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Sample records for anti cd-20 c2b8

  1. High-dose myeloablative versus conventional low-dose radioimmunotherapy (RIT) of mantle cell lymphoma (MCL) with the chimeric anti-CD20 antibody C2B8

    International Nuclear Information System (INIS)

    Behr, T.M.; Gotthardt, M.; Schipperm, M.L.; Gratz, S.; Behe, M.P.; Brittinger, G.; Woermann, B.; Becker, W.

    2002-01-01

    CD20 has been used as target molecule for low-dose as well as high-dose, myeloablative RIT of B-cell NHL. MCL is an especially aggressive, prognostically unfavorable form of B-cell NHL. The aim of this study was to investigate whether high-dose, myeloablative RIT with the 131 I-labeled chimeric anti-CD20 antibody C2B8 (rituxan, Mabthera, Roche) may be therapeutically more effective than conventional low-dose therapy in MCL. A total of twelve patients with chemorefractory or relapsed mantle cell lymphoma were studied so far (all of them having relapsed after high-dose chemotherapy, seven of them combined with 12 Gy TBI). A diagnostic-dosimetric study was performed with 10 mCi of 131 I-C2B8 at a protein dose of 2.5 mg/kg. In case of splenic pooling, the protein dose was increased until a more 'favorable' biodistribution was obtained. Therapy was performed with conventional (30-75 mCi; n=4) or myeloablative activities (261-515 mCi; n=8) of 131 I-C2B8 at the previously optimized protein dose, aiming at whole-body doses of ≤ 0.8 Gy (for low-dose RIT) or lung doses of ≤ 27 Gy (for high-dose RIT). Clinical follow-up was obtained for up to 42 months. Overall, in 11 patients the 2.5 mg/kg protein dose was used, whereas in one patient with marked splenomegaly, 10 mg/kg were necessary to overcome the splenic antigenic sink. In the high-dose patients, non-hematologic toxicity was restricted to mild to moderate nausea, fever, transient bilirubin or liver enzyme elevations. Despite thyroid blocking, 6/8 high-dose (in contrast to 0/4 low-dose) patients developed hypothyroidism, requiring thyroxine substitution at 6-18 months after RIT. The response rate in the low-dose arm was only 1(PR)/4, whereas 7/8 high-dose patients experienced complete and the remainder a partial remission. 6 high-dose patients are still in CR (one of them relapsed locally at 3 months, one systemically at 26 months after RIT), and 7 are still alive for up to 42+ months. In contrast to low-dose therapy

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

    International Nuclear Information System (INIS)

    Kang, Hye Jin; Park, Yeon Hee; Kim, Sung Eun and others

    2005-01-01

    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∼70 mg) immediately prior to administration of therapeutic dose (51.4∼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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. [{sup 177}Lu]DOTA-anti-CD20: Labeling and pre-clinical studies

    Energy Technology Data Exchange (ETDEWEB)

    Audicio, Paola F., E-mail: paudicio@cin.edu.u [Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo (Uruguay); Castellano, Gustavo, E-mail: gcas@famaf.unc.edu.a [FaMAF, Universidad Nacional de Cordoba, Ciudad Universitaria, 5016 Cordoba (Argentina); Tassano, Marcos R.; Rezzano, Maria E.; Fernandez, Marcelo [Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo (Uruguay); Riva, Eloisa [Clinica Hematologica ' Prof. Dra. L. Diaz' , Hospital de Clinicas. Av. Italia. sn, Montevideo (Uruguay); Robles, Ana; Cabral, Pablo; Balter, Henia; Oliver, Patricia [Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo (Uruguay)

    2011-07-15

    Anti-CD20 (Rituximab), a specific chimeric monoclonal antibody used in CD20-positive Non-Hodgkin's Lymphoma, was conjugated to a bifunctional quelate (DOTA) and radiolabeled with {sup 177}Lu through a simple method. [{sup 177}Lu]-DOTA-anti-CD20 was obtained with a radiochemical purity higher than 97%, and showed good chemical and biological stability, maintaining its biospecificity to CD20 antigens. Monte Carlo simulation showed high doses deposited on a spheroid tumor mass model. This method seems to be an appropriate alternative for the production of [{sup 177}Lu]-DOTA-anti-CD20 as therapeutic radiopharmaceutical.

  5. 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)

    Torres G, E.

    2007-01-01

    The purpose of this investigation was to prepare 131 I-anti-CD20 and 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 131 I-anti-CD20 and 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. 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 188 Re-anti-CD20, 125 I-anti-CD20 (positive control) and 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. 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 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 188 Re-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

  6. 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

    Energy Technology Data Exchange (ETDEWEB)

    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

  7. 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

    Energy Technology Data Exchange (ETDEWEB)

    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 healthy organs. The absorbed dose

  8. Compartmental and dosimetric studies of anti-CD20 labelled with {sup 188}Re; Estudo compartimental e dosimetrico do Anti-CD20 marcado com {sup 188}Re

    Energy Technology Data Exchange (ETDEWEB)

    Kuramoto, Graciela Barrio

    2016-10-01

    The radioimmunotherapy (RIT) uses MAbs conjugated to radionuclides α or β{sup -} emitters, both for therapy. Your treatment is based on the irradiation and tumor destruction, preserving the normal organs as the excess radiation. Radionuclides β{sup -} emitters as {sup 131}I, {sup 90}Y, {sup 188}Re {sup 177}Lu and are useful for the development of therapeutic radiopharmaceuticals and, when coupled with MAb and Anti-CD20 it is important mainly for the treatment of non-Hodgkin's lymphomas (NHL). {sup 188}Re (E{sub β} = 2.12 MeV; E{sub γ} = 155 keV; t1/2 = 16.9 h) is an attractive radionuclide for RIT. However, {sup 188}Re can be obtained from a radionuclide generator of {sup 188}W/{sup 188}Re, commercially available, making it convenient for use in research and for clinical routine. The CR of IPEN has a project aimed at the production of radiopharmaceutical {sup 188}Re-Anti-CD20, where the radionuclide can be obtained from a generator system {sup 188}W/{sup 188}Re. With this proposed a study to assess the efficiency of this labeling technique for treatment in accordance compartmental and dosimetry. The objective of this study was to compare the marking of anti-CD20 MAb with {sup 188}Re with the marking of the antibody with {sup 90}Y, {sup 131}I, {sup 177}Lu and {sup 99m}Tc (for their similar chemical characteristics) and {sup 211}At, {sup 213}Bi, {sup 223}Ra and {sup 225}Ac); through the study of labeling techniques reported in literature, the proposal of a compartmental model to evaluate its pharmacokinetic and dosimetric studies, high interest for therapy. The result of the study shows a favorable kinetics for {sup 188}Re, by their physical and chemical characteristics compared to the other evaluated radionuclides. The compartment proposed study describes the metabolism of {sup 188}Reanti- CD20 through a compartment mammillary model, which by their pharmacokinetic analysis, performed compared to products emitters β{sup -131}I-labeled anti CD20, {sup 177

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  10. N-glycan engineering of a plant-produced anti-CD20-hIL-2 immunocytokine significantly enhances its effector functions.

    Science.gov (United States)

    Marusic, Carla; Pioli, Claudio; Stelter, Szymon; Novelli, Flavia; Lonoce, Chiara; Morrocchi, Elena; Benvenuto, Eugenio; Salzano, Anna Maria; Scaloni, Andrea; Donini, Marcello

    2018-03-01

    Anti-CD20 recombinant antibodies are among the most promising therapeutics for the treatment of B-cell malignancies such as non-Hodgkin lymphomas. We recently demonstrated that an immunocytokine (2B8-Fc-hIL2), obtained by fusing an anti-CD20 scFv-Fc antibody derived from C2B8 mAb (rituximab) to the human interleukin 2 (hIL-2), can be efficiently produced in Nicotiana benthamiana plants. The purified immunocytokine (IC) bearing a typical plant protein N-glycosylation profile showed a CD20 binding activity comparable to that of rituximab and was efficient in eliciting antibody-dependent cell-mediated cytotoxicity (ADCC) of human PBMC against Daudi cells, indicating its fuctional integrity. In this work, the immunocytokine devoid of the typical xylose/fucose N-glycosylation plant signature (IC-ΔXF) and the corresponding scFv-Fc-ΔXF antibody not fused to the cytokine, were obtained in a glyco-engineered ΔXylT/FucT N. benthamiana line. Purification yields from agroinfiltrated plants amounted to 20-35 mg/kg of leaf fresh weight. When assayed for interaction with FcγRI and FcγRIIIa, IC-ΔXF exhibited significantly enhanced binding affinities if compared to the counterpart bearing the typical plant protein N-glycosylation profile (IC) and to rituximab. The glyco-engineered recombinant molecules also exhibited a strongly improved ADCC and complement-dependent cytotoxicity (CDC). Notably, our results demonstrate a reduced C1q binding of xylose/fucose carrying IC and scFv-Fc compared to versions that lack these sugar moieties. These results demonstrate that specific N-glycosylation alterations in recombinant products can dramatically affect the effector functions of the immunocytokine, resulting in an overall improvement of the biological functions and consequently of the therapeutic potential. © 2017 Wiley Periodicals, Inc.

  11. 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...

  12. Radiolabeling of anti-CD20 with Re0-188: liquid kit

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Carla Roberta; Osso Junior, Joao Alberto [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)]. E-mail: carlarobertab@yahoo.com.br; jaosso@ipen.br

    2007-07-01

    Radioimmunotherapy uses the targeting features of monoclonal antibody to deliver radiation from an attached radionuclide. The radionuclide {sup 188}Re is currently produced from the father nuclide {sup 188}W through a transportable generator system. Because of its easy availability and suitable nuclear properties (E{sub {beta}}{sub MAX} =2.1 MeV, t{sub 1/2}=16.9 h, E{sub {gamma}}=155 keV), this radionuclide is considered an attractive candidate for application as therapeutic agents and could be conveniently utilized for imaging and dosimetric purposes. The objective of this work is the optimization of radiolabeling of anti-CD20 with {sup 188}Re using a liquid formulation. Anti-CD20 was reduced by incubation with 2-ME and purified over a PD-10 column. The number of resulting free SH was assayed with Ellman's reagent. Optimization of radiolabeling was achieved by varying parameters: antibody mass, reducing agent, reaction time and {sup 188}Re volume in the liquid kit. Radiochemical purity of {sup 188}Re-anti-CD20 was evaluated. An average of 12 SH groups per mol in the reductions was found. The best labeling efficiency (> 93%) was achieved in the following conditions: 1 mg anti-CD20; 82.8 mg sodium tartrate; 1 mg SnCl{sub 2}; 0.25 mg gentisic acid, 1 mL {sup 188}Re and reaction time of 1 hour at room temperature. (author)

  13. Radiolabeling of anti-CD20 with Re0-188: liquid kit

    International Nuclear Information System (INIS)

    Dias, Carla Roberta; Osso Junior, Joao Alberto

    2007-01-01

    Radioimmunotherapy uses the targeting features of monoclonal antibody to deliver radiation from an attached radionuclide. The radionuclide 188 Re is currently produced from the father nuclide 188 W through a transportable generator system. Because of its easy availability and suitable nuclear properties (E βMAX =2.1 MeV, t 1/2 =16.9 h, E γ =155 keV), this radionuclide is considered an attractive candidate for application as therapeutic agents and could be conveniently utilized for imaging and dosimetric purposes. The objective of this work is the optimization of radiolabeling of anti-CD20 with 188 Re using a liquid formulation. Anti-CD20 was reduced by incubation with 2-ME and purified over a PD-10 column. The number of resulting free SH was assayed with Ellman's reagent. Optimization of radiolabeling was achieved by varying parameters: antibody mass, reducing agent, reaction time and 188 Re volume in the liquid kit. Radiochemical purity of 188 Re-anti-CD20 was evaluated. An average of 12 SH groups per mol in the reductions was found. The best labeling efficiency (> 93%) was achieved in the following conditions: 1 mg anti-CD20; 82.8 mg sodium tartrate; 1 mg SnCl 2 ; 0.25 mg gentisic acid, 1 mL 188 Re and reaction time of 1 hour at room temperature. (author)

  14. Development of a lyophilized formulation for preparing the radiopharmaceutical 177Lu-DOTA-Anti-CD20

    International Nuclear Information System (INIS)

    Serrano E, L. A.

    2015-01-01

    The radiolabeled proteins are molecules of interest in nuclear medicine for their diagnostic and therapeutic application in cancer. Antibodies, such as chimeric monoclonal antibody Anti-CD20 rituximab, have established themselves as suitable vectors of radionuclides (e.g. 177 Lu) , introducing high affinity by the surface antigens over- expressed and widely distributed in cells involved in certain diseases. The aim of this work was to design, optimize and document the production process of radiopharmaceutical 177 Lu-DOTA-Anti-CD20 for sanitary registration request to the Comision Federal para la Proteccion contra Riesgos Sanitarios (COFEPRIS). First, a raw material analysis using the Ft-Mir technique and gamma spectrometry was performed. Then, was carried out the development of the lyophilized formulation for the preparation of 177 Lu-DOTA-Anti-CD20, in which an ANOVA was performed where the dependent variable was the radiochemical purity. The optimal pharmaceutical formulation was: 5 mg DOTA-CD20 and 80 mg Mannitol to be reconstituted with 1 m L of acetate buffer 0.25 M, ph 7, with an incubation time of 15 min at 37 degrees Celsius in a dry bath. Once completed the development of the lyophilized formulation, we proceeded to the optimization of the production process, development and validation of the analytical method. Three batches were prepared under protocols of Good Manufacturing Practice, which met pre-established specifications as sterile and endotoxin-free of bacterial formulations, with greater that 95% of radiochemical purity. Currently, is conducting the study of shelf stability. Upon completion of the stability studies, the legal record of 177 Lu-DOTA-Anti-CD20 will be integrated with documented evidence of the quality and stability of the formulation of this radiopharmaceutical. (Author)

  15. Compartmental and dosimetric studies of anti-CD20 labelled with 188Re

    International Nuclear Information System (INIS)

    Kuramoto, Graciela Barrio

    2016-01-01

    The radioimmunotherapy (RIT) uses MAbs conjugated to radionuclides α or β - emitters, both for therapy. Your treatment is based on the irradiation and tumor destruction, preserving the normal organs as the excess radiation. Radionuclides β - emitters as 131 I, 90 Y, 188 Re 177 Lu and are useful for the development of therapeutic radiopharmaceuticals and, when coupled with MAb and Anti-CD20 it is important mainly for the treatment of non-Hodgkin's lymphomas (NHL). 188 Re (E β = 2.12 MeV; E γ = 155 keV; t1/2 = 16.9 h) is an attractive radionuclide for RIT. However, 188 Re can be obtained from a radionuclide generator of 188 W/ 188 Re, commercially available, making it convenient for use in research and for clinical routine. The CR of IPEN has a project aimed at the production of radiopharmaceutical 188 Re-Anti-CD20, where the radionuclide can be obtained from a generator system 188 W/ 188 Re. With this proposed a study to assess the efficiency of this labeling technique for treatment in accordance compartmental and dosimetry. The objective of this study was to compare the marking of anti-CD20 MAb with 188 Re with the marking of the antibody with 90 Y, 131 I, 177 Lu and 99m Tc (for their similar chemical characteristics) and 211 At, 213 Bi, 223 Ra and 225 Ac); through the study of labeling techniques reported in literature, the proposal of a compartmental model to evaluate its pharmacokinetic and dosimetric studies, high interest for therapy. The result of the study shows a favorable kinetics for 188 Re, by their physical and chemical characteristics compared to the other evaluated radionuclides. The compartment proposed study describes the metabolism of 188 Reanti- CD20 through a compartment mammillary model, which by their pharmacokinetic analysis, performed compared to products emitters β -131 I-labeled anti CD20, 177 Luanti- CD20, the γ emitter 99m Tc-Anti-CD20 and α emitter 211 At-Anti-CD20 presented a elimination constant of approximately 0.05 hours

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

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Chia-Yen; Chen, Gregory J.; Tai, Pei-Han; Yang, Yu-Chen [Institute of Biologics, Development Center for Biotechnology, New Taipei City, Taiwan (China); Hsu, Yu-Shen, E-mail: yshsu@advagene.com.tw [Laboratory of Biopharmaceutical Research, Advagene Biopharma, Taipei, Taiwan (China); Chang, Mingi, E-mail: mingi.chang@advagene.com.tw [Laboratory of Biopharmaceutical Research, Advagene Biopharma, Taipei, Taiwan (China); Hsu, Chuan-Lung, E-mail: fabio@dcb.org.tw [Institute of Biologics, Development Center for Biotechnology, New Taipei City, Taiwan (China)

    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. - Highlights: • A bispecific antibody (bsAb) can increase immunotherapeutic efficacy. • A tetravalent bsAb with binding specificity for the CD20 and CD3 antigens is proposed. • A linker-hinge domain (LHD) within the bsAb results in improved antibody properties.

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

    International Nuclear Information System (INIS)

    Pantoja H, I.E.

    2004-01-01

    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 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

  18. Anti-CD20 B-cell depletion enhances monocyte reactivity in neuroimmunological disorders

    Directory of Open Access Journals (Sweden)

    Hohlfeld Reinhard

    2011-10-01

    Full Text Available Abstract Background Clinical trials evaluating anti-CD20-mediated B-cell depletion in multiple sclerosis (MS and neuromyelitis optica (NMO generated encouraging results. Our recent studies in the MS model experimental autoimmune encephalomyelitis (EAE attributed clinical benefit to extinction of activated B-cells, but cautioned that depletion of naïve B-cells may be undesirable. We elucidated the regulatory role of un-activated B-cells in EAE and investigated whether anti-CD20 may collaterally diminish regulatory B-cell properties in treatment of neuroimmunological disorders. Methods Myelin oligodendrocyte glycoprotein (MOG peptide-immunized C57Bl/6 mice were depleted of B-cells. Functional consequences for regulatory T-cells (Treg and cytokine production of CD11b+ antigen presenting cells (APC were assessed. Peripheral blood mononuclear cells from 22 patients receiving anti-CD20 and 23 untreated neuroimmunological patients were evaluated for frequencies of B-cells, T-cells and monocytes; monocytic reactivity was determined by TNF-production and expression of signalling lymphocytic activation molecule (SLAM. Results We observed that EAE-exacerbation upon depletion of un-activated B-cells closely correlated with an enhanced production of pro-inflammatory TNF by CD11b+ APC. Paralleling this pre-clinical finding, anti-CD20 treatment of human neuroimmunological disorders increased the relative frequency of monocytes and accentuated pro-inflammatory monocyte function; when reactivated ex vivo, a higher frequency of monocytes from B-cell depleted patients produced TNF and expressed the activation marker SLAM. Conclusions These data suggest that in neuroimmunological disorders, pro-inflammatory APC activity is controlled by a subset of B-cells which is eliminated concomitantly upon anti-CD20 treatment. While this observation does not conflict with the general concept of B-cell depletion in human autoimmunity, it implies that its safety and

  19. Change of CD20 Expression in Diffuse Large B-Cell Lymphoma Treated with Rituximab, an Anti-CD20 Monoclonal Antibody: A Study of the Osaka Lymphoma Study Group

    Directory of Open Access Journals (Sweden)

    Naoki Wada

    2009-10-01

    Full Text Available Change of CD20 expression was examined in cases of diffuse large B-cell lymphoma (DLBCL. CD20 expression after treatment with anti-CD20 antibody (rituximab, Rx for DLBCL was examined in 23 cases who received serial biopsy by immunohistochemistry (IHC and flow cytometry (FCM. CD20– by IHC and/or FCM was defined as CD20–. Four cases were CD20– at initial biopsy but became CD20+ after chemotherapy with Rx (CH-R (group A. Recurrent tumors in three group A cases became resistant to CH-R. Initial and recurrent tumors were CD20+ before and after CH-R in 17 cases (group B. Tumors before CH-R were CD20– in two cases (group C and continued to be CD20– in one and turned CD20+ in the other with survival time after the relapse of 8 and 23 months, respectively. Evaluation of CD20 expression with immunohistochemical and flow cytometric methods is used for the prediction of responsiveness of relapsed DLBCL for CH-R.

  20. 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 natural killer cells...

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

    International Nuclear Information System (INIS)

    Perera Pintado, Alejandro; Leyva Montaña, René; Prats Capote, Anaís; Góngora Bravo, Magdiel; Alberti Ramírez, Alejandro; León, Mariela; Hernández González, Ignacio; Dorvignit, Denise

    2016-01-01

    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 90 Sr- 90 Y 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

  2. Enhanced efficacy of gemcitabine in combination with anti-CD20 monoclonal antibody against CD20+ non-Hodgkin's lymphoma cell lines in vitro and in scid mice

    Directory of Open Access Journals (Sweden)

    Jin Fang

    2005-08-01

    Full Text Available Abstract Background Despite exciting new targeted therapeutics against non-Hodgkin's lymphoma (NHL, chemotherapy remains a cornerstone of therapy. While purine nucleoside analogs have significant activity in low grade NHL, the pyrimidine nucleoside analog gemcitabine has been less extensively studied, but has important activity. Use of the anti-CD20 monoclonal antibody rituximab in combination with chemotherapy for B-NHL is becoming prevalent in clinical practice, but has not been extensively studied in pre-clinical models. Methods We have tested the activity of gemcitabine ± rituximab in vitro and in scid/human NHL xenograft models. We used two t(14;18+, CD20+ follicular B cell NHL cell lines, DoHH2 a transformed NHL line and WSU-FSCCL isolated from pleural fluid of a patient with indolent NHL. Results Gemcitabine is cytotoxic to DoHH2 and WSU-FSCCL cells in vitro, and the IC50 is 2–3 fold lower in the presence of rituximab. Apoptosis is also enhanced in the presence of rituximab. Clearance of NHL cells from ascites in scid mice is prolonged by the combination, as compared with either agent alone. Most importantly, survival of scid mice bearing human NHL cells is significantly prolonged by the combination of gemcitabine + rituximab. Conclusion Based on our pre-clinical data showing prolonged survival of mice bearing human lymphoma cell line xenografts after treatment with gemcitabine + anti-CD20 antibody, this combination, expected to have non-overlapping toxicity profiles, should be explored in clinical trials.

  3. Interactions between ibrutinib and anti-CD20 antibodies; competing effects on the outcome of combination therapy

    Science.gov (United States)

    Skarzynski, Martin; Niemann, Carsten U; Lee, Yuh Shan; Martyr, Sabrina; Maric, Irina; Salem, Dalia; Stetler-Stevenson, Maryalice; Marti, Gerald E; Calvo, Katherine R; Yuan, Constance; Valdez, Janet; Soto, Susan; Farooqui, Mohammed Z.H.; Herman, Sarah E.M.; Wiestner, Adrian

    2015-01-01

    Purpose Clinical trials of ibrutinib combined with anti-CD20 monoclonal antibodies (mAbs) for chronic lymphocytic leukemia (CLL) report encouraging results. Paradoxically, in pre-clinical studies in vitro ibrutinib was reported to decrease CD20 expression and inhibits cellular effector mechanisms. We therefore set out to investigate effects of in vivo ibrutinib treatment that could explain this paradox. Experimental Design Patients received single agent ibrutinib (420mg daily) on an investigator-initiated phase 2 trial. Serial blood samples were collected pre-treatment and during treatment for ex vivo functional assays to examine the effects on CLL cell susceptibility to anti-CD20 mAbs. Results We demonstrate that CD20 expression on ibrutinib was rapidly and persistently down-regulated (median reduction 74%, day 28, Pibrutinib were less susceptible to anti-CD20 mAb-mediated complement-dependent cytotoxicity than pre-treatment cells (median reduction 75%, Pibrutinib, providing a likely mechanism for the preserved C3d opsonization. Additionally, ibrutinib significantly inhibited trogocytosis, a major contributor to antigen loss and tumor escape during mAb therapy. Conclusions Our data indicate that ibrutinib promotes both positive and negative interactions with anti-CD20 mAbs, suggesting that successfully harnessing maximal anti-tumor effects of such combinations requires further investigation. PMID:26283682

  4. Interactions between Ibrutinib and Anti-CD20 Antibodies: Competing Effects on the Outcome of Combination Therapy.

    Science.gov (United States)

    Skarzynski, Martin; Niemann, Carsten U; Lee, Yuh Shan; Martyr, Sabrina; Maric, Irina; Salem, Dalia; Stetler-Stevenson, Maryalice; Marti, Gerald E; Calvo, Katherine R; Yuan, Constance; Valdez, Janet; Soto, Susan; Farooqui, Mohammed Z H; Herman, Sarah E M; Wiestner, Adrian

    2016-01-01

    Clinical trials of ibrutinib combined with anti-CD20 monoclonal antibodies (mAb) for chronic lymphocytic leukemia (CLL) report encouraging results. Paradoxically, in preclinical studies, in vitro ibrutinib was reported to decrease CD20 expression and inhibit cellular effector mechanisms. We therefore set out to investigate effects of in vivo ibrutinib treatment that could explain this paradox. Patients received single-agent ibrutinib (420 mg daily) on an investigator-initiated phase II trial. Serial blood samples were collected pretreatment and during treatment for ex vivo functional assays to examine the effects on CLL cell susceptibility to anti-CD20 mAbs. We demonstrate that CD20 expression on ibrutinib was rapidly and persistently downregulated (median reduction 74%, day 28, P ibrutinib were less susceptible to anti-CD20 mAb-mediated complement-dependent cytotoxicity than pretreatment cells (median reduction 75%, P ibrutinib, providing a likely mechanism for the preserved C3d opsonization. In addition, ibrutinib significantly inhibited trogocytosis, a major contributor to antigen loss and tumor escape during mAb therapy. Our data indicate that ibrutinib promotes both positive and negative interactions with anti-CD20 mAbs, suggesting that successfully harnessing maximal antitumor effects of such combinations requires further investigation. ©2015 American Association for Cancer Research.

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

    Science.gov (United States)

    Roit, Fabio Da; Engelberts, Patrick J.; 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 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 natural killer cells, and antibody-dependent cellular cytotoxicity by these cells, as well as phagocytosis by macrophages or neutrophils were inhibited by ibrutinib with a half maximal effective concentration of 0.3–3 μM. Analysis of anti-CD20 mediated activation of natural killer cells isolated from patients on continued oral ibrutinib treatment suggested that repeated drug dosing inhibits these cells in vivo. Finally we show that the phosphatidyl-4-5-biphosphate 3-kinase-δ inhibitor idelalisib similarly inhibited the immune cell-mediated mechanisms induced by anti-CD20 antibodies, although the effects of this drug at 10 μM were weaker than those observed with ibrutinib at the same concentration. We conclude that the design of combined treatment schedules of anti-CD20 antibodies with these kinase inhibitors should consider the multiple negative interactions between these two classes of drugs. PMID:25344523

  6. Anti-CD20 Cell Therapies in Multiple Sclerosis—A Fixed Dosing Schedule for Ocrelizumab is Overkill

    Directory of Open Access Journals (Sweden)

    Jagannadha Avasarala

    2017-10-01

    Full Text Available Anti-CD 20 therapies have found significant uses in multiple sclerosis (MS. Based singularly on the accumulated evidence with the use of rituximab (RTX; Rituxan, Genentech, and Biogen in neuroimmunological diseases, ocrelizumab (OCR; Ocrevus, Genentech was developed as a treatment option for MS and selectively targets CD20 B cells, a cell surface antigen found on pre-B cells, mature, and memory B cells, but not on lymphoid stem cells and plasma cells. On the basis of indirect evidence, elimination of the antigen-presenting capabilities and antigen nonspecific immune functions of B cells appear to be central to the therapeutic efficacy of anti-CD20 B-cell therapies. An important question is this—Why does the drug need to be dosed at fixed intervals and not based on a measurable endpoint, such as tracking peripheral CD20 cell counts? There is minimal scientific validity in infusing the drug every 6 months particularly if CD20 cell counts are negligible in the peripheral blood. In this analysis, a case is made for following CD19 cell populations as a surrogate for CD20 cells on a monthly basis to guide OCR redosing parameters and does not follow a scheduled dosing parameter.

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

    International Nuclear Information System (INIS)

    Dias, Carla Roberta de Barros Rodrigues

    2010-01-01

    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 ( 99m Tc) and rhenium-188 ( 188 Re) are an attractive radionuclide pair for clinical use due to their favorable decay properties for diagnosis ( 99m Tc: T 1/2 = 6 h, γ radiation = 140 keV) and therapy ( 188 Re: T 1/2 = 17 h, maximum β energy = 2.12 MeV) and to their availability in the form of 99 Mo/ 99 mTc and 188 W/ 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 188 Re using two techniques: the direct labeling method [ 188 Re(V)] and the labeling method via the carbonyl nucleus [ 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 188 Re(V), in a study of several parameters in order to reach an optimized formulation. The labeling via the carbonyl nucleus both 99 mTc and 188 Re were employed through 2 different procedures: (1) labeling of intact RTX with 99 mTc(I) and (2) reduced RTX (RTX red ) labeled with 99 mTc(I)/ 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 via carbonyl group, the results showed that the - SH groups of RTX red are a possible way of labeling

  8. Radiolabeling and Preclinical Evaluation of 131I-anti-CD20 for Non-Hodgkin's Lymphomas Therapy

    International Nuclear Information System (INIS)

    Kullaprawittaya, Usa; Khongpetch, Pranom; Ngamprayad, Tippanan; Nuanchuen, Suphatphong

    2007-08-01

    Full text: In this study, a monoclonal anti-CD20 was developed for radioimmunotherapy of non-Hodgkin's B-cell lymphoma by reacting anti-CD20 with iodine-131 using iodogen procedure. It was found that radiochemical yield was > 95 % independently of incubation time and the antibody could be conjugated with iodine-131 up to 10 mCi/mg. The radiolabeled antibody exhibited excellent retention of immunoreactivity with radio incorporations >95% for 6 hr at 4 o C. In vitro stability tests showed minimal loss of iodine-131 from the conjugate in the presence of cysteine and in human serum at 37 o C. Biodistribution study in normal ICR mice showed higher uptake by the liver, kidney and intestines but lower thyroid uptake compared to 131 I -MIBG. Biodistribution studies confirmed the in vitro stability of 131 I -anti-CD20. In particular, excellent in vivo retention of iodine-131 was demonstrated by lower thyroid accumulation over 48 hr. A favorable biological distribution of 131 I -anti-CD20 suggests this radiopharmaceutical may be effectively used in the therapy of non-Hodgkin's lymphoma

  9. Development of a lyophilized formulation for preparing the radiopharmaceutical {sup 177}Lu-DOTA-Anti-CD20; Desarrollo de una formulacion liofilizada para la preparacion del radiofarmaco {sup 177}-DOTA-Anti-CD20

    Energy Technology Data Exchange (ETDEWEB)

    Serrano E, L. A.

    2015-07-01

    The radiolabeled proteins are molecules of interest in nuclear medicine for their diagnostic and therapeutic application in cancer. Antibodies, such as chimeric monoclonal antibody Anti-CD20 rituximab, have established themselves as suitable vectors of radionuclides (e.g. {sup 177}Lu) , introducing high affinity by the surface antigens over- expressed and widely distributed in cells involved in certain diseases. The aim of this work was to design, optimize and document the production process of radiopharmaceutical {sup 177}Lu-DOTA-Anti-CD20 for sanitary registration request to the Comision Federal para la Proteccion contra Riesgos Sanitarios (COFEPRIS). First, a raw material analysis using the Ft-Mir technique and gamma spectrometry was performed. Then, was carried out the development of the lyophilized formulation for the preparation of {sup 177}Lu-DOTA-Anti-CD20, in which an ANOVA was performed where the dependent variable was the radiochemical purity. The optimal pharmaceutical formulation was: 5 mg DOTA-CD20 and 80 mg Mannitol to be reconstituted with 1 m L of acetate buffer 0.25 M, ph 7, with an incubation time of 15 min at 37 degrees Celsius in a dry bath. Once completed the development of the lyophilized formulation, we proceeded to the optimization of the production process, development and validation of the analytical method. Three batches were prepared under protocols of Good Manufacturing Practice, which met pre-established specifications as sterile and endotoxin-free of bacterial formulations, with greater that 95% of radiochemical purity. Currently, is conducting the study of shelf stability. Upon completion of the stability studies, the legal record of {sup 177}Lu-DOTA-Anti-CD20 will be integrated with documented evidence of the quality and stability of the formulation of this radiopharmaceutical. (Author)

  10. 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

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

    International Nuclear Information System (INIS)

    Hassan Yousefnia; Amir Reza Jalilian; Ali Bahrami-Samani; Simindokht Shirvani-Arani; Mohammad Ghannadi-Maragheh; Azim Arbabi; Edalat Radfar

    2011-01-01

    Rituximab was successively labeled with 177 Lu-lutetium chloride. 177 Lu chloride was obtained by thermal neutron flux (4 x 1013 n cm -2 s -1 ) of natural Lu 2 O 3 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 CH 2 Cl 2 . 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 177 Lu-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)

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

    International Nuclear Information System (INIS)

    Dias, C.R.; Osso Junior, J.A.

    2008-01-01

    Radioimmunotherapy (RIT) uses target-specific monoclonal antibodies or fragments labeled with a radioactive isotope to combine humoral and radiolytic functions and has the advantage of targeting not only the cell to which the antibody is bound but also the surrounding tumor cells and microenvironment. The most successful clinical studies of RIT in patients with Non-Hodgkin's Lymphoma (NHL) have targeted CD20+ Bcell tumors. 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 ( 188 Re) is currently produced from the father nuclide 188 W through a transportable generator system. Because of its easy availability and suitable nuclear properties (E βMAX = 2.1 MeV, t1/2 = 16.9 h, E γ = 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 objective of this work is the optimization of direct radiolabeling method of anti-CD20 with 188 Re using a liquid formulation. Anti-CD20 was reduced by incubation with 2-mercaptoethanol at room temperature. The number of resulting free sulphydryl groups was assayed with Ellman's reagent. Optimization of radiolabeling was achieved by varying parameters: antibody mass, reducing agent mass, tartrate mass, stability and reaction time, 188 Re volume and activity. Radiochemical purity of 188 Re-anti-CD20 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 but further studies will be carried out in order to improve the labeling yields and consequently the specific activity of the product. (author)

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

    International Nuclear Information System (INIS)

    Miranda O, R. M.

    2014-01-01

    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

  14. 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

  15. 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 CD20

  16. Evaluation of cell cycle changes activated by the administration of {sup 177}Lu-DOTA-antiCD20; Evaluacion de cambios en el ciclo celular activados por la administracion de {sup 177}Lu-DOTA-antiCD20

    Energy Technology Data Exchange (ETDEWEB)

    Ramos B, J. C.

    2016-07-01

    In the present project, cytometric evaluation of cell cycle changes induced by the {sup 177}Lu-DOTA-antiCD20 thermostatic radiopharmaceutical was performed, in which a cell culture of Raji cells from Burkitts lymphoma were used, which are CD20+; for flow cytometry different parameters were measured in which the cells were synchronized in G0/G1 and G2/M, to calculate the dose to nucleus that were given to the cells the Monte Carlo method was used at a dose interval from 1 to 5 Gy. The purpose of this work is to be able to observe by flow cytometry the arrest in the cell cycle with a lower dose interval than the one applied in other papers. (Author)

  17. 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

  18. Evaluation of cell cycle changes activated by the administration of "1"7"7Lu-DOTA-antiCD20

    International Nuclear Information System (INIS)

    Ramos B, J. C.

    2016-01-01

    In the present project, cytometric evaluation of cell cycle changes induced by the "1"7"7Lu-DOTA-antiCD20 thermostatic radiopharmaceutical was performed, in which a cell culture of Raji cells from Burkitts lymphoma were used, which are CD20+; for flow cytometry different parameters were measured in which the cells were synchronized in G0/G1 and G2/M, to calculate the dose to nucleus that were given to the cells the Monte Carlo method was used at a dose interval from 1 to 5 Gy. The purpose of this work is to be able to observe by flow cytometry the arrest in the cell cycle with a lower dose interval than the one applied in other papers. (Author)

  19. Compartmental and dosimetric studies of anti-CD20 labeled with 188Re

    International Nuclear Information System (INIS)

    Barrio Kuramoto Graciela; Mie Nakamura Matsuda Margareth; Osso Joao Jr, Alberto

    2016-01-01

    Radioimmunotherapy has the potential to deliver lethal radiation energy directly to malignant cells via targeting of radioisotope-conjugated monoclonal antibodies (MAbs) to specific antigens. Rituximab (RTX) is specifically targeted against CD20, a surface antigen expressed by B-lymphocytes. The use of 188 Re from a 188 W/ 188 Re generator system represents an alternative radionuclide for therapy. Rhenium has chemical properties similar to technetium and 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 and pharmacokinetic studies that are also required by the Brazilian Regulatory Agency. (author)

  20. 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

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

    International Nuclear Information System (INIS)

    Forrer, Flavio; Mueller-Brand, Jan; Chen, Jianhua; Fani, Melpomeni; Powell, Pia; Maecke, Helmut R.; Lohri, Andreas; Moldenhauer, Gerhard

    2009-01-01

    131 I- and 90 Y-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 ( 177 Lu or 90 Y. 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 10 5 times excess of diethylenetriaminepentaacetic acid (DTPA, 37 C, 7 days). Two patients with relapsed NHL were treated with 740 MBq/m 2 body surface 177 Lu-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 177 Lu-DOTA-rituximab was tolerated well. Our results show that DOTA-rituximab (4:1) can be labelled with 177 Lu with sufficient stability while the immunoconjugate retains its immunoreactivity. 177 Lu-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.)

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

    International Nuclear Information System (INIS)

    Barrio, Graciela; Osso Junior, Joao A.

    2011-01-01

    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 188 W/ 188 Re generator system represents an attractive alternative radionuclide for therapy. 188 Re is produced from beta decay of the 188 W parent. In addition to the emission of high-energy electrons (Eβ= 2118 keV), 188 Re also decays with emission of a gamma photon with an energy of 155 keV in 15% abundance. Besides the therapeutic usefulness of 188 Re, the emission of gamma photon is an added advantage since the biodistribution of 188 Re-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)

  3. Dosimetric evaluation of anti-CD20 labelled with {sup 188}Re

    Energy Technology Data Exchange (ETDEWEB)

    Barrio, Graciela; Osso Junior, Joao A., E-mail: gracielabarrio@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    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 {sup 188}W/{sup 188}Re generator system represents an attractive alternative radionuclide for therapy. {sup 188}Re is produced from beta decay of the {sup 188}W parent. In addition to the emission of high-energy electrons (E{beta}= 2118 keV), {sup 188}Re also decays with emission of a gamma photon with an energy of 155 keV in 15% abundance. Besides the therapeutic usefulness of {sup 188}Re, the emission of gamma photon is an added advantage since the biodistribution of {sup 188}Re-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)

  4. B cell-targeted therapy with anti-CD20 monoclonal antibody in a mouse model of Graves' hyperthyroidism.

    Science.gov (United States)

    Ueki, I; Abiru, N; Kobayashi, M; Nakahara, M; Ichikawa, T; Eguchi, K; Nagayama, Y

    2011-03-01

    Graves' disease is a B cell-mediated and T cell-dependent autoimmune disease of the thyroid which is characterized by overproduction of thyroid hormones and thyroid enlargement by agonistic anti-thyrotrophin receptor (TSHR) autoantibody. In addition to antibody secretion, B cells have recently been recognized to function as antigen-presenting/immune-modulatory cells. The present study was designed to evaluate the efficacy of B cell depletion by anti-mouse (m) CD20 monoclonal antibody (mAb) on Graves' hyperthyroidism in a mouse model involving repeated injection of adenovirus expressing TSHR A-subunit (Ad-TSHR289). We observe that a single injection of 250 µg/mouse anti-mCD20 mAb eliminated B cells efficiently from the periphery and spleen and to a lesser extent from the peritoneum for more than 3 weeks. B cell depletion before immunization suppressed an increase in serum immunoglobulin (Ig)G levels, TSHR-specific splenocyte secretion of interferon (IFN)-γ, anti-TSHR antibody production and development of hyperthyroidism. B cell depletion 2 weeks after the first immunization, a time-point at which T cells were primed but antibody production was not observed, was still effective at inhibiting antibody production and disease development without inhibiting splenocyte secretion of IFN-γ. By contrast, B cell depletion in hyperthyroid mice was therapeutically ineffective. Together, these data demonstrate that B cells are critical not only as antibody-producing cells but also as antigen-presenting/immune-modulatory cells in the early phase of the induction of experimental Graves' hyperthyroidism and, although therapeutically less effective, B cell depletion is highly efficient for preventing disease development. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

  5. B cell-targeted therapy with anti-CD20 monoclonal antibody in a mouse model of Graves' hyperthyroidism

    Science.gov (United States)

    Ueki, I; Abiru, N; Kobayashi, M; Nakahara, M; Ichikawa, T; Eguchi, K; Nagayama, Y

    2011-01-01

    Graves' disease is a B cell-mediated and T cell-dependent autoimmune disease of the thyroid which is characterized by overproduction of thyroid hormones and thyroid enlargement by agonistic anti-thyrotrophin receptor (TSHR) autoantibody. In addition to antibody secretion, B cells have recently been recognized to function as antigen-presenting/immune-modulatory cells. The present study was designed to evaluate the efficacy of B cell depletion by anti-mouse (m) CD20 monoclonal antibody (mAb) on Graves' hyperthyroidism in a mouse model involving repeated injection of adenovirus expressing TSHR A-subunit (Ad-TSHR289). We observe that a single injection of 250 µg/mouse anti-mCD20 mAb eliminated B cells efficiently from the periphery and spleen and to a lesser extent from the peritoneum for more than 3 weeks. B cell depletion before immunization suppressed an increase in serum immunoglobulin (Ig)G levels, TSHR-specific splenocyte secretion of interferon (IFN)-γ, anti-TSHR antibody production and development of hyperthyroidism. B cell depletion 2 weeks after the first immunization, a time-point at which T cells were primed but antibody production was not observed, was still effective at inhibiting antibody production and disease development without inhibiting splenocyte secretion of IFN-γ. By contrast, B cell depletion in hyperthyroid mice was therapeutically ineffective. Together, these data demonstrate that B cells are critical not only as antibody-producing cells but also as antigen-presenting/immune-modulatory cells in the early phase of the induction of experimental Graves' hyperthyroidism and, although therapeutically less effective, B cell depletion is highly efficient for preventing disease development. PMID:21235532

  6. Characterization of a Novel Humanized Anti-CD20 Antibody with Potent Anti-Tumor Activity against Non-Hodgkin's Lymphoma

    Directory of Open Access Journals (Sweden)

    Haifeng Zhang

    2013-09-01

    Full Text Available Background: Rituximab, a mouse Fab and human Fc chimeric antibody, has been widely used to treat Non-Hodgkin's lymphoma (NHL. However, only 48% of patients respond to the treatment and complete response rate is below 10%. Also, immunogenicity was reported in 17-20% patients receiving the treatment, making it unsuitable for long term diseases such as autoimmune disorders. It has been a hot research field to “humanize” rituximab toward improved efficacy and reduced immunogenicity. Methods: In this study, an advanced antibody humanization technology was applied to the sequence of the anti-CD20 antibody 2B8, its sequence of which was based on the original murine monoclonal antibody of rituximab in Roche. The complementarity-determining regions (CDRs of the humanized antibodies were further optimized through computer-aided molecular dock. Results: Five novel humanized anti-CD20 antibodies 1-5(1635, 1534, 3637, 1634 and 1536 were generated and their immunogenicity was significantly decreased when compared to rituximab. The novel humanized anti-CD20 antibodies 1-5 retained the binding activity of their murine counterpart, as demonstrated by the fluorescence-activated cell-sorting analysis (FACS. When compared to rituximab, the humanized antibodies still have the similar properties on both complement-dependent cytotoxicity (CDC and antibody-dependent cell-mediated cytotoxicity (ADCC. Furthermore, its anti-tumor efficacy in xenograft model is comparable to that of rituximab. Conclusion: The humanized anti-CD20 antibodies 1-5 have lower immunogenicity than rituximab. And at the same time, they still retain the anti-tumor effect both in vitro and vivo.

  7. A Preclinical Population Pharmacokinetic Model for Anti-CD20/CD3 T-Cell-Dependent Bispecific Antibodies.

    Science.gov (United States)

    Ferl, Gregory Z; Reyes, Arthur; Sun, Liping L; Cheu, Melissa; Oldendorp, Amy; Ramanujan, Saroja; Stefanich, Eric G

    2018-05-01

    CD20 is a cell-surface receptor expressed by healthy and neoplastic B cells and is a well-established target for biologics used to treat B-cell malignancies. Pharmacokinetic (PK) and pharmacodynamic (PD) data for the anti-CD20/CD3 T-cell-dependent bispecific antibody BTCT4465A were collected in transgenic mouse and nonhuman primate (NHP) studies. Pronounced nonlinearity in drug elimination was observed in the murine studies, and time-varying, nonlinear PK was observed in NHPs, where three empirical drug elimination terms were identified using a mixed-effects modeling approach: i) a constant nonsaturable linear clearance term (7 mL/day/kg); ii) a rapidly decaying time-varying, linear clearance term (t ½  = 1.6 h); and iii) a slowly decaying time-varying, nonlinear clearance term (t ½  = 4.8 days). The two time-varying drug elimination terms approximately track with time scales of B-cell depletion and T-cell migration/expansion within the central blood compartment. The mixed-effects NHP model was scaled to human and prospective clinical simulations were generated. © 2018 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  8. Antigenic modulation limits the effector cell mechanisms employed by type I anti-CD20 monoclonal antibodies.

    Science.gov (United States)

    Tipton, Thomas R W; Roghanian, Ali; Oldham, Robert J; Carter, Matthew J; Cox, Kerry L; Mockridge, C Ian; French, Ruth R; Dahal, Lekh N; Duriez, Patrick J; Hargreaves, Philip G; Cragg, Mark S; Beers, Stephen A

    2015-03-19

    Following the success of rituximab, 2 other anti-CD20 monoclonal antibodies (mAbs), ofatumumab and obinutuzumab, have entered clinical use. Ofatumumab has enhanced capacity for complement-dependent cytotoxicity, whereas obinutuzumab, a type II mAb, lacks the ability to redistribute into lipid rafts and is glycoengineered for augmented antibody-dependent cellular cytotoxicity (ADCC). We previously showed that type I mAbs such as rituximab have a propensity to undergo enhanced antigenic modulation compared with type II. Here we assessed the key effector mechanisms affected, comparing type I and II antibodies of various isotypes in ADCC and antibody-dependent cellular-phagocytosis (ADCP) assays. Rituximab and ofatumumab depleted both normal and leukemic human CD20-expressing B cells in the mouse less effectively than glycoengineered and wild-type forms of obinutuzumab, particularly when human immunoglobulin G1 (hIgG1) mAbs were compared. In contrast to mouse IgG2a, hIgG1 mAbs were ineffective in ADCC assays with murine natural killer cells as effectors, whereas ADCP was equivalent for mouse IgG2a and hIgG1. However, rituximab's ability to elicit both ADCC and ADCP was reduced by antigenic modulation, whereas type II antibodies remained unaffected. These data demonstrate that ADCP and ADCC are impaired by antigenic modulation and that ADCP is the main effector function employed in vivo. © 2015 by The American Society of Hematology.

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

    International Nuclear Information System (INIS)

    Dias, Carla R.; Osso Junior, Joao A.

    2009-01-01

    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 ( 188 Re) is currently produced from the father nuclide tungsten-188 ( 188 W) through a transportable generator system. Because of its easy availability and suitable nuclear properties (EβMAX = 2.1 MeV, t 1/2 = 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 188 Re. 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 188 Re-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)

  10. Sensitive Detection of the Natural Killer Cell-Mediated Cytotoxicity of Anti-CD20 Antibodies and Its Impairment by B-Cell Receptor Pathway Inhibitors

    Directory of Open Access Journals (Sweden)

    Floyd Hassenrück

    2018-01-01

    Full Text Available The antibody-dependent cell-mediated cytotoxicity (ADCC of the anti-CD20 monoclonal antibodies (mAbs rituximab and obinutuzumab against the cell line Raji and isolated CLL cells and its potential impairment by kinase inhibitors (KI was determined via lactate dehydrogenase release or calcein retention, respectively, using genetically modified NK92 cells expressing CD16-176V as effector cells. Compared to peripheral blood mononuclear cells, recombinant effector cell lines showed substantial alloreactivity-related cytotoxicity without addition of mAbs but afforded determination of ADCC with reduced interassay variability. The cytotoxicity owing to alloreactivity was less susceptible to interference by KI than the ADCC of anti-CD20 mAbs, which was markedly diminished by ibrutinib, but not by idelalisib. Compared to rituximab, the ADCC of obinutuzumab against primary CLL cells showed approximately 30% higher efficacy and less interference with KI. Irreversible BTK inhibitors at a clinically relevant concentration of 1 μM only weakly impaired the ADCC of anti-CD20 mAbs, with less influence in combinations with obinutuzumab than with rituximab and by acalabrutinib than by ibrutinib or tirabrutinib. In summary, NK cell line-based assays permitted the sensitive detection of ADCC of therapeutic anti-CD20 mAbs against CLL cells and of the interference of KI with this important killing mechanism.

  11. Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Coiffier, Bertrand; Lepretre, Stéphane; Pedersen, Lars Møller

    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...

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

    International Nuclear Information System (INIS)

    Massicano, Adriana V.F.; Akanji, Akinkunmi G.; Santos, Josefina S.; Pujatti, Priscilla B.; Couto, Renata M.; Massicano, Felipe; Araujo, Elaine Bortoleti de

    2009-01-01

    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 177 Lu, 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 177 Lu-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 177 LuCl3 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)

  13. Evaluation of dry blood spot technique for quantification of an Anti-CD20 monoclonal antibody drug in human blood samples.

    Science.gov (United States)

    Lin, Yong-Qing; Zhang, Yilu; Li, Connie; Li, Louis; Zhang, Kelley; Li, Shawn

    2012-01-01

    To evaluate the dried blood spot (DBS) technique in ELISA quantification of larger biomolecular drugs, an anti-CD20 monoclonal antibody drug was used as an example. A method for the quantification of the anti-CD20 drug in human DBS was developed and validated. The drug standard and quality control samples prepared in fresh human blood were spotted on DBS cards and then extracted. A luminescent ELISA was used for quantification of the drug from DBS samples. The assay range of the anti-CD20 drug standards in DBS was 100-2500ng/mL. The intra-assay precision (%CV) ranged from 0.4% to 10.1%, and the accuracy (%Recovery) ranged from 77.9% to 113.9%. The inter assay precision (%CV) ranged from 5.9% to 17.4%, and the accuracy ranged from 81.5% to 110.5%. The DBS samples diluted 500 and 50-fold yielded recovery of 88.7% and 90.7%, respectively. The preparation of DBS in higher and lower hematocrit (53% and 35%) conditions did not affect the recovery of the drug. Furthermore, the storage stability of the anti-CD20 drug on DBS cards was tested at various conditions. It was found that the anti-CD20 drug was stable for one week in DBS stored at room temperature. However, it was determined that the stability was compro]mised in DBS stored at high humidity, high temperature (55°C), and exposed to direct daylight for a week, as well as for samples stored at room temperature and high humidity conditions for a month. Stability did not change significantly in samples that underwent 3 freeze/thaw cycles. Our results demonstrated a successful use of DBS technique in ELISA quantification of an anti-CD20 monoclonal antibody drug in human blood. The stability data provides information regarding sample storage and shipping for future clinical studies. It is, therefore, concluded that the DBS technique is applicable in the quantification of other large biomolecule drugs or biomarkers. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. A phase I study of PRO131921, a novel anti-CD20 monoclonal antibody in patients with relapsed/refractory CD20+ indolent NHL: correlation between clinical responses and AUC pharmacokinetics.

    Science.gov (United States)

    Casulo, Carla; Vose, Julie M; Ho, William Y; Kahl, Brad; Brunvand, Mark; Goy, Andre; Kasamon, Yvette; Cheson, Bruce; Friedberg, Jonathan W

    2014-09-01

    PRO131921 is a third-generation, humanized anti-CD20 monoclonal antibody with increased antibody-dependent cytotoxicity and complement-dependent cytotoxicity compared to rituximab. In this phase I study, PRO131921 was administered as a single agent to patients with CD20+, relapsed or refractory, indolent non-Hodgkin lymphoma (NHL) who had been treated with a prior rituximab-containing regimen. The primary aim of this study was safety and tolerability of PRO131921. The secondary aim of the study, and focus of this report, was to determine the pharmacokinetics (PK) profile of PRO131921 and establish a correlation between drug exposure and clinical efficacy. Patients were treated with PRO131921 by intravenous infusion weekly for 4 weeks and the dose was escalated based on safety in a 3+3 design. Twenty-four patients were treated with PRO131921 at doses from 25mg/m(2) to 800 mg/m(2). Analysis of PK data demonstrated a correlation between higher normalized drug exposure (normalized AUC) and tumor shrinkage (p = .0035). Also, normalized AUC levels were higher among responders and subjects displaying tumor shrinkage versus subjects progressing or showing no regression (p = 0.030). In conclusion, PRO131921 demonstrated clinical activity in rituximab-relapsed and refractory indolent NHL patients. The observation that higher normalized AUC may be associated with improved clinical responses has potential implications in future trials of monoclonal antibody-based therapies, and emphasizes the importance of early PK studies to optimize antibody efficacy. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. 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

  16. Evaluation of the cell death mechanisms activated by the radiopharmaceutical 177Lu-DOTA-anti-CD20 in a dose range of 1 to 5 Gy

    International Nuclear Information System (INIS)

    Azorin V, E.P.; Rojas C, E. L.; Martinez V, B. E.; Ramos B, J. C.; Jimenez M, N. P.; Ferro F, G.

    2016-10-01

    The radio immunotherapy with anti-CD20 antibodies significantly increases the remission rate of patients with B-cell lymphomas over expressing the CD20. The radiolabeled antibodies directed to surface antigens allow delivering scaled doses of radiation to specific targets thus limiting the dose to healthy tissue. The anti-CD20 causes cell death by two major pathways; activating the immune system to destroy malignant cells and inducing the activation of cell death pathways. The 177 Lu is a beta particle emitter (max. 0.497 MeV) with a maximum reach on soft tissue of 0.7 mm and a half-life of 6.7 days. Several clinical studies have established a maximum tolerated dose (45 m Ci/m 2 ) for 177 Lu-DOTA-rituximab, which shows a favorable clinical response without hematological toxicity. However, the molecular mechanisms of action by synergistic effect of anti-CD20 and radionuclide have not been studied. In this work was evaluated; by flow cytometry, the activation kinetics of the cell death mechanisms induced by the treatment with 177 Lu-DOTA-Anti-CD20 in non-Hodgkin (Raji) lymphoma cells. The absorbed radiation dose delivered to the cell nucleus was calculated by Monte Carlo simulation, considering the contribution of the beta emissions of the radiopharmaceutical present in the cell membrane and surrounding environment, as well as crossfire. This work shows that the application of radiation doses of 1 to 5 Gy of the radiopharmaceutical 177 Lu-DOTA-anti-CD20, are sufficient to induce cell death by apoptosis and arrest of the cell cycle. The combination of these factors (continuous delivery of radiation, activation of repair mechanisms and increased radio sensitivity) causes the acute activation of the apoptotic program resulting in significant cell death after 96 h of treatment. The temporal analysis of cell death suggests the early activation of apoptosis that is counteracted by the activation of repair processes caused by sustained irradiation, which leads to cell

  17. HPMA copolymer conjugates with reduced anti-CD20 antibody for cell-specific drug targeting. I. Synthesis and in vitro evaluation of binding efficacy and cytostatic activity

    Czech Academy of Sciences Publication Activity Database

    Etrych, Tomáš; Strohalm, Jiří; Kovář, Lubomír; Kabešová, Martina; Říhová, Blanka; Ulbrich, Karel

    2009-01-01

    Roč. 140, č. 1 (2009), s. 18-26 ISSN 0168-3659 R&D Projects: GA MŠk 1M0505; GA AV ČR IAAX00500803 Institutional research plan: CEZ:AV0Z40500505; CEZ:AV0Z50200510 Keywords : HPMA copolymers * drug delivery systems * doxorubicin * monoclonal anti-CD20 antibody * drug targeting Subject RIV: CD - Macromolecular Chemistry Impact factor: 5.949, year: 2009

  18. 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.

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

    Science.gov (United States)

    Sineh sepehr, Koushan; Baradaran, Behzad; Majidi, Jafar; Abdolalizadeh, Jalal; Aghebati, leili; Zare Shahneh, Fatemeh

    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 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. PMID:24312821

  20. The different clinical effects of anti-BLyS, anti-APRIL and anti-CD20 antibodies point at a critical pathogenic role of γ-herpesvirus infected B cells in the marmoset EAE model.

    Science.gov (United States)

    Anwar Jagessar, S; Fagrouch, Zahra; Heijmans, Nicole; Bauer, Jan; Laman, Jon D; Oh, Luke; Migone, Thi; Verschoor, Ernst J; 't Hart, Bert A

    2013-06-01

    The robust and rapid clinical effect of depleting anti-CD20 monoclonal antibodies (mAb) in multiple sclerosis (MS) demonstrates a critical pathogenic contribution of B cells. The clinical effect of anti-CD20 mAb has been replicated in a relevant preclinical MS model, experimental autoimmune encephalomyelitis (EAE) in marmoset monkeys (Callithrix jacchus). By contrast, treatment with mAbs against two essential cytokines in B cell activation growth and survival, i.e. BlyS/BAFF and APRIL, was only partially effective. All three mAbs induced depletion of CD20+ B cells from the circulation, albeit with different kinetics and based on distinct mechanisms of action. In the current study we analyzed whether the different clinical effect of anti-CD20 mAb or the anti-BLyS and anti-APRIL mAbs is due to different depletion of B cells infected with the EBV of marmosets, CalHV3. Employing a novel PCR-based assay, half of the colony of group-housed marmosets was tested positive for CalHV3 DNA in secondary lymphoid organs. The same prevalence was observed in placebo-treated monkeys. In marmosets treated with anti-CD20 mAb the load of CalHV3 DNA in lymphoid organs was substantially reduced, while this was not observed in the monkeys treated with anti-BLyS or anti-APRIL mAbs. To examine the pathogenic role of virus-transformed B cells, we infused EBV-transformed B lymphoblastic cell (BLC) lines presenting the immunodominant MOG34-56 peptide. We observed in the recipients of MOG34-56 pulsed BLC, but not in their fraternal siblings infused with non-pulsed BLC, activation of anti-MOG34-56 T cells and meningeal inflammation. Collectively, the data show that among CD20+ B cells, the herpesvirus-transformed subset has a particularly important pathogenic role in the marmoset EAE model.

  1. Unusual Closure of the Ten-Vertex Nido Cage via Alkylation: Regiospecific Synthesis of 3-Alkyl Derivatives of closo-1,2-C2B8H10

    Czech Academy of Sciences Publication Activity Database

    Bakardjiev, Mario; Štíbr, Bohumil; Tok, Oleg L.; Holub, Josef

    2018-01-01

    Roč. 57, č. 3 (2018), s. 1368-1372 ISSN 0020-1669 R&D Projects: GA ČR(CZ) GA16-01618S Institutional support: RVO:61388980 Keywords : electrophilic halogenation * nido-5,6-c2b8h12 * carboranes * decaborane * boranes * 5,6-dicarba-nido-decaborane(12) Subject RIV: CA - Inorganic Chemistry OBOR OECD: Inorganic and nuclear chemistry Impact factor: 4.857, year: 2016

  2. Subcutaneous injections of low-dose veltuzumab (humanized anti-CD20 antibody) are safe and active in patients with indolent non-Hodgkin's lymphoma.

    Science.gov (United States)

    Negrea, George O; Elstrom, Rebecca; Allen, Steven L; Rai, Kanti R; Abbasi, Rashid M; Farber, Charles M; Teoh, Nick; Horne, Heather; Wegener, William A; Goldenberg, David M

    2011-04-01

    Subcutaneous injections of anti-CD20 antibodies may offer benefits to both patients and the healthcare system for treatment of B-cell malignancies. A pilot study was undertaken to evaluate the potential for subcutaneous dosing with 2(nd) generation anti-CD20 antibody veltuzumab in patients with CD20(+) indolent non-Hodgkin's lymphoma. Patients with previously untreated or relapsed disease received 4 doses of 80, 160, or 320 mg veltuzumab injected subcutaneously every two weeks. Responses were assessed by computed tomography scans, with other evaluations including adverse events, safety laboratories, B-cell blood levels, serum veltuzumab levels, and human anti-veltuzumab antibody (HAHA) titers. Seventeen patients (14 follicular lymphoma; 13 stage III or IV disease; 5 treatment-naive) completed treatment with only occasional, mild-moderate, transient injection reactions and no other safety issues. Subcutaneous veltuzumab demonstrated a slow release pattern over several days, achieving a mean Cmax of 19, 25 and 63 μg/mL at 80, 160, and 320 mg doses for a total of 4 administrations, respectively. Depletion of circulating B cells occurred after the first injection. The objective response rate (partial responses plus complete responses plus complete responses unconfirmed) was 47% (8/17) with a complete response/complete response unconfirmed rate of 24% (4/17); 4 of 8 objective responses continued for 60 weeks or more. All serum samples evaluated for human anti-veltuzumab antibody were negative. Subcutaneous injections of low-dose veltuzumab are convenient, well tolerated, and capable of achieving sustained serum levels, B-cell depletion, and durable objective responses in indolent non-Hodgkin's lymphoma. (Clinicaltrials.gov identifier: NCT00546793).

  3. Subcutaneous injections of low-dose veltuzumab (humanized anti-CD20 antibody) are safe and active in patients with indolent non-Hodgkin’s lymphoma

    Science.gov (United States)

    Negrea, George O.; Elstrom, Rebecca; Allen, Steven L.; Rai, Kanti R.; Abbasi, Rashid M.; Farber, Charles M.; Teoh, Nick; Horne, Heather; Wegener, William A.; Goldenberg, David M.

    2011-01-01

    Background Subcutaneous injections of anti-CD20 antibodies may offer benefits to both patients and the healthcare system for treatment of B-cell malignancies. Design and Methods A pilot study was undertaken to evaluate the potential for subcutaneous dosing with 2nd generation anti-CD20 antibody veltuzumab in patients with CD20+ indolent non-Hodgkin’s lymphoma. Patients with previously untreated or relapsed disease received 4 doses of 80, 160, or 320 mg veltuzumab injected subcutaneously every two weeks. Responses were assessed by computed tomography scans, with other evaluations including adverse events, safety laboratories, B-cell blood levels, serum veltuzumab levels, and human anti-veltuzumab antibody (HAHA) titers. Results Seventeen patients (14 follicular lymphoma; 13 stage III or IV disease; 5 treatment-naive) completed treatment with only occasional, mild-moderate, transient injection reactions and no other safety issues. Subcutaneous veltuzumab demonstrated a slow release pattern over several days, achieving a mean Cmax of 19, 25 and 63 μg/mL at 80, 160, and 320 mg doses for a total of 4 administrations, respectively. Depletion of circulating B cells occurred after the first injection. The objective response rate (partial responses plus complete responses plus complete responses unconfirmed) was 47% (8/17) with a complete response/complete response unconfirmed rate of 24% (4/17); 4 of 8 objective responses continued for 60 weeks or more. All serum samples evaluated for human anti-veltuzumab antibody were negative. Conclusions Subcutaneous injections of low-dose veltuzumab are convenient, well tolerated, and capable of achieving sustained serum levels, B-cell depletion, and durable objective responses in indolent non-Hodgkin’s lymphoma. (Clinicaltrials.gov identifier: NCT00546793) PMID:21173095

  4. Cloning and molecular characterization of the cDNAs encoding the variable regions of an anti-CD20 monoclonal antibody.

    Science.gov (United States)

    Shanehbandi, Dariush; Majidi, Jafar; Kazemi, Tohid; Baradaran, Behzad; Aghebati-Maleki, Leili

    2017-01-01

    CD20-based targeting of B-cells in hematologic malignancies and autoimmune disorders is associated with outstanding clinical outcomes. Isolation and characterization of VH and VL cDNAs encoding the variable regions of the heavy and light chains of monoclonal antibodies (MAb) is necessary to produce next generation MAbs and their derivatives such as bispecific antibodies (bsAb) and single-chain variable fragments (scFv). This study was aimed at cloning and characterization of the VH and VL cDNAs from a hybridoma cell line producing an anti-CD20 MAb. VH and VL fragments were amplified, cloned and characterized. Furthermore, amino acid sequences of VH, VL and corresponding complementarity-determining regions (CDR) were determined and compared with those of four approved MAbs including Rituximab (RTX), Ibritumomab tiuxetan, Ofatumumab and GA101. The cloned VH and VL cDNAs were found to be functional and follow a consensus pattern. Amino acid sequences corresponding to the VH and VL fragments also indicated noticeable homologies to those of RTX and Ibritumomab. Furthermore, amino acid sequences of the relating CDRs had remarkable similarities to their counterparts in RTX and Ibritumomab. Successful recovery of VH and VL fragments encourages the development of novel CD20 targeting bsAbs, scFvs, antibody conjugates and T-cells armed with chimeric antigen receptors.

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

    Energy Technology Data Exchange (ETDEWEB)

    Forrer, Flavio; Mueller-Brand, Jan [University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); Chen, Jianhua; Fani, Melpomeni; Powell, Pia; Maecke, Helmut R. [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); Lohri, Andreas [Basel University Medical Clinic, Liestal (Switzerland); Moldenhauer, Gerhard [German Cancer Research Center, Division of Molecular Immunology, Heidelberg (Germany)

    2009-09-15

    {sup 131}I- and {sup 90}Y-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 (<20 min) with either {sup 177}Lu or {sup 90}Y. 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 10{sup 5} times excess of diethylenetriaminepentaacetic acid (DTPA, 37 C, 7 days). Two patients with relapsed NHL were treated with 740 MBq/m{sup 2} body surface {sup 177}Lu-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 {sup 177}Lu-DOTA-rituximab was tolerated well. Our results show that DOTA-rituximab (4:1) can be labelled with {sup 177}Lu with sufficient stability while the immunoconjugate retains its immunoreactivity. {sup 177}Lu-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. Evaluation of cell death mechanisms activated by the administration of the theranostics radiopharmaceutical {sup 177}Lu-DOTA-anti-CD20 in a dose range of 1-5 Gy; Evaluacion de los mecanismos de muerte celular activados por la administracion del radiofarmaco teranostico {sup 177}Lu-DOTA-anti-CD20 en un rango de dosis de 1-5 Gy

    Energy Technology Data Exchange (ETDEWEB)

    Martinez V, B. E.

    2016-07-01

    Radio-immunotherapy with anti-CD20 antibodies significantly increases the rate of remission in patients with CD20 over expressing B-cell lymphomas. Radio-labeled antibodies directed to surface antigens allow delivering scaled doses of radiation to specific targets thus limiting the dose to healthy tissue. Anti-CD20 causes cell death by two major pathways; activating the immune system to destroy malignant cells and inducing the activation of cell death pathways. The {sup 177}Lu is a beta particle emitter (max. 0.497 MeV) with a maximum soft tissue reach of 0.7 mm and a half-life of 6.7 days. Several clinical studies have established a maximum tolerated dose (45m Ci/m{sup 2}) for {sup 177}Lu-DOTA-rituximab, which shows a favorable clinical response without hematological toxicity. However, the molecular mechanisms of synergistic activation of anti-CD20 and radionuclide have not been studied. In this work we evaluated by flow cytometry, the activation kinetics of the cell death mechanisms induced by the treatment with {sup 177}Lu-DOTA-anti-CD20 from non-Hod king lymphoma cells (Raji). The absorbed radiation dose delivered to the cell nucleus was calculated by Monte Carlo simulation, considering the contribution of the beta emissions of the radiopharmaceutical present in the cell membrane and surrounding environment, as well as crossfire. This work shows that the application of radiation doses of 1 to 5 Gy of the radiopharmaceutical {sup 177}Lu-DOTA-anti-CD20 are sufficient to induce cell death by apoptosis and arrest of the cell cycle. The combination of these factors (continuous delivery of radiation activation of repair mechanisms and increased radio-sensitivity) causes acute activation of the apoptotic program resulting in significant cell death after 96 h of treatment. The temporal analysis of cell death suggests the early activation of apoptosis that is counteracted by the activation of repair processes caused by sustained irradiation, which leads to cell arrest

  7. Evaluation of the cell death mechanisms activated by the radiopharmaceutical {sup 177}Lu-DOTA-anti-CD20 in a dose range of 1 to 5 Gy; Evaluacion de los mecanismos de muerte celular activados por el radiofarmaco {sup 177}Lu-DOTA-anti-CD20 en un intervalo de dosis de 1 a 5 Gy

    Energy Technology Data Exchange (ETDEWEB)

    Azorin V, E.P.; Rojas C, E. L.; Martinez V, B. E.; Ramos B, J. C.; Jimenez M, N. P.; Ferro F, G., E-mail: erica.azorin@inin.gob.mx [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2016-10-15

    The radio immunotherapy with anti-CD20 antibodies significantly increases the remission rate of patients with B-cell lymphomas over expressing the CD20. The radiolabeled antibodies directed to surface antigens allow delivering scaled doses of radiation to specific targets thus limiting the dose to healthy tissue. The anti-CD20 causes cell death by two major pathways; activating the immune system to destroy malignant cells and inducing the activation of cell death pathways. The {sup 177}Lu is a beta particle emitter (max. 0.497 MeV) with a maximum reach on soft tissue of 0.7 mm and a half-life of 6.7 days. Several clinical studies have established a maximum tolerated dose (45 m Ci/m{sup 2}) for {sup 177}Lu-DOTA-rituximab, which shows a favorable clinical response without hematological toxicity. However, the molecular mechanisms of action by synergistic effect of anti-CD20 and radionuclide have not been studied. In this work was evaluated; by flow cytometry, the activation kinetics of the cell death mechanisms induced by the treatment with {sup 177}Lu-DOTA-Anti-CD20 in non-Hodgkin (Raji) lymphoma cells. The absorbed radiation dose delivered to the cell nucleus was calculated by Monte Carlo simulation, considering the contribution of the beta emissions of the radiopharmaceutical present in the cell membrane and surrounding environment, as well as crossfire. This work shows that the application of radiation doses of 1 to 5 Gy of the radiopharmaceutical {sup 177}Lu-DOTA-anti-CD20, are sufficient to induce cell death by apoptosis and arrest of the cell cycle. The combination of these factors (continuous delivery of radiation, activation of repair mechanisms and increased radio sensitivity) causes the acute activation of the apoptotic program resulting in significant cell death after 96 h of treatment. The temporal analysis of cell death suggests the early activation of apoptosis that is counteracted by the activation of repair processes caused by sustained irradiation

  8. 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.

  9. Increased T cell proliferative responses to islet antigens identify clinical responders to anti-CD20 monoclonal antibody (rituximab) therapy in type 1 diabetes.

    Science.gov (United States)

    Herold, Kevan C; Pescovitz, Mark D; McGee, Paula; Krause-Steinrauf, Heidi; Spain, Lisa M; Bourcier, Kasia; Asare, Adam; Liu, Zhugong; Lachin, John M; Dosch, H Michael

    2011-08-15

    Type 1 diabetes mellitus is believed to be due to the autoimmune destruction of β-cells by T lymphocytes, but a single course of rituximab, a monoclonal anti-CD20 B lymphocyte Ab, can attenuate C-peptide loss over the first year of disease. The effects of B cell depletion on disease-associated T cell responses have not been studied. We compare changes in lymphocyte subsets, T cell proliferative responses to disease-associated target Ags, and C-peptide levels of participants who did (responders) or did not (nonresponders) show signs of β-cell preservation 1 y after rituximab therapy in a placebo-controlled TrialNet trial. Rituximab decreased B lymphocyte levels after four weekly doses of mAb. T cell proliferative responses to diabetes-associated Ags were present at baseline in 75% of anti-CD20- and 82% of placebo-treated subjects and were not different over time. However, in rituximab-treated subjects with significant C-peptide preservation at 6 mo (58%), the proliferative responses to diabetes-associated total (p = 0.032), islet-specific (p = 0.048), and neuronal autoantigens (p = 0.005) increased over the 12-mo observation period. This relationship was not seen in placebo-treated patients. We conclude that in patients with type 1 diabetes mellitus, anti-B cell mAb causes increased proliferative responses to diabetes Ags and attenuated β-cell loss. The way in which these responses affect the disease course remains unknown.

  10. 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)

    Akanji, Akinkunmi Ganiyu

    2006-01-01

    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

  11. 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)

    Akanji, Akinkunmi Ganiyu

    2006-01-01

    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 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

  12. 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)

    Liu, S Y.; Eary, Janet F.; Petersdorf, S H.; Martin, P J.; Maloney, D G.; Applebaum, F. R.; Matthews, D. C.; Bush, S A.; Durack, L. D.; Fisher, Darrell R.; Gooley, T A.; Bernstein, I. D.; Press, O. W.

    1997-01-01

    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

  13. The challenge of treating hepatitis C virus-associated cryoglobulinemic vasculitis in the era of anti-CD20 monoclonal antibodies and direct antiviral agents.

    Science.gov (United States)

    Roccatello, Dario; Sciascia, Savino; Rossi, Daniela; Solfietti, Laura; Fenoglio, Roberta; Menegatti, Elisa; Baldovino, Simone

    2017-06-20

    Mixed cryoglobulinemia syndrome (MC) is a systemic vasculitis involving kidneys, joints, skin, and peripheral nerves. While many autoimmune, lymphoproliferative, and neoplastic disorders have been associated with this disorder, hepatitis C virus (HCV) is known to be the etiologic agent in the majority of patients. Therefore, clinical research has focused on anti-viral drugs and, more recently, on the new, highly potent Direct-acting Antiviral Agents (DAAs). These drugs assure sustained virologic response (SVR) rates >90%. Nevertheless, data on their efficacy in patients with HCV-associated cryoglobulinemic vasculitis are disappointing, possibly due to the inability of the drugs to suppress the immune-mediated process once it has been triggered.Despite the potential risk of exacerbation of the infection, immunosuppression has traditionally been regarded as the first-line intervention in cryoglobulinemic vasculitis, especially if renal involvement is severe. Biologic agents have raised hopes for more manageable therapeutic approaches, and Rituximab (RTX), an anti CD20 monoclonal antibody, is the most widely used biologic drug. It has proved to be safer than conventional immunosuppressants, thus substantially changing the natural history of HCV-associated cryoglobulinemic vasculitis by providing long-term remission, especially with intensive regimens.The present review focuses on the new therapeutic opportunities offered by the combination of biological drugs, mainly Rituximab, with DAAs.

  14. 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

    Ofatumumab is a unique monoclonal antibody that targets a distinct small loop epitope on the CD20 molecule. Preclinical data show that ofatumumab is active against B-cell lymphoma/chronic lymphocytic leukemia cells with low CD20-antigen density and high expression of complement inhibitory molecules...

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

    Science.gov (United States)

    2018-03-13

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

  16. Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case series

    Directory of Open Access Journals (Sweden)

    Mella Olav

    2009-07-01

    Full Text Available Abstract Background Chronic fatigue syndrome (CFS is a disease of unknown aetiology. A patient with CFS had unexpected, marked recovery of CFS symptoms lasting for five months during and after cytotoxic chemotherapy for Hodgkin's disease. We reasoned that the transient CFS recovery was related to methotrexate treatment, which induces immunomodulation in part through B-cell depletion. Methods In a case series, this patient and two additional CFS patients were B-cell depleted by infusion of the monoclonal anti-CD20 antibody rituximab. Results All three had improvement of all CFS symptoms. Patients 1 and 2 had major amelioration from 6 weeks after intervention, patient 3 slight improvement from the same time, but then improved markedly from 26 weeks after intervention. The symptomatic effect lasted until weeks 16, 18 and 44, respectively. At relapse, all were retreated with a single (patient 1 or double rituximab infusion (patients 2 and 3. Again, all three had marked symptom improvement, mimicking their first response. After new symptom recurrence, patients 1 and 2 were given weekly oral methotrexate, patient 1 having effect also from this agent. Patients 1 and 2 were again treated for a third rituximab infusion after new relapse, again with a marked clinical benefit. No unexpected toxicity was seen. Conclusion These observations suggest that B-lymphocytes are involved in CFS pathogenesis for a subset of patients. Benefit for all CFS symptoms, the delayed symptom relief following B-cell depletion, the kinetics of relapses, and the effect also from methotrexate treatment, provide suggestive evidence that B-cells play a significant role in the ongoing clinical features, and that CFS may be amenable to therapeutic interventions aimed at modifying B-cell number and function. More systematic investigations of this therapeutic strategy, and of its biological basis, are now needed.

  17. Evaluation of cell death mechanisms activated by the administration of the theranostics radiopharmaceutical "1"7"7Lu-DOTA-anti-CD20 in a dose range of 1-5 Gy

    International Nuclear Information System (INIS)

    Martinez V, B. E.

    2016-01-01

    Radio-immunotherapy with anti-CD20 antibodies significantly increases the rate of remission in patients with CD20 over expressing B-cell lymphomas. Radio-labeled antibodies directed to surface antigens allow delivering scaled doses of radiation to specific targets thus limiting the dose to healthy tissue. Anti-CD20 causes cell death by two major pathways; activating the immune system to destroy malignant cells and inducing the activation of cell death pathways. The "1"7"7Lu is a beta particle emitter (max. 0.497 MeV) with a maximum soft tissue reach of 0.7 mm and a half-life of 6.7 days. Several clinical studies have established a maximum tolerated dose (45m Ci/m"2) for "1"7"7Lu-DOTA-rituximab, which shows a favorable clinical response without hematological toxicity. However, the molecular mechanisms of synergistic activation of anti-CD20 and radionuclide have not been studied. In this work we evaluated by flow cytometry, the activation kinetics of the cell death mechanisms induced by the treatment with "1"7"7Lu-DOTA-anti-CD20 from non-Hod king lymphoma cells (Raji). The absorbed radiation dose delivered to the cell nucleus was calculated by Monte Carlo simulation, considering the contribution of the beta emissions of the radiopharmaceutical present in the cell membrane and surrounding environment, as well as crossfire. This work shows that the application of radiation doses of 1 to 5 Gy of the radiopharmaceutical "1"7"7Lu-DOTA-anti-CD20 are sufficient to induce cell death by apoptosis and arrest of the cell cycle. The combination of these factors (continuous delivery of radiation activation of repair mechanisms and increased radio-sensitivity) causes acute activation of the apoptotic program resulting in significant cell death after 96 h of treatment. The temporal analysis of cell death suggests the early activation of apoptosis that is counteracted by the activation of repair processes caused by sustained irradiation, which leads to cell arrest and increases

  18. Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study.

    Directory of Open Access Journals (Sweden)

    Øystein Fluge

    Full Text Available Chronic fatigue syndrome (CFS is a disease of unknown aetiology. Major CFS symptom relief during cancer chemotherapy in a patient with synchronous CFS and lymphoma spurred a pilot study of B-lymphocyte depletion using the anti-CD20 antibody Rituximab, which demonstrated significant clinical response in three CFS patients.In this double-blind, placebo-controlled phase II study (NCT00848692, 30 CFS patients were randomised to either Rituximab 500 mg/m(2 or saline, given twice two weeks apart, with follow-up for 12 months. Xenotropic murine leukemia virus-related virus (XMRV was not detected in any of the patients. The responses generally affected all CFS symptoms. Major or moderate overall response, defined as lasting improvements in self-reported Fatigue score during follow-up, was seen in 10 out of 15 patients (67% in the Rituximab group and in two out of 15 patients (13% in the Placebo group (p = 0.003. Mean response duration within the follow-up period for the 10 responders to Rituximab was 25 weeks (range 8-44. Four Rituximab patients had clinical response durations past the study period. General linear models for repeated measures of Fatigue scores during follow-up showed a significant interaction between time and intervention group (p = 0.018 for self-reported, and p = 0.024 for physician-assessed, with differences between the Rituximab and Placebo groups between 6-10 months after intervention. The primary end-point, defined as effect on self-reported Fatigue score 3 months after intervention, was negative. There were no serious adverse events. Two patients in the Rituximab group with pre-existing psoriasis experienced moderate psoriasis worsening.The delayed responses starting from 2-7 months after Rituximab treatment, in spite of rapid B-cell depletion, suggests that CFS is an autoimmune disease and may be consistent with the gradual elimination of autoantibodies preceding clinical responses. The present findings will impact

  19. Intraläsionale Therapie niedrig maligner primär kutaner B-Zell-Lymphome mit Anti-CD20-Antikörper: Nebenwirkungen korrelieren mit gutem klinischen Ansprechen.

    Science.gov (United States)

    Eberle, Franziska C; Holstein, Julia; Scheu, Alexander; Fend, Falko; Yazdi, Amir S

    2017-03-01

    Die intraläsionale Gabe von Anti-CD20-Antikörpern (Rituximab) wurde als effektive Therapieoption für Patienten mit niedrig malignen primär kutanen B-Zell-Lymphomen beschrieben. Bis heute wurden allerdings keine Parameter identifiziert, welche reproduzierbar ein gutes klinisches Ansprechen dieser Therapie vorhersagen. Ziel dieser Studie ist, sowohl das klinische Ansprechen und die unerwünschten Nebenwirkungen als auch die Patientenwahrnehmung hinsichtlich intraläsionaler Injektionen von anti-CD20-Antikörpern zur Behandlung indolenter primär kutaner B-Zell-Lymphome im Vergleich mit anderen Therapien zu evaluieren. Elf Patienten mit einem primär kutanen B-Zell-Lymphom, namentlich primär kutanes Keimzentrumslymphom (n = 9) und primär kutanes Marginalzonenlymphom (n = 2), welche mittels intraläsionalem Anti-CD20-Antikörper behandelt wurden, wurden retrospektiv evaluiert hinsichtlich der Ansprechrate und unerwünschter Nebenwirkungen sowie in Bezug auf deren Selbsteinschätzung dieser und anderer Therapien des primär kutanen B-Zell-Lymphoms. Patienten, deren primär kutanes B-Zell-Lymphom mittels intraläsionaler Gabe von Anti-CD20-Antikörper behandelt wurde, zeigten ein komplettes oder partielles Ansprechen in 45 % beziehungsweise 27 % aller Patienten. Speziell Patienten mit grippeähnlichen Symptomen nach erfolgter Injektion zeigten ein gutes Ansprechen. Die Mehrheit der Patienten empfand die Therapie mit Rituximab als die beste Therapie im Vergleich zu anderen Therapien wie beispielsweise chirurgische Exzision oder Radiotherapie. Intraläsionales Rituximab ist eine effektive Therapie mit hoher Patientenzufriedenheit. Starke therapiebedingte Nebenwirkungen wie Fieber, Schüttelfrost und Kopfschmerzen nach Gabe von Rituximab könnten als Indikator für gute Wirksamkeit dienen. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  20. Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Baslund, Bo; Rigby, William

    2010-01-01

    To investigate the safety and efficacy of ofatumumab, a novel human anti-CD20 monoclonal antibody (mAb), in patients with active rheumatoid arthritis (RA) whose disease did not respond to > or = 1 disease-modifying antirheumatic drug....

  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. Radioimmunotherapy of indolent non-Hodgkin's lymphoma with Yttrium-90 labeled anti-CD20 monoclonal antibody therapy does not preclude subsequent chemotherapy or autologous hematologic stem cell transplantation therapy in most patients

    International Nuclear Information System (INIS)

    Wiseman, G.A.; Witzig, T.E.; Ansell, S.M.; Ristow, K.M.

    2002-01-01

    Introduction: Yttrium-90 (Y-90) labeled anti-CD20 monoclonal antibody (ibritumomab tiuxetan or Zevalin TM ) is a novel therapy for patients with relapsed CD20+ B-cell non-Hodgkin's lymphoma (NHL). Patients treated with Zevalin radioimmunotherapy (RIT) are limited from higher doses due to transient and reversible platelet and neutrophil suppression. Patients with indolent NHL who relapse or are refractory to chemotherapy have a 70-80% overall response rate and a 20-30% complete response rate when treated with Zevalin RIT. Therefore additional treatment is required in a minority of patients shortly after Zevalin therapy and in many others at relapse. Relapsed patients are generally treated with chemotherapy alone or high dose chemotherapy followed by autologous transplantation. We wanted to evaluate the ability of patients to tolerate subsequent therapy given at relapse following Zevalin RIT. Methods: We had 58 patients who relapsed after receiving Zevalin RIT and later received additional therapy. The clinical records and lab results were reviewed and compared with a matched control group of patients treated prior to Zevalin availability who received chemotherapy without prior Zevalin RIT. Results: The toxicity in 58 patients treated with Zevalin RIT and subsequent therapy was not significantly different from the control group who did not receive Zevalin RIT. Patients had a median of two subsequent therapies (range, 1-7) after Zevalin. Twenty eight percent required blood cell growth factor support with subsequent chemotherapy and 2 patients required reductions from the standard chemotherapy doses due to prolonged myelosuppression. Eight patients subsequently had successful autologous hematologic stem cell transplant with cells collected after Zevalin. Thirteen of the 58 patients (28%) treated with standard dose chemotherapy were hospitalized for neutropenic fever or thrombocytopenia. Conclusions: Chemotherapy or high dose chemotherapy with autologous transplantation

  3. Desensitization with plasmapheresis and anti-Cd20 for ABO incompatible kidney transplantation from living donor: experience of a single center in Italy.

    Science.gov (United States)

    Silvestre, C; Furian, L; Marson, P; Tison, T; Valente, M; Marchini, F; Rossi, B; Bonfante, L; Valerio, F; Cozzi, E; Rigotti, P

    2014-09-01

    Blood group incompatibility in kidney transplants from a living donor can be successfully overcome by using various desensitization protocols: intravenous immunoglobulin, plasmapheresis (PP), immunoadsorption, and double filtration PP. From July 2010 to October 2013, we performed 10 ABO incompatible kidney transplantation (KT) procedures from a living donor. The desensitization protocol was based on rituximab and PP+cytomegalovirus immune globulin. All patients received induction with basiliximab, except 1 case treated with Thymoglobuline® (ATG) for the simultaneous presence of donor-specific antibody. Tacrolimus and mycophenolate mofetil were initiated at the time of desensitization and continued after the transplant. After a mean follow-up of 11.6±10.4 months, all patients are alive with a functioning graft. The mean serum creatinine concentration at 1 month, 3 months, 6 months, and 1 year was 1.48±0.29, 1.47±0.18, 1.47±0.27, and 1.5±0.27 mg/dl. Three episodes of acute cellular rejection occurred in 2 patients. There was only 1 case of BK virus infection, treated with reduction of immunosuppressive therapy. The protocol biopsy specimens at 1, 3, and 6 months were C4d positive in the absence of acute rejection. Desensitization with rituximab, PP, and anti-cytomegalovirus immune globulin allowed us to perform transplants from living donors to ABO incompatible recipients with excellent results and reduced costs. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. CD20-based Immunotherapy of B-cell Derived Hematologic Malignancies.

    Science.gov (United States)

    Shanehbandi, Dariush; Majidi, Jafar; Kazemi, Tohid; Baradaran, Behzad; Aghebati-Maleki, Leili

    2017-01-01

    CD20 is a surface antigen, which is expressed at certain stages of B-cell differentiation. Targeting the CD20-positive B-cells with therapeutic monoclonal antibodies (MAbs) has been an effectual strategy in the treatment of hematologic malignancies such as non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Initial success with Rituximab (RTX) has encouraged the creation and development of more effective CD20 based therapeutics. However, treatment with conventional MAbs has not been adequate to overcome the problems such as refractory/ relapsed disease. In this regard, new generations of MAbs with enhanced affinity or improved anti-tumor properties have been developed. CD20 directed therapeutics have heterogeneous features and mechanisms of action. Hence, having sufficient knowledge on the immunological and molecular aspects of CD20 based cancer therapy is necessary for predicting the clinical outcomes and taking the necessary measures. An extensive search was performed in PubMed and similar databases for peer-reviewed articles concerning the biology, function and characteristics of CD20 molecule as well as the mechanisms of action and evolutionary process of CD20 targeting agents. This review provides information about the current situation of CD20 targeting immunotherapeutics including MAbs, bispecific antibodies (which exert multiple functions or involve Tcells in tumor elimination) and CAR T-cells (engineered T-cells armed with chimeric antigen receptors). Moreover, limitations, challenges and available solutions regarding the application of CD20 targeting treatments are addressed. Utilization of CD20-targeted therapeutics, due to their diverse properties, requires special considerations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Immuno-biosensor for Detection of CD20-Positive Cells Using Surface Plasmon Resonance

    Science.gov (United States)

    Shanehbandi, Dariush; Majidi, Jafar; Kazemi, Tohid; Baradaran, Behzad; Aghebati-Maleki, Leili; Fathi, Farzaneh; Ezzati Nazhad Dolatabadi, Jafar

    2017-01-01

    Purpose: Surface plasmon resonance (SPR) sensing confers a real-time assessment of molecular interactions between biomolecules and their ligands. This approach is highly sensitive and reproducible and could be employed to confirm the successful binding of drugs to cell surface targets. The specific affinity of monoclonal antibodies (MAb) for their target antigens is being utilized for development of immuno-sensors and therapeutic agents. CD20 is a surface protein of B lymphocytes which has been widely employed for immuno-targeting of B-cell related disorders. In the present study, binding ability of an anti-CD20 MAb to surface antigens of intact target cells was investigated by SPR technique. Methods: Two distinct strategies were used for immobilization of the anti-CD20 MAb onto gold (Au) chips. MUA (11-mercaptoundecanoic acid) and Staphylococcus aureus protein A (SpA) were the two systems used for this purpose. A suspension of CD20-positive Raji cells was injected in the analyte phase and the resulting interactions were analyzed and compared to those of MOLT-4 cell line as CD20-negative control. Results: Efficient binding of anti-CD20 MAb to the surface antigens of Raji cell line was confirmed by both immobilizing methods, whereas this MAb had not a noticeable affinity to the MOLT-4 cells. Conclusion: According to the outcomes, the investigated MAb had acceptable affinity and specificity to the target antigens on the cell surface and could be utilized for immuno-detection of CD20-positive intact cells by SPR method. PMID:28761820

  6. The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20

    NARCIS (Netherlands)

    Teeling, J.L.; Mackus, W.J.M.; Wiegman, L.; Brakel, van den J.H.N.; Beers, S.A.; French, R.R.; Meerten, van T.; Ebeling, S.; Vink, T.; Slootstra, J.W.; Parren, P.; Glennie, M.J.; Winkel, van de J.G.J.

    2006-01-01

    We have previously defined a panel of fully human CD20 mAb. Most of these were unexpectedly efficient in their ability to recruit C1q to the surface of CD20-positive cells and mediate tumor lysis via activation of the classical pathway of complement. This complement-dependent cytotoxicity (CDC)

  7. Identification of relevant drugable targets in diffuse large B-cell lymphoma using a genome-wide unbiased CD20 guilt-by association approach

    NARCIS (Netherlands)

    de Jong, Mathilde R. W.; Visser, Lydia; Huls, Gerwin; Diepstra, Arjan; van Vugt, Marcel; Ammatuna, Emanuele; van Rijn, Rozemarijn S.; Vellenga, Edo; van den Berg, Anke; Fehrmann, Rudolf S. N.; van Meerten, Tom

    2018-01-01

    Forty percent of patients with diffuse large B-cell lymphoma (DLBCL) show resistant disease to standard chemotherapy (CHOP) in combination with the anti-CD20 monoclonal antibody rituximab (R). Although many new anti-cancer drugs were developed in the last years, it is unclear which of these drugs

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

    Energy Technology Data Exchange (ETDEWEB)

    Mishima, Y [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Olympas Bio-Imaging Lab, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Terui, Y [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Takeuchi, K [Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo (Japan); Matsumoto-Mishima, Y; Matsusaka, S [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Utsubo-Kuniyoshi, R [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Olympas Bio-Imaging Lab, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Hatake, K [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan)

    2011-04-01

    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.

  9. File list: InP.Bld.50.AllAg.CD20+ [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.50.AllAg.CD20+ hg19 Input control Blood CD20+ SRX186673,SRX199873,SRX189978...,SRX199853,SRX189980 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Bld.50.AllAg.CD20+.bed ...

  10. Automated Manufacturing of Potent CD20-Directed Chimeric Antigen Receptor T Cells for Clinical Use.

    Science.gov (United States)

    Lock, Dominik; Mockel-Tenbrinck, Nadine; Drechsel, Katharina; Barth, Carola; Mauer, Daniela; Schaser, Thomas; Kolbe, Carolin; Al Rawashdeh, Wael; Brauner, Janina; Hardt, Olaf; Pflug, Natali; Holtick, Udo; Borchmann, Peter; Assenmacher, Mario; Kaiser, Andrew

    2017-10-01

    The clinical success of gene-engineered T cells expressing a chimeric antigen receptor (CAR), as manifested in several clinical trials for the treatment of B cell malignancies, warrants the development of a simple and robust manufacturing procedure capable of reducing to a minimum the challenges associated with its complexity. Conventional protocols comprise many open handling steps, are labor intensive, and are difficult to upscale for large numbers of patients. Furthermore, extensive training of personnel is required to avoid operator variations. An automated current Good Manufacturing Practice-compliant process has therefore been developed for the generation of gene-engineered T cells. Upon installation of the closed, single-use tubing set on the CliniMACS Prodigy™, sterile welding of the starting cell product, and sterile connection of the required reagents, T cells are magnetically enriched, stimulated, transduced using lentiviral vectors, expanded, and formulated. Starting from healthy donor (HD) or lymphoma or melanoma patient material (PM), the robustness and reproducibility of the manufacturing of anti-CD20 specific CAR T cells were verified. Independent of the starting material, operator, or device, the process consistently yielded a therapeutic dose of highly viable CAR T cells. Interestingly, the formulated product obtained with PM was comparable to that of HD with respect to cell composition, phenotype, and function, even though the starting material differed significantly. Potent antitumor reactivity of the produced anti-CD20 CAR T cells was shown in vitro as well as in vivo. In summary, the automated T cell transduction process meets the requirements for clinical manufacturing that the authors intend to use in two separate clinical trials for the treatment of melanoma and B cell lymphoma.

  11. Activatory and Inhibitory Fcγ Receptors Augment Rituximab-mediated Internalization of CD20 Independent of Signaling via the Cytoplasmic Domain*

    Science.gov (United States)

    Vaughan, Andrew T.; Chan, Claude H. T.; Klein, Christian; Glennie, Martin J.; Beers, Stephen A.; Cragg, Mark S.

    2015-01-01

    Type I anti-CD20 mAb such as rituximab and ofatumumab engage with the inhibitory FcγR, FcγRIIb on the surface of B cells, resulting in immunoreceptor tyrosine-based inhibitory motif (ITIM) phosphorylation. Internalization of the CD20·mAb·FcγRIIb complex follows, the rate of which correlates with FcγRIIb expression. In contrast, although type II anti-CD20 mAb such as tositumomab and obinutuzumab also interact with and activate FcγRIIb, this interaction fails to augment the rate of CD20·mAb internalization, raising the question of whether ITIM phosphorylation plays any role in this process. We have assessed the molecular requirements for the internalization process and demonstrate that in contrast to internalization of IgG immune complexes, FcγRIIb-augmented internalization of rituximab-ligated CD20 occurs independently of the FcγRIIb ITIM, indicating that signaling downstream of FcγRIIb is not required. In transfected cells, activatory FcγRI, FcγRIIa, and FcγRIIIa augmented internalization of rituximab-ligated CD20 in a similar manner. However, FcγRIIa mediated a slower rate of internalization than cells expressing equivalent levels of the highly homologous FcγRIIb. The difference was maintained in cells expressing FcγRIIa and FcγRIIb lacking cytoplasmic domains and in which the transmembrane domains had been exchanged. This difference may be due to increased degradation of FcγRIIa, which traffics to lysosomes independently of rituximab. We conclude that the cytoplasmic domain of FcγR is not required for promoting internalization of rituximab-ligated CD20. Instead, we propose that FcγR provides a structural role in augmenting endocytosis that differs from that employed during the endocytosis of immune complexes. PMID:25568316

  12. Dissection of a circulating CD3+ CD20+ T cell subpopulation in patients with psoriasis.

    Science.gov (United States)

    Niu, J; Zhai, Z; Hao, F; Zhang, Y; Song, Z; Zhong, H

    2018-05-01

    CD3 + CD20 + T cells are a population of CD3 + T cells that express CD20 and identified in healthy donors and autoimmune diseases. However, the nature and role of these cells in patients with psoriasis remain unclear. In this study, we aimed to investigate the level, phenotype, functional and clinical relevance of CD3 + CD20 + T cells in the peripheral blood of patients with psoriasis. We found that a small subset of CD3 + T cells expressed CD20 molecule in the peripheral blood of patients with psoriasis, and their levels were similar to those in healthy donors. Circulating CD3 + CD20 + T cells in patients with psoriasis were enriched in CD4 + cells and displayed an activated effector phenotype, as these cells contained fewer CD45RA + -naive and CCR7 + cells with increased activity than those of CD3 + T cells lacking CD20. In addition, compared with healthy donors, circulating CD3 + CD20 + T cells in patients with psoriasis produced more cytokines, interleukin (IL)-17A, tumour necrosis factor (TNF)-α and IL-21, but not IL-4 and IFN-γ. Furthermore, a significantly positive correlation was found between the levels of IL-17A, TNF-α and IL-21-production CD3 + CD20 + T cells with Psoriasis Area and Severity Index scores. Our findings suggest that CD3 + CD20 + T cells may play a role in the pathogenesis of psoriasis. © 2018 British Society for Immunology.

  13. [Refractory CD20-positive peripheral T-cell lymphoma showing loss of CD20 expression after rituximab therapy and gain of CD20 expression after administration of vorinostat and gemcitabine].

    Science.gov (United States)

    Teshima, Kazuaki; Ohyagi, Hideaki; Kume, Masaaki; Takahashi, Satsuki; Saito, Masahiro; Takahashi, Naoto

    A 79-year-old male patient presented with systemic lymphadenopathy. A lymph node biopsy revealed effacement of the normal nodal architecture with diffuse proliferation of medium-sized atypical lymphoid cells. Southern blot analyses demonstrated rearrangement of the T-cell receptor gene but not the immunoglobulin heavy chain gene. He was diagnosed with CD20-positive peripheral T-cell lymphoma (PTCL), NOS. Although he achieved partial remission after six cycles of R-CHOP, he relapse occurred after 2 months. CD20-negative conversion was confirmed in the lymph node, which was positive for CCR4, and the skin at the time of relapse. The patient received the GDP regimen as salvage therapy with the addition of vorinostat for skin involvement; however, he failed to respond, and the disease systemically progressed. Furthermore, he also exhibited progression in the skin after stopping vorinostat due to hematologic toxicity. A lymph node biopsy at progression revealed CD20 re-expression by immunohistochemistry. At progression, the patient received mogamulizumab but failed to respond, and he died owing to disease progression 8 months after relapse. In this case, we demonstrated CD20-negative conversion following rituximab and CD20-positive reversion after using vorinostat and gemcitabine.

  14. The in vivo mechanism of action of CD20 monoclonal antibodies depends on local tumor burden

    Science.gov (United States)

    Boross, Peter; Jansen, J.H. Marco; de Haij, Simone; Beurskens, Frank J.; van der Poel, Cees E.; Bevaart, Lisette; Nederend, Maaike; Golay, Josée; van de Winkel, Jan G.J.; Parren, Paul W.H.I.; Leusen, Jeanette H.W.

    2011-01-01

    Background CD20 monoclonal antibodies are widely used in clinical practice. Antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and direct cell death have been suggested to be important effector functions for CD20 antibodies. However, their specific contributions to the in vivo mechanism of action of CD20 immunotherapy have not been well defined. Design and Methods Here we studied the in vivo mechanism of action of type I (rituximab and ofatumumab) and type II (HuMab-11B8) CD20 antibodies in a peritoneal, syngeneic, mouse model with EL4-CD20 cells using low and high tumor burden. Results Interestingly, we observed striking differences in the in vivo mechanism of action of CD20 antibodies dependent on tumor load. In conditions of low tumor burden, complement was sufficient for tumor killing both for type I and type II CD20 antibodies. In contrast, in conditions of high tumor burden, activating FcγR (specifically FcγRIII), active complement and complement receptor 3 were all essential for tumor killing. Our data suggest that complement-enhanced antibody-dependent cellular cytotoxicity may critically affect tumor killing by CD20 antibodies in vivo. The type II CD20 antibody 11B8, which is a poor inducer of complement activation, was ineffective against high tumor burden. Conclusions Tumor burden affects the in vivo mechanism of action of CD20 antibodies. Low tumor load can be eliminated by complement alone, whereas elimination of high tumor load requires multiple effector mechanisms. PMID:21880632

  15. 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: 4.186, year: 2015

  16. Electrophilic Halogenation of closo-1,2-C2B8H10.

    Czech Academy of Sciences Publication Activity Database

    Bakardjiev, Mario; Růžička, A.; Růžičková, Z.; Holub, Josef; Tok, Oleg L.; Štíbr, Bohumil

    2017-01-01

    Roč. 56, č. 10 (2017), s. 5971-5975 ISSN 0020-1669 R&D Projects: GA ČR(CZ) GA16-01618S Institutional support: RVO:61388980 Keywords : molecular-structure * ortho-carboranes * spectroscopy Subject RIV: CA - Inorganic Chemistry OBOR OECD: Inorganic and nuclear chemistry Impact factor: 4.857, year: 2016

  17. Activatory and inhibitory Fcγ receptors augment rituximab-mediated internalization of CD20 independent of signaling via the cytoplasmic domain.

    Science.gov (United States)

    Vaughan, Andrew T; Chan, Claude H T; Klein, Christian; Glennie, Martin J; Beers, Stephen A; Cragg, Mark S

    2015-02-27

    Type I anti-CD20 mAb such as rituximab and ofatumumab engage with the inhibitory FcγR, FcγRIIb on the surface of B cells, resulting in immunoreceptor tyrosine-based inhibitory motif (ITIM) phosphorylation. Internalization of the CD20·mAb·FcγRIIb complex follows, the rate of which correlates with FcγRIIb expression. In contrast, although type II anti-CD20 mAb such as tositumomab and obinutuzumab also interact with and activate FcγRIIb, this interaction fails to augment the rate of CD20·mAb internalization, raising the question of whether ITIM phosphorylation plays any role in this process. We have assessed the molecular requirements for the internalization process and demonstrate that in contrast to internalization of IgG immune complexes, FcγRIIb-augmented internalization of rituximab-ligated CD20 occurs independently of the FcγRIIb ITIM, indicating that signaling downstream of FcγRIIb is not required. In transfected cells, activatory FcγRI, FcγRIIa, and FcγRIIIa augmented internalization of rituximab-ligated CD20 in a similar manner. However, FcγRIIa mediated a slower rate of internalization than cells expressing equivalent levels of the highly homologous FcγRIIb. The difference was maintained in cells expressing FcγRIIa and FcγRIIb lacking cytoplasmic domains and in which the transmembrane domains had been exchanged. This difference may be due to increased degradation of FcγRIIa, which traffics to lysosomes independently of rituximab. We conclude that the cytoplasmic domain of FcγR is not required for promoting internalization of rituximab-ligated CD20. Instead, we propose that FcγR provides a structural role in augmenting endocytosis that differs from that employed during the endocytosis of immune complexes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Type I CD20 Antibodies Recruit the B Cell Receptor for Complement-Dependent Lysis of Malignant B Cells

    NARCIS (Netherlands)

    Engelberts, Patrick J.; Voorhorst, Marleen; Schuurman, Janine; van Meerten, Tom; Bakker, Joost M.; Vink, Tom; Mackus, Wendy J. M.; Breij, Esther C. W.; Derer, Stefanie; Valerius, Thomas; van de Winkel, Jan G. J.; Parren, Paul W. H. I.; Beurskens, Frank J.

    2016-01-01

    Human IgG1 type I CD20 Abs, such as rituximab and ofatumumab (OFA), efficiently induce complement-dependent cytotoxicity (CDC) of CD20(+) B cells by binding of C1 to hexamerized Fc domains. Unexpectedly, we found that type I CD20 Ab F(ab ')2 fragments, as well as C1q-binding-deficient IgG mutants,

  19. 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 rituximab in relapsed indolent lymphoma. The primary end point of this study was the overall response rate (ORR) in patients with follicular lymphoma after induction and safety in patients with indolent lymphoma. Patients and Methods A total of 175 patients with relapsed CD20(+) indolent lymphoma requiring...... maintenance therapy every 2 months for up to 2 years. Results Among patients with follicular lymphoma (n = 149), ORR seemed higher for obinutuzumab than rituximab (44.6% v 33.3%; P = .08). This observation was also demonstrated by a blinded independent review panel that measured a higher ORR for obinutuzumab...

  20. CD20-targeted therapy: a breakthrough in the treatment of non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    van Meerten, T.; Hagenbeek, A.

    2009-01-01

    Targeting the CD20 antigen on B lymphocytes with the monoclonal antibody rituximab has greatly improved the outcome of patients with B-cell malignancies. Despite the success of rituximab, resistance occurs in about half of the patients, resulting in non-response to treatment or early relapse of the

  1. Click Dehydrogenation of Carbon-Substituted nido-5,6-C2B8H12 Carboranes: A General Route to closo-1,2-C2B8H10 Derivatives

    Czech Academy of Sciences Publication Activity Database

    Tok, Oleg L.; Bakardjiev, Mario; Štíbr, Bohumil; Hnyk, Drahomír; Holub, Josef; Padělková, Z.; Růžička, A.

    2016-01-01

    Roč. 55, č. 17 (2016), s. 8839-8843 ISSN 0020-1669 R&D Projects: GA ČR(CZ) GA16-01618S Institutional support: RVO:61388980 Keywords : magnetic-resonance-spectroscopy * structural-characterization * monocarbaborane chemistry Subject RIV: CA - Inorganic Chemistry Impact factor: 4.857, year: 2016

  2. Type i CD20 antibodies recruit the B cell receptor for complement-dependent lysis of malignant B cells

    DEFF Research Database (Denmark)

    Engelberts, P. J.; Voorhorst, M.; Schuurman, J.

    2016-01-01

    . We hypothesized that CD20 Ab-induced clustering of the IgM or IgG BCR was involved in accessory CDC. Indeed, accessory CDC was consistently observed in B cell lines expressing an IgM BCR and in some cell lines expressing an IgG BCR, but it was absent in BCR- B cell lines. A direct relationship...... between BCR expression and accessory CDC was established by transfecting the BCR into CD20+ cells: OFA-F(ab')2 fragments were able to induce CDC in the CD20+BCR+ cell population, but not in the CD20+BCR- population. Importantly, OFA-F(ab')2 fragments were able to induce CDC ex vivo in malignant B cells...... isolated from patients with mantle cell lymphoma and Waldenström macroglobulinemia. In summary, accessory CDC represents a novel effector mechanism that is dependent on type I CD20 Ab-induced BCR clustering. Accessory CDC may contribute to the excellent capacity of type I CD20 Abs to induce CDC...

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

    Czech Academy of Sciences Publication Activity Database

    Bakardjiev, Mario; Štíbr, Bohumil; Holub, Josef; Tok, Oleg L.; Švec, Petr; Růžičková, Z.; Růžička, A.

    2016-01-01

    Roč. 55, č. 14 (2016), s. 7068-7074 ISSN 0020-1669 R&D Projects: GA ČR(CZ) GA16-01618S Institutional support: RVO:61388980 Keywords : boranes * derivatives * magnetic - resonance -spectroscopy Subject RIV: CA - Inorganic Chemistry Impact factor: 4.857, year: 2016

  4. Disseminated Infections with Talaromyces marneffei in Non-AIDS Patients Given Monoclonal Antibodies against CD20 and Kinase Inhibitors

    OpenAIRE

    Chan, Jasper F.W.; Chan, Thomas S.Y.; Gill, Harinder; Lam, Frank Y.F.; Trendell-Smith, Nigel J.; Sridhar, Siddharth; Tse, Herman; Lau, Susanna K.P.; Hung, Ivan F.N.; Yuen, Kwok-Yung; Woo, Patrick C.Y.

    2015-01-01

    Infections with the fungus Talaromyces (formerly Penicillium) marneffei are rare in patients who do not have AIDS. We report disseminated T. marneffei infection in 4 hematology patients without AIDS who received targeted therapy with monoclonal antibodies against CD20 or kinase inhibitors during the past 2 years. Clinicians should be aware of this emerging complication, especially in patients from disease-endemic regions.

  5. 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)

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

    International Nuclear Information System (INIS)

    Akanji, Akinkunmi Ganiyu

    2012-01-01

    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®). 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)

  7. Is Efficacy of the Anti-Cd20 Antibody Rituximab Preventing Hemolysis Due to Passenger Lymphocyte Syndrome?

    Science.gov (United States)

    Tsujimura, Kazuma; Ishida, Hideki; Tanabe, Kazunari

    2017-02-01

    Passenger lymphocyte syndrome (PLS) often occurs after ABO-mismatched solid organ and/or bone marrow transplantation between a donor and recipient. Viable donor B-lymphocytes transferred during organ transplantation produce antibodies against recipient red cell antigens, leading to hemolysis. The incidence of PLS has been reported to be around 9% after renal transplantation. A previous report showed that rituximab (Rit) was useful for treatment of PLS in allogeneic stem cell transplantation, bowel transplant and severe cases of hemolysis. However, the effectiveness of Rit in preventing PLS after renal transplantation has not yet been evaluated. The participants in this study were 85 patients who had undergone ABO-mismatched renal transplantation from January 2005 to April 2013. Rit was administered to these patients before transplantation. None of the patients that received Rit treatment developed PLS. Thus administration of Rit before transplantation effectively controlled the production of antibodies by B-lymphocytes, which probably prevented the development of PLS. © 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

  8. Testing of mechanisms of action of rituximab and clinical results in high-risk patients with aggressive CD20+ lymphoma

    International Nuclear Information System (INIS)

    Jezersek Novakovic, B.; Juznic Setina, T.; Vovk, M.; Kotnik, V.; Novakovic, S.

    2007-01-01

    Rituximab has been applied successfully in the treatment of indolent and aggressive CD20 positive B cell lymphomas, yet the exact in vivo mechanisms of its action have not been unambiguously explained. This study was therefore aimed to confirm the presumed major mechanisms of action of rituximab and concomitantly to assess the effectiveness of first-line chemo immunotherapy in high-risk patients with aggressive CD20 lymphomas. The activity of rituximab was tested in vitro on Raji and SU-DHL-4 cells using the cell proliferation assay and flow cytometry. In the clinical part of the study, 20 high-risk patients with aggressive CD 20 lymphomas were treated with R-CHOP. Only complement-mediated cytotoxicity was observed under the in vitro applied experimental conditions. Neither the direct apoptotic effect nor the antibody-dependent cell-mediated cytotoxicity was detected probably due to a too low concentration of rituximab and a too low ratio of cytotoxic lymphocytes to tumor cells. The treatment outcome in patients was excellent since complete remissions were achieved in 90% of poor-risk patients at the end of primary treatment and 80% of patients were disease-free at 18.5 months median observation period. According to our results, the complement-dependent cytotoxicity is an important mechanism of rituximab action in vitro. To achieve direct apoptosis, higher concentrations than 20 μg/ml of rituximab should be used, while for an effective antibody-dependent cell-mediated cytotoxicity, the ratio of cytotoxic lymphocytes to tumor cells should be higher than 1:1. In the high-risk patients with aggressive CD20 lymphomas, the addition of rituximab to CHOP substantially improves the therapeutic results. (author)

  9. 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 copolymers * drug delivery systems * doxorubicin Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.465, year: 2015

  10. 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 (CD20......TM, 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...

  11. 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.

  12. 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

  13. 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.

  14. Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models.

    Science.gov (United States)

    Herter, Sylvia; Herting, Frank; Mundigl, Olaf; Waldhauer, Inja; Weinzierl, Tina; Fauti, Tanja; Muth, Gunter; Ziegler-Landesberger, Doris; Van Puijenbroek, Erwin; Lang, Sabine; Duong, Minh Ngoc; Reslan, Lina; Gerdes, Christian A; Friess, Thomas; Baer, Ute; Burtscher, Helmut; Weidner, Michael; Dumontet, Charles; Umana, Pablo; Niederfellner, Gerhard; Bacac, Marina; Klein, Christian

    2013-10-01

    We report the first preclinical in vitro and in vivo comparison of GA101 (obinutuzumab), a novel glycoengineered type II CD20 monoclonal antibody, with rituximab and ofatumumab, the two currently approved type I CD20 antibodies. The three antibodies were compared in assays measuring direct cell death (AnnexinV/PI staining and time-lapse microscopy), complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), and internalization. The models used for the comparison of their activity in vivo were SU-DHL4 and RL xenografts. GA101 was found to be superior to rituximab and ofatumumab in the induction of direct cell death (independent of mechanical manipulation required for cell aggregate disruption formed by antibody treatment), whereas it was 10 to 1,000 times less potent in mediating CDC. GA101 showed superior activity to rituximab and ofatumumab in ADCC and whole-blood B-cell depletion assays, and was comparable with these two in ADCP. GA101 also showed slower internalization rate upon binding to CD20 than rituximab and ofatumumab. In vivo, GA101 induced a strong antitumor effect, including complete tumor remission in the SU-DHL4 model and overall superior efficacy compared with both rituximab and ofatumumab. When rituximab-pretreated animals were used, second-line treatment with GA101 was still able to control tumor progression, whereas tumors escaped rituximab treatment. Taken together, the preclinical data show that the glyoengineered type II CD20 antibody GA101 is differentiated from the two approved type I CD20 antibodies rituximab and ofatumumab by its overall preclinical activity, further supporting its clinical investigation. ©2013 AACR.

  15. CD20 positivity and white blood cell count predict treatment outcomes in Philadelphia chromosome-negative acute lymphoblastic leukemia patients ineligible for pediatric-inspired chemotherapy.

    Science.gov (United States)

    Isshiki, Yusuke; Ohwada, Chikako; Sakaida, Emiko; Onoda, Masahiro; Aotsuka, Nobuyuki; Tanaka, Hiroaki; Fukazawa, Motoharu; Cho, Ryuko; Sugawara, Takeaki; Kawaguchi, Takeharu; Hara, Satoru; Yokota, Akira

    2017-11-01

    The efficacy of conventional chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been controversial as post-remission therapies for adult Philadelphia chromosome-negative acute lymphoblastic leukemia patients. We retrospectively analyzed 96 adolescent and adult cases of Philadelphia chromosome-negative acute lymphoblastic leukemia to evaluate whether allo-HSCT should be performed after first complete remission (1CR). In total, 34 patients received chemotherapy followed by allo-HSCT (HSCT group) and 62 received chemotherapy alone (chemotherapy group). No significant differences in the event-free survival (EFS) or overall survival were observed between the two groups. In the chemotherapy group, use of pediatric regimens was significantly associated with favorable EFS, while high white blood cell (WBC) count and CD20 positivity were associated with poor outcome. In patients who received pediatric regimens, subsequent allo-HSCT did not influence EFS. In patients who received conventional chemotherapy (adult regimen), subsequent allo-HSCT did not improve EFS. High WBC count and CD20 positivity were also significantly associated with poor EFS in patients who received adult regimens. Patients with low WBC count and absence of CD20 who received adult regimens did not benefit from allo-HSCT. Allo-HSCT may not be required in the pediatric regimen-eligible patients; however, pediatric regimen-ineligible patients with either CD20 positivity or high WBC count should receive allo-HSCT after achieving 1CR. This study was registered at http://www.umin.ac.jp/ctr/ as #C000016287. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.

  18. The rationale for B lymphocyte depletion in Graves' disease. Monoclonal anti-CD20 antibody therapy as a novel treatment option

    DEFF Research Database (Denmark)

    El Fassi, Daniel; Nielsen, Claus H; Hasselbalch, Hans K

    2006-01-01

    We have reviewed the immunology of thyroid autoimmunity with special reference to the importance of B lymphocytes (B cells) in thyroidal and extrathyroidal Graves' disease (GD), thus providing a framework for the hypothesis that B cell depletion may be beneficial in GD. Additionally, after...

  19. Safety of Repeated Open-Label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Quattrocchi, Emilia; Ostergaard, Mikkel; Taylor, Peter C.

    2016-01-01

    Objectives To investigate the safety of ofatumumab retreatment in rheumatoid arthritis. Methods Patients with active rheumatoid arthritis participating in two phase III trials (OFA110635 and OFA110634) and a phase II extension trial (OFA111752) received individualised open-label ofatumumab retrea...

  20. Target Antigen Density Governs the Efficacy of Anti-CD20-CD28-CD3 zeta Chimeric Antigen Receptor-Modified Effector CD8(+) T Cells

    NARCIS (Netherlands)

    Watanabe, Keisuke; Terakura, Seitaro; Martens, Anton C.; van Meerten, Tom; Uchiyama, Susumu; Imai, Misa; Sakemura, Reona; Goto, Tatsunori; Hanajiri, Ryo; Imahashi, Nobuhiko; Shimada, Kazuyuki; Tomita, Akihiro; Kiyoi, Hitoshi; Nishida, Tetsuya; Naoe, Tomoki; Murata, Makoto

    2015-01-01

    The effectiveness of chimeric Ag receptor (CAR)-transduced T (CAR-T) cells has been attributed to supraphysiological signaling through CARs. Second-and later-generation CARs simultaneously transmit costimulatory signals with CD3 zeta signals upon ligation, but may lead to severe adverse effects

  1. Bone marrow dosimetry using blood-based models for 131i-anti-cd20 rituximab radioimmunotherapy of non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Kwon, J. H.; Kim, H. G.; Choi, T. H.

    2005-01-01

    Accurate estimations of radiation absorbed dose are essential part of evaluating the risks and benefits associated with radiotherapy. Determination of red marrow dose is important because myelotoxicity is often dose limiting in radioimmunotherapy. The aim of this study is to set up the procedures of dosimetry with activities in the blood and whole-body and to estimate the dose of patients according to MIRD schema. Therapy activities of 131I (136, 185, 200 mCi) were administrated to patients (n=3). Blood activity concentrations and whole-body images by gamma camera were collected from patients with non-Hodgkin's lymphoma (5min, 6h, 24h, 48h, 72h, 2week). Two kinds of patient specific approaches based on Sgouros bone marrow dosimetry methodology were considered to estimate bone marrow dose. The mean effective half-life in blood and whole-body were 25.2h and 27.1h respectively and the mean absorbed dose to bone marrow was 0.48Gy (0.22∼0.93Gy). The dominant contribution of dose was found to be from bone marrow self-dose (over 60%). The procedures of dosimetry with blood and gamma camera image were established. These enable to estimate the radioimmunotherapy patient's dose retrospectively. Some parts of the procedures need to be elaborated to obtain more accurate dose in the near future

  2. The rationale for B lymphocyte depletion in Graves' disease. Monoclonal anti-CD20 antibody therapy as a novel treatment option

    DEFF Research Database (Denmark)

    El Fassi, Daniel; Nielsen, Claus H; Hasselbalch, Hans K

    2006-01-01

    We have reviewