in vivo. PMID:23365136

  13. Veterans health administration hepatitis B testing and treatment with anti-CD20 antibody administration

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    Hunt, Christine M; Beste, Lauren A; Lowy, Elliott; Suzuki, Ayako; Moylan, Cynthia A; Tillmann, Hans L; Ioannou, George N; Lim, Joseph K; Kelley, Michael J; Provenzale, Dawn

    2016-01-01

    AIM: To evaluate pretreatment hepatitis B virus (HBV) testing, vaccination, and antiviral treatment rates in Veterans Affairs patients receiving anti-CD20 Ab for quality improvement. METHODS: We performed a retrospective cohort study using a national repository of Veterans Health Administration (VHA) electronic health record data. We identified all patients receiving anti-CD20 Ab treatment (2002-2014). We ascertained patient demographics, laboratory results, HBV vaccination status (from vaccination records), pharmacy data, and vital status. The high risk period for HBV reactivation is during anti-CD20 Ab treatment and 12 mo follow up. Therefore, we analyzed those who were followed to death or for at least 12 mo after completing anti-CD20 Ab. Pretreatment serologic tests were used to categorize chronic HBV (hepatitis B surface antigen positive or HBsAg+), past HBV (HBsAg-, hepatitis B core antibody positive or HBcAb+), resolved HBV (HBsAg-, HBcAb+, hepatitis B surface antibody positive or HBsAb+), likely prior vaccination (isolated HBsAb+), HBV negative (HBsAg-, HBcAb-), or unknown. Acute hepatitis B was defined by the appearance of HBsAg+ in the high risk period in patients who were pretreatment HBV negative. We assessed HBV antiviral treatment and the incidence of hepatitis, liver failure, and death during the high risk period. Cumulative hepatitis, liver failure, and death after anti-CD20 Ab initiation were compared by HBV disease categories and differences compared using the χ2 test. Mean time to hepatitis peak alanine aminotransferase, liver failure, and death relative to anti-CD20 Ab administration and follow-up were also compared by HBV disease group. RESULTS: Among 19304 VHA patients who received anti-CD20 Ab, 10224 (53%) had pretreatment HBsAg testing during the study period, with 49% and 43% tested for HBsAg and HBcAb, respectively within 6 mo pretreatment in 2014. Of those tested, 2% (167/10224) had chronic HBV, 4% (326/7903) past HBV, 5% (427

  14. Rituximab and Other New Anti-CD20 MAbs for Non-Hodgkin’s Lymphoma Treatment

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    Letizia Polito

    2013-10-01

    Full Text Available Non-Hodgkin’s lymphomas (NHLs are a heterogeneous group of different haematological cancers with a wide range of aggressiveness. NHLs represent >80% of lymphomas and the majority of NHLs involve B cells. CD20 represents a good target for NHL immunotherapy because it is largely expressed on B cell NHL and not on B cell precursors and plasma cells. The anti-CD20 monoclonal antibody (mAb rituximab (RTX was the first antibody approved by the FDA for lymphoma therapy and has revolutionised B cell lymphoma treatment. Several clinical trials have demonstrated the high efficacy of RTX, resulting in a significant improvement in overall response rates and in NHL patient survival. However, RTX, both as a single agent and in combination with chemotherapy, induces several side-effects and resistance mechanisms. Remarkable efforts have been made to improve RTX efficacy, including conjugation to an active moiety (radionuclide, toxin, enzyme, or drug and the development of new anti-CD20 mAbs. This review summarises the characteristics of RTX and other anti-CD20 mAbs for NHL treatment; the results of the main clinical trials are reported.

  15. Tetravalent anti-CD20/CD3 bispecific antibody for the treatment of B cell lymphoma.

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    Lu, Chia-Yen; Chen, Gregory J; Tai, Pei-Han; Yang, Yu-Chen; Hsu, Yu-Shen; Chang, Mingi; Hsu, Chuan-Lung

    2016-05-13

    Bispecific antibodies (bsAbs) are second generation antibodies for therapeutic application in immunotherapy. One of the major strategies of the bsAb platform is the recruitment of immune effector T cells by incorporating an anti-CD3 domain. A bispecific T-cell engager (BiTE), with one end having an affinity for CD3 and the other end with affinity for CD19, has been approved in the US and Europe for the treatment of acute lymphoblastic leukemia. However, due to their small size and lack of Fc region, these single-chain variable fragment (scFv) bsAbs have short half-lives in vivo. Additionally, poor solubility, structural instability, and low production yields have also become major challenges in the bulk production process. To overcome these challenges, we have engineered a tetravalent bsAb with bivalent binding specificity for the CD20 and CD3 antigen in an immunoglobulin G (IgG) format. The fusion of the anti-CD3 scFvs to the CD20 antibody via a linker-hinge domain (LHD) results in improved antibody stabilization and properties. Here we demonstrate this antibody's highly efficient cancer cell elimination in a dose-dependent manner in a CD20-expressing B lymphoblastoid cell line in vitro. Our data suggest the potential clinical application of this bsAb for the treatment of CD20-expressing B cell malignancies. PMID:27040766

  16. Preparation of the radiopharmaceutical 131I-Anti-CD20 for the treatment of lymphomas

    International Nuclear Information System (INIS)

    At the present time they are considered to the lymphomas like a problem of first magnitude since has happened it is necessary to be the fifth cancer cause in the world. Different treatments focused to the lymphoma like the chemotherapy and the radiotherapy, have been employees to counteract the No-Hodgkin lymphoma, without these they don't exclude the healthy tissue of the toxicity. It is for it that is taking a new direction with the employment of the directed radioimmunotherapy since this it allows to kill wicked cells selectively with radiation dose joined to the apoptosis and cytotoxicity induced by the own one bio molecule. The radioimmunotherapy with radiolabelled antibodies directed to the surface antigen CD20 represents a new modality for the treatment of No-Hodgkin lymphoma and potentially other illnesses. In this work the parameters of optimization are presented for the preparation, control of quality and evaluation of the stability in vitro and in vivo of the monoclonal antibody anti-CD20 labelled with 131 I for the treatment of No-Hodgkin lymphoma. The anti-CD20 labelled by the chloramine-T method with high radiochemical purity (>98%), it is stable in solution for but of a half life of the radionuclide (8.04 days) The 131 I-anti-CD20 doesn't present dehalogenation in vitro (human serum) during 24 h of incubation at 37 C. According to the tests carried out to establish the immunoreactivity, a percentage of union to cells was obtained (B lymphocytes) bigger to 30%. The biodistribution in mice balb/c one hour after their administration, it shows that there is not high reception in mucous neither kidneys, what indicates that the complex is stable in vivo. In conclusion, the radiopharmaceutical 131 I-anti-CD20 was obtained in sterile injectable solution and free of pyrogens with a radiochemical purity bigger to 98% and a specific activity of 296 MBq. The radiolabelled molecule maintains its biological recognition for the receiving CD20 highly expressed in

  17. Highly potent anti-CD20-RLI immunocytokine targeting established human B lymphoma in SCID mouse.

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    Vincent, Marie; Teppaz, Géraldine; Lajoie, Laurie; Solé, Véronique; Bessard, Anne; Maillasson, Mike; Loisel, Séverine; Béchard, David; Clémenceau, Béatrice; Thibault, Gilles; Garrigue-Antar, Laure; Jacques, Yannick; Quéméner, Agnès

    2014-01-01

    Rituximab (RTX), a chimeric IgG1 monoclonal antibody directed against the CD20 antigen, has revolutionized the treatment of B-cell malignancies. Nevertheless, the relapsed/refractory rates are still high. One strategy to increase the clinical effectiveness of RTX is based on antibody-cytokine fusion protein (immunocytokine; ICK) vectorizing together at the tumor site the antibody effector activities and the cytokine co-signal required for the generation of cytotoxic cellular immunity. Such ICKs linking various antibody formats to interleukin (IL)-2 are currently being investigated in clinical trials and have shown promising results in cancer therapies. IL-15, a structurally-related cytokine, is now considered as having a better potential than IL-2 in antitumor immunotherapeutic strategies. We have previously engineered the fusion protein RLI, linking a soluble form of human IL-15Rα-sushi+ domain to human IL-15. Compared with IL-15, RLI displayed better biological activities in vitro and higher antitumor effects in vivo in murine and human cancer models. In this study, we investigated the advantages of fusing RLI to RTX. Anti-CD20-RLI kept its binding capacity to CD20, CD16 and IL-15 receptor and therefore fully retained both antibody effector functions (ADCC and CDC), and the cytokine potential of RLI. In a severe combined immunodeficiency (SCID) mouse model of disseminated residual lymphoma, anti-CD20-RLI was found to induce long-term survival of 90% of mice up to at least 120 days whereas RLI and RTX, alone or in combination, just delayed the disease onset (100% of death at 28, 40 and 51 days respectively). These findings suggest that such ICK could improve the clinical efficacy of RTX, particularly in patients with refractory B-cell lymphoma. PMID:25072059

  18. Ibrutinib interferes with the cell-mediated anti-tumor activities of therapeutic CD20 antibodies: implications for combination therapy

    DEFF Research Database (Denmark)

    Da Roit, F.; Engelberts, P. J.; Taylor, R. P.;

    2015-01-01

    The novel Bruton tyrosine kinase inhibitor ibrutinib and phosphatidyl-4-5-biphosphate 3-kinase-delta inhibitor idelalisib are promising drugs for the treatment of chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma, either alone or in combination with anti-CD20 antibodies. We investigated...... the possible positive or negative impact of these drugs on all known mechanisms of action of both type I and type II anti-CD20 antibodies. Pretreatment with ibrutinib for 1 hour did not increase direct cell death of cell lines or chronic lymphocytic leukemia samples mediated by anti-CD20 antibodies....... Pre-treatment with ibrutinib did not inhibit complement activation or complement-mediated lysis. In contrast, ibrutinib strongly inhibited all cell-mediated mechanisms induced by anti-CD20 antibodies rituximab, ofatumumab or obinutuzumab, either in purified systems or whole blood assays. Activation of...

  19. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura

    DEFF Research Database (Denmark)

    Braendstrup, Peter; Bjerrum, Ole W; Nielsen, Ove J;

    2005-01-01

    . Recent studies have shown that rituximab, a chimeric anti-CD20 monoclonal antibody, is useful in the treatment of these patients, with overall response rates of about 50%. Most published reports have included a small number patients including case reports. The present study reports the results of a...... retrospective Danish multicenter study of rituximab in the treatment of adult patients with refractory ITP. Thirty-five patients (median age 52 years, range 17-82 years, 17 males) were included. One patient had immune thrombocytopenia and neutropenia. All patients had received prednisolone (Pred). Next to Pred...

  20. Preparation and quality control of 177Lu-DOTA-anti-CD20 for Radio immunotherapy

    OpenAIRE

    Hassan Yousefnia; Amir Reza Jalilian; Samaneh Zolghadri; Simindokht Shirvani-Arani; Ali Bahrami-Samani; Mohammad Ghannadi-Maragheh

    2010-01-01

    Introduction: The importance of existence and application of radiolabeled anti-CD20 monoclonal antibodies at nonmyeloablative doses in treating B-cell NHL is well recognized throughout the world. In this work, Rituximab was successively labeled with 177Lu-lutetium chloride. Methods: Lu-177 chloride was obtained by thermal neutron flux (4 × 1013 n.cm-2.s-1) of natural Lu2O3 sample with a specific activity of 2.6-3 GBq/mg. The macrocyclic bifunctional chelating agent, N-succinimidyl-1...

  1. Labeling an anti-CD20 monoclonal antibody with 90Y

    International Nuclear Information System (INIS)

    Lymphomas are among the 10 leading causes of death, both in Cuba and in the world, with an increasing incidence in recent years. Follicular lymphoma low-grade (indolent) is one of the most common in the Western world, representing 1/3 of all non-Hodgkin lymphomas (NHL). More than 90% of patients present with disseminated disease at diagnosis and generally have a slow evolution and good response to conventional treatment; but radically changed its forecast to relapse, resistance to therapeutic and histologic transformation can occur. The monoclonal antibody therapy has been a promising therapeutic. In this respect CD20 antigen it has been considered one of the most attractive targets in the therapy of follicular B cell lymphoma This is expressed in more than 90% of cases, while not present in stem cells and lines progenitors. Despite the success of immunotherapy, the relapse rate is still considerable. In order to increase the cytotoxic potential of immunotherapy, marked with beta emitting radionuclides alpha particles or monoclonal antibodies are used today. Despite encouraging results in patients with non-Hodgkin lymphomas refractory to other treatments, the extremely high costs of these commercial radiopharmaceuticals have greatly limited its application, even in the first world. A sustainable alternative is the marking of other anti-CD20 monoclonal antibodies, so researchers from several countries have concentrated their efforts on rituximaby other similar antibodies labeled with therapeutic radionuclides, as a possible cost-effectively to more problem. Today in Cuba it has an electrolytic generator 90Sr-90Y Isotope Center, which ensures the availability of the radionuclide. In addition, the chimeric MAb rituximab is applied as part of the therapy of NHL in its health system and, recently, the Center for Molecular Immunology has obtained a chimeric monoclonal anti-CD20 antibody biosimilar rituximab, which is in phase clinical trial; which opens prospects for the

  2. Comparative studies of antibody anti-CD20 labeled with {sup 188}Re; Estudo comparativo da marcacao do anticorpo anti-CD20 com {sup 188}Re

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Carla Roberta de Barros Rodrigues

    2010-07-01

    Nuclear Medicine is an unique and important modality in oncology and the development of new tumor-targeted radiopharmaceuticals for both diagnosis and therapy is an area of interest for researchers. Rituximab (RTX) is a quimeric monoclonal antibody (mAb) (IgG 1) that specifically binds to CD20 antigen with high affinity and has been successfully used for the treatment of Non-Hodgkin Lymphoma (NHL) of cell B. The CD20 antigen is expressed over more than 90% of cell B NHL. Technetium-99m ({sup 99m}Tc) and rhenium-188 ({sup 188}Re) are an attractive radionuclide pair for clinical use due to their favorable decay properties for diagnosis ({sup 99m}Tc: T{sub 1/2} = 6 h, {gamma} radiation = 140 keV) and therapy ({sup 188}Re: T{sub 1/2} = 17 h, maximum {beta} energy = 2.12 MeV) and to their availability in the form of {sup 99}Mo/{sup 99}mTc and {sup 188}W/{sup 188}Re generators. The radionuclides can be conjugated to mAb using similar chemical procedures. The aim of this work was to study the labeling of anti-CD20 mAb (RTX) with {sup 188}Re using two techniques: the direct labeling method [{sup 188}Re(V)] and the labeling method via the carbonyl nucleus [{sup 188}Re(I)]. Besides the quality control, the radiolabeled mAb was submitted to in vivo, in vitro and ex vivo biological studies. For the direct labeling, RTX was reducing by incubation with 2-mercaptoethanol for generating sulphydryl groups (-SH) and further labeled with {sup 188}Re(V), in a study of several parameters in order to reach an optimized formulation. The labeling via the carbonyl nucleus both {sup 99}mTc and {sup 188}Re were employed through 2 different procedures: (1) labeling of intact RTX with {sup 99}mTc(I) and (2) reduced RTX (RTX{sub red}) labeled with {sup 99}mTc(I)/{sup 188}Re(I). Also a parameter study was performed to obtain an optimized formulation. The quality control method for evaluating the radiochemical purity showed a good labeling yield (93%) for the direct method. The labeling method

  3. Recombinant anti-CD20 antibody fragments for microPET imaging of B-cell lymphoma

    Science.gov (United States)

    Olafsen, Tove; Betting, David; Kenanova, Vania E.; Salazar, Felix B.; Clarke, Pat; Said, Jonathan; Raubitschek, Andrew A.; Timmerman, John M.; Wu, Anna M.

    2010-01-01

    The CD20 cell surface antigen is expressed at high levels by over 90% of B cell non-Hodgkin lymphomas (NHL), and is the target of the anti-CD20 monoclonal antibody rituximab. To provide more sensitive, tumor-specific positron emission tomography (PET) imaging of NHL, we sought to develop PET imaging agents targeting CD20. Methods Two recombinant anti-CD20 rituximab fragments, a minibody (scFv-CH3 dimer, 80 kDa) and a modified scFv-Fc fragment (105 kDa), designed to clear rapidly, were generated. Both fragments were radiolabeled with 124I, and the minibody was additionally radiometal labeled with 64Cu following conjugation to 1,4,7,10-tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid (DOTA). The radioiodinated fragments and the radiometal labeled minibody were evaluated in mice as microPET imaging agents for in vivo imaging of human CD20-expressing lymphomas. Results Rapid and specific localization to CD20-positive tumors was observed with the radioiodinated fragments. However, their tumor uptakes and blood activities differed, resulting in different levels of contrast in the images. The best candidate was the minibody, with superior uptake (2-fold higher than the scFv-Fc) in CD20-positive tumor and low uptake in CD20-negative tumor. Positive tumor to negative tumor ratios were 7.0(±3.1) and 3.9(±0.7) for the minibody and scFv-Fc, respectively at 21 hours. About a 5-fold lower ratio was achieved with the 64Cu-DOTA-minibody at 19 hours due to higher residual background activity in CD20 negative tumor. Conclusion Radioiodinated minibody and scFv-Fc fragment produced excellent, high-contrast images in vivo. These new immunoPET agents may prove useful for the imaging CD20 positive lymphomas in preclinical models and in humans with NHL. PMID:19690034

  4. 188Re-labelled anti-CD20 monoclonal antibody: Labelling and quality control studies

    International Nuclear Information System (INIS)

    Immunotherapy with human chimeric antibody rituximab (Rituxan, IDEC pharmaceuticals) has been a major advance in treatments of patients with CD20-positive B-cell non Hodgkin's lymphoma (NHL). Radioimmunotherapy (RIT) uses the targeting features of monoclonal antibody to deliver radiation from an attached readionuclide and it is an appeling concept that has received widespread attention. Here, we report our experience using rhenium-188 (188Re)- radiolabeled chimeric anti-CD20 antibody (rituximab). A stable antibody-labeling technique had been developed for 188Re. The 188Re-direct labeling of anti-CD20 monoclonal antibody, the methods for quality control: paper chromatography, instant thin layer chromatographysilica gel (ITLC-SG) and HPLC technique, the immunoreactivity and biological recognition of the target antigen assessment of the radiolabeled molecule, in vitro stability and the assessment of in vivo stability through biodistribution studies in normal WISTAR rats are described. For the direct radiolabeling, the reduction of monoclonal antibody (mAb) was performed with 2-mercaptoethanol (2-ME), based on Schwarz's method at a molar ratio 2000:1 (2- ME:mAb). By means of this method some of the disulfide bonds of the antibody are reduced to sulfhydryl groups (we obtained 4-5 groups) and these groups provide sites for the formation of very strong bond between the reduced rhenium and the antibody. The methodology used in this work has been tested in a phase I radioimmunotherapy clinical trial using the humanized mAb hR3 for loco-regional treatment of brain tumours. The labeling efficiency (> 95 %) of this method showed that the final product needs no further purification for clinical purposes (low level formation of colloidal species). In vitro stability studies of the labeled anti-CD20 were performed at room temperature at 4 h, 24 h and 48 h in cysteine, human serum and saline. In the presence of normal human serum, during the first 4h, transchelation of about 15

  5. Ibrutinib interferes with the cell-mediated anti-tumor activities of therapeutic CD20 antibodies: implications for combination therapy

    OpenAIRE

    Roit, Fabio Da; Patrick J Engelberts; Taylor, Ronald P.; Breij, Esther C.W.; Gritti, Giuseppe; Rambaldi, Alessandro; Introna, Martino; Parren, Paul W H I; Beurskens, Frank J; Golay, Josée

    2015-01-01

    The novel Bruton tyrosine kinase inhibitor ibrutinib and phosphatidyl-4-5-biphosphate 3-kinase-δ inhibitor idelalisib are promising drugs for the treatment of chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma, either alone or in combination with anti-CD20 antibodies. We investigated the possible positive or negative impact of these drugs on all known mechanisms of action of both type I and type II anti-CD20 antibodies. Pretreatment with ibrutinib for 1 hour did not increase direct ...

  6. Preparation and quality control of [67Ga]-labeled anti-CD20 using DOTA for biodistribution studies

    OpenAIRE

    A.R. Jalilian; L. Mirsadeghi; R. Hajhosseini; A. Khorami; S. Moradkhani; Y.Yari Kamrani; S. Daneshvari; N. Shadanpour "; A. Rajamand "

    2006-01-01

    Objectives: Anti-CD20 is being used in the therapy of lymphomas in free or radiolabeled form throuout the world. Many radiolabeld anti-CD20 antibodies have been used in the therapy of B-cell lymphomes, like Bexaar and Zevalin. most of new radiolabeld antibodies contain DOTA as conjugating agent. DOTA conjugates can be easily labeld with wide variety of radioisotopes such as 111In, 66,68Ga, 86Y, 64,67Cu etc…In this study a DOTA conjugated Rituximab compound is prepared and biodistribution stud...

  7. Anti-CD20 single chain variable antibody fragment–apolipoprotein A-I chimera containing nanodisks promote targeted bioactive agent delivery to CD20-positive lymphomas

    Science.gov (United States)

    Crosby, Natasha M.; Ghosh, Mistuni; Su, Betty; Beckstead, Jennifer A.; Kamei, Ayako; Simonsen, Jens B.; Luo, Bing; Gordon, Leo I.; Forte, Trudy M.; Ryan, Robert O.

    2015-01-01

    A fusion protein comprising an α-CD20 single chain variable fragment (scFv) antibody, a spacer peptide, and human apolipoprotein (apo) A-I was constructed and expressed in Escherichia coli. The lipid interaction properties intrinsic to apoA-I as well as the antigen recognition properties of the scFv were retained by the chimera. scFv•apoA-I was formulated into nanoscale reconstituted high-density lipoprotein particles (termed nanodisks; ND) and incubated with cultured cells. α-CD20 scFv•apoA-I ND bound to CD20-positive non-Hodgkins lymphoma (NHL) cells (Ramos and Granta) but not to CD20-negative T lymphocytes (i.e., Jurkat). Binding to NHL cells was partially inhibited by pre-incubation with rituximab, a monoclonal antibody directed against CD20. Confocal fluorescence microscopy analysis of Granta cells following incubation with α-CD20 scFv•apoA-I ND formulated with the intrinsically fluorescent hydrophobic polyphenol, curcumin, revealed α-CD20 scFv•apoA-I localizes to the cell surface, while curcumin off-loads and gains entry to the cell. Compared to control incubations, viability of cultured NHL cells was decreased upon incubation with α-CD20 scFv•apoA-I ND harboring curcumin. Thus, formulation of curcumin ND with α-CD20 scFv•apoA-I as the scaffold component confers cell targeting and enhanced bioactive agent delivery, providing a strategy to minimize toxicity associated with chemotherapeutic agents. PMID:25994015

  8. Anti-CD20 single chain variable antibody fragment-apolipoprotein A-I chimera containing nanodisks promote targeted bioactive agent delivery to CD20-positive lymphomas.

    Science.gov (United States)

    Crosby, Natasha M; Ghosh, Mistuni; Su, Betty; Beckstead, Jennifer A; Kamei, Ayako; Simonsen, Jens B; Luo, Bing; Gordon, Leo I; Forte, Trudy M; Ryan, Robert O

    2015-08-01

    A fusion protein comprising an α-CD20 single chain variable fragment (scFv) antibody, a spacer peptide, and human apolipoprotein (apo) A-I was constructed and expressed in Escherichia coli. The lipid interaction properties intrinsic to apoA-I as well as the antigen recognition properties of the scFv were retained by the chimera. scFv•apoA-I was formulated into nanoscale reconstituted high-density lipoprotein particles (termed nanodisks; ND) and incubated with cultured cells. α-CD20 scFv•apoA-I ND bound to CD20-positive non-Hodgkins lymphoma (NHL) cells (Ramos and Granta) but not to CD20-negative T lymphocytes (i.e., Jurkat). Binding to NHL cells was partially inhibited by pre-incubation with rituximab, a monoclonal antibody directed against CD20. Confocal fluorescence microscopy analysis of Granta cells following incubation with α-CD20 scFv•apoA-I ND formulated with the intrinsically fluorescent hydrophobic polyphenol, curcumin, revealed α-CD20 scFv•apoA-I localizes to the cell surface, while curcumin off-loads and gains entry to the cell. Compared to control incubations, viability of cultured NHL cells was decreased upon incubation with α-CD20 scFv•apoA-I ND harboring curcumin. Thus, formulation of curcumin ND with α-CD20 scFv•apoA-I as the scaffold component confers cell targeting and enhanced bioactive agent delivery, providing a strategy to minimize toxicity associated with chemotherapeutic agents. PMID:25994015

  9. Comparative studies of antibody anti-CD20 labeled with 188Re

    International Nuclear Information System (INIS)

    Nuclear Medicine is an unique and important modality in oncology and the development of new tumor-targeted radiopharmaceuticals for both diagnosis and therapy is an area of interest for researchers. Rituximab (RTX) is a quimeric monoclonal antibody (mAb) (IgG 1) that specifically binds to CD20 antigen with high affinity and has been successfully used for the treatment of Non-Hodgkin Lymphoma (NHL) of cell B. The CD20 antigen is expressed over more than 90% of cell B NHL. Technetium-99m (99mTc) and rhenium-188 (188Re) are an attractive radionuclide pair for clinical use due to their favorable decay properties for diagnosis (99mTc: T1/2 = 6 h, γ radiation = 140 keV) and therapy (188Re: T1/2 = 17 h, maximum β energy = 2.12 MeV) and to their availability in the form of 99Mo/99mTc and 188W/188Re generators. The radionuclides can be conjugated to mAb using similar chemical procedures. The aim of this work was to study the labeling of anti-CD20 mAb (RTX) with 188Re using two techniques: the direct labeling method [188Re(V)] and the labeling method via the carbonyl nucleus [188Re(I)]. Besides the quality control, the radiolabeled mAb was submitted to in vivo, in vitro and ex vivo biological studies. For the direct labeling, RTX was reducing by incubation with 2-mercaptoethanol for generating sulphydryl groups (-SH) and further labeled with 188Re(V), in a study of several parameters in order to reach an optimized formulation. The labeling via the carbonyl nucleus both 99mTc and 188Re were employed through 2 different procedures: (1) labeling of intact RTX with 99mTc(I) and (2) reduced RTX (RTXred) labeled with 99mTc(I)/188Re(I). Also a parameter study was performed to obtain an optimized formulation. The quality control method for evaluating the radiochemical purity showed a good labeling yield (93%) for the direct method. The labeling method via carbonyl group, the results showed that the - SH groups of RTXred are a possible way of labeling. The formulation of 99m

  10. Expression and biological characterization of an anti-CD20 biosimilar candidate antibody: A case study

    OpenAIRE

    Dorvignit, Denise; Palacios, Julio L.; Merino, Maylin; Hernández, Tays; Sosa, Katya; Casacó, Angel; López-Requena, Alejandro; Mateo de Acosta, Cristina

    2012-01-01

    The CD20 molecule is a non-glycosylated protein expressed mainly on the surface of B lymphocytes. In some pathogenic B cells, it shows an increased expression, thus becoming an attractive target for diagnosis and therapy. Rituximab is a chimeric antibody that specifically recognizes the human CD20 molecule. This antibody is indicated for the treatment of non-Hodgkin lymphomas and autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. In this work, we describe the ...

  11. Multivalent system for therapy of non-Hod king lymphomas based on Anti-CD20 conjugated to gold nanoparticles; Sistema multivalente para terapia de linfomas no-Hodking basado en Anti-CD20 conjugado a nanoparticulas de oro

    Energy Technology Data Exchange (ETDEWEB)

    Miranda O, R. M.

    2014-07-01

    In recent publications has been reported that gold nanoparticles have an effect in reducing the expression of the oncogene Bcl -2 and have a high biocompatibility , this is the importance for using gold nanoparticles for this work. The antibody CD20 is an antibody that specifically binds to that over expressed CD20 antigen on the cell membrane of B lymphoma cell non- Hodgkin (cell line Raji) behold the importance of combining this bio molecule to gold nanoparticles since they have a high specificity with CD20 positive cells , also to carry out the antigen- antibody immunological reactions triggered mediating cell lysis, possibly by cytotoxicity and apoptosis. Therefore, this system must have characteristics of both components to eliminate B cell non- Hodgkin lymphoma.In this work it was studied a multivalent system composed of gold nanoparticles and anti-CD20 antibody, the term multi valency refers to the number of biomolecules attached to the surface of the gold nanoparticle. The synthesis and characterization of the gold nanoparticles and the multivalent system was performed and the effect of the multivalent system on the expression of oncogene Bcl-2 (group of proteins associated with the apoptotic pathway) was evaluated. Characterization of raw materials and the multivalent system was performed using spectroscopic and microscopic techniques, this to verify structural changes in raw materials and thus confirm the formation of CD20 binding to the surface of the nanoparticle gold by the bond between gold and sulfur in the cysteines of CD20. Taking advantage that the metal nanoparticles have the optical property of surface plasmon resonance, the absorption of gold nanoparticles was measured on the UV-Vis as it is affected by the surface molecules bind to it, showing a bathochromic displacement effected. The hydrodynamic diameter of the gold nanoparticles was measured to verify that the antibody is bound to the surface; this evidence was complemented by micrographs

  12. Sequential Camouflage of the arachno-6,9-C2B8H14 Cage by Substituents.

    Science.gov (United States)

    Bakardjiev, Mario; Štíbr, Bohumil; Holub, Josef; Tok, Oleg L; Švec, Petr; Růžičková, Zdeňka; Růžička, Aleš

    2016-07-18

    Sequential methylation of arachno-6,9-C2B8H14 (1) led to a series of methyl derivatives and finally to the camouflaging of all boron positions by mixed persubstitution. Thus, deprotonation of 1 produced the [arachno-6,9-C2B8H13] anion (1(-)), the methylation of which with MeI in tetrahydrofuran proceeded on the open-face boron vertexes with the formation of 5-Me-arachno-6,9-C2B8H13 (2; yield 28%) and 5,8-Me2-arachno-6,9-C2B8H12 (3; yield 36%). Observed in this reaction was also a side formation of 2-Me-closo-1,6-C2B8H9 (4; yield 6%).The electrophilic AlCl3-catalyzed CH3(+) attack of the neutral 1 in neat MeI at ambient temperature afforded 1,3-Me2-arachno-6,9-C2B8H12 (5), while a 76-h heating at 120 °C generated a mixture of the di- and triiodo derivatives 1,2,3,4,8,10-Me6-5,7-I2-arachno-6,9-C2B8H6 (6) and 1,2,3,4,7-Me5-5,7,10-I3-arachno-6,9-C2B8H6 (7). On the other hand, a HOTf-catalyzed reaction between 1 and MeOTf at reflux resulted in the isolation of 2-TfO-1,3.4,5,7,8,10-Me7-arachno-6,9-C2B8H6 (8; Tf = CF3SO2; yield 65%). The compounds were characterized by multinuclear ((11)B, (1)H, (13)C, and (19)F) NMR spectroscopy, mass spectrometry, and elemental analysis, and the structures of compounds 1, 1(-), 5, and 6 were established by X-ray diffraction analysis. PMID:27351461

  13. [One amino acid mutation in an anti-CD20 antibody fragment that affects the yield bacterial secretion and the affinity].

    Science.gov (United States)

    Liu, Yin-Xing; Xiong, Dong-Sheng; Fan, Dong-Mei; Shao, Xiao-Feng; Xu, Yuan-Fu; Zhu, Zhen-Ping; Yang, Chun-Zheng

    2003-05-01

    Monoclonal antibodies (mAb) directed against CD20, either unmodified or in radiolabeled forms, have been successfully exploited in clinic as effective therapeutic agents in the management of non-Hodgkin's B-cell lymphoma. The antibody fragment is a potential agent in image and therapy of tumor. To further improve the soluble expression of anti-CD20 antibody Fab' fragment, PCR was used to mutate the anti-CD20 VL and VH genes and its biological activity was identified. The expression vector of chimeric antibody Fab' was constructed and expressed in E. coli. The data of mutant clone DNA sequence showed that the amino acid of light chain gene of the parent anti-CD20 antibody (H47) was successful mutated as Ser (GAG)-Asn (CAG). The soluble expression of mutated anti-CD20 Fab' (CD20-7) was 3.8 mg/g dry cell weight, while the parent (CD20-2) was 1.3 mg/g dry cell weight. The affinity constant Ka of CD20-7 was 2.2 x 10(9) L/mol. The primary results of competitive assays by FACS showed that CD20-7 could partially block the sites through which parent antibody (HI47) bind to Raji cells. There was difference in the Raji cells (CD20+)-binding activity between the mutant CD20-7 and parent CD20-2. The site mutation of anti-CD20 Fab' gene make it possible that the anti-CD20 antibody fragment was succeeded to obtain higher expression. In this thesis, we succeeded in completing mutation and expression of anti-CD20 Fab' genes, distinguishing its biological activity, and obtaining its highly expression. These period results will lay a foundation for development of other kind of anti-CD20 engineering antibody (for instance: Fab' Diabody and miniantibody), and make it possible for anti-CD20 antibody to be applied to tumor therapy in civil in the future. PMID:15969005

  14. Development of 177Lu-DOTA-anti-CD20 for radioimmunotherapy

    International Nuclear Information System (INIS)

    Rituximab was successively labeled with 177Lu-lutetium chloride. 177Lu chloride was obtained by thermal neutron flux (4 x 1013 n cm-2 s-1) of natural Lu2O3 sample with a specific activity of 2.6-3 GBq/mg. The macrocyclic bifunctional chelating agent, N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) was prepared at 25 deg C using DOTA, N-hydroxy succinimide (NHS) in CH2Cl2. DOTA-rituximab was obtained by the addition of 1 mL of a rituximab pharmaceutical solution (5 mg/mL, in phosphate buffer, pH 7.8) to a glass tube pre-coated with DOTA-NHS (0.01-0.1 mg) at 25 deg C with continuous mild stirring for 15 h. Radiolabeling was performed at 37 deg C in 24 h. Radio-thin layer chromatography showed an overall radiochemical purity of >98% at optimized conditions (specific activity = 444 MBq/mg, labeling efficacy; 82%). The final isotonic 177Lu-DOTA-rituximab complex was checked by gel electrophoresis for structure integrity control. Radio-TLC was performed to ensure that only one species was present after filtration through a 0.22 μm filter. Preliminary biodistribution studies in normal rats were carried out to determine complex distribution of the radioimmunoconjugate up to 168 h. The biodistribution data were in accordance with other antiCD20 radioimmunoconjugates already reported. (author)

  15. Multivalent system for therapy of non-Hod king lymphomas based on Anti-CD20 conjugated to gold nanoparticles

    International Nuclear Information System (INIS)

    In recent publications has been reported that gold nanoparticles have an effect in reducing the expression of the oncogene Bcl -2 and have a high biocompatibility , this is the importance for using gold nanoparticles for this work. The antibody CD20 is an antibody that specifically binds to that over expressed CD20 antigen on the cell membrane of B lymphoma cell non- Hodgkin (cell line Raji) behold the importance of combining this bio molecule to gold nanoparticles since they have a high specificity with CD20 positive cells , also to carry out the antigen- antibody immunological reactions triggered mediating cell lysis, possibly by cytotoxicity and apoptosis. Therefore, this system must have characteristics of both components to eliminate B cell non- Hodgkin lymphoma.In this work it was studied a multivalent system composed of gold nanoparticles and anti-CD20 antibody, the term multi valency refers to the number of biomolecules attached to the surface of the gold nanoparticle. The synthesis and characterization of the gold nanoparticles and the multivalent system was performed and the effect of the multivalent system on the expression of oncogene Bcl-2 (group of proteins associated with the apoptotic pathway) was evaluated. Characterization of raw materials and the multivalent system was performed using spectroscopic and microscopic techniques, this to verify structural changes in raw materials and thus confirm the formation of CD20 binding to the surface of the nanoparticle gold by the bond between gold and sulfur in the cysteines of CD20. Taking advantage that the metal nanoparticles have the optical property of surface plasmon resonance, the absorption of gold nanoparticles was measured on the UV-Vis as it is affected by the surface molecules bind to it, showing a bathochromic displacement effected. The hydrodynamic diameter of the gold nanoparticles was measured to verify that the antibody is bound to the surface; this evidence was complemented by micrographs

  16. Preparation of the radiopharmaceutical {sup 131}I-Anti-CD20 for the treatment of lymphomas; Preparacion del radiofarmaco {sup 131}I-Anti-CD20 para el tratamiento de linfomas

    Energy Technology Data Exchange (ETDEWEB)

    Pantoja H, I.E

    2004-07-01

    At the present time they are considered to the lymphomas like a problem of first magnitude since has happened it is necessary to be the fifth cancer cause in the world. Different treatments focused to the lymphoma like the chemotherapy and the radiotherapy, have been employees to counteract the No-Hodgkin lymphoma, without these they don't exclude the healthy tissue of the toxicity. It is for it that is taking a new direction with the employment of the directed radioimmunotherapy since this it allows to kill wicked cells selectively with radiation dose joined to the apoptosis and cytotoxicity induced by the own one bio molecule. The radioimmunotherapy with radiolabelled antibodies directed to the surface antigen CD20 represents a new modality for the treatment of No-Hodgkin lymphoma and potentially other illnesses. In this work the parameters of optimization are presented for the preparation, control of quality and evaluation of the stability in vitro and in vivo of the monoclonal antibody anti-CD20 labelled with {sup 131} I for the treatment of No-Hodgkin lymphoma. The anti-CD20 labelled by the chloramine-T method with high radiochemical purity (>98%), it is stable in solution for but of a half life of the radionuclide (8.04 days) The {sup 131} I-anti-CD20 doesn't present dehalogenation in vitro (human serum) during 24 h of incubation at 37 C. According to the tests carried out to establish the immunoreactivity, a percentage of union to cells was obtained (B lymphocytes) bigger to 30%. The biodistribution in mice balb/c one hour after their administration, it shows that there is not high reception in mucous neither kidneys, what indicates that the complex is stable in vivo. In conclusion, the radiopharmaceutical {sup 131} I-anti-CD20 was obtained in sterile injectable solution and free of pyrogens with a radiochemical purity bigger to 98% and a specific activity of 296 MBq. The radiolabelled molecule maintains its biological recognition for the receiving

  17. Binding Activity Difference of Anti-CD20 scFv-Fc Fusion Protein Derived from Variable Domain Exchange

    Institute of Scientific and Technical Information of China (English)

    Shusheng Geng; Beifen Shen; Jiannan Feng; Yan Li; Yingxun Sun; Xin Gu; Ying Huang; Yugang Wang; Xianjiang Kang; Hong Chang

    2006-01-01

    Two novel engineered antibody fragments binding to antigen CD20 were generated by fusing a murine IgM-type anti-CD20 single-chain Fv fragment (scFv) to the human IgG1 CH2 (I.e., Cγ2) and CH3 (I.e., Cγ3) domains with the human IgG1 hinge (I.e. Hγ). Given the relationship between structure and function of protein, the 3-D structures of the two engineered antibody fragments were modeled using computer-aided homology modeling method.Furthermore, the relationship between 3-D conformation and their binding activity was evaluated theoretically.Due to the change of active pocket formed by CDRs, the HL23 (VH-Linker-VL-Hγ-Cγ2-Cγ3) remained its activity because of its preserved conformation, while the binding activity of the LH23 (VL-Linker-VH-Hγ-Cγ2-Cγ3) was impaired severely. Experimental studies by flow cytometry and fluorescence microscopy showed that HL23 possessed significantly superior binding activity to CD20-expressing target cells than LH23. That is to say, the order of variable regions could influence the binding activity of the fusion protein to CD20+ cell lines, which was in accordance with the theoretical results. The study highlights the potential relationship between the antibody binding activity and their 3-D conformation, which appears to be worthwhile in providing direction for future antibody design of recombinant antibody.

  18. Specific energy from Auger and conversion electrons of 131I, 188Re-anti-CD20 to a lymphocyte's nucleus

    Science.gov (United States)

    Torres-García, E.; Carrillo-Cazares, T. A.

    2011-01-01

    The typical radionuclides used to label anti-CD20 in the treatment of non-Hodgkin's lymphoma are 90Y, 131I, and 188Re, with the emission of beta particles, Auger electrons, and conversion electrons for the latter two. The aim of the present work was to calculate the contribution of high linear energy transfer radiation as Auger electrons (AE) and conversion electrons (CE) of 131I and 188Re-anti-CD20 to mean specific energy into the cell nucleus by Monte Carlo simulation (MCS), so as to infer therapeutic effectiveness on a dosimetric basis. MCS was used to quantify the frequency-mean specific energy into the cell nucleus, where the cell was modeled by two concentric spheres, considering two cell models. The results showed that 10% and 33% of the mean-specific energies (z¯) per disintegration imparted to the cell nucleus for both geometries are due to AE and CE; on the other hand, if the hit of AE and CE occurs, the contribution to (z¯) is about 64% and 86% for 131I and 188Re, respectively. According to the amount of specific energy from AE and CE into the cell nucleus by positive event, they can cause catastrophic effects in the nuclear DNA in the treatment of non-Hodgkin's lymphoma with 131I, 188Re-anti-CD20.

  19. I-131 rituximab (chimeric anti Cd 20 mab) radioimmunotherapy of non-Hodgkins lymphoma

    International Nuclear Information System (INIS)

    Full text: Commercially available anti-CD 20 monoclonal antibody, rituximab (MabThera) may be efficiently radioiodinated with 131I using standard Chloramine-T methodology in a hospital radiopharmacy, under appropriate regulatory authority approvals. Multicentre clinical trials of 131I-rituximab radioimmunotherapy have been performed in patients with relapsed or refractory low grade non-Hodgkins lymphoma with therapeutically effective administered activities being determined on the basis of individualised prospective patient dosimetry. A non-myeloablative regimen of 131I-radioimmunotherapy predicated upon a maximum prescribed dose of 0.75 Gy to whole body has been used to minimise myelotoxicity in patients undergoing radioimmunotherapy, even when they have been heavily pre-treated with chemotherapy and/or there is tumour infiltration of bone marrow greater than 25%. Provided that baseline leucocytes exceeded an absolute neutrophil count of 1.5 x 109/L and platelets > 100 x 109 /L, the incidence of grade IV haematological toxicity was 16% for neutrophils and 4 % for platelets which was self-limited. The red marrow radiation absorbed dose in selected patients receiving 131I activities estimated to deliver 0.75 Gy to whole body was calculated to be less than 2 Gy using Monte Carlo methodology on post therapy CT/SPECT imaging. Predictive dosimetry was performed by serial whole body imaging following IV administration of a standard 200 MBq 131I-rituximab tracer and determination of individual pharmacokinetics of the radiolabelled antibody in each patient. A standard dose of 375 mg/m2 unlabelled rituximab (MabThera) was administered IV immediately prior to the tracer and therapy doses of 131I-rituximab to minimise nonspecific uptake of the radiolabelled antibody and to optimise the tumour to background activity. The administration of a standard course of 4 cycles of cold rituximab (MabThera) in association with the prescribed maximum activity of 131I-rituximab constitutes

  20. Monte Carlo microdosimetry of {sup 188}Re- and {sup 131}I-labelled anti-CD20

    Energy Technology Data Exchange (ETDEWEB)

    Torres-GarcIa, E [Coordinacion de Posgrado, Facultad de Medicina, Universidad Autonoma del Estado de Mexico, Paseo Tollocan S/N, Toluca, Estado de Mexico 50180 (Mexico); Garnica-Garza, H M [Coordinacion de Posgrado, Facultad de Medicina, Universidad Autonoma del Estado de Mexico, Paseo Tollocan S/N, Toluca, Estado de Mexico 50180 (Mexico); Ferro-Flores, G [Instituto Nacional de Investigaciones Nucleares, Carretera Mexico-Toluca, Ocoyoacac, Estado de Mexico 52750 (Mexico)

    2006-10-07

    The radiolabelled monoclonal antibody anti-CD20 has the property of binding to the CD20 antigen expressed on the cell surface of B-lymphocytes, thus making it a useful tool in the treatment of non-Hodgkin's lymphoma. In this work, the event-by-event Monte Carlo code NOREC is used to calculate the single-event distribution function f{sub 1}(z) in the cell nucleus using the beta spectra of the {sup 188}Re and {sup 131}I radionuclides. The simulated geometry consists of two concentric spheres representing the nucleus and the cell surface embedded in a semi-infinite water medium. An isotropic point source was placed on the cell surface to simulate the binding of the anti-CD20 labelled with either {sup 188}Re or {sup 131}I. The simulations were carried out for two combinations of cell surface and nucleus radii. A method was devised that allows one to calculate the contribution of betas of energy greater than 1 MeV, which cannot be simulated by the NOREC code, to the single-event distribution function. It is shown that disregarding this contribution leads to an overestimation of the frequency-mean specific energy of the order of 9-12%. In general, the antibody radiolabelled with {sup 131}I produces single-event distribution functions that yield higher frequency-mean specific energies. (note)

  1. Construction and characterization of an anti-CD20 mAb nanocomb with exceptionally excellent lymphoma-suppressing activity

    Directory of Open Access Journals (Sweden)

    Li H

    2015-07-01

    Full Text Available Hua-Fei Li,1–3,* Cong Wu,4,* Ting Chen,5,* Ge Zhang,1 He Zhao,1 Chang-Hong Ke,1 Zheng Xu21International Joint Cancer Institute, Translation Medicine Institute, 2Planning Division, Scientific Research Department, 3Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, 4Department of Laboratory Diagnosis, Changhai Hospital, 5Department of Cardiology, Changhai Hospital, the Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: The CD20-directed monoclonal antibody rituximab (RTX established a new era in the treatment of non-Hodgkin lymphoma (NHL; however, suboptimal response and/or resistance to RTX still limit its clinical merits. Although four effector mechanisms are validated to participate in CD20-based immunotherapy, including complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, caspase-dependent apoptosis, and lysosome-mediated programmed cell death (PCD, they could hardly be synchronously activated by any anti-CD20 mAb or mAb derivative until now. Herein, a novel mAb nanocomb (polyethylenimine polymer–RTX–tositumomab [PPRT nanocomb] was firstly constructed through mass arming two different anti-CD20 mAbs (RTX and tositumomab to one polymer by nanotechnology. Comparing with free mAbs, PPRT nanocomb possesses a comparable binding ability and reduced “off-rate” to surface CD20 of NHL cells. When treated by PPRT nanocomb, the caspase-dependent apoptosis was remarkably enhanced except for concurrently eliciting complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and lysosome-mediated PCD. Besides, “cross-cell link”-assisted homotypic adhesion by PPRT nanocomb further enhanced the susceptibility to PCD of lymphoma cells. Pharmacokinetic assays revealed that PPRT nanocomb experienced a relatively reduced clearance from peripheral blood compared with free antibodies. With

  2. Potential therapeutic strategy for non-Hodgkin lymphoma by anti-CD20scFvFc/CD28/CD3zeta gene tranfected T cells

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    Zheng Yihu

    2010-09-01

    Full Text Available Abstract Background Anti-CD20 monoclonal antibody treatment has not only increased survival and cure rates in many non-Hodgkin lymphomas, but also has prompted an explosion in the development of novel antibodies and biologically active substances with specific cellular targets in the field of malignancies treatment. Since the robust immune responses are elicited by the gene-modified T cells, gene based T cell therapy may also provide a powerful tool for cancer immunotherapy. Methods In this study, we developed a vector construction encoding a chimeric T cell receptor that recognizes the CD20 antigen and delivers co-stimulatory signals to achieve T cell activation. One non-Hodgkin lymphoma cell line Raji cells co-cultured with peripheral blood-derived T cells were stably transfected with anti-CD20scFvFc/CD28/CD3zeta gene or anti-CD20scFvFc gene. T cells expressing anti-CD20scFvFc/CD28/CD3zeta or anti-CD20scFvFc gene co-cultured with CD20 positive Raji cells for different times. Cell lysis assay was carried by [3H]TdR release assay. The expressions of Fas, Bcl-2 and Caspase-3 of Raji cells were detected by flow cytometric. The secretion of IFN-gamma and IL-2 in co-culture medium was tested by ELISA assay. Activity of AP-1 was analyzed by EMSA. Results Following efficient transduction of peripheral blood-derived T cells with anti-CD20scFvFc/CD28/CD3zeta gene, an obvious cell lysis of Raji cells was observed in co-culture. T cells transduced anti-CD20scFvFc/CD28/CD3zeta gene had superior secretion of IFN-gamma and IL-2 compared to T cells transduced anti-CD20scFvFc gene. Also it led to a much stronger Fas-induced apoptosis signaling transduction in target cancer cells. Conclusion So adoptively T cells transduced anti-CD20scFvFc/CD28/CD3zeta gene mediates enhanced anti-tumor activities against CD20 positive tumor cells, suggesting a potential of gene-based immunotherapy for non-Hodgkin lymphoma.

  3. Targeted alpha-therapy using [Bi-213]anti-CD20 as novel treatment option for radio- and chemoresistant non-Hodgkin lymphoma cells

    Science.gov (United States)

    Roscher, Mareike; Hormann, Inis; Leib, Oliver; Marx, Sebastian; Moreno, Josue; Miltner, Erich; Friesen, Claudia

    2013-01-01

    Radioimmunotherapy (RIT) is an emerging treatment option for non-Hodgkin lymphoma (NHL) producing higher overall response and complete remission rates compared with unlabelled antibodies. However, the majority of patients treated with conventional or myeloablative doses of radiolabelled antibodies relapse. The development of RIT with alpha-emitters is attractive for a variety of cancers because of the high linear energy transfer (LET) and short path length of alpha-radiation in human tissue, allowing higher tumour cell kill and lower toxicity to healthy tissues. In this study, we investigated the molecular effects of the alpha-emitter Bi-213 labelled to anti-CD20 antibodies ([Bi-213]anti-CD20) on cell cycle and cell death in sensitive and radio-/chemoresistant NHL cells. [Bi-213]anti-CD20 induced apoptosis, activated caspase-3, caspase-2 and caspase-9 and cleaved PARP specifically in CD20-expressing sensitive as well as in chemoresistant, beta-radiation resistant and gamma-radiation resistant NHL cells. CD20 negative cells were not affected by [Bi-213]anti-CD20 and unspecific antibodies labelled with Bi-213 could not kill NHL cells. Breaking radio-/chemoresistance in NHL cells using [Bi-213]anti-CD20 depends on caspase activation as demonstrated by complete inhibition of [Bi-213]anti-CD20-induced apoptosis with zVAD.fmk, a specific inhibitor of caspases activation. This suggests that deficient activation of caspases was reversed in radioresistant NHL cells using [Bi-213]anti-CD20. Activation of mitochondria, resulting in caspase-9 activation was restored and downregulation of Bcl-xL and XIAP, death-inhibiting proteins, was found after [Bi-213]anti-CD20 treatment in radio-/chemosensitive and radio-/chemoresistant NHL cells. [Bi-213]anti-CD20 seems to be a promising radioimmunoconjugate to improve therapeutic success by breaking radio- and chemoresistance selectively in CD20-expressing NHL cells via re-activating apoptotic pathways through reversing deficient

  4. Targeted tumor imaging of anti-CD20-polymeric nanoparticles developed for the diagnosis of B-cell malignancies

    Directory of Open Access Journals (Sweden)

    Capolla S

    2015-06-01

    Full Text Available Sara Capolla,1 Chiara Garrovo,2 Sonia Zorzet,1 Andrea Lorenzon,3 Enrico Rampazzo,4 Ruben Spretz,5 Gabriele Pozzato,6 Luis Núñez,7 Claudio Tripodo,8 Paolo Macor,1,9 Stefania Biffi2 1Department of Life Sciences, University of Trieste, 2Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”, Trieste, 3Animal Care Unit, Cluster in Biomedicine (CBM scrl, Trieste, Italy; 4Department of Chemistry “G. Ciamician”, University of Bologna, Bologna, Italy; 5LNK Chemsolutions LLC, Lincoln, NE, USA; 6Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy; 7Bio-Target, Inc., University of Chicago, Chicago, IL, USA; 8Department of Human Pathology, University of Palermo, Palermo, Italy; 9Callerio Foundation Onlus, Institutes of Biological Researches, Trieste, Italy Abstract: The expectations of nanoparticle (NP-based targeted drug delivery systems in cancer, when compared with convectional therapeutic methods, are greater efficacy and reduced drug side effects due to specific cellular-level interactions. However, there are conflicting literature reports on enhanced tumor accumulation of targeted NPs, which is essential for translating their applications as improved drug-delivery systems and contrast agents in cancer imaging. In this study, we characterized biodegradable NPs conjugated with an anti-CD20 antibody for in vivo imaging and drug delivery onto tumor cells. NPs’ binding specificity mediated by anti-CD20 antibody was evaluated on MEC1 cells and chronic lymphocytic leukemia patients’ cells. The whole-body distribution of untargeted NPs and anti-CD20 NPs were compared by time-domain optical imaging in a localized human/mouse model of B-cell malignancy. These studies provided evidence that NPs’ functionalization by an anti-CD20 antibody improves tumor pharmacokinetic profiles in vivo after systemic administration and increases in vivo imaging of tumor mass compared to non-targeted NPs. Together

  5. In vitro characterization of 177Lu-radiolabelled chimeric anti-CD20 monoclonal antibody and a preliminary dosimetry study

    International Nuclear Information System (INIS)

    131I- and 90Y-labelled anti-CD20 antibodies have been shown to be effective in the treatment of low-grade, B-cell non-Hodgkin's lymphoma (NHL). However, the most appropriate radionuclide in terms of high efficiency and low toxicity has not yet been established. In this study we evaluated an immunoconjugate formed by the anti-CD20 antibody rituximab and the chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). DOTA-rituximab was prepared as a kit formulation and can be labelled in a short time (177Lu or 90Y. Immunoconjugates with different numbers of DOTA molecules per rituximab were prepared using p-SCN-Bz-DOTA. In vitro immunoreactivity and stability were tested and preliminary dosimetric results were acquired in two patients. The immunological binding properties of DOTA-rituximab to the CD20 antigen were found to be retained after conjugation with up to four chelators. The labelled product was stable against a 105 times excess of diethylenetriaminepentaacetic acid (DTPA, 37 C, 7 days). Two patients with relapsed NHL were treated with 740 MBq/m2 body surface 177Lu-DOTA-rituximab. Scintigraphic images showed specific uptake at tumour sites and acceptable dosimetric results. The mean whole-body dose was found to be 314 mGy. The administration of 177Lu-DOTA-rituximab was tolerated well. Our results show that DOTA-rituximab (4:1) can be labelled with 177Lu with sufficient stability while the immunoconjugate retains its immunoreactivity. 177Lu-DOTA-rituximab is an interesting, well-tolerated radiolabelled antibody with clinical activity in a low dose range, and provides an approach to the efficient treatment with few side effects for patients with relapsed NHL. (orig.)

  6. Transient B-cell depletion with anti-CD20 in combination with proinsulin DNA vaccine or oral insulin: immunologic effects and efficacy in NOD mice.

    Directory of Open Access Journals (Sweden)

    Ghanashyam Sarikonda

    Full Text Available A recent type 1 diabetes (T1D clinical trial of rituximab (a B cell-depleting anti-CD20 antibody achieved some therapeutic benefit in preserving C-peptide for a period of approximately nine months in patients with recently diagnosed diabetes. Our previous data in the NOD mouse demonstrated that co-administration of antigen (insulin with anti-CD3 antibody (a T cell-directed immunomodulator offers better protection than either entity alone, indicating that novel combination therapies that include a T1D-related autoantigen are possible. To accelerate the identification and development of novel combination therapies that can be advanced into the clinic, we have evaluated the combination of a mouse anti-CD20 antibody with either oral insulin or a proinsulin-expressing DNA vaccine. Anti-CD20 alone, given once or on 4 consecutive days, produced transient B cell depletion but did not prevent or reverse T1D in the NOD mouse. Oral insulin alone (twice weekly for 6 weeks was also ineffective, while proinsulin DNA (weekly for up to 12 weeks showed a trend toward modest efficacy. Combination of anti-CD20 with oral insulin was ineffective in reversing diabetes in NOD mice whose glycemia was controlled with SC insulin pellets; these experiments were performed in three independent labs. Combination of anti-CD20 with proinsulin DNA was also ineffective in diabetes reversal, but did show modest efficacy in diabetes prevention (p = 0.04. In the prevention studies, anti-CD20 plus proinsulin resulted in modest increases in Tregs in pancreatic lymph nodes and elevated levels of proinsulin-specific CD4+ T-cells that produced IL-4. Thus, combination therapy with anti-CD20 and either oral insulin or proinsulin does not protect hyperglycemic NOD mice, but the combination with proinsulin offers limited efficacy in T1D prevention, potentially by augmentation of proinsulin-specific IL-4 production.

  7. Dosimetric evaluation of anti-CD20 labelled with 188Re

    International Nuclear Information System (INIS)

    Radioimmunotherapy has the potential to deliver lethal radiation energy directly to malignant cells via targeting of radioisotope-conjugated monoclonal antibodies (MAbs) to specific antigens. B-cell lymphoma is a particularly good candidate for radioimmunotherapy because the disease is inherently radiosensitive, malignant cells in the blood, bone marrow, spleen and lymphonodes are accessible, and MAbs have been developed to B-cell surface antigens that do not shed or modulate. Rituximab (RTX), the human IgG1-type chimeric form of the parent murine antibody ibritumomab, is specifically targeted against CD20, a surface antigen expressed by pre-B and mature human B lymphocytes. The use of rhenium-188 from a 188W/188Re generator system represents an attractive alternative radionuclide for therapy. 188Re is produced from beta decay of the 188W parent. In addition to the emission of high-energy electrons (Eβ= 2118 keV), 188Re also decays with emission of a gamma photon with an energy of 155 keV in 15% abundance. Besides the therapeutic usefulness of 188Re, the emission of gamma photon is an added advantage since the biodistribution of 188Re-labeled antibodies can be evaluated in vivo with a gamma camera. Also, rhenium has chemical properties similar to technetium. Thus, both can be conjugated to antibodies using similar chemistry methods. The objective of this work is to prove the usefulness of this radiopharmaceutical based on dosimetric studies, that are also required by the Brazilian Regulatory Agency (ANVISA). (author)

  8. Progress in anti-CD20 monoclonal antibodies and their clinical application%抗CD20单抗的研究进展及其临床应用

    Institute of Scientific and Technical Information of China (English)

    梁碧华; 樊翌明; 朱慧兰

    2011-01-01

    Anti-CD20 monoclonal antibodies have been applied to the treatment of many autoimmune diseases and severe urticaria with favourable outcomes. Current researches about anti-CD20 monoclonal antibodies are focused on their application in refractory urticaria such as autoimmune urticaria and urticarial vasculitis. Their mechanism of action has not been defined. B cell depletion mechanism is considered to be associated with complement-dependent cytotoxicity, antibody dependent cellular cytotoxicity, direct induction of apoptosis, etc. This paper outlines the progress in researches on anti-CD20 monoclonal antibodies and their application in autoimmune diseases and urticaria, in order to provide evidence for their use in urticaria, and to predict their perspectives in the treatment of refractory urticaria.%抗CD20单克隆抗体目前已用于治疗较多的自身免疫性疾病,并有研究将其用于严重荨麻疹的治疗,且取得良好疗效.但相关的研究主要局限在自身免疫性荨麻疹或荨麻疹性血管炎等难治性荨麻疹中的应用,其作用机制尚未明确.B细胞清除机制认为与补体依赖性细胞毒性反应、抗体依赖细胞介导的细胞毒作用及直接诱导B淋巴细胞凋亡等有关.概述抗CD20单克隆抗体目前的研究进展及其在自身免疫性疾病和荨麻疹中的临床应用,旨在进一步揭示其可用于荨麻疹治疗的证据,从而更好地了解其在难治性荨麻疹中应用的前景.

  9. Efficient inhibition of B-cell lymphoma xenografts with a novel recombinant fusion protein: anti-CD20Fab-LDM.

    Science.gov (United States)

    Xin, C; Ye, S; Ming, Y; Shenghua, Z; Qingfang, M; Hongxing, G; Xu, S; Yuanfu, X; Yuan, Z; Dongmei, F; Juanni, L; Yingdai, G; Lianfang, J; Rongguang, S; Zhenping, Z; Jianxiang, W; Tao, C; Chunzheng, Y; Dongsheng, X; Yongsu, Z

    2010-10-01

    Lidamycin (LDM) is a new member of enediyne antitumor antibiotics family that can be separated and reconstituted. It consists of a labile active enediyne chromophore (AE) and a noncovalently bound apoprotein (LDP). LDM is now in phase II clinical trials. In this study, we described the antitumor features of a fusion protein of LDM, anti-CD20Fab-LDM, targeted to CD20 expressed by B-lymphoid malignancies. Especially, LDM was prepared by a novel two-step method including DNA recombination and molecular reconstitution. Anti-CD20Fab-LDM exerted potent cytotoxicity against CD20+ B-cell lymphoma cell lines in vitro (IC50: 10-30 pM) and in the Raji xenograft model. Two Raji xenografts were allowed to grow to an initial mass of 80 and 500 mm³, respectively, and then anti-CD20Fab-LDM was administered intravenously with the highest dose of 4 nmol kg⁻¹ . The inhibition rates of tumor growth were 90.1 and 85%, which were saliently superior to those of nontargeted LDM. It is noteworthy that anti-CD20Fab-LDM can inhibit the growth of patient-derived cells, including rituximab-resistant patient-derived cells. Thus, CD20-targeted delivery of LDM is a specific and potent therapeutic strategy for B-lymphoid malignancies. In addition, the two-step approach could serve as a new technology platform for making a series of highly potent engineered antibody-based drugs. PMID:20463754

  10. Immunotherapy with the trifunctional anti-CD20 x anti-CD3 antibody FBTA05 (Lymphomun) in paediatric high-risk patients with recurrent CD20-positive B cell malignancies.

    Science.gov (United States)

    Schuster, Friedhelm R; Stanglmaier, Michael; Woessmann, Wilhelm; Winkler, Beate; Siepermann, Meinolf; Meisel, Roland; Schlegel, Paul G; Hess, Jürgen; Lindhofer, Horst; Borkhardt, Arndt; Buhmann, Raymund

    2015-04-01

    Children with B cell malignancies refractory to standard therapy are known to have a poor prognosis and very limited treatment options. Here, we report on the treatment and follow-up of ten patients diagnosed with relapsed or refractory mature B-cell Non Hodgkin Lymphoma (B-NHL), Burkitt leukaemia (B-AL) or pre B-acute lymphoblastic leukaemia (pre B-ALL). All children were treated with FBTA05 (now designated Lymphomun), an anti-CD3 x anti-CD20 trifunctional bispecific antibody (trAb) in compassionate use. Within individual treatment schedules, Lymphomun was applied (a) after allogeneic stem cell transplantation (allo-SCT, n = 6) to induce sustained long-term remission, or (b) stand alone prior to subsequent chemotherapy to eradicate residual disease before allo-SCT (n = 4). Nine of ten children displayed a clinical response: three stable diseases (SD), one partial remission (PR) and five induced or sustained complete remissions (CR). Five of these nine responders died during follow-up. The other patients still maintain CR with a current overall survival of 874-1424 days (median: 1150 days). In conclusion, despite the dismal clinical prognosis of children refractory to standard therapy, immunotherapy with Lymphomun resulted in a favourable clinical outcome in this cohort of refractory paediatric patients. PMID:25495919

  11. Radiolabeling of anti-CD20 with Re-188 for treatment of non-Hodgkin's lymphoma: radiochemical control

    International Nuclear Information System (INIS)

    The development of tumor-selective radiopharmaceuticals is clinically desirable as a means of detecting or confirming the presence and location of primary and metastatic lesions and monitoring tumor response to (chemo)therapy. In addition, the application of targeted radiotherapeutics provides a unique and effective modality for direct tumor treatment. In this manner the radioimmunotherapy (RIT) uses the targeting features of monoclonal antibody to deliver radiation from an attached radionuclide. Antibody therapy directed against the CD20 antigen on the surface of B-cells is considered one of the first successful target-specific therapies in oncology. The radionuclide rhenium-188 (188Re) is currently produced from the father nuclide tungsten-188 (188W) through a transportable generator system. Because of its easy availability and suitable nuclear properties (EβMAX = 2.1 MeV, t1/2 = 16.9 h, Eγ = 155 keV), this radionuclide is considered an attractive candidate for application as therapeutic agent and could be conveniently utilized for imaging and dosimetric purposes. The purpose of this work is to show the radiochemical control of the optimized formulation (solution) and lyophilized formulation (kit) of labeled rituximab (anti-CD20) with 188Re. Rituximab was reduced by incubation with 2-mercaptoethanol at room temperature. The number of resulting free sulfhydryl groups was assayed with Ellman's reagent. Radiochemical purity of 188Re-rituximab was evaluated using instant thin layer chromatography-silica gel (ITLC-SG). Quality control methods for evaluation of radiochemical purity showed good labeling yield of the antibody. (author)

  12. Overcoming bortezomib resistance in human B cells by anti-CD20/rituximab-mediated complement-dependent cytotoxicity and epoxyketone-based irreversible proteasome inhibitors

    Directory of Open Access Journals (Sweden)

    Verbrugge Sue Ellen

    2013-01-01

    Full Text Available Abstract Background In clinical and experimental settings, antibody-based anti-CD20/rituximab and small molecule proteasome inhibitor (PI bortezomib (BTZ treatment proved effective modalities for B cell depletion in lymphoproliferative disorders as well as autoimmune diseases. However, the chronic nature of these diseases requires either prolonged or re-treatment, often with acquired resistance as a consequence. Methods Here we studied the molecular basis of acquired resistance to BTZ in JY human B lymphoblastic cells following prolonged exposure to this drug and examined possibilities to overcome resistance by next generation PIs and anti-CD20/rituximab-mediated complement-dependent cytotoxicity (CDC. Results Characterization of BTZ-resistant JY/BTZ cells compared to parental JY/WT cells revealed the following features: (a 10–12 fold resistance to BTZ associated with the acquisition of a mutation in the PSMB5 gene (encoding the constitutive β5 proteasome subunit introducing an amino acid substitution (Met45Ile in the BTZ-binding pocket, (b a significant 2–4 fold increase in the mRNA and protein levels of the constitutive β5 proteasome subunit along with unaltered immunoproteasome expression, (c full sensitivity to the irreversible epoxyketone-based PIs carfilzomib and (to a lesser extent the immunoproteasome inhibitor ONX 0914. Finally, in association with impaired ubiquitination and attenuated breakdown of CD20, JY/BTZ cells harbored a net 3-fold increase in CD20 cell surface expression, which was functionally implicated in conferring a significantly increased anti-CD20/rituximab-mediated CDC. Conclusions These results demonstrate that acquired resistance to BTZ in B cells can be overcome by next generation PIs and by anti-CD20/rituximab-induced CDC, thereby paving the way for salvage therapy in BTZ-resistant disease.

  13. Internal radiotherapy. 2. Treatment of non-hodgkin's lymphoma with 90Y-labeled anti-CD20 monoclonal antibody

    International Nuclear Information System (INIS)

    This paper describes recent trends of radioimmunotherapy using specific monoclonal antibodies against tumors, its principle and outcomes, with major emphasis on the title. When the antibodies like rituximab (rit), anti-CD20 antibody against B-cell malignant lymphoma, are labeled by a certain radioisotope, they become more active in specifically killing malignant cells by their immune cytotoxicity following binding plus lethal effect of radiation (beta ray). In Western areas, 90Y-labeled (ibritumomab, ibrit) or 131I-labeled rit is now available for the purpose. The efficacy of the former ibrit in the phase III trial has been reported to be 83%, in contrast to that of rit alone, 56%, with the similar safety to rit, in out-patients with the tumor. The protocol for the therapy is consisted from the first therapy with intravenous rit and imaging by 111In-labeled rit on day 1 and the second with the rit and ibrit (0.4 mCi/kg) on day 8. Patients are excluded from the latter therapy when the image by 111In shows the abnormal distribution in the liver and bone marrow. In Japan, phase I/II clinical trials of ibrit have been conducted to confirm its efficacy and safety and the agent is to be approved within this year. The radioimmunotherapy is thought to become more popular. (T.I.)

  14. Standardization of methodology to derivatization and radiolabeling of the anti-CD20 monoclonal antibody from bifunctional chelator DOTA-NHS-Ester

    International Nuclear Information System (INIS)

    Lymphomas are cancers of the lymphatic system, being the most common the non-Hodgkin lymphoma (NHL). The Radioimmunotherapy (RIT), that increase the cytotoxic effect of monoclonal antibodies (mAb), therefore labeling these Mab with different radioisotopes. RIT combines the specificity of the antibody and the toxicity of the radionuclides. The mAb anti-CD20 is used for treatment of relapse or refractory NHL. The labeling of anti- CD20 with 177Lu, requires a bifunctional chelating agent that is designed to make a 'connect bridge' between the mAb and the radionuclide. The incorporation of the chelating group in mAb structure is called derivatization. The aim of this work is to study the derivatization of anti-CD20 antibody with DOTA-NHS-ester chelating group and labeling parameters to produce 177Lu-DOTA-Anti CD20. Five milligrams of anti-CD20 were purified by dialysis against phosphate buffer pH 8.0 and derivatized with DOTA-NHS-ester in 1:250, 1:500 and 1:1000 molar ratios. The reaction was conducted for 1 hour in gently mixing at room temperature and remained under refrigeration for 48 hours. The reaction mixture was purified in gel column Sephadex G-50 ; the aliquots that presented greater protein concentration, were mixed and concentrated. The purified antibody conjugated was added to 111-185MBq (3-5mCi) of 177LuCl3 diluted in 0.4 M acetate buffer pH 5.5. Radiochemical purity was less than 95% in all the molar ratios, indicating necessity of the purification after the labeling. The mAb derivatized showed stable when stored for to 1 month to 4 deg C and 4 days at -20 deg C. (author)

  15. Human IgG1 Cγ1 Domain Is Crucial for the Bioactivity of the Engineered Anti-CD20 Antibodies

    Institute of Scientific and Technical Information of China (English)

    Shusheng Geng; Jiannan Feng; Yan Li; Xianjiang Kang; Yingxun Sun; Xin Gu; Ying Huang; Hong Chang; Beifen Shen

    2007-01-01

    In this study, we discussed the necessity of human IgG1 Cγ1 domain for recombinant antibody using computeraided homology modeling method and experimental studies. The heavy (VH) and light (VL) chain variable regions of 1-28, a murine IgM-type anti-CD20 mAb, were ligated by linker peptide (Gly4Ser)3 to form the single-chain Fv fragment (scFv). Then, the engineered antibody (LH1-3) was generated by fusing scFv with the entire IgG1 heavy constant regions. The 3-D structure of LH1-3 was modeled using computer-aided homology modeling method and the binding activity of LH1-3 was evaluated theoretically. Compared to the 3-D structure of the Fv fragment of the parent antibody, the conformation of the active pocket of LH1-3 was remained because of the rigid support of Cγ1.Further experimental results of flow cytometry showed that the engineered anti-CD20 antibody possessed specifically binding activity to CD20-expressing target cells. The anti-CD20 antibody fragments could also mediate complement-dependent cytotoxicity (CDC) of human B-lymphoid cell lines. Our study highlights some interests and advantages of a methodology based on the homology modeling and analysis of molecular structural properties.

  16. Mass-Production and Characterization of Anti-CD20 Monoclonal Antibody in Peritoneum of Balb/c Mice

    OpenAIRE

    Leili Aghebati; Jalal Abdolalizadeh; Jafar Majidi; Behzad Baradaran; Koushan Sineh Sepehr; Fatemeh Zare Shahneh

    2013-01-01

    Purpose: Monoclonal antibodies are important tools are used in basic research as well as, in diagnosis, imaging and treatment of immunodeficiency diseases, infections and cancers. The purpose of this study was to produce large scale of monoclonal antibody against CD20 in order to diagnostic application in leukemia and lymphomas disorders. Methods: Hybridoma cells that produce monoclonal antibody against human CD20 were administered into the peritoneum of the Balb/c mice which have previously ...

  17. Anti-CD20 Immunoglobulin G Radiolabeling with a 99mTc-Tricarbonyl Core: In Vitro and In Vivo Evaluations.

    Science.gov (United States)

    Carpenet, Hélène; Cuvillier, Armelle; Monteil, Jacques; Quelven, Isabelle

    2015-01-01

    In recent years, the diagnostic and therapeutic uses of radioisotopes have shown significant progress. Immunoglobulin (Ig) appears to be a promising tracer, particularly due to its ability to target selected antigens. The main objective of this study is to optimize and assess an Ig radiolabeling method with Technetium 99m (99mTc), an attractive radioelement used widely for diagnostic imaging. Monoclonal anti-CD20 IgG was retained to study in vitro and in vivo radiolabeling impact. After IgG derivatization with 2-iminothiolane, IgG-SH was radiolabeled by an indirect method, using a 99mTc-tricarbonyl core. Radiolabeling stability was evaluated over 24h by thin-layer chromatography. IgG integrity was checked by sodium dodecyl sulfate-polyacrylamide gel electrophoresis coupled with Western blot and autoradiography. The radiolabeled Ig's immunoaffinity was assessed in vitro by a radioimmunoassay method and binding experiments with cells (EL4-hCD20 and EL4-WT). Biodistribution studies were performed in normal BALB/c mice. Tumor uptake was assessed in mice bearing EL4-hCD20 and EL4-WT subcutaneous xenografts. With optimized method, high radiolabeling yields were obtained (95.9 ± 3.5%). 99mTc-IgG-SH was stable in phosphate-buffered saline (4°C and 25°C) and in serum (37°C), even if important sensitivity to transchelation was observed. IgG was not degraded by derivatization and radiolabeling, as shown by Western blot and autoradiography results. 99mTc-anti-CD20 IgG-SH immunoaffinity was estimated with Kd = 35 nM by both methods. In vivo biodistribution studies for 48h showed significant accumulation of radioactivity in plasma, liver, spleen, lungs and kidneys. Planar scintigraphy of mice bearing tumors showed a significant uptake of 99mTc-anti-CD20 IgG-SH in CD20+ tumor versus CD20- tumor. Radiolabeling of derivatized IgG with 99mTc-tricarbonyl was effective, stable and required few antibody amounts. This attractive radiolabeling method is "antibody safe" and preserves

  18. Anti-CD20 Immunoglobulin G Radiolabeling with a 99mTc-Tricarbonyl Core: In Vitro and In Vivo Evaluations.

    Directory of Open Access Journals (Sweden)

    Hélène Carpenet

    Full Text Available In recent years, the diagnostic and therapeutic uses of radioisotopes have shown significant progress. Immunoglobulin (Ig appears to be a promising tracer, particularly due to its ability to target selected antigens. The main objective of this study is to optimize and assess an Ig radiolabeling method with Technetium 99m (99mTc, an attractive radioelement used widely for diagnostic imaging. Monoclonal anti-CD20 IgG was retained to study in vitro and in vivo radiolabeling impact. After IgG derivatization with 2-iminothiolane, IgG-SH was radiolabeled by an indirect method, using a 99mTc-tricarbonyl core. Radiolabeling stability was evaluated over 24h by thin-layer chromatography. IgG integrity was checked by sodium dodecyl sulfate-polyacrylamide gel electrophoresis coupled with Western blot and autoradiography. The radiolabeled Ig's immunoaffinity was assessed in vitro by a radioimmunoassay method and binding experiments with cells (EL4-hCD20 and EL4-WT. Biodistribution studies were performed in normal BALB/c mice. Tumor uptake was assessed in mice bearing EL4-hCD20 and EL4-WT subcutaneous xenografts. With optimized method, high radiolabeling yields were obtained (95.9 ± 3.5%. 99mTc-IgG-SH was stable in phosphate-buffered saline (4°C and 25°C and in serum (37°C, even if important sensitivity to transchelation was observed. IgG was not degraded by derivatization and radiolabeling, as shown by Western blot and autoradiography results. 99mTc-anti-CD20 IgG-SH immunoaffinity was estimated with Kd = 35 nM by both methods. In vivo biodistribution studies for 48h showed significant accumulation of radioactivity in plasma, liver, spleen, lungs and kidneys. Planar scintigraphy of mice bearing tumors showed a significant uptake of 99mTc-anti-CD20 IgG-SH in CD20+ tumor versus CD20- tumor. Radiolabeling of derivatized IgG with 99mTc-tricarbonyl was effective, stable and required few antibody amounts. This attractive radiolabeling method is "antibody safe

  19. Comparative efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

    International Nuclear Information System (INIS)

    Purpose Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice. Methods Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma) or Granta (mantle cell lymphoma) xenografts, utilizing an anti-CD20 antibodystreptavidin conjugate (1F5-SA) and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin second step reagent. Results The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq) as for 177Lu (0.6 Gy/MBq). More importantly, therapy with 90Y-DOTAbiotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes. Conclusion 90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT approaches in

  20. Comparative efficacy of 177Lu and 90Y for anti-CD20 pretargeted radioimmunotherapy in murine lymphoma xenograft models.

    Directory of Open Access Journals (Sweden)

    Sofia H L Frost

    Full Text Available Pretargeted radioimmunotherapy (PRIT is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y and lutetium-177 (177Lu are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice.Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma or Granta (mantle cell lymphoma xenografts, utilizing an anti-CD20 antibody-streptavidin conjugate (1F5-SA and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-biotin second step reagent.The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq as for 177Lu (0.6 Gy/MBq. More importantly, therapy with 90Y-DOTA-biotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes.90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT approaches in these human lymphoma

  1. Antitumor effects of an engineered and energized fusion protein consisting of an anti-CD20 scFv fragment and lidamycin.

    Science.gov (United States)

    Fang, Hong; Miao, Qingfang; Zhang, Shenghua; Cheng, Xin; Xiong, Dongsheng; Zhen, Yongsu

    2011-03-01

    Antibody-based fusion proteins are the next generation of antibody therapies for cancer and other diseases. CD20 antigen, which is overexpressed on cell membranes in nearly 95% of cases of B-cell Non-Hodgkin's Lymphoma, is an attractive target for the therapy of B-lymphoid malignancies. Lidamycin (LDM) is a potent enediyne-containing antitumor antibiotic that now has entered phase II clinical trials. In this study, we prepared an engineered fusion protein, scFv-LDP, consisting of an anti-CD20 scFv fragment and the apoprotein LDP of LDM using DNA recombination. After purification and refolding, scFv-LDP was found to bind specifically to CD20-positive lymphoma cells using ELISA and indirect immunofluorescent cytochemical staining assays. The energized fusion protein scFv-LDP-AE was obtained using molecular reconstitution of the active chromophore AE of LDM and scFv-LDP. MTT assay revealed potent cytotoxicity of scFv-LDP-AE to CD20-positive Raji and Daudi cells, with IC(50) values of 1.21×10(-11) and 6.24×10(-11) mol L(-1), respectively. An in vivo subcutaneous xenograft model of CD20-positive B cell lymphoma in BALB/c (nu/nu) mice was also utilized. Drugs were given intravenously on day 14 and 21 after tumor transplantation. In terms of maximal tolerated doses, scFv-LDP-AE at 0.3 mg kg(-1) suppressed tumor growth by 79.3%, and LDM at 0.05 mg kg(-1) by 68.6% (P<0.05). Results suggested scFv-LDP-AE could be a potential candidate for tumor-targeting therapy. PMID:21416325

  2. Intratumoral but not systemic delivery of CpG oligodeoxynucleotide augments the efficacy of anti-CD20 monoclonal antibody therapy against B cell lymphoma.

    Science.gov (United States)

    Betting, David J; Yamada, Reiko E; Kafi, Kamran; Said, Jonathan; van Rooijen, Nico; Timmerman, John M

    2009-01-01

    The anti-CD20 monoclonal antibody rituximab (Rituxan) has become a mainstay in the treatment of B cell non-Hodgkin lymphomas. The mechanisms of action for rituximab include antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity, and apoptosis induction. Combination of anti-CD20 antibodies with immunostimulatory agents may improve their efficacy via enhancement of one or more of these mechanisms. Toll-like receptor 9 agonist CpG oligodeoxynucleotides administered systemically have been studied in clinical trials with and without rituximab. However, recent data suggest that intratumoral (IT) delivery of CpG has advantages in the treatment of tumors. Using a syngeneic murine B cell lymphoma line expressing human CD20, we found that IT, but not systemically administered CpG significantly improved the efficacy of rituximab against 7-day established tumors. Rituximab plus IT CpG could eradicate tumors from 42% of mice, whereas systemically administered CpG, with or without rituximab, did not achieve tumor eradication. Both natural killer cells and complement participated in the cure of tumors by rituximab plus IT CpG, apparently by increasing tumor cell sensitivity to complement and ADCC lysis, and by augmenting the cytotoxicity of ADCC effectors. No role for T cells in mediating tumor eradication was demonstrated in this model. These results suggest that previous clinical trials in B cell lymphoma combining systemic administration of CpG with rituximab may have employed suboptimal routes of CpG delivery. Future trials combining IT CpG with anti-CD20 antibodies or the antibody-mediated targeting of CpG directly to the sites of B cell lymphoma may thus be warranted. PMID:19483647

  3. Mass-Production and Characterization of Anti-CD20 Monoclonal Antibody in Peritoneum of Balb/c Mice

    Directory of Open Access Journals (Sweden)

    Leili Aghebati

    2013-02-01

    Full Text Available Purpose: Monoclonal antibodies are important tools are used in basic research as well as, in diagnosis, imaging and treatment of immunodeficiency diseases, infections and cancers. The purpose of this study was to produce large scale of monoclonal antibody against CD20 in order to diagnostic application in leukemia and lymphomas disorders. Methods: Hybridoma cells that produce monoclonal antibody against human CD20 were administered into the peritoneum of the Balb/c mice which have previously been primed with 0.5 ml Pristane. After twelve days, approximately 7 ml ascetic fluid was harvested from the peritoneum of each mouse. Evaluation of mAb titration was assessed by ELISA method. In the present study, we describe a protocol for large scale production of MAbs. Results: We prepared monoclonal antibodies (mAbs with high specificity and sensitivity against human CD20 by hybridoma method and characterized them by ELISA. The subclass of antibody was IgG2a and its light chain was kappa. Ascetic fluid was purified by Protein-A Sepharose affinity chromatography and the purified monoclonal antibody was conjugated with FITC and Immunofluorescence was done for confirming the specific binding. Conclusion: The conjugated monoclonal antibody could have application in diagnosis B-cell lymphomas, hairy cell leukemia, B-cell chronic lymphocytic leukemia, and melanoma cancer stem cells.

  4. Transient B-Cell Depletion with Anti-CD20 in Combination with Proinsulin DNA Vaccine or Oral Insulin: Immunologic Effects and Efficacy in NOD Mice

    OpenAIRE

    Ghanashyam Sarikonda; Sowbarnika Sachithanantham; Yulia Manenkova; Tinalyn Kupfer; Amanda Posgai; Clive Wasserfall; Philip Bernstein; Laura Straub; Pagni, Philippe P.; Darius Schneider; Teresa Rodriguez Calvo; Marilyne Coulombe; Kevan Herold; Gill, Ronald G.; Mark Atkinson

    2013-01-01

    A recent type 1 diabetes (T1D) clinical trial of rituximab (a B cell-depleting anti-CD20 antibody) achieved some therapeutic benefit in preserving C-peptide for a period of approximately nine months in patients with recently diagnosed diabetes. Our previous data in the NOD mouse demonstrated that co-administration of antigen (insulin) with anti-CD3 antibody (a T cell-directed immunomodulator) offers better protection than either entity alone, indicating that novel combination therapies that i...

  5. ImmunoPET imaging of B-cell lymphoma using 124I-anti-CD20 scFv dimers (diabodies).

    Science.gov (United States)

    Olafsen, Tove; Sirk, Shannon J; Betting, David J; Kenanova, Vania E; Bauer, Karl B; Ladno, Waldemar; Raubitschek, Andrew A; Timmerman, John M; Wu, Anna M

    2010-04-01

    Rapid clearing engineered antibody fragments for immunoPET promise high sensitivity at early time points. Here, tumor targeting of anti-CD20 diabodies (scFv dimers) for detection of low-grade B-cell lymphomas were evaluated. In addition, the effect of linker length on oligomerization of the diabody was investigated. Four rituximab scFv variants in the V(L)-V(H) orientation with different linker lengths between the V domains (scFv-1, scFv-3, scFv-5, scFv-8), plus the scFv-5 with a C-terminal cysteine (Cys-Db) for site-specific modification were generated. The scFv-8 and Cys-Db were radioiodinated with (124)I for PET imaging, and biodistribution of (131)I-Cys-Db was carried out at 2, 4 10 and 20 h. The five anti-CD20 scFv variants were expressed as fully functional dimers. Shortening the linker to three or one residue did not produce higher order of multimers. Both (124)I-labeled scFv-8 and Cys-Db exhibited similar tumor targeting at 8 h post injection, with significantly higher uptakes than in control tumors (P < 0.05). At 20 h, less than 1% ID/g of (131)I-labeled Cys-Db was present in tumors and tissues. Specific tumor targeting and high contrast images were achieved with the anti-CD20 diabodies. These agents extend the repertoire of reagents that can potentially be used to improve detection of low-grade lymphomas. PMID:20053640

  6. Veltuzumab, an anti-CD20 mAb for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and immune thrombocytopenic purpura.

    Science.gov (United States)

    Milani, Cannon; Castillo, Jorge

    2009-04-01

    Veltuzumab is a humanized, second-generation anti-CD20 mAb currently under development by Immunomedics Inc for the potential treatment of B-cell non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Licensee Nycomed is developing veltuzumab for the potential treatment of rheumatoid arthritis and immune thrombocytopenic purpura (ITP). Veltuzumab contains 90 to 95% human antibody sequences with identical antigen framework regions to epratuzumab (a humanized anti-CD22 mAb) and similar antigen-binding determinants to rituximab (chimeric, anti-CD20 mAb and the first-line treatment of aggressive and indolent NHL). In vitro studies have demonstrated that veltuzumab has enhanced binding avidities and a stronger effect on complement-dependent cytotoxicity compared with rituximab in selected cell lines. In dose-finding phase I/II clinical trials in patients with low-grade NHL, intravenous veltuzumab demonstrated a substantial rate of complete responses in concurrence with shorter and more tolerable infusions compared with rituximab. Currently there has been no evidence of an immune response to repeated administrations, and no serious adverse events related to veltuzumab treatment in patients with NHL. Veltuzumab is undergoing clinical trials using a low-dose subcutaneous formulation in patients with NHL, CLL and ITP. Prospective, randomized clinical trials are needed to clarify the role veltuzumab will play in a market where the therapy of B-cell lymphoproliferative disorders is dominated by rituximab. PMID:19330725

  7. Association among heterogeneity of intratumoral anti-CD20 antibody distribution, glucose metabolism and therapeutic response in radioimmunotherapy for B-cell lymphoma

    International Nuclear Information System (INIS)

    Full text of publication follows. Aim: in Zevalin therapy for CD20 positive low-grade lymphoma, heterogeneity of intratumoral anti-CD20 antibody distribution as well as status of lesional glucose metabolism prior to therapy may affect tumor response. The aim of this study was to evaluate association of heterogeneity of intratumoral In-111 Zevalin (In-Zevalin), accumulation of F-18 FDG (FDG), and therapeutic response in patients receiving Zevalin therapy. Methods: 16 patients with CD20 positive B-cell non-Hodgkin's lymphoma who underwent Y-90 Zevalin therapy after imaging with In-Zevalin SPECT/CT and FDG PET/CT were enrolled. Patients received In-Zevalin, followed by SPECT/CT scanning at 48 hours after administration. SUVmax of FDG of lesions was measured on PET/CT while lesion accumulation of In-Zevalin as %ID/g and SUVmax of In-Zevalin (In-Zevalin SUVmax) was measured on SPECT/CT. To evaluate heterogeneity of anti-CD20 antibody distribution, skewness and kurtosis of voxel distribution were calculated by placing there-dimensional volumes of interest (3-D VOIs) on SPECT/CT images. As another intratumoral heterogeneity index, cumulative SUVmax-volume histograms describing percentage of total tumor volume above thresholds of In-Zevalin SUVmax (AUC-CSH) were calculated by placing 3-D VOIs. All lesions (n=42) were classified into responders and non-responders lesion-by-lesion on pre- and post-therapeutic CT images. Results: by lesion-based analysis, a positive correlation was observed between FDG SUVmax and accumulation of In-Zevalin. Accumulation of In-Zevalin was 0.0022 ± 0.0009 and 0.0024 ± 0.0008 %ID/g (n.s.), and 2.74 ± 1.43 and 3.29 ± 1.47 SUVmax (n.s.) for responders and non-responders, respectively. In contrast, voxel distribution of In-Zevalin demonstrated skewness of 0.58 ± 0.16 and 0.73 ± 0.24 (p<0.05), kurtosis of 2.39 ± 0.32 and 2.78 ± 0.53 (p<0.02), and AUC-CSH of 0.37 ± 0.04 and 0.34 ± 0.05 (p<0.05) for responders and non

  8. Influence of anti-CD20 monoclonal antibody combined with IL-10 on immune function of spleen in NOD mice%Anti-CD20与 IL-10联合应用对非肥胖型糖尿病小鼠脾脏免疫功能的影响

    Institute of Scientific and Technical Information of China (English)

    任安霞; 于淑凤; 张丽娟; 陈志红; 李堂

    2015-01-01

    Objective To observe the influence of anti-CD20 monoclonal antibody ( Anti-CD20 ) combined with inter-leukin 10 ( IL-10) on the immune function of spleen in non-obese diabetic ( NOD) mouse.Methods Twenty-four NOD mice were randomly divided into four groups , 6 mice in each group:groups A, B, C and D, which were caudal venously injected with 250μg Anti-CD20 , 250μg Anti-CD20 +0.1 mL IL-10, 0.1 mL IL-10 and 0.1 mL normal saline at day 1, 8, 15 and 21, respectively.All mice were sacrificed 12 weeks after first injection and the spleens were immediately taken out . The number of CD4+T cells, CD3+T cells and the levels of IL-10 and IL-27 were detected by immunohistochemistry . Results Compared with group D, the number of CD+4 T cells, CD+3 T cells and the levels of IL-10 and IL-27 in the spleen tissues were increased in the groups A , B and C (all P<0.01).Compared with groups A and C , the number of CD4+T cells, CD+3 T cells and the levels of IL-10 and IL-27 in the spleen tissues were increased in the group B (all P<0.01). Conclusion The combined administration of Anti-CD20 and IL-10 increases the number of CD+4 T cells, CD+3 T cells and the levels of IL-10 and IL-27 in the spleen tissues , and thus it regulates the immune microenvironment and prevents the oc-currence of diabetes .%目的:观察抗CD20单克隆抗体(Anti-CD20)与白细胞介素10(IL-10)联合应用对非肥胖型糖尿病(NOD)小鼠脾脏免疫功能的影响。方法将24只NOD小鼠随机分为A、B、C、D组各6只,分别于第1、8、15、21天尾静脉注射Anti-CD20250μg、Anti-CD20250μg +IL-100.1 mL、IL-100.1 mL和生理盐水0.1 mL。首次用药后第12周断颈处死小鼠,立即取出脾脏,采用免疫组化法检测脾脏组织中的CD4+、CD3+T细胞及IL-27、IL-10。结果与D组比较,A、B、C组脾脏组织中CD4+、CD3+T细胞数量及IL-27、IL-10表达增加( P均<0.01);与A、C组比较,B组脾脏组织中CD+4、CD+3 T

  9. Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Green, Damian J.; Shadman, Mazyar; Jones, Jon C.; Frayo, Shani; Kenoyer, Aimee L.; Hylarides, Mark; Hamlin, Donald K.; Wilbur, D. Scott; Balkan, Ethan R.; Lin, Yukang; Miller, Brian W.; Frost, Sophia; Gopal, Ajay K.; Orozco, Johnnie J.; Gooley, Ted; Laird, Kelley L.; Till, B. G.; Back, Tom; Sandmaier, B. M.; Pagel, John M.; Press, Oliver W.

    2015-03-26

    Alpha emitting radionuclides release a large amount of energy within a few cell diameters and may be particularly effective for radioimmunotherapy targeting minimal residual disease (MRD) conditions in which micrometastatic disease satellites are broadly distributed. To evaluate this hypothesis, 211At conjugated 1F5 mAb (anti-CD20) was studied in both bulky lymphoma tumor xenograft and MRD animal models. Superior treatment responses to 211At conjugated 1F5 mAb were evident in the MRD setting. Lymphoma xenograft tumor bearing animals treated with doses of up to 48µCi of anti-CD20 211At-decaborate [211At-B10-1F5] experienced modest responses (0% cures but 2-3-fold prolongation of survival compared to negative controls). In contrast, 70% of animals in the MRD lymphoma model demonstrated complete eradication of disease when treated with 211At-B10-1F5 at a radiation dose that was less than one-third (15 µCi) of the highest dose given to xenograft animals. Tumor progression among untreated control animals in both models was uniformly lethal. After 130 days, no significant renal or hepatic toxicity is observed in the cured animals receiving 15 µCi of 211At-B10-1F5. These findings suggest that in a MRD lymphoma model, where isolated cells and tumor microclusters prevail, α-emitters may be uniquely efficacious.

  10. Specific Conjugation of the Hinge Region for Homogeneous Preparation of Antibody Fragment-Drug Conjugate: A Case Study for Doxorubicin-PEG-anti-CD20 Fab' Synthesis.

    Science.gov (United States)

    Zhou, Zhan; Zhang, Jing; Zhang, Yan; Ma, Guanghui; Su, Zhiguo

    2016-01-20

    Conventional preparation strategies for antibody-drug conjugates (ADCs) result in heterogeneous products with various molecular sizes and species. In this study, we developed a homogeneous preparation strategy by site-specific conjugation of the anticancer drug with an antibody fragment. The model drug doxorubicin (DOX) was coupled to the Fab' fragment of anti-CD20 IgG at its permissive sites through a heterotelechelic PEG linker, generating an antibody fragment-drug conjugate (AFDC). Anti-CD20 IgG was digested and reduced specifically with β-mercaptoethylamine to generate the Fab' fragment with two free mercapto groups in its hinge region. Meanwhile, DOX was conjugated with α-succinimidylsuccinate ω-maleimide polyethylene glycol (NHS-PEG-MAL) to form MAL-PEG-DOX, which was subsequently linked to the free mercapto containing Fab' fragment to form a Fab'-PEG-DOX conjugate. The dual site-specific bioconjugation was achieved through the combination of highly selective reduction of IgG and introduction of heterotelechelic PEG linker. The resulting AFDC provides an utterly homogeneous product, with a definite ratio of one fragment to two drugs. Laser confocal microscopy and cell ELISA revealed that the AFDC could accumulate in the antigen-positive Daudi tumor cell. In addition, the Fab'-PEG-DOX retained appreciable targeting ability and improved antitumor activity, demonstrating an excellent therapeutic effect on the lymphoma mice model for better cure rate and significantly reduced side effects. PMID:26700095

  11. Autosomal Recessive Chronic Granulomatous Disease, IgA Deficiency and Refractory Autoimmune Thrombocytopenia Responding to Anti-CD20 Monoclonal Antibody

    Directory of Open Access Journals (Sweden)

    Shahin Shamsian Bibi

    2008-09-01

    Full Text Available Immunodeficiency and autoimmune disease may occur concomitantly in the same individual. Some of the immunodeficiency syndromes, especially humoral defects are associated with autoimmune disorders. Hematological manifestations such as thrombocytopenia and hemolytic anemia are the most common presentations. Persistent antigen stimulation due to an inherent defect in the ability of the immune system to eradicate pathogens is the primary cause leading to autoimmunity in patients with primary immunodeficiency states.We describe a 10 year old Iranian girl with chronic granulomatous disease -the autosomal recessive type with mutation of NCF1 gene P47- associated with selective IgA deficiency, refractory immune thrombocytopenia that showed an excellent response to Rituximab (Anti-CD20 monoclonal antibody.Patients with primary immunodeficiencies may have variable autoimmune manifestations. So for early detection and appropriate treatment, autoimmune diseases should always be suspected in such patients.

  12. The study of labeling with iodine-131 of monoclonal antibody anti-CD20 used for the treatment of non-Hodgkin lymphoma

    International Nuclear Information System (INIS)

    Lymphomas are malignancies of the lymphatic system, described by Thomas Hodgkin in 1932. Traditionally, lymphomas are classified in two basic groups: Hodgkin disease and non-Hodgkin lymphoma (NHL). Patients with NHL were earlier treated with radiotherapy alone or in combination with immunotherapy using monoclonal antibody anti-CD20 (ex., Rituximab-Mabthera, Roche). However, Radioimmunotherapy is a new modality of treatment for patients with NHL, in which cytotoxic radiation from therapeutic radioisotopes is delivered to tumors through monoclonal antibodies. This study focused on labeling conditions of monoclonal anti-CD20 (ex., Rituximab-Mabthera, Roche) with iodine-131, by direct radioiodination method using Chloramine-T as oxidizing agent. Labeling parameters investigated were: Radiochemical purity (RP), method of purification, incubation time, antibody mass, oxidative agent mass, stability in vitro, immunoreactivity and biological distribution performed in normal Swiss mouse. Product of high radiochemical purity was obtained with no notable difference between the methods applied. No clear evidence of direct influence of incubation time on radiochemical purity of the labeled antibody was observed. Whereas, a clear evidence of direct influence of activity on radiochemical purity of the labeled antibody was varied. After purification the labeled product presented radiochemical purity of approximately 100 %. Product of superior radiochemical yield was observed when standard condition of labeling was used. The labeled product presented variation in radiochemical purity using five different stabilizer conditions. The condition in which gentisic acid combined with freeze appears more suitable and capable of minimizing autoradiolysis of the antibody labeled with freeze appears more suitable and capable of minimizing autoradiolysis of the antibody labeled with high therapeutic activity of iodine-131. The labeled product presented low immunoreactivity when compared to the

  13. The study of labeling with Iodine-131 of monoclonal antibody anti-CD20 used for the treatment of non-Hodgkin lymphoma

    International Nuclear Information System (INIS)

    Lymphomas are malignancies of the lymphatic system, described by Thomas Hodgkin in 1932. Traditionally, lymphomas are classified in two basic groups: Hodgkin disease and non-Hodgkin lymphoma (NHL). Patients with NHL were earlier treated with radiotherapy alone or in combination with immunotherapy using monoclonal antibody anti-CD20 (ex., Rituximab-Mabthera, Roche). However, Radioimmunotherapy is a new modality of treatment for patients with NHL, in which cytotoxic radiation from therapeutic radioisotopes is delivered to tumors through monoclonal antibodies. This study focused on labeling conditions of monoclonal antibody anti-CD20 (Rituximab-Mabthera, Roche) with iodine-131, by direct radioiodination method using Chloramine-T as oxidizing agent. Labeling parameters investigated were: Radiochemical purity (RP), method of purification, incubation time, antibody mass, oxidative agent mass, stability in vitro, stability in vivo, immunoreactivity and biological distribution performed in normal Swiss mouse. Product of high radiochemical purity was obtained with no notable difference between the methods applied. No clear evidence of direct influence of incubation time on radiochemical purity of the labeled antibody was observed. Whereas, a clear evidence of direct influence of activity on radiochemical purity of the labeled antibody was observed when antibody mass was varied. After purification, the labeled product presented radiochemical purity of approximately 100 %. Product of superior radiochemical yield was observed when standard condition of labeling was used. The labeled product presented variation in radiochemical purity using five different stabilizer conditions. The condition in which gentisic acid was combined with freeze appears more suitable and capable of minimizing autoradiolysis of the antibody labeled with high therapeutic activity of iodine-131. The labeled product presented low immunoreactivity when compared to the literature. Biological distribution in

  14. Follow-up of relapsed B-cell lymphoma patients treated with iodine-131-labeled anti-CD20 antibody and autologous stem-cell rescue

    International Nuclear Information System (INIS)

    Radioimmunotherapy (RIT) is a promising treatment approach for B-cell lymphomas. This is our first opportunity to report long-term follow-up data and late toxicities in 29 patients treated with myeloablative doses of iodine-131-anti-CD20 antibody (anti-B1) and autologous stem-cell rescue. PATIENTS AND METHODS: Trace-labeled biodistribution studies first determined the ability to deliver higher absorbed radiation doses to tumor sites than to lung, liver, or kidney at varying amounts of anti-B1 protein (0.35, 1.7, or 7 mg/kg). Twenty- nine patients received therapeutic infusions of single-agent (131)I- anti-B1, given at the protein dose found optimal in the biodistribution study, labeled with amounts of (131)I (280 to 785 mCi[10.4 to 29.0 GBq]) calculated to deliver specific absorbed radiation doses to the normal organs, followed by autologous stem-cell support. RESULTS: Major responses occurred in 25 patients (86%), with 23 complete responses (CRs; 79%). The nonhematopoietic do se-limiting toxicity was reversible cardiopulmonary insufficiency, which occurred in two patients at RIT doses that delivered > or = 27 Gy to the lungs. With a median follow-up time of 42 months, the estimated overall and progression-free survival rates are 68% and 42%, respectively. Currently, 14 of 29 patients remain in unmaintained remissions that range from 27+ to 87+ months after RIT. Late toxicities have been uncommon except for elevated thyroid-stimulating hormone (TSH) levels found in approximately 60% of the subjects. Two patients developed second malignancies, but none have developed myelodysplasia (MDS). CONCLUSION: Myeloablative (131)I-anti- B1 RIT is relatively well tolerated when given with autologous stem- cell support and often results in prolonged remission durations with few late toxicities

  15. Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1-2 study

    DEFF Research Database (Denmark)

    Coiffier, B.; Lepretre, S.; Pedersen, L.M.;

    2008-01-01

    Safety and efficacy of the fully human anti-CD20 monoclonal antibody, ofatumumab, was analyzed in a multicenter dose-escalating study including 33 patients with relapsed or refractory chronic lymphocytic leukemia. Three cohorts of 3 (A), 3 (B), and 27 (C) patients received 4, once weekly, infusio...

  16. CD20单克隆抗体治疗老年弥漫性B细胞淋巴瘤的研究%Study on the anti CD20 monoclonal antibody treatment of senile diffuse course B cel lymphoma

    Institute of Scientific and Technical Information of China (English)

    李玉巧; 梁志伟; 罗国桢

    2014-01-01

    目的:观察抗CD20单克隆抗体治疗老年弥漫性B细胞淋巴瘤的临床疗效。方法:将我院收治的老年B细胞淋巴瘤28例分为两组,一组为R-CHOP组15例,另一组为对照组CHOP组,4-6个疗程进行疗效评价。结果:RCHOP方案组总缓解率为73.3.%,对照组CHOP方案治疗总缓解率为46.2%,不良反应与对照组无明显增加。结论:抗CD20单克隆抗体联合化疗治疗老年B细胞淋巴瘤疗效好,不良反应少。%Objective:To observe the anti CD20 monoclonal antibody the clinical curative effect of the treatment of senile diffuse B cel lymphoma,Method:The aged B cel lymphoma in our hospital 28 cases were divided into two groups,A group of 15 patients in the R-CHOP group,Another group was control group CHOP group,To evaluate the curative effect of 4-6 Results: the RCHOP regimen group total remission rate was 73.3.%,The control group of CHOP regimen in the treatment of the total response rate was 46.2%,Adverse reactions and control group had no obvious increase.Conclusion: Anti CD20 monoclonal antibody combined with chemotherapy efficacy in the treatment of aged B cel lymphoma, less adverse reaction.

  17. The study of labeling with Iodine-131 of monoclonal antibody anti-CD20 used for the treatment of non-Hodgkin lymphoma; Estudo de marcacao com Iodo-131 de anticorpo monoclonal anti-CD20 na terapia de linfoma nao-Hodgkin

    Energy Technology Data Exchange (ETDEWEB)

    Akanji, Akinkunmi Ganiyu

    2006-07-01

    Lymphomas are malignancies of the lymphatic system, described by Thomas Hodgkin in 1932. Traditionally, lymphomas are classified in two basic groups: Hodgkin disease and non-Hodgkin lymphoma (NHL). Patients with NHL were earlier treated with radiotherapy alone or in combination with immunotherapy using monoclonal antibody anti-CD20 (ex., Rituximab-Mabthera, Roche). However, Radioimmunotherapy is a new modality of treatment for patients with NHL, in which cytotoxic radiation from therapeutic radioisotopes is delivered to tumors through monoclonal antibodies. This study focused on labeling conditions of monoclonal antibody anti-CD20 (Rituximab-Mabthera, Roche) with iodine-131, by direct radioiodination method using Chloramine-T as oxidizing agent. Labeling parameters investigated were: Radiochemical purity (RP), method of purification, incubation time, antibody mass, oxidative agent mass, stability in vitro, stability in vivo, immunoreactivity and biological distribution performed in normal Swiss mouse. Product of high radiochemical purity was obtained with no notable difference between the methods applied. No clear evidence of direct influence of incubation time on radiochemical purity of the labeled antibody was observed. Whereas, a clear evidence of direct influence of activity on radiochemical purity of the labeled antibody was observed when antibody mass was varied. After purification, the labeled product presented radiochemical purity of approximately 100 %. Product of superior radiochemical yield was observed when standard condition of labeling was used. The labeled product presented variation in radiochemical purity using five different stabilizer conditions. The condition in which gentisic acid was combined with freeze appears more suitable and capable of minimizing autoradiolysis of the antibody labeled with high therapeutic activity of iodine-131. The labeled product presented low immunoreactivity when compared to the literature. Biological distribution in

  18. Effectiveness and side effects of anti-CD20 therapy for autoantibody-mediated blistering skin diseases: A comprehensive survey of 71 consecutive patients from the Initial use to 2007

    OpenAIRE

    Peterson, Jennifer D; Chan, Lawrence S

    2008-01-01

    Jennifer D Peterson1, Lawrence S Chan2,3,41Department of Dermatology, Texas Tech University Health Sciences Center at Lubbock, Lubbock, TX, USA; 2Department of Dermatology; 3Department of Microbiology/Immunology, University of Illinois at Chicago, Chicago, IL, USA; 4Medicine Service, Jesse Brown VA Medical Center, Chicago, IL, USAAbstract: In order to examine the efficacy and side effects of the monoclonal antibody anti-CD20 (rituximab) on autoimmune blistering skin diseases, we performed a c...

  19. Anti-CD20 Radioimmunotherapy Before Chemotherapy and Stem Cell Transplant in Treating Patients With High-Risk B-Cell Malignancies

    Science.gov (United States)

    2016-06-13

    Adult Burkitt Lymphoma; Adult Diffuse Large B-Cell Lymphoma; CD20-Positive Neoplastic Cells Present; Indolent Adult Non-Hodgkin Lymphoma; Mantle Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Refractory Mature B-Cell Non-Hodgkin Lymphoma

  20. Efficacy and safety of an anti-CD20 monoclonal antibody (Reditux™) for the treatment of patients with moderate to severe rheumatoid arthritis following the failure of conventional synthetic disease-modifying anti-rheumatic drugs.

    Science.gov (United States)

    Bhati, Manjeet; Bandyopadhyay, Syamasis

    2016-08-01

    Rituximab (anti-CD20 monoclonal antibody) has shown to improve symptoms in rheumatoid arthritis (RA) patients with inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). An anti-CD20 monoclonal antibody (Reditux™) developed by Dr. Reddy's Laboratories, India, is currently approved for use both in rheumatology and oncology patients. This retrospective report evaluates the efficacy and safety data from the real-world use of Reditux™ over a 6-month period in Indian patients with RA. All consecutive moderate to severe RA patients who failed therapy with at least two DMARDs including methotrexate (MTX) for 6 months, TNFα inhibitor naive, and willing to take Reditux™ were included. They were prescribed two doses of 1 g Reditux™, at least 15 days apart, with continued stable doses of methotrexate. Efficacy and safety after 24 weeks relative to baseline was assessed using various health assessment variables. A total of 39 patients (mean age of 46 years; 67.5 % females) treated with Reditux™ were evaluated. Statistically significant differences were observed in mean changes of DAS28-CRP, DAS28-ESR, SDAI, HAQ and Patient Global Assessment scores from baseline to 24 weeks (p serious adverse events over 24 weeks. Though limited by number of patients and retrospective in nature, this analysis serves as a real-world evidence of efficacy and safety of Dr. Reddy's rituximab (Reditux™) in the treatment of csDMARD-failed patients with RA over a 6-month period. PMID:27334114

  1. Effectiveness and side effects of anti-CD20 therapy for autoantibody-mediated blistering skin diseases: A comprehensive survey of 71 consecutive patients from the Initial use to 2007

    Directory of Open Access Journals (Sweden)

    Jennifer D Peterson

    2008-11-01

    Full Text Available Jennifer D Peterson1, Lawrence S Chan2,3,41Department of Dermatology, Texas Tech University Health Sciences Center at Lubbock, Lubbock, TX, USA; 2Department of Dermatology; 3Department of Microbiology/Immunology, University of Illinois at Chicago, Chicago, IL, USA; 4Medicine Service, Jesse Brown VA Medical Center, Chicago, IL, USAAbstract: In order to examine the efficacy and side effects of the monoclonal antibody anti-CD20 (rituximab on autoimmune blistering skin diseases, we performed a comprehensive survey of 71 consecutive patients from initial use up to 2007, using the PubMed database. A heterogeneous group of patients, including 51 patients with pemphigus vulgaris, one with pemphigus vegetans, nine with pemphigus foliaceus, five with paraneoplastic pemphigus, four with epidermolysis bullosa acquisita, and one with both bullous pemphigoid and graft vs host disease was included in this survey. Overall the monoclonal antibody seems to be effective in that 69% of patients showed complete response, 25% of patients showed partial response, whereas 6% of patients showed progressive disease. Six deaths occurred in association with the treatment, with four of these deaths in patients with paraneoplastic pemphigus, a disease characteristically resistant to conventional medication and with a high mortality rate. Of note, 11 patients who received combined rituximab and intravenous immune globulin treatments had the best outcome: complete response without any serious side effects. Therefore further investigation on rituximab with controlled clinical trial is a worthy pursuit.Keywords: blistering diseases, skin, anti-CD20, pemphigus, epidermolysis bullosa acquisita

  2. Synergistic anti-tumor activity of acadesine (AICAR) in combination with the anti-CD20 monoclonal antibody rituximab in in vivo and in vitro models of mantle cell lymphoma.

    Science.gov (United States)

    Montraveta, Arnau; Xargay-Torrent, Sílvia; López-Guerra, Mónica; Rosich, Laia; Pérez-Galán, Patricia; Salaverria, Itziar; Beà, Silvia; Kalko, Susana G; de Frias, Mercè; Campàs, Clara; Roué, Gaël; Colomer, Dolors

    2014-02-15

    Mantle cell lymphoma (MCL) is considered one of the most challenging lymphoma, with limited responses to current therapies. Acadesine, a nucleoside analogue has shown antitumoral effects in different preclinical cancer models as well as in a recent phase I/II clinical trial conducted in patients with chronic lymphocytic leukemia. Here we observed that acadesine exerted a selective antitumoral activity in the majority of MCL cell lines and primary MCL samples, independently of adverse cytogenetic factors. Moreover, acadesine was highly synergistic, both in vitro and in vivo, with the anti-CD20 monoclonal antibody rituximab, commonly used in combination therapy for MCL. Gene expression profiling analysis in harvested tumors suggested that acadesine modulates immune response, actin cytoskeleton organization and metal binding, pointing out a substantial impact on metabolic processes by the nucleoside analog. Rituximab also induced changes on metal binding and immune responses.The combination of both drugs enhanced the gene signature corresponding to each single agent, showing an enrichment of genes involved in inflammation, metabolic stress, apoptosis and proliferation. These effects could be important as aberrant apoptotic and proinflammatory pathways play a significant role in the pathogenesis of MCL. In summary, our results suggest that acadesine exerts a cytotoxic effect in MCL in combination with rituximab, by decreasing the proliferative and survival signatures of the disease, thus supporting the clinical examination of this strategy in MCL patients. PMID:24519895

  3. High-Dose [131I]Tositumomab (anti-CD20) Radioimmunotherapy and Autologous Hematopoietic Stem Cell Transplantation for Adults (ge) 60 Years Old with Relapsed or Refractory B-Cell Lymphoma

    International Nuclear Information System (INIS)

    Purpose: The majority of patients with relapsed or refractory B-cell, non-Hodgkin's lymphoma (NHL) are over 60 years of age, yet they are often denied potentially curative high-dose therapy and autologous stem cell transplants (ASCT) due to the risk of excessive treatment-related morbidity and mortality. Myeloablative anti-CD20 radioimmunotherapy (RIT) can deliver curative radiation doses to tumor sites while limiting exposure to normal organs and may be particularly suited for older adults requiring high-dose therapy. Methods: Patients over age 60 with relapsed B-NHL received infusions of tositumomab anti-CD20 antibody labeled with 5-10mCi I-131 tracer for dosimetry purposes followed 10 days later by individualized therapeutic infusions of I-131-tositumomab (median 525 mCi, range 328-1154 mCi) to deliver 25-27Gy to the critical normal organ receiving the highest radiation dose. ASCT was performed approximately 2 weeks after therapy. Results: Twenty-four patients with a median age of 64 (range 60-76) who had received a median of four prior regimens (range 2-14) were treated. Thirteen (54%) had chemotherapy-resistant disease. The estimated 3-year overall and progression-free survivals were 59% and 51%, respectively with a median follow-up of 2.9 years (range 1-6 years). All patients experienced expected myeloablation with engraftment of platelets ((ge) 20K/(micro)L) and neutrophils ((ge)500/(micro)L) occurring a median of 9 and 15 days, respectively following ASCT. There were no treatment-related deaths, and only two patients experienced grade 4 non-hematologic toxicity. Conclusions: Myeloablative RIT and ASCT is a safe and effective therapeutic option for older adults with relapsed B-NHL

  4. Validation of prospective whole-body bone marrow dosimetry by SPECT/CT multimodality imaging in {sup 131}I-anti-CD20 rituximab radioimmunotherapy of non-Hodgkin's lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Boucek, Jan A. [Fremantle Hospital, Department of Nuclear Medicine, Fremantle (Australia); Turner, J. Harvey [Fremantle Hospital, Department of Nuclear Medicine, Fremantle (Australia); University of Western Australia, School of Medicine and Pharmacology (Australia)

    2005-04-01

    Radioimmunotherapy (RIT) for relapsed non-Hodgkin's lymphoma is emerging as a promising treatment strategy. Myelosuppression is the dose-limiting toxicity and may be particularly problematic in patients heavily pretreated with chemotherapy. Reliable dosimetry is likely to minimise toxicity and improve treatment efficacy, and the aim of this study was to elucidate the complex problems of dosimetry of RIT by using an integrated SPECT/CT system. As a part of a clinical trial of {sup 131}I-anti-CD20 rituximab RIT of non-Hodgkin's lymphoma, we employed a patient-specific prospective dosimetry method utilising the whole-body effective half-life of antibody and the patient's ideal weight to calculate the administered activity for RIT corresponding to a prescribed radiation absorbed dose of 0.75 Gy to the whole body. A novel technique of quantitation of bone marrow uptake with hybrid SPECT/CT imaging was developed to validate this methodology by using post-RIT extended imaging and data collection. A strong, statistically significant correlation (p=0.001) between whole-body effective half-life of antibody and effective marrow half-life was demonstrated. Furthermore, it was found that bone marrow activity concentration was proportional to administered activity per unit weight, height or body surface area (p<0.001). The results of this study show the proposed whole-body dosimetry method to be valid and clinically applicable for safe, effective RIT. (orig.)

  5. The future of CD20 monoclonal antibody therapy in B-cell malignancies.

    Science.gov (United States)

    Czuczman, Myron S; Gregory, Stephanie A

    2010-06-01

    Limitations of therapeutic options for chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) have necessitated the development of novel treatments/strategies. Rituximab (chimeric anti-CD20 monoclonal antibody [mAb]) considerably improved therapeutic outcomes for patients with B-cell malignancies, particularly when combined with chemotherapy; outcomes, however, are limited by rituximab resistance or reduced response upon re-treatment. Novel anti-CD20 mAbs are in development that may enhance mAb therapy. Ofatumumab (human anti-CD20 mAb) induces highly potent cell lysis, including in cells with low CD20 expression, and is the most clinically advanced new anti-CD20 mAb. Positive phase III interim data for ofatumumab in fludarabine-refractory CLL that is also refractory to alemtuzumab or less suitable for alemtuzumab due to bulky (>5 cm) lymphadenopathy has led to FDA approval of this agent in this population. Preclinical and early clinical assessment of other novel anti-CD20 mAbs include: ocrelizumab, veltuzumab, GA101, AME-133v, and PRO131921; data suggest potential for improved efficacy over rituximab that will require substantiation in large-scale clinical trials. New treatment strategies and novel anti-CD20 mAbs have the potential to enhance long-term outcomes for CLL and NHL. PMID:20367564

  6. Perspectives of ofatumumab as CD20 targeted therapy in rheumatoid arthritis and other autoimmune diseases.

    Science.gov (United States)

    Pers, Yves Marie; Jorgensen, Christian

    2016-09-01

    Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune condition viewed as a severe destructive disease. The treatment strategies include anti-CD20 monoclonal antibody (mAb)-targeting B cells. Ofatumumab specifically targets a membrane-proximal epitope on the CD20 molecule distinct from other anti-CD20 antibodies including rituximab and ocrelizumab, and bind the epitope located on the large loop of CD20. This explains a more durable B-cell depletion and a different pharmacodynamic. We review the pharmacodynamic of B-cell depletion and analyze the results in RA and other B-cell-mediated autoimmune diseases. The randomized trial in RA showed clinical efficacy comparable to rituximab at week 24. However, structural impact has not been demonstrated. Studies including RA patients refractory to rituximab would be useful to define the optimal strategy of ofatumumab therapy. PMID:27485081

  7. Functional Recombinant Extra Membrane Loop of Human CD20, an Alternative of the Full Length CD20 Antigen

    OpenAIRE

    Anbouhi, Mahdi Habibi; Baraz, Aida Feiz; Bouzari, Saeid; Abolhassani, Mohsen; Khanahmad, Hossein; Golkar, Majid; Aghasadeghi, Mohammad Reza; Behdani, Mahdi; Najafabadi, Ali Jahanian; Shokrgozar, Mohammad Ali

    2012-01-01

    Background: Targeting of CD20 antigen with monoclonal antibodies has become the mainstay in the treatment of non-Hodgkin's lymphomas and immunotherapeutic depletion of malignant B cells. Accessibility of antigen is one of the crucial factors in development of monoclonal antibodies against this antigen. One major problem in expression of full length CD20 is aggregation and misfolding. Therefore, production of an alternative polypeptide is easer and favorable comparing to that of a full length ...

  8. Novel CD20 monoclonal antibodies for lymphoma therapy

    Directory of Open Access Journals (Sweden)

    Cang Shundong

    2012-10-01

    Full Text Available Abstract Rituximab (RTX, a monoclonal antibody (mAb against CD20, has been widely used for lymphoma therapy. RTX in combination with cyclophosphamide /doxorubicin /vincristine /prednisone (R-CHOP remains the standard frontline regimen for diffuse large B-cell lymphoma. However, suboptimal response and /or resistance to rituximab have remained a challenge in the therapy of B-cell non-Hodgkin’s lymphoma (NHL. Novel agents are under active clinical trials. This review will summarize the latest development in new mAbs against CD20, which include second-generation mAbs, ofatumumab, veltuzumab (IMMU-106, ocrelizumab (PRO70769, and third-generation mAbs, AME-133v (ocaratuzumab, PRO131921 and GA101 (obinutumumab.

  9. The Development of a Recombinant scFv Monoclonal Antibody Targeting Canine CD20 for Use in Comparative Medicine.

    Science.gov (United States)

    Jain, Saurabh; Aresu, Luca; Comazzi, Stefano; Shi, Jianguo; Worrall, Erin; Clayton, John; Humphries, William; Hemmington, Sandra; Davis, Paul; Murray, Euan; Limeneh, Asmare A; Ball, Kathryn; Ruckova, Eva; Muller, Petr; Vojtesek, Borek; Fahraeus, Robin; Argyle, David; Hupp, Ted R

    2016-01-01

    Monoclonal antibodies are leading agents for therapeutic treatment of human diseases, but are limited in use by the paucity of clinically relevant models for validation. Sporadic canine tumours mimic the features of some human equivalents. Developing canine immunotherapeutics can be an approach for modeling human disease responses. Rituximab is a pioneering agent used to treat human hematological malignancies. Biologic mimics that target canine CD20 are just being developed by the biotechnology industry. Towards a comparative canine-human model system, we have developed a novel anti-CD20 monoclonal antibody (NCD1.2) that binds both human and canine CD20. NCD1.2 has a sub-nanomolar Kd as defined by an octet red binding assay. Using FACS, NCD1.2 binds to clinically derived canine cells including B-cells in peripheral blood and in different histotypes of B-cell lymphoma. Immunohistochemical staining of canine tissues indicates that the NCD1.2 binds to membrane localized cells in Diffuse Large B-cell lymphoma, Marginal Zone Lymphoma, and other canine B-cell lymphomas. We cloned the heavy and light chains of NCD1.2 from hybridomas to determine whether active scaffolds can be acquired as future biologics tools. The VH and VL genes from the hybridomas were cloned using degenerate primers and packaged as single chains (scFv) into a phage-display library. Surprisingly, we identified two scFv (scFv-3 and scFv-7) isolated from the hybridoma with bioactivity towards CD20. The two scFv had identical VH genes but different VL genes and identical CDR3s, indicating that at least two light chain mRNAs are encoded by NCD1.2 hybridoma cells. Both scFv-3 and scFv-7 were cloned into mammalian vectors for secretion in CHO cells and the antibodies were bioactive towards recombinant CD20 protein or peptide. The scFv-3 and scFv-7 were cloned into an ADEPT-CPG2 bioconjugate vector where bioactivity was retained when expressed in bacterial systems. These data identify a recombinant anti-CD20

  10. The Development of a Recombinant scFv Monoclonal Antibody Targeting Canine CD20 for Use in Comparative Medicine

    Science.gov (United States)

    Jain, Saurabh; Aresu, Luca; Comazzi, Stefano; Shi, Jianguo; Worrall, Erin; Clayton, John; Humphries, William; Hemmington, Sandra; Davis, Paul; Murray, Euan; Limeneh, Asmare A.; Ball, Kathryn; Ruckova, Eva; Muller, Petr; Vojtesek, Borek; Fahraeus, Robin; Argyle, David; Hupp, Ted R.

    2016-01-01

    Monoclonal antibodies are leading agents for therapeutic treatment of human diseases, but are limited in use by the paucity of clinically relevant models for validation. Sporadic canine tumours mimic the features of some human equivalents. Developing canine immunotherapeutics can be an approach for modeling human disease responses. Rituximab is a pioneering agent used to treat human hematological malignancies. Biologic mimics that target canine CD20 are just being developed by the biotechnology industry. Towards a comparative canine-human model system, we have developed a novel anti-CD20 monoclonal antibody (NCD1.2) that binds both human and canine CD20. NCD1.2 has a sub-nanomolar Kd as defined by an octet red binding assay. Using FACS, NCD1.2 binds to clinically derived canine cells including B-cells in peripheral blood and in different histotypes of B-cell lymphoma. Immunohistochemical staining of canine tissues indicates that the NCD1.2 binds to membrane localized cells in Diffuse Large B-cell lymphoma, Marginal Zone Lymphoma, and other canine B-cell lymphomas. We cloned the heavy and light chains of NCD1.2 from hybridomas to determine whether active scaffolds can be acquired as future biologics tools. The VH and VL genes from the hybridomas were cloned using degenerate primers and packaged as single chains (scFv) into a phage-display library. Surprisingly, we identified two scFv (scFv-3 and scFv-7) isolated from the hybridoma with bioactivity towards CD20. The two scFv had identical VH genes but different VL genes and identical CDR3s, indicating that at least two light chain mRNAs are encoded by NCD1.2 hybridoma cells. Both scFv-3 and scFv-7 were cloned into mammalian vectors for secretion in CHO cells and the antibodies were bioactive towards recombinant CD20 protein or peptide. The scFv-3 and scFv-7 were cloned into an ADEPT-CPG2 bioconjugate vector where bioactivity was retained when expressed in bacterial systems. These data identify a recombinant anti-CD20

  11. A plasmablast biomarker for nonresponse to antibody therapy to CD20 in rheumatoid arthritis.

    Science.gov (United States)

    Owczarczyk, Kasia; Lal, Preeti; Abbas, Alexander R; Wolslegel, Kristen; Holweg, Cecile T J; Dummer, Wolfgang; Kelman, Ariella; Brunetta, Paul; Lewin-Koh, Nicholas; Sorani, Marco; Leong, Diane; Fielder, Paul; Yocum, David; Ho, Carole; Ortmann, Ward; Townsend, Michael J; Behrens, Timothy W

    2011-09-21

    An important goal for personalized health care is the identification of biomarkers that predict the likelihood of treatment responses. Here, we tested the hypothesis that quantitative mRNA assays for B lineage cells in blood could serve as baseline predictors of therapeutic response to B cell depletion therapy in subjects with rheumatoid arthritis (RA). In samples from the REFLEX trial of rituximab in inadequate responders to antibodies to tumor necrosis factor-α, a 25% subgroup of treated subjects with elevated baseline mRNA levels of IgJ, a marker for antibody-secreting plasmablasts, showed reduced clinical response rates. There were no significant efficacy differences in the placebo arm subjects stratified by this marker. Prospective testing of the IgJ biomarker in the DANCER and SERENE rituximab clinical trial cohorts and the SCRIPT ocrelizumab cohort confirmed the utility of this marker to predict nonresponse to anti-CD20 therapy. A combination mRNA biomarker, IgJhiFCRL5lo, showed improved test performance over IgJhi alone. This study demonstrates that baseline blood levels of molecular markers for late-stage B lineage plasmablasts identify a ~20% subgroup of active RA subjects who are unlikely to gain substantial clinical benefit from anti-CD20 B cell depletion therapy. PMID:21937757

  12. A Recombinant Bispecific CD20×CD95 Antibody With Superior Activity Against Normal and Malignant B-cells.

    Science.gov (United States)

    Nalivaiko, Kristina; Hofmann, Martin; Kober, Karina; Teichweyde, Nadine; Krammer, Peter H; Rammensee, Hans-Georg; Grosse-Hovest, Ludger; Jung, Gundram

    2016-02-01

    Monoclonal antibodies directed to the B-cell-specific CD20-antigen are successfully used for the treatment of lymphomas and autoimmune diseases. Here, we compare the anti-B-cell activity of three different antibodies directed to CD20: (i) a chimeric, monospecific antibody, (ii) an Fc-optimized variant thereof, and (iii) a bispecific CD20×CD95-antibody in a newly developed recombinant format, termed Fabsc. The bispecific antibody specifically triggers the CD95 death receptor on malignant, as well as activated, normal B-cells. We found that the capability of this antibody to suppress the growth of malignant B-cells in vitro and in vivo and to specifically deplete normal, activated B-cells from peripheral blood mononuclear cell (PBMC) cultures was superior to that of the Fc-optimized monospecific antibody. This antibody in turn was more effective than its nonoptimized variant. Moreover, the bispecific antibody was the only reagent capable of significantly suppressing antibody production in vitro. Our findings imply that the bispecific CD20×CD95-antibody might become a new, prototypical reagent for the treatment of B-cell-mediated autoimmune disease. PMID:26581163

  13. Targeting CD138-/CD20+ Clonogenic Myeloma Precursor Cells Decreases These Cells and Induces Transferable Antimyeloma Immunity.

    Science.gov (United States)

    Lum, Lawrence G; Thakur, Archana; Kondadasula, Sri Vidya; Al-Kadhimi, Zaid; Deol, Abhinav; Tomaszewski, Elyse N; Yano, Hiroshi; Schalk, Dana L; Ayash, Lois; Zonder, Jeffrey A; Uberti, Joseph P; Abidi, Muneer H; Ratanatharathorn, Voravit

    2016-05-01

    This phase Ib clinical trial evaluated whether pretargeting of CD20(+) clonogenic myeloma precursor cells (CMPCs) with anti-CD3 × anti-CD20 bispecific antibody-armed T cells (BATs) before autologous stem cell transplantation (SCT) in patients with standard-risk and high-risk multiple myeloma would induce antimyeloma immunity that could be detected and boosted after SCT. All 12 patients enrolled in this study received 2 BATs infusions before SCT, and 4 patients received a booster infusion of BATs after SCT. Pretargeting CD138(-)/CD20(+) CMPCs with BATs before SCT was safe and reduced levels of CMPCs by up to 58% in the postinfusion bone marrow in patients who remained in remission. Four of 5 patients who remained in remission had a >5-fold increase in IFN-γ enzyme-linked immunospot responses. SOX2 antibody increased after BATs infusions and persisted after SCT. The median anti-SOX2 level at 3 months after SCT was 28.1 ng/mL (range, 4.6 to 256 ng/mL) in patients who relapsed and 46 ng/mL (range, 28.3 to 73.3 ng/mL) in patients who remained in remission. The immune correlates suggest that infusions of targeted T cells given before SCT were able to reduce CMPC levels and induced cellular and humoral antimyeloma immunity that could be transferred and boosted after SCT. PMID:26827660

  14. The identification of irreversible rituximab-resistant lymphoma caused by CD20 gene mutations

    International Nuclear Information System (INIS)

    C-terminal mutations of CD20 constitute part of the mechanisms that resist rituximab therapy. Most CD20 having a C-terminal mutation was not recognized by L26 antibody. As the exact epitope of L26 has not been determined, expression and localization of mutated CD20 have not been completely elucidated. In this study, we revealed that the binding site of L26 monoclonal antibody is located in the C-terminal cytoplasmic region of CD20 molecule, which was often lost in mutated CD20 molecules. This indicates that it is difficult to distinguish the mutation of CD20 from under expression of the CD20 protein. To detect comprehensive CD20 molecules including the resistant mutants, we developed a novel monoclonal antibody that recognizes the N-terminal cytoplasm region of CD20 molecule. We screened L26-negative cases with our antibody and found several mutations. A rituximab-binding analysis using the cryopreserved specimen that mutation was identified in CD20 molecules indicated that the C-terminal region of CD20 undertakes a critical role in presentation of the large loop in which the rituximab-binding site locates. Thus, combination of antibodies of two kinds of epitope permits the identification of C-terminal CD20 mutations associated with irreversible resistance to rituximab and may help the decision of the treatment strategy

  15. Consistent, multi-instrument single tube quantification of CD20 in antibody bound per cell based on CD4 reference.

    Science.gov (United States)

    Degheidy, Heba; Abbasi, Fatima; Mostowski, Howard; Gaigalas, Adolfas K; Marti, Gerald; Bauer, Steven; Wang, Lili

    2016-03-01

    Detecting changes in the expression levels of cell antigens could provide critical information for the diagnosis of many diseases, for example, leukemia, lymphoma, and immunodeficiency diseases, detecting minimal residual disease, monitoring immunotherapies and discovery of meaningful clinical disease markers. One of the most significant challenges in flow cytometry is how to best ensure measurement quality and generate consistent and reproducible inter-laboratory and intra-laboratory results across multiple cytometer platforms and locations longitudinally over time. In a previous study, we developed a procedure for instrument standardization across four different flow cytometer platforms from the same manufacturer. CD19 quantification was performed on three of the standardized instruments relative to CD4 expression on T lymphocytes with a known amount of antibody bound per cell (ABC) as a quantification standard. Consistent and reliable measures of CD19 expression were obtained independent of fluorochrome used demonstrating the utility of this approach. In the present investigation, quantification of CD20 relative to CD4 reference marker was implemented within a single tube containing both antibodies. Relative quantification of CD20 was performed using anti-CD20 antibody (clone L27) in three different fluorochromes relative to anti-CD4 antibody (clone SK3). Our results demonstrated that cell surface marker quantification can be performed robustly using the single tube assay format with novel gating strategies. The ABC values obtained for CD20 expression levels using PE, APC, or PerCP Cy5.5 are consistent over the five different instrument platforms for any given apparently healthy donor independent of the fluorochrome used. © 2015 International Clinical Cytometry Society. PMID:26013593

  16. Randomized Phase II Trial Comparing Obinutuzumab (GA101) With Rituximab in Patients With Relapsed CD20(+) Indolent B-Cell Non-Hodgkin Lymphoma

    DEFF Research Database (Denmark)

    Sehn, L. H.; Goy, A.; Offner, F. C.;

    2015-01-01

    Purpose Obinutuzumab (GA101), a novel glycoengineered type II anti-CD20 monoclonal antibody, demonstrated responses in single-arm studies of patients with relapsed/refractory non-Hodgkin lymphoma. This is the first prospective, randomized study comparing safety and efficacy of obinutuzumab with r...

  17. CD20 antibody primes B lymphocytes for type I interferon production.

    Directory of Open Access Journals (Sweden)

    Dongsheng Xu

    Full Text Available CD20 is a B cell surface marker that is expressed in various stages in B lymphocytes and certain lymphomas. Clinical administration of CD20 antibody, such as rituximab, is used widely to treat human B-cell lymphomas and other diseases. However, CD20 antibody failed to treat systemic lupus erythematosus (SLE or lupus. The reason for the failure is currently unknown. Type I interferons (IFN are a major component for the host innate immunity, and a key pathogenic factor in lupus. We found that CD20 antibody potentiated human B cells for its production of IFNs in vitro. This function was specific to CD20-expressing cells and the potentiation function seems to be instant. In addition, ectopic expression of CD20 in non-B-lymphocytes increased the IFN promoter reporter activities. Because IFNs are a key pathogenic factor in lupus, our data suggest that, in the presence of virus infection, the CD20-antibody-mediated enhancement of IFN production might be related to its failure in lupus treatments. This work may provide new insights for CD20-Ab therapeutic applications.

  18. Simple Synthesis, Halogenation, and Rearrangement of closo-1,6-C2B8H10

    Czech Academy of Sciences Publication Activity Database

    Bakardjiev, Mario; Štíbr, Bohumil; Holub, Josef; Padělková, Z.; Růžička, A.

    2015-01-01

    Roč. 34, č. 2 (2015), s. 450-454. ISSN 0276-7333 R&D Projects: GA ČR(CZ) GAP207/11/0705 Institutional support: RVO:61388980 Keywords : MAGNETIC-RESONANCE-SPECTROSCOPY * ORGANOELEMENTAL DERIVATIVES * CLOSO-BORANES * CARBORANES * 5,6-DICARBA-NIDO-DECABORANE(12) Subject RIV: CA - Inorganic Chemistry Impact factor: 4.126, year: 2014

  19. T Cells Expressing CD19/CD20 Bispecific Chimeric Antigen Receptors Prevent Antigen Escape by Malignant B Cells.

    Science.gov (United States)

    Zah, Eugenia; Lin, Meng-Yin; Silva-Benedict, Anne; Jensen, Michael C; Chen, Yvonne Y

    2016-06-01

    The adoptive transfer of T cells expressing anti-CD19 chimeric antigen receptors (CARs) has shown remarkable curative potential against advanced B-cell malignancies, but multiple trials have also reported patient relapses due to the emergence of CD19-negative leukemic cells. Here, we report the design and optimization of single-chain, bispecific CARs that trigger robust cytotoxicity against target cells expressing either CD19 or CD20, two clinically validated targets for B-cell malignancies. We determined the structural parameters required for efficient dual-antigen recognition, and we demonstrate that optimized bispecific CARs can control both wild-type B-cell lymphoma and CD19(-) mutants with equal efficiency in vivo To our knowledge, this is the first bispecific CAR capable of preventing antigen escape by performing true OR-gate signal computation on a clinically relevant pair of tumor-associated antigens. The CD19-OR-CD20 CAR is fully compatible with existing T-cell manufacturing procedures and implementable by current clinical protocols. These results present an effective solution to the challenge of antigen escape in CD19 CAR T-cell therapy, and they highlight the utility of structure-based rational design in the development of receptors with higher-level complexity. Cancer Immunol Res; 4(6); 498-508. ©2016 AACRSee related Spotlight by Sadelain, p. 473. PMID:27059623

  20. Preparation, quality control and biodistribution studies of [67Ga]-DOTA-anti-CD20

    International Nuclear Information System (INIS)

    Rituximab was successively labeled with [67Ga]-gallium chloride. The macrocyclic bifunctional chelating agent, N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) was prepared at 25 C using DOTA, N-hydroxy succinimide (NHS) in CH2Cl2. DOTA-Rituximab was obtained by the addition of 1 mL of a Rituximab pharmaceutical solution (5 mg/mL, in phosphate buffer, pH=7.8) to a glass tube pre-coated with DOTA-NHS (0.01-0.1 mg) at 25 C with continuous mild stirring for 15 h. Radiolabeling was performed at 37 C in 3 h. Radio-thin layer chromatography showed an overall radiochemical purity of 90%-95% at optimized conditions (specific activity = 30 GBq/mg, labeling efficacy; 82%). The final isotonic 67Ga-DOTA-rituximab complex was checked by gel electrophoresis for radiolysis. Radio-TLC was performed to ensure that only one species was present after filtration through a 0.22 μm filter. Preliminary biodistribution studies in normal rat model performed to determine complex distribution of the radioimmunoconjugate up to 28 h. (orig.)

  1. Two courses of rituximab (anti-CD20 monoclonal antibody) for recalcitrant pemphigus vulgaris

    DEFF Research Database (Denmark)

    Faurschou, A.; Gniadecki, R.

    2008-01-01

    Background Pemphigus vulgaris (PV) is a severe autoimmune blistering disease involving the skin and mucous membranes. The response to therapy varies greatly amongst patients and treatment may be challenging. Rituximab is a chimeric monoclonal antibody that selectively targets cell surface antigen...

  2. Development of [64Cu]-DOTA-anti-CD20 for targeted therapy

    International Nuclear Information System (INIS)

    Copper-64 was produced as a by-product of 55Co via 64Ni(p,n)64Cu by 15 MeV proton bombardment of natNi resulting in a thick target yield of 5.31 MBq/μAh (143.5 μCi/μAh) and a radiochemical separation yield of 95% (radionuclide purity >97% after 25 hours of bombardment). Rituximab was successively labeled with [64Cu]-CuCl2. N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) was prepared at 25 deg C using DOTA and N-hydroxy succinimide (NHS) in CH2Cl2 followed by the addition of 1 ml of a Rituximab pharmaceutical solution. Radiolabeling was performed at 37 deg C in 3 hours. Radio thin-layer chromatography showed an overall radiochemical purity of 90-95% at optimized conditions (specific activity=30 GBq/mg, labeling efficacy; 82%) using various chromatography systems. The final isotonic 64Cu- DOTA-Rituximab complex was passed through a 0.22 μm filter and checked by gel electrophoresis for radiolysis control. Stability of the final product was checked in the formulation and in presence of human serum at 37 deg C. (author)

  3. The Role of CD16+, CD56+, NK (CD16+/CD56+ and B CD20+ Cells in the Outcome of Pregnancy in Women with Recurrent Spontaneous Abortion

    Directory of Open Access Journals (Sweden)

    Mehri Ghafourian

    2015-01-01

    Full Text Available Objectives: Recurrent Spontaneous Abortion (RSA is the most common complication of pregnancy. It is considered as one of the most important issues of reproduction in the world. RSA is defined as having three or more miscarriages in the first trimester of pregnancy. Increase in peripheral blood lymphocytes may be associated with abortion; therefore,the study was aimed to investigate and compare the peripheral blood CD16+, CD56+, NK(CD16+/CD56+ and B CD20+ cells populations in diagnosis and on pregnancy outcome in women with abortion. Materials and Methods: In this case-control study, 25 non-pregnant women with at least 3 abortions without obvious reason and 25 non-pregnant women with a living child without history of previous abortion participated. Using monoclonal antibodies anti (CD16, CD56 and CD20 and flow cytometry method, the percentage of cells with these markers was determined. Data analysis was performed by with SPSS 15 software and T-test. Results: CD16+, CD56+ and NK (CD16+/CD56+ cells significantly increased in women with RSA compared with control group (P≤0.05 but there were no significant differences in the percentage of B CD20+ cells between the experimental and control groups (P>0.05. Conclusion: According to the results of the present study, increased percentage of NK cells may be considered as a risk factor for RSA but involvement and the role of B CD20+ lymphocytes in RSA cannot be confirmed; however, in regard to important role of B and NK cell in the management of the immune responses, more studies are required to understand the behavior of these cells in the different stages of pregnancy more efficiently

  4. Levels of expression of CD19 and CD20 in chronic B cell leukaemias.

    Science.gov (United States)

    Ginaldi, L; De Martinis, M; Matutes, E; Farahat, N; Morilla, R; Catovsky, D

    1998-01-01

    AIMS: To investigate whether the antigen levels of the B cell lineage markers CD19 and CD20 can distinguish between normal and neoplastic B cells or characterise distinct expression patterns among the chronic B cell leukaemias. METHODS: Peripheral blood cells from 70 patients with B cell disorders and 17 healthy donors were analysed by quantitative flow cytometry. Direct immunofluorescence staining was performed with phycoerythrin conjugated CD19 and CD20 monoclonal antibodies. Standard microbeads with different capacities to bind mouse immunoglobulins were used to convert the mean fluorescence intensity (MFI) values into number of antigen molecules/cell, expressed as antibody binding capacity (ABC). RESULTS: CD19 and CD20 ABC values in leukaemic B cells differed from those of normal blood B lymphocytes. The results identified distinct profiles of CD19 and CD20 expression in the various types of B cell leukaemias. In all leukaemias studied except hairy cell leukaemia (HCL), CD19 expression was significantly lower than the mean (SD) value in normal B cells (22 (7) x 10(3) molecules/cell), as follows: chronic lymphocytic leukaemia (CLL), 13 (7) x 10(3); B prolymphocytic leukaemia (B-PLL), 16 (9) x 10(3); splenic lymphoma with villous lymphocytes (SLVL), 15 (11) x 10(3); mantle cell lymphoma (MCL), 10 (7) x 10(3). In HCL there was strong CD19 expression (38 (16) x 10(3)). In contrast, the level of expression of membrane CD20 was higher than the mean (SD) value in normal B cells (94 (16) x 10(3) molecules/cell) in MCL (123 (51) x 10(3)); B-PLL (129 (47) x 10(3)); SLVL (167 (72) x 10(3)); and HCL (312 (110) x 10(3)); while it was significantly lower (65 (11) x 10(3)) in CLL compared with normal B cells and the other B cell leukaemias. CONCLUSIONS: Quantitative determination of CD19 and CD20 may provide useful diagnostic information for the study of B lymphoproliferative disorders. PMID:9708202

  5. Galectin-1 drives lymphoma CD20 immunotherapy resistance: validation of a preclinical system to identify resistance mechanisms.

    Science.gov (United States)

    Lykken, Jacquelyn M; Horikawa, Mayuka; Minard-Colin, Veronique; Kamata, Masahiro; Miyagaki, Tomomitsu; Poe, Jonathan C; Tedder, Thomas F

    2016-04-14

    Non-Hodgkin lymphoma (NHL) is the most commonly diagnosed hematologic cancer of adults in the United States, with the vast majority of NHLs deriving from malignant B lymphocytes that express cell surface CD20. CD20 immunotherapy (rituximab) is widely used to treat NHL, even though the initial effectiveness of rituximab varies widely among patients and typically wanes over time. The mechanisms through which lymphomas initially resist or gain resistance to immunotherapy are not well established. To address this, a preclinical mouse model system was developed to comprehensively identify lymphoma transcriptomic changes that confer resistance to CD20 immunotherapy. The generation of spontaneous primary and familial lymphomas revealed that sensitivity to CD20 immunotherapy was not regulated by differences in CD20 expression, prior exposure to CD20 immunotherapy, or serial in vivo passage. An unbiased forward exome screen of these primary lymphomas was used to validate the utility of this expansive lymphoma cohort, which revealed that increased lymphoma galectin-1 (Gal-1) expression strongly correlated with resistance to immunotherapy. Genetically induced lymphoma Gal-1 expression ablated antibody-dependent lymphoma phagocytosis in vitro and lymphoma sensitivity to CD20 immunotherapy in vivo. Human NHLs also express elevated Gal-1 compared with nonmalignant lymphocytes, demonstrating the ability of this preclinical model system to identify molecular targets that could be relevant to human therapy. This study therefore established a powerful preclinical model system that permits the comprehensive identification of the dynamic lymphoma molecular network that drives resistance to immunotherapy. PMID:26888257

  6. Ocrelizumab, a humanized monoclonal antibody against CD20 for inflammatory disorders and B-cell malignancies.

    Science.gov (United States)

    Hutas, Gabor

    2008-11-01

    Biogen Idec Inc, Genentech Inc, Roche Holding AG and Chugai Pharmaceutical Co Ltd are developing ocrelizumab, a humanized mAb against CD20, for the potential treatment of inflammatory disorders and B-cell malignancies. Ocrelizumab is undergoing phase III clinical trials for rheumatoid arthritis and lupus nephritis, and phase II trials for multiple sclerosis and hematological cancer. Previously, ocrelizumab was also being developed for the treatment of systemic lupus erythematosus (SLE) and neuromyelitis optica; however, development for SLE has been discontinued. No development has been reported for neuromyelitis optica and as of January 2007, this indication had been removed from the company pipeline. PMID:18951300

  7. Conventional and Pretargeted Radioimmunotherapy Using Bismuth-213 to Target and Treat Non-Hodgkin Lymphomas Expressing CD20: A Preclinical Model toward Optimal Consolidation Therapy to Eradicate Minimal Residual Disease

    International Nuclear Information System (INIS)

    Radioimmunotherapy (RIT) with α-emitting radionuclides is an attractive approach for the treatment of minimal residual disease (MRD) because the short path lengths and high energies of α-particles produce optimal cytotoxicity at small target sites while minimizing damage to surrounding normal tissues. Pretargeted RIT (PRIT) using antibody-streptavidin (Ab-SA) constructs and radiolabeled biotin allows rapid, specific localization of radioactivity at tumor sites, making it an optimal method to target α-emitters with short half-lives, such as bismuth-213 (213Bi). Athymic mice bearing Ramos lymphoma xenografts received anti-CD20 1F5(scFv)4SA fusion protein (FP), followed by a dendrimeric clearing agent and (213Bi)DOTA-biotin. After 90 min, tumor uptake for 1F5(scFv)4SA was 16.5 ± 7.0 % injected dose per gram (ID/g) compared with 2.3 ± 0.9 % ID/g for the control FP. Mice treated with anti-CD20 PRIT and 600 (micro)Ci (213Bi)DOTA-biotin exhibited marked tumor growth delays compared to controls (mean tumor volume 0.01 ± 0.02 vs. 203.38 ± 83.03 mm3 after 19 days, respectively). The median survival for the 1F5(scFv)4SA group was 90 days compared to 23 days for the control FP (p 213Bi-labeled anti-CD20 PRIT.

  8. CD20阳性淋巴细胞在慢性移植肾肾病组织中浸润的意义%Significance of CD20-positive lymphocytes infiltrating in renal allograft biopsies with chronic allograft nephropathy

    Institute of Scientific and Technical Information of China (English)

    胡建敏; 赵明; 郭颖; 陈桦; 李民

    2012-01-01

    目的 探讨肾移植术后慢性移植物肾病(CAN)组织CD20阳性淋巴细胞浸润的临床意义及其机制.方法 选择肾移植术后2年内活检证实为CAN病例为研究对象,应用免疫组织化学方法检测补体C4d的沉积和CD20阳性淋巴细胞在移植肾组织的浸润,同时分析临床随访资料.结果 人选CAN病例44例,其中CD20阳性淋巴细胞浸润13例(29.5%),CD20阴性为31例(70.5%),移植肾组织不同病理分级者中CD20阳性者所占比例的差异无统计学意义(P>0.05).44例中,12例(27.3%)出现管周毛细血管内皮细胞(PTC)补体C4d的线性沉积,CD20阳性和阴性者中补体C4d表达阳性率的差异无统计学意义(P>0.05).确诊为CAN时移植肾组织CD20为阴性和阳性者的肾功能分别为( 140.8±22.0)μmol/L和(183.5±25.5) μmol/L(P<0.01),1年后分别为(165.6±37.6)μmol/L和(242.2±59.1 )μmol/L(P<0.01).结论 CD20阳性淋巴细胞在移植肾组织的浸润与移植物的预后相关,其机制可能不是通过慢性体液免疫反应.%Objective To investigate the action mechanism of CD20 lymphocyte infiltration in the renal allograft biopsy with chronic allograft nephropathy (CAN).Methods CAN cases confirmed by renal biopsy within 2 years after renal transplantation served as study subjects. By using immunohistochemistry,the deposition of C4d and the CD20-positive lymphocytes infiltration in the renal grafts were examined.The clinical follow-up data were analyzed.Results Forty-four cases of CAN were enrolled in the study, including 13 cases (29.5% ) of CD20-positive lymphocytes infiltration,and 31 cases (70.5% ) of CD20-negative lymphocytes infiltration. CD20-positive lymphocytes in biopsy showed nodular and scattered lymphocytes infiltration.There were 5 (26.3%)cases of CAN Ⅰ,4 cases (25.0%) of CAN Ⅱ,and 4 (44.4%) of CAN Ⅲ in CD20-positive group.There was no statistically significant difference between the only CAN group and CAN with AR group in

  9. The study of conjugation of anti-CD20 monoclonal antibody for labeling with metallic or lanthanides radionuclides; Estudo de conjugacao do anticorpo anti-CD20 para marcacao com radionuclideos metalicos ou lantanideos

    Energy Technology Data Exchange (ETDEWEB)

    Akanji, Akinkunmi Ganiyu

    2012-07-01

    Lymphomas are malignancies or cancers that start from the malign transformation of a lymphocyte in the lymphatic system. Generally, lymphomas start from the lymph nodes or from the agglomeration of the lymphatic tissues, organs like stomach, intestines, in some cases it can involve the bone marrow and the blood, it can also disseminate to other organs. Lymphomas are divided in two major categories: Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). Patient with NHL are generally treated with radiotherapy alone or combined with immunotherapy using monoclonal antibody rituximab (MabThera Registered-Sign ). Currently, monoclonal antibodies (Acm) conjugated with bifunctional chelate agents and radiolabeled with metallic or lanthanides radionuclides are a treatment reality for patients with NHL by the principle of radioimmunotherapy (RIT). This study focused on the conditions of conjugation of Acm rituximab (MabThera Registered-Sign ) with bifunctional chelating agents DOTA and DTPA. Various parameters were studied: method of Acm purification, conditions of Acm conjugation, the method for determination of number of chelate agent coupled to the Acm, method for purification of the conjugated antibody Acm, conditions of labeling of the conjugated antibody with lutetium-177, method of purification of the radiolabeled immuno conjugate, method of radiochemical purity (RP), specific binding in vitro Raji cells (Human Burkitt) and biological distribution performed in normal Balb-c mouse. The three methodologies employed in pre-purification of Acm (dialysis, size exclusion chromatograph and dial filtration) demonstrated to be efficient; they provided sample recovery exceeding 90%. However, the methodology of dial filtration presents minimal sample loss, and gave the final recovery of the sample in micro liters; thereby facilitating sample use in subsequent experiments. Numbers of chelators attached to the Acm molecule was proportional to the molar ratio studied. When we evaluated the influence of different conditions of conjugation in the number of chelators bounded to the Acm, no notable differences were observed. The RP < 80% was observed in all the methods applied. Purification of the conjugated antibody by dialysis and size exclusion chromatography demonstrated to be efficient, but deficient in terms of high sample volume recovered. The dial filtration was efficient and practical besides it provided sample recovery in micro liters. The optimized conditions for purification of the conjugated antibody preserved the protein integrity. When the conjugated Acm was labeled with lutetium-177 a product with low RP was observed in all molar ratios studied. The methodology used in the control of RP of the radiolabeled antibody was efficient in the discrimination of radiochemical species presented in the reaction mixture. The method of purification of the conjugated antibody applied, proved to be efficient in separating the labeled antibody from free lutetium. The results of specific cell binding studies performed with the conjugated Acm showed high percentage of nonspecific binding. Biological distribution in normal Balb-c mice demonstrated higher uptake of the labeled antibody by kidney and liver. The relatively high uptake observed by bone tissue may indicate some in vivo instability. However, results obtained in this study showed to be close related in literature. Thus, these data confirm the potential of antibody conjugated to DOTA and DTPA labeled with lutetium-177 for radioimmunotherapy of non-Hodgkin lymphoma. (author)

  10. Comparative Efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

    Energy Technology Data Exchange (ETDEWEB)

    Frost, Sophia; Frayo, Shani; Miller, Brian W.; Orozco, Johnnie J.; Booth, Garrett C.; Hylarides, Mark; Lin, Yukang; Green, Damian J.; Gopal, Ajay K.; Pagel, John M.; Back, Tom; Fisher, Darrell R.; Press, Oliver W.

    2015-03-01

    Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice.

  11. The study of conjugation of anti-CD20 monoclonal antibody for labeling with metallic or lanthanides radionuclides

    International Nuclear Information System (INIS)

    Lymphomas are malignancies or cancers that start from the malign transformation of a lymphocyte in the lymphatic system. Generally, lymphomas start from the lymph nodes or from the agglomeration of the lymphatic tissues, organs like stomach, intestines, in some cases it can involve the bone marrow and the blood, it can also disseminate to other organs. Lymphomas are divided in two major categories: Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). Patient with NHL are generally treated with radiotherapy alone or combined with immunotherapy using monoclonal antibody rituximab (MabThera®). Currently, monoclonal antibodies (Acm) conjugated with bifunctional chelate agents and radiolabeled with metallic or lanthanides radionuclides are a treatment reality for patients with NHL by the principle of radioimmunotherapy (RIT). This study focused on the conditions of conjugation of Acm rituximab (MabThera®) with bifunctional chelating agents DOTA and DTPA. Various parameters were studied: method of Acm purification, conditions of Acm conjugation, the method for determination of number of chelate agent coupled to the Acm, method for purification of the conjugated antibody Acm, conditions of labeling of the conjugated antibody with lutetium-177, method of purification of the radiolabeled immuno conjugate, method of radiochemical purity (RP), specific binding in vitro Raji cells (Human Burkitt) and biological distribution performed in normal Balb-c mouse. The three methodologies employed in pre-purification of Acm (dialysis, size exclusion chromatograph and dial filtration) demonstrated to be efficient; they provided sample recovery exceeding 90%. However, the methodology of dial filtration presents minimal sample loss, and gave the final recovery of the sample in micro liters; thereby facilitating sample use in subsequent experiments. Numbers of chelators attached to the Acm molecule was proportional to the molar ratio studied. When we evaluated the influence of different conditions of conjugation in the number of chelators bounded to the Acm, no notable differences were observed. The RP < 80% was observed in all the methods applied. Purification of the conjugated antibody by dialysis and size exclusion chromatography demonstrated to be efficient, but deficient in terms of high sample volume recovered. The dial filtration was efficient and practical besides it provided sample recovery in micro liters. The optimized conditions for purification of the conjugated antibody preserved the protein integrity. When the conjugated Acm was labeled with lutetium-177 a product with low RP was observed in all molar ratios studied. The methodology used in the control of RP of the radiolabeled antibody was efficient in the discrimination of radiochemical species presented in the reaction mixture. The method of purification of the conjugated antibody applied, proved to be efficient in separating the labeled antibody from free lutetium. The results of specific cell binding studies performed with the conjugated Acm showed high percentage of nonspecific binding. Biological distribution in normal Balb-c mice demonstrated higher uptake of the labeled antibody by kidney and liver. The relatively high uptake observed by bone tissue may indicate some in vivo instability. However, results obtained in this study showed to be close related in literature. Thus, these data confirm the potential of antibody conjugated to DOTA and DTPA labeled with lutetium-177 for radioimmunotherapy of non-Hodgkin lymphoma. (author)

  12. CD20-positive primary gastric T-cell lymphoma poorly responding to initial treatment with rituximab plus CHOP, and a literature review.

    Science.gov (United States)

    Kakinoki, Yasutaka; Hashiguchi, Junichi; Ishio, Takashi; Chiba, Koji; Niino, Daisuke; Ohshima, Koichi

    2015-12-01

    There have been rare reported cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) that co-expressed CD20. A 44-year-old Japanese male was initially misdiagnosed as CD20-positive diffuse large B-cell lymphoma with a background of reactive CD3-positive T-cells in the stomach. After four cycles of R-CHOP [rituximab plus cyclophosphamide (CY), doxorubicin, vincristine, and prednisolone (PSL)], total gastrectomy with regional lymph node dissection was performed due to the poor response to R-CHOP. A final diagnosis of CD20-positive primary gastric PTCL-NOS was made based on the immunohistochemical, flow cytometric, and molecular genetic findings. In the present case, CD20 immunostaining for T-cell lymphoma cells in tumor tissue varied; in a large part, these were strong to weak-positive, and in some parts, absent. We additionally reviewed the literature focusing on CD20-positive PTCL-NOS treated with rituximab. The administration of rituximab has been performed as an initial treatment in 11 cases, including the case reported here. The response was good in cases with high expression of CD20, while it was poor in cases with variable intensity in CD20 staining, which is consistent with our experience in the present case. The efficacy of rituximab may be associated with intensity of CD20 expression in T cells and its homogeneity in the tumor tissue. PMID:26251099

  13. CD20 antigen expression by lymphoma cells in lung allograft recipients is associated with higher remission rate and superior survival: A study on heart and lung transplant recipients

    Directory of Open Access Journals (Sweden)

    Aghil Gholipour-Shoiili

    2014-01-01

    Full Text Available Post-transplant lymphoproliferative disorders (PTLD are one of the fatal complications of transplantation, and there is scarcity of data on the relevance of antigen expression by tumor cells in PTLD. In the current study, we aimed to investigate the potential effects of CD20 antigen expression by PTLD lesions developing in heart/lung transplant recipients. A comprehensive search was performed for reports indicating CD20 antigen tests in PTLD lesions developing in heart and/or lung transplant recipients. For data accumulation, we developed a standard questionnaire and data of patients presented in different published reports were entered into it. Finally, data from 26 previously published reports from different centers around the world were included in the analysis. CD20-positive PTLD lesions are significantly more likely to be of the B cell type (P = 0.006. PTLD in patients with a CD20-positive test represented relevantly shorter time from transplantation to PTLD, although it did not reach a significance level (P = 0.08. At the last follow-up, 53% patients were dead. Survival analysis showed no prognosis difference regarding CD20 test. When data were reanalyzed separately for heart and lung transplant recipients, lung recipients developing PTLD with a CD20-positive test were significantly more likely to represent remission episodes (P = 0.03, and also represented a significantly better outcome than CD20-negative PTLD patients (P = 0.04. CD20-positive PTLD lesions in heart/lung recipients are more likely of the B cell type and develop PTLD lesions earlier than their CD20-negative counterparts. Lung recipients developing CD20-positive PTLD lesions represented higher remission rates and better outcome. Further studies with prospective follow-up of patients are needed for confirming our findings.

  14. CD20 mutations involving the rituximab epitope are rare in diffuse large B-cell lymphomas and are not a significant cause of R-CHOP failure

    OpenAIRE

    Johnson, Nathalie A.; Leach, Stephen; Woolcock, Bruce; deLeeuw, Ronald J; Bashashati, Ali; Sehn, Laurie H.; Connors, Joseph M; Chhanabhai, Mukesh; Brooks-Wilson, Angela; Gascoyne, Randy D.

    2009-01-01

    The findings of this study indicate that CD20 mutations nvolving the rituximab epitope are rare in both de novo and relapsed diffuse large B-cell lymphoma, and do not represent a significant cause of R-CHOP resistance.

  15. Safety and efficacy of intrathecal rituximab in children with B cell lymphoid CD20+ malignancies: An international retrospective study.

    Science.gov (United States)

    Ceppi, Francesco; Weitzman, Sheila; Woessmann, Wilhelm; Davies, Kimberly; Lassaletta, Alvaro; Reismüller, Bettina; Mellgren, Karin; Uyttebroeck, Anne; Maia, Iris; Abdullah, Shaker; Miakova, Natasha; Glaser, Darryl; Cohn, Richard; Abla, Oussama; Attarbaschi, Andishe; Alexander, Sarah

    2016-05-01

    Central nervous system (CNS) involvement in patients with mature B non-Hodgkin lymphoma, post-transplantation proliferative disorder and acute lymphoblastic leukemia confers a significantly inferior prognosis as compared to patients without CNS disease. Intrathecal (IT) or intraventricular administration of rituximab is an option for this group of patients. We report 25 children with CNS involvement of CD20+ B lymphoid malignancies who received in total 163 IT/intraventricular rituximab doses. The median number of doses received by each patient was 6, with a median dose of 25 mg. The most common adverse events were Grades 1 and 2 peripheral neuropathies in five patients (20%), allergy in two patients, and headache in two patients. These events were self-limited, occurring in the 48 hours after treatment and resolving within 24 hr. Three patients presented with more severe though transient side effects, one with a Grade III neuropathy and two with seizure. Eighteen patients (72%) of those treated with IT/intraventricular rituximab, with or without other CNS directed treatment, achieved a CNS remission. This case series suggests that IT/intraventricular rituximab has therapeutic efficacy and relatively limited toxicity. Prospective trials of IT/intraventricular rituximab for patients with CNS involvement of CD20 + B lymphoid malignancies are warranted. Am. J. Hematol. 91:486-491, 2016. © 2016 Wiley Periodicals, Inc. PMID:26872652

  16. CD20-negative de novo diffuse large B-cell lymphoma in HIV-negative patients: A matched case-control analysis in a single institution

    Directory of Open Access Journals (Sweden)

    Li Ya-Jun

    2012-05-01

    Full Text Available Abstract Background HIV-negative, CD20-negative de novo diffuse large B-cell lymphoma (DLBCL patients has rarely been reported. To elucidate the nature of this entity, we retrospectively reviewed the data of 1,456 consecutive de novo DLBCL patients who were treated at Sun Yat-Sen University Cancer Center between January 1999 and March 2011. Methods The pathologic characteristics of CD20-negative patients, clinical features, response to initial treatment, and outcomes of 28 patients with available clinical data (n = 21 were reviewed. Then, a matched case-control (1:3 analysis was performed to compare patients with CD20-negative and -positive DLBCL. Results The median age of the 28 CD20-negative DLBCL patients was 48 years, with a male-female ratio of 20:8. Seventeen of 22 (77.3% CD20-negative DLBCL cases were of the non-germinal centre B-cell (non-GCB subtype. High Ki67 expression (≥80%, an index of cell proliferation, was demonstrated in 17 of 24 (70.8% cases. Extranodal involvement (≥ 1 site was observed in 76.2% of the patients. Following initial therapy, 9 of 21 (42.9% cases achieved complete remission, 4 (19% achieved partial remission, 1 (4.8% had stable disease, and 7 (33.3% had disease progression. The median overall survival was 23 months. The 3-year progression-free survival (PFS and overall survival (OS rates were 30.5% and 35%, respectively. A matched case-control analysis showed that patients with CD20-negative and -positive DLBCL did not exhibit a statistically significant difference with respect to the main clinical characteristics (except extranodal involvement, whereas the patients with CD20-positive DLBCL had a better survival outcome with 3-year PFS (P = 0.008 and OS (P = 0.008 rates of 52% and 74.1%, respectively. Conclusions This study suggests that HIV-negative, CD20-negative de novo DLBCL patients have a higher proportion of non-GCB subtype, a higher proliferation index, more frequent extranodal involvement, a poorer

  17. Positron Emission Tomography of (64)Cu-DOTA-Rituximab in a Transgenic Mouse Model Expressing Human CD20 for Clinical Translation to Image NHL

    DEFF Research Database (Denmark)

    Natarajan, Arutselvan; Gowrishankar, Gayatri; Nielsen, Carsten Haagen;

    2012-01-01

    PURPOSE: This study aims to evaluate (64)Cu-DOTA-rituximab (PETRIT) in a preclinical transgenic mouse model expressing human CD20 for potential clinical translation. PROCEDURES: (64)Cu was chelated to DOTA-rituximab. Multiple radiolabeling, quality assurance, and imaging experiments were performed....... The human CD20 antigen was expressed in B cells of transgenic mice (CD20TM). The mice groups studied were: (a) control (nude mice, n¿=¿3) that received 7.4 MBq/dose, (b) with pre-dose (CD20TM, n¿=¿6) received 2 mg/kg pre-dose of cold rituximab prior to PETRIT of 7.4 MBq/dose, and (c) without pre......-dose (CD20TM, n¿=¿6) PETRIT alone received 7.4 MBq/dose. Small animal PET was used to image mice at various time points (0, 1, 2, 4, 24, 48, and 72 h). The OLINDA/EXM software was used to determine the human equivalent dose for individual organs. RESULTS: PETRIT was obtained with a specific activity of 545...

  18. Bone marrow infiltration of CD20-negative follicular lymphoma after rituximab therapy: a histological mimicker of hematogones and B-cell acute lymphoblastic leukemia/lymphoma

    Science.gov (United States)

    Matsuda, Ikuo; Hirota, Seiichi

    2015-01-01

    Rituximab is a monoclonal antibody against CD20. Rituximab combined with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy, termed R-CHOP, have improved the overall survival of patients with B-cell lymphoma in comparison with that of CHOP therapy. However, as with other molecularly-targeted therapies, resistance to rituximab could emerge sooner or later after rituximab administration. A number of mechanisms for rituximab resistance have been proposed, including downregulation of CD20 protein expression. Differential diagnosis of B-cell proliferation with reduced or lost CD20 expression includes not only B-cell lymphomas with CD20 downregulation, but also other tumorous and non-tumorous lesions. These include precursor B-cell neoplasms such as B acute lymphoblastic leukemia/lymphoblastic lymphoma (B-ALL/LBL) and hematogones, a normal precursor B-cell proliferation during regeneration of hematopoiesis, typically observed following bone marrow suppression by chemotherapy. It is important to distinguish these possibilities because distinct therapies are required for each. In this paper, we report a case where bone marrow infiltration of follicular lymphoma histopathologically mimicked hematogones or B-ALL/LBL when CD20 expression was downregulated in follicular lymphoma after R-CHOP therapy. PMID:26464748

  19. Anti-lymphoma efficacy comparison of anti-Cd20 monoclonal antibody-targeted and non-targeted star-shaped polymer-prodrug conjugates

    Czech Academy of Sciences Publication Activity Database

    Lidický, Ondřej; Janoušková, Olga; Strohalm, Jiří; Alam, M.; Klener, P.; Etrych, Tomáš

    2015-01-01

    Roč. 20, č. 11 (2015), s. 19849-19864. ISSN 1420-3049 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109; GA ČR(CZ) GA15-02986S; GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : HPMA copolymer s * drug delivery systems * doxorubicin Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.416, year: 2014

  20. Impact of CD68/(CD3+CD20 ratio at the invasive front of primary tumors on distant metastasis development in breast cancer.

    Directory of Open Access Journals (Sweden)

    Noemí Eiró

    Full Text Available Tumors are infiltrated by macrophages, T and B-lymphocytes, which may favor tumor development by promoting angiogenesis, growth and invasion. The aim of this study was to investigate the clinical relevance of the relative amount of macrophages (CD68⁺, T-cells (CD3⁺ and B-cells (CD20⁺ at the invasive front of breast carcinomas, and the expression of matrix metalloproteases (MMPs and their inhibitors (TIMPs either at the invasive front or at the tumor center. We performed an immunohistochemical study counting CD3, CD20 and CD68 positive cells at the invasive front, in 102 breast carcinomas. Also, tissue sections were stained with MMP-2, -9, -11, -14 and TIMP-2 antibodies, and immunoreactivity location, percentage of reactive area and intensity were determined at the invasive front and at the tumor center. The results showed that an increased CD68 count and CD68/(CD3+CD20 ratio were directly associated with both MMP-11 and TIMP-2 expression by mononuclear inflammatory cells at the tumor center (p = 0.041 and p = 0.025 for CD68 count and p = 0.001 and p = 0.045 for ratio, respectively for MMP-11 and TIMP-2. In addition, a high CD68/(CD3+CD20 ratio (>0.05 was directly associated with a higher probability of shortened relapse-free survival. Multivariate analysis revealed that CD68/(CD3+CD20 ratio was an independent factor associated with distant relapse-free survival (RR: 2.54, CI: (1.23-5.24, p<0.01. Therefore, CD68/(CD3+CD20 ratio at the invasive front could be used as an important prognostic marker.

  1. Inflammation in disseminated lesions: an analysis of CD4+, CD20+, CD68+, CD31+ and vW+ cells in non-ulcerated lesions of disseminated leishmaniasis

    Directory of Open Access Journals (Sweden)

    Dayana Santos Mendes

    2013-02-01

    Full Text Available Disseminated leishmaniasis (DL differs from other clinical forms of the disease due to the presence of many non-ulcerated lesions (papules and nodules in non-contiguous areas of the body. We describe the histopathology of DL non-ulcerated lesions and the presence of CD4-, CD20-, CD68-, CD31- and von Willebrand factor (vW-positive cells in the inflamed area. We analysed eighteen biopsies from non-ulcerated lesions and quantified the inflamed areas and the expression of CD4, CD20, CD68, CD31 and vW using Image-Pro software (Media Cybernetics. Diffuse lymphoplasmacytic perivascular infiltrates were found in dermal skin. Inflammation was observed in 3-73% of the total biopsy area and showed a significant linear correlation with the number of vW+ vessels. The most common cells were CD68+ macrophages, CD20+ B-cells and CD4+ T-cells. A significant linear correlation between CD4+ and CD20+ cells and the size of the inflamed area was also found. Our findings show chronic inflammation in all DL non-ulcerated lesions predominantly formed by macrophages, plasmacytes and T and B-cells. As the inflamed area expanded, the number of granulomas and extent of the vascular framework increased. Thus, we demonstrate that vessels may have an important role in the clinical evolution of DL lesions.

  2. CD20单克隆抗体在重症系统性红斑狼疮患儿治疗中的应用%Rituximab therapy for severe pediatric systemic lupus erythematosus

    Institute of Scientific and Technical Information of China (English)

    苏改秀; 吴凤岐; 王芳; 周志轩; 黄小兰; 鲁杰

    2012-01-01

    目的 探讨CD20单克隆抗体(利妥昔单抗)治疗重症儿童系统性红斑狼疮(SLE)的有效性和安全性.方法 诊断依据1997年美国风湿病学会SLE的分类标准.纳入标准:年龄≤16岁,至少1个以上重要器官受累,SLEDA1评分>10分,常规治疗反应欠佳.治疗方法:抗CD20单抗剂量375 mg/(m2·次),于第0、14天分次静脉输注.于CD20单抗治疗前及治疗后2周、1、3、6、12个月评估疗效,并监测不良反应.结果 共20例SLE患儿,男女比1∶3,年龄5~16岁,病程(3.0±2.5)年,平均随访(27.0±7.8)个月.10例狼疮脑病患儿谵妄、认知障碍等在1个月内明显改善;15例狼疮肾炎患儿中14例用药2~3个月后改善,1例无明显缓解;4例狼疮肺炎患儿用药1个月内症状减轻;18例血细胞减少患儿中16例在1个月内恢复.95%患儿(19/20)2周内B细胞清除,90%患儿(18/20)B淋巴细胞计数于1年内恢复.SLEDAI评分用药后明显降低,用药1年泼尼松剂量从( 45.0±4.7)mg/m2降至(12.0 ±2.7) mg/m2(P<0.001).用药半年内5例患儿出现肺炎,其中2例重症肺炎分别为曲霉菌肺炎及卡氏肺囊虫肺炎,均治疗后好转,无死亡病例.随B细胞恢复,2例患儿分别于治疗15、18个月后病情反复,给予第2疗程抗CD20单抗后,1例病情再次缓解,另外1例病情缓解不明显.结论 抗CD20单抗治疗重症儿童SLE疗效肯定,耐受性较好,部分病例可能发生严重感染.%Objective To analyze the safety and efficacy of anti-CD20 monoclonal antibody in treatment of severe pediatric systemic lupus erythematosus (PSLE). Method The diagnosis of PSLE was made according to the criteria for the classification of systemic lupus erythematosus revised by the American College of Rheumatology in 1997. Severe cases with PSLE was selected by the following criteria:age ≤ 16 years,number of important organs involved > 1,SLEDAI score > 10 points and poor response to conventional immunosuppressive treatment

  3. Carbon Insertion into arachno-6,9-C2B8H14 via Acyl Chlorides. Skeletal Alkylcarbonation (SAC) Reactions: A New Route for Tricarbollides

    Czech Academy of Sciences Publication Activity Database

    Bakardjiev, Mario; Štíbr, Bohumil; Holub, Josef; Padělková, Z.; Růžička, A.

    2013-01-01

    Roč. 52, č. 15 (2013), s. 9087-9093. ISSN 0020-1669 R&D Projects: GA ČR(CZ) GAP207/11/0705 Institutional support: RVO:61388980 Keywords : MAGNETIC-RESONANCE-SPECTROSCOPY * STRUCTURAL CHARACTERIZATIONS * 12-VERTEX FERRATRICARBOLLIDES Subject RIV: CA - Inorganic Chemistry Impact factor: 4.794, year: 2013

  4. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: A prospective randomized HOVON trial

    OpenAIRE

    Vellenga, Edo; van Putten, Wim; Veer, Mars; Zijlstra, Josée; Fibbe, Willem; Oers, Marinus; Verdonck, Leo; Wijermans, Pierre; van Imhoff, Gustaaf; Lugtenburg, Pieternella; Huijgens, Peter

    2008-01-01

    textabstractWe evaluated the role of rituximab during remission induction chemotherapy in relapsed aggressive CD20+non-Hodgkin lymphoma. Of 239 patients, 225 were evaluable for analysis. Randomized to DHAP (cisplatin-cytarabine- dexamethasone)-VIM (etoposide-ifosfamide-methotrexate)-DHAP (cisplatin- cytarabine-dexamethasone) chemotherapy with rituximab (R; R-DHAP arm) were 119 patients (113 evaluable) and to chemotherapy without rituximab (DHAP arm) 120 patients (112 evaluable). Patients in c...

  5. Combining a CD20 chimeric antigen receptor and an inducible caspase 9 suicide switch to improve the efficacy and safety of T cell adoptive immunotherapy for lymphoma.

    Directory of Open Access Journals (Sweden)

    Lihua E Budde

    Full Text Available Modification of T cells with chimeric antigen receptors (CAR has emerged as a promising treatment modality for human malignancies. Integration of co-stimulatory domains into CARs can augment the activation and function of genetically targeted T cells against tumors. However, the potential for insertional mutagenesis and toxicities due to the infused cells have made development of safe methods for removing transferred cells an important consideration. We have genetically modified human T cells with a lentiviral vector to express a CD20-CAR containing both CD28 and CD137 co-stimulatory domains, a "suicide gene" relying on inducible activation of caspase 9 (iC9, and a truncated CD19 selectable marker. Rapid expansion (2000 fold of the transduced T cells was achieved in 28 days after stimulation with artificial antigen presenting cells. Transduced T cells exhibited effective CD20-specific cytotoxic activity in vitro and in a mouse xenograft tumor model. Activation of the iC9 suicide switch resulted in efficient removal of transduced T cells both in vitro and in vivo. Our work demonstrates the feasibility and promise of this approach for treating CD20(+ malignancies in a safe and more efficient manner. A phase I clinical trial using this approach in patients with relapsed indolent B-NHL is planned.

  6. Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors.

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    Katy Milne

    Full Text Available BACKGROUND: Tumor-infiltrating T cells are associated with survival in epithelial ovarian cancer (EOC, but their functional status is poorly understood, especially relative to the different risk categories and histological subtypes of EOC. METHODOLOGY/PRINCIPAL FINDINGS: Tissue microarrays containing high-grade serous, endometrioid, mucinous and clear cell tumors were analyzed immunohistochemically for the presence of lymphocytes, dendritic cells, neutrophils, macrophages, MHC class I and II, and various markers of activation and inflammation. In high-grade serous tumors from optimally debulked patients, positive associations were seen between intraepithelial cells expressing CD3, CD4, CD8, CD45RO, CD25, TIA-1, Granzyme B, FoxP3, CD20, and CD68, as well as expression of MHC class I and II by tumor cells. Disease-specific survival was positively associated with the markers CD8, CD3, FoxP3, TIA-1, CD20, MHC class I and class II. In other histological subtypes, immune infiltrates were less prevalent, and the only markers associated with survival were MHC class II (positive association in endometrioid cases and myeloperoxidase (negative association in clear cell cases. CONCLUSIONS/SIGNIFICANCE: Host immune responses to EOC vary widely according to histological subtype and the extent of residual disease. TIA-1, FoxP3 and CD20 emerge as new positive prognostic factors in high-grade serous EOC from optimally debulked patients.

  7. Distribution of immune cells in head and neck cancer: CD8+ T-cells and CD20+ B-cells in metastatic lymph nodes are associated with favourable outcome in patients with oro- and hypopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Tumour infiltrating lymphocytes (TIL) are generally considered to represent a host immune response directed against tumour antigens. TIL are also increasingly recognised as possible prognostic parameters. However, the effects observed are variable indicating that results cannot be extrapolated from type of tumour to another. Moreover, it has been suggested that primary solid tumours may be ignored by the immune system and that a meaningful immune response is only mounted in regional lymph nodes. We have examined the local distribution of immune cells in tumour-related compartments in head and neck squamous cell carcinomas (HNSCC). In a second step, the prognostic impact of these cells on disease-free survival (DFS) was analysed. A total of 198 tissue cores from 33 patients were evaluated using tissue mircroarray technique and immunohistochemistry. Tumour-infiltrating immune cells were identified using antibodies specific for CD3, CD8, GranzymeB, FoxP3, CD20 and CD68 and quantified using an image analysis system. We demonstrate a relative expansion of FoxP3+ regulatory T-cells (Treg) and of cytotoxic T-cells among tumour infitrating T-cells. We also show that intratumoural CD20+ B-cells are significantly more frequent in metastatic deposits than in primary tumours. Furthermore, we observed a reduced number of peritumoural CD8+ T-cells in metastatic lymph nodes as compared to univolved regional nodes suggesting a local down-modulation of cellular immunity. All other immune cells did not show significant alterations in distribution. We did not observe an association of tumour infiltrating immune cells at the primary site with outcome. However, increased numbers of intraepithelial CD8+ TIL in metastatic tumours as well as large numbers of peritumoural B-cells in lymph node metastases were associated with favourable outcome. Unexpectedly, no effect on patient outcome was observed for Treg in any compartment. Our results suggest that alterations in lymphocyte

  8. Development of [{sup 62}Zn/{sup 62}Cu]-DOTA-rituximab as a possible novel in vivo PET generator for anti-CD20 antigen imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gholipour, Nazila [Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of). Dept. of Radiopharmacy; Jalilian, Amir R.; Fazaeli, Yousef; Moradkhani, Sedigheh; Bolourinovin, Fateme [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of); Sabzevari, Omid [Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of). Dept. of Toxicology and Pharmacology; Khalaj, Ali [Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of). Dept. of Medical Chemistry

    2014-07-01

    In this study, zinc-62 was prepared at radiopharmaceutical grade (for {sup 62}Zn/{sup 62}Cu generator production) using {sup nat}Cu(p, xn) reaction with the production yield of 5.9 mCi/μAh at 30 MeV proton energy (radiochemical separation yield >95%, radionuclidic purity >99% and radiochemical purity >99%). In the next step, rituximab was successively labeled with [{sup 62}Zn]-ZnCl{sub 2} after conjugation with p-SCN-Bz-DOTA followed by molecular filtration and determination of the average number of DOTA conjugated per mAb (6:1) by spectrophotometric method. Radiochemical purity (>97%, measured by ITLC and HPLC), integrity of protein after radiolabeling (gel electrophoresis) and stability of [{sup 62}Zn]-DOTA-rituximab (in final formulation, and human serum) were determined 1-8 h as well as biodistribution studies in wild-type rats followed by coincidence imaging for 6 h. However, the accumulation of the radiolabeled antibody was not consistent with the former reported rituximab conjugates. [{sup 62}Zn]-labeled monoclonal antibodies and fragments can be prepared as potential in vivo PET generators for molecular imaging however, the search for application of stable zinc complexes must be continued.

  9. First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma

    DEFF Research Database (Denmark)

    Hagenbeek, Anton; Gadeberg, Ole Vestergaard; Johnson, Peter;

    2008-01-01

    lactate dehydrogenase. No safety concerns or maximum tolerated dose was identified. A total of 274 adverse events were reported; 190 were judged related to ofatumumab, most occurring on the first infusion day with Common Terminology Criteria grade 1 or 2. Eight related events were grade 3. Treatment...

  10. High-Dose 131I-Tositumomab (Anti-CD20) Radioimmunotherapy for Non-Hodgkin's Lymphoma: Adjusting Radiation Absorbed Dose to Actual Organ Volumes

    International Nuclear Information System (INIS)

    Radioimmunotherapy (RIT) using 131I-tositumomab has been used successfully to treat relapsed or refractory B-cell non-Hodgin's lymphoma (NHL). Our approach to treatment planning has been to determine limits on radiation absorbed close to critical nonhematopoietic organs. This study demonstrates the feasibility of using CT to adjust for actual organ volumes in calculating organ-specific absorbed dose estimates. Methods: Records of 84 patients who underwent biodistribution studies after a trace-labeled infusion of 131I-tositumomab for RIT (January 1990 and April 2003) were reviewed. Serial planar -camera images and whole-body Nal probe counts were obtained to estimate 131I-antibody source-organ residence times as recommended by the MIRD Committee. The source-organ residence times for standard man or woman were adjusted by the ratio of the MIRD phantom organ mass to the CT-derived organ mass. Results: The mean radiation absorbed doses (in mGy/MBq) for our data using the MIRD model were lungs= 1.67; liver= 1.03; kidneys= 1.08; spleen= 2.67; and whole body= 0.3; and for CT volume-adjusted organ volumes (in mGy/MBq) were lungs= 1.30; liver= 0.92; kidneys= 0.76; spleen= 1.40; and whole body= 0.22. We determined the following correlation coefficients between the 2 methods for the various organs; lungs, 0.49; (P= 0.0001); liver, 0.64 (P= 0.004); kidneys, 0.45 (P= 0.0001), for the residence times. For therapy, patients received mean 131I administered activities of 19.2 GBq (520 mCi) after adjustment for CT-derived organ mass compared with 16.0 GBq (433 mCi) that would otherwise have been given had therapy been based only using standard MIRD organ volumes--a statistically significant difference (P= 0.0001). Conclusion: We observed large variations in organ masses among our patients. Our treatments were planned to deliver the maximally tolerated radiation dose to the dose-limiting normal organ. This work provides a simplified method for calculating patient-specific radiation doses by adjusting for the actual organ mass and shows the value of this approach in treatment planning for RIT

  11. Targeted alpha-therapy using [Bi-213]anti-CD20 as novel treatment option for radio- and chemoresistant non-Hodgkin lymphoma cells

    OpenAIRE

    Roscher, Mareike; Hormann, Inis; Leib, Oliver; Marx, Sebastian; Moreno, Josue; Miltner, Erich; Friesen, Claudia

    2013-01-01

    Radioimmunotherapy (RIT) is an emerging treatment option for non-Hodgkin lymphoma (NHL) producing higher overall response and complete remission rates compared with unlabelled antibodies. However, the majority of patients treated with conventional or myeloablative doses of radiolabelled antibodies relapse. The development of RIT with alpha-emitters is attractive for a variety of cancers because of the high linear energy transfer (LET) and short path length of alpha-radiation in human tissue, ...

  12. MS4a4B, a CD20 homologue in T cells, inhibits T cell propagation by modulation of cell cycle.

    Directory of Open Access Journals (Sweden)

    Hui Xu

    Full Text Available MS4a4B, a CD20 homologue in T cells, is a novel member of the MS4A gene family in mice. The MS4A family includes CD20, FcεRIβ, HTm4 and at least 26 novel members that are characterized by their structural features: with four membrane-spanning domains, two extracellular domains and two cytoplasmic regions. CD20, FcεRIβ and HTm4 have been found to function in B cells, mast cells and hematopoietic cells respectively. However, little is known about the function of MS4a4B in T cell regulation. We demonstrate here that MS4a4B negatively regulates mouse T cell proliferation. MS4a4B is highly expressed in primary T cells, natural killer cells (NK and some T cell lines. But its expression in all malignant T cells, including thymoma and T hybridoma tested, was silenced. Interestingly, its expression was regulated during T cell activation. Viral vector-driven overexpression of MS4a4B in primary T cells and EL4 thymoma cells reduced cell proliferation. In contrast, knockdown of MS4a4B accelerated T cell proliferation. Cell cycle analysis showed that MS4a4B regulated T cell proliferation by inhibiting entry of the cells into S-G2/M phase. MS4a4B-mediated inhibition of cell cycle was correlated with upregulation of Cdk inhibitory proteins and decreased levels of Cdk2 activity, subsequently leading to inhibition of cell cycle progression. Our data indicate that MS4a4B negatively regulates T cell proliferation. MS4a4B, therefore, may serve as a modulator in the negative-feedback regulatory loop of activated T cells.

  13. Influência do CD 20 na refratariedade do linfoma de Hodgkin clássico ao tratamento inicial com o esquema ABVD, no Ceará, Brasil Influence of CD 20 antigen expression in the refractoriness of classical Hodgkin lymphoma in the first line treatment with ABVD protocol in Ceará state, Brazil

    Directory of Open Access Journals (Sweden)

    Rogério Pinto Giesta

    2009-06-01

    Full Text Available INTRODUÇÃO: A significância prognóstica do marcador imunológico CD 20 no linfoma de Hodgkin clássico (LHc ainda é incerta, particularmente no que se refere à refratariedade ao tratamento inicial. OBJETIVOS: Avaliar a influência da positividade do marcador CD 20 na refratariedade do LHc ao tratamento poliquimioterápico inicial, com o esquema doxorubicina 25 mg/m², bleomicina 10 mg/m², vinblastina 6 mg/m² e dacarbazina 375 mg/m² (ABVD, no Ceará, Brasil. MATERIAL E MÉTODOS: Estudo analítico incluindo 97 pacientes com diagnóstico de LHc firmado entre janeiro de 2000 e dezembro de 2004. A análise foi realizada avaliando variáveis demográficas, clínicas e laboratoriais. RESULTADOS: Foi evidenciada uma positividade do CD 20 em 38,1% dos pacientes. Na análise bivariada, CD 20 positivo (razão de chance [RC] = 4,02; intervalo de confiança [IC] = 1,09 - 8,54; p = 0,02, a presença de sintomas B (RC = 4,02; IC = 1,18-17,51; p = 0,01 e a elevação da desidrogenase lática (mediana não-refratários 248,5 [200,5 - 389,5]; mediana refratários 356 [208,5 - 545]; p = 0,03 apresentaram relação de pior prognóstico quanto à refratariedade. Na regressão logística, o CD 20 positivo (RC ajustada = 3,6; IC = 0,99 - 13,09; p = 0,05 e a presença de sintomas B (RC ajustada = 5,41; IC = 1,16 - 25,34; p = 0,03 continuaram apresentando pior prognóstico. DISCUSSÃO: Esses dados coincidem com a literatura, em que a positividade do marcador CD 20 está relacionada com pior resposta ao tratamento com ABVD. CONCLUSÃO: Os nossos dados indicam que o tratamento com ABVD não é completamente adequado para a abordagem terapêutica inicial deste subgrupo de pacientes e novas pesquisas precisam ser realizadas no sentido de aperfeiçoar o tratamento destes pacientes.INTRODUCTION: The prognostic value of CD20 antigen expression in classical Hodgkin lymphoma (cHL is uncertain, particularly regarding the refractoriness to first-line treatment. OBJECTIVES

  14. Pharmacokinetics and pharmacokinetic/pharmacodynamic associations of ofatumumab, a human monoclonal CD20 antibody, in patients with relapsed or refractory chronic lymphocytic leukaemia: a phase 1-2 study

    DEFF Research Database (Denmark)

    Coiffier, Bertrand; Losic, Nedjad; Rønn, Birgitte Biilmann;

    2010-01-01

    The purpose of this phase 1-2 study was to investigate the association between the pharmacokinetic properties of ofatumumab, a human monoclonal CD20 antibody, and outcomes in 33 patients with relapsed/refractory chronic lymphocytic leukaemia receiving 4 weekly infusions of ofatumumab. The...

  15. Combination of two anti-CD5 monoclonal antibodies synergistically induces complement-dependent cytotoxicity of chronic lymphocytic leukaemia cells

    DEFF Research Database (Denmark)

    Klitgaard, Josephine L; Koefoed, Klaus; Geisler, Christian;

    2013-01-01

    The treatment of chronic lymphocytic leukaemia (CLL) has been improved by introduction of monoclonal antibodies (mAbs) that exert their effect through secondary effector mechanisms. CLL cells are characterized by expression of CD5 and CD23 along with CD19 and CD20, hence anti-CD5 Abs that engage ...

  16. Synergistic anti-tumor activity of acadesine (AICAR) in combination with the anti-CD20 monoclonal antibody rituximab in in vivo and in vitro models of mantle cell lymphoma

    OpenAIRE

    Montraveta, Arnau; Xargay-Torrent, Sílvia; López-Guerra, Mónica; Rosich, Laia; Pérez-Galán, Patricia; Salaverria, Itziar; Beà, Silvia; Kalko, Susana G.; de Frias, Mercè; Campàs, Clara; Roué, Gaël; Colomer, Dolors

    2014-01-01

    Mantle cell lymphoma (MCL) is considered one of the most challenging lymphoma, with limited responses to current therapies. Acadesine, a nucleoside analogue has shown antitumoral effects in different preclinical cancer models as well as in a recent phase I/II clinical trial conducted in patients with chronic lymphocytic leukemia. Here we observed that acadesine exerted a selective antitumoral activity in the majority of MCL cell lines and primary MCL samples, independently of adverse cytogene...

  17. Chemoimmunotherapy for relapsed/refractory and progressive 17p13-deleted chronic lymphocytic leukemia (CLL) combining pentostatin, alemtuzumab, and low-dose rituximab is effective and tolerable and limits loss of CD20 expression by circulating CLL cells.

    Science.gov (United States)

    Zent, Clive S; Taylor, Ronald P; Lindorfer, Margaret A; Beum, Paul V; LaPlant, Betsy; Wu, Wenting; Call, Timothy G; Bowen, Deborah A; Conte, Michael J; Frederick, Lori A; Link, Brian K; Blackwell, Sue E; Veeramani, Suresh; Baig, Nisar A; Viswanatha, David S; Weiner, George J; Witzig, Thomas E

    2014-07-01

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients with purine analog refractory disease or TP53 dysfunction still have limited treatment options and poor survival. Alemtuzumab-containing chemoimmunotherapy regimens can be effective but frequently cause serious infections. We report a Phase II trial testing the efficacy and tolerability of a short-duration regimen combining pentostatin, alemtuzumab, and low-dose high-frequency rituximab designed to decrease the risk of treatment-associated infections and to limit the loss of CD20 expression by CLL cells. The study enrolled 39 patients with progressive CLL that was either relapsed/refractory (n = 36) or previously untreated with 17p13 deletion (17p13-) (n = 3). Thirteen (33%) patients had both 17p13- and TP53 mutations predicted to be dysfunctional, and eight patients had purine analog refractory CLL without TP53 dysfunction. Twenty-six (67%) patients completed therapy, with only five (13%) patients having treatment-limiting toxicity and no treatment-related deaths. Twenty-two (56%) patients responded to treatment, with 11 (28%) complete responses (four with incomplete bone marrow recovery). Median progression-free survival was 7.2 months, time to next treatment was 9.1 months, and overall survival was 34.1 months. The majority of deaths (82%) were caused by progressive disease, including transformed diffuse large B-cell lymphoma (n = 6). Correlative studies showed that low-dose rituximab activates complement and natural killer cells without a profound and sustained decrease in expression of CD20 by circulating CLL cells. We conclude that pentostatin, alemtuzumab, and low-dose high-frequency rituximab is a tolerable and effective therapy for CLL and that low-dose rituximab therapy can activate innate immune cytotoxic mechanisms without substantially decreasing CD20 expression. PMID:24723493

  18. Therapeutic Effect Evaluation of the Combination Regimen of Rituximab and CHOP for CD20 Positive Diffuse Large B-cell Lymphoma%R-CHOP方案初治CD20阳性弥漫大B细胞淋巴瘤的临床疗效评价

    Institute of Scientific and Technical Information of China (English)

    刘爱学; 张容榕; 李明淑; 周泽强; 冯天举

    2012-01-01

    目的:观察利妥昔单抗联合CHOP方案(R-CHOP方案)初治弥漫大B细胞淋巴瘤的疗效及不良反应.方法:对20例初治弥漫大B细胞淋巴瘤患者,给予6周期~8周期R-CHOP方案治疗.利妥昔单抗375mg/m2,静滴,d1;环磷酰胺750mg/m2,iv,d1;阿霉素50mg/m2,iv,d1;长春新碱1.4mg/m2,iv,d1;强的松100mg/d,口服,d1-5;21天为一周期.结果:20例患者中,完全缓解13例,部分缓解3例,稳定1例,进展3例,客观缓解率80%.主要毒副反应为血液学毒性,轻度胃肠道反应,无利妥昔单抗不良反应.结论:R-CHOP方案初治CD20阳性弥漫大B细胞淋巴瘤缓解率高,毒副反应可以耐受.%Objective: To observe the effect and toxicity of combination treatment of rituximab and CHOP-regimen for diffuse large B cell lymphoma( DLBCL ). Methods: 20 patients initially diagnosed as DLBCL received R-CHOP regimen of 6 - 8 cycles: rituximab 375mg/m intravenously infused on dayl, cyclophosphamide 750mg/m on clayl, adriamycin 50mg/m2 on clayl and vincristine 1. 4mg/m on day 1, prednisone lOOmg/d taken orally on day 1 ~5; 21days as one cycle. Results: In all 20 patients, 13 got complete response and 3 partial response, 1 SD, 3 PD. The overall response rate was 80. 0%. Main toxicity included myelosuppression, slightly gastrointestinal reaction. No rituximab related toxicity was observed in all the patients. Conclusion: R-CHOP regimen has high efficacy with mild toxicity in the treatment of initially diagnosed diffuse large B cell lymphoma.

  19. Tumour targeting and radiation dose of radioimmunotherapy with {sup 90}Y-rituximab in CD20+ B-cell lymphoma as predicted by {sup 89}Zr-rituximab immuno-PET: impact of preloading with unlabelled rituximab

    Energy Technology Data Exchange (ETDEWEB)

    Muylle, Kristoff [Vrije Universiteit Brussel, MIMA Research Group, Brussels (Belgium); Universite Libre de Bruxelles, Department of Nuclear Medicine, Jules Bordet Institute, Brussels (Belgium); Flamen, Patrick; Guiot, Thomas; Ghanem, Ghanem; Meuleman, Nathalie; Bourgeois, Pierre; Vanderlinden, Bruno; Vaes, Melanie; Bron, Dominique [Universite Libre de Bruxelles, Jules Bordet Institute, Brussels (Belgium); Vugts, Danielle J.; Dongen, Guus A.M.S. van [VU University Medical Centre, Amsterdam (Netherlands); Everaert, Hendrik [Vrije Universiteit Brussel, UZ Brussel, Brussels (Belgium); Vrije Universiteit Brussel, MIMA Research Group, Brussels (Belgium)

    2015-07-15

    To compare using immuno-PET/CT the distribution of {sup 89}Zr-labelled rituximab without and with a preload of unlabelled rituximab to assess the impact of preloading with unlabelled rituximab on tumour targeting and radiation dose of subsequent radioimmunotherapy with {sup 90}Y-labelled rituximab in CD20+ B-cell lymphoma. Five patients with CD20+ B-cell lymphoma and progressive disease were prospectively enrolled. All patients underwent three study phases: initial dosimetric phase with baseline {sup 89}Zr-rituximab PET/CT imaging without a cold preload, followed 3 weeks later by a second dosimetric phase with administration of a standard preload (250 mg/m{sup 2}) of unlabelled rituximab followed by injection of {sup 89}Zr-rituximab, and a therapeutic phase 1 week later with administration of unlabelled rituximab followed by {sup 90}Y-rituximab. PET/CT imaging and tracer uptake by organs and lesions were assessed. With a cold rituximab preload, the calculated whole-body dose of {sup 90}Y-rituximab was similar (mean 0.87 mSv/MBq, range 0.82-0.99 mSv/MBq) in all patients. Without a preload, an increase in whole-body dose of 59 % and 87 % was noted in two patients with preserved circulating CD20+ B cells. This increase in radiation dose was primarily due to a 12.4-fold to 15-fold higher dose to the spleen without a preload. No significant change in whole-body dose was noted in the three other patients with B-cell depletion. Without a preload, consistently higher tumour uptake was noticed in patients with B-cell depletion. Administration of the standard preload of unlabelled rituximab impairs radioconjugate tumour targeting in the majority of patients eligible for radioimmunotherapy, that is patients previously treated with rituximab-containing therapeutic regimens. This common practice may need to be reconsidered and further evaluated as the rationale for this high preload has its origin in the ''prerituximab era''. (orig.)

  20. A clinical study on the therapeutic effect of rituximab in combination with autologous peripheral blood stem cell transplantation in treatment of CD20+ B cellulous non-Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    Yong-sheng CHEN

    2013-07-01

    Full Text Available Objective To investigate the therapeutic effect of autologous peripheral blood stem cell transplantation (APBSCT in combination with rituximab in treatment of CD20+ B cellulous non-Hodgkin's lymphoma (B-NHL. Methods Sixty patients with CD20+ aggressive or refractory and recurrent B-NHL and treated with APBSCT in our department from Jan. 2005 to Jan. 2011 were admitted. All the subjects were divided into 2 groups according to their own choice: 25 patients received rituximab treatment (treatment group and 35 patients were treated without rituximab treatment (control group. All patients underwent chemotherapy and APBSCT. For patients in treatment group, rituximab was used with CHOP before collecting the stem cells and after the transplantation. After transplantation, rituximab and IL-2 were used in treatment group every 3-6 months as maintenance treatment. Results No side effect was observed during the use of rituximab either before or after transplantation. The mononuclear cell count in treatment and control group was (8.2±2.9×108/kg and (8.4±3.9×108/kg (P=0.822, respectively; CD34+cell count was (12.3±12.7×106/kg and (13.2±13.9×106/kg (P=0.799, respectively. Haemopoiesis reconstruction was successfully achieved in the patients of treatment group, while 3 patients in control group failed to have haemopoiesis reconstruction. No significant difference was found between two groups on the recovery time of neutrophilic granulocytes and platelets. All patients achieved complete remission. The average follow-up time was 22 months. The disease relapsed in two patients in treatment group and six in control group. The 3-year overall survival rate in treatment group (91.6% was a little higher than that in control group (69.5%, P=0.060. Conclusion To patients of CD20+ B lymphoma, the use of rituximab shows no side effect before or after collection of stem cell and hemopoiesis reconstruction, and the overall survival rate may be improved.

  1. B-cell inhibition by cross-linking CD79b is superior to B-cell depletion with anti-CD20 antibodies in treating murine collagen-induced arthritis

    Czech Academy of Sciences Publication Activity Database

    Bruhl, H.; Cihak, J.; Talke, Y.; Rodriguez-Gomez, M.; Hermann, F.; Goebel, N.; Renner, K.; Plachý, Jiří; Stangassinger, M.; Archemann, S.; Nimmerjahn, F.; Mack, M.

    2015-01-01

    Roč. 45, č. 3 (2015), s. 705-715. ISSN 0014-2980 Institutional support: RVO:68378050 Keywords : Arthritis * B cells * B-cell depletion * B-cell inhibition * CD79b * Humoral immune response Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.034, year: 2014

  2. High in Vitro Anti-Tumor Efficacy of Dimeric Rituximab/Saporin-S6 Immunotoxin.

    Science.gov (United States)

    Bortolotti, Massimo; Bolognesi, Andrea; Battelli, Maria Giulia; Polito, Letizia

    2016-01-01

    The anti-CD20 mAb Rituximab has revolutionized lymphoma therapy, in spite of a number of unresponsive or relapsing patients. Immunotoxins, consisting of toxins coupled to antibodies, are being investigated for their potential ability to augment Rituximab efficacy. Here, we compare the anti-tumor effect of high- and low-molecular-weight Rituximab/saporin-S6 immunotoxins, named HMW-IT and LMW-IT, respectively. Saporin-S6 is a potent and stable plant enzyme belonging to ribosome-inactivating proteins that causes protein synthesis arrest and consequent cell death. Saporin-S6 was conjugated to Rituximab through an artificial disulfide bond. The inhibitory activity of HMW-IT and LMW-IT was evaluated on cell-free protein synthesis and in two CD20⁺ lymphoma cell lines, Raji and D430B. Two different conjugates were separated on the basis of their molecular weight and further characterized. Both HMW-IT (dimeric) and LMW-IT (monomeric) maintained a high level of enzymatic activity in a cell-free system. HMW-IT, thanks to a higher toxin payload and more efficient antigen capping, showed stronger in vitro anti-tumor efficacy than LMW-IT against lymphoma cells. Dimeric HMW-IT can be used for lymphoma therapy at least for ex vivo treatments. The possibility of using HMW-IT augments the yield in immunotoxin preparation and allows the targeting of antigens with low internalization rates. PMID:27338475

  3. High in Vitro Anti-Tumor Efficacy of Dimeric Rituximab/Saporin-S6 Immunotoxin

    Directory of Open Access Journals (Sweden)

    Massimo Bortolotti

    2016-06-01

    Full Text Available The anti-CD20 mAb Rituximab has revolutionized lymphoma therapy, in spite of a number of unresponsive or relapsing patients. Immunotoxins, consisting of toxins coupled to antibodies, are being investigated for their potential ability to augment Rituximab efficacy. Here, we compare the anti-tumor effect of high- and low-molecular-weight Rituximab/saporin-S6 immunotoxins, named HMW-IT and LMW-IT, respectively. Saporin-S6 is a potent and stable plant enzyme belonging to ribosome-inactivating proteins that causes protein synthesis arrest and consequent cell death. Saporin-S6 was conjugated to Rituximab through an artificial disulfide bond. The inhibitory activity of HMW-IT and LMW-IT was evaluated on cell-free protein synthesis and in two CD20+ lymphoma cell lines, Raji and D430B. Two different conjugates were separated on the basis of their molecular weight and further characterized. Both HMW-IT (dimeric and LMW-IT (monomeric maintained a high level of enzymatic activity in a cell-free system. HMW-IT, thanks to a higher toxin payload and more efficient antigen capping, showed stronger in vitro anti-tumor efficacy than LMW-IT against lymphoma cells. Dimeric HMW-IT can be used for lymphoma therapy at least for ex vivo treatments. The possibility of using HMW-IT augments the yield in immunotoxin preparation and allows the targeting of antigens with low internalization rates.

  4. Regulation of serum matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 following rituximab therapy in patients with rheumatoid arthritis refractory to anti-tumor necrosis factor blockers

    OpenAIRE

    Klimiuk, Piotr Adrian; Domysławska, Izabela; Sierakowski, Stanisław; Chwiećko, Justyna

    2014-01-01

    In our article, we evaluated the regulatory effects of the infusions of rituximab, a monoclonal antibody directed against CD20+ B cells, on the serum matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels in patients with active rheumatoid arthritis (RA) not responding to anti-tumor necrosis factor (anti-TNF) therapy. Twelve RA patients were planned to receive four infusions of 1,000 mg of rituximab at weeks 0, 2, 24 and 26. The therapy was combined with...

  5. Stromal Vascular Fraction Transplantation as an Alternative Therapy for Ischemic Heart Failure: Anti-inflammatory Role

    Directory of Open Access Journals (Sweden)

    Lin Xue

    2011-03-01

    Full Text Available Abstract Background The aims of this study were: (1 to show the feasibility of using adipose-derived stromal vascular fraction (SVF as an alternative to bone marrow mono nuclear cell (BM-MNC for cell transplantation into chronic ischemic myocardium; and (2 to explore underlying mechanisms with focus on anti-inflammation role of engrafted SVF and BM-MNC post chronic myocardial infarction (MI against left ventricular (LV remodelling and cardiac dysfunction. Methods Four weeks after left anterior descending coronary artery ligation, 32 Male Lewis rats with moderate MI were divided into 3 groups. SVF group (n = 12 had SVF cell transplantation (6 × 106 cells. BM-MNC group (n = 12 received BM-MNCs (6 × 106 and the control (n = 10 had culture medium. At 4 weeks, after the final echocardiography, histological sections were stained with Styrus red and immunohistochemical staining was performed for α-smooth muscle actin, von Willebrand factor, CD3, CD8 and CD20. Results At 4 weeks, in SVF and BM-MNC groups, LV diastolic dimension and LV systolic dimension were smaller and fractional shortening was increased in echocardiography, compared to control group. Histology revealed highest vascular density, CD3+ and CD20+ cells in SVF transplanted group. SVF transplantation decreased myocardial mRNA expression of inflammatory cytokines TNF-α, IL-6, MMP-1, TIMP-1 and inhibited collagen deposition. Conclusions Transplantation of adipose derived SVF cells might be a useful therapeutic option for angiogenesis in chronic ischemic heart disease. Anti-inflammation role for SVF and BM transplantation might partly benefit for the cardioprotective effect for chronic ischemic myocardium.

  6. After anti-racism?

    OpenAIRE

    Lentin, Alana

    2008-01-01

    Abstract Anti-racism as a political discourse and a form of collective social action has long been ignored as a serious field of research. In contrast, I envision the study of anti-racism as a vital lens on both 'race' and racism. First, the heterogeneity of anti-racism is demonstrated, spanning both pro- and anti-state-based analyses of the origins of racism. Second, a parallel discourse of 'anti-anti-racism' within the radical Left reveals the reluctance of many on the Left to id...

  7. Photon anti bunching versus phantom anti bunching?

    International Nuclear Information System (INIS)

    Photon anti bunching defined by two-time correlation functions has hitherto, to our best knowledge, been considered to constitute a unique, well defined effect. We show explicitly that this is by no means the case. We analyze two of the most famous definitions showing that both anti bunching and bunching effects according to one definition can be accompanied by arbitrary photon correlation effects according to another. As an example we discuss a model of parametric frequency conversion. (authors)

  8. The Anti-Cloak

    OpenAIRE

    Chen, Huanyang; Luo, Xudong; Ma, Hongru; Chan, C. T.

    2008-01-01

    A kind of transformation media, which we shall call the "anti-cloak", is proposed to partially defeat the cloaking effect of the invisibility cloak. An object with an outer shell of "anti-cloak" is visible to the outside if it is coated with the invisible cloak. Fourier-Bessel analysis confirms this finding by showing that external electromagnetic wave can penetrate into the interior of the invisibility cloak with the help of the anti-cloak.

  9. Anti-addiction vaccines

    OpenAIRE

    Shen, Xiaoyun; Orson, Frank M.; Kosten, Thomas R.

    2011-01-01

    Despite intensive efforts to eradicate it, addiction to both legal and illicit drugs continues to be a major worldwide medical and social problem. Anti-addiction vaccines can produce the antibodies to block the effects of these drugs on the brain, and have great potential to ameliorate the morbidity and mortality associated with illicit drug intoxications. This review provides a current overview of anti-addiction vaccines that are under clinical trial and pre-clinical research evaluation. It ...

  10. SITUASI PATEN OBAT ANTI DIABETES, ANTI HIPERTENSI, ANTI MALARIA DAN ANTI TUBERKULOSIS DI INDONESIA

    OpenAIRE

    Basundari Sri Utami; Sekar Tuti; Anggita Bunga Anggraini; Mukhlissul Faatih; Siswanto Siswanto; Trihono Trihono

    2014-01-01

    AbstrakIndonesia merupakan negara berpenduduk keempat terbanyak setelah Cina, India dan Amerika. Indonesia sedang mengalami transisi epidemiologi, dimana terjadi peningkatan penyakit tidak menular (PTM), sementara penyakit menular (PM) seperti malaria, tuberkulosis dan demam dengue prevalensinya masih tinggi. Tingginya morbiditas merupakan lahan yang bagus untuk melaksanakan obat anti PM dan anti PTM yang mendapat paten karena pangsa pasarnya yang sangat luas. Sayangnya potensi pasar yang mas...

  11. A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Not four letter words.

    Science.gov (United States)

    Mirick, G R; Bradt, B M; Denardo, S J; Denardo, G L

    2004-12-01

    The United States Food and Drug Administration (FDA) has approved unconjugated monoclonal antibodies (MAbs) for immunotherapy (IT) of B-cell lymphoma, breast cancer and acute myeloid leukemia. More recently, approval has been given for conjugated ZevalinTM ((90)yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM ((131)I-tositumomab, Corixa, Corp., Seattle, WA and GlaxoSmithKline, Philadelphia, PA) anti-CD20 MAbs for use in radioimmunotherapy (RIT) of non-Hodgkin's lymphoma (NHL), thus redefining the standard care of cancer patients. Because of, and despite a lack of basis for concern about allergic reactions due to human antibody responses to these foreign proteins, assays were developed to determine HAGA (human anti-globulin antibody) levels that developed in patient sera following treatment with MAbs. Strategies were also devised to ''humanize'' MAbs and to temporarily block patient immune function with drugs in order to decrease the seroconversion rates, with considerable success. On the other hand, a survival advantage has been observed in some patients who developed a HAGA following treatment. This correlates with development of an anti-idiotype antibody cascade directed toward the MAbs used to treat these patients. What follows is a selective review of HAGA and its effect on cancer treatment over the past 2 decades. PMID:15640788

  12. A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Not four letter words

    Energy Technology Data Exchange (ETDEWEB)

    Mirick, G. R.; Bradt, B. M.; Denardo, S. J.; Denardo, G. L. [Calfornia Univ., Sacramento (United States). Davis Medical Center

    2004-12-01

    The United States Food and Drugs Administration (FDA) has approved unconjugated monoclonal antibodies (MAbs) for immunotherapy (IT) of B-cell lymphoma, breast cancer and acute myeloid leukemia. More recently, approval has been given for conjugated ZevalinTM ({sup 9}0yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM ({sup 1}31I-tositumomab, Corixa, Corp., Seattle, WA and GlaxoSmithKline, Philadelphia, PA) antiCD20 MAns for use in radioimmunotherapy (RIT) of non-Hodgikin's lymphoma (NHL), thus redefining the standard care of cancer patients. Because of, and despite a lack of basis for concern about allergic reactions due to human antibody responses to these foreign proteins, essays were developed to determine HAGE (human anti-globulin antibody) levels that developed in patient sera following treatment with MAbs. Strategies were also devised to humanize MAbs and to temporarily block patient immune function with drugs in order to decrease the seroconversion rates, with considerable success. On the other hand, a survival advantage has been observed in some patients who developed a HAGA following treatment. This correlates with development of an anti-idiotype antibody cascade directed toward the MAbs used to treat these patients. What follows is a selective review of HAGA and its effect on cancer treatment over the past 2 decades.

  13. A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Not four letter words

    International Nuclear Information System (INIS)

    The United States Food and Drugs Administration (FDA) has approved unconjugated monoclonal antibodies (MAbs) for immunotherapy (IT) of B-cell lymphoma, breast cancer and acute myeloid leukemia. More recently, approval has been given for conjugated ZevalinTM (90yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM (131I-tositumomab, Corixa, Corp., Seattle, WA and GlaxoSmithKline, Philadelphia, PA) antiCD20 MAns for use in radioimmunotherapy (RIT) of non-Hodgikin's lymphoma (NHL), thus redefining the standard care of cancer patients. Because of, and despite a lack of basis for concern about allergic reactions due to human antibody responses to these foreign proteins, essays were developed to determine HAGE (human anti-globulin antibody) levels that developed in patient sera following treatment with MAbs. Strategies were also devised to humanize MAbs and to temporarily block patient immune function with drugs in order to decrease the seroconversion rates, with considerable success. On the other hand, a survival advantage has been observed in some patients who developed a HAGA following treatment. This correlates with development of an anti-idiotype antibody cascade directed toward the MAbs used to treat these patients. What follows is a selective review of HAGA and its effect on cancer treatment over the past 2 decades

  14. Multiculturalists and Anti-Semitism.

    Science.gov (United States)

    Alexander, Edward

    1994-01-01

    Discusses how anti-Semitism is perpetuated as a political ideology in the 20th century. It briefly examines the Palestinian cause and its effect on black anti-Semites (especially the Black Muslims), shows how multiculturalists and diversity training breed anti-Semitism, and explains why impoverished minorities sometimes resort to anti-Semitism.…

  15. Discrete anti-gravity

    International Nuclear Information System (INIS)

    Discrete physics, because it replaces time evolution generated by the energy operator with a global bit-string generator (program universe) and replaces ''fields'' with the relativistic Wheeler-Feynman ''action at a distance,'' allows the consistent formulation of the concept of signed gravitational charge for massive particles. The resulting prediction made by this version of the theory is that free anti-particles near the surface of the earth will ''fall'' up with the same acceleration that the corresponding particles fall down. So far as we can see, no current experimental information is in conflict with this prediction of our theory. The experiment crusis will be one of the anti-proton or anti-hydrogen experiments at CERN. Our prediction should be much easier to test than the small effects which those experiments are currently designed to detect or bound. 23 refs

  16. Anti-nutritional Factors.

    Science.gov (United States)

    2016-01-01

    Anti-nutritional factors such as trypsin inhibitor, phytic acid and cyanogen are as important as nutritional content of any edible plant part. The anti-nutritional factors can be defined as those substances generated in natural food substances by the normal metabolism of species and by different mechanisms (e.g. inactivation of some nutrients, diminution of the digestive process or metabolic utilization of feed) which exert effects contrary to optimum nutrition. Hence, trypsin inhibitor, phytic acid and cyanogens present in edibles with the methods in the chapter would be helpful. PMID:26939264

  17. Anti- CC-Groups and Anti-PC-Groups

    Directory of Open Access Journals (Sweden)

    Francesco Russo

    2007-01-01

    subgroup H of G. An anti-PC group G is a group in which each nonfinitely generated subgroup K has the quotient group G/coreG(NG(K which is a polycyclic-by-finite group. Anti-CC groups and anti-PC groups are the subject of the present article.

  18. SITUASI PATEN OBAT ANTI DIABETES, ANTI HIPERTENSI, ANTI MALARIA DAN ANTI TUBERKULOSIS DI INDONESIA

    Directory of Open Access Journals (Sweden)

    Basundari Sri Utami

    2014-10-01

    Full Text Available AbstrakIndonesia merupakan negara berpenduduk keempat terbanyak setelah Cina, India dan Amerika. Indonesia sedang mengalami transisi epidemiologi, dimana terjadi peningkatan penyakit tidak menular (PTM, sementara penyakit menular (PM seperti malaria, tuberkulosis dan demam dengue prevalensinya masih tinggi. Tingginya morbiditas merupakan lahan yang bagus untuk melaksanakan obat anti PM dan anti PTM yang mendapat paten karena pangsa pasarnya yang sangat luas. Sayangnya potensi pasar yang masih luas ini hanya ditangkap oleh luar negeri. Data dari Direktorat Jendral Hak Kekayaan Intelektual (Ditjen HKI pada tahun 2010 menunjukkan pemohon paten dalam negeri yang mendapatkan persetujuan perlindungan paten (granted hanya 4,6% sedangkan dari luar negeri sebanyak 92,03%. Hal yang sangat ironis bagi Indonesia yang merupakan negara dengan potensi bahan dasar obat alam dan keanekaragaman hayati terbanyak ketiga setelah Brazil dan Cina. Tujuan penelitian ini untuk mengevaluasi situasi paten obat yang terdaftar di Direktorat Paten, Ditjen HKI, Kementerian Hukum dan Hak Asasi Manusia RI dalam 7 tahun terakhir (tahun 2005 sampai 2011 untuk PM (malaria dan tuberkulosis dan PTM (hipertensi dan diabetes. Metode observasional dengan penelusuran dokumen paten dari alamat web instansi terkait. Hasilnya Indonesia hanya mendaftarkan 4,9% dari seluruh paten yang didaftarkan di Dirjen HKI dari tahun 2005 sampai dengan 2011, sebagai berikut untuk obat anti-hipertensi 3,4% dari 89 paten, anti-diabetes hanya 4,8% dari 250 paten, anti malaria 21,1% dari 18 paten anti-tuberkulosis 7,1% dari 14 paten. Sebagian besar paten yang didaftarkan oleh pendaftar Indonesia merupakan paten obat ekstrak herbal atau komposisinya. Kesimpulan dari penelitian ini adalah paten obat untuk PTM dan PM di Indonesia masih didominasi paten luar negeri.Kata Kunci : Situasi paten, obat, Ditjen HKI, IndonesiaAbstractIndonesia is the fourth most populous country after China, India and America. There

  19. Chronic Renal Transplant Rejection and Possible Anti-Proliferative Drug Targets.

    Science.gov (United States)

    Bhatti, Adnan Bashir; Usman, Muhammad

    2015-01-01

    The global prevalence of renal transplants is increasing with time, and renal transplantation is the only definite treatment for end-stage renal disease. We have limited the acute and late acute rejection of kidney allografts, but the long-term survival of renal tissues still remains a difficult and unanswered question as most of the renal transplants undergo failure within a decade of their transplantation. Among various histopathological changes that signify chronic allograft nephropathy (CAN), tubular atrophy, fibrous thickening of the arteries, fibrosis of the kidney interstitium, and glomerulosclerosis are the most important. Moreover, these structural changes are followed by a decline in the kidney function as well. The underlying mechanism that triggers the long-term rejection of renal transplants involves both humoral and cell-mediated immunity. T cells, with their related cytokines, cause tissue damage. In addition, CD 20+ B cells and their antibodies play an important role in the long-term graft rejection. Other risk factors that predispose a recipient to long-term graft rejection include HLA-mismatching, acute episodes of graft rejection, mismatch in donor-recipient age, and smoking. The purpose of this review article is the analyze current literature and find different anti-proliferative agents that can suppress the immune system and can thus contribute to the long-term survival of renal transplants. The findings of this review paper can be helpful in understanding the long-term survival of renal transplants and various ways to improve it. PMID:26677426

  20. Pharmacological profile of MEDI-551, a novel anti-CD19 antibody, in human CD19 transgenic mice.

    Science.gov (United States)

    Gallagher, Sandra; Turman, Sean; Yusuf, Isharat; Akhgar, Ahmad; Wu, Yuling; Roskos, Lorin K; Herbst, Ronald; Wang, Yue

    2016-07-01

    B cell depletion therapy is beneficial for patients with B cell malignancies and autoimmune diseases. CD19, a transmembrane protein, is expressed on a vast majority of normal and neoplastic B cells, making it a suitable target for monoclonal antibody (MAb) mediated immunotherapy. We have developed MEDI-551, an affinity optimized and afucosylated IgG1 MAb targeting human CD19 for B cell depletion. MEDI-551 is currently under investigation in multiple clinical trials. Because MEDI-551 does not cross react with rodent and non-human primate CD19, the pharmacological characteristics of the MAb were evaluated in human CD19 transgenic mice (hCD19 Tg). Here we show that MEDI-551 potently depletes tissue and circulating B cells in hCD19 Tg mice and is more efficacious than the anti-CD19 MAb with intact fucose. The length of B cell depletion depends on MEDI-551 dose; and, B cell recovery in the circulation follows stepwise phenotypic maturation. Furthermore, intravenous (IV) and subcutaneous (SC) administration of MEDI-551 results in comparable efficacy. Lastly, the combination of MEDI-551 with the anti-CD20 MAb, rituximab, further prolongs the duration of B cell depletion. In summary, the pharmacological profile of MEDI-551 presented in hCD19 Tg mice supports further testing of MEDI-551 in clinical trials involving B cell malignancies and autoimmune diseases. PMID:27163209

  1. Anti-Insurance

    OpenAIRE

    Robert D. Cooter; Porat, Ariel

    2002-01-01

    In standard models of contracts, efficient incentives require the promisor to pay damages for non-performance and the promisee to receive no damages. To give efficient incentives to both parties, we propose a novel contract requiring the promisor to pay damages for nonperformance to a third party, not to the promisee. In exchange for the right to damages, the third party pays the promisor and promisee in advance before performance or nonperformance occurs. We call this novel contract "anti-in...

  2. Anti-Corrosion Coating

    Science.gov (United States)

    1986-01-01

    SuperSpan RM 8000 is an anti-corrosion coating which effectively counteracts acid degradation, abrasive wear, and cracking in power industry facilities. It was developed by RM Industrial Products Company, Inc. with NERAC assistance. It had previously been necessary to shut down plants to repair or replace corroded duct-work in coal burning utilities. NASA-developed technology was especially useful in areas relating to thermoconductivity of carbon steel and the bonding characteristics of polymers. The product has sold well.

  3. Anti-Microtubule Drugs.

    Science.gov (United States)

    Florian, Stefan; Mitchison, Timothy J

    2016-01-01

    Small molecule drugs that target microtubules (MTs), many of them natural products, have long been important tools in the MT field. Indeed, tubulin (Tb) was discovered, in part, as the protein binding partner of colchicine. Several anti-MT drug classes also have important medical uses, notably colchicine, which is used to treat gout, familial Mediterranean fever (FMF), and pericarditis, and the vinca alkaloids and taxanes, which are used to treat cancer. Anti-MT drugs have in common that they bind specifically to Tb in the dimer, MT or some other form. However, their effects on polymerization dynamics and on the human body differ markedly. Here we briefly review the most-studied molecules, and comment on their uses in basic research and medicine. Our focus is on practical applications of different anti-MT drugs in the laboratory, and key points that users should be aware of when designing experiments. We also touch on interesting unsolved problems, particularly in the area of medical applications. In our opinion, the mechanism by which any MT drug cures or treats any disease is still unsolved, despite decades of research. Solving this problem for particular drug-disease combinations might open new uses for old drugs, or provide insights into novel routes for treatment. PMID:27193863

  4. Prescription Nonsteroidal Anti-Inflammatory Medicines

    Science.gov (United States)

    MENU Return to Web version Prescription Nonsteroidal Anti-Inflammatory Medicines Prescription Nonsteroidal Anti-Inflammatory Medicines How do prescription nonsteroidal anti-inflammatory drugs work? Nonsteroidal anti-inflammatory drugs (also called NSAIDs) stop cyclooxygenase ...

  5. Anti-Sharing

    OpenAIRE

    Kirstein, Roland; Cooter, Robert

    2005-01-01

    The paper proposes a mechanism that may implement first-best effort in simultaneous teams. Within the framework of this mechanism, each team members is obliged to make a fixed, non-contingent payment, and chooses his individual effort. After the output is produced, each team member receives a gross payment that equals the actual team output. We demonstrate that a Nash equilibrium exists in which each team member chooses first-best effort. We call this mechanism ?Anti-Sharing? since it solves ...

  6. Anti-inflammatory Activity.

    Science.gov (United States)

    2016-01-01

    Inflammation is the body's first response to infection or injury and is critical for both innate and adaptive immunity. It can be considered as part of the complex biological response of vascular tissues to harmful stimuli such as pathogens, damaged cells, or irritants. The search for natural compounds and phytoconstituents that are able to interfere with these mechanisms by preventing a prolonged inflammation could be useful for human health. Here, the anti-inflammatory properties of plant-based drugs are put together with both in vitro and acute (carrageenan, egg albumin and croton oil) and chronic (cotton pellet) in vivo models. PMID:26939273

  7. The Anti-Landscape

    DEFF Research Database (Denmark)

    longer sustain life. This history includes T. S. Eliot’s Wasteland and Cormac McCarthy’s The Road as well as air pollution, recycled railway lines, photography and landfills. It links theories of aesthetics, politics, tourism, history, geography, and literature into the new synthesis of the environmental...... humanities. The Anti-Landscape provides an interdisciplinary approach that moves beyond the false duality of nature vs. culture, and beyond diagnosis and complaint to the recuperation of damaged sites into our complex heritage. Collection of essays based on a conference held at SDU in 2011....

  8. Criminalising Anti-Social Behaviour

    OpenAIRE

    Andrew CORNFORD

    2012-01-01

    This paper considers the justifiability of criminalising anti-social behaviour through two-step prohibitions such as the Anti-Social Behaviour Order (ASBO). The UK government has recently proposed to abolish and replace the ASBO; however, the proposed new orders would retain many of its most controversial features. The paper begins by criticising the definition of anti-social behaviour employed in both the current legislation and the new proposals. This definition is objectionable because it ...

  9. General quantum anti-brackets

    International Nuclear Information System (INIS)

    The recently introduced quantum anti-brackets are further generalized which makes it possible the odd Q operator to be arbitrary one. Obvious formulae for higher quantum anti-brackets of arbitrary orders and their Jacobian generalized identities are presented. The limitation, leading to an ordinary quantum anti-bracket, which is characterized by the same properties as its classical analogue, is considered. The attachments to the Batalin-Vilkovisky-Fradkin quantizations are considered. Some remarks on the corresponding properties and the quantum Sp(2) anti-brackets attachments are presented

  10. Anti-sulfotyrosine antibodies

    Science.gov (United States)

    Bertozzi, Carolyn R.; Kehoe, John; Bradbury, Andrew M.

    2009-09-15

    The invention provides anti-sulfotyrosine specific antibodies capable of detecting and isolating polypeptides that are tyrosine-sulfated. The sulfotyrosine antibodies and antibody fragments of the invention may be used to discriminate between the non-sulfated and sulfated forms of such proteins, using any number of immunological assays, such ELISAs, immunoblots, Western Blots, immunoprecipitations, and the like. Using a phage-display system, single chain antibodies (scFvs) were generated and screened against tyrosine-sulfated synthetic peptide antigens, resulting in the isolation of scFvs that specifically recognize sulfotyrosine-containing peptides and/or demonstrate sulfotyrosine-specific binding in tyrosine sulfated proteins. The VH and VL genes from one such sulfotyrosine-specific scFv were employed to generate a full length, sulfotyrosine-specific immunoglobulin.

  11. Anti-Semitism on Campus.

    Science.gov (United States)

    Malaney, Gary D.; Williams, Elizabeth A.

    1994-01-01

    Investigated and compared Jewish (n=219) and non-Jewish (n=197) students' perceptions of the anti-Semitic atmosphere at University of Massachusetts at Amherst. Jewish students were significantly more likely to perceive anti-Semitic environment than were non-Jewish students. Nonetheless, 71.4% of non-Jewish students believed Jewish students were…

  12. Exotic N anti N resonances

    International Nuclear Information System (INIS)

    Some experimental suggestions for detecting exotic N anti N resonances were previously reviewed. Some additional possibilities not directly related to bump hunting are mentioned. The discussion includes the magnitude of Reggeon-exchange contributions to baryon--antibaryon total cross sections, the smallness of S-wave annihilation rates, and the precision of symmetry description of anti NN annihilations at rest

  13. Low energy anti p physics at FNAL

    International Nuclear Information System (INIS)

    The charmonium formation experiment is the only low energy anti p experiment at FNAL. This paper describes the performance of the Fermilab anti p Accumulator during fixed target run for the experiment and the planned upgrades. We also discuss the proposal for the direct CP violation search in anti p+p→anti Λ+Λ→ anti pπ++pπ-. (orig.)

  14. Modern anti-Semitism and anti-Israeli attitudes.

    Science.gov (United States)

    Cohen, Florette; Jussim, Lee; Harber, Kent D; Bhasin, Gautam

    2009-08-01

    Anti-Semitism is resurgent throughout much of the world. A new theoretical model of anti-Semitism is presented and tested in 3 experiments. The model proposes that mortality salience increases anti-Semitism and that anti-Semitism often manifests as hostility toward Israel. Study 1 showed that mortality salience led to greater levels of anti-Semitism and lowered support for Israel. This effect occurred only in a bogus pipeline condition, indicating that social desirability masks hostility toward Jews and Israel. Study 2 showed that mortality salience caused Israel, but no other country, to perceptually loom large. Study 3 showed that mortality salience increased punitiveness toward Israel's human rights violations more than it increased hostility toward the identical human rights violations committed by Russia or India. Collectively, results suggest that Jews constitute a unique cultural threat to many people's worldviews, that anti-Semitism causes hostility to Israel, and that hostility to Israel may feed back to increase anti-Semitism. PMID:19634976

  15. Anti-nuclear movements

    International Nuclear Information System (INIS)

    Nuclear power, heralded in the years after World War II as the answer to the world's energy needs, has in more recent times become the focus of intense ecological, political and economic debate. In this study, the current worldwide opposition to nuclear power is examined from its origins in expert dissent to the widespread development of grassroots activity. Chapter headings include: Social Movements: A Theoretical Framework; Creating the Preconditions for Public Protest; Local and Regional Opposition: Mobilizing the Grass Roots; Local Opposition and the Politicization of Nuclear Power; The Use of Local Opposition as a Political Resource; Local Opposition and Social Movement Analysis; The Removal of Political Stimuli: The Unpolitics of Nuclear Siting; Analyzing Host Community Attitudes: The Survey Evidence; Attitudes and Political Action of Nuclear Host Communities: Approaches and Explanations; Novel Siting Approaches and their Political Implications; Siting and Social Movement Analysis; Patterns and Outcomes of Nuclear Energy Conflicts; The Future of the Nuclear Energy Conflict. Throughout the text, analysis and theory are blended with detailed accounts of the growth and activities of individual anti-nuclear organizations in different countries. (author)

  16. Anti-androgen treatments.

    Science.gov (United States)

    Bachelot, Anne; Chabbert-Buffet, Nathalie; Salenave, Sylvie; Kerlan, Véronique; Galand-Portier, Marie-Béatrice

    2010-02-01

    1. Estrogen plus progestin contraceptives (EPP) are the first-line treatment of moderate hirsutism and acne in women of child bearing age (grade C). 2. CPA, 50mg/day, 20 days out of 28, associated with estrogen is the first-line treatment of "moderate to severe hirsutism" in women of childbearing age (grade C). 3. Spironolactone, given as a contraceptive, can be proposed as a second-line treatment in case of side effects or counter-indications to CPA in moderate to severe hirsutism (grade C) in women of childbearing age. No market authorization in this indication. 4. Flutamide or Finasteride are "only" to be used under the guise of contraception as a "thirdline therapy" in cases of severe hirsutism, the presence of side effects or counter-indications to EPP, CPA 50mg/day or spironolactone (grade C). No market authorization in this indication 5. There is no indication for GnRH analogs as an anti-androgen treatment in women of childbearing age given the current therapeutic alternatives (grade C) 6. Only long-term hair removal treatments can be proposed (grade C): electrolysis or laser hair removal. PMID:20096826

  17. Anti-parallel triplexes

    DEFF Research Database (Denmark)

    Kosbar, Tamer R.; Sofan, Mamdouh A.; Waly, Mohamed A.;

    2015-01-01

    -parallel TFO strand was modified with Y with one or two insertions at the end of the TFO strand, the thermal stability was increased 1.2 °C and 3 °C at pH 7.2, respectively, whereas one insertion in the middle of the TFO strand decreased the thermal stability 1.4 °C compared to the wild type oligonucleotide......-1-yl chain, especially at the end of the TFO strand. On the other hand, the thermal stability of the anti-parallel triplex was dramatically decreased when the TFO strand was modified with the LNA monomer analog Z in the middle of the TFO strand (ΔTm = -9.1 °C). Also the thermal stability...... decreased about 6.1 °C when the TFO strand was modified with Z and the Watson-Crick strand with adenine-LNA (AL). The molecular modeling results showed that, in case of nucleobases Y and Z a hydrogen bond (1.69 and 1.72 Å, respectively) was formed between the protonated 3-aminopropyn-1-yl chain...

  18. Anomalous expression of Thy1 (CD90) in B-cell lymphoma cells and proliferation inhibition by anti-Thy1 antibody treatment

    Energy Technology Data Exchange (ETDEWEB)

    Ishiura, Yoshihito [Department of Biochemistry, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kotani, Norihiro, E-mail: kotani@kochi-u.ac.jp [CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kochi System Glycobiology Center, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); Yamashita, Ryusuke [Department of Biochemistry, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Yamamoto, Harumi [Laboratory of Membrane Biochemistry and Biophysics, Graduate School of Biostudies, Kyoto University, Yoshida Shimo-Adachi, Sakyo, Kyoto 606-8501 (Japan); Kozutsumi, Yasunori [CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Laboratory of Membrane Biochemistry and Biophysics, Graduate School of Biostudies, Kyoto University, Yoshida Shimo-Adachi, Sakyo, Kyoto 606-8501 (Japan); Honke, Koichi [Department of Biochemistry, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kochi System Glycobiology Center, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan)

    2010-05-28

    The anti-CD20 monoclonal antibody (Ab) rituximab is accepted to be an effective therapeutic Ab for malignant B-cell lymphoma; however, discovery of other cell surface antigens is required for the option of antibody medicine. Considering that many tumor-associated antigens are glycans, we have searched glycoconjugates for the candidate antigens that therapeutic Abs target. To this end, we first focused on the difference in the glycogenes expression in terms of Epstein-Barr virus (EBV) infection of a Burkitt's lymphoma cell line, Akata. Using DNA array, flow cytometry and Western blotting, we found that Thy1 was highly expressed in EBV-positive Akata cells. Subsequently, Thy1 was found to be expressed in other B-cell lymphoma cell lines: BJAB, MutuI, and MutuIII, irrespective of EBV infection. Treatment of these cells with an anti-Thy1 monoclonal antibody inhibited proliferation more strongly than the therapeutic Ab rituximab. The B-cell lymphoma cell lines were classified based on the extent of the proliferation inhibition, which was not correlated with the expression level of Thy1. It is suggested that stable residence of receptor tyrosine kinases in lipid rafts sustains cell growth in B-cell lymphoma cells.

  19. A fuzzy distinction: Anti-Judaism and anti-Semitism

    OpenAIRE

    FAVRET-SAADA, Jeanne

    2014-01-01

    Scholarly contributions on the responsibility of the churches for the extermination of the Jews during the Second World War contrast Nazi "anti-Semitism" (the aversion toward the Jews as a racial group) with Christian "anti-Judaism" (the Christian aversion toward the Jewish religion), as one would oppose the new to the old, the modern to the traditional, the political to the religious, science to theology. The author shows, using four examples (Léon Poliakov, Hannah Arendt, Colette Guillaumin...

  20. The anti pp yields anti λ λ reaction near threshold

    International Nuclear Information System (INIS)

    Measurements of differential and integrated cross sections as well as final state polarizations for the anti p p → anti Λ Λ reaction are presented. The reaction was studied at two incident antiproton momenta (1476.5 MeV/c and 1507.5 MeV/c) corresponding to total center of mass energies of 15.5 MeV and 26.4 MeV above the reaction threshold. The trajectories of charged decay products of the anti Λ and Λ were observed in a multiwire proportional chamber and in two sets of drift chambers. The data were analyzed with a computer program which reconstructed anti p p → anti Λ Λ → anti p π+pπ- events and performed kinematic fitting. The results are compared to several recent meson exchange calculations, and a one-gluon exchange calculation. The experiment was performed at the Low Energy Antiproton Ring (LEAR) at CERN. The data presented represent the first results of the PS185 collaboration's study of the threshold production of hyperon-antihyperon states

  1. Study of anti-deuterons, anti-tritons and anti-{sup 3}He at Belle

    Energy Technology Data Exchange (ETDEWEB)

    Kuenze, Stephanie; Galuska, Martin; Gessler, Thomas; Kuehn, Wolfgang; Lange, Jens Soeren; Muenchow, David; Semmler, Diego; Spruck, Bjoern; Ullrich, Matthias; Werner, Marcel [2. Physikalisches Institut, Universitaet Giessen (Germany)

    2010-07-01

    Events of the type e{sup +}e{sup -}{yields} anti d+X, anti t+X, anti-{sup 3}He+X, are rare events in e{sup +}e{sup -} collisions as they require the production of several anti-quarks together with their corresponding quarks (6+6 in the deuteron case, 9+9 for triton and {sup 3}He). In addition, in order to form a bound state, the anti-quarks must be close in phasespace, so that coalescence (i.e. overlap of the wave functions) can be applied. Preliminary results from Belle at {radical}(s){approx_equal}10.6 GeV with a data set of 589fb{sup -1}, using dE/dx in the Belle drift chamber for particle identification, are presented. The momentum distribution of the anti-nuclei can be compared to a fireball model. Preliminary results of the search for anti-{sup 4}He are also presented.

  2. Anti-oxidant, anti-inflammatory and anti-proliferative activities of Moroccan commercial essential oils.

    Science.gov (United States)

    Aazza, Smail; Lyoussi, Badiaa; Megías, Cristina; Cortés-Giraldo, Isabel; Vioque, Javier; Figueiredo, A Cristina; Miguel, Maria G

    2014-04-01

    Essential oils (EO) possess antimicrobial, anti-inflammatory, insect repellent, anti-cancer, and antioxidant properties, among others. In the present work, the antioxidant, anti-inflammatory and anti-proliferative activities of Moroccan commercial EOs (Citrus aurantium, C. limon, Cupressus sempervirens, Eucalyptus globulus, Foeniculum vulgare and Thymus vulgaris) were evaluated and compared with their main constituents. T. vulgaris EO showed the best free radicals scavenging capacity. This EO was also the most effective against lipid peroxidation along with C. limon and F. vulgare EOs. C. sempervirens EO was the most effective in scavenging NO free radicals, whereas C. limon EO showed the best chelating power. Not all of the major compounds of the EO were responsible for the whole activity of the EOs. T. vulgaris EO showed the best anti-proliferative activity against THP-1 cells in contrast to that of F. vulgare. The antioxidant and anti-inflammatory activities of the EOs were plant species dependent and not always attributable to the EOs main components. Nevertheless, the EOs anti-proliferative activities were more related to their main components, as with T. vulgaris, C. limon, E. globulus and C. sempervirens. PMID:24868891

  3. Neue Anti-Spam-Techniken

    OpenAIRE

    Richter, Frank

    2004-01-01

    Workshop "Netz- und Service-Infrastrukturen" Dieser Beitrag zum Workshop "Netz- und Service-Infrastrukturen" 2004 analysiert den Stand der Anti-Spam-Maßnahmen an der TU Chemnitz und zeigt neue Techniken auf.

  4. Anti-reflux surgery - children

    Science.gov (United States)

    ... stomach). Problems with these muscles can lead to gastroesophageal reflux disease (GERD). This surgery can also be done during a ... Anti-reflux surgery is usually done to treat GERD in children only after medicines have not worked ...

  5. Narrow n anti n resonances

    International Nuclear Information System (INIS)

    The present status of the problem of quasinuclear states in systems of nucleons and antinucleons is reviewed. The theoretical predictions are compared with experimental data on narrow meson resonances near N anti N threshold which appeared in 1971-74

  6. Online Anti-Brand Herds

    DEFF Research Database (Denmark)

    Langley, David J.; Tan, Chee-Wee; Worm, Daniël;

    The online environment offers a fertile breeding ground for anti-brand herds of disgruntled consumers. Firms are often caught off guard by the unpredictability of such herds and, as a consequence, are forced into a reactive, defensive stance. We conduct a social media analysis that aims to shed l...... guide theory development in this area....... light on the formation, growth, and dissolution of online anti-brand herds. First we expand on the concept of environmental turbulence to advance core properties unique to online herd behavior. Next, based on evidence gathered from 40 online anti-brand herd episodes targeting two prominent firms from...... the Netherlands, we develop an analytical model to investigate drivers of herd formation, growth, and dissolution. Finally, combining environmental turbulence literature with our empirical findings, we derive a novel typology of online anti-brand herd behaviors, and put forward six propositions to...

  7. Anti Rh Hemolytic Disease due to Anti C Antibody: Is Testing for Anti D Antibodies Enough?

    OpenAIRE

    Negi, Gita; Singh, Gaur Dushyant

    2011-01-01

    Rh blood group system is a complex blood group system. Rh antibodies are produced in Rh negative individuals following exposure to foreign RBCs after transfusion or pregnancy. Anti C is a rare cause of hemolytic disease of newborn and is very scarcely reported in the literature. The aim of the present case report of Hemolytic disease caused by Anti C antibody is to bring out the fact that antibodies other than anti D should be considered in cases that give a suggestive history but no evidence...

  8. Solidarity, authenticity and anti racism

    OpenAIRE

    Dinesh Wadiwel

    2009-01-01

    Anti Racist struggles often aim to construct alliances between groups under the banner of "solidarity" in order to achieve change. Using Foucault's Society Must be Defended lectures as a basis, this paper interrogates the difficulties associated with creating solidarity in anti racist movements, when conflict and war might be treated as the basis for racial stratifications. Following from this, it is argued that friendships in spite of differences are possible under the guise of "truce": that...

  9. Anti-inflammatory and anti-cancer activity of mulberry (Morus alba L.) root bark

    OpenAIRE

    Eo, Hyun Ji; Park, Jae Ho; Park, Gwang Hun; Lee, Man Hyo; Lee, Jeong Rak; Koo, Jin Suk; Jeong, Jin Boo

    2014-01-01

    Background Root bark of mulberry (Morus alba L.) has been used in herbal medicine as anti-phlogistic, liver protective, kidney protective, hypotensive, diuretic, anti-cough and analgesic agent. However, the anti-cancer activity and the potential anti-cancer mechanisms of mulberry root bark have not been elucidated. We performed in vitro study to investigate whether mulberry root bark extract (MRBE) shows anti-inflammatory and anti-cancer activity. Methods In anti-inflammatory activity, NO was...

  10. Garcinol: Current status of its anti-oxidative, anti-inflammatory and anti-cancer effects.

    Science.gov (United States)

    Liu, Chaoqun; Ho, Paul Chi-Lui; Wong, Fang Cheng; Sethi, Gautam; Wang, Ling Zhi; Goh, Boon Cher

    2015-06-28

    Garcinol is the main medicinal component of the dried fruit rind of Garcinia indica (G. indica), which has traditionally been extensively used to treat gastric ailments and skin irritation. In vitro studies of garcinol revealed its potential therapeutic effects, such as its anti-oxidative, anti-inflammatory and anti-cancer properties. Similarly, in vivo studies in animal models also demonstrated the efficacy of garcinol for the treatment of various inflammatory and cancerous conditions. Despite being well tolerated in preclinical studies, the toxicological profile of garcinol remains elusive. More importantly, systematic pharmacokinetics (PK) studies of garcinol to establish an appropriate route of administration and its effective concentration range under physiological conditions have not yet been performed. PK studies play an essential role in translating the preclinical findings of garcinol from cell line models and animal species to humans, thereby facilitating dose selection, the characterization of the therapeutic index, identification of a metabolic pathway, and the determination of garcinol's potency and tolerability. This paper reviews the current studies of garcinol as a potential anti-oxidant, anti-inflammatory and anti-cancer agent and highlights the importance of performing preclinical PK and toxicological studies on garcinol for its development pipeline. PMID:25796441

  11. Selective anti-cancer agents as anti-aging drugs

    OpenAIRE

    Blagosklonny, Mikhail V.

    2013-01-01

    Recent groundbreaking discoveries have revealed that IGF-1, Ras, MEK, AMPK, TSC1/2, FOXO, PI3K, mTOR, S6K, and NFκB are involved in the aging process. This is remarkable because the same signaling molecules, oncoproteins and tumor suppressors, are well-known targets for cancer therapy. Furthermore, anti-cancer drugs aimed at some of these targets have been already developed. This arsenal could be potentially employed for anti-aging interventions (given that similar signaling molecules are inv...

  12. Is anti-Semitism a homogeneous construct?

    OpenAIRE

    Kempf, Wilhelm

    2009-01-01

    The present paper investigates how the distinction of different facets of anti-Semitism is to be understood from a methodological point of view. Does it mean that there is a unique (quantitative) dimension of anti-Semitism on which the participants can be ordered due to a variety of expressions of anti-Semitic prejudice, or does it imply that these facets are independent dimensions of anti-Semitism, which combine themselves into (qualitatively) different syndromes of anti-Semitism?After discu...

  13. On Mathematical Anti-Evolutionism

    Science.gov (United States)

    Rosenhouse, Jason

    2016-03-01

    The teaching of evolution in American high schools has long been a source of controversy. The past decade has seen an important shift in the rhetoric of anti-evolutionists, toward arguments of a strongly mathematical character. These mathematical arguments, while different in their specifics, follow the same general program and rely on the same underlying model of evolution. We shall discuss the nature and history of this program and model and describe general reasons for skepticism with regard to any anti-evolutionary arguments based upon them. We shall then survey the major arguments used by anti-evolutionists, to show how our general considerations make it possible to quickly identify their weakest points.

  14. The Anti-Doping Movement.

    Science.gov (United States)

    Willick, Stuart E; Miller, Geoffrey D; Eichner, Daniel

    2016-03-01

    Historical reports of doping in sports date as far back as the ancient Greek Olympic Games. The anti-doping community considers doping in sports to be cheating and a violation of the spirit of sport. During the past century, there has been an increasing awareness of the extent of doping in sports and the health risks of doping. In response, the anti-doping movement has endeavored to educate athletes and others about the health risks of doping and promote a level playing field. Doping control is now undertaken in most countries around the world and at most elite sports competitions. As athletes have found new ways to dope, however, the anti-doping community has endeavored to strengthen its educational and deterrence efforts. It is incumbent upon sports medicine professionals to understand the health risks of doping and all doping control processes. PMID:26972261

  15. Bayesian anti-sparse coding

    CERN Document Server

    Elvira, Clément; Dobigeon, Nicolas

    2015-01-01

    Sparse representations have proven their efficiency in solving a wide class of inverse problems encountered in signal and image processing. Conversely, enforcing the information to be spread uniformly over representation coefficients exhibits relevant properties in various applications such as digital communications. Anti-sparse regularization can be naturally expressed through an $\\ell_{\\infty}$-norm penalty. This paper derives a probabilistic formulation of such representations. A new probability distribution, referred to as the democratic prior, is first introduced. Its main properties as well as three random variate generators for this distribution are derived. Then this probability distribution is used as a prior to promote anti-sparsity in a Gaussian linear inverse problem, yielding a fully Bayesian formulation of anti-sparse coding. Two Markov chain Monte Carlo (MCMC) algorithms are proposed to generate samples according to the posterior distribution. The first one is a standard Gibbs sampler. The seco...

  16. Solidarity, authenticity and anti racism

    Directory of Open Access Journals (Sweden)

    Dinesh Wadiwel

    2009-08-01

    Full Text Available Anti Racist struggles often aim to construct alliances between groups under the banner of "solidarity" in order to achieve change. Using Foucault's Society Must be Defended lectures as a basis, this paper interrogates the difficulties associated with creating solidarity in anti racist movements, when conflict and war might be treated as the basis for racial stratifications. Following from this, it is argued that friendships in spite of differences are possible under the guise of "truce": that is through allegiances that begin by acknowledging the fact of war.

  17. Skin anti-aging strategies

    OpenAIRE

    Ganceviciene, Ruta; Liakou, Aikaterini I.; Theodoridis, Athanasios; Makrantonaki, Evgenia; Zouboulis, Christos C.

    2012-01-01

    Skin aging is a complex biological process influenced by a combination of endogenous or intrinsic and exogenous or extrinsic factors. Because of the fact that skin health and beauty is considered one of the principal factors representing overall “well-being” and the perception of “health” in humans, several anti-aging strategies have been developed during the last years. It is the intention of this article to review the most important anti-aging strategies that dermatologists have nowadays in...

  18. Anti-creationism in America

    Science.gov (United States)

    Park, Hee-Joo

    This thesis documents the development of organised anti-creationism in America. The revival of creationism culminated in the late 1970s with the success of creationists' national campaign for the introduction of legislation mandating "equal-time" for scientific creationism and evolution in the public schools. This prompted a proliferation of local protest groups which were eventually linked by the network called the Committees of Correspondence. This network became the political arm of the anti-creation movement at the grass-roots level. On the other hand, a small group of evolutionists responded to the creationist arguments by launching a journal, Creation/Evolution, which disseminated anti-creationism arguments. At the educational front, the National Association of Biology Teachers led the battle. These political, polemical and educational efforts were combined and evolved into the National Center for Science Education in 1986. With the NCSE, the evolution camp for the first time had its own full-time defenders to oppose large well-financed anti-evolution efforts. It appears, however, that the impact of organised anti-creationism was fairly limited. Evidence suggests that, despite anti-creationists' concerted efforts, the creationist movement in the nineties is as vigorous as ever and its influence on public beliefs about origins of the organic world remains strong. Gallup Polls have consistently shown that almost half of the adult population in the U.S. believes in the creation of humans about 10,000 years ago. Despite this dismal situation, major scientific bodies have failed to become directly engaged in the anti-creationism campaign due to their concern over public relation. Scientific organisations depend on public support for their research funds and therefore they generally do not want to offend the public by directly challenging its cherished beliefs such as creationism. Therefore, the ongoing battle has been largely left in the hands of individual

  19. Anti-Oxidant, Anti-Inflammatory and Anti-Angiogenic Properties of Resveratrol in Ocular Diseases

    Directory of Open Access Journals (Sweden)

    Allan Lançon

    2016-03-01

    Full Text Available Resveratrol (3,4′,5 trihydroxy-trans-stilbene is one of the best known phytophenols with pleiotropic properties. It is a phytoalexin produced by vine and it leads to the stimulation of natural plant defenses but also exhibits many beneficial effects in animals and humans by acting on a wide range of organs and tissues. These include the prevention of cardiovascular diseases, anti-cancer potential, neuroprotective effects, homeostasia maintenance, aging delay and a decrease in inflammation. Age-related macular degeneration (AMD is one of the main causes of deterioration of vision in adults in developed countries This review deals with resveratrol and ophthalmology by focusing on the antioxidant, anti-inflammatory, and anti-angiogenic effects of this molecule. The literature reports that resveratrol is able to act on various cell types of the eye by increasing the level of natural antioxidant enzymatic and molecular defenses. Resveratrol anti-inflammatory effects are due to its capacity to limit the expression of pro-inflammatory factors, such as interleukins and prostaglandins, and also to decrease the chemo-attraction and recruitment of immune cells to the inflammatory site. In addition to this, resveratrol was shown to possess anti-VEGF effects and to inhibit the proliferation and migration of vascular endothelial cells. Resveratrol has the potential to be used in a range of human ocular diseases and conditions, based on animal models and in vitro experiments.

  20. Targeted anti-cancerous therapies

    International Nuclear Information System (INIS)

    Crowning decades of efforts in fundamental and applied research, the first generation of targeted anti cancerous drugs is now on the market. Drugs coming from a new approach, conceived from molecular knowledge of cancer and directed against beforehand identified targets. In theory: a miracle of precision and technical success. In practice: a new sources of questions and new problems. (N.C.)

  1. Acute hemolytic transfusion reactions due to multiple alloantibodies including anti-E, anti-c and anti-Jkb.

    Science.gov (United States)

    Park, Tae Sung; Kim, Ki Uk; Jeong, Woo Jin; Kim, Hyung Hoi; Chang, Chulhun L; Chung, Joo Seop; Cho, Goon Jae; Lee, Eun Yup; Son, Han Chul

    2003-12-01

    We report a case of two consecutive episodes of acute hemolytic transfusion reactions (HTRs) due to multiple alloantibodies in a 34-yr-old man who suffered from avascular necrosis of left femoral head. He received five units of packed red blood cells (RBCs) during surgery. Then the transfusion of packed RBCs was required nine days after the surgery because of the unexplained drop in hemoglobin level. The transfusion of the first two units resulted in fever and brown-colored urine, but he received the transfusion of another packed RBCs the next day. He experienced even more severe symptoms during the transfusion of the first unit. We performed antibody screening test, and it showed positive results. Multiple alloantibodies including anti-E, anti-c and anti-Jkb were detected by antibody identification study. Acute HTRs due to multiple alloantibodies were diagnosed, and the supportive cares were done for 6 days. We suggest the antibody screening test should be included in the panel of pretransfusion tests for safer transfusion, and it is particularly mandatory for the patients with multiple transfusions, pregnant women, and preoperative patients. PMID:14676451

  2. Anti-TNFa treatment in patients with rheumatoid arthritis and anti-Ro/SSA antibodies

    OpenAIRE

    Airò, P; R. Gorla; M. Vianelli; M. Frassi; Danieli, E; F. Franceschini; I. Cavazzana; Cattaneo, R

    2011-01-01

    Objective: To analyse clinical efficacy, onset of new autoantibodies or symptoms of autoimmune disease in patients affected by rheumatoid arthritis with anti-Ro/SSA treated with anti-TNFa agents. Methods: Six anti-Ro/SSA positive subjects with RA were studied every six months until 24th month of treatment in order to detect ANA titer (IFI), anti-dsDNA (Farr), anti-cardiolipin and anti-beta2glycoprotein I (ELISA), anti-ENA (CIE). The titre of anti-Ro/SSA were analysed by ELISA. Four patients w...

  3. The Scientist as Anti-Hero

    Science.gov (United States)

    Goran, Morris

    1976-01-01

    Suggests a new strategy for the proponents of science to rebut the cultural anti-science wave. This strategy involves publicizing the anti-hero scientist and presents a number of candidates from the past as examples. (GS)

  4. Laparoscopic Anti-Reflux (GERD) Surgery

    Science.gov (United States)

    ... Exhibit Opportunities Sponsorship Opportunities Login Laparoscopic Anti-Reflux (GERD) Surgery Patient Information from SAGES Print PDF Find ... to have laparoscopic anti-reflux surgery What is Gastroesophageal Reflux Disease (GERD)? Although “heartburn” is often used to ...

  5. Clinical Scenarios for Discordant Anti-Xa

    OpenAIRE

    Jesus Vera-Aguilera; Hindi Yousef; Diego Beltran-Melgarejo; Teng Hugh Teng; Ramos Jan; Mary Mok; Carlos Vera-Aguilera; Eduardo Moreno-Aguilera

    2016-01-01

    Anti-Xa test measures the activity of heparin against the activity of activated coagulation factor X; significant variability of anti-Xa levels in common clinical scenarios has been observed. Objective. To review the most common clinical settings in which anti-Xa results can be bias. Evidence Review. Guidelines and current literature search: we used PubMed, Medline, Embase, and MEDION, from 2000 to October 2013. Results. Anti-Xa test is widely used; however the assay underestimates heparin co...

  6. The semileptonic anti B → Dl anti ν and anti Bs → Dsl anti ν decays in Isgur-Wise approach

    International Nuclear Information System (INIS)

    We consider a combination of linear confining and Hulthen potentials in the Hamiltonian and, via the perturbation approach, report the corresponding Isgur-Wise function parameters. Next, we investigate the Isgur-Wise function for anti B → Dl anti ν and anti Bs → Dsl anti ν semileptonic decays and report the decay width, branching ratio, and vertical stroke Vcb vertical stroke CKM matrix element. A comparison with other models and experimental values is included. (orig.)

  7. The dataset from administration of single or combined immunomodulation agents to modulate anti-FVIII antibody responses in FVIII plasmid or protein primed hemophilia A mice.

    Science.gov (United States)

    Liu, Chao Lien; Lyle, Meghan J; Shin, Simon C; Miao, Carol H

    2016-06-01

    Hemophilia A mice with pre-existing inhibitory antibodies against factor VIII (FVIII) were treated with single agents, AMD3100 and GCS-F, respectively. Inhibitor titers in treated mice and control HemA inhibitors mice were followed over time. Total B cells and plasma cells (PCs) were characterized by flow cytometry. HemA inhibitor mice were then treated with a combination regimen of IL-2/IL-2mAb complexes plus rapamycin and AMD3100. Finally, HemA inhibitor mice were treated with a new combination therapy using include IL-2/IL-2mAb complexes + Anti-CD20+AMD3100+G-CSF. The timeline of combination therapy was illustrated. Inhibitor titers following treatment in FVIII plasmid or protein induced inhibitor mice were evaluated overtime. A representative figure and gating strategies to characterize the subsets of Treg cells and B cells are presented. Please see http://dx.doi.org/10.1016/j.cellimm.2016.01.005 [1] for interpretation and discussion of these data and results. PMID:27081675

  8. Immunotherapy of non-Hodgkin's lymphoma with hLL2 (epratuzumab, an anti-CD22 monoclonal antibody) and Hu1D10 (apolizumab).

    Science.gov (United States)

    Leonard, John P; Link, Brian K

    2002-02-01

    Clinical activity of anti-CD20 monoclonal antibodies both in the unlabeled (rituximab [Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA]) and radiolabeled forms, as well as radioimmunoconjugates targeting other antigens, has resulted in the exploration of alternative targets for immunotherapeutic strategies in lymphoma. We report on the rationale for and initial efforts in the development of two unlabeled, humanized monoclonal antibodies directed against molecules commonly expressed in B-cell malignancies. hLL2 (epratuzumab; Immunomedics, Inc, Morris Plains, NJ) binds to the CD22 antigen, while Hu1D10 (apolizumab; Protein Design Labs, Inc, Fremont, CA) reacts with a polymorphism on the HLA-DR beta chain. Preclinical studies and early clinical evaluations suggest that these agents have a potential role as novel therapeutic targets for lymphoma with acceptable toxicity profiles. Further efforts will explore optimal clinical settings for their use, as well as define treatment regimens either as single agents or in combination with chemotherapy or other biologics. PMID:11842393

  9. CERN anti-fraud policy

    CERN Multimedia

    2013-01-01

    In 2011, a working group on improved fraud prevention and management was established. The group was composed of the Director of Administration and General Infrastructure, the Head of the Human Resources Department, and the Heads of the Legal Service and Internal Audit. It recommended the adoption of a global fraud prevention and management policy.   The global fraud prevention and management policy was implemented through the CERN Anti-Fraud Policy, which was endorsed by the Enlarged Directorate in May 2012 and approved by the Director-General for entry into force on 1 January 2013. The CERN Anti-Fraud Policy defines the Organization’s policy in matters of fraud.  CERN has a zero tolerance approach towards fraud, as it would compromise the accomplishment of its objectives and undermine its functioning, credibility and reputation. The policy also states CERN’s commitment to the prevention, identification and investigation of fraud. All CERN contributors have a key rol...

  10. Compact anti-radon facility

    Energy Technology Data Exchange (ETDEWEB)

    Fajt, L.; Kouba, P.; Mamedov, F.; Smolek, K.; Štekl, I., E-mail: ivan.stekl@utef.cvut.cz [Institute of Experimental and Applied Physics, Czech Technical University in Prague, Horská 3a/22, 128 00 Prague 2 (Czech Republic); Fojtík, P.; Hýža, M.; Hůlka, J.; Jílek, K. [SÚRO (NRPI) National Radiation Protection Institute, Bartoškova 1450/28, 140 00 Prague 4 (Czech Republic); Stoček, P.; Veselý, J. [ATEKO a.s., Resslova 956/13, 501 01Hradec Králové, Czech Republic. (Czech Republic); Busto, J. [CPPM, Universite de Marseille, CNRS/IN2P3, F-13288 Marseille (France)

    2015-08-17

    Suppression of radon background is one of main tasks in ultra-low background experiments. The most promising technique for suppression of radon is its adsorption on charcoal. Within the frame of the NEMO-3 experiment, radon trapping facility (RTF) was installed in Modane underground laboratory in 2004. Based on long-term experience with this facility a new compact transportable anti-radon facility was constructed in cooperation among IEAP CTU, SÚRO and ATEKO company. The device provides 20m{sup 3}/h of purified air (air radon activity at the output ∼10mBq/m{sup 3}). The basic features and preliminary results of anti-radon device testing are presented.

  11. Anti-clogging filter system

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Erik P.

    2015-05-19

    An anti-clogging filter system for filtering a fluid containing large particles and small particles includes an enclosure with at least one individual elongated tubular filter element in the enclosure. The individual elongated tubular filter element has an internal passage, a closed end, an open end, and a filtering material in or on the individual elongated tubular filter element. The fluid travels through the open end of the elongated tubular element and through the internal passage and through the filtering material. An anti-clogging element is positioned on or adjacent the individual elongated tubular filter element and provides a fluid curtain that preferentially directs the larger particulates to one area of the filter material allowing the remainder of the filter material to remain more efficient.

  12. Anti-spoofing: Fingerprint Databases

    OpenAIRE

    GALBALLY HERRERO JAVIER

    2013-01-01

    Anti-spoofing may be defined as the pattern recognition problem of automatically differentiating between real and fake biometric samples produced with a synthetically manufactured artefact (e.g., latex or silicone finger). As in any other machine learning problem the availability of data is a critical factor to be able to successfully address this challenging task. Furthermore, these data should be public, so that the performance of different protection methods may be compared in a fully fair...

  13. THEORETICAL PRINCIPLES OF ANTI-BLOCKING AND ANTI-SLIPPAGE SYSTEMS OF NEW GENERATION

    Directory of Open Access Journals (Sweden)

    N. N. Hurski

    2014-12-01

    Full Text Available A new approach on creation of anti-blocking and anti-slippage systems of mobile machines based on observation of actual forces/moment values in «road-wheel-car» contact and their derivatives is considered in the given paper. The paper describes theoretical principles and an operational algorithm of anti-blocking and anti-slippage systems.

  14. Time separated anti p beam

    International Nuclear Information System (INIS)

    In 1974, Fainberg and Kalogeropoulos measured the time structure of a resonant extracted beam from the AGS with the RF kept on the maintain tight bunching. The external pulses were found to be unexpectedly narrow (FWHM = 2.4 nsec after correction for counter resolution). An explanation for this and some pertinent comments were put forth by Barton in a subsequent report. The original motivation for the study was to examine the extent to which single counter time of flight (TOF) measurements would be feasible, making it possible to measure velocities of neutral secondary particles from a target. The encouraging result led later to a proposal by Kalogeropoulos to use the tightly bunched protons to produce a secondary time separated beam (TSB) of anti-protons, i.e., a beam with a long flight path over which the lower velocity particles (anti p's) separate longitudinally from the more numberous fast particles (π's) so that the anti p interactions can be studied independently by suitably gated detectors. Production and transport of such a beam is described

  15. Marine algal natural products with anti-oxidative, anti-inflammatory, and anti-cancer properties

    OpenAIRE

    Lee, Jin-Ching; Hou, Ming-Feng; Huang, Hurng-Wern; Chang, Fang-Rong; Yeh, Chi-Chen; Tang, Jen-Yang; Chang, Hsueh-Wei

    2013-01-01

    For their various bioactivities, biomaterials derived from marine algae are important ingredients in many products, such as cosmetics and drugs for treating cancer and other diseases. This mini-review comprehensively compares the bioactivities and biological functions of biomaterials from red, green, brown, and blue-green algae. The anti-oxidative effects and bioactivities of several different crude extracts of algae have been evaluated both in vitro and in vivo. Natural products derived from...

  16. anti p production and momentum spread reduction of anti p's

    International Nuclear Information System (INIS)

    The anti p source for SSC discussed at the ANL/UC workshop assumes the possibility of reducing momentum spread from +/- 3% to +/- .25% on a 10 GeV debunching orbit. Where parameters had not been defined at the workshop, reasonable values were chosen for a proton accelerator and debuncher to check whether this expectation is realistic. These parameters have been chosen by scaling from the Fermilab design and making some conservative extrapolations from the results of accelerator experiments. The relevant parameters of the proton accelerator and the debunching orbit parameters are given

  17. Guideline for radioimmunotherapy of CD20+ follicular B-cell non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    This guideline is a prerequisite for the quality management in the treatment of non-Hodgkon-lymphomas in patients with relapsed or refractory follicular lymphoma after rituximab therapy and as consolidation therapy after first remission following CHOP like treatment using radioimmunotherapy. It is based on an interdisciplinary consensus and contains background information and definitions as well as specified indications and detailed contraindications of treatment. Essential topics are the requirements for institutions performing the therapy. For instance, presence of an expert for medical physics, intense cooperation with all colleagues committed to treatment of lymphomas, and a certificate of instruction in radiochemical labelling and quality control are required. Furthermore, it is specified which patient data have to be available prior to performance of therapy and how treatment has to be carried out technically. Here, quality control and documentation of labelling are of great importance. After treatment, clinical quality control is mandatory (work-up of therapy data and follow-up of patients). Essential elements of follow-up are specified in detail. The complete treatment inclusive after-care has to be realised in close cooperation with those colleagues (hemato-oncologists) who propose, in general, radioimmuno-therapy under consideration of the development of the disease. (orig.)

  18. Anti-Cyclic Citrullinated Peptide (Anti-CCP and Anti-Mutated Citrullinated Vimentin (Anti-MCV Relation with Extra-Articular Manifestations in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Laura Gonzalez-Lopez

    2014-01-01

    Full Text Available We evaluated the association between anti-cyclic citrullinated peptide antibodies (anti-CCP and anti-mutated citrullinated vimentin antibodies (anti-MCV with the presence of extra-articular (ExRA manifestations in 225 patients with rheumatoid arthritis (RA. Ninety-five patients had ExRA and 130 had no ExRA. There was no association of anti-CCP and anti-MCV levels with the presence of ExRA as total group (P=0.40 and P=0.91, resp.. Making an analysis of individual manifestations, rheumatoid nodules were associated with positivity for rheumatoid factor (RF; (P=0.01, anti-CCP (P=0.048, and anti-MCV (P=0.02. Instead, RF, anti-CCP, or anti-MCV were not associated with SS, chronic anemia, or peripheral neuropathy. Levels of anti-CCP correlated with the score of the Health Assessment Questionnaire-Disability Index (HAQ-Di (r=0.154, P=0.03, erythrocyte sedimentation rate (ESR; (r=0.155, P=0.03, and RF (P=0.254, P<0.001, whereas anti-MCV titres only correlated with RF (r=0.169, P=0.02. On adjusted analysis, ExRA was associated with longer age (P=0.015, longer disease duration (P=0.007, higher DAS-28 score (P=0.002, and higher HAQ-DI score (P=0.007, but serum levels of anti-CCP and anti-MCV were not associated. These findings show the need to strengthen the evaluation of the pathogenic mechanisms implied in each specific ExRA manifestation.

  19. Anti-backlash gear bearings

    Science.gov (United States)

    Vranish, John M. (Inventor)

    2009-01-01

    A gear bearing having a first gear and a second gear, each having a plurality of teeth. Each gear operates on two non-parallel surfaces of the opposing gear teeth to perform both gear and bearing functions simultaneously. The gears are moving at substantially the same speed at their contact points. The gears may be roller gear bearings or phase-shifted gear bearings, and may be arranged in a planet/sun system or used as a transmission. One preferred embodiment discloses and describes an anti-backlash feature to counter ''dead zones'' in the gear bearing movement.

  20. Christianity and Anti-Semitism

    OpenAIRE

    Henry, Martin

    2005-01-01

    Matricide is an awe-inspiring crime. To kill another human being is vile enough, to kill one’s own mother, to deprive of life the person who gave one life, is to move into a different dimension of horror. It represents an almost metaphysical assault on the very order of reality. Yet, if scholars are correct who tell us that Christianity sprang from Judaism, then Christian anti-Semitism, which has frequently in the course of history not stopped short of murder, could be interpreted as a form...

  1. The anti-Einstein equations

    OpenAIRE

    Chaliasos, Evangelos

    2006-01-01

    As we know, from the Einstein equations the vanishing of the four-divergence of the energy-momentum tensor follows. This is the case because the four-divergence of the Einstein tensor vanishes identically. Inversely, we find that from the vanishing of the four-divergence of the energy-momentum tensor not only the Einstein equations follow. Besides, the so-named anti-Einstein equations follow. These equations must be considered as complementary to the Einstein equations. And while from the Ein...

  2. Various Anti IP Spoofing Techniques

    OpenAIRE

    Patel, Sonal; Jha, Vikas

    2015-01-01

    Anti IP Spoofing techniques prevent your system or your Network from the IP Spoofing. IP Spoofing is attack that takes place in Network. It is used to gain unauthorized access to computer by spoofing the IP Address from the IP (Internet Protocol) Packet Header. The main Purpose of IP Spoofing attack is to hide the true identity of the attacker. IP Spoofing is used by the popular attacks like Dos (Denial o Service), DDos (Distributed Denial of Service), and Man in Middle. This Paper Describe v...

  3. The anti-zombie argument

    OpenAIRE

    Frankish, Keith

    2007-01-01

    The zombie argument has come to occupy a central role in the case for a non-physicalist view of consciousness. This paper seeks to turn the tables on defenders of the argument ('zombists') by showing that a parallel argument can be run for physicalism. The argument invokes what I call anti-zombies – purely physical creatures that are nonetheless conscious. I show that, using the same resources as those employed by zombists, it is possible to construct an argument from the conceivability of an...

  4. From image segmentation to anti-textons.

    Science.gov (United States)

    van Tonder, G J; Ejima, Y

    2000-01-01

    We apply the 'patchwork engine' (PE; van Tonder and Ejima, 2000 Neural Networks forthcoming) to encode spaces between textons in an attempt to find a suitable feature representation of anti-textons [Williams and Julesz, 1991, in Neural Networks for Perception volume 1: Human and Machine Perception Ed. H Wechsler (San Diego, CA: Academic Press); 1992, Proceedings of the National Academy of Sciences of the USA 89 6531-6534]. With computed anti-textons it is possible to show that tessellation and distribution of anti-textons can differ from that of textons depending on the ratio of texton size to anti-texton size. From this we hypothesise that variability of anti-textons can enhance texture segregation, and test our hypothesis in two psychophysical experiments. Texture segregation asymmetry is the topic of the first test. We found that targets on backgrounds with regular anti-textons segregate more strongly than on backgrounds with highly variable anti-textons. This neatly complements other explanations for texture segregation asymmetry (e.g. Rubenstein and Sagi, 1990 Journal of the Optical Society of America A 7 1632-1643). Second the relative significance of textons and anti-textons in human texture segregation is investigated for a limited set of texture patterns. Subjects consistently judged a combination of texton and anti-texton gradients as more conspicuous than texton-only gradients, and judged texton-only gradients as being more conspicuous than anti-texton-only gradients. In the absence of strong texton gradients the regularity versus irregularity of anti-textons agrees with perceived texture segregation. Using PE outputs as anti-texton features thus enabled the conception of various useful tests on texture segregation. The PE is originally intended as a general image segmentation method based on symmetry axes. With this paper we therefore hope to relate anti-textons with visual processing in a wider sense. PMID:11220214

  5. Short-Term Outcomes of ABO-Incompatible Living Donor Kidney Transplantation With Uniform Protocol: Significance of Baseline Anti-ABO Titer.

    Science.gov (United States)

    Lee, K W; Park, J B; Oh, D K; Na, B G; Choi, J Y; Cho, W T; Lee, S H; Park, H J; Cho, D; Huh, W S; Kim, S J

    2016-04-01

    Antibody-mediated rejection (AMR) is one of the major causes of poor outcomes in ABO-incompatible kidney transplantation (ABOi KT). Studies investigating AMR risk factors found that anti-ABO titer is a major issue. However, the significance of antibody titer has been debated. This retrospective study analyzed AMR risk factors in 59 patients who underwent ABOi KT between August 2010 and January 2015. We also analyzed AMR risk factors in recipients with high anti-ABO baseline titers (≥1:64 on dithiothreitol at 37°C phase or ≥1:256 on antihuman globulin phase). The 2-year patient survival rate was 95.8%, and the 2-year graft survival rate was 94.9%. Nine patients (15.3%) experienced clinical (6 of 59 [10.2%]) or subclinical (3 of 59 [5.1%]) AMR. One patient experienced graft loss from hyperacute rejection. AMR risk factor analysis revealed that baseline antibody titer was associated with incidence of AMR. In patients with high baseline titers, low doses of rituximab (200-mg single-dose), an antibody against CD20, was predictive for AMR. Six patients who received pretransplant intravenous immunoglobulin did not experience AMR even when they had high baseline antibody titers. Our results indicate that a high baseline antibody titer affected the incidence of AMR. ABOi KT candidates with high baseline titers need to undergo an intensified preconditioning protocol, including high-dose rituximab (375 mg/m(2)) and intravenous immunoglobulin. PMID:27234744

  6. Hemolytic disease of the fetus and newborn caused by anti-D and anti-S alloantibodies: a case report

    OpenAIRE

    Yousuf Rabeya; Abdul Aziz Suria; Yusof Nurasyikin; Leong Chooi-Fun

    2012-01-01

    Abstract Introduction Hemolytic disease of the fetus and newborn is most commonly caused by anti-D alloantibody. It is usually seen in Rhesus D (RhD)-negative mothers that have been previously sensitized. We report here a case of hemolytic disease of the fetus and newborn in a newborn baby caused by anti-D and anti-S alloantibodies, born to a mother who was RhD negative, but with no previous serological evidence of RhD alloimmunization. Case presentation A one-day-old Chinese baby boy was bor...

  7. [Anti-basal ganglia antibody].

    Science.gov (United States)

    Hayashi, Masaharu

    2013-04-01

    Sydenham's chorea (SC) is a major manifestation of rheumatic fever, and the production of anti-basal ganglia antibodies (ABGA) has been proposed in SC. The pathogenesis is hypothesized as autoimmune targeting of the basal ganglia via molecular mimicry, triggered by streptococcal infection. The spectrum of diseases in which ABGA may be involved has been broadened to include other extrapyramidal movement disorders, such as tics, dystonia, and Parkinsonism, as well as other psychiatric disorders. The autoimmune hypothesis in the presence and absence of ABGA has been suggested in Tourette's syndrome (TS), early onset obsessive-compulsive disorders (OCD), and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Recently, the relationship between ABGA and dopamine neurons in the basal ganglia has been examined, and autoantibodies against dopamine receptors were detected in the sera from patients with basal ganglia encephalitis. In Japan, the occurrence of subacute encephalitis, where patients suffer from episodes of altered behavior and involuntary movements, has increased. Immune-modulating treatments are effective, indicating the involvement of an autoimmune mechanism. We aimed to detect the anti-neuronal autoantibodies in such encephalitis, using immunohistochemical assessment of patient sera. The sera from patients showing involuntary movements had immunoreactivity for basal ganglia neurons. Further epitopes for ABGA will be investigated in basal ganglia disorders other than SC, TS, OCD, and PANDAS. PMID:23568985

  8. Environmentally friendly anti-icing

    Science.gov (United States)

    Lockyer, Robert T. (Inventor); Zuk, John (Inventor); Haslim, Leonard A. (Inventor)

    1998-01-01

    The present invention describes an aqueous, non-electrolytic, non-toxic, biodegradable, continuous single phase liquid anti-icing or deicing composition for use on the surfaces of, for example, aircraft, airport pavements, roadways, walkways, bridges, entrances, structures, canals, locks, components, vessels, nautical components, railroad switches, and motor vehicles. The anti-icing or deicing composition comprises: (a) water; (b) a non-toxic freezing point depressant selected from the group consisting of monohydric alcohols having from 2 to 6 carbon atoms, polyhydric alcohols having from 3 to 12 carbon atoms, monomethyl or ethyl ethers of polyhydric alcohols having from 3 to 12 atoms or mixtures thereof, wherein the freezing point depressant present is between about 14 to 60 percent by weight; (c) a thickener which is present in between about 0.01 and 10 percent by weight; and (d) optionally a corrosion inhibitor which is present in between about 0.01 and 0.1 percent by weight of the total composition. In one embodiment, the deicing composition further includes (e) a monohydric primary aliphatic unbranched alcohol as a means of forming a thin layer of the composition on the surface of the structure to be given ice protection, and/or as means of forming a homogenized foam with xanthan thickener; which alcohol is selected from the group consisting of alcohols having between 8 to 24 carbon atoms, preferably, 1-dodecanol. Compositions of water, propylene glycol, and/or propanol and xanthan are preferred.

  9. Search for new physics in anti b → anti s e+e- decays

    International Nuclear Information System (INIS)

    In summer 2014 the LHCb collaboration published their results on the measurement of the observable RK = B(anti B → anti Kμ+μ-)/B(anti B → anti Ke+e-), which revealed a deviation of 2.6σ from the Standard Model prediction. I check whether the deviation can be explained by scalar and pseudo-scalar dimension-six operators and investigate constraints from other measurements in a model-independent way. Furthermore, I analyse the contributions of the new operators to the angular distribution of anti B → anti Ke+e- decays.

  10. Investigation of the decays anti B0 → D*+l-anti ν and anti B → D**l-anti ν

    International Nuclear Information System (INIS)

    Exclusive semileptonic B decays with a D*+ meson in the final state have been studied using the ARGUS detector at the DORIS II storage ring. The branching ratio for the decay anti B0→D*+l-anti ν, where l- is either e- or μ-, has been measured to be (5.2±0.5±0.6)%. A significant rate for the decay anti B→D**l-anti ν has been observed. From an angular analysis of the cascade anti B0→D*+(→D0π+)l-anti ν the forward-backward asymmetry AFB and the D*+ polarization parameter α have been determined to be AFB=0.20±0.08±0.06 and α=1.1±0.4±0.2. (orig.)

  11. Perfect anti-reflection from first principles

    Science.gov (United States)

    Kim, Kyoung-Ho; Q-Han Park

    2013-01-01

    Reducing unwanted reflections through impedance matching, called anti-reflection, has long been an important challenge in optics and electrical engineering. Beyond trial and error optimization, however, a systematic way to realize anti-reflection is still absent. Here, we report the discovery of an analytic solution to this long standing problem. For electromagnetic waves, we find the graded permittivity and permeability that completely remove any given impedance mismatch. We demonstrate that perfect broadband anti-reflection is possible when a dispersive, graded refractive index medium is used for the impedance-matching layer. We also present a design rule for the ultra-thin anti-reflection coating which we confirm experimentally by showing the anti-reflection behavior of an exemplary λ/25-thick coating made of metamaterials. This work opens a new path to anti-reflection applications in optoelectronic device, transmission line and stealth technologies.

  12. Aromatase inhibitors and anti-synthetase syndrome.

    Science.gov (United States)

    Mascella, Fabio; Gianni, Lorenzo; Affatato, Alessandra; Fantini, Manuela

    2016-09-01

    Adjuvant therapy in postmenopausal women with endocrine-responsive breast cancer (BC) is actually centered on the use of anti-aromatase inhibitors (AI). Several reports, however, are emerging in literature associating the use of this drugs to rheumatic disorders. This case report describes the first case of anti-synthetase syndrome diagnosis after treatment with anti-estrogen agents in a patient with pre-existing rheumatoid arthritis. PMID:27225465

  13. On Anti-Elite Prime Numbers

    Science.gov (United States)

    M"Uller, Tom

    2007-09-01

    An odd prime number p is called anti-elite if only finitely many Fermat numbers are quadratic non-residues to p. This concept is the exact opposite to that of elite prime numbers. We study some fundamental properties of anti-elites and show that there are infinitely many of them. A computational search among all the numbers up to 100 billion yielded 84 anti-elite primes.

  14. Atypical anti-glomerular basement membrane disease

    OpenAIRE

    Troxell, Megan L.; Donald C Houghton

    2015-01-01

    Background Anti-glomerular basement membrane (anti-GBM) disease classically presents with aggressive necrotizing and crescentic glomerulonephritis, often with pulmonary hemorrhage. The pathologic hallmark is linear staining of GBMs for deposited immunoglobulin G (IgG), usually accompanied by serum autoantibodies to the collagen IV alpha-3 constituents of GBMs. Methods Renal pathology files were searched for cases with linear anti-GBM to identify cases with atypical or indolent course. Histopa...

  15. Anti S enigma in a pregnant patient.

    Science.gov (United States)

    Kaur, Paramjit; Kaur, Gagandeep; Basu, Sabita; Kaur, Ravneet

    2014-04-01

    Among the antibodies of the MNS blood group system, anti S antibody is generally IgG antibody reacting at 37 °C. It is rarely implicated in hemolytic transfusion reaction; however, it can lead to potentially severe transfusion reactions. Anti S is also capable of causing mild to severe fatal hemolytic disease of newborn. We report a case of anti S antibody in a pregnant patient with complicated falciparum malaria. PMID:24485071

  16. Evidence for Clinical Use of Honey in Wound Healing as an Anti-bacterial, Anti-inflammatory Anti-oxidant and Anti-viral Agent: A Review

    OpenAIRE

    Yaghoobi, Reza; Kazerouni, Afshin; kazerouni, Ory

    2013-01-01

    Context To provide an updated review of published literature on the anti-oxidant, anti-bacterial and anti-inflammatory properties of honey. Evidence Acquisition CINAHL, BioMed Central, Cochrane Library, Medline and Embase data bases and reference lists were used to find randomized controlled trials and review articles. Randomized controlled trials using honey with a comparator were reviewed, along with published review articles to determine the relative benefits of tropical honey. These metho...

  17. Multinationals and Anti-sweatshop Activism

    OpenAIRE

    Ann Harrison; Jason Scorse

    2010-01-01

    During the 1990s, anti-sweatshop activists campaigned to improve conditions for workers in developing countries. This paper analyzes the impact of anti-sweatshop campaigns in Indonesia on wages and employment. Identification is based on comparing the wage growth of workers in foreign-owned and exporting firms in targeted regions or sectors before and after the initiation of anti-sweatshop campaigns. We find the campaigns led to large real wage increases for targeted enterprises. There were so...

  18. Anti-tetanus immunisation in orienteers.

    OpenAIRE

    Folan, J. C.

    1985-01-01

    The present state of anti-tetanus immunisation amongst orienteering runners from 20 countries was assessed by questioning the orienteers as to when they last received an anti-tetanus injection. The results demonstrate that approximately 55% were within five years of their last injection, 18% were within 5-10 years, 12% were greater than 10 years and a further 15% did not know when or had never had an anti-tetanus injection.

  19. Hemolytic disease of the fetus and newborn caused by anti-D and anti-S alloantibodies: a case report

    Directory of Open Access Journals (Sweden)

    Yousuf Rabeya

    2012-02-01

    Full Text Available Abstract Introduction Hemolytic disease of the fetus and newborn is most commonly caused by anti-D alloantibody. It is usually seen in Rhesus D (RhD-negative mothers that have been previously sensitized. We report here a case of hemolytic disease of the fetus and newborn in a newborn baby caused by anti-D and anti-S alloantibodies, born to a mother who was RhD negative, but with no previous serological evidence of RhD alloimmunization. Case presentation A one-day-old Chinese baby boy was born to a mother who was group A RhD negative. The baby was jaundiced with hyperbilirubinemia, but with no evidence of infection. His blood group was group A RhD positive, his direct Coombs' test result was positive and red cell elution studies demonstrated the presence of anti-D and anti-S alloantibodies. Investigations performed on the maternal blood during the 22 weeks of gestation showed the presence of anti-S antibodies only. Repeat investigations performed post-natally showed the presence of similar antibodies as in the newborn and an anti-D titer of 1:32 (0.25 IU/mL, which was significant. A diagnosis of hemolytic disease of the fetus and newborn secondary to anti-D and anti-S was made. The baby was treated with phototherapy and close monitoring. He was discharged well after five days of phototherapy. Conclusions This case illustrates the possibility of an anamnestic response of allo-anti-D from previous sensitization in a RhD-negative mother, or the development of anti-D in mid-trimester. Thus, it highlights the importance of thorough antenatal ABO, RhD blood grouping and antibody screening, and if necessary, antibody identification and regular monitoring of antibody screening and antibody levels for prevention or early detection of hemolytic disease of the fetus and newborn, especially in cases of mothers with clinically significant red cell alloantibody.

  20. Transformations in French Anti-Semitism

    OpenAIRE

    Mayer, Nonna

    2007-01-01

    The increase in the number of anti-Semitic acts since the start of the Second Intifada has sparked off a broad debate on the return of anti-Semitism in France. This article focuses on the question whether this anti-Semitism is still based on the alleged superiority of the Aryan race as in the time of Nazism, or if it represents the birth of a “new Judeophobia” that is more based on anti-Zionism and the polemical mixing of “Jews,” “Israelis,” and “Zionists.” One supposed effect of this transfo...

  1. Anti-semitismo na Europa hoje

    OpenAIRE

    Bila Sorj

    2007-01-01

    O termo "anti-semitismo" é utilizado nas manifestações de hostilidade contra os judeus desde a Antiguidade. No entanto, como fenômeno histórico, o anti-semitismo é parte integrante das dinâmicas socioculturais e políticas de cada sociedade. Este artigo enfoca particularmente as especificidades que ele assume hoje na Europa Ocidental.The term "anti-Semitism" is employed in manifestations of hostility against Jews since Antiquity. However, as a historical phenomenon, the anti-Semitism is part o...

  2. EU Lobbying and Anti-Dumping Policy

    DEFF Research Database (Denmark)

    Nielsen, Jørgen Ulff-Møller; Svendsen, Gert Tinggaard

    2012-01-01

    Lobbying in the EU is difficult to measure. It varies in intensity and modes of expression across different policy areas and EU countries. By looking at a specific EU policy area this paper suggests to measure differences in the lobbying activity across EU countries by the combination...... of petitioning firms and Council voting in the case of anti-dumping policy. If the political position of countries in anti-dumping cases is influenced by domestic lobbying efforts, we expect that the empirical pattern of country distribution of petitioning firms in EU anti-dumping cases corresponds closely...... position of countries in the special case of EU anti-dumping policy....

  3. The Superheavy Elements and Anti-Gravity

    Science.gov (United States)

    Anastasovski, Petar K.

    2004-02-01

    The essence of any propulsion concept is to overcome gravity. Anti-gravity is a natural means to achieve this. Thus, the technology to pursue anti-gravity, by using superheavy elements, may provide a new propulsion paradigm. The theory of superluminal relativity provides a hypothesis for existence of elements with atomic number up to Z = 145, some of which may possess anti-gravity properties. Analysis results show that curved space-time exists demonstrating both gravitic and anti-gravitic properties not only around nuclei but inside the nuclei as well. Two groups of elements (Z Hawking, in honour of Stephen W. Hawking.

  4. In vitro screening for anti-acetylcholiesterase, anti-oxidant, anti-glucosidase, anti-inflammatory and anti-bacterial effect of three traditional medicinal plants

    OpenAIRE

    Ghareeb, Doaa A; ElAhwany, Amani M.D.; El-mallawany, Sherif M.; Saif, Ashraf A.

    2014-01-01

    In this study we investigated the phytoconstituents Calluna vulgaris, Ferula hermonis and Tribulus terrestris, and then assessed their possible biological activities by using standard methods. A preliminary phytochemical investigation of the three extracts revealed the presence of alkaloids, flavonoids, proteins, lipids, phenolic compounds, saponins, sterols and amino acids. Three extracts showed anti-oxidant effect as they inhibited the 1,1-diphenyl-2-picryl hydrazyl (DPPH) oxidation and pro...

  5. The anti-nuclear disinformation

    International Nuclear Information System (INIS)

    After having briefly identified the origin of anti-nuclear disinformation in France in the ecologist movement, the author recalls the very different information that were spread after the Chernobyl accident, and how some aspects were immediately exploited by antinuclear ecologists. He also comments the various information and data which were published on this accident during the following years, notably about the victims, casualties and health impacts. He comments data published by international and French bodies or agencies (Nuclear Energy Agency, UNSCEAR, InVS). He outlines a continuous practice of disinformation by media, notably about wastes, evokes the consequences in terms of safety, risks and risk perception. He finally browses several issues related to the Fukushima accident

  6. Science and anti-science

    CERN Document Server

    Holton, Gerald

    1997-01-01

    What is good science? What goal--if any--is the proper end of scientific activity? Is there a legitimating authority that scientists mayclaim? Howserious athreat are the anti-science movements? These questions have long been debated but, as Gerald Holton points out, every era must offer its own responses. This book examines these questions not in the abstract but shows their historic roots and the answers emerging from the scientific and political controversies of this century. Employing the case-study method and the concept of scientific thematathat he has pioneered, Holton displays the broad scope of his insight into the workings of science: from the influence of Ernst Mach on twentiethcentury physicists, biologists, psychologists, and other thinkers to the rhetorical strategies used in the work of Albert Einstein, Niels Bohr, and others; from the bickering between Thomas Jefferson and the U.S. Congress over the proper form of federal sponsorship of scientific research to philosophical debates since Oswald...

  7. Anti-cancer Lead Molecule

    KAUST Repository

    Sagar, Sunil

    2014-04-17

    Derivatives of plumbagin can be selectively cytotoxic to breast cancer cells. Derivative `A` (Acetyl Plumbagin) has emerged as a lead molecule for testing against estrogen positive breast cancer and has shown low hepatotoxicity as well as overall lower toxicity in nude mice model. The toxicity of derivative `A` was determined to be even lower than vehicle control (ALT and AST markers). The possible mechanism of action identified based on the microarray experiments and pathway mapping shows that derivative `A` could be acting by altering the cholesterol-related mechanisms. The low toxicity profile of derivative `A` highlights its possible role\\'as future anti-cancer drug and/or as an adjuvant drug to reduce the toxicity of highly toxic chemotherapeutic\\'drugs

  8. Anti-E Alloimmunization: A Rare Cause of Severe Fetal Hemolytic Disease Resulting in Pregnancy Loss

    OpenAIRE

    Reyin Lien; Yao-Lung Chang; Szu Ying Ho; Angel Chao; An-Shine Chao

    2010-01-01

    We report a case of severe intrauterine hemolysis caused by sole anti-E alloimmunization. A 36-year-old multipara woman presented with hydrops fetalis at 27 weeks of gestation. She had a history of previous neonatal death. In this pregnancy, she was found to have very high titer of anti-E antibody. Ultrasonography detected marked skin edema, cardiomegaly, hepatosplenomegaly, pleural effusion, ascites, placentomegaly, and polyhydramnios. The Doppler peak systolic velocity in the middle cerebra...

  9. Developing Anti-tick Vaccines.

    Science.gov (United States)

    Rodríguez-Mallon, Alina

    2016-01-01

    Ticks are responsible for the transmission of viral, bacterial, and protozoal diseases of man and animals and also produce significant economic losses to cattle industry. The use of acaricides constitutes a major component of integrated tick control strategies. However, this is accompanied by the selection of acaricide-resistant ticks and contamination of environment and milk and meat products with drug residues. These issues highlight the need for alternative approaches to control tick infestations and have triggered the search for tick protective antigens for vaccine development. Vaccination as a tick control method has been practiced since the introduction of TickGARD and Gavac that were developed using the midgut glycoprotein Bm86 as antigen. Gavac within integrated tick management systems has proven to reduce the number of acaricidal applications per year that are required to control some strains of R. microplus ticks in different geographical regions. Nevertheless, it has limited or no efficacy against other tick species. These issues have stimulated research for additional tick protective antigens with critical functions in the tick. This chapter presents methodologies for the design and test of molecules as antigens against ticks. Considerations about different methods for the tick control compared to the immunological methods, the desirable characteristics for an anti-tick vaccine and the obstacles encountered for developing this kind of vaccines are discussed. Detailed methodologies for the establishment of a biological model to test new molecules as immunogens against ticks and to perform challenge trials with this model are presented. General considerations in the efficacy calculation for any anti-tick vaccine are also discussed. PMID:27076303

  10. SCIENCE LOOKS AT ANTI-SEMITISM.

    Science.gov (United States)

    Institute of Human Rights, New York, NY.

    THE CENTRAL FACT THAT EMERGES FROM RESEARCH ON ANTI-SEMITISM IS THAT PREJUDICE PERFORMS A PSYCHOLOGICAL FUNCTION. TO THE INTENSE BIGOT, PREJUDICE IS AN EMOTIONAL OUTLET ESSENTIAL FOR MAINTAINING A SENSE OF SELF-IMPORTANCE. EVEN TO THE MODERATE OR MILD ANTI-SEMITE, PREJUDICE IS A SUBSTITUTE FOR A TRUE FEELING OF PERSONAL OR GROUP WORTH. THERE ARE…

  11. Anti-Semitism: A Warrant for Genocide.

    Science.gov (United States)

    Wieser, Paul

    1995-01-01

    Presents a high school lesson plan illustrating the breadth and scope of German anti-Semitism before and during World War II. Includes four lists describing anti-Semitic and German Jewry laws. Includes student objectives, instructional procedures, and instructions for students. (CFR)

  12. Anti-Semitism: Background to the Holocaust.

    Science.gov (United States)

    Kleg, Milton

    1995-01-01

    Contends that teaching only about the 1933-1945 period of German persecution of Jews serves a very limited purpose. Argues that the foundations of anti-Semitic beliefs and practices have a long history and should be part of Holocaust education. Describes the origins, development, and key events in anti-Semitism in Europe. (CFR)

  13. Anti-Dumping on and from China

    Institute of Scientific and Technical Information of China (English)

    Patrick H. Zhao

    2007-01-01

    @@ The past years saw an increased cases of anti-dumping on China mostly from the developed countries, some from developing countries. But Pakistan, a friendly neighbor to China, recently adds up to that list of ranks for an anti-dumping investigation on China.

  14. Anti-influenza M2e antibody

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew M.

    2013-04-16

    Humanized recombinant and monoclonal antibodies specific for the ectodomain of the influenza virus M2 ion channel protein are disclosed. The antibodies of the invention have anti-viral activity and may be useful as anti-viral therapeutics and/or prophylactic/vaccine agents for inhibiting influenza virus replication and for treating individuals infected with influenza.

  15. Anti-influenza M2e antibody

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew M. (Santa Fe, NM)

    2011-12-20

    Humanized recombinant and monoclonal antibodies specific for the ectodomain of the influenza virus M2 ion channel protein are disclosed. The antibodies of the invention have anti-viral activity and may be useful as anti-viral therapeutics and/or prophylactic/vaccine agents for inhibiting influenza virus replication and for treating individuals infected with influenza.

  16. Using Anti-VEGF in Diabetic Retinopathy

    Science.gov (United States)

    Marashi, Ameen

    2016-01-01

    Vascular endothelium growth factor is the main pathological factor in diabetic retinopathy and diabetic macular edema (DME), Anti-VEGF agents are safe and effective in DME treatment, there are multiple Anti-VEGF agents, choosing between them is essential to individualize treatment for each patient to achieve the optimum results. PMID:27419238

  17. Transformations in French Anti-Semitism

    Directory of Open Access Journals (Sweden)

    Nonna Mayer

    2007-01-01

    Full Text Available The increase in the number of anti-Semitic acts since the start of the Second Intifada has sparked off a broad debate on the return of anti-Semitism in France. This article focuses on the question whether this anti-Semitism is still based on the alleged superiority of the Aryan race as in the time of Nazism, or if it represents the birth of a “new Judeophobia” that is more based on anti-Zionism and the polemical mixing of “Jews,” “Israelis,” and “Zionists.” One supposed effect of this transformation is that anti-Semitism is in the process of changing camps and migrating from the extreme right to the extreme left of the political arena, to the “altermondialistes,” the communists, and the “neo-Trotskyists.”

  18. Poliarterite nodosa due to anti elastase antibody

    Directory of Open Access Journals (Sweden)

    Caterina Defendenti

    2008-09-01

    Full Text Available The Authors related one case of polyarteritis nodosa occurred to a men forty eight years old.The clinical was characterized by mesenteric and femoral arteries occlusion and chronic cutaneous ulcers to legs. There were bioptical aspects of systemic vasculitis with necrotizing inflammation and a paucity of immune deposit. It was effective oral cyclophosphamide plus steroids. This disease was closely associated with antibodies anti elastase (HLE.The patient had not a history of cocaine abuse or LES disease but the nucleolar pattern ANA was positive >1:640 (anti-nDNA negative. Similar case ANA positive associated with the anti-elastase antibodies, was described by Nassberger (Lancet 1989 for 6/104 patients with LES, anti-nDNA negative. The patient with the highest anti-elastase concentration subsequentely died after very rapid development of severe brain and kidney involvement.

  19. Secapin, a bee venom peptide, exhibits anti-fibrinolytic, anti-elastolytic, and anti-microbial activities.

    Science.gov (United States)

    Lee, Kwang Sik; Kim, Bo Yeon; Yoon, Hyung Joo; Choi, Yong Soo; Jin, Byung Rae

    2016-10-01

    Bee venom contains a variety of peptide constituents that have various biological, toxicological, and pharmacological actions. However, the biological actions of secapin, a venom peptide in bee venom, remain largely unknown. Here, we provide the evidence that Asiatic honeybee (Apis cerana) secapin (AcSecapin-1) exhibits anti-fibrinolytic, anti-elastolytic, and anti-microbial activities. The recombinant mature AcSecapin-1 peptide was expressed in baculovirus-infected insect cells. AcSecapin-1 functions as a serine protease inhibitor-like peptide that has inhibitory effects against plasmin, elastases, microbial serine proteases, trypsin, and chymotrypsin. Consistent with these functions, AcSecapin-1 inhibited the plasmin-mediated degradation of fibrin to fibrin degradation products, thus indicating the role of AcSecapin-1 as an anti-fibrinolytic agent. AcSecapin-1 also inhibited both human neutrophil and porcine pancreatic elastases. Furthermore, AcSecapin-1 bound to bacterial and fungal surfaces and exhibited anti-microbial activity against fungi and gram-positive and gram-negative bacteria. Taken together, our data demonstrated that the bee venom peptide secapin has multifunctional roles as an anti-fibrinolytic agent during fibrinolysis and an anti-microbial agent in the innate immune response. PMID:27208884

  20. Anti-TNFa treatment in patients with rheumatoid arthritis and anti-Ro/SSA antibodies

    Directory of Open Access Journals (Sweden)

    P. Airò

    2011-09-01

    Full Text Available Objective: To analyse clinical efficacy, onset of new autoantibodies or symptoms of autoimmune disease in patients affected by rheumatoid arthritis with anti-Ro/SSA treated with anti-TNFa agents. Methods: Six anti-Ro/SSA positive subjects with RA were studied every six months until 24th month of treatment in order to detect ANA titer (IFI, anti-dsDNA (Farr, anti-cardiolipin and anti-beta2glycoprotein I (ELISA, anti-ENA (CIE. The titre of anti-Ro/SSA were analysed by ELISA. Four patients were diagnosed as overlap RA/SS. Results: Six female patients (mean age 58ys, SD 9.8ys, with long-standing RA (mean 7ys, range 5-22 ys were treated with anti-TNFa agents for a mean of 31 months (SD: 20.4 m: 4 with Infliximab and 2 with Etanercept. All the patients showed a significant reduction of DAS until 24th month (p<0.006 with stability of sicca symptoms. The titer of ANA and anti-Ro/SSA was stable, while 4 subjects developed anti-dsDNA at low titer within 6-12 months. One patient withdrawn the treatment, because of lupus-like features; another one, with HCV hepatitis, interrupted Etanercept because of elevation of liver enzymes. No anticardiolipin or antibeta2GPI antibodies were detected. One subject with RA-SS also presented a primary biliary cirrhosis: clinical and histological features of cholangitis remained stable during Etanercept treatment. Conclusions: Anti-TNFa treatment showed good efficacy and safety in anti-Ro/SSA positive patients with RA. Anti-ds- DNA antibodies at low titer appeared in most patients while the onset of lupus-like disease could be considered a rare event also in RA patients with a rich autoimmune repertoire.

  1. A Surge of Anti-Semitism or McCarthyism?

    Science.gov (United States)

    Bartlett, Thomas

    2002-01-01

    Discusses how faculty members nationwide are reacting to a Web site that tracks professors' anti-Israel statements, and to a speech by Harvard's president, who linked an anti-Israel petition to anti-Semitism. (EV)

  2. Electromagnetic anti-jam telemetry tool

    Science.gov (United States)

    Ganesan, Harini; Mayzenberg, Nataliya

    2008-02-12

    A mud-pulse telemetry tool includes a tool housing, a motor disposed in the tool housing, and a magnetic coupling coupled to the motor and having an inner shaft and an outer shaft. The tool may also include a stator coupled to the tool housing, a restrictor disposed proximate the stator and coupled to the magnetic coupling, so that the restrictor and the stator adapted to generate selected pulses in a drilling fluid when the restrictor is selectively rotated. The tool may also include a first anti-jam magnet coupled to the too housing, and an second anti-jam magnet disposed proximate the first anti-jam magnet and coupled to the inner shaft and/or the outer shaft, wherein at least one of the first anti-jam magnet and the second anti-jam magnet is an electromagnet, and wherein the first anti-jam magnet and the second anti-jam magnet are positioned with adjacent like poles.

  3. Novel agents for anti-platelet therapy

    Directory of Open Access Journals (Sweden)

    Ji Xuebin

    2011-11-01

    Full Text Available Abstract Anti-platelet therapy plays an important role in the treatment of patients with thrombotic diseases. The most commonly used anti-platelet drugs, namely, aspirin, ticlopidine, and clopidogrel, are effective in the prevention and treatment of cardio-cerebrovascular diseases. Glycoprotein IIb/IIIa antagonists (e.g., abciximab, eptifibatide and tirofiban have demonstrated good clinical benefits and safety profiles in decreasing ischemic events in acute coronary syndrome. However, adverse events related to thrombosis or bleeding have been reported in cases of therapy with glycoprotein IIb/IIIa antagonists. Cilostazol is an anti-platelet agent used in the treatment of patients with peripheral ischemia, such as intermittent claudication. Presently, platelet adenosine diphosphate P2Y(12 receptor antagonists (e.g., clopidogrel, prasugrel, cangrelor, and ticagrelor are being used in clinical settings for their pronounced protective effects. The new protease-activated receptor antagonists, vorapaxar and atopaxar, potentially decrease the risk of ischemic events without significantly increasing the rate of bleeding. Some other new anti-platelet drugs undergoing clinical trials have also been introduced. Indeed, the number of new anti-platelet drugs is increasing. Consequently, the efficacy of these anti-platelet agents in actual patients warrants scrutiny, especially in terms of the hemorrhagic risks. Hopefully, new selective platelet inhibitors with high anti-thrombotic efficiencies and low hemorrhagic side effects can be developed.

  4. Reactive oxygen species and anti-proteinases.

    Science.gov (United States)

    Siddiqui, Tooba; Zia, Mohammad Khalid; Ali, Syed Saqib; Rehman, Ahmed Abdur; Ahsan, Haseeb; Khan, Fahim Halim

    2016-01-01

    Reactive oxygen species (ROS) cause damage to macromolecules such as proteins, lipids and DNA and alters their structure and function. When generated outside the cell, ROS can induce damage to anti-proteinases. Anti-proteinases are proteins that are involved in the control and regulation of proteolytic enzymes. The damage caused to anti-proteinase barrier disturbs the proteinase-anti-proteinases balance and uncontrolled proteolysis at the site of injury promotes tissue damage. Studies have shown that ROS damages anti-proteinase shield of the body by inactivating key members such as alpha-2-macroglobulin, alpha-1-antitrypsin. Hypochlorous acid inactivates α-1-antitrypsin by oxidizing a critical reactive methionine residue. Superoxide and hypochlorous acid are physiological inactivators of alpha-2-macroglobulin. The damage to anti-proteinase barrier induced by ROS is a hallmark of diseases such as atherosclerosis, emphysema and rheumatoid arthritis. Thus, understanding the behaviour of ROS-induced damage to anti-proteinases may helps us in development of strategies that could control these inflammatory reactions and diseases. PMID:26699123

  5. Studies of anti pp->anti nn and anti np annihilation at incident momenta of 700 and 760 MeV/c

    International Nuclear Information System (INIS)

    Results are presented on the charge exchange reaction anti pp->anti nn and anti np annihilations from bubble chamber exposures to antiproton beam of momenta 700 and 760 MeV/c. The differential cross section of anti pp->anti nn shows a forward spike followed by a clear dip bump structure. Total annihilation cross section of anti np for average anti n momentum of 700 MeV/c has been evaluated to be 55.4+-2.2 mb. The multiplicity, Feynman x and psub(T)2 distributions for inclusive charged pions in anti pp and anti np annihilations are found to be similar. The emission of charged pions from anti np annihilations are found to be consistent with thermodynamic models with temperature proportional110 MeV. (orig.)

  6. Anti-Modernism and Discourses of Melancholy

    OpenAIRE

    David J. ROSNER

    2006-01-01

    This paper explores anti-modernism, a conservative reaction to Europe’s spiritual disintegration in the period between the World Wars. Most specifically, this anti-modernism will be analyzed in the work of Martin Heidegger, but attention will also be paid to a number of other sources. Because it reflected a longing for the traditions and certainties which held true before the advent of modernity,just as itsoughta futile return to a lost world, the anti-modernist movement will be analyzed in t...

  7. The anti-proton charge radius

    CERN Document Server

    Crivelli, P; Heiss, M W

    2016-01-01

    The upcoming operation of the Extra Low ENergy Antiprotons (ELENA) ring at CERN, the upgrade of the anti-proton decelerator (AD), and the installation in the AD hall of an intense slow positron beam with an expected flux of $10^{8}$ e$^+$/s will open the possibility for new experiments with anti-hydrogen ($\\bar{\\text{H}}$). Here we propose a scheme to measure the Lamb shift of $\\bar{\\text{H}}$. For a month of data taking, we anticipate an uncertainty of 100 ppm. This will provide a test of CPT and the first determination of the anti-proton charge radius at the level of 10%.

  8. Anti-Dumping on and from China

    Institute of Scientific and Technical Information of China (English)

    Patrick; H.Zhao

    2007-01-01

    The past years saw an increased cases of anti-dumping on China mostly from the developed countries,some from developing countries.But Pakistan,a friendly neighbor to China,recently adds up to that list of ranks for an anti-dumping investigation on China.It is the national interests that count most,after all. It gives out a signal that anti-dumping would be a frequent tool to defend or to attack. Evidences show China is a target for this trade remedy,but is also targeting others.

  9. Gauge theories in anti-selfdual variables

    OpenAIRE

    Bochicchio, M.; Pilloni, A.

    2013-01-01

    Some years ago the Nicolai map, viewed as a change of variables from the gauge connection in a fixed gauge to the anti-selfdual part of the curvature, has been extended by the first named author to pure YM from its original definition in N=1 SUSY YM. We study here the perturbative 1PI effective action in the anti-selfdual variables of any gauge theory, in particular pure YM, QCD and N=1 SUSY YM. We prove that the one-loop 1PI effective action of a gauge theory mapped to the anti-selfdual vari...

  10. Human rights against anti-terrorist laws

    OpenAIRE

    Georg Friðgeir Ísaksson

    2009-01-01

    In this essay I will try to answer the question: Are human rights in the UK in jeopardy because of the nation’s increasing anti-terrorist laws? I will focus on the UK, how anti-terrorist laws have been implemented and how they have been used in the UK after the events of the terrorist attacks on 9/11. I chose the UK because of its long tradition of anti-terrorist laws since their dealings with the IRA in the last few decades of the last century. I wanted to take a look at different count...

  11. Anti-Microbial, Anti-Oxidant and Anti-Ulcerogenic Effects of Shilajit on Gastric Ulcer in Rats

    Directory of Open Access Journals (Sweden)

    Mohamed-I. Kotb El-Sayed

    2012-01-01

    Full Text Available Problem statement: To evaluate the effects and mechanisms of action involved in anti-ulcer, antioxidant and antimicrobial activities of different native shilajit samples. Approach: Shilajit samples were collected in the mountain region of Yemen (Al-Jouf and Rayma, Russia (Tien-Shan and India (Kumoan. Stomach ulcers were induced in rats by oro-gastric ingestion of ethanol/HCl. Pre-treatment with ranitidine (100 mg kg-1, p.o. and shilajit samples (600 mg kg-1, p.o. occurred for 14 days before the ulcer induction. Plasma lipids, TBARs, SOD, GSH, catalase activity and gastric mucosal histological changes in rat stomach tissue were evaluated. Antimicrobial efficacy of shilajit (500, 300 and 100 μg disc-1 was also studied against fungi, gram positive and negative bacteria. Results: Data had shown the hypo-lipidemic and anti-oxidant effects of studied shilajit samples on ethanol/HCl-induced ulcer model via decreasing TGs, Tc, TBARs while increasing HDLc, SOD, catalase and GSH than saline or ranitidine pre-treated groups. Al-Jouf and Indian shilajit samples inhibit both ulcer score and lesion area by greater percentages than either ranitidine or other samples. Rayma and Russian samples showed a strongest antimicrobial effect than either Al-Jouf or Indian samples. Conclusion/Recommendations: Some of studied shilajit samples have anti-oxidant and anti-ulcer against induced gastric ulcer, while others showed anti-microbial activities against tested microbes; mightily due to combined mechanisms of shilajit’s constituents, including hypolipidemic, antioxidant, anti-inflammatory, anti-stress, anti-anxiety, regenerative, repairing and healing mechanisms.

  12. Anti-Atlas Mountains, Morocco

    Science.gov (United States)

    2003-01-01

    The Anti-Atlas Mountains of Morocco formed as a result of the collision of the African and Eurasian tectonic plates about 80 million years ago. This collision destroyed the Tethys Ocean; the limestone, sandstone, claystone, and gypsum layers that formed the ocean bed were folded and crumpled to create the Atlas and Anti-Atlas Mountains. In this ASTER image, short wavelength infrared bands are combined to dramatically highlight the different rock types, and illustrate the complex folding. The yellowish, orange and green areas are limestones, sandstones and gypsum; the dark blue and green areas are underlying granitic rocks. The ability to map geology using ASTER data is enhanced by the multiple short wavelength infrared bands, that are sensitive to differences in rock mineralogy. This image was acquired on June 13, 2001 by the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) on NASA's Terra satellite. With its 14 spectral bands from the visible to the thermal infrared wavelength region, and its high spatial resolution of 15 to 90 meters (about 50 to 300 feet), ASTER images Earth to map and monitor the changing surface of our planet.ASTER is one of five Earth-observing instruments launched December 18, 1999, on NASA's Terra satellite. The instrument was built by Japan's Ministry of Economy, Trade and Industry. A joint U.S./Japan science team is responsible for validation and calibration of the instrument and the data products.The broad spectral coverage and high spectral resolution of ASTER will provide scientists in numerous disciplines with critical information for surface mapping, and monitoring of dynamic conditions and temporal change. Example applications are: monitoring glacial advances and retreats; monitoring potentially active volcanoes; identifying crop stress; determining cloud morphology and physical properties; wetlands evaluation; thermal pollution monitoring; coral reef degradation; surface temperature mapping of soils and

  13. Anti-semitismo na Europa hoje

    Directory of Open Access Journals (Sweden)

    Bila Sorj

    2007-11-01

    Full Text Available O termo "anti-semitismo" é utilizado nas manifestações de hostilidade contra os judeus desde a Antiguidade. No entanto, como fenômeno histórico, o anti-semitismo é parte integrante das dinâmicas socioculturais e políticas de cada sociedade. Este artigo enfoca particularmente as especificidades que ele assume hoje na Europa Ocidental.The term "anti-Semitism" is employed in manifestations of hostility against Jews since Antiquity. However, as a historical phenomenon, the anti-Semitism is part of the sociocultural dynamic and politics of each society. This article focuses particularly on its specificities in Western Europe today.

  14. Anti-C1q autoantibodies.

    Science.gov (United States)

    Kallenberg, Cees G M

    2008-09-01

    Autoantibodies to complement components are associated with various diseases. Anti-C1q antibodies are present in all patients with hypocomplementemic urticarial vasculitis, but also, with varying prevalence, in other conditions. In SLE, these antibodies are neither sensitive nor specific for this condition. They occur, however, more frequently in (proliferative) lupus nephritis, particularly during active disease. Furthermore, levels of anti-C1q rise, in many cases, prior to a relapse of lupus nephritis, suggesting a pathogenic role for the autoantibodies. Indeed, experimental studies strongly support a pathogenic role for anti-C1q in immune complex-mediated renal disease. In addition, anti-C1q may interfere with the clearance of apoptotic cells, so influencing induction and expression of autoimmunity. PMID:18606253

  15. Entanglement in joint Λ anti Λ decay

    International Nuclear Information System (INIS)

    We investigate the joint Λ anti Λ decay in the reaction e+e- → γΛ(→ pπ-) anti Λ(→ anti pπ+). This reaction may provide information on the electromagnetic form factors of the Lambda baryon, in the time-like region. We present a conventional diagram-based calculation where production and decay steps are coherent and summations over final-state proton and anti-proton spins are performed. The resulting cross-section distribution is explicitly covariant as it is expressed in scalar products of the four-momentum vectors of the participating particles. We compare this calculation with that of the folding method which we extend and make explicitly covariant. In the folding method production and decay distributions, not amplitudes, are folded together. Of particular importance is then a correct counting of the number of possible intermediate-hyperon-spin states. (orig.)

  16. From anti-conformism to extremism

    CERN Document Server

    Weisbuch, Gérard

    2015-01-01

    We here present a model of the dynamics of extremism based on opinion dynamics in order to understand the circumstances which favour its emergence and development in large fractions of the general public. Our model is based on the bounded confidence hypothesis and on the evolution of initially anti-conformist agents to extreme positions. Numerical analyses demonstrate that a few anti-conformists are able to drag a large fraction of conformists agents to their position provided that they express their views more often than the conformists. The most influential parameter controlling the outcome of the dynamics is the uncertainty of the conformist agents; the higher their uncertainty, the higher is the influence of anti-conformists. Systematic scans of the parameter space show the existence of two regime transitions, one following the conformists uncertainty parameter and the other one following the anti-conformism strength.

  17. Entanglement in joint Λ anti Λ decay

    Energy Technology Data Exchange (ETDEWEB)

    Faeldt, Goeran [Uppsala University, Department of Physics and Astronomy, Uppsala (Sweden)

    2015-07-15

    We investigate the joint Λ anti Λ decay in the reaction e{sup +}e{sup -} → γΛ(→ pπ{sup -}) anti Λ(→ anti pπ{sup +}). This reaction may provide information on the electromagnetic form factors of the Lambda baryon, in the time-like region. We present a conventional diagram-based calculation where production and decay steps are coherent and summations over final-state proton and anti-proton spins are performed. The resulting cross-section distribution is explicitly covariant as it is expressed in scalar products of the four-momentum vectors of the participating particles. We compare this calculation with that of the folding method which we extend and make explicitly covariant. In the folding method production and decay distributions, not amplitudes, are folded together. Of particular importance is then a correct counting of the number of possible intermediate-hyperon-spin states. (orig.)

  18. National Health Care Anti-Fraud Association

    Science.gov (United States)

    ... Conference Tracks Credit Opportunities Anti-Fraud Expo Registration Hotel & Travel Information Sponsors Programs In-Person Programs NETS Webinars Distance Learning Sponsored Webinar Budget Adequately for 2017 Trainings Credit Tracking Accreditation About ...

  19. Anti-CD40-mediated cancer immunotherapy

    DEFF Research Database (Denmark)

    Hassan, Sufia Butt; Sørensen, Jesper Freddie; Olsen, Barbara Nicola;

    2014-01-01

    activation and thus enhancement of immune responses. Treatment with anti-CD40 monoclonal antibodies has been exploited in several cancer immunotherapy studies in mice and led to the development of anti-CD40 antibodies for clinical use. Here, Dacetuzumab and Lucatumumab are in the most advanced stage...... with other cancer immunotherapies, in particular interleukin (IL)-2. An in-depth analysis of this immunotherapy is provided elsewhere. In the present review, we provide an update of the most recent clinical trials with anti-CD40 antibodies. We present and discuss recent and ongoing clinical trials...... in this field, including clinical studies which combine anti-CD40 treatment with other cancer-treatments, such as Rituximab and Tremelimumab....

  20. Are isothiocyanates potential anti-cancer drugs?

    Institute of Scientific and Technical Information of China (English)

    Xiang WU; Qing-hua ZHOU; Ke XU

    2009-01-01

    Isothiocyanates are naturally occurring small molecules that are formed from glucosinolate precursors of cruciferous vegetables. Many isothiocyanates, both natural and synthetic, display anticarcinogenic activity because they reduce activation of carcinogens and increase their detoxification. Recent studies show that they exhibit anti-tumor activity by affecting multiple pathways including apoptosis, MAPK signaling, oxidative stress, and cell cycle progression. This review summarizes the current knowledge on isothiocyanates and focuses on their role as potential anti-cancer agents.

  1. Observations on fluxes near anti-branes

    OpenAIRE

    Cohen-Maldonado, Diego; Diaz Dorronsoro, Juan; Van Riet, Thomas; Vercnocke, Bert

    2016-01-01

    We revisit necessary conditions for gluing local (anti-)D3 throats into flux throats with opposite charge. These consistency conditions typically reveal singularities in the three-form fluxes whose meaning is being debated. In this note we prove, under well-motivated assumptions, that unphysical singularities can potentially be avoided when the anti-branes polarise into spherical NS5 branes with a specific radius. If a consistent solution can then indeed be found, our analysis seems to sugges...

  2. Canadian National Identity and Anti-Americanism

    Institute of Scientific and Technical Information of China (English)

    谭万宏

    2015-01-01

    Canadian national identity is closely related to anti-Americanism and for Canadians,comparing with America has become the main way to identify themselves.So some scholars argue that Canada lacks a real national identity and this is the main reason of its anti-American tradition.However,the author remarks Canada has its national identity.In this paper,the author will present three reasons to support her view.

  3. Canadian National Identity and Anti-Americanism

    Institute of Scientific and Technical Information of China (English)

    谭万宏

    2015-01-01

    Canadian national identity is closely related to antiAmericanism and for Canadians,comparing with America has become the main way to identify themselves.So some scholars argue that Canada lacks a real national identity and this is the main reason of its anti-American tradition.However,the author remarks Canada has its national identity.In this paper,the author will present three reasons to support her view.

  4. Preeclampsia and the Anti-Angiogenic State

    OpenAIRE

    Agarwal, Isha; Karumanchi, S. Ananth

    2011-01-01

    Preeclampsia is a major cause of maternal and fetal morbidity and mortality worldwide, however, its etiology remains unclear. Abnormal placental angiogenesis during pregnancy resulting from high levels of anti-angiogenic factors, soluble Flt1 (sFlt1) and soluble endoglin (sEng), has been implicated in preeclampsia pathogenesis. Accumulating evidence also points to a role for these anti-angiogenic proteins as serum biomarkers for the clinical diagnosis and prediction of preeclampsia. Uncoverin...

  5. Aspherical Photon and Anti-Photon Surfaces

    CERN Document Server

    Gibbons, G W

    2016-01-01

    In this note we identify photon surfaces and anti-photon surfaces in some physically interesting spacetimes, which are not spherically symmetric. All of our examples solve physically reasonable field equations, including for some cases the vacuum Einstein equations, albeit they are not asymptotically flat. Our examples include the vacuum C-metric, the Melvin solution of Einstein-Maxwell theory and generalisations including dilaton fields. The (anti-)photon surfaces are not round spheres, and the lapse function is not always constant.

  6. New Anti-Merger Theories: A Critique

    OpenAIRE

    Edward J. López

    2005-01-01

    The purpose of this paper is to evaluate two new anti-merger instruments, innovation markets and unilateral effects, on the basis of economic theory and evidence. I first discuss how the economics of antitrust has developed over the years, with the intention of characterizing the intellectual inheritance of 1990s’ antitrust regulators. Within this context, I then discuss each anti-merger instrument, how it has been applied in specific cases, and how it accords with underlying economic science...

  7. Perfect anti-reflection from first principles

    OpenAIRE

    Kim, Kyoung-Ho; Q-Han Park

    2013-01-01

    Reducing unwanted reflections through impedance matching, called anti-reflection, has long been an important challenge in optics and electrical engineering. Beyond trial and error optimization, however, a systematic way to realize anti-reflection is still absent. Here, we report the discovery of an analytic solution to this long standing problem. For electromagnetic waves, we find the graded permittivity and permeability that completely remove any given impedance mismatch. We demonstrate that...

  8. Anti-aircraft Missiles and Gun Control

    OpenAIRE

    BLOCK, Walter

    2016-01-01

    Abstract. Gun control is a highly debatable topic both in the popular and scholarly media. But what about anti-aircraft missiles? Should they be banned? On the one hand, there are fewer of them around, so their challenge is more tractable. On the other hand, they can do far more damage than handguns. The present paper is an attempt to wrestle with this challenge.Keywords. Gun control, Second amendment, Libertarianism, Anti-aircraft missiles.JEL. K15.

  9. Resveratrol: Anti-Obesity Mechanisms of Action

    OpenAIRE

    Leixuri Aguirre; Alfredo Fernández-Quintela; Noemí Arias; Maria P. Portillo

    2014-01-01

    Resveratrol is a non-flavonoid polyphenol which belongs to the stilbenes group and is produced naturally in several plants in response to injury or fungal attack. Resveratrol has been recently reported as preventing obesity. The present review aims to compile the evidence concerning the potential mechanisms of action which underlie the anti-obesity effects of resveratrol, obtained either in cultured cells lines and animal models. Published studies demonstrate that resveratrol has an anti-adip...

  10. Confinement in Anti-de Sitter Space

    CERN Document Server

    Aharony, Ofer; Tong, David; Yankielowicz, Shimon

    2012-01-01

    Four dimensional gauge theories in anti-de Sitter space, including pure Yang-Mills theory, exhibit a quantum phase transition between a deconfined phase and a confined phase as the gauge coupling is varied. We explore various mechanisms by which this may occur, both in a fixed background and in the presence of gravity. We also make a number of observations on the dynamics of four dimensional supersymmetric gauge theories in anti-de Sitter space.

  11. Sterols from Mytilidae Show Anti-Aging and Neuroprotective Effects via Anti-Oxidative Activity

    OpenAIRE

    Yujuan Sun; Yanfei Lin; Xueli Cao; Lan Xiang; Jianhua Qi

    2014-01-01

    For screening anti-aging samples from marine natural products, K6001 yeast strain was employed as a bioassay system. The active mussel extract was separated to give an active sterol fraction (SF). SF was further purified, and four sterol compounds were obtained. Their structures were determined to be cholesterol (CHOL), brassicasterol, crinosterol, and 24-methylenecholesterol. All compounds showed similar anti-aging activity. To understand the action mechanism involved, anti-oxidative experim...

  12. Synthesis, Anti-Inflammatory and Anti-oxidant activity of some substituted Benzimidazole Derivatives

    OpenAIRE

    Rajasekaran S; Abhiskek Chatterjee; Gopalkrishna Rao

    2012-01-01

    Benzimidazoles are an important class of compounds with a wide spectrum of biological activity ranging from anti-hypertensive, anti-viral, anti-fungal, antitumor and anthelmintic activity. In addition, few N-substituted benzimidazole derivatives have shown to exhibit significant activity against several viruses, including HIV, herpes simplex (HSV-1), influenza, picorna, human cytomegalovirus (HCMV) and hepatitis C virus. The five membered heterocyclic moiety 1,3,4-oxadiazole also confers for ...

  13. HIF-dependent Anti-tumorigenic Effect of Anti-oxidants In Vivo

    OpenAIRE

    Gao, Ping; Zhang, Huafeng; Dinavahi, Ramani; Li, Feng; Xiang, Yan; Raman, Venu; Bhujwalla, Zaver M; Felsher, Dean W.; Cheng, Linzhao; Pevsner, Jonathan; Lee, Linda A; Semenza, Gregg L.; Dang, Chi V.

    2007-01-01

    The anti-tumorigenic activity of anti-oxidants has been presumed to arise from their ability to squelch DNA damage and genomic instability mediated by reactive oxygen species (ROS). Here we report that anti-oxidants inhibited three tumorigenic models in vivo. Inhibition of a MYC-dependent human B lymphoma model was unassociated with genomic instability, but was linked to diminished hypoxia inducible factor (HIF)-1 levels in a prolyl hydroxylase 2 and von Hippel-Lindau protein dependent manner...

  14. Investigation of the reaction anti pp→anti YY close to threshold at LEAR

    International Nuclear Information System (INIS)

    For the reaction anti pp → anti ΛΛ from threshold up to 1.7 GeV/c total and different cross section data, polarisations and spin correlations have been obtained. The data indicate a remarkably strong p-wave contribution even close to the reaction threshold. The anti Λ-Λ spin correlations are compatible with a pure triplet state. (orig.)

  15. Anti-foam System design description

    International Nuclear Information System (INIS)

    The Anti-foam System is a sub-system of the 242-A Evaporator facility. The Anti-foam is used within the C-A-1 Vapor-Liquid Separator, to reduce the effect of foaming and reduce fluid bumping while the vapor and liquid are separated within the C-A-1 Vapor-Liquid Separator. Excessive foaming within the vessel may possibly cause the liquid slurry mixture in the evaporator vessel to foul the de-entrainment pads and cause plant shutdown. The Anti-foam System consists of the following primary elements: the Anti-foam Tank and the Metering Pump. The upgrades to Anti-foam System include the following: installation of a new pump, instruments, and valves; and connection of the instruments, pump and agitator associated with the Anti-foam System to the Monitoring and Control System (MCS). The 242-A Evaporator is a waste treatment facility designed to reduce liquid waste volumes currently stored in the Hanford Area double shell Waste Storage Tanks. The evaporator uses evaporative concentration to achieve this volume reduction, returning the concentrated slurry to the double-shell tanks for storage and, at the same time, releasing the process effluent to a retention facilities for eventual treatment and release to the environment

  16. The Superheavy Elements and Anti-Gravity

    International Nuclear Information System (INIS)

    The essence of any propulsion concept is to overcome gravity. Anti-gravity is a natural means to achieve this. Thus, the technology to pursue anti-gravity, by using superheavy elements, may provide a new propulsion paradigm. The theory of superluminal relativity provides a hypothesis for existence of elements with atomic number up to Z = 145, some of which may possess anti-gravity properties. Analysis results show that curved space-time exists demonstrating both gravitic and anti-gravitic properties not only around nuclei but inside the nuclei as well. Two groups of elements (Z < 64 and 63 < Z <145) exist that demonstrate these capabilities. The nuclei of the first group of elements have the masses with only the property of gravity. The nuclei of the elements of the second group have the masses with both properties: gravity and anti-gravity in two different ranges of curved space-time around the nuclei.. The hypothetical element with Z = 145 is the unique among all elements whose nucleus has only anti-gravity property. It is proposed that this element be named Hawking, in honour of Stephen W. Hawking

  17. Preclinical testing of Peruvian anti-bothropic anti-venom against Bothrops andianus snake venom.

    Science.gov (United States)

    Schneider, Francisco S; Starling, Maria C; Duarte, Clara G; Machado de Avila, Ricardo; Kalapothakis, Evanguedes; Silva Suarez, Walter; Tintaya, Benigno; Flores Garrido, Karin; Seraylan Ormachea, Silvia; Yarleque, Armando; Bonilla, César; Chávez-Olórtegui, Carlos

    2012-11-01

    Bothrops andianus is a venomous snake found in the area of Machu Picchu (Peru). Its venom is not included in the antigenic pool used for production of the Peruvian anti-bothropic anti-venom. B. andianus venom can elicit many biological effects such as hemorrhage, hemolysis, proteolytic activity and lethality. The Peruvian anti-bothropic anti-venom displays consistent cross-reactivity with B. andianus venom, by ELISA and Western Blotting and is also effective in neutralizing the venom's toxic activities. PMID:22796381

  18. Hemolytic disease of the fetus and newborn caused by anti-E

    OpenAIRE

    Adiyyatu Sa′idu Usman; Rapiaah Mustaffa; Noraida Ramli; Diggi, Sirajo A.

    2013-01-01

    Objective: Maternal allo-antibody production is stimulated when fetal red blood cells are positive for an antigen absent on the mother's red cells. The maternal IgG antibodies produced will pass through the placenta and attack fetal red cells carrying the corresponding antigen. Allo-immune hemolytic disease of the fetus and newborn caused by anti-E rarely occurs. Case summary: We report two cases of anti-E hemolytic diseases in neonates. One of the neonates had severe hemolysis presenting wit...

  19. Anti-idiotypes against a monoclonal anti-haloperidol antibody bind to dopamine receptor

    International Nuclear Information System (INIS)

    Anti-idiotypic antibodies were raised in rabbits by immunization with a monoclonal anti-haloperidol antibody. Some of these anti-idiotypic antibodies bind in a concentration dependent manner to bovine striatal membranes. Following affinity purification, these antibodies inhibit haloperidol binding to striatal membranes and deplete [3H]-spiperone binding sites from a solubilized preparation of striatal membranes. It is thus concluded that these anti-idiotypic antibodies are an internal image of haloperidol and as such can interact with D2-dopamine receptors

  20. Anti-TJa alloimmunization (anti-PP1Pk): two consecutive pregnancies of an anti-TJa-carrying patient.

    Science.gov (United States)

    Haentjens-Verbeke, K; Dufour, P h; Vinatier, D; Tordjeman, N; Monnier, J C; Manessier, L

    1996-01-01

    Anti-TJa alloimmunization is an extremely rare condition which can cause miscarriages during the first and second terms of pregnancy. At 20-year-old female patient, an anti-TJa carrier, was given plasma transfusions in the course of her first two pregnancies. The cordocentesis, which was the main follow-up test during the first pregnancy, could not be carried out during the second pregnancy due to the presence of a huge subchorionic hematoma. Both pregnancies were characterized by fetal growth retardation, which was particularly considerable in one. Due to chronic fetal distress, both infants were delivered prematurely by cesarean section. The immunohematological data concerning anti-TJa alloimmunization and the different palliative treatments available to date are reviewed. PMID:8838768

  1. In vitro anti-proliferative and anti-angiogenic activities of thalidomide dithiocarbamate analogs.

    Science.gov (United States)

    El-Aarag, Bishoy Y A; Kasai, Tomonari; Zahran, Magdy A H; Zakhary, Nadia I; Shigehiro, Tsukasa; Sekhar, Sreeja C; Agwa, Hussein S; Mizutani, Akifumi; Murakami, Hiroshi; Kakuta, Hiroki; Seno, Masaharu

    2014-08-01

    Inhibition of angiogenesis is currently perceived as a promising strategy in the treatment of cancer. The anti-angiogenicity of thalidomide has inspired a second wave of research on this teratogenic drug. The present study aimed to investigate the anti-proliferative and anti-angiogenic activities of two thalidomide dithiocarbamate analogs by studying their anti-proliferative effects on human umbilical vein endothelial cells (HUVECs) and MDA-MB-231 human breast cancer cell lines. Their action on the expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 was also assessed. Furthermore, their effect on angiogenesis was evaluated through wound healing, migration, tube formation, and nitric oxide (NO) assays. Results illustrated that the proliferation of HUVECs and MDA-MB-231 cells was not significantly affected by thalidomide at 6.25-100μM. Thalidomide failed to block angiogenesis at similar concentrations. By contrast, thalidomide dithiocarbamate analogs exhibited significant anti-proliferative action on HUVECs and MDA-MB-231 cells without causing cytotoxicity and also showed powerful anti-angiogenicity in wound healing, migration, tube formation, and NO assays. Thalidomide analogs 1 and 2 demonstrated more potent activity to suppress expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 than thalidomide. Analog 1 consistently, showed the highest potency and efficacy in all the assays. Taken together, our results support further development and evaluation of novel thalidomide analogs as anti-tumor and anti-angiogenic agents. PMID:24859059

  2. Defining an "Anti" Stance: Key Pedagogical Questions about Engaging Anti-Racism in College Classrooms

    Science.gov (United States)

    Rebollo-Gil, Guillermo; Moras, Amanda

    2006-01-01

    This paper draws from social science literature on Whiteness and anti-racism as well as personal classroom experience to examine the obstacles educators face in teaching anti-racism to White college students. Emphasis is placed on popular perceptions and common definitions of the word "racism" as it is used in mainstream American society. The…

  3. PREPARATION OF ANTI-IDIOTYPIC ANTIBODIES SPECIFIC FOR ANTI- HEL AND ANALYSIS OF THEIR FUNCTIONAL MIMICRY

    Institute of Scientific and Technical Information of China (English)

    李明远; 肖玉; 肖丽英; 李虹; 蒋中华; 牟家琬; 王道若

    2000-01-01

    Objective. This study is to investigate the functional mimicry by using anfi-idiotypic antibodies of enzymes. Methods. Monoclonal anti-idiotypic antibodies against anfi-HEL(hen egg-white lysozyme, HEL) antibodies were obtained by fusion of Sp2/0 myeloma ceils with spleen ceils of syngeneic mice immunized with monoclonal anti-HEL antibodies against HEL's different antigenic epitopes. Then bacteriolysis of the anti-idiotypic antibodies were ohserved. Results. Eight hybridomas strains secreting anti-idiotypic antibodies were observed and characterized. It was shown that two of eight anti-idiotypic antibodies secreted by two hybridomas( 1A10C9 and 2AllC1B3) could mimic HEL catalytic activity to lyse Micrococcus lysodeikticus and that the catalytic effect of mixed anti-idiotypic antibodies of 1A10 G9 and 2A11C1B3 was stronger than that of one of them, but less than HEL. Conclusion. The results demonstrated that the anti-idiotypic antibodies that could mimic enzyme activity existed in the idiotype network during anti-enzymatic immune response.

  4. Anti-inflammatory and anti-hyperalgesic activities of Acanthopanax trifoliatus (L Merr leaves

    Directory of Open Access Journals (Sweden)

    Roslida Abdul Hamid

    2013-01-01

    Full Text Available Context: Acanthopanax trifoliatus is a ginseng-like plant, which has been widely used to treat various diseases including inflammatory-related diseases. Aims: The present study has been designed to investigate the anti-inflammatory and anti-hyperalgesic effects of various fractions of Acanthopanax trifoliatus leaves ethanolic extract in rats. Materials and Methods: Anti-inflammatory activity was studied by using carrageenan-induced edema on rat paw whilst anti-hyperalgesic was assessed by using carrageenan-evoked thermal hyperalgesia on plantar test. Statistical Analysis Used: Data were analyzed using Student t-test to compare with control.Multiple comparisons for difference between control and extract-treated groups were evaluated by Tukey HSD (Honestly Significant Difference test. P values less than 0.05 (P < 0.05 is considered significant. Results: Among three different fractions i.e., hexane, dichloromethane, and methanol tested, methanolic fraction displayed the most potent fraction amongst those three. It gave significant anti-inflammatory effect at highest dose, 500 mg/kg, with 77.24% of inhibition. Whilst for anti-hyperalgesic activity, methanolic fraction showed the highest efficacy at 375 mg/kg. Administration of methanolic fraction of Acanthopanax trifoliatus inhibited paw edema in a dose- dependent manner. The inhibition for both activities might be due to possible composition of polar compounds, which are flavonoids and phenolics content. Conclusions: Methanol fraction of Acanthopanax trifoliatus leaves has potential effect as anti-inflammatory and anti-hyperalgesia in acute inflammation model.

  5. The nontoxic natural compound Curcumin exerts anti-proliferative, anti-migratory, and anti-invasive properties against malignant gliomas

    International Nuclear Information System (INIS)

    New drugs are constantly sought after to improve the survival of patients with malignant gliomas. The ideal substance would selectively target tumor cells without eliciting toxic side effects. Here, we report on the anti-proliferative, anti-migratory, and anti-invasive properties of the natural, nontoxic compound Curcumin observed in five human glioblastoma (GBM) cell lines in vitro. We used monolayer wound healing assays, modified Boyden chamber trans-well assays, and cell growth assays to quantify cell migration, invasion, and proliferation in the absence or presence of Curcumin at various concentrations. Levels of the transcription factor phospho-STAT3, a potential target of Curcumin, were determined by sandwich-ELISA. Subsequent effects on transcription of genes regulating the cell cycle were analyzed by quantitative real-time PCR. Effects on apoptosis were determined by caspase assays. Curcumin potently inhibited GBM cell proliferation as well as migration and invasion in all cell lines contingent on dose. Simultaneously, levels of the biologically active phospho-STAT3 were decreased and correlated with reduced transcription of the cell cycle regulating gene c-Myc and proliferation marking Ki-67, pointing to a potential mechanism by which Curcumin slows tumor growth. Curcumin is part of the diet of millions of people every day and is without known toxic side effects. Our data show that Curcumin bears anti-proliferative, anti-migratory, and anti-invasive properties against GBM cells in vitro. These results warrant further in vivo analyses and indicate a potential role of Curcumin in the treatment of malignant gliomas

  6. Clinical Scenarios for Discordant Anti-Xa

    Directory of Open Access Journals (Sweden)

    Jesus Vera-Aguilera

    2016-01-01

    Full Text Available Anti-Xa test measures the activity of heparin against the activity of activated coagulation factor X; significant variability of anti-Xa levels in common clinical scenarios has been observed. Objective. To review the most common clinical settings in which anti-Xa results can be bias. Evidence Review. Guidelines and current literature search: we used PubMed, Medline, Embase, and MEDION, from 2000 to October 2013. Results. Anti-Xa test is widely used; however the assay underestimates heparin concentration in the presence of significant AT deficiency, pregnancy, end stage renal disease, and postthrombolysis and in patients with hyperbilirubinemia; limited published data evaluating the safety and effectiveness of anti-Xa assays for managing UH therapy is available. Conclusions and Relevance. To our knowledge this is the first paper that summarizes the most common causes in which this assay can be affected, several “day to day” clinical scenarios can modify the outcomes, and we concur that these rarely recognized scenarios can be affected by negative outcomes in the daily practice.

  7. Clinical Scenarios for Discordant Anti-Xa

    Science.gov (United States)

    Vera-Aguilera, Jesus; Yousef, Hindi; Beltran-Melgarejo, Diego; Teng, Teng Hugh; Jan, Ramos; Mok, Mary; Vera-Aguilera, Carlos; Moreno-Aguilera, Eduardo

    2016-01-01

    Anti-Xa test measures the activity of heparin against the activity of activated coagulation factor X; significant variability of anti-Xa levels in common clinical scenarios has been observed. Objective. To review the most common clinical settings in which anti-Xa results can be bias. Evidence Review. Guidelines and current literature search: we used PubMed, Medline, Embase, and MEDION, from 2000 to October 2013. Results. Anti-Xa test is widely used; however the assay underestimates heparin concentration in the presence of significant AT deficiency, pregnancy, end stage renal disease, and postthrombolysis and in patients with hyperbilirubinemia; limited published data evaluating the safety and effectiveness of anti-Xa assays for managing UH therapy is available. Conclusions and Relevance. To our knowledge this is the first paper that summarizes the most common causes in which this assay can be affected, several “day to day” clinical scenarios can modify the outcomes, and we concur that these rarely recognized scenarios can be affected by negative outcomes in the daily practice. PMID:27293440

  8. Anti-icing performance of superhydrophobic surfaces

    International Nuclear Information System (INIS)

    This article studies the anti-ice performance of several micro/nano-rough hydrophobic coatings with different surface chemistry and topography. The coatings were prepared by spin-coating or dip coating and used organosilane, fluoropolymer or silicone rubber as a top layer. Artificially created glaze ice, similar to the naturally accreted one, was deposited on the nanostructured surfaces by spraying supercooled water microdroplets (average size ∼80 μm) in a wind tunnel at subzero temperature (-10 deg. C). The ice adhesion strength was evaluated by spinning the samples in a centrifuge at constantly increasing speed until ice delamination occurred. The results show that the anti-icing properties of the tested materials deteriorate, as their surface asperities seem to be gradually broken during icing/de-icing cycles. Therefore, the durability of anti-icing properties appears to be an important point for further research. It is also shown that the anti-icing efficiency of the tested superhydrophobic surfaces is significantly lower in a humid atmosphere, as water condensation both on top and between surface asperities takes place, leading to high values of ice adhesion strength. This implies that superhydrophobic surfaces may not always be ice-phobic in the presence of humidity, which can limit their wide use as anti-icing materials.

  9. Anti-icing performance of superhydrophobic surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Farhadi, S.; Farzaneh, M. [CIGELE/INGIVRE, Department of Applied Sciences, Universite du Quebec a Chicoutimi, 555 University blvd., Saguenay, PQ, G7H 2B1 (Canada); Kulinich, S.A., E-mail: skulinic@uqac.ca [CIGELE/INGIVRE, Department of Applied Sciences, Universite du Quebec a Chicoutimi, 555 University blvd., Saguenay, PQ, G7H 2B1 (Canada)

    2011-05-01

    This article studies the anti-ice performance of several micro/nano-rough hydrophobic coatings with different surface chemistry and topography. The coatings were prepared by spin-coating or dip coating and used organosilane, fluoropolymer or silicone rubber as a top layer. Artificially created glaze ice, similar to the naturally accreted one, was deposited on the nanostructured surfaces by spraying supercooled water microdroplets (average size {approx}80 {mu}m) in a wind tunnel at subzero temperature (-10 deg. C). The ice adhesion strength was evaluated by spinning the samples in a centrifuge at constantly increasing speed until ice delamination occurred. The results show that the anti-icing properties of the tested materials deteriorate, as their surface asperities seem to be gradually broken during icing/de-icing cycles. Therefore, the durability of anti-icing properties appears to be an important point for further research. It is also shown that the anti-icing efficiency of the tested superhydrophobic surfaces is significantly lower in a humid atmosphere, as water condensation both on top and between surface asperities takes place, leading to high values of ice adhesion strength. This implies that superhydrophobic surfaces may not always be ice-phobic in the presence of humidity, which can limit their wide use as anti-icing materials.

  10. EVALUATION OF ANTI-NOCICEPTIVE AND ANTI-INFLAMMATORY ACTIVITY OF PUNICA GRANATUM SEED EXTRACT

    Directory of Open Access Journals (Sweden)

    Gupta Jeetendra Kumar

    2011-12-01

    Full Text Available The plant Punica granatum of family Punicaceae is distributed throughout India and reputed to have numerous applications in traditional medicine system. In order to justify its folkloric use in nociception and inflammation, the study was performed.In this study, the extraction of Punica granatum seed extract was carried out in aqueous media. In order to explore its potency, various experimental models of anti-nociceptive and anti-inflammatory activities were taken. The oral administration of the extract 100mg and 200mg per kg body weight showed significant pharmacological action. Furthermore the anti-ulcer activity was carried out with the help of Indomethacin induced ulceration model using Mesoprostol as standard drug and it showed no ulcerogenic effect in wistar albino rats.Overall, the extract was found to be significant anti-nociceptive and anti-inflammatory activity with no ulcerogenic adverse effect.

  11. Anti-implantation effect of droloxifene in rats and its relationship with anti-estrogenic activity

    Institute of Scientific and Technical Information of China (English)

    Yong HUANG; Yu SHEN; Ying FENG; Lin CAO; Ying LENG

    2005-01-01

    Aim: To investigate the anti-implantation effect of droloxifene and study the possible relationship between the anti-estrogenic activity of droloxifene and its antiimplantation effect. Methods: Pregnant rats were treated orally with droloxifene at 10:00 AM on d 2 at doses of 1.25-20 mg/kg to observe anti-implantation effects,and then doses of 14 mg/kg or 2.5 mg/kg were given at different time on d 2 to d 5to determine the optimal administration time for anti-implantation effects. Pregnant rats were treated with a combination of droloxifene (2.5 mg/kg, ig) and E2 (0.5-8.0 μg/kg, sc) on the optimal administration time to observe the antagonistic effect of external estrogen on the anti-implantation effect of droloxmene. Serum estrogen and progesterone levels were measured by carrying out radioimmunoas says on d 1 to d 6 in droloxifene-treated and control rats to determine the surge time for nidatory estrogen and the effect of droloxifene on ovary function. Results:Droloxifene has anti-implantation effects in rats. The optimal oral administration time was at 22:00 PM on d 4, which was after the surge time for nidatory estrogen (on d 4 at 10:00 AM). This suggests that the anti-implantation effect of droloxifene is not attributable to antagonism of the surge in secretion of nidatory estrogen.External estrogen did not antagonize the anti-implantation effect of droloxifene.Droloxifene had no effect on the serum levels of estrogen and progesterone on d 5 or d 6 when administered on d 4 at 22:00 PM. Conclusion: Droloxifene has an anti-implantation effect in rats, and the effect appears to be not completely due to its anti-estrogenic activity.

  12. Observations on fluxes near anti-branes

    Science.gov (United States)

    Cohen-Maldonado, Diego; Diaz, Juan; Van Riet, Thomas; Vercnocke, Bert

    2016-01-01

    We revisit necessary conditions for gluing local (anti-)D3 throats into flux throats with opposite charge. These consistency conditions typically reveal singularities in the 3-form fluxes whose meaning is being debated. In this note we prove, under well-motivated assumptions, that unphysical singularities can potentially be avoided when the anti-branes polarise into spherical NS5 branes, with a specific radius. If a consistent solution can then indeed be found, our analysis seems to suggests a rather large correction to the radius of the polarization sphere compared to the probe result. We furthermore comment on the gluing conditions at finite temperature and point out that one specific assumption of a recent no-go theorem can be broken if anti-branes are indeed to polarise into spherical NS5 branes at zero temperature.

  13. Observations on fluxes near anti-branes

    CERN Document Server

    Cohen-Maldonado, Diego; Van Riet, Thomas; Vercnocke, Bert

    2015-01-01

    We revisit necessary conditions for gluing local (anti)-D3 throats into flux throats with opposite charge. These consistency conditions typically reveal singularities in the 3-form fluxes whose meaning is being debated. In this note we prove, under well-motivated assumptions, that singularities remain even when the anti-D3 branes are puffed up into spherical NS5 branes. It does not seem possible to ascribe the singular flux to the self-energy of the 5-branes but rather to the singular clumping of the background fluxes. We furthermore comment on the gluing conditions at finite temperature and point out that one specific assumption of a recent no-go theorem can be broken if anti-branes are to polarise into spherical NS5 branes at zero temperature. Our first result, however, casts some doubt on whether this gap in the no-go theorem can be successfully employed to construct finite temperature solutions.

  14. Anti-Americanism in Contemporary Indonesia

    Directory of Open Access Journals (Sweden)

    Saiful Mujani

    2005-08-01

    Full Text Available This paper attempts to explore these two basic arguments. To that end we need first to discuss what is meant by "anti-Americanism," then what is meant by "unjust American foreign policies," and thirdly what is meant by "civilization" in the context of Indonesian Muslim society. "Anti-Americanism" in the international context is an individual or group attitude or action that reflects a feeling of dislike, hatred or intolerance toward America as a nation, or America as defined by the attitudes or behavior of the American government toward other countries. It is not easy to decide how to measure these anti-American attitudes or actions.Copyright (c 2014 by SDI. All right reserved.DOI: 10.15408/sdi.v12i2.588

  15. Anti-Integrin Therapy for Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Eiji Kawamoto

    2012-01-01

    Full Text Available Integrins are the foremost family of cell adhesion molecules that regulate immune cell trafficking in health and diseases. Integrin alpha4 mediates organ-specific migration of immune cells to the inflamed brain, thereby playing the critical role in the pathogenesis of multiple sclerosis. Anti-alpha4 integrin therapy aiming to block infiltration of autoreactive lymphocytes to the inflamed brain has been validated in several clinical trials for the treatment of multiple sclerosis. This paper provides readers with an overview of the molecular and structural bases of integrin activation as well as rationale for using anti-alpha4 integrin therapy for multiple sclerosis and then chronicles the rise and fall of this treatment strategy using natalizumab, a humanized anti-alpha4 integrin.

  16. Anti-Ma and anti-Ta associated paraneoplastic neurological syndromes: 22 newly diagnosed patients and review of previous cases

    OpenAIRE

    Hoffmann, L. A.; Jarius, S.; Pellkofer, Hannah Luise; Schueller, M.; Krumbholz, Markus; Koenig, F.; Johannis, W.; La Fougere, Christian; Newman, T.; Vincent, A; Voltz, Raymond

    2008-01-01

    Background: Paraneoplastic neurological syndromes (PNS) are indirect remote effects of cancer on the nervous system, often associated with the presence of specific serum antibodies. The most recently described PNS defining reactivity is anti-Ma/anti-Ta. Here we present 22 newly diagnosed patients with anti-Ma or anti-Ta reactivity, refine the associated clinical picture and review all published patients to date.Patients and methods: Patients were identified by testing for PNMA1 and PNMA2 anti...

  17. The Modern Anti-Semitism Israel Model: An empirical relationship between modern anti-Semitism and opposition to Israel

    OpenAIRE

    Florette Cohen; Lee Jussim; Gautam Bhasin; Elizabeth Salib

    2011-01-01

    The current paper reviews our program of research that has examined some of the causes and consequences of anti-Semitism in which a new theoretical model of anti-Semitism is presented and tested in six experiments. The model proposes that mortality salience increases anti-Semitism and that anti-Semitism often manifests as hostility towards Israel. In accord with predictions, results show that existential fears lead to higher anti-Semitism and reduced support for Israel. Collectively, these re...

  18. Overview of Anti-tank Mines

    Institute of Scientific and Technical Information of China (English)

    Manfred Held

    2006-01-01

    First the different anti-tank mines laying possibilities are shortly summarized: hand emplaced, with mine layers, ground or helicopter relatively topographical well defined, and with cluster systems of projectiles, rockets and aircraft dispensers. Then examples of the three generations of anti-tank mines are presented:Ⅰ generation: detonating only beneath the track; Ⅱ generation: detonating beneath the track and belly;Ⅲ generation: mines with off-route actions. Weight and cost comparisons are strongly favoring the off-route Ⅲ-generation mines.

  19. Anti p-p collider group

    International Nuclear Information System (INIS)

    While this small group was largely occupied in interacting with other groups, there are some conclusions of general interest. The anti p-p lattice and beam avoidance scheme for a single ring collider, as presented by T. Collins, was accepted as a proof-by-example that a collider could be built with a substantial luminosity. There were no suggestions for improvement, in fact the limitations of this design are not likely to be improved. A production rate of 109 anti p's/sec provides for a total luminosity of 3 x 1033 or 5 x 1032 in each of six interaction regions

  20. Strange anti-baryons---QGP versus HC

    International Nuclear Information System (INIS)

    We study quark-gluon plasma (QGP) and hadronic gas (HG) models of the central fireball presumed to be the source of abundantly produced strange (anti-)baryons in S→W collisions at 200 GeV A. We consider how multi-strange (anti-)baryon multiplicities depend on strangeness conservation and compare the HG and QGP fireball scenarios. We argue that the total particle multiplicity emerging from the central rapidity region as well as the variation of production rates with changes in the beam energy allows to distinguish between the two reaction scenarios

  1. Naturally occurring anti M complicating ABO grouping

    Directory of Open Access Journals (Sweden)

    Safoorah Khalid

    2011-01-01

    Full Text Available Anti M is considered a naturally occurring antibody that is usually active at temperatures below 37°C and is thus of no clinical significance. This antibody, if present in an individual, can lead to a discrepancy between forward and reverse ABO grouping and thus creates diagnostic difficulties for blood bank staff. We report a case of a 58-year-old lady who had an unexpected reaction in reverse grouping due to anti M that posed a problem for us in the interpretation of results of her blood group. We also reviewed the literature to find out the significance of such discrepancy in blood grouping.

  2. Naturally occurring anti M complicating ABO grouping.

    Science.gov (United States)

    Khalid, Safoorah; Dantes, Roelyn; Varghese, Sunu; Al Hakawati, Imadeddin

    2011-01-01

    Anti M is considered a naturally occurring antibody that is usually active at temperatures below 37°C and is thus of no clinical significance. This antibody, if present in an individual, can lead to a discrepancy between forward and reverse ABO grouping and thus creates diagnostic difficulties for blood bank staff. We report a case of a 58-year-old lady who had an unexpected reaction in reverse grouping due to anti M that posed a problem for us in the interpretation of results of her blood group. We also reviewed the literature to find out the significance of such discrepancy in blood grouping. PMID:21393909

  3. Naturally occurring anti M complicating ABO grouping

    OpenAIRE

    Safoorah Khalid; Roelyn Dantes; Sunu Varghese; Imadeddin Al Hakawati

    2011-01-01

    Anti M is considered a naturally occurring antibody that is usually active at temperatures below 37°C and is thus of no clinical significance. This antibody, if present in an individual, can lead to a discrepancy between forward and reverse ABO grouping and thus creates diagnostic difficulties for blood bank staff. We report a case of a 58-year-old lady who had an unexpected reaction in reverse grouping due to anti M that posed a problem for us in the interpretation of results of her blood gr...

  4. Cannabis in Sport: Anti-Doping Perspective

    OpenAIRE

    Huestis, Marilyn A.; Mazzoni, Irene; Rabin, Olivier

    2011-01-01

    Since 2004, when the World Anti-Doping Agency assumed the responsi-bility for establishing and maintaining the list of prohibited substances and methods in sport (i.e. the Prohibited List), cannabinoids have been prohibited in all sports during competition. The basis for this prohibition can be found in the World Anti-Doping Code, which defines the three criteria used to consider banning a substance. In this context, we discuss the potential of can-nabis to enhance sports performance, the ris...

  5. Anti-atherosclerotic effects of konjac

    Directory of Open Access Journals (Sweden)

    Hidekatsu Yanai

    2015-04-01

    Full Text Available Definition: The Konjac plant comes from the genus Amorphophallus. Japanese food uses Konjac cake. Konjac contains almost no calories and a great amount of dietary fiber. Here, we reviewed possible anti-atherosclerotic effects of konjac, using the search Pubmed ®. Konjac ingestion is likely beneficially associated with obesity, blood pressure, lipid and glucose metabolism. However, evidence is lacking on the relationship between konjac ingestion and development of atherosclerotic diseases. To more fully understand the anti-atherosclerotic effects of konjac, future studies, preferably with larger numbers of subjects, will be performed.

  6. Immunogenicity of Anti-TNF-α Biotherapies

    DEFF Research Database (Denmark)

    Bendtzen, Klaus

    2015-01-01

    patients do not respond and about 50% of those who do loose response with time. Furthermore, safety may be compromised by immunogenicity with the induction of anti-drug-antibodies (ADA). Assessment of drug pharmacokinetics and ADA is increasingly recognized as a requirement for safe and rational use of...... article - and the accompanying article - is to discuss the reasons for recommending assessments of circulating drug and ADA levels in patients treated with anti-TNF biopharmaceuticals and to detail some of the methodological issues that obscure cost-effective and safer therapies....

  7. High luminosity anti p-p ring

    International Nuclear Information System (INIS)

    The basic problem in obtaining high luminosity in a single ring anti p-p collider is devising a method of having very many bunches in the ring without extraneous collisions which devour the anti p's. The author demonstrates a numerical example that a practical lattice can be constructed which accommodates a separation scheme, that the close-encounter beam-beam effects in the arcs are not serious, and that the aperture required is not excessive. The example is not complete in that it does not include injection and abort straight sections, but these will not affect beam separation design

  8. Effects of Egg Shell Membrane Hydrolysates on Anti-Inflammatory, Anti-Wrinkle, Anti-Microbial Activity and Moisture-Protection

    OpenAIRE

    Yoo, JinHee; Park, Kimoon; Yoo, Youngji; Kim, Jongkeun; Yang, Heejin; Shin, Youngjae

    2014-01-01

    This study was conducted to examine the effects of eggshell membrane hydrolysates (ESMH) on the anti-inflammatory, anti-wrinkle, anti-microbial activity, and moisture-protection for cosmetic use. Whole ESMH (before fractionation), and fraction I (>10 kDa), fraction II (3-10 kDa), and fraction III (

  9. ANTI-MICROBIAL AND ANTI-AMOEBIC ACTIVITY SOME AZOMETHINES - POTENTIAL TEXTILE DYESTUFFS

    Directory of Open Access Journals (Sweden)

    DJORDJEVIC Dragan

    2016-05-01

    Full Text Available In this paper, new synthesized three azomethine derivatives applied in dyeing textiles checking the anti-microbial properties of active components, at the same time [1-3]. The emphasis is thrown on the verification of anti-microbial properties that are important for obtaining textile with significantly improved performance. All compounds were characterized and evaluated for their anti-microbial activity against 7 pathogenic bacteria, 1 parasitic protozoan and 1 fungus. It estimated anti-bacterial activity in vitro against the following microorganisms Staphylococcus aureus, Bacillus anthracis, Streptococcus faecalis, Enterobacter sp., Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, and Candida albicans. The anti-amoebic activity in vitro was evaluated against the HM1: IMSS strain of Entamoeba histolytica and the results were compared with the standard drug, metronidazole. The synthesized azomethines, showed very good substantivity for wool fibers, gave fine coloring, with good degree of exhaustion after dyeing. The combination of extended synthetic analogues of natural molecules leads to discovery of chemical entities which might be excellent anti-microbial and anti-amoebic compounds as depicted in our results. Being highly the effects this compound can be explored in future as an option for decreasing pathogenic potential of infecting from different sources. Azomethines containing hydrazone (dyestuff 1 and phenylhydrazone (dyestuff 2 as moiety show average yield and moderate inhibition activity while azomethines containing thiosemicarbazone (dyestuff 3 as moiety show higher yield and greater inhibition activity towards gram-negative and gram-positive bacteria as well as a fungus.

  10. Anti-inflammatory and anti-arthritic effects of yucca schidigera: A review

    Directory of Open Access Journals (Sweden)

    Piacente S

    2006-03-01

    Full Text Available Abstract Yucca schidigera is a medicinal plant native to Mexico. According to folk medicine, yucca extracts have anti-arthritic and anti-inflammatory effects. The plant contains several physiologically active phytochemicals. It is a rich source of steroidal saponins, and is used commercially as a saponin source. Saponins have diverse biological effects, including anti-protozoal activity. It has been postulated that saponins may have anti-arthritic properties by suppressing intestinal protozoa which may have a role in joint inflammation. Yucca is also a rich source of polyphenolics, including resveratrol and a number of other stilbenes (yuccaols A, B, C, D and E. These phenolics have anti-inflammatory activity. They are inhibitors of the nuclear transcription factor NFkappaB. NFkB stimulates synthesis of inducible nitric oxide synthase (iNOS, which causes formation of the inflammatory agent nitric oxide. Yucca phenolics are also anti-oxidants and free-radical scavengers, which may aid in suppressing reactive oxygen species that stimulate inflammatory responses. Based on these findings, further studies on the anti-arthritic effects of Yucca schidigera are warranted.

  11. Anti-Cancer Effects of Green Tea by Either Anti- or Pro- Oxidative Mechanisms.

    Science.gov (United States)

    Hayakawa, Sumio; Saito, Kieko; Miyoshi, Noriyuki; Ohishi, Tomokazu; Oishi, Yumiko; Miyoshi, Mamoru; Nakamura, Yoriyuki

    2016-01-01

    Tea derived from the leaves and buds of Camellia sinensis (Theaceae) is consumed worldwide. Green tea contains various components with specific health-promoting effects, and is believed to exert protective effects against diseases including cancer, diabetes and hepatitis, as well as obesity. Of the various tea components, the polyphenol catechins have been the subject of extensive investigation and among the catechins, (-)-epigallocatechin gallate has the strongest bioactivity in most cases. Our research group has postulated that hepatocyte nuclear factor-4α, sterol regulatory element-binding proteins, and tumor necrosis factor-α are targets of green tea constituents including (-)-epigallocatechin gallate for their anti-diabetes, anti-obesity, and anti-hepatitis effects, respectively. Published papers were reviewed to determine whether the observed changes in these factors can be correlated with anti-cancer effects of green tea. Two major action mechanisms of (-)-epigallocatechin gallate have been proposed; one associated with its anti-oxidative properties and the other with its pro-oxidative activity. When reactive oxygen species are assumed to be involved, our findings that (-)-epigallocatechin gallate down- regulated hepatocyte nuclear factor-4α, sterol regulatory element-binding proteins, and tumor necrosis factor-α may explain the anti-cancer effect of green tea as well. However, further studies are required to elucidate which determinant directs (-)-epigallocatechin gallate action as an anti-oxidant or a pro-oxidant for favorable activity. PMID:27221834

  12. Anti-beta2 glycoprotein 1 and the anti-phospholipid syndrome.

    LENUS (Irish Health Repository)

    Keane, Pearse A

    2012-02-03

    PURPOSE: To describe a patient who presented with bilateral retinal vascular occlusion and the use of anti-beta2 glycoprotein 1 (GPI) antibody testing in the diagnosis of antiphospholipid syndrome. DESIGN: Observational case report. METHODS: Hematological investigations were performed on a 49-year-old man who presented with rapid onset of bilateral severe central retinal vein occlusion. RESULTS: Lupus anticoagulant and anticardiolipin antibody testing was negative. Markedly raised titers of anti-beta2 GPI antibodies were detected on two separate occasions. CONCLUSIONS: The raised titers of anti-beta2 GPI antibodies were considered to strongly suggest an underlying diagnosis of the antiphospholipid syndrome.

  13. Measurement of (anti)deuteron and (anti)proton production in DIS at HERA

    International Nuclear Information System (INIS)

    The first observation of (anti)deuterons in deep inelastic scattering at HERA has been made with the ZEUS detector at a centre-of-mass energy of 300-318 GeV using an integrated luminosity of 120 pb-1. The measurement was performed in the central rapidity region for transverse momentum per unit of mass in the range 0.3T/M<0.7. The particle rates have been extracted and interpreted in terms of the coalescence model. The (anti)deuteron production yield is smaller than the (anti)proton yield by approximately three orders of magnitude, consistent with the world measurements. (orig.)

  14. Anti-S100A4 Antibody Suppresses Metastasis Formation by Blocking Stroma Cell Invasion

    OpenAIRE

    Jörg Klingelhöfer; Birgitte Grum-Schwensen; Beck, Mette K.; Rikke Stagaard Petersen Knudsen; Mariam Grigorian; Eugene Lukanidin; Noona Ambartsumian

    2012-01-01

    The small Ca-binding protein, S100A4, has a well-established metastasis-promoting activity. Moreover, its expression is tightly correlated with poor prognosis in patients with numerous types of cancer. Mechanistically, the extracellular S100A4 drives metastasis by affecting the tumor microenvironment, making it an attractive target for anti-cancer therapy. In this study, we produced a function-blocking anti-S100A4 monoclonal antibody with metastasis-suppressing activity. Antibody treatment si...

  15. Measurement of (anti)deuteron and (anti)proton production in DIS at HERA

    CERN Document Server

    Chekanov, S; Magill, S; Musgrave, B; Nicholass, D; Repond, J; Yoshida, R; Mattingly, M C K; Jechow, M; Pavel, N; Yagues-Molina, A G; Antonelli, S; Antonioli, P; Bari, G; Basile, M; Bellagamba, L; Bindi, M; Boscherini, D; Bruni, A; Bruni, G; Cifarelli, L; Cindolo, F; Contin, A; Corradi, M; De Pasquale, S; Iacobucci, G; Margotti, A; Nania, R; Polini, A; Sartorelli, G; Zichichi, A; Bartsch, D; Brock, I; Goers, S; Hartmann, H; Hilger, E; Jakob, H P; Jüngst, M; Kind, O M; Nuncio-Quiroz, A E; Paul, E; Renner, R; Samson, U; Schonberg, V; Shehzadi, R; Wlasenko, M; Brook, N H; Heath, G P; Morris, J D; Namsoo, T; Capua, M; Fazio, S; Mastroberardino, A; Schioppa, M; Susinno, G; Tassi, E; Kim, J Y; Ma, K J; Ibrahim, Z A; Kamaluddin, B; Wan-Abdullah, W A T; Ning, Y; Ren, Z; Sciulli, F; Chwastowski, J; Eskreys, A; Figiel, J; Galas, A; Gil, M; Olkiewicz, K; Stopa, P; Zawiejski, L; Adamczyk, L; Bold, T; Grabowska-Bold, I; Kisielewska, D; Lukasik, J; Przybycien, M; Suszycki, L; Kotanski, A; Slominski, W; Adler, V; Behrens, U; Bloch, I; Blohm, C; Bonato, A; Borras, K; Ciesielski, R; Coppola, N; Dossanov, A; Drugakov, V; Fourletova, J; Geiser, A; Gladkov, D; Göttlicher, P; Grebenyuk, J; Gregor, I; Haas, T; Hain, W; Horn, C; Huttmann, A; Kahle, B; Katkov, I I; Klein, U; Kötz, U; Kowalski, H; Lobodzinska, E; Löhr, B; Mankel, R; Melzer-Pellmann, I A; Miglioranzi, S; Montanari, A; Notz, D; Rinaldi, L; Roloff, P; Rubinsky, I; Santamarta, R; Schneekloth, U; Spiridonov, A; Stadie, H; Szuba, D; Szuba, J; Theedt, T; Wolf, G; Wrona, K; Youngman, C; Zeuner, W; Lohmann, W; Schlenstedt, S; Barbagli, G; Gallo, E; Pelfer, P G; Bamberger, A; Dobur, D; Karstens, F; Vlasov, N N; Bussey, P J; Doyle, A T; Dunne, W; Ferrando, J; Forrest, M; Saxon, D H; Skillicorn, I O; Gialas, I; Papageorgiu, K; Gosau, T; Holm, U; Klanner, R; Lohrmann, E; Salehi, H; Schleper, P; Schörner-Sadenius, T; Sztuk, J; Wichmann, K; Wick, K; Foudas, C; Fry, C; Long, K R; Tapper, A D; Kataoka, M; Matsumoto, T; Nagano, K; Tokushuku, K; Yamada, S; Yamazaki, Y; Barakbaev, A N; Boos, E G; Pokrovskiy, N S; Zhautykov, B O; Aushev, V; Son, D; De Favereau, J; Piotrzkowski, K; Barreiro, F; Glasman, C; Jiménez, M; Labarga, L; Del Peso, J; Ron, E; Soares, M; Terron, J; Zambrana, M; Corriveau, F; Liu, C; Walsh, R; Zhou, C; Tsurugai, T; Antonov, A; Dolgoshein, B A; Sosnovtsev, V; Stifutkin, A; Suchkov, S; Dementiev, R K; Ermolov, P F; Gladilin, L K; Khein, L A; Korzhavina, I A; Kuzmin, V A; Levchenko, B B; Lukina, O Yu; Proskuryakov, A S; Shcheglova, L M; Zotkin, D S; Zotkin, S A; Abt, I; Büttner, C; Caldwell, A; Kollar, D; Schmidke, W B; Sutiak, J; Grigorescu, G; Keramidas, A; Koffeman, E; Kooijman, P; Pellegrino, A; Tiecke, H; Vázquez, M; Wiggers, L; Brümmer, N; Bylsma, B; Durkin, L S; Lee, A; Ling, T Y; Allfrey, P D; Bell, M A; Cooper-Sarkar, A M; Cottrell, A; Devenish, R C E; Foster, B; Korcsak-Gorzo, K; Patel, S; Roberfroid, V; Robertson, A; Straub, P B; Uribe-, C; Estrada; Walczak, R; Bellan, P; Bertolin, A; Brugnera, R; Carlin, R; Dal Corso, F; Dusini, S; Garfagnini, A; Limentani, S; Longhin, A; Stanco, L; Turcato, M; Oh, B Y; Raval, A; Ukleja, J; Whitmore, J J; Iga, Y; D'Agostini, G; Marini, G; Nigro, A; Cole, J E; Hart, J C; Abramowicz, H; Gabareen, A; Ingbir, R; Kananov, S; Levy, A; Kuze, M; Maeda, J; Hori, R; Kagawa, S; Okazaki, N; Shimizu, S; Tawara, T; Hamatsu, R; Kaji, H; Kitamura, S; Ota, O; Ri, Y D; Ferrero, M I; Monaco, V; Sacchi, R; Solano, A; Arneodo, M; Ruspa, M; Fourletov, S; Martin, J F; Boutle, S K; Butterworth, J M; Gwenlan, C; Jones, T W; Loizides, J H; Sutton, M R; Wing, M; Brzozowska, B; Ciborowski, J; Grzelak, G; Kulinski, P; Luzniak, P; Malka, J; Nowak, R J; Pawlak, J M; Tymieniecka, T; Ukleja, A; Zarnecki, A F; Adamus, M; Plucinsky, P P; Eisenberg, Y; Giller, I; Hochman, D; Karshon, U; Rosin, M; Brownson, E; Danielson, T; Everett, A; Kcira, D; Reeder, D D; Ryan, P; Savin, A A; Smith, W H; Wolfe, H; Bhadra, S; Catterall, C D; Cui, Y; Hartner, G; Menary, S; Noor, U; Standage, J; Whyte, J

    2007-01-01

    The first observation of (anti)deuterons in deep inelastic scattering at HERA has been made with the ZEUS detector at a centre-of-mass energy of 300--318 GeV using an integrated luminosity of 120 pb-1. The measurement was performed in the central rapidity region for transverse momentum per unit of mass in the range 0.3anti)deuteron production yield is smaller than the (anti)proton yield by approximately three orders of magnitude, consistent with the world measurements.

  16. Anti-idiotypes against anti-H-2 monoclonal antibodies: structural analysis of the molecules induced by in vivo anti-idiotype treatment.

    OpenAIRE

    Bluestone, J A; Krutzsch, H C; Auchincloss, H.; Cazenave, P A; Kindt, T. J.; Sachs, D. H.

    1982-01-01

    Previous studies have shown that treatment of mice in vivo with xenogeneic anti-idiotype produced against a monoclonal anti-H-2Kk antibody, 11-4.1, leads to the induction of molecules (Id') that inhibit the binding of anti-idiotype to idiotype. To investigate the nature of these Id' molecules, spleens from such anti-idiotype-treated mice were fused with the SP2/0 myeloma to produce monoclonal Id' antibodies. All four monoclonal Id' antibodies were found to react with goat and rabbit anti-11-4...

  17. Novel anti-inflammatory agents in COPD

    DEFF Research Database (Denmark)

    Loukides, Stelios; Bartziokas, Konstantinos; Vestbo, Jørgen;

    2013-01-01

    Inflammation plays a central role in chronic obstructive pulmonary disease (COPD). COPD related inflammation is less responsive to inhaled steroids compared to asthma. There are three major novel anti-inflammatory approaches to the management of COPD. The first approach is phosphodiesterase...

  18. Anti-inflammatory Agents: Present and Future.

    NARCIS (Netherlands)

    Dinarello, C.A.

    2010-01-01

    Inflammation involving the innate and adaptive immune systems is a normal response to infection. However, when allowed to continue unchecked, inflammation may result in autoimmune or autoinflammatory disorders, neurodegenerative disease, or cancer. A variety of safe and effective anti-inflammatory a

  19. Cultural Diversity and Anti-Poverty Policy

    Science.gov (United States)

    Lamont, Michele; Small, Mario Luis

    2010-01-01

    This article examines how anti-poverty policy has considered the role of culture and how it ought to do so. While some have explained poverty as a function of the presumed cultural deficiency or distinctiveness of the poor, we suggest that these explanations have not been convincing and that policy requires a broader and more sophisticated…

  20. Anti-Mullerian hormone and ovarian dysfunction

    NARCIS (Netherlands)

    Broekmans, Frank J.; Visser, Jenny A.; Laven, Joop S. E.; Broer, Simone L.; Themmen, Axel P. N.; Fauser, Bart C.

    2008-01-01

    Anti-Mullerian hormone (AMH) has important roles in postnatal ovarian function. Produced by ovarian granulosa cells, AMH is involved in initial follicle development. In fact, serum AMH level correlates with ovarian follicle number. In patients with polycystic ovary syndrome (PCOS), AMH levels are el

  1. Anti-Luck (Too Weak) Virtue Epistemology

    DEFF Research Database (Denmark)

    Broncano-Berrocal, Fernando

    2014-01-01

    I argue that Duncan Pritchard’s anti-luck virtue epistemology is insufficient for knowledge. I show that Pritchard fails to achieve the aim that motivates his adoption of a virtue-theoretic condition in the first place: to guarantee the appropriate direction of fit that known beliefs have. Finally...

  2. Anti-Semitism in First Year Composition

    Science.gov (United States)

    Levy, Matthew; Myers, Gerald M.

    2011-01-01

    Robert Cohen, Assistant Professor English at Fairbanks University, has just completed a contentious meeting of his First Year Composition class, which had discussed a paper written by one of the students. Joe Anderson's paper contained statements that have been historically used as anti-Semitic slogans. Cohen attempted to avoid embarrassing…

  3. SCREENING OF PLANTS FOR ANTI DERMATOPHYTE ACTIVITY

    Directory of Open Access Journals (Sweden)

    V.S. Chauhan, A. Suthar, V. Naik and K. Salkar*

    2012-05-01

    Full Text Available Mycotic infections of skin are caused by dermatophytes. Screening of plants for anti dermatophyte activity was carried out based on the literature search done. Native plants of Maharashtra (India were screened for anti dermatophyte activity. Various plant parts from different regions were collected and then extracted with three different solvents viz. alcohol, hydro-alcohol and aqueous. The obtained extracts were subjected for anti dermatophyte activity using agar-well diffusion technique. Three different concentrations of extract were checked for activity. Two species of dermatophytes, viz. - Trichophyton and Microsporum were used in the screening assay. Out of the twenty-eight plants screened by agar diffusion method, seven were found to be active with different activity profile. Methanol extract was the most active extract. Pterospermum suberifolium, Trachyspermum ammi, Peltaphorum pterocarpum, Ixora coccinia, Persicaria glabra, Terminallia elliptica and Cicca acida showed activity at different concentrations against the two species of dermatophytes. The data obtained can be used for further studying the anti dermatophyte potential of active plants.

  4. Λ(anti Λ) beams at FNAL

    International Nuclear Information System (INIS)

    The discussion of the lambda anti lambda beams involves how to make polarized protons from lambda decay so that experiments on polarization at very high energies may be possible. The aspect studied is the amount of polarization and how to get it

  5. Structural Liberalism and Anti-Bullying Legislation

    Science.gov (United States)

    Vaught, Sabina E.

    2014-01-01

    This article investigates the legal, semantic, and material implications of Massachusetts' anti-bullying law through an analytic framework of structural liberalism. Specifically, this article asks how the law produces categories of fit and unfit subjects of the state through raced and gendered practices of individualism, paternalism,…

  6. Anti-D: mechanisms of action.

    Science.gov (United States)

    Ware, R E; Zimmerman, S A

    1998-01-01

    Immunoglobulin that recognizes and binds specifically to the erythrocyte D antigen (anti-D globulin, WinRho SDF; Nabi, Boca Raton, FL) has recently been shown to be an effective therapy for many patients with idiopathic thrombocytopenic purpura (ITP). Its mechanisms of action are not completely understood. Intravenous (IV) infusion of anti-D into a D-positive recipient leads to antibody coating of circulating erythrocytes that are cleared primarily by the spleen. This immune-mediated clearance of sensitized erythrocytes occupies the reticuloendothelial system and allows survival of antibody-coated platelets. Based on clinical observations, experimental data, and theoretical calculations, the efficacy of anti-D therapy in ITP depends on several factors that influence the amount of erythrocyte sensitization and the rate of immune-mediated erythrocyte clearance by the spleen. Antibody characteristics, including the antibody concentration, binding affinity, and dissociation constants, may be important, as well as the number of D-antigen binding sites on the erythrocytes. Although the primary mechanism of action of anti-D is believed to be immunologic blockade of Fc receptors (FcR) within the reticuloendothelial system (RES), other immunomodulatory effects are also possible. PMID:9523745

  7. Renormalized quark-anti-quark free energy

    OpenAIRE

    Zantow, F.; Kaczmarek, O.; Karsch, F.; Petreczky, P.

    2003-01-01

    We present results on the renormalized quark-anti-quark free energy in SU(3) gauge theory at finite temperatures. We discuss results for the singlet, octet and colour averaged free energies and comment on thermal relations which allow to extract separately the potential energy and entropy from the free energy.

  8. Anti-C1q autoantibodies

    NARCIS (Netherlands)

    Kallenberg, Cees G. M.

    2008-01-01

    Autoantibodies to complement components are associated with various diseases. Anti-C1q antibodies are present in all patients with hypocomplementemic urticarial vasculitis, but also, with varying prevalence, in other conditions. In SLE, these antibodies are neither sensitive nor specific for this co

  9. Anti-forensics of chromatic aberration

    Science.gov (United States)

    Mayer, Owen; Stamm, Matthew C.

    2015-03-01

    Over the past decade, a number of information forensic techniques have been developed to identify digital image manipulation and falsification. Recent research has shown, however, that an intelligent forger can use anti-forensic countermeasures to disguise their forgeries. In this paper, an anti-forensic technique is proposed to falsify the lateral chromatic aberration present in a digital image. Lateral chromatic aberration corresponds to the relative contraction or expansion between an image's color channels that occurs due to a lens's inability to focus all wavelengths of light on the same point. Previous work has used localized inconsistencies in an image's chromatic aberration to expose cut-and-paste image forgeries. The anti-forensic technique presented in this paper operates by estimating the expected lateral chromatic aberration at an image location, then removing deviations from this estimate caused by tampering or falsification. Experimental results are presented that demonstrate that our anti-forensic technique can be used to effectively disguise evidence of an image forgery.

  10. Utopian Education and Anti-Utopian Anthropology

    Science.gov (United States)

    Papastephanou, Marianna

    2013-01-01

    This article explores the connection of education, utopia and anthropology, aiming to tease out some educational implications of anti-utopian anthropological essentialism and to show why these should be staved off. It will be shown how an anthropology that tarnishes human nature operates and how it affects educational intervention in the shaping…

  11. Anti-viral Responses in Insects

    Science.gov (United States)

    Although the study of anti-viral responses in insects has lagged behind studies of responses to other types of pathogens, progress has begun to rapidly accelerate over the past few years. Insects are subject to infection by many different kinds of DNA and RNA viruses. These include viruses that ar...

  12. Quantum Zeno and anti-Zeno paradoxes

    Indian Academy of Sciences (India)

    S M Roy

    2001-02-01

    Continuous observation of a time independent projection operator is known to prevent change of state (the quantum Zeno paradox). We discuss the recent result that generic continuous measurement of time dependent projection operators will in fact ensure change of state: an anti-Zeno paradox.

  13. For an anti-atoms handful

    International Nuclear Information System (INIS)

    On the fourth of January 1996, Geneva: the announcing of making of nine antimatter atoms makes reappear old questions. Is it possible that in our universe, far anti galaxies exist. Ambitious space programs will try to detect them. In waiting for this, the exploration of this fascinating symmetry is continuing in laboratory

  14. Anti-Sharing as a Theory of Partnerships and Firms

    OpenAIRE

    Kirstein, Roland; Cooter, Robert D.

    2006-01-01

    Anti-Sharing may improve the efficiency of teams. The Anti-Sharer collects a fixed payment from all team members; he receives the actual output and pays out its value to them. However, if a team members assumes the role of an "internal" Anti-Sharer, he will be unproductive in equilibrium. Hence, internal Anti-Sharing fails to yield the first-best outcome. External Anti-sharing may induce the team members to choose efficient effort. The paper presents possible applications of Anti-Sharing: whi...

  15. Anti-inflammatory activity of cationic lipids.

    Science.gov (United States)

    Filion, M C; Phillips, N C

    1997-10-01

    1. The effect of liposome phospholipid composition has been assumed to be relatively unimportant because of the presumed inert nature of phospholipids. 2. We have previously shown that cationic liposome formulations used for gene therapy inhibit, through their cationic component, the synthesis by activated macrophages of the pro-inflammatory mediators nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha). 3. In this study, we have evaluated the ability of different cationic lipids to reduce footpad inflammation induced by carrageenan and by sheep red blood cell challenge. 4. Parenteral (i.p. or s.c) or local injection of the positively charged lipids dimethyldioctadecylammomium bromide (DDAB), dioleyoltrimethylammonium propane (DOTAP), dimyristoyltrimethylammonium propane (DMTAP) or dimethylaminoethanecarbamoyl cholesterol (DC-Chol) significantly reduced the inflammation observed in both models in a dose-dependent manner (maximum inhibition: 70-95%). 5. Cationic lipids associated with dioleyol- or dipalmitoyl-phosphatidylethanolamine retained their anti-inflammatory activity while cationic lipids associated with dipalmitoylphosphatidylcholine (DPPC) or dimyristoylphosphatidylglycerol (DMPG) showed no anti-inflammatory activity, indicating that the release of cationic lipids into the macrophage cytoplasm is a necessary step for anti-inflammatory activity. The anti-inflammatory activity of cationic lipids was abrogated by the addition of dipalmitoylphosphatidylethanolamine-poly(ethylene)glycol-2000 (DPPE-PEG2000) which blocks the interaction of cationic lipids with macrophages. 6. Because of the significant role of protein kinase C (PKC) in the inflammatory process we have determined whether the cationic lipids used in this study inhibit PKC activity. The cationic lipids significantly inhibited the activity of PKC but not the activity of a non-related protein kinase, PKA. The synthesis of interleukin-6 (IL-6), which is not dependent on PKC activity for its

  16. Anti-Oxidant, Anti-Aging, and Anti-Melanogenic Properties of the Essential Oils from Two Varieties of Alpinia zerumbet

    Directory of Open Access Journals (Sweden)

    Pham Thi Be Tu

    2015-09-01

    Full Text Available Here, we investigated the anti-oxidant and anti-aging effects of essential oils (EOs from the leaves of Alpinia zerumbet (tairin and shima in vitro and anti-melanogenic effects in B16F10 melanoma cells. The anti-oxidant activities were performed with 2,2-diphenyl-1-picrylhydrazyl (DPPH; 2,2ʹ-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid diammonium salt (ABTS; nitric oxide; singlet oxygen; hydroxyl radical scavenging; and xanthine oxidase. The inhibitory activities against collagenase, elastase, hyaluronidase, and tyrosinase were employed for anti-aging. The anti-melanogenic was assessed in B16F10 melanoma cells by melanin synthesis and intracellular tyrosinase inhibitory activity. The volatile chemical composition of the essential oil was analyzed with gas chromatography-mass spectrometry (GC/MS. The EO was a complex mixture mainly consisting of monoterpenes and sesquiterpenes. The results revealed that tairin and shima EOs showed strong anti-oxidant activities against DPPH and nitric oxide, hydroxyl radical scavenging activity, and xanthine oxidase inhibition. Compared to shima EO; tairin EO exhibited strong anti-aging activity by inhibiting collagenase, tyrosinase, hyaluronidase, and elastase (IC50 = 11 ± 0.1; 25 ± 1.2; 83 ± 1.6; and 213 ± 2 μg/mL, respectively. Both EOs inhibited intracellular tyrosinase activity; thus, reducing melanin synthesis. These results suggest that tairin EO has better anti-oxidant/anti-aging activity than shima EO, but both are equally anti-melanogenic.

  17. Neonatal molecular pathologies induced by maternal anti-Ro and anti-La antibodies

    Directory of Open Access Journals (Sweden)

    Herrera-Esparza R

    2015-08-01

    Full Text Available Maternal antinuclear antibodies with anti-Ro or anti-La specificity might be pathogenic to the fetus and could induce molecular neonatal pathologies, such as neonatal lupus (NL with or without congenital heart block (CHB. The cutaneous manifestations of neonatal lupus appear at birth or a few weeks later, and skin lesions may persist for weeks. While CHB is characterized by intrauterine bradycardia or low heart rates at birth and may persist for months, depending on the degree of blockage. Clinical and experimental data demonstrated that anti-Ro and anti-La autoantibodies functionally inhibit L-type calcium channels and induce abnormalities in electrical conduction of the cardiac myocytes. It has been 38 years since the first clinical description of CHB. Presently, the pathophysiology of CHB has been clarified through clinical and basic research studies.

  18. The Puzzle of Simultaneous Anti-Dumping and Anti-Subsidy Measures

    DEFF Research Database (Denmark)

    Nielsen, Jørgen Ulff-Møller; Hansen, Jørgen Drud

    Quite frequently an anti-subsidy investigation in the EU is paired with an anti-dumping investigation against the same non-EU producers. The final outcome may be a two-component duty where one duty addresses the ‘unfairness’ of the subsidy and the other the dumping behavior. The procedure may...... be a surprise, as the same total level of protection may be obtained by using the anti-dumping procedure exclusively. When calculating the two duties in the EU the outcome depends on whether the subsidies are export subsidies or domestic subsidies and this may also cause surprise. This paper addresses......’ competition completely and because a parallel investigation may increase the probability of a successful outcome for the petitioners. In contrast, we find that the different assumptions about the effect of export subsidies and domestic production subsidies on the dumping margin in the EU dual anti...

  19. Synthesis, Anti-Inflammatory and Anti-oxidant activity of some substituted Benzimidazole Derivatives

    Directory of Open Access Journals (Sweden)

    Rajasekaran S

    2012-09-01

    Full Text Available Benzimidazoles are an important class of compounds with a wide spectrum of biological activity ranging from anti-hypertensive, anti-viral, anti-fungal, antitumor and anthelmintic activity. In addition, few N-substituted benzimidazole derivatives have shown to exhibit significant activity against several viruses, including HIV, herpes simplex (HSV-1, influenza, picorna, human cytomegalovirus (HCMV and hepatitis C virus. The five membered heterocyclic moiety 1,3,4-oxadiazole also confers for various biological activity. Hence a series of benzimidazole derivatives fused with oxadiazole ring system have been synthesized, characterized by UV, IR and 1H NMR spectral data and evaluated for their in vitro and in vivo anti-inflammatory and antioxidant activity.

  20. Kan vericilerde HBsAg, anti-HCV, anti-HIV ve Sifilis seroprevalansı

    OpenAIRE

    Altındiş, Mustafa; Aslan, Savaş; Kalaycı, Raike

    2011-01-01

    Bu çalışmada Afyon Kocatepe Üniversitesi Tıp Fakültesi Kan Merkezi'ne başvuran donörlerde HBsAg, anti-HCV, anti-HIV 1/2 ve RPR seroprevalansının tespiti ve oranların yıllara ve cinsiyete göre dağılımının belirlenmesi amaçlanmıştır. Ocak'2001 ve Aralık'2010 tarihleri arasında Kan Merkezi'ne başvuran 37343 kan donörünün HBsAg, anti-HCV, anti-HIV ½ tarama testleri mikropartikül ELISA (Vitros, Ortho-Clinical Diagnostics) yöntemi ile Ortho-Clinical Diagnostics (HBsAg, HCV 3.jenerasyon, HIV 1/2) ki...

  1. Anti-E Alloimmunization: A Rare Cause of Severe Fetal Hemolytic Disease Resulting in Pregnancy Loss

    Directory of Open Access Journals (Sweden)

    An-Shine Chao

    2009-01-01

    Full Text Available We report a case of severe intrauterine hemolysis caused by sole anti-E alloimmunization. A 36-year-old multipara woman presented with hydrops fetalis at 27 weeks of gestation. She had a history of previous neonatal death. In this pregnancy, she was found to have very high titer of anti-E antibody. Ultrasonography detected marked skin edema, cardiomegaly, hepatosplenomegaly, pleural effusion, ascites, placentomegaly, and polyhydramnios. The Doppler peak systolic velocity in the middle cerebral artery was 0.8 m/s, indicating severe fetal anemia. Multiple intrauterine transfusions for the anemic fetus were administered. However, persistent severe fetal anemia and placentomegaly caused poor neonatal death and mirror syndrome in the mother. Uncommon red blood cell alloimmunization has to be watched for early in any population, especially in a woman with a history of unexplained perinatal loss.

  2. The Modern Anti-Semitism Israel Model: An empirical relationship between modern anti-Semitism and opposition to Israel

    Directory of Open Access Journals (Sweden)

    Florette Cohen

    2011-04-01

    Full Text Available The current paper reviews our program of research that has examined some of the causes and consequences of anti-Semitism in which a new theoretical model of anti-Semitism is presented and tested in six experiments. The model proposes that mortality salience increases anti-Semitism and that anti-Semitism often manifests as hostility towards Israel. In accord with predictions, results show that existential fears lead to higher anti-Semitism and reduced support for Israel. Collectively, these results may serve as a preliminary contribution to explaining the continuation of anti-Semitism.

  3. Neonatal molecular pathologies induced by maternal anti-Ro and anti-La antibodies

    OpenAIRE

    Herrera-Esparza R.; Avalos-Díaz E

    2015-01-01

    Maternal antinuclear antibodies with anti-Ro or anti-La specificity might be pathogenic to the fetus and could induce molecular neonatal pathologies, such as neonatal lupus (NL) with or without congenital heart block (CHB). The cutaneous manifestations of neonatal lupus appear at birth or a few weeks later, and skin lesions may persist for weeks. While CHB is characterized by intrauterine bradycardia or low heart rates at birth and may persist for months, depending on the degree of blockage....

  4. EVALUATION OF ANTI-NOCICEPTIVE AND ANTI-INFLAMMATORY ACTIVITY OF PUNICA GRANATUM SEED EXTRACT

    OpenAIRE

    Gupta Jeetendra Kumar; Sharma Sandeep Kumar; Misra Vimlesh; Patel Kanika

    2011-01-01

    The plant Punica granatum of family Punicaceae is distributed throughout India and reputed to have numerous applications in traditional medicine system. In order to justify its folkloric use in nociception and inflammation, the study was performed.In this study, the extraction of Punica granatum seed extract was carried out in aqueous media. In order to explore its potency, various experimental models of anti-nociceptive and anti-inflammatory activities were taken. The oral administration of ...

  5. Anti-EU and Anti-LGBT Attitudes in Poland: Considering Quantitative and Qualitative Evidence

    Directory of Open Access Journals (Sweden)

    Chojnicka Joanna

    2015-10-01

    Full Text Available The purpose of this study is to investigate anti-EU and anti- LGBT attitudes in Poland on the basis of quantitative evidence (statistical data and qualitative evidence (discourse analysis of statements expressed on the Internet. As Euroscepticism seems to frequently appear in conjunction with prejudice against LGBT (lesbian, gay, bisexual and transsexual or transgender persons, the task of this article is to find out whether they may have a common foundation and what it may be.

  6. Anti-microbial and anti-biofilm compounds from Indonesian medicinal plants

    OpenAIRE

    Pratiwi, Sylvia U.T.

    2015-01-01

    Microbial biofilms causing elevated resistance to both most anti-microbial drugs and the host defense systems, which often results in persistent and difficult-to-treat infections. The discovery of anti-infective agents which are active against planktonic and biofilm microorganisms are therefore urgently required to deal with these biofilm-mediated infections. Plants are a rich source of new molecules with pharmacological properties for the development of new drugs. Indonesia is one of the cou...

  7. IN VIVO ANTI INFLAMMATORY AND ANTI ARTHRITIC ACTIVITY OF ETHANOLIC EXTRACT OF ASPARAGUS RACEMOSUS ROOTS

    Directory of Open Access Journals (Sweden)

    Suchita Mittal

    2013-04-01

    Full Text Available The present study is aimed to appraise the anti-inflammatory and anti-arthritic activity of ethanolic extract of Asparagus racemosus roots belonging to family Liliaceae. Carrageenan is used to induce inflammation and Freund’s Complete Adjuvant is used to induce arthritis. The result of this study revealed that Asparagus racemosus show potent effect on both the condition at a dose of 200mg/kg and 400mg/kg respectively.

  8. Anti-Tumor Effect and Anti-Inflammatory Activity of Boschniakia rossica

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the anti-tumor effect and anti-inflammatory activity of Boschniakia rossica (BR). Methods: The expression of tumor marker, GST-P, p53 and p21ras proteins in promotion stage of rat chemical hepatocarcinogenesis were examined by immunohistochemical technique ABC method. Anti-tumor effect of BR was investigated by inhibitory test on Sarcoma180. Anti-inflammatory activity of BR was tested by xylene-induced mouse ear swelling method. Results: BR-H2O extract (the H2O extract fractionated from BR-Methanol extract with CH2Cl2 and H2O) 500 mg/kg has inhibitory effect on the formation of diethylnitrosamine (DEN)-induced glutathione S-transferase placental form (GST-P) positive foci in rat liver with the expression of mutant p53 and p21ras proteins lower than those of non-treated hepatic preneoplastic lesions. BR extract showed inhibitory effect on Sarcoma180 and anti-inflammatory effect in mice by xylene-induced mouse ear swelling tests. Conclusion: BR- H2O extract exerted inhibitory effect on DEN-induced preneoplastic hepatic foci in promotion stage of rat chemical hepatocarcinogenesis and might suppress the growth of solid Sarcoma180 in mice. Both CH2Cl2 and H2O extract from BR exerted anti-inflammatory effect in mice.

  9. Analgesic, anti-inflammatory and anti-arthritic activity of Cassia uniflora Mill

    Institute of Scientific and Technical Information of China (English)

    She S Chaudhari; Sanjay R Chaudhari; Machindra J Chavan

    2012-01-01

    Objective: To evaluate the analgesic, anti-inflammatory and anti-arthritic activity of leaves of Cassia uniflora (C. uniflora) Mill. Methods: Petroleum ether, ethyl acetate and methanolic extract of C. uniflora (100 and 200 mg/kg, body weight) was screened for analgesic (Eddy's hot plate and acetic acid induced writhing), anti-inflammatory (Carrageenan induced paw edema) and anti-arthritic (Complete Freund's Adjuvant induced arthritis). In Complete Freund's Adjuvant arthritis model degree of inflammation was evaluated by hind paw swelling, body weight, and biochemical parameters and supported by radiological analysis. Results: Treatment with extracts of C. uniflora showed significant (P<0.05) and dose dependant increase in paw licking time in Eddy's hot plate method. In writhing test, extracts were significantly reduced the number of writhes. A dose dependant and significant inhibition of edema was observed in carrageenan induced paw edema. Petroleum ether extract at a dose of 100 mg/kg body weight showed most potent and significant activity which is supported by the results of body weight, biochemical parameters and radiological analysis in complete Freund's Adjuvant arthritis model. Conclusion:The extract possesses analgesic, anti-inflammatory and anti-arthritic activity which may be mediated through the phytochemical constituents of the plant.

  10. Sterols from Mytilidae Show Anti-Aging and Neuroprotective Effects via Anti-Oxidative Activity

    Directory of Open Access Journals (Sweden)

    Yujuan Sun

    2014-11-01

    Full Text Available For screening anti-aging samples from marine natural products, K6001 yeast strain was employed as a bioassay system. The active mussel extract was separated to give an active sterol fraction (SF. SF was further purified, and four sterol compounds were obtained. Their structures were determined to be cholesterol (CHOL, brassicasterol, crinosterol, and 24-methylenecholesterol. All compounds showed similar anti-aging activity. To understand the action mechanism involved, anti-oxidative experiments, reactive oxygen species (ROS assays, and malondialdehyde (MDA tests were performed on the most abundant compound, CHOL. Results indicated that treatment with CHOL increases the survival rate of yeast under oxidative stress and decreases ROS and MDA levels. In addition, mutations of uth1, skn7, sod1, and sod2, which feature a K6001 background, were employed and the lifespans of the mutations were not affected by CHOL. These results demonstrate that CHOL exerts anti-aging effects via anti-oxidative stress. Based on the connection between neuroprotection and anti-aging, neuroprotective experiments were performed in PC12 cells. Paraquat was used to induce oxidative stress and the results showed that the CHOL and SF protect the PC12 cells from the injury induced by paraquat. In addition, these substance exhibited nerve growth factor (NGF mimic activities again confirmed their neuroprotective function.

  11. IGFBP-4 Anti-Angiogenic and Anti-Tumorigenic Effects Are Associated with Anti-Cathepsin B Activity

    OpenAIRE

    María J. Moreno; Marguerite Ball; Marina Rukhlova; Jacqueline Slinn; Denis L'Abbe; Umar Iqbal; Robert Monette; Martin Hagedorn; Maureen D O'Connor-McCourt; Yves Durocher; Stanimirovic, Danica B

    2013-01-01

    Insulin-like growth factor-binding protein 4 (IGFBP-4/IBP-4) has potent IGF-independent anti-angiogenic and antitumorigenic effects. In this study, we demonstrated that these activities are located in the IGFBP-4 C-terminal protein fragment (CIBP-4), a region containing a thyroglobulin type 1 (Tg1) domain. Proteins bearing Tg1 domains have been shown to inhibit cathepsins, lysosomal enzymes involved in basement membrane degradation and implicated in tumor invasion and angiogenesis. In our stu...

  12. IGFBP-4 Anti-Angiogenic and Anti-Tumorigenic Effects Are Associated with Anti-Cathepsin B Activity1

    OpenAIRE

    María J. Moreno; Ball, Marguerite; Rukhlova, Marina; Slinn, Jacqueline; L'Abbe, Denis; Iqbal, Umar; Monette, Robert; Hagedorn, Martin; O'Connor-McCourt, Maureen D.; Durocher, Yves; Stanimirovic, Danica B

    2013-01-01

    Insulin-like growth factor-binding protein 4 (IGFBP-4/IBP-4) has potent IGF-independent anti-angiogenic and antitumorigenic effects. In this study, we demonstrated that these activities are located in the IGFBP-4 C-terminal protein fragment (CIBP-4), a region containing a thyroglobulin type 1 (Tg1) domain. Proteins bearing Tg1 domains have been shown to inhibit cathepsins, lysosomal enzymes involved in basement membrane degradation and implicated in tumor invasion and angiogenesis. In our stu...

  13. How to Create an Anti-Aging Skin Care Plan

    Science.gov (United States)

    ... library Find a dermatologist How to create an anti-aging skin care plan Skin care in your 40s ... Years of research supports each of these recommendations. Anti-aging skin care tips Protect your skin from the ...

  14. Can HB vaccine yield a booster effect on individuals with positive serum anti-HBs and anti-HBc markers?

    Institute of Scientific and Technical Information of China (English)

    Ru-Xiang Wang; Christina Y. Shi; Ying Guo; Chang-Hong Yang; Yu Song; Juan Chen; Fu-Sheng Pang; Shao-Ping Lei; Xiao-Ming Jia; Jin-Ying Wen

    2004-01-01

    AIM: To evaluate if HB vaccination can yield a booster effecton the anti-HBs level of those naturally acquired HBV positivemarkers.METHODS: Sera were collected from 1399 newly enrolleduniversity students aged between 18-20 years at theentrance medical examination in 2001. Forty-four students(28 males and 16 females) with positive serum anti-HBs and anti-HBc markers served as an observation group and another 44 students (24 males and 20 females) without any HBV markers as the control. HB vaccination was given to all the students without positive serum HBs Ag according to 0,1, 6 month regimen and the peripheral venous blood was sampled from those of both observation and control groups for anti-HBs detection one month after the second and third doses. Anti-HBs levels were measured by ELISA.RESULTS: The seroconversion rate of anti-HBs in the control group was 100% after the second dose, but the geometric mean titers (GMTs) were low. The tendency of serum anti-HBs changes after the 3rd dose was completely different between the two groups. Although more than half of those with positive anti-HBs and anti-HBc showed a mild increase of anti-HBs levels after the 2nd boosting dose (mean anti-HBs level was 320:198 mIU), but the increase of serum anti-HBs titer was much smaller than that in the control group. The averages of their initial serum anti-HBs levelsand the levels after the 2nd and 3rd doses were 198, 320 and 275 mIU respectively. All the subjects from the control group had an obvious increase in their serum anti-HBs levels which was nearly 4 times the baseline level (302:78 mIU).CONCLUSION: HB vaccination can not enhance anti-HBs levels in those with positive serum anti-HBs and anti-HBc markers.

  15. Preparation of national standard product of Anti-TgAb and Anti-TpoAb in our laboratory

    International Nuclear Information System (INIS)

    Objective: To standardize the China-made quantitative immunoassay kits of Anti-TgAb and Anti-TpoAb with a national standdized product of Anti-TgAb and And-TpoAb developed in our laboratory. Methods and Results: Higher titer Anti - TgAb and Anti-TpoAb serum specimens were pooled and treated with centrifuging and filtering, then freeze-dried and packaged into 2ml anpoules for preparing the national standard candidate. The results of the collaborative study showed that, the immuno-activity of the Anti-TgAb was 3916 IU/Amp in term of the 65/093, and the immuno-activity of the Anti-TpoAb was 434 IU/Amp in term of the 66/387. Conclusion: On the basis of the present study, it is proposed that the candidate standard be established as the National Standard for Anti-TgAb and Anti-TpoAb for immunoassay, the immunoactivity of the Anti-TgAb 4000IU/Amp, and that of Anti - TpoAb is 430IU/Amp. A comparative study on the quality of immunoassay kits of Anti-TgAb and Anti-TpoAb by Axsym System, Immulite 1000, Modular Analytics El70, ADVIA Centaur Assay (the most commonly used types in China) is also presented. (authors)

  16. Biological Characterization of Cynara cardunculus L. Methanolic Extracts: Antioxidant, Anti-proliferative, Anti-migratory and Anti-angiogenic Activities

    Directory of Open Access Journals (Sweden)

    Maria Duarte

    2012-12-01

    Full Text Available Cynara cardunculus (Cc is a multipurpose species; beyond its use in southwestern European cuisine, it is also used for the production of solid biofuel, seed oil, biodiesel, paper pulp and cheese, as well as animal feed. In addition, Cc has a long tradition of use in folk medicine as a diuretic and liver protector. The value of this species as a source of bioactive compounds is known; however, pharmacological use would further increase its cultivation. The main goal of the current work was to evaluate the potential of Cc as source of anti-carcinogenic phytochemicals. Different methanolic extracts obtained from wild and cultivated plants were tested for antioxidant activity and effect on breast tumor cell viability. The most effective extract, both as antioxidant and inhibition of tumor cell viability, was tested for effects on angiogenesis and tumor cell migration capacity. All the extracts tested had high antioxidant activity; however, only green leaves and dry head extracts exhibit anti-proliferative activity. Green cultivated leaves (GCL were the most effective extract both as antioxidant and inhibiting the proliferation of tumor cells; it is equally active inhibiting tumor cell migration and in vivo angiogenesis. GCL extract is an effective inhibitor of several key points in tumor development and thus a promising source of anti-carcinogenic phytochemicals.

  17. IGFBP-4 Anti-Angiogenic and Anti-Tumorigenic Effects Are Associated with Anti-Cathepsin B Activity

    Directory of Open Access Journals (Sweden)

    María J Moreno

    2013-05-01

    Full Text Available Insulin-like growth factor-binding protein 4 (IGFBP-4/IBP-4 has potent IGF-independent anti-angiogenic and antitumorigenic effects. In this study, we demonstrated that these activities are located in the IGFBP-4 C-terminal protein fragment (CIBP-4, a region containing a thyroglobulin type 1 (Tg1 domain. Proteins bearing Tg1 domains have been shown to inhibit cathepsins, lysosomal enzymes involved in basement membrane degradation and implicated in tumor invasion and angiogenesis. In our studies, CIBP-4 was shown to internalize and co-localize with lysosomal-like structures in both endothelial cells (ECs and glioblastoma U87MG cells. CIBP-4 also inhibited both growth factor-induced EC tubulogenesis in Matrigel and the concomitant increases in intracellular cathepsin B (CatB activity. In vitro assays confirmed CIBP-4 capacity to block recombinant CatB activity. Biodistribution analysis of intravenously injected CIBP-4-Cy5.5 in a glioblastoma tumor xenograft model indicated targeted accumulation of CIBP-4 in tumors. Most importantly, CIBP-4 reduced tumor growth in this animal model by 60%. Pleiotropic anti-angiogenic and anti-tumorigenic activities of CIBP-4 most likely underlie its observed therapeutic potential against glioblastoma.

  18. IGFBP-4 Anti-Angiogenic and Anti-Tumorigenic Effects Are Associated with Anti-Cathepsin B Activity1

    Science.gov (United States)

    Moreno, María J; Ball, Marguerite; Rukhlova, Marina; Slinn, Jacqueline; L'Abbe, Denis; Iqbal, Umar; Monette, Robert; Hagedorn, Martin; O'Connor-McCourt, Maureen D; Durocher, Yves; Stanimirovic, Danica B

    2013-01-01

    Insulin-like growth factor-binding protein 4 (IGFBP-4/IBP-4) has potent IGF-independent anti-angiogenic and antitumorigenic effects. In this study, we demonstrated that these activities are located in the IGFBP-4 C-terminal protein fragment (CIBP-4), a region containing a thyroglobulin type 1 (Tg1) domain. Proteins bearing Tg1 domains have been shown to inhibit cathepsins, lysosomal enzymes involved in basement membrane degradation and implicated in tumor invasion and angiogenesis. In our studies, CIBP-4 was shown to internalize and co-localize with lysosomal-like structures in both endothelial cells (ECs) and glioblastoma U87MG cells. CIBP-4 also inhibited both growth factor-induced EC tubulogenesis in Matrigel and the concomitant increases in intracellular cathepsin B (CatB) activity. In vitro assays confirmed CIBP-4 capacity to block recombinant CatB activity. Biodistribution analysis of intravenously injected CIBP-4-Cy5.5 in a glioblastoma tumor xenograft model indicated targeted accumulation of CIBP-4 in tumors. Most importantly, CIBP-4 reduced tumor growth in this animal model by 60%. Pleiotropic anti-angiogenic and anti-tumorigenic activities of CIBP-4 most likely underlie its observed therapeutic potential against glioblastoma. PMID:23633927

  19. Radioimmunotherapy using {sup 131}I-rituximab in patients with advanced stage B-cell non-Hodgkin's lymphoma: initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Bienert, Maren; Reisinger, Ingrid; Humplik, Beatrice I.; Reim, Christel; Kroessin, Thomas; Avril, Norbert; Munz, Dieter L. [Charite - Universitaetsmedizin Berlin, Clinic for Nuclear Medicine, Berlin (Germany); Srock, Stefanie; Pezzutto, Antonio [Charite - Universitaetsmedizin Berlin, Department of Haematology and Oncology, Berlin (Germany)

    2005-10-01

    The aim of this study was to evaluate the safety, toxicity and therapeutic response of non-myeloablative radioimmunotherapy using {sup 131}I-rituximab in previously heavily treated patients with B-cell non-Hodgkin's lymphoma (B-NHL). Nine patients with relapsed, refractory or transformed B-NHL received ten radioimmunotherapies. Patients had a median of 5 (range 2-7) prior standard therapies. Four patients had received prior high-dose chemotherapy followed by autologous stem cell transplantation, and eight had received prior rituximab therapy. Histopathology consisted of four mantle cell, one follicular and four diffuse large B-cell lymphomas. Rituximab, a monoclonal chimeric anti-CD20 antibody (IDEC-C2B8), was labelled with {sup 131}I using the Iodogen method. The administered activity (2,200{+-}600 MBq) was based on a dosimetrically calculated 45 cGy total-body radiation dose. All patients received an infusion of 2.5 mg/kg of rituximab prior to administration of the radiopharmaceutical. No acute adverse effects were observed after the administration of{sup 131}I-rituximab. Radioimmunotherapy was safe in our patient group and achieved one complete response ongoing at 14 months and two partial responses progressing at 12 and 13 months after treatment. One partial responder was re-treated with radioimmunotherapy and achieved an additional progression-free interval of 7 months. Four non-responders with bulky disease died 4.8{+-}2.0 months after therapy. Three patients had an elevated serum lactate dehydrogenase (LDH) level prior to radioimmunotherapy and none of the patients responded. Of two patients who received radioimmunotherapy as an additional treatment after salvage chemotherapy, one continues to be disease-free at 9 months and one relapsed at 5 months' follow-up. Reversible grade 3 or 4 haematological toxicity occurred in seven of nine patients. Median nadirs were 35 days for platelets, 44 days for leucocytes and 57 days for erythrocytes. (orig.)

  20. Anti-microbial antibodies in celiac disease: Trick or treat?

    Institute of Scientific and Technical Information of China (English)

    Maria Papp; Ildiko Foldi; Istvan Altorjay; Eszter Palyu; Miklos Udvardy; Judit Tumpek; Sandor Sipka; Ilma Rita Korponay-Szabo; Eva Nemes; Gabor Veres; Tamas Dinya; Attila Tordai; Hajnalka Andrikovics; Gary L Norman; Peter Laszlo Lakatos

    2009-01-01

    AIM: To determine the prevalence of a new set of anti-glycan and anti-outer membrane protein (anti- OMP) antibodies in a Hungarian cohort of adult Celiac disease (CD) patients. METHODS: 190 consecutive CD patients [M/F: 71/119, age:39.9 (SD:14.1) years], 100 healthy, and 48 gastrointestinal controls were tested for glycan anti- Saccharomyces cerevisiae (gASCA), anti-laminaribioside (ALCA), anti-chitobioside, anti-mannobioside, anti-OMP antibodies and major NOD2/CARD15 mutations. Thirty out of 82 CD patients enrolled at the time of diagnosis were re-evaluated for the same antibodies after longstanding gluten-free diet (GFD).RESULTS: 65.9% of the CD patients were positive for at least one of the tested antibodies at the time of the diagnosis. Except anti-OMP and ALCA, antimicrobial antibodies were exclusively seen in untreated CD; however, the overall sensitivity was low. Any glycan positivity (LR+: 3.13; 95% CI: 2.08-4.73)was associated with an increased likelihood ratio for diagnosing CD. Significant correlation was found between the levels of anti-glycan and anti-endomysial or anti-transglutaminase antibodies. Anti-glycan positivity was lost after longstanding GFD. Anti-glycan antibody titers were associated with symptoms at presentation, but not the presence of NOD2/CARD15 mutations. Patients with severe malabsorption more frequently had multiple antibodies at diagnosis ( P = 0.019).CONCLUSION: The presence of anti-glycan antibodies in CD seems to be secondary to the impaired small bowel mucosa which can lead to increased antigen presentation.Furthermore, anti-glycan positivity may be considered an additional marker of CD and dietary adherence.

  1. ANTI-PHOSPHATIDYLSERINE ANTIBODIES IN ACUTE MYOCARDIAL INFARCTION

    OpenAIRE

    Abdolreza Sotoodeh Jahromi; Mohammad Shojaei; Mohammad Reza Farjam; Abdolhossien Madani

    2013-01-01

    Acute Myocardial Infarction (AMI) is the combined result of environmental factors and personal predispositions. Many factors play a role in AMI including anti-Phospholipid (aPL) antibodies, that may act in the induction of immunological response leading to the development of AMI. Anti-Phosphatidylserine (PS) antibody is detected in various diseases like rheumatoid arthritis, systemic lupus erythematosus and anti-phospholipid antibody syndrome. The study of anti-PS antibody in AMI might shed l...

  2. Keynesian Historiography and the Anti-Semitism Question

    OpenAIRE

    E. Roy Weintraub

    2012-01-01

    Historians’ treatment of John Maynard Keynes’s putative anti-Semitism raises complex historiographic issues. Melvin W. Reder’s 2000 HOPE article “The Anti-Semitism of Some Eminent Economists” considered whether the term ambivalent anti-Semitism could be applied variously to John Maynard Keynes, Joseph Schumpeter, and Friedrich Hayek by arguing that those three important economists evinced attitudes or made remarks that today would be characterized as anti-Semitic. I am not concerned here to a...

  3. Current anti-doping policy: a critical appraisal

    OpenAIRE

    Mauron Alexandre; Kayser Bengt; Miah Andy

    2007-01-01

    Abstract Background Current anti-doping in competitive sports is advocated for reasons of fair-play and concern for the athlete's health. With the inception of the World Anti Doping Agency (WADA), anti-doping effort has been considerably intensified. Resources invested in anti-doping are rising steeply and increasingly involve public funding. Most of the effort concerns elite athletes with much less impact on amateur sports and the general public. Discussion We review this recent development ...

  4. Diagnosis and classification of Goodpastures disease (anti-GBM)

    OpenAIRE

    Hellmark, Thomas; Segelmark, Mårten

    2014-01-01

    Goodpastures disease or anti-glomerular basement membrane disease (anti-GBM-disease) is included among immune complex small vessel vasculitides. The definition of anti-GBM disease is a vasculitis affecting glomerular capillaries, pulmonary capillaries, or both, with GBM deposition of anti-GBM auto-antibodies. The disease is a prototype of autoimmune disease, where the patients develop auto-antibodies that bind to the basement membranes and activate the classical pathway of the complement syst...

  5. Democratization System about Anti-corruption and Uphold Integrity

    OpenAIRE

    Peiyong Hou

    2009-01-01

    This article outlines the inevitability of democratization system of anti-corruption and uphold integrity, and analyzes the current situation and causes concerned, thereby introducing the idea of democratization system of anti-corruption and uphold integrity. It Points on relevant solutions of anti-corruption and uphold integrity, intensifying public democracy education and improvement democratization system in anti-corruption and uphold integrity, at the same time, it more try to find out th...

  6. Anti-synchronization Between Coupled Networks with Two Active Forms

    International Nuclear Information System (INIS)

    This paper studies anti-synchronization and its control between two coupled networks with nonlinear signal's connection and the inter-network actions. If anti-synchronization does not exist between two such networks, adaptive controllers are designed to anti-synchronize them. Different node dynamics and nonidentical topological structures are considered and useful criteria for anti-synchronization between two networks are given. Numerical examples are presented to show the efficiency of our derived results. (general)

  7. Potential Anti-HIV Agents from Marine Resources: An Overview

    OpenAIRE

    Thanh-Sang Vo; Se-Kwon Kim

    2010-01-01

    Human immunodeficiency virus (HIV) infection causes acquired immune deficiency syndrome (AIDS) and is a global public health issue. Anti-HIV therapy involving chemical drugs has improved the life quality of HIV/AIDS patients. However, emergence of HIV drug resistance, side effects and the necessity for long-term anti-HIV treatment are the main reasons for failure of anti-HIV therapy. Therefore, it is essential to isolate novel anti-HIV therapeutics from natural resources. Recently, a great de...

  8. Screening of Tanzanian medicinal plants for anti-Candida activity

    OpenAIRE

    Joseph Cosam C; Ngassapa Olipa D; Matee Mecky IN; Runyoro Deborah KB; Mbwambo Zakaria H

    2006-01-01

    Abstract Background Candida albicans has become resistant to the already limited, toxic and expensive anti-Candida agents available in the market. These factors necessitate the search for new anti-fungal agents. Methods Sixty-three plant extracts, from 56 Tanzanian plant species obtained through the literature and interviews with traditional healers, were evaluated for anti-Candida activity. Aqueous methanolic extracts were screened for anti-Candida activity by bioautography agar overlay meth...

  9. Uncertainties in the Anti-neutrino Production at Nuclear Reactors

    OpenAIRE

    Djurcic, Z.; Detwiler, J. A.; Piepke, A; Foster Jr., V. R.; Miller, L.; Gratta, G.

    2008-01-01

    Anti-neutrino emission rates from nuclear reactors are determined from thermal power measurements and fission rate calculations. The uncertainties in these quantities for commercial power plants and their impact on the calculated interaction rates in electron anti-neutrino detectors is examined. We discuss reactor-to-reactor correlations between the leading uncertainties and their relevance to reactor anti-neutrino experiments.

  10. 48 CFR 352.203-70 - Anti-lobbying.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Anti-lobbying. 352.203-70... SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts of Provisions and Clauses 352.203-70 Anti-lobbying. As prescribed in 303.808-70, the Contracting Officer shall insert the following clause: Anti-Lobbying...

  11. 15 CFR 742.9 - Anti-terrorism: Syria.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Anti-terrorism: Syria. 742.9 Section... BASED CONTROLS § 742.9 Anti-terrorism: Syria. (a) License requirements. (1) If AT Column 1 of the... required for export and reexport to Syria for anti-terrorism purposes. (2) The Secretary of State...

  12. 15 CFR 742.19 - Anti-terrorism: North Korea.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Anti-terrorism: North Korea. 742.19...-CCL BASED CONTROLS § 742.19 Anti-terrorism: North Korea. (a) License Requirements. (1) All items on... anti-terrorism reasons require a license for export or reexport to North Korea. This includes all...

  13. 15 CFR 742.10 - Anti-terrorism: Sudan.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Anti-terrorism: Sudan. 742.10 Section...-CCL BASED CONTROLS § 742.10 Anti-terrorism: Sudan. (a) License requirements. (1) If AT column 1 or AT... ECCN, a license is required for export to Sudan for anti-terrorism purposes. 1 AT column 1 refers...

  14. 15 CFR 742.8 - Anti-terrorism: Iran.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Anti-terrorism: Iran. 742.8 Section... BASED CONTROLS § 742.8 Anti-terrorism: Iran. (a) License Requirements. (1) A license is required for anti-terrorism purposes to export or reexport to Iran any item for which AT column 1 or AT column 2...

  15. Rhesus anti-D immunoglobulin in chronic autoimmune neuropathy

    NARCIS (Netherlands)

    de Jager, AEJ; van der Hoeven, JH

    1998-01-01

    Objective - To investigate the effect of Rhesus anti-D immunoglobulin (anti-D) in patients with an autoimmune demyelinating neuropathy. Material and methods - Three patients with an autoimmune mediated neuropathy received 1000 IU anti-D weekly for 2 months. Results - Two patients worsened gradually

  16. 76 FR 76896 - International Anti-Fouling System Certificate

    Science.gov (United States)

    2011-12-09

    ... Security FR Federal Register IAFS International Anti-fouling System NAICS North American Industry... SECURITY Coast Guard 46 CFR Part 8 RIN 1625-AB79 International Anti-Fouling System Certificate AGENCY... Anti-fouling System Certificate'' in the Federal Register (76 FR 54419). We did not receive...

  17. Reengineered tricyclic anti-cancer agents.

    Science.gov (United States)

    Kastrinsky, David B; Sangodkar, Jaya; Zaware, Nilesh; Izadmehr, Sudeh; Dhawan, Neil S; Narla, Goutham; Ohlmeyer, Michael

    2015-10-01

    The phenothiazine and dibenzazepine tricyclics are potent neurotropic drugs with a documented but underutilized anti-cancer side effect. Reengineering these agents (TFP, CPZ, CIP) by replacing the basic amine with a neutral polar functional group (e.g., RTC-1, RTC-2) abrogated their CNS effects as demonstrated by in vitro pharmacological assays and in vivo behavioral models. Further optimization generated several phenothiazines and dibenzazepines with improved anti-cancer potency, exemplified by RTC-5. This new lead demonstrated efficacy against a xenograft model of an EGFR driven cancer without the neurotropic effects exhibited by the parent molecules. Its effects were attributed to concomitant negative regulation of PI3K-AKT and RAS-ERK signaling. PMID:26372073

  18. Medicinal plants with anti-inflammatory activities.

    Science.gov (United States)

    Maione, Francesco; Russo, Rosa; Khan, Haroon; Mascolo, Nicola

    2016-06-01

    Medicinal plants have been the main remedy to treat various ailments for a long time and nowadays, many drugs have been developed from traditional medicine. This paper reviews some medicinal plants and their main constituents which possess anti-inflammatory activities useful for curing joint inflammation, inflammatory skin disorders, cardiovascular inflammation and other inflammatory diseases. Here, we provide a brief overview of quick and easy reading on the role of medicinal plants and their main constituents in these inflammatory diseases. We hope that this overview will shed some light on the function of these natural anti-inflammatory compounds and attract the interest of investigators aiming at the design of novel therapeutic approaches for the treatment of various inflammatory conditions. PMID:26221780

  19. Asymptotically anti-de Sitter Proca Stars

    CERN Document Server

    Duarte, Miguel

    2016-01-01

    We show that complex, massive spin-1 fields minimally coupled to Einstein's gravity with a negative cosmological constant, admit asymptotically anti-de Sitter self-gravitating solutions. Focusing on 4-dimensional spacetimes, we start by obtaining analytical solutions in the test-field limit, where the Proca field equations can be solved in a fixed anti-de Sitter background, and then find fully non-linear solutions numerically. These solutions are a natural extension of the recently found asymptotically flat Proca stars and share similar properties with scalar boson stars. In particular, we show that they are stable against spherically symmetric linear perturbations for a range of fundamental frequencies limited by their point of maximum mass. We finish with an overview of the behavior of Proca stars in $5$ dimensions.

  20. Anti-scaling agents in kraft pulping

    Directory of Open Access Journals (Sweden)

    Felissia, F. E.

    2007-05-01

    Full Text Available Scale formation in the digester during kraft pulping represents a great problem in pulp mills. Scaling reduces pulping control and efficiency, increasing energy costs and leading to cleaning breakdowns, with subsequent losses in productivity. The kraft process promotes CaCO3 scaling due to high calcium ion and carbonate concentrations, as well as high alkalinity and temperature levels, which increase the speed with which liquors reach a state of supersaturation. This work examines the action of diethylene triamine penta(methylene phosphonic acid (DTPMPA, either alone or combined with commercial anti-scaling agents, as an inhibitor of calcium carbonate precipitation in the kraft pulping of Pinus taeda. The theoretical amount of calcium deposited in the digester was obtained by mass balance. Soluble calcium was stable throughout cooking when using the phosphonates alone or combined with anti-scaling agents. When adding only DTPMPA, calcium stays in the pulp, rather than forming deposits.

  1. Anti-fogging and anti-frosting behaviors of layer-by-layer assembled cellulose derivative thin film

    Science.gov (United States)

    Shibraen, Mahmoud H. M. A.; Yagoub, Hajo; Zhang, Xuejian; Xu, Jian; Yang, Shuguang

    2016-05-01

    Two cellulose derivatives, quaternized cellulose (QC) and carboxymethyl cellulose (CMC), were layer-by-layer (LbL) assembled to prepare a thin film. QC was also LbL assembled with two synthetic polyelectrolytes, poly(acrylic acid) (PAA) and poly(styrene sulfonate) (PSS), separately. The anti-fogging and anti-frosting properties of the assembled films were studied. QC/CMC thin film exhibits anti-fogging and anti-frosting behaviors, whereas QC/PAA and QC/PSS films do not have capacity for anti-fogging and anti-frosting. The anti-fogging and anti-frosting properties of QC/CMC film are attributed to that water molecules can be quickly adsorbed into the matrix of the film. The water adsorption of QC/CMC film was illustrated by the optical thickness increment.

  2. Anti-inflammatory and anti-granuloma activity of Berberis aristata DC. in experimental models of inflammation

    Directory of Open Access Journals (Sweden)

    Rohit Kumar

    2016-01-01

    Conclusion: The result of the present study thus demonstrates the anti-inflammatory and anti-granuloma activity of BAHE which may be attributed to its inhibitory activity on macrophage-derived cytokine and mediators.

  3. Prospects for Anti-Biofilm Pharmaceuticals

    OpenAIRE

    Stewart, Philip S.

    2015-01-01

    This commentary highlights several avenues currently being pursued in research labs to the development of new anti-biofilm pharmaceuticals. There is a real need for alternative therapeutic modalities for treating the persistent infections that sometimes form on implanted medical devices or compromised niches within the body. Strategies being researched include discovering new antimicrobial agents that kill microorganisms in biofilms more effectively than do existing antibiotics, designing dru...

  4. Preparing Teachers for Anti-oppressive Education

    DEFF Research Database (Denmark)

    Baber, Sikunder Ali

    2004-01-01

    important to learn about the unique as well as shared challenges facing teacher educators around the globe. In this article, teacher educators from Asia, Africa, North America and South America offer a sampling of initiatives in anti-oppressive teacher education; that is, initiatives to prepare teachers to...... teach various subject matters to various age groups, addressing various forms of oppression in various cultural and community contexts....

  5. Anti-thromboembolic strategies in atrial fibrillation.

    Science.gov (United States)

    Cocco, Giuseppe; Amiet, Philpp; Jerie, Paul

    2016-01-01

    Oral anticoagulation (OAC) is highly effective for stroke prevention in high-risk-patients with atrial fibrillation (AF). AF is also a risk for dementia, and effective OAC reduces the risk of dementia. Up to 30% of patients with AF have a coronary artery disease and antiplatelets are used to avoid thrombotic complications. Patients with AF often have an acute coronary syndrome (ACS) and undergo a percutaneous intervention with stent-implantation. These patients require a triple therapy, i.e. the combination of OAC with dual-antiplatelet therapy. It is obvious that OAC may induce bleeding with potentially deleterious effects on mortality. Even the occurrence of minor bleeding is problematic. The review describes available data on used anti-thromboembolic regimens in patients treated with OAC (vitamin K antagonists and non-vitamin K antagonists) who need a triple therapy (i.e. anticoagulation and antiplatelets). Most data are from patients who were treated for an ACS and cannot be directly extrapolated for patients with AF. The impact of used stents and novel P2Y12 antagonist-antiplatelets and duration of triple therapy is discussed. Often some high-risk patients with AF would need anticoagulation but cannot be given this therapy be-cause of excessive bleeding risks or contraindicating comorbidities: in these patients left atrial appendage closure with an occluding device can be used as an alternative to anti-thromboem-bolic therapy. The unavoidable anti-thromboembolic triple therapy carries a strong potential for bleeding events, which increase mortality. We have many data and several recommendations are offered. Nonetheless, we lack solid data on the best anti-thromboembolic regimen in patients with AF who need anticoagulation and antiplatelets. PMID:26779967

  6. Anti-Integrin Therapy for Multiple Sclerosis

    OpenAIRE

    Motomu Shimaoka; Hiroshi Imai; Takayuki Okamoto; Susumu Nakahashi; Eiji Kawamoto

    2012-01-01

    Integrins are the foremost family of cell adhesion molecules that regulate immune cell trafficking in health and diseases. Integrin alpha4 mediates organ-specific migration of immune cells to the inflamed brain, thereby playing the critical role in the pathogenesis of multiple sclerosis. Anti-alpha4 integrin therapy aiming to block infiltration of autoreactive lymphocytes to the inflamed brain has been validated in several clinical trials for the treatment of multiple sclerosis. This paper pr...

  7. Gravitational collapse in anti de Sitter space

    International Nuclear Information System (INIS)

    A numerical and analytic treatment is presented here of the evolution of initial data of the kind that was conjectured by Hertog, Horowitz and Maeda to lead to a violation of cosmic censorship. That initial data is essentially a thick domain wall connecting two regions of anti de Sitter space. The evolution results in no violation of cosmic censorship, but rather the formation of a small black hole

  8. Hormonal Factors of Anti-Mutagenesis Regulation

    OpenAIRE

    RZA, Mekhtizadeh Emin

    2009-01-01

    The genetic activity of phytohormones (Phs) was studied. The investigation was conducted with 4 plants (Allium fistulosum, Lycopersicon esculentum, Triticum aestivum, and Gossypium hirsutum). The action of Phs on plant genetic processes was evaluated by chromosome aberration testing. It was observed that the exogenic Phs exerted a stabilizing effect on spontaneous plant mutagenesis. The use of Phs before and after the action of mutagenic factors contributed to an increase in the anti-mutation...

  9. European Anti-dumping Law and China

    Directory of Open Access Journals (Sweden)

    Piet Eeckhout

    1997-04-01

    Full Text Available The paper examines recent developments in the European Union's anti-dumping policy, as it is applied towards China. It concentrates on recent court cases involving dumping from China and on the basic non-market economy issue. The author essentially argues that the European Union's policy does not take account sufficiently of China's development towards a market economy, and that there are various legal flaws in the way the policy is applied.

  10. Dual anti-HIV mechanism of clofarabine

    OpenAIRE

    Daly, Michele B.; Roth, Megan E.; Bonnac, Laurent; Maldonado, José O.; Xie, Jiashu; Clouser, Christine L; Patterson, Steven E.; Kim, Baek; Louis M. Mansky

    2016-01-01

    Background HIV-1 replication kinetics inherently depends on the availability of cellular dNTPs for viral DNA synthesis. In activated CD4+ T cells and other rapidly dividing cells, the concentrations of dNTPs are high and HIV-1 reverse transcription occurs in an efficient manner. In contrast, nondividing cells such as macrophages have lower dNTP pools, which restricts efficient reverse transcription. Clofarabine is an FDA approved ribonucleotide reductase inhibitor, which has shown potent anti...

  11. Potential Anti-cancer Activity of Furanodiene

    Institute of Scientific and Technical Information of China (English)

    Zhen-zhen Ba; Yan-ping Zheng; Hui Zhang; Xiu-yan Sun; Dong-hai Lin

    2009-01-01

    Objective: To study the anti-tumor activities of furanodiene (C15H20O), a primary sesquiterpene compound isolated from the essential oil of the rhizome of Curcuma wenyujin YH Chen et C. Ling(Wen Ezhu), in vitro and in vivo.Methods: In vitro MTT assay was used to further study the effects of time and dosage on anti-proliferation of furanodiene against the sensitive Hela, Hep-2,HL-60, U251 cells, based on the cytotoxic effects of furanodiene on 12 human malignant tumor cell lines with the essential oil of Wen Ezhu as control., and the half-inhibitory concentration (IC50) was observed. In vivo uterine cervix (U14) tumor cell was selected and the conventional assay method of anti-tumor activity was employed. Furanodiene liposome was administered intraperitoneally, and tumor-inhibitory rate, thymus and spleen indexes were observed.Results: The inhibitive effects on cell proliferation were shown in all of the twelve cell lines and the cytotoxic effects of furanodiene against Hela, Hep-2, HL-60, U251 cells were observed after 12 h of administration, the effect could last for at least 48 h in a dose dependent manner, and the IC50 values were 0.6, 1.7, 1.8, 7.0 μg/ml, respectively. Furanodiene was also found to show inhibitive effects on the proliferation of uterine cervix (U14) tumor induced in mice. The tumor inhibition rates were 36.09% (40 mg/kg), 41.55% (60 mg/kg), 58.29% (80 mg/kg), respectively.Conclusion: Furanodiene is one of primary anti-cancer active components in the essential oil of Wen Ezhu, and also a very effective agent against uterine cervix cancer, and has protection effect on the immune function.

  12. Anti-atherosclerotic effects of konjac

    OpenAIRE

    Hidekatsu Yanai; Hiroki Adachi; Hisayuki Katsuyama; Hidetaka Hamasaki; Akahito Sako

    2015-01-01

    Definition: The Konjac plant comes from the genus Amorphophallus. Japanese food uses Konjac cake. Konjac contains almost no calories and a great amount of dietary fiber. Here, we reviewed possible anti-atherosclerotic effects of konjac, using the search Pubmed ®. Konjac ingestion is likely beneficially associated with obesity, blood pressure, lipid and glucose metabolism. However, evidence is lacking on the relationship between konjac ingestion and development of atherosclerotic diseases. To ...

  13. ANTI-DEPRESSANT POTENTIAL OF GHIYA

    Directory of Open Access Journals (Sweden)

    Kaur Satbir

    2012-04-01

    Full Text Available Lagenaria siceraria (Cucurbitaceae, popularly known as bottle gourd, lauki or ghiya, is a climbing plant, which bears hard-shelled and bottle-shaped gourds as fruits. Ghiya forms an excellent diet for people having digestive problems being rich in vitamins, iron and minerals. Since, it contains low calories, bottle gourd is an awesome foodstuff for shedding extra calories. The fruit possesses diuretic, emetic, and refrigerant properties. The ghiya (lauki juice is helpful in constipation, premature graying hair, urinary disorders and insomnia. However, there are no reports in literature pertaining to CNS actions of Lagenaria siceraria fruit. In the light of above, the present study was undertaken to test the anti-depressant potential of Lagenaria siceraria juice (LSJ. Lagenaria siceraria juice was administered at various concentrations ranging from 4%-16% v/v orally to Swiss mice (30g, once daily for 15 successive days. The anti-depressant activity was measured using Forced Swim Test (FST and Tail Suspension Test (TST. The efficacy of Lagenaria siceraria was compared to standard anti-depressant drugs viz: fluoxetine (20mg/kg, p.o, imipramine (15mg/kg, p.o and phenelzine (20 mg/kg, p.o. Lagenaria siceraria significantly reduced the immobility time of mice in both FST and TST. Prazosin, Baclofen, Sulpiride and p-CPA significantly antagonized this reduction in immobility duration. Furthermore, Lagenaria siceraria juice inhibited the monoamine oxidase (MAO enzyme and reduced significantly malondialdehyde (MDA levels. These findings reveal the anti-depressant potential of ghiya.

  14. (Anti-)Biography and Neo-Impressionism

    OpenAIRE

    Foa, Michelle

    2012-01-01

    This article analyzes neo-impressionism in relation to the biographical model of art criticism and art history that became increasingly prevalent in France over the course of the 19th century. Examining the critical response to the neo-impressionists, as well as some of their pictures and writings, I argue for the centrality of questions of authorship, individuality, and subjectivity to the group and its reception. I identify a distinctly anti-biographical tendency in the movement, one that d...

  15. Anti-surveillance app for Android

    OpenAIRE

    Mazaheri, Nima

    2013-01-01

    The widespread use of smart phones and apps with extensive access rights has left businesses vulnerable to a whole new range of attacks. Seemingly legit apps can activate the microphone or camera and during meetings or situations where sensitive information is discussed. Both users and businesses are left with few tools to ensure that no such recording can take place.This assignment will develop an anti-surveillance app to let users and businesses control access to audio and video recordings ...

  16. Multinationals and Anti-sweatshop Activism

    OpenAIRE

    Harrison, Ann; Scorse, Jason

    2010-01-01

    During the 1990s, anti-sweatshop activists campaigned to improve conditions for workers in developing countries. This paper analyzes the impact of antisweatshop campaigns in Indonesia on wages and employment. Identification is based on comparing the wage growth of workers in foreign-owned and exporting firms in targeted regions or sectors before and after the initiation of antisweatshop campaigns. We find the campaigns led to large real wage increases for targeted enterprises. There were some...

  17. Anti-Microbial activity of Talakeshwara Ras

    OpenAIRE

    Prasanna Kumar Tirupati; Srilakshmi Dasari; Ragamala K C; Geeta Balakrishna; Shwetha Seshagiri

    2011-01-01

    Rasa Shastra, one of the Pharmaco-therapeutic branches of Ayurveda where metals, minerals, poisonous plants and animal products are used after proper processing for internal administration. Talakeshwara Ras is one of Khalvi rasayanas where Emblica officinalis (Dhatri) and minerals Arsenic tri sulphide (Haratala) & Borax (Tankana) are the ingredients. It is indicated for Sarva Kushta at one Masha (1 gm) dose. Anti -Microbial activity of Talakeshwara Ras was done with an intention to evalua...

  18. MANAJEMEN KURIKULUM DALAM PERSPEKTIF ANTI-RADIKALISME

    Directory of Open Access Journals (Sweden)

    Kisbiyanto Kisbiyanto

    2016-02-01

    Full Text Available The curriculum management in the college of Islamic religious affairs (PTKIN has a strategic role in achieving the vision of the implementation of the higher education especially in Indonesia that has the majority muslim population. PTKIN is responsible in the development of religious harmony and transform the Islamic values that peace and anti-radicalism. The purpose of this research is: (1 designing the Islamic education policy in anti-radicalism perspective at STAIN Kudus; (2 the contents of the curriculum for Islamic education anti-radicalism perspective in STAIN Kudus. This research is used qualitative approach. The data collected by the documentation technique and the triangulation validity. Data analysis by interactive. The results of this research is: (1 Curriculum planning policy Islamic Education department STAIN Kudus is arrangement periodically start from the curriculum 1997, 2003, and 2008. The three periods of curriculum is re-arrange and evaluated by involve the lecturers and experts. This curriculum pattern is called curriculum corelated approach; it is classified from one family courses. This means that the curriculum 2008 is not the curriculum with subject pattern matte curriculum aproach, it emphasizes on courses in a separate settlements. The elective courses is clasified into five groups, namely personality development courses (MPK, scholarly and skills (MKK, courses work (MKB, behavior courses work (MPB, social life courses (MBB. (2 The Islamic education curriculum substance is spread in almost all courses and content on the tendency of the anti-radicalism curriculum and learning, it is a Islamic movements and discourse that give education and peacefull dakwah as a prior, tolerance, humanity, and respect differences as a mercy for the universe.

  19. Radioimmunoscintigraphy with anti-thyroglobulin monoclonal antibodies

    International Nuclear Information System (INIS)

    Monoclonal mouse antibodies to human thyroglobulin were conjugated to the cyclic dianhydride of DTPA. After radiolabelling with 111In this compound was injected into nude mice bearing various human thyroid carcinomas. Repeated imaging studies were carried out 15 min to 50 h after tracer administration. In both papillary and undifferentiated thyroid carcinoma no significant uptake of radiolabelled anti-hTG-MAb was observed. (orig.)

  20. Anti-oxidant and anti-inflammatory activity of leaf extracts and fractions of Mangifera indica

    Institute of Scientific and Technical Information of China (English)

    Mohan CG; Deepak M; Viswanatha GL; Savinay G; Hanumantharaju V; Rajendra CE; Praveen D Halemani

    2013-01-01

    Objective: To evaluate the anti-oxidant and anti-inflammatory activity of leaf extracts and fractions of Mangifera indica in in vitro conditions. Methods: In vitro DPPH radical scavenging activity and lipoxygenase (LOX) inhibition assays were used to evaluate the anti-oxidant and anti-inflammatory activities respectively. Methanolic extract (MEMI), successive water extract (SWMI) and ethyl acetate fraction (EMEMI), n-butanol fraction (BMEMI) and water soluble fraction (WMEMI) of methanolic extract were evaluated along with respective reference standards. Results: In in vitro DPPH radical scavenging activity, the MEMI, EMEMI and BMEMI have offered significant antioxidant activity with IC50 values of 13.37, 3.55 and 14.19 μg/mL respectively. Gallic acid, a reference standard showed significant antioxidant activity with IC50 value of 1.88 and found to be more potent compared to all the extracts and fractions. In in vitro LOX inhibition assay, the MEMI, EMEMI and BMEMI have showed significant inhibition of LOX enzyme activity with IC50 values of 96.71, 63.21 and 107.44 μg/mL respectively. While, reference drug Indomethacin also offered significant inhibition against LOX enzyme activity with IC50 of 57.75. Furthermore, MEMI was found to more potent than SWMI and among the fractions EMEMI was found to possess more potent antioxidant and anti-inflammatory activity. Conclusions: These findings suggest that the MEMI and EMEMI possess potent anti-oxidant and anti-inflammatory activities in in vitro conditions.

  1. Anti-Inflammatory Effect of Allium ursinum

    Directory of Open Access Journals (Sweden)

    Alina Elena PÂRVU

    2014-03-01

    Full Text Available The aim of the present study was to evaluate Allium ursinum leaves and flowers extract anti-inflammatory effect. Plant extract 1:1 (w:v was prepared from A. ursinum leaves by a modified Squibb repercolation method. The in vivo anti-inflammatory effects were evaluated on a rat turpentine oil-induced inflammation (i.m. 6 mL/kg BW. The animals were randomly assigned to nine groups (n=8: negative control, inflammation, A. ursinum flower extract (AUF, A. ursinum leaves extract (AUL, indomethacin (INDO (20 mg/kg BW, aminoguanidine (AG (50 mg/kg b.w./d i.p. as a selective NOS2 inhibitor, NG-nitro L-arginine methyl ester (NAME (5 mg/kg b.w./d i.p. as a nonselective NOS inhibitor, L-arginine (ARG (100 mg/kg b.w./d i.p., NO synthesis substrate, and Trolox (20 mg/kg b.w./d i.p as an antioxidant. At 24h from inflammation induction total oxidative status (TOS, oxidative stress index (OSI, nitric oxide (NOx and in vitro phagocytosis test were reduced and the total antioxidative reactivity (TAR was increased by the testes plant extracts. AUF had a better inhibitory effect than AUL. In conclusion, we provided evidence for the hypothesis that A. ursinum leaves and flowers extract exerts anti-inflammatory activity by inhibiting the phagocytosis through the reduction of the nitro-oxidative stress.

  2. Diversity of wheat anti-microbial peptides.

    Science.gov (United States)

    Egorov, Tsezi A; Odintsova, Tatyana I; Pukhalsky, Vitaliy A; Grishin, Eugene V

    2005-11-01

    From seeds of Triticum kiharae Dorof. et Migusch., 24 novel anti-microbial peptides were isolated and characterized by a combination of three-step HPLC (affinity, size-exclusion and reversed-phase) with matrix-assisted laser-desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and Edman degradation. Based on sequence similarity and cysteine motifs, partially sequenced peptides were assigned to 7 families: defensins, thionins, lipid-transfer proteins, hevein-like peptides, knottin-like peptides, glycine-rich peptides, and MBP-1 homologs. A novel subfamily of defensins consisting of 6 peptides and a new family of glycine-rich (8 peptides with different repeat motifs) were identified. Three 6-cysteine knottin-like peptides represented by N- and C-terminally truncated variants revealed no sequence homology to any known plant anti-microbial peptides. A new 8-cysteine hevein-like peptide and three 4-cysteine peptides homologous to MBP-1 from maize were isolated. This is the first communication on the occurrence of nearly all families of plant anti-microbial peptides in a single species. PMID:16269343

  3. ANTI-ULCER ACTIVITY OF LEGUMINOSAE PLANTS

    Directory of Open Access Journals (Sweden)

    Noemi D. PAGUIGAN

    2014-03-01

    Full Text Available Context Ulcer is the most common gastrointestinal disturbance resulting from an inadequate gastric mucosal defense. Several drugs are available in the market to address the disease; however, these drugs are associated with unnecessary side effects. Objectives Previous research have confirmed the efficacy of plant extracts for possible treatment of the disease. This research aims to evaluate the anti-ulcer properties of medicinal plants. Methods Methanol extracts from the leaves of Intsia bijuga, Cynometra ramiflora, Tamarindus indica, Cassia javanica, Cassia fistula, Bauhini purpurea, Senna spectabilis, Senna siamea and Saraca thaipingensis were evaluated for their anti-ulcer activity using HCl-ethanol as ulcerogen. Results All extracts showed inhibitory activity with I. bijuga, T. indica, S. spectabilis and S. thaipingensis exhibiting more than 50% inhibition. S. thaipingensis showed the highest activity at 80%. S. spectabilis and S. thaipingensis were partitioned further into hexane, ethyl acetate and aqueous fractions. The aqueous and ethyl acetate fractions of S. spectabilis showed significant increased in its activity while the hexane and ethyl acetate fractions of S. thaipingensis gave higher activity than its aqueous portions. Conclusions We conclude that plant extracts are potential sources of new anti-ulcer agents.

  4. Anti-inflammatory properties of cryptolepine.

    Science.gov (United States)

    Olajide, Olumayokun A; Ajayi, Abayomi M; Wright, Colin W

    2009-10-01

    Cryptolepine is the major alkaloid of the West African shrub, Cryptolepis sanguinolenta. Cryptolepine has been shown to inhibit nitric oxide production, and DNA binding of Nuclear Factor-kappa B following inflammatory stimuli in vitro. In order to validate the anti-inflammatory property of this compound in vivo, we investigated its effects on a number of animal models of inflammation. Cryptolepine (10-40 mg/kg i.p.) produced significant dose-dependent inhibition of the carrageenan-induced rat paw oedema, and carrageenan-induced pleurisy in rats. These effects were compared with those of the non-steroidal anti-inflammatory drug indomethacin (10 mg/kg). At doses of 10-40 mg/kg i.p., cryptolepine inhibited lipopolysaccharide (LPS)-induced microvascular permeability in mice in a dose-related fashion. Oral administration of up to 40 mg/kg of the compound for four consecutive days did not induce gastric lesion formation in rats. Analgesic activity was also exhibited by cryptolepine through a dose-related (10-40 mg/kg i.p.) inhibition of writhing induced by i.p. administration of acetic acid in mice. The results of this study reveal that cryptolepine possesses in vivo anti-inflammatory activity. PMID:19288476

  5. Rituximab for the treatment of refractory simultaneous anti-glomerular basement membrane (anti-GBM) and membranous nephropathy

    OpenAIRE

    Bandak, Ghassan; Jones, Bruce A.; Li, Jian; Yee, Jerry; Umanath, Kausik

    2014-01-01

    Antibody-mediated anti-glomerular basement membrane (anti-GBM) disease occurs rarely in the presence of another B-cell disorder, membranous nephropathy. The coexistence of these two autoimmune disorders would be anticipated to require differing, specific therapies targeted to each disease process. We describe a case of concomitant membranous nephropathy and anti-GBM disease in which conventional therapy, including steroids, plasmapheresis and cyclophosphamide, failed to attenuate the anti-GBM...

  6. Solvability conditions for algebra inverse eigenvalue problem over set of anti-Hermitian generalized anti-Hamiltonian matrices

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhong-zhi; HAN Xu-li

    2005-01-01

    By using the characteristic properties of the anti-Hermitian generalized anti-Hamiltonian matrices, we prove some necessary and sufficient conditions of the solvability for algebra inverse eigenvalue problem of anti-Hermitian generalized anti-Hamiltonian matrices, and obtain a general expression of the solution to this problem. By using the properties of the orthogonal projection matrix, we also obtain the expression of the solution to optimal approximate problem of an n× n complex matrix under spectral restriction.

  7. Limited ability of humoral immune responses in control of viremia during infection with SIVsmmD215 strain

    Energy Technology Data Exchange (ETDEWEB)

    Ribiero, Ruy M [Los Alamos National Laboratory

    2009-01-01

    To investigate the impact of humoral immunity on SIV replication, 11 rhesus macaques (RMs) were inoculated with the neutralization-sensitive strain SIVsmmD215. Seven RMs were treated every three weeks, with 50 mglkg of an anti-CD20 antibody (Rituxan, gift from Genentech) starting from day -7 p.i., as follows: four RMs were treated for two months, and three were treated for five months. The remaining four RMs were used as controls. Three RMs were completely depleted of CD20 cells. Four RMs only partially depleted CD20 cells in the LNs and intestine. The efficacy of tissue CD20 depletion predicted the ablation of antibody production, with SIVsmm seroconversion being delayed in the animals with complete tissue CD20 depletion, and neutralizing antibody production being significantly delayed and at low levels in all CD20-depleted RMs. There was no significant difference in acute or chronic VLs between CD20-depleted RMs and control monkeys, with a tendency for lower set-point VLs in CD20-depleted RMs. At 6 weeks p.i., cellular immune responses were significantly stronger in CD20 depleted RMs than in controls. After two years p.i., there was no significant difference in survival between CD20-depleted and control RMs. We concluded that CD20 depletion plays no significant role in the control of SIV replication or disease progression in SIVsmmD215-infected RMs.

  8. Anti-cancer and potential chemopreventive actions of ginseng by activating Nrf2 (NFE2L2) anti-oxidative stress/anti-inflammatory pathways

    OpenAIRE

    Wu Qing; Saw Constance; Kong Ah-Ng Tony

    2010-01-01

    Abstract This article reviews recent basic and clinical studies of ginseng, particularly the anti-cancer effects and the potential chemopreventive actions by activating the transcriptional factor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2 or NFE2L2)-mediated anti-oxidative stress or anti-inflammatory pathways. Nrf2 is a novel target for cancer prevention as it regulates the antioxidant responsive element (ARE), a critical regulatory element in the promoter region of genes encoding cel...

  9. Anti-Oxidative, Anti-Tumor-Promoting, and Anti-Carcinogensis Activities of Nitroastaxanthin and Nitrolutein, the Reaction Products of Astaxanthin and Lutein with Peroxynitrite

    OpenAIRE

    Hideo Etoh; Hideaki Kato; Takashi Maoka; Harukuni Tokuda; Nobutaka Suzuki

    2012-01-01

    Astaxanthin captured peroxynitrite to form nitroastaxanthins. 15-Nitroastaxanthin was a major reaction product of astaxanthin with peroxynitrite. Here, the anti-oxidative, anti-tumor-promoting, and anti-carcinogensis activities of 15-nitroastaxanthin were investigated. In addition to astaxanthin, 15-nitroastaxanthin showed excellent singlet oxygen quenching activity. Furthermore, 15-nitroastaxanthin showed inhibitory effects of in vitro Epstein-Barr virus early antigen ac...

  10. Human rights orientation and modern anti-Semitism

    OpenAIRE

    Johannes Kopf-Beck

    2011-01-01

    The manifestations of anti-Semitism in Germany have changed since the end of WWII. Whereas in the past German anti-Semitism was overtly racist, today it is characterized more by subtle and latent facets. How are these modern facets, such as secondary anti-Semitism, latent anti-Semitism and anti-Semitic criticism of Israel, related to human rights orientations? A survey of experts and a pre-study provided the basis for developing the Human Rights Orientation Scale, which includes the four s...

  11. Anti-C1q antibodies in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Orbai, A-M; Truedsson, L; Sturfelt, G;

    2015-01-01

    OBJECTIVE: Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. METHODS: Information...... serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis....

  12. Anti-D3's - Singular to the Bitter End

    OpenAIRE

    Iosif Bena; Mariana Grana; Stanislav Kuperstein(Institut de Physique Théorique, CEA Saclay, CNRS URA 2306, F-91191 Gif-sur-Yvette, France); Stefano Massai

    2012-01-01

    We study the full backreaction of anti-D3 branes smeared over the tip of the deformed conifold. Requiring the 5-form flux and warp factor at the tip to be that of anti-D3 branes, we find a simple power counting argument showing that if the three-form fluxes have no IR singularity, they will be necessarily imaginary-anti-self-dual. Hence the only solution with anti-D3 branes at the tip of the conifold that is regular in the IR and the UV is the anti-Klebanov-Strassler solution, and there is no...

  13. Influence of sway motion on passive anti-rolling tank

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The passive anti-rolling tank is one of important ship stabilizers widely used today. But at present, research of the tank is most aimed at its rolling movement. In this paper, the influence of sway motion on the passive anti-rolling tank is considered, the mathematical model of "ship-passive anti-rolling tank" system coupled with sway motion is developed basing on the U-shaped passive anti-rolling tank theory. Both simulation results and experimental data indicate that it is necessary to consider the influence of sway motion on the anti-rolling tank, which is more agreeable to the actual circumstance.

  14. Hemolytic disease of the fetus and newborn caused by anti-E

    Directory of Open Access Journals (Sweden)

    Adiyyatu Sa′idu Usman

    2013-01-01

    Full Text Available Objective: Maternal allo-antibody production is stimulated when fetal red blood cells are positive for an antigen absent on the mother′s red cells. The maternal IgG antibodies produced will pass through the placenta and attack fetal red cells carrying the corresponding antigen. Allo-immune hemolytic disease of the fetus and newborn caused by anti-E rarely occurs. Case summary: We report two cases of anti-E hemolytic diseases in neonates. One of the neonates had severe hemolysis presenting with severe anemia, thrombocytopenia, and conjugated hyperbilirubinemia, while the other had moderate anemia and unconjugated hyperbilrubinemia. Although both the neonates were treated by phototherapy and intravenous immunoglobulin, one of them received double volume exchange transfusion. Conclusion: There appeared to be an increase in the occurrence of hemolytic disease of the fetus and newborn caused by Rh antibodies other than anti-D. In this case report, both patients presented with anemia and hyperbilirubinemia but were successfully treated, with a favorable outcome.

  15. Anti-allergic and anti-anaphylactic activities of Dolichos biflorus

    Directory of Open Access Journals (Sweden)

    Anupama Ashok Suralkar

    2013-01-01

    Full Text Available Background: The seeds of Dolichos biflorus (DB have been traditionally used in the treatment of cough and asthma. Aim: Based on the traditional claim, the present study was planned to evaluate the anti-allergic and anti-anaphylactic activities of DB. Materials and Methods: The ethanolic extract of the seeds of DB was prepared by cold maceration process. DB was subjected to phytochemical screening, acute toxicity studies, mast cell-stabilizing activity using compound 48/80 and anti-allergic activity using milk-induced leukocytosis and eosinophilia and passive paw anaphylaxis. Statistical Analysis: Statistical analysis was done by using one-way analysis of variance followed by Dunnett′s test. Results: The phytochemical investigation showed presence of proteins, flavonoids and glycosides. DB extract inhibited milk-induced leukocytosis and eosinophilia and also the compound 48/80 induced mast cell degranulation. DB extract significantly reduced passive paw anaphylaxis in a dose-dependent manner. Conclusion : The results demonstrated that DB extract possesses anti-allergic and anti-anaphylactic potentials that might be useful in the management of asthma.

  16. Bioactivity screening of microalgae for antioxidant, anti-inflammatory, anticancer, anti-diabetes and antibacterial activities

    Directory of Open Access Journals (Sweden)

    Chiara eLauritano

    2016-05-01

    Full Text Available Marine microalgae are considered a potentially new and valuable source of biologically active molecules for applications in the food industry as well as in the pharmaceutical, nutraceutical and cosmetic sectors. They can be easily cultured, have short generation times and enable an environmentally-friendly approach to drug discovery by overcoming problems associated with the over-utilization of marine resources and the use of destructive collection practices. In this study, 21 diatoms, 7 dinoflagellates and 4 flagellate species were grown in three different culturing conditions and the corresponding extracts were tested for possible antioxidant, anti-inflammatory, anticancer, anti-diabetes, antibacterial and anti-biofilm activities. In addition, for two diatoms we also tested two different clones to disclose diversity in clone bioactivity. Six diatom species displayed specific anti-inflammatory, anticancer (blocking human melanoma cell proliferation and anti-biofilm (against the bacteria Staphylococcus epidermidis activities whereas, none of the other microalgae were bioactive against the conditions tested for. Furthermore, none of the 6 diatom species tested were toxic on normal human cells. Culturing conditions (i.e. nutrient starvation conditions greatly influenced bioactivity of the majority of the clones/species tested. This study denotes the potential of diatoms as sources of promising bioactives for the treatment of human pathologies.

  17. Anti-Oxidant, Anti-Aging, and Anti-Melanogenic Properties of the Essential Oils from Two Varieties of Alpinia zerumbet

    OpenAIRE

    Pham Thi Be Tu; Shinkichi Tawata

    2015-01-01

    Here, we investigated the anti-oxidant and anti-aging effects of essential oils (EOs) from the leaves of Alpinia zerumbet (tairin and shima) in vitro and anti-melanogenic effects in B16F10 melanoma cells. The anti-oxidant activities were performed with 2,2-diphenyl-1-picrylhydrazyl (DPPH); 2,2ʹ-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS); nitric oxide; singlet oxygen; hydroxyl radical scavenging; and xanthine oxidase. The inhibitory activities against collagenase...

  18. Combinatorial Chemotherapeutic Efficacy in non-Hodgkins Lymphoma can be Predicted by a Signaling Model of CD20 Pharmacodynamics

    OpenAIRE

    Harrold, John M.; Straubinger, Robert M.; Mager, Donald E.

    2012-01-01

    Combination chemotherapy represents the standard-of-care for non-Hodgkins lymphoma. However, the development of new therapeutic regimens is empirical and this approach cannot be used prospectively to identify novel or optimal drug combinations. Quantitative system pharmacodynamic models could promote the discovery and development of combination regimens based upon first principles. In this study, we developed a mathematical model that integrates temporal patterns of drug exposure, receptor oc...

  19. Redirection of CMV-specific CTL towards B-CLL via CD20-targeted HLA/CMV complexes

    NARCIS (Netherlands)

    R. Mous; P. Savage; E.B.M. Remmerswaal; R.A.W. van Lier; E. Eldering; M.H.J. van Oers

    2006-01-01

    B-cell chronic lymphocytic leukaemia (B-CLL) is a slowly progressing malignancy of CD5(+) B cells, for which at present no curative treatment is available. In our current study, we apply a novel bridging reagent to redirect cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CTL) to target B-CLL

  20. Anti-Microbial, Anti-Oxidant and Anti-Ulcerogenic Effects of Shilajit on Gastric Ulcer in Rats

    OpenAIRE

    Mohamed-I. Kotb El-Sayed; Hatem-K. Amin; Ali-G. Al-Kaf

    2012-01-01

    Problem statement: To evaluate the effects and mechanisms of action involved in anti-ulcer, antioxidant and antimicrobial activities of different native shilajit samples. Approach: Shilajit samples were collected in the mountain region of Yemen (Al-Jouf and Rayma), Russia (Tien-Shan) and India (Kumoan). Stomach ulcers were induced in rats by oro-gastric ingestion of ethanol/HCl. Pre-treatment with ranitidine (100 mg kg-1, p.o.) and shilajit samples (600 mg kg-1, p.o.) occurred for 14 days bef...

  1. Anti-S100A4 antibody suppresses metastasis formation by blocking stroma cell invasion

    DEFF Research Database (Denmark)

    Klingelhöfer, Jörg; Grum-Schwensen, Birgitte; Beck, Mette K;

    2012-01-01

    microenvironment, making it an attractive target for anti-cancer therapy. In this study, we produced a function-blocking anti-S100A4 monoclonal antibody with metastasis-suppressing activity. Antibody treatment significantly reduced metastatic burden in the lungs of experimental animals by blocking the recruitment......The small Ca-binding protein, S100A4, has a well-established metastasis-promoting activity. Moreover, its expression is tightly correlated with poor prognosis in patients with numerous types of cancer. Mechanistically, the extracellular S100A4 drives metastasis by affecting the tumor...... of T cells to the site of the primary tumor. In vitro studies demonstrated that this antibody efficiently reduced the invasion of T cells in a fibroblast monolayer. Moreover, it was capable of suppressing the invasive growth of human and mouse fibroblasts. We presume therefore that the antibody...

  2. ANTI-INFLAMMATORY AND ANTI-ARTHRITIC ACTIVITIES OF DELONIX ELATA BARK EXTRACTS

    Directory of Open Access Journals (Sweden)

    G. Murugananthan

    2011-06-01

    Full Text Available Delonix elata (D. elata, has long been used in traditional herbal medicine for the treatment of arthritis pain. In the present study an attempt was made to study the effect of D. elata barks for its anti-inflammatory and anti-arthritic effect in animal models. Barks were subjected for extraction with pet. ether, chloroform and 40% hydroalcohol successively and evaporated under rotary evaporator to get the concentrated extract. All the extracts were subjected for acute oral toxicity studies in rats and found to be safe up to the dose of 5g/kg body weight. Anti-inflammatory screening by carrageenan-induced paw oedema and cotton pellet induced granuloma method, the hydro alcohol extract of D. elata barks showed significant protection against the inflammation. In Complete Freund’s Adjuvant induced arthritis model also the hydro alcohol exhibited significant protection on day 7 onwards.

  3. Anti-bacterial and anti-leishmanial studies of 4, 6-diarylpyrimidin-2-amines

    International Nuclear Information System (INIS)

    Seven new chalcones along with nine already reported ones were synthesized from aryl aldehydes and substituted acetophenones by Claisen-Schmidt condensation. Each chalcone was treated with guanidine hydrochloride followed by oxidation with H/sub 2/O/sub 2/ which yielded substituted 4, 6-diarylpyrimidin-2-amines with good to excellent yields. The titled compounds were characterized by spectroscopic techniques (NMR, IR, MS) and elemental analysis. All the compounds were screened for the first time for anti-bacterial and anti-leishmanial activities which exhibited marked biological activity. Compound 4 showed significant activity against E. coli and S. aureus. Compounds 7, 8, 10, 12, 15 and 16 exhibited IC/sub 50/ values comparable to the standard drug Amphotericin B in anti-leishmanial studies. (author)

  4. Anti-obesity activity of hen egg anti-lipase immunoglobulin yolk, a novel pancreatic lipase inhibitor

    OpenAIRE

    Hirose, Mai; Ando, Taishi; Shofiqur, Rahman; Umeda, Kouji; Kodama, Yoshikatsu; Van Nguyen, Sa; Goto, Tsuyoshi; Shimada, Masaya; Nagaoka, Satoshi

    2013-01-01

    Background There is completely no report about both hen egg anti-lipase immunoglobulin yolk (IgY) and its anti-obesity action. Thus, we tried to isolate and characterize a novel anti-lipase immunoglobulin from hen egg yolk. Moreover, we investigated whether hen egg yolk anti-lipase IgY inhibits pancreatic lipase activity in vitro, and examined its ability to prevent obesity in a murine high fat diet-induced obesity model. Methods We determined the inhibitory action of Anti-lipase IgY on lipas...

  5. The inclusive semileptonic decay Zerfall anti B → Xcl anti νl in effective field theories

    International Nuclear Information System (INIS)

    The exact determination of the absolute values of the CKM elements Vub and Vcb is of central importance for testing the unitarity of the CKM matrix and hence the quark-flavour sector of the Standard Model. The inclusive semileptonic decay anti B →Xcl anti νl provides the most accurate determination of vertical stroke Vcb vertical stroke, where the αs corrections to the (ΛQCD/mb)2 terms in the Heavy Quark Expansion represent the major theoretical uncertainties. Values for vertical stroke Vub vertical stroke can be extracted both from anti B → πl anti νl and anti B → Xul anti νl. After introducing cuts in phase space to suppress the large background from anti B → Xcl anti νl, data for anti B → Xul anti νl are mainly available in the region of phase space where the decay rate is proportional to the hadronic shape function of the B meson. In this work, a method is developed that allows to evaluate the QCD corrections of order αs to the decay anti B → Xcl anti νl numerically. This is especially important for the calculation of the αs corrections to the (ΛQCD/mb)2 terms, where an analytic treatment does not look feasible due to the complexity of the occurring terms. As infrared divergences are treated in Dimensional Regularization, the formalism is gauge-invariant, so that it is particularly suitable for the calculation of the corrections proportional to the chromomagnetic operator. By making use of the extension of Soft-Collinear Effective Theory (SCET) to describe massive collinear quarks, which is also presented in this work, the decay anti B → Xcl anti νl is examined in the shapefunction region. For this purpose, the power counting mc ∝ √(mbΛQCD) is used for the charm-quark mass and similar cuts in phase space are introduced as for anti B → Xul anti νl. Decay spectra are calculated to next-to-leading order in the ΛQCD/mb expansion at tree level. In addition, the αs corrections to the leading order term in the ΛQCD/mb expansion

  6. The (Sea)Quest to map anti-up and anti-down quarks

    Science.gov (United States)

    Diefenthaler, Markus

    2015-10-01

    The SeaQuest experiment at Fermilab continues a series of Drell-Yan measurements to explore the antiquark content of the nucleon and to study the modifications to nucleon structure when the nucleon is embedded into a nuclei. To extend existing measurements to larger values of Bjorken-x, a 120 GeV proton beam extracted from Fermilab's Main Injector is used, resulting in 50 times more luminosity than previous experiments and enabling access to values of x up to 0.9. One of the key physics goals of the SeaQuest collaboration is the exploration of the origin of the intrinsic nucleon sea. The scale dependence observed in high-energy scattering experiments reflects the quantum fluctuations predicted by QCD. A sea of virtual gluons arises in the nucleon; these gluons radiate other gluons or pairs of quarks and antiquarks. Gluon splitting, e.g. into an u anti-u quark pair or a d anti-d quark pair, is a perturbative QCD process and flavor symmetric. However, there is clear experimental evidence that the nucleon sea is not flavor symmetric. The distributions for anti-d quarks and anti-u quarks differ by up to 50% and suggest a substantial role of non-perturbative QCD processes in the creation of the nucleon sea. Measuring the ratio of the anti-d quark and anti-u quark distributions with high accuracy and within a large x-range is the key measurement of the SeaQuest experiment. The SeaQuest results will help to identify effective theories that can describe the intrinsic nucleon sea and help to explore its origin. On behalf of the SeaQuest Collaboration.

  7. Seropositivity of HBsAg, anti-HCV and anti-HIV in preoperative patients

    Directory of Open Access Journals (Sweden)

    Berrin Karaayak Uzun

    2014-12-01

    Full Text Available Objective: The infections caused by human immunodeficiency virus (HIV, hepatitis B (HBV and C (HCV viruses pose a serious occupational risk for the healthcare workers especially those in emergency services, laboratories and surgery wards. Vaccination and establishment of the strict biosafety procedures are the main principles to prevent blood-borne infections in healthcare workers. Additionally, serological screening of the preoperative patients could decrease the risk for exposure. In this study, we aimed to determine the seroprevalence of HBsAg, anti-HCV, anti-HIV 1/2 in preoperative patients. Methods: Hospital automation records were evaluated retrospectively for 4.367 patients who were scheduled for surgery and scanned for anti-HIV 1/2, HBsAg and anti-HCV as preoperative procedures in the preparation period of operation between January 2012 and December 2012. Results: HBsAg positivity rate was found in 7.7% (n=336, anti-HCV positivity rate was found in 2.3% (n=101. A two (0.05% of five patients were positive for anti-HIV 1/2 was found positive verification test and the other three samples were accepted as false positive test results. Conclusion: All healthcare workers must be trained about occupational diseases and vaccinated against Hepatitis B. Universal precautions must be strictly followed particularly in the operating room. In addition, all patients should be considered as potential carriers regarded as a carrier of the potential for infection. J Clin Exp Invest 2013; 4 (4: 449-452

  8. Neurobiologia do transtorno de personalidade anti-social Neurobiology of anti-social personality disorder

    OpenAIRE

    Cristina Marta Del-Ben

    2005-01-01

    Nos últimos anos, tem havido um interesse crescente a respeito de uma melhor compreensão sobre o comportamento anti-social. O aumento da criminalidade e violência urbanas pode ter contribuído para esse maior interesse. Além de fatores psicossociais, outros biológicos têm sido implicados na fisiopatogenia do transtorno de personalidade anti-social (TPAS). Estudos de neuroimagem apontam o envolvimento de estruturas cerebrais frontais, especialmente o córtex orbitofrontal, e a amígdala. Também t...

  9. Wie rassistisch sind Anti-Rassist/-innen? How Racist are Anti-Racists?

    OpenAIRE

    Ilka Borchardt

    2003-01-01

    Anja Weiß beschäftigt sich mit einem all zu oft emotional behandelten Thema: dem Rassismus anti-rassistisch Engagierter. Sie versucht die häufig widersprüchlichen Auseinandersetzungen und Emotionen um Rassismus und Rassismus-Vorwürfe versucht Weiß kreativ im Forschungsprozess zu verwenden.Anja Weiß does a very thorough and committed job of presenting a difficult topic, investigating the racism of those who self-identify as anti-racist activists. This topic may often seem paradoxical, and is u...

  10. New observables in the decay mode anti-B --> anti-K*0 l+ l-

    OpenAIRE

    Egede, U.; Hurth, T.; Matias, J.; Ramon, M.; Reece, W.(CERN, European Organization for Nuclear Research, Geneva, Switzerland)

    2008-01-01

    We discuss the large set of observables available from the angular distributions of the decay anti-B --> anti-K*0 l+ l-. We present a NLO analysis of all observables based on the QCD factorization approach in the low-dilepton mass region and an estimate of \\Lambda/m_b corrections. Moreover, we discuss their sensitivity to new physics. We explore the experimental sensitivities at LHCb (10 fb^-1) and Super-LHCb (100 fb^-1) based on a full-angular fit method and explore the sensitivity to right ...

  11. The Necessity of Anti-Piracy and Anti-Monopoly in Software Industry

    Directory of Open Access Journals (Sweden)

    Jingfeng Meng

    2009-05-01

    Full Text Available The piracy and monopoly in the software industry is analyzed in this article which shows that they will ultimately endanger the national industry but not the foreign monopoly enterprises. The author considers that the low price of the pirated software and the internets monopoly form are the two reasons to form monopoly. Anti-pirate and anti-monopoly are both imperative ways to develop Chinese software industry. A general strategy regulation in the software industry elicited by this article is to strike piracy in the protected period, shorten moderately protection period of the software product and limit the monopoly manufacturers to some extent.

  12. Anti-Angiogenesis and Anti-Tumor Effect of Shark Cartilage Extract

    Institute of Scientific and Technical Information of China (English)

    王锋; 王漪涛; 谢莉萍; 张荣庆

    2001-01-01

    The effect of shark cartilage extract (SCE), purified in this laboratory, on angiogenesis in chick chorioallantoic membrane (CAM), on the activity of collagenase IV and on human umbilical vein endothelial cell (ECV-304) proliferation and apoptosis was investigated in vitro. The results showed that SCE caused a decline in CAM blood vessels and significantly prevented collagenase-induced collagenolysis. Moreover, SCE produced a dose-dependent decline in ECV-304 proliferation and altered its normal cell cycle. These results suggest that the anti-angiogenesis and anti-tumor effects of shark cartilage may be due to inhibition of endothelial cells as well as collagenolysis.

  13. Book review: anti-porn: the resurgence of anti-pornography feminism

    OpenAIRE

    Spoto, Stephanie

    2013-01-01

    Countering the ongoing ‘pornification’ of Western culture and society, with lads’ mags on the middle shelf and lap-dancing clubs in residential areas, anti-porn movements are re-emerging among a new generation of feminist activists worldwide. This guide to the problems with porn starts with a history of modern pro and anti political stances before examining the ways in which the new arguments and campaigns around pornography are articulated, deployed and received. If you’re looking for a hist...

  14. Delayed Serological Transfusion Reaction After Platelet Transfusion Due to Anti-e.

    Science.gov (United States)

    Sachan, Deepti; Kumar, Aswin; Jothimani, Dinesh; Rela, Mohamed

    2016-06-01

    Delayed serological transfusion reaction (DSTR) is defined as absence of clinical signs of hemolysis and demonstration of new, clinically-significant antibodies against red blood cells after a transfusion, by either positive direct antiglobulin test or positive antibody screen with newly identified RBC alloantibody. Various delayed hemolytic transfusion reaction cases are reported after red cell transfusions. However, the incidence of DSTR after platelet transfusion due to non-Rh(D) antibodies is not much documented. We report here a case of DSTR due to anti-e Rh antibody in a multiply red cell alloimmunized female patient after single donor platelets transfusion. PMID:27408414

  15. NLO QCD corrections to pp → t anti-t b anti-b

    International Nuclear Information System (INIS)

    The production of t anti-t b anti-b final states represents one of the most important background processes for Higgs production in association with top-quark pairs at the LHC. A good background control is indispensable for an analysis of the ttH(→bb) signal, requiring next-to-leading order (NLO) predictions for both signal and background. The talk describes a recently completed NLO QCD calculation for pp→ttbb at the LHC, a calculation that is at the calculational frontier of NLO predictions for so-called multi-leg processes. Moreover, results from a phenomenologically driven analysis are discussed. (author)

  16. Anti-reflective and anti-soiling coatings for self-cleaning properties

    Energy Technology Data Exchange (ETDEWEB)

    Brophy, Brenor L.; Nair, Vinod; Dave, Bakul Champaklal

    2016-05-31

    The disclosure discloses abrasion resistant, persistently hydrophobic and oleophobic, anti-reflective and anti-soiling coatings for glass. The coatings described herein have wide application, including for example the front cover glass of solar modules. Methods of applying the coatings using various apparatus are disclosed. Methods for using the coatings in solar energy generation plants to achieve greater energy yield and reduced operations costs are disclosed. Coating materials are formed by combinations of hydrolyzed silane-base precursors through sol-gel processes. Several methods of synthesis and formulation of coating materials are disclosed.

  17. Sequential occurrence of anti-glomerular basement membrane disease 9 years after anti-neutrophil cytoplasmic antibody-associated vasculitis

    Science.gov (United States)

    Chan, Pui Shan Julia; Leung, Moon Ho

    2016-01-01

    We report a case of 63-year-old Chinese man, having a history of anti-myeloperoxidase (MPO) antibody anti-neutrophil cytoplasmic antibody (ANCA)-associated pulmonary-renal syndrome 9 years ago, presented with second episode of rapidly progressive glomerulonephritis (RPGN) and alveolar haemorrhage compatible with anti-glomerular basement membrane (GBM) disease. In first presentation, his anti-GBM antibody was negative. This time, anti-MPO antibody was negative, but anti-GBM antibody was positive. The long interval of sequential development of anti-GBM disease after ANCA-associated vasculitis in this patient may provide clues to the potential immunological links between these two distinct conditions. Clinicians should be aware of such double-positive association.

  18. Erdosteine: antitussive and anti-inflammatory effects.

    Science.gov (United States)

    Dal Negro, Roberto W

    2008-01-01

    Erdosteine is a multifactorial drug currently used in COPD for its rheologic activity on bronchial secretions and its positive effects on bacterial adhesiveness. Erdosteine produces an active metabolite (Met 1) which was shown to produce antioxidant effects during the respiratory burst of human PMNs, due to the presence of an SH group. The substantial antitussive effects of erdosteine were first documented in clinical trials even though mucolytic agents are regarded as not consistently effective in ameliorating cough in patients with bronchitis, although they may be of benefit to this population in other ways. Actually, a mucolytic drug could exert antitussive effects if it also affects mucus consistency and enhances ciliary function. In the last decade, data from several studies on animal models pointed to the possible antitussive and anti-inflammatory properties of erdosteine and an indirect anti-inflammatory mechanism of action was suggested. Recently, data from some controlled versus placebo studies documented the antioxidant properties of erdosteine in humans and in current smokers with COPD. The mechanism of action was described as related to erdosteine's ability to inhibit some inflammatory mediators and some pro-inflammatory cytokines that are specifically involved in oxidative stress. As oxidative stress is also presumed to impair beta-adrenoceptor function and contribute to airway obstruction, specific controlled studies recently investigated the effect of antioxidant intervention on short-term airway response to salbutamol in nonreversible COPD, according to a double-blind design versus placebo and NAC. Only erdosteine consistently restored a significant short-term reversibility in COPD subjects, previously unresponsive to beta(2) adrenergics. This peculiar activity of erdosteine (to our knowledge never previously assessed) proved related to the ROS scavenging activity (which actually proved equal to that of N), and its significant inhibiting effect on

  19. Quantum Anti-de Sitter Space

    OpenAIRE

    Chang, Zhe

    1999-01-01

    The quantum Anti-de Sitter (AdS) group and quantum AdS space is discussed. Ways of getting the quantum AdS group from real forms of quantum orthogonal group are presented. Differential calculus on the quantum AdS space are also introduced. In particular, reality of differential calculus are given. We set up explicit relationships between quantum group and quantum algebra, which can be refereed as the quantum counterpart of the classical exponential. By this way, quantum AdS algebra is deduced...

  20. Recent Developments in Anti-Tank Ammunition

    Directory of Open Access Journals (Sweden)

    N. S. Venkatesan

    1985-04-01

    Full Text Available Every advance in anti-tank ammunition has been matched by advances in armour material or vice-versa. This applies both to kinetic energy and chemicai energy type of ammunition. Today the kinetic energy ammunition appears to have an upper hand over armour. In t his paper, a brief survey of the modern FSAPDS ammunition, its design aspects and its material technology is made.The capabilities of HEAT type of ammunition are also discussed and the likely trends in ammunition technology are indicated. Some futuristic developments in the field of propulsion are briefly mentioned.

  1. Anti-noise Protective Agents in Tractors

    OpenAIRE

    Hudec, Miroslav

    2010-01-01

    The aim of my bachelor´s thesis is anti-noise protective agents in tractors. In this work I focused on influence of wanted and unwanted noise to humans and the results of it. In other part I concerned with simple calculation of noise, each sources´ vibration and sound transmission of solids. These calculations are very complicated and complex but for my purpose I simplified them and used only the basic ones. The next procedure is to clear out the noise by constructional alterations, which are...

  2. A Tale of Two Anti-Americanisms

    OpenAIRE

    Pierre Guerlain

    2007-01-01

    There is, of course no single American tradition or single American set of values. There are, and always have been, many Americas. We each of us remember and appeal to the Americas we prefer. Immanuel Wallerstein What does the term mean? That you’re anti-jazz? Or that you’re opposed to free speech? That you don’t delight in Toni Morrison or John Updike? That you have a quarrel with giant sequoias? Does it mean that you don’t admire the hundreds of thousands of American citizens who marched ag...

  3. A radioimmunoassay for determination of anti-actin antibodies

    International Nuclear Information System (INIS)

    The reaction of spontaneously occurring human anti-actin antibodies and experimentally produced rabbit anti-actin antibodies was investigated in a solid-phase radioimmunoassay (RIA). Three structurally different in vitro forms of actin, monomeric G-actin, filamentous F-actin and aggregated denatured actin were used as antigens. Human anti-actin antibodies reacted with F- and G-actin but not with aggregated actin, while rabbit anti-actin antibodies gave a strong reaction with all 3 forms of actin indicating differences in antibody specificities. The results of the anti-actin RIA were compared with those obtained by indirect immunofluorescence (IFL) on cryostat sections of rat stomach. The anti-actin RIA discriminated between patients' sera and control sera in most cases, although the indirect IFL test gave more conclusive results. The seemingly low sensitivity of the anti-actin RIA compared with that of indirect IFL test for detection of human anti-actin antibodies is probably due to favourable antigen distribution in tissue, not available in the solid phase. The anti-actin RIA was able to detect anti-actin antibodies in 8 out of 8 immunized rabbits although only two produced antibodies detectable by indirect IFL. The differences in reactivity between the two methods may depend on the presence of aggregated denatured actin in the antigen preparation used for immunization and exposure of the corresponding antigenic determinants of actin on the solid phase. (Auth.)

  4. A possible anti-proliferative and anti-metastatic effect of irradiated riboflavin in solid tumours

    NARCIS (Netherlands)

    de Souza Queiroz, Karla Cristiana; Zambuzzi, Willian Fernando; de Souza, Ana Carolina Santos; da Silva, Rodrigo Augusto; Machado, Daisy; Justo, Giselle Zenker; Carvalho, Hernandes F.; Peppelenbosch, Maikel P.; Ferreira, Carmen Verissima

    2007-01-01

    Riboflavin is a potent photosensitizer as well as part of the vitamin B complex. Recently we demonstrated that the products generated by irradiation of riboflavin have potential as anti-leukaemic therapy. The possible action, however, of the riboflavin photoproducts in solid cancers has not been add

  5. Anti Moppel : logistikafirmadel ei tasu ELi karta / Anti Moppel ; interv. Rivo Sarapik

    Index Scriptorium Estoniae

    Moppel, Antti, 1968-

    2003-01-01

    Ilmunud ka: Delovõje Vedomosti : Avtomobili i transport 15. okt. lk. 10-11. Majandus- ja kommunikatsiooniministeeriumi osakonnajuhataja Anti Moppel vastab küsimustele, mis puudutavad logistikafirmade ootusi EL-ist, Eesti transpordituru arengut, transpordifirmade valmisolekut Eesti liitumiseks EL-iga, ministeeriumi pakutavat infot EL-i kohta

  6. The anti-obesity drug orlistat reveals anti-viral activity.

    Science.gov (United States)

    Ammer, Elisabeth; Nietzsche, Sandor; Rien, Christian; Kühnl, Alexander; Mader, Theresa; Heller, Regine; Sauerbrei, Andreas; Henke, Andreas

    2015-12-01

    The administration of drugs to inhibit metabolic pathways not only reduces the risk of obesity-induced diseases in humans but may also hamper the replication of different viral pathogens. In order to investigate the value of the US Food and Drug Administration-approved anti-obesity drug orlistat in view of its anti-viral activity against different human-pathogenic viruses, several anti-viral studies, electron microscopy analyses as well as fatty acid uptake experiments were performed. The results indicate that administrations of non-cytotoxic concentrations of orlistat reduced the replication of coxsackievirus B3 (CVB3) in different cell types significantly. Moreover, orlistat revealed cell protective effects and modified the formation of multi-layered structures in CVB3-infected cells, which are necessary for viral replication. Lowering fatty acid uptake from the extracellular environment by phloretin administrations had only marginal impact on CVB3 replication. Finally, orlistat reduced also the replication of varicella-zoster virus moderately but had no significant influence on the replication of influenza A viruses. The data support further experiments into the value of orlistat as an inhibitor of the fatty acid synthase to develop new anti-viral compounds, which are based on the modulation of cellular metabolic pathways. PMID:25680890

  7. Combined Anti-PLGF and Anti-Endostatin Treatments Inhibit Ocular Hemangiomas

    Directory of Open Access Journals (Sweden)

    Hua Jiang

    2015-06-01

    Full Text Available Background/Aims: The degree of neovascularization determines the aggressiveness of ocular hemangiomas (OH. So far, the anti-angiogenic treatments using either antagonists against vascular endothelial growth factor A (VEGF-A, or endostatin, do not always lead to satisfactory therapeutic outcome. Methods: We examined the VEGF receptor 1 (VEGFR1 levels in the OH specimen. We compared the effects of anti-PLGF, endostatin, as well as their combined treatments on the growth of OH in a mouse model, using bioluminescence imaging in living animals. We also examined vascularization by CD31 expression. Results: We detected higher VEGFR1 levels in the OH, compared to paired normal tissue. Thus, we hypothesize that as a major ligand for VEGFR1, placental growth factor (PLGF may also play a role in the neovascularization and tumorigenesis of OH. In an implanted OH model in mice, we found that both anti-PLGF and endostatin significantly decreased OH growth as well as vascularization, while combined treatments had a significantly more pronounced effect. Conclusion: Our data suggest that combined anti-PLGF and endostatin may be a more effective therapy for inhibition of ocular vascularization and the tumor growth in OH.

  8. EVALUATION OF ANTI-INFLAMMATORY AND ANTI-ARTHRITIC ACTIVITIES OF FLOATING MICROSPHERES OF HERBAL DRUG

    Directory of Open Access Journals (Sweden)

    Kapil Kumar

    2012-01-01

    Full Text Available The aim of the present studies was to prepare and evaluate floating microspheres of curcumin for anti-inflammatory and anti-arthritic effect. Floating microsphere were prepared using hydroxyl propyl methylcellulose (HPMC, ethyl cellulose (EC, polyvinyl pyrrolidone K30 (PVPK30, eudragit RS 100 polymer in different ratio and dichloromethane and heavy liquid paraffin as solvent by emulsion solvent diffusion method. The floating microspheres were evaluated for flow properties based on parameters such as angle of repose and compressibility index, as well as for various other physicochemical properties including particle size, incorporation efficiency, in-vitro floatability, and in-vitro drug release. The shape and surface morphology of the microspheres were characterised by scanning electron microscopy. Scanning electron microscopy showed pores on the surface and interior of the microspheres. Anti-inflammatory, anti-arthritic effect of formulation C4 and E1 were compared with standard market product Indomethacin. The effect of formulation C4 and E1 was evaluated for acute inflammation in carrageenan induced rat paw edema and for chronic inflammation in complete Freud’s adjuvant (CFA induced arthritis in rats. Further histopathological and radiographic evaluation was performed. It may be concluded that Curcumin microspheres would be promising drug delivery system for oral administration of Curcumin to sustained the drug release. Incorporation of herbal drugs in novel drug delivery system may lead to an excellent result.

  9. Anti-hepatotoxic and anti-oxidant defense potential of Tridax procumbens

    Directory of Open Access Journals (Sweden)

    Hemalatha Reddipalli

    2008-01-01

    Full Text Available Tridax procumbens is a widely occurring medicinal herb used by ethnomedical practitioners. With increased use of chemicals and alcohol besides growing incidence of viruses and autoimmune diseases, the incidence of liver injury is growing for which conventional drugs used for treatment are often inadequate. Various models are adopted in pharmological studies for inducing hepatitis/ liver injury similar to those observed in human viral hepatitis, diabetes and oxidative stress. D-galactosamine with lipopolysacchride (LPS, carbontetrachloride (CCl 4 and paracetamol intoxication, diabetes induced with alloxan are widely used on rodents for this purpose. In vitro studies on Tridax procumbens (TP revealed the anti-oxidant potential of the herb with chloroform fraction of the ethanolic extract showing maximum activity. It is also reported to possess anti-oxidant minerals such as iron, magnesium, copper and zinc. In vivo studies on rodents on the anti-oxidant potential of TP induced through LPS, CCl 4, alloxan and paracetamol intoxication induced hepatitis confirmed the results from in vitro studies as a potential anti-hepatotoxic herb.

  10. Studies on the anti-inflammatory and anti-nociceptive properties of Blepharis maderaspatensis leaves

    Directory of Open Access Journals (Sweden)

    Abimbola Sowemimo

    2013-10-01

    Full Text Available Blepharis maderaspatensis(L. B. Heyne ex Roth, Acanthaceae, is a procumbent or scrambling perennial herb used traditionally for treatment of snakebites, wounds, edema and gout. The anti-inflammatory and anti-nociceptive properties of the ethanol extract of the whole plant of B. maderaspatensis was investigated using carrageenan-induced paw edema in rats, xyleneinduced edema in mice, mouse writhing and tail clip tests respectively. The effect of the extract on inflammatory mediators, serotonin and histamine, using the most active dose (75 mg/kg was also carried out. The results showed that the extract of B. maderaspatensis in carrageenan-induced test caused a significant inhibition (84.5%, 90 min of paw edema at a dose of 75 mg/kg while the xylene-induced test caused a significant inhibition (62.65% at 50 mg/kg. The histamine-induced test showed significant inhibition (90.9%, 90 min while serotonin-induced test showed moderate inhibition (54.10%, 180 min. In the mouse writhing and tail clip tests, the extract produced a significant inhibition of 66.21% and 15.81% at 75 mg/kg, respectively. These results collectively demonstrate that the ethanol extract of B. maderaspatensis possesses anti-inflammatory and anti-nociceptive properties, and this supports the ethnopharmacological use of the plant in the treatment of inflammation.

  11. Wogonin attenuates diabetic cardiomyopathy through its anti-inflammatory and anti-oxidative properties.

    Science.gov (United States)

    Khan, Shahzad; Zhang, Deling; Zhang, Yemin; Li, Mingxin; Wang, Changhua

    2016-06-15

    Among diabetic cardiovascular complications cardiomyopathy is major event which if not well controlled culminates in cardiac failure. Wogonin from the root of Scutellaria baicalensis Georgi has shown specific anti-diabetes bioactivity. However, its effect on diabetic complications remains unclear. The main purpose of this study is to investigate the potential effects of wogonin on diabetic cardiomyopathy and to figure out its underlying mechanism. We found that wogonin administration suppressed hyperglycemia, improved cardiac function, and mitigated cardiac fibrosis in STZ-induced diabetic mice. Wogonin supplementation also attenuated diabetic-induced cardiomyocyte apoptosis and necrosis. In addition, wogonin treatment exhibited the properties of anti-oxidative stress and anti-inflammation in STZ diabetic mice, evidenced by improved activities of anti-oxidases including SOD1/2 and CAT, decreased ROS and MDA production, suppressed expression of inflammation factors such as IL-1β, IL-6, TNFα, and PAI-1, and inhibited NF-κB signaling. These results suggested that wogonin potentially mitigate hyperglycemia-related cardiomyocyte impairment through inhibiting inflammation and oxidative stress. PMID:27013352

  12. High gain durable anti-reflective coating

    Energy Technology Data Exchange (ETDEWEB)

    Maghsoodi, Sina; Brophy, Brenor L.; Colson, Thomas E.; Gonsalves, Peter R.; Abrams, Ze' ev R.

    2016-07-26

    Disclosed herein are polysilsesquioxane-based anti-reflective coating (ARC) compositions, methods of preparation, and methods of deposition on a substrate. In one embodiment, the polysilsesquioxane of this disclosure is prepared in a two-step process of acid catalyzed hydrolysis of organoalkoxysilane followed by addition of tetralkoxysilane that generates silicone polymers with >40 mol % silanol based on Si-NMR. These high silanol siloxane polymers are stable and have a long shelf-life in polar organic solvents at room temperature. Also disclosed are low refractive index ARC made from these compositions with and without additives such as porogens, templates, thermal radical initiator, photo radical initiators, crosslinkers, Si--OH condensation catalyst and nano-fillers. Also disclosed are methods and apparatus for applying coatings to flat substrates including substrate pre-treatment processes, coating processes and coating curing processes including skin-curing using hot-air knives. Also disclosed are coating compositions and formulations for highly tunable, durable, highly abrasion-resistant functionalized anti-reflective coatings.

  13. Optical enhancing durable anti-reflective coating

    Energy Technology Data Exchange (ETDEWEB)

    Maghsoodi, Sina; Varadarajan, Aravamuthan; Movassat, Meisam

    2016-07-05

    Disclosed herein are polysilsesquioxane based anti-reflective coating (ARC) compositions, methods of preparation, and methods of deposition on a substrate. In embodiments, the polysilsesquioxane of this disclosure is prepared in a two-step process of acid catalyzed hydrolysis of organoalkoxysilane followed by addition of tetralkoxysilane that generates silicone polymers with >40 mol % silanol based on Si-NMR. These high silanol siloxane polymers are stable and have a long shelf-life in the polar organic solvents at room temperature. Also disclosed are low refractive index ARC made from these compositions with and without additives such as porogens, templates, Si--OH condensation catalyst and/or nanofillers. Also disclosed are methods and apparatus for applying coatings to flat substrates including substrate pre-treatment processes, coating processes including flow coating and roll coating, and coating curing processes including skin-curing using hot-air knives. Also disclosed are coating compositions and formulations for highly tunable, durable, highly abrasion-resistant functionalized anti-reflective coatings.

  14. Farmacoeconomic impact of anti-TNFα

    Directory of Open Access Journals (Sweden)

    E. Vaccaro

    2011-09-01

    Full Text Available The anti-TFNα are undoubtedly an efficacious cure in the treatment of rheumatoid arthritis, but their costs are so high that a thorough pharmacoeconomical evaluation is needed in order to identify the specific conditions in which their use is to be considered convenient. For this reason there are related the most important experiences that have studied the cost-efficacy and cost-utility relationships of anti-TFNα drugs, which have been made marketable in Italy. The data available, unfortunately, are too various to allow a final settlement of the chart of convenience between the different therapeutic alternatives. Moreover the socio-medical reality in Italy is so much different from the ones in other countries that it is impossible to try and use the foreign experiences. In a country of high social commitment like Italy, a fair judgment can thereafter be made only when the issue is considered related to our society, taking in account the summation of the medical costs endured by the National Health System, the patient’s expenses and the ones that are a consequence of the loss of productivity.

  15. Anti IH: An antibody worth mention

    Directory of Open Access Journals (Sweden)

    Nithya Mohanan

    2016-01-01

    Full Text Available A 72-year-old female with co-morbidities posted for surgical correction of fracture neck of femur without any history of transfusions was noted to have a hemoglobin level of 7 g/dl and packed red blood cells transfusion was ordered. Pretransfusion tests demonstrated A1B group with D positive on forward grouping. Reverse grouping showed a varying grade of agglutination with A, B, and O cells. Agglutination being stronger at 4°C. Antibody screening showed pan-agglutination, direct Coomb's test and auto control were negative. The serum reacted with adult O cells (OIadult but not with adult Bombay cells (Oh Iadult or O cord (Oicord cells. A possibility of a compound cold antibody anti IH was made and A1B compatible cells were transfused to the patient. This case report illustrates anti-IH cold agglutinin with broad thermal amplitude. Uniqueness of this case report was O group incompatibility with A1B group, which was detected earlier and a catastrophic transfusion reaction being subverted.

  16. Anti-diarrheal constituents of Alpinia oxyphylla.

    Science.gov (United States)

    Zhang, Junqing; Wang, Sheng; Li, Yonghui; Xu, Peng; Chen, Feng; Tan, Yinfeng; Duan, Jinao

    2013-09-01

    Isolation, screening and in vivo assays have been used for evaluating anti-diarrhea bioactive of Alpinia oxyphylla. Preliminary experimental results showed that 95% ethanol extract and 90% ethanol elution significantly extended the onset time of diarrhea and reduced the wet feces proportion, however 50% ethanol election had no effect on diarrhea. Chemical analysis results displayed that Nootkatone, Tectochrysin and yakuchinone A may be bioactive ingredients for curing diarrhea. Duodenum in vitro experiment showed that Tectochrysin 50, 100 μM reduces carbachol-induced contraction, while yakuchinone A and Nootkatone had no effect. Bioinformatic computational method as molecular docking has been complementary to experimentally work to explore the potential mechanism. The study of pathogenesis of diarrhea in humans and animal models suggested that Na(+)/H(+) exchanger3 (NHE3) and aquaporin4 (AQP4) are causative agents of diarrhea. The analysis was done on the basis of scoring and binding ability and the docking analysis showed that Tectochrysin has maximum potential against NHE3 (PDB ID: 2OCS) and AQP4 (PDB ID: 3GD8). Tectochrysin indicated minimum energy score and the highest number of interactions with active site residues. These results suggested that A. oxyphylla might exhibit its anti-diarrhea effect partially by affecting the proteins of NHE3 and AQP4 with its active ingredient Tectochrysin. PMID:23583435

  17. Oral anti-diabetics in Ramadan.

    Science.gov (United States)

    Islam, Najmul

    2015-05-01

    A large proportion of Muslim patients with type 2 diabetes fast during the month of Ramadan worldwide. Hypoglycaemia is one of the major complications associated with long periods without food during the fasting hours. There is also a risk of hyperglycaemia due to over indulgence in food during the two main meals of Suhur and Iftar. Healthcare providers need to be cognizant of the risk of fasting and be competent to provide Ramadan adjusted diabetes care particularly adjustment of oral anti diabetics. This review article has taken into consideration observational studies, randomized trial data, pathophysiology and practical experience in recommending adjustment in oral anti-diabetics during fasting in type-2 diabetics. Metformin and Thiazolidinediones (TZD'S) being insulin sensitizers need minimum adjustment with low risk of hypoglycaemia. Older generation Sulphonylureas (SU) pose a high risk of hypoglycaemia but the newer generations of Sulphonylureas have a reasonable safety profile. Alpha- Glucosidase inhibitors are safe during fasting but their use is limited due to the side effects. PMID:26013783

  18. Nonsteroid Anti-inflammatory Drugs and Kidney

    Directory of Open Access Journals (Sweden)

    Yaşar Yıldırım1

    2016-03-01

    Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs are often used in the treatment of chronic and acute pain and inflammation as an analgesic and anti-inflammatory agent. They inhibit the synthesis of prostaglandins which have influence on glomerular capillaries, vasa recta and tubular functions. They lead to significant complications such as hyperkalemia, hyponatremia, edema and hypertension. Usage of NSAIDs is a risk factor for acute kidney injury in some conditions such as advanced age, dehydration, vomiting, diuretics, ACE/ARB therapy, heart failure, nephrotic syndrome, cirrhosis and chronic kidney disease. Acute interstitial nephritis is not dependent on the drug dose and it is characterized by immunological inflammatory reaction and a decrease in creatinine clearance. Besides the classical findings, glomerules can be involved and minimal change disease or membranous glomerulonephritis can develop. Analgesic nephropathy is characterized by interstitial nephritis and papillary necrosis. Metabolites of NSAIDs are accumulated in renal medulla which has lowest oxygen pressure in kidney and they disrupt the renal parencymal perfusion by vasoconstriction. Respectively, papillar necrosis, glomerular sclerosis, interstitial fibrosis and cortical atrophy can develop insidiously.

  19. [Anti-inflammatory, analgesic and anti-pyretic activities of a non-steroidal anti-inflammatory drug, etofenamate, in experimental animals].

    Science.gov (United States)

    Nakamura, H; Motoyoshi, S; Imazu, C; Ishii, K; Yokoyama, Y; Seto, Y; Kadokawa, T; Shimizu, M

    1982-08-01

    Anti-inflammatory, analgesic, and anti-pyretic activities of orally administered etofenamate, the diethylene glycol ester of flufenamic acid, were investigated in experimental animals. Against acetic acid-induced vascular permeability in mice and ultra-violet light-induced erythema in guinea pigs, etofenamate produced a dose related inhibition at doses of 40--320 mg/kg and 5--20 mg/kg, respectively. In rats, felt-pellet-induced granuloma formation and adjuvant-induced arthritis were significantly inhibited by repeated administration of etofenamate at doses of 20 mg/kg/day for 5 days and 40 mg/kg/day for 21 days, respectively. Etofenamate showed an inhibitory activity on the squeak response caused by flexing and extending the silver nitrate-induced arthritic joint in rats; and it produced a dose related anti-writhing activity at doses of 50--300 mg/kg and 10--80 mg/kg in mice and rats, respectively, in the acetic acid-induced writhing test. Etofenamate showed a significant anti-pyretic activity at doses of 0.2 mg/kg or more. These potencies of etofenamate were 0.5 to 1.6 times those of flufenamic acid. In particular, the anti-erythema, anti-arthritis, and anti-pyretic activities of etofenamate were approximately equivalent to or superior to those of flufenamic acid. From these results, it was suggested that etofenamate given orally, like other non-steroidal anti-inflammatory drugs, showed anti-inflammatory, analgesic, and anti-pyretic activities in experimental animals. PMID:6983482

  20. A Study of Anti Beta-2 Glycoprotein I and Anti-Prothrombin Antibodies in Patients with Unexplained Recurrent Pregnancy Losses.

    Science.gov (United States)

    Singh, Angad; Nangia, Anita; Sharma, Sunita; Puri, Manju

    2016-06-01

    To compare the levels of IgG and IgM anti beta-2 glycoprotein I antibodies and IgG and IgM anti prothrombin antibodies among women with unexplained recurrent pregnancy losses and women with at least 2 live issues. To compare the prevalence of newer anti beta-2 glycoprotein I & anti prothrombin antibodies with conventional Lupus anticoagulant & anticardiolipin antibodies. 50 women with recurrent pregnancy losses & 50 matched controls were evaluated for the presence of: Lupus anticoagulant-screened by LA sensitive aPTT& DRVV and confirmatory Staclot Assay. ELISA kits were used for detecting IgG & IgM anticardiolipin, anti beta-2 glycoprotein I & anti prothrombin antibodies. 11/50 (22 %) women in study group and none in control group had circulating antiphospholipid antibodies. 2 cases (4 %) had lupus anticoagulant. 1 case (2 %) had anticardiolipin antibody & 6 cases (12 %) were positive for anti beta-2 Glycoprotein I antibody (p value = 0.027). 3 cases (6 %) had anti prothrombin antibody. All were mutually exclusive except for one. Women with recurrent pregnancy losses should be tested for anti beta-2 Glycoprotein I antibodies & anti prothrombin antibodies in addition to conventional lupus anticoagulant and anticardiolipin antibodies. This approach can decrease the incidence of SNAP (seronegative antiphospholipid syndrome) cases while establishing the true prevalence of antiphospholipid syndrome. PMID:27065583

  1. Anti-oxidative and anti-inflammatory effects of Tagetes minuta essential oil in activated macrophages

    Institute of Scientific and Technical Information of China (English)

    Parastoo Karimian; Gholamreza Kavoosi; Zahra Amirghofran

    2014-01-01

    Objective:To investigate antioxidant and anti-inflammatory effects of Tagetes minuta (T. minuta) essential oil. Methods:In the present study T. minuta essential oil was obtained from leaves of T. minuta via hydro-distillation and then was analyzed by gas chromatography-mass spectrometry. The anti-oxidant capacity of T. minuta essential oil was examined by measuring reactive oxygen, reactive nitrogen species and hydrogen peroxide scavenging. The anti-inflammatory activity of T. minuta essential oil was determined through measuring NADH oxidase, inducible nitric oxide synthase and TNF-αmRNA expression in lipopolysacharide-stimulated murine macrophages using real-time PCR. Results:Gas chromatography-mass spectrometry analysis indicated that the main components in the T. minuta essential oil were dihydrotagetone (33.86%), E-ocimene (19.92%), tagetone (16.15%), cis-β-ocimene (7.94%), Z-ocimene (5.27%), limonene (3.1%) and epoxyocimene (2.03%). The T. minuta essential oil had the ability to scavenge all reactive oxygen/reactive nitrogen species radicals with IC50 12-15 μg/mL, which indicated a potent radical scavenging activity. In addition, T. minuta essential oil significantly reduced NADH oxidase, inducible nitric oxide synthaseand TNF-αmRNA expression in the cells at concentrations of 50 μg/mL, indicating a capacity of this product to potentially modulate/diminish immune responses. Conclusions:T. minuta essential oil has radical scavenging and anti-inflammatory activities and could potentially be used as a safe effective source of natural anti-oxidants in therapy against oxidative damage and stress associated with some inflammatory conditions.

  2. Buformin exhibits anti-proliferative and anti-invasive effects in endometrial cancer cells

    Science.gov (United States)

    Kilgore, Joshua; Jackson, Amanda L; Clark, Leslie H; Guo, Hui; Zhang, Lu; Jones, Hannah M; Gilliam, Timothy P; Gehrig, Paola A; Zhou, Chunxiao; Bae-Jump, Victoria L

    2016-01-01

    Objective: Biguanides are anti-diabetic drugs that are thought to have anti-tumorigenic effects. Most pre-clinical studies have focused on metformin for cancer treatment and prevention; however, buformin may be potentially more potent than metformin. Given this, our goal was to evaluate the effects of buformin on cell growth, adhesion and invasion in endometrial cancer cell lines. Methods: The ECC-1 and Ishikawa endometrial cancer cell lines were used. Cell proliferation was assessed by MTT assay. Apoptosis and cell cycle analysis was performed by FITC Annexin V assay and propidium iodide staining, respectively. Adhesion was analyzed using the laminin adhesion assay. Invasion was assessed using the transwell invasion assay. The effects of buformin on the AMPK/mTOR pathway were determined by Western immunoblotting. Results: Buformin and metformin inhibited cell proliferation in a dose-dependent manner in both endometrial cancer cell lines. IC50s were 1.4-1.6 mM for metformin and 8-150 μM for buformin. Buformin induced cell cycle G1 phase arrest in the ECC-1 cells and G2 phase arrest in the Ishikawa cells. For both ECC-1 and Ishikawa cells, treatment with buformin resulted in induction of apoptosis, reduction in adhesion and invasion, activation of AMPK and inhibition of phosphorylated-S6. Buformin potentiated the anti-proliferative effects of paclitaxel in both cell lines. Conclusion: Buformin has significant anti-proliferative and anti-metastatic effects in endometrial cancer cells through modulation of the AMPK/mTOR pathway. IC50 values were lower for buformin than metformin, suggesting that buformin may be more potent for endometrial cancer treatment and worthy of further investigation. PMID:27398153

  3. Pre-Stressed Rope Reinforced Anti-Sliding Pile

    Institute of Scientific and Technical Information of China (English)

    XU Jun; WANG Chenghua

    2006-01-01

    Pre-stressed rope reinforced anti-sliding pile is a composite anti-sliding structure. It is made up of pre-stressed rope and general anti-sliding pile. It can bring traditional anti-sliding pile's retaining performance into full play, and to treat with landslide fast and economically. The difference between them is that the pre-stressed rope will transfix the whole anti-sliding pile through a prearranged pipe in this structure. The working mechanics, the design method and economic benefit are studied. The results show that the pre-stressed rope reinforced anti-sliding pile can treat with the small and middle landslides or high slopes well and possess the notable advantage of technology and economic.

  4. Test Production of Anti-Corrosive Paint in Laboratory Scale

    International Nuclear Information System (INIS)

    The main purpose of this project is to produce the anti-corrosive paint in laboratory scale. In these experiments, local raw materials, natural resin (shellac), pine oil, turpentine and ethyl alcohol wer applied basically. Laboratory trials were undrtaken to determine the suitablity of raw materials ane their composition for anti-corrosive paint manufacture.The results obtained show that the anti-corrosive paint from experiment No.(30) is suitable for steel plate and this is also considered commercially economics

  5. Anti-aging cosmetics and its efficacy assessment methods

    Science.gov (United States)

    Li, Xiang

    2015-07-01

    The mechanisms of skin aging, the active ingredients used in anti-aging cosmetics and evaluation methods for anti-aging cosmetics were surmised in this paper. And the mechanisms of skin aging were introduced in the intrinsic and extrinsic ways. Meanwhile, the anti-aging cosmetic active ingredients were classified in accordance with the mechanism of action. Various evaluation methods such as human evaluation, in vitro evaluation were also summarized.

  6. Israel-criticism and modern anti-Semitism

    OpenAIRE

    Kempf, Wilhelm

    2009-01-01

    After the Third Reich was defeated, the expression of openly anti-Semitic attitudes was, to be sure, discredited in the German public, but anti-Semitism did not, however, disappear entirely. It was instead camouflaged in various ways, and even found socially and politically compatible expression in the criticism of Israeli Palestine policy.Previous research in this area gives evidence that modern anti-Semitism represents a complex formation constituted from a variety of facets which range fro...

  7. Topical anti-inflammatory activity of yacon leaf extracts

    OpenAIRE

    Rejane B. Oliveira; Daniela A. Chagas-Paula; Adriana Secatto; Thaís H. Gasparoto; Faccioli, Lúcia H.; Campanelli, Ana P.; Fernando B. Da Costa

    2013-01-01

    Smallanthus sonchifolius (Poepp.) H. Rob. , Asteraceae, known as yacon, is an herb that is traditionally used for the treatment of diabetes in folk medicine. However, recent studies have demonstrated that this plant has other interesting properties such as anti-microbial and anti-inflammatory actions. Thus, the purpose of this study was to evaluate the topical anti-inflammatory property of different extracts prepared from yacon leaves and analyze the role of different chemical classes in this...

  8. Lectins with Anti-HIV Activity: A Review

    OpenAIRE

    Ouafae Akkouh; Tzi Bun Ng; Senjam Sunil Singh; Cuiming Yin; Xiuli Dan; Yau Sang Chan; Wenliang Pan; Randy Chi Fai Cheung

    2015-01-01

    Lectins including flowering plant lectins, algal lectins, cyanobacterial lectins, actinomycete lectin, worm lectins, and the nonpeptidic lectin mimics pradimicins and benanomicins, exhibit anti-HIV activity. The anti-HIV plant lectins include Artocarpus heterophyllus (jacalin) lectin, concanavalin A, Galanthus nivalis (snowdrop) agglutinin-related lectins, Musa acuminata (banana) lectin, Myrianthus holstii lectin, Narcissus pseudonarcissus lectin, and Urtica diocia agglutinin. The anti-HIV al...

  9. The Role of Functional Foods in Cutaneous Anti-aging

    OpenAIRE

    Cho, Soyun

    2014-01-01

    Oral supplementation of micronutrients, or functional foods, to prevent aging has gained much attention and popularity as society ages and becomes more affluent, and as science reveals the pathological mechanisms of aging. Aging of the skin combines biologic aging and extrinsic aging caused predominantly by sunlight and other environmental toxins. Anti-aging functional foods exert their influence mostly through their anti-oxidant and anti-inflammatory effects, thereby abrogating collagen degr...

  10. Multiple Mechanisms of Anti-Cancer Effects Exerted by Astaxanthin

    OpenAIRE

    Li Zhang; Handong Wang

    2015-01-01

    Astaxanthin (ATX) is a xanthophyll carotenoid which has been approved by the United States Food and Drug Administration (USFDA) as food colorant in animal and fish feed. It is widely found in algae and aquatic animals and has powerful anti-oxidative activity. Previous studies have revealed that ATX, with its anti-oxidative property, is beneficial as a therapeutic agent for various diseases without any side effects or toxicity. In addition, ATX also shows preclinical anti-tumor efficacy both i...

  11. 26 CFR 1.737-4 - Anti-abuse rule.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Anti-abuse rule. 1.737-4 Section 1.737-4...) INCOME TAXES Distributions by A Partnership § 1.737-4 Anti-abuse rule. (a) In general. The rules of... all the facts and circumstances. See § 1.704-4(f) for an anti-abuse rule and examples in the...

  12. Paroxetine versus other anti-depressive agents for depression

    OpenAIRE

    Cipriani, Andrea; Furukawa, Toshi A.; Veronese, Antonio; Watanabe, Norio; Churchill, Rachel; McGuire, Hugh; Barbui, Corrado

    2007-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the efficacy of paroxetine in comparison with other anti-depressive agents in alleviating the acute symptoms of major depressive disorder.To review acceptability of treatment with paroxetine in comparison with other anti-depressive agents.To investigate the adverse effects of paroxetine in comparison with other anti-depressive agents.

  13. Anti-viral RNA silencing: do we look like plants ?

    OpenAIRE

    Lecellier Charles-Henri; Saumet Anne

    2006-01-01

    Abstract The anti-viral function of RNA silencing was first discovered in plants as a natural manifestation of the artificial 'co-suppression', which refers to the extinction of endogenous gene induced by homologous transgene. Because silencing components are conserved among most, if not all, eukaryotes, the question rapidly arose as to determine whether this process fulfils anti-viral functions in animals, such as insects and mammals. It appears that, whereas the anti-viral process seems to ...

  14. Human rights orientation and modern anti-Semitism

    Directory of Open Access Journals (Sweden)

    Johannes Kopf-Beck

    2011-04-01

    Full Text Available The manifestations of anti-Semitism in Germany have changed since the end of WWII. Whereas in the past German anti-Semitism was overtly racist, today it is characterized more by subtle and latent facets. How are these modern facets, such as secondary anti-Semitism, latent anti-Semitism and anti-Semitic criticism of Israel, related to human rights orientations? A survey of experts and a pre-study provided the basis for developing the Human Rights Orientation Scale, which includes the four subscales of Endorsement, Application, Restriction and Willingness to engage in human rights activity. In a study of 304 German subjects, data was collected on human rights orientations and facets of modern anti-Semitism. The present paper introduces the questionnaire, discusses the relevance of the study for determining the relationships between human rights orientations and facets of modern anti-Semitism and summarizes the study's implications for viewing secondary anti-Semitism and prejudicial criticism of Israel as facets of modern anti-Semitism.

  15. Antička naselja uz rijeku Savu

    OpenAIRE

    Buzov, Marija

    2011-01-01

    Za proučavanje razvoja antičkih gradova kao i antičkog urbanizma od presudne su važnosti antički materijalni ostaci, spisi starijih pisaca, pregled starih katastarskih mapa i planova, zračni snimci koji nam u postupku inspekcije i rekognosciranja mogu poslužiti za prepoznavanje i identifikaciju starih naselja. Urbanizam antičkog grada znači proučavati njegov život, a arheologija svojim sredstvima prati taj razvitak, datira nalaze, uočava i konstatira promjene gdje je to moguće, registrira ino...

  16. Anti-Dumping Procedures In The Eurasec Customs Union

    OpenAIRE

    Alexander A. Yalbulganov

    2014-01-01

    The creation of the EurAsEC Customs Union and Russia’s ascension into the WTO has led to a radical change in Russia’s anti-dumping legislation. Anti-dumping regulation ceased to fall under national jurisdiction and was transferred to the Eurasian Economic Commission, a supranational regulator. This article analyzes the new anti-dumping legislation of the EurAsEC Customs Union, anti-dumping procedures, their principles, participants, and main stages, as well as the legal treatment of informati...

  17. Terrorism, Anti-Terrorism, and the Copycat Effect

    DEFF Research Database (Denmark)

    Jensen, Thomas

    an increase in anti-terrorism makes it more likely that cells will plan small rather than large attacks. Furthermore, we see that an increase in anti-terrorism can make a terrorist attack more likely. Analyzing the problem of optimal anti-terrorism we see that the introduction of a copycat effect...... rationalizes an increase in the level of anti-terrorism after a large attack. Using this result we show how the copycat effect changes the dynamic pattern of terrorism attacks and what the long run consequences are...

  18. Anti-D prophylaxis: past, present and future.

    Science.gov (United States)

    de Haas, M; Finning, K; Massey, E; Roberts, D J

    2014-02-01

    The new British Committee for Standards in Haematology (BCSH) guidelines for the use of anti-D immunoglobulin in pregnancy provide a welcome clarification of the use of anti-D in ectopic pregnancy and after red cell salvage during caesarean section, of dosing with different preparations and distinguishing non-immune and immune anti-D. The routine use of anti-D prophylaxis (RAADP) to prevent Rhesus (Rh) D alloimmunisation during the third trimester is well established and requires careful and well-audited local implementation to achieve the maximum public health benefit. In the UK, such scrutiny may be provided by the reporting of failed anti-D prophylaxis at women who have produced an immune anti-D that is detectable for the first time in the current pregnancy through the voluntary Serious Hazards of Transfusion reporting scheme (SHOT). Application of fetal RHD genotyping would avoid giving anti-D to RhD negative women carrying an RhD negative fetus. RAADP is directed by fetal RHD genotyping in some countries in Northern Europe led by the Netherlands and Denmark. The economic case for RAADP directed by fetal RHD genotyping needs to be carefully evaluated and in England is under consideration by National Institute for Health and Clinical Excellence (NICE). Possible future developments include the use of monoclonal anti-D preparations, now in advanced clinical trials, and also testing the hypothesis that directed RAADP from early in the second trimester may further reduce anti-D immunisation. PMID:25121157

  19. Yeast killer toxin-like anti-idiotypic antibodies.

    OpenAIRE

    POLONELLI, L.; Morace, G

    1988-01-01

    Anti-idiotypic antibodies (anti-Ids) were raised in a rabbit against a murine monoclonal antibody (MAb) neutralizing the yeast killer toxin produced by a strain of Pichia (Hansenula) anomala. In an immunodiffusion test, the anti-Ids produced in the rabbit recognized the antigen-binding site of the MAb used as the immunogen (KT4) but not that of another heterologous MAb. The absence of any significant cross-reactivity among the anti-Ids raised in a rabbit for a heterologous MAb suggested that ...

  20. How do Viruses Attack Anti-Virus Programs

    OpenAIRE

    Mishra, Umakant

    2013-01-01

    As the anti-viruses run in a trusted kernel level any loophole in the anti-virus program can enable attackers to take full control over the computer system and steal data or do serious damages. Hence the anti-virus engines must be developed with proper security in mind. The ant-virus should be able to any type of specially created executable files, compression packages or documents that are intentionally created to exploit the anti-virus weakness. Viruses are present in almost every system ev...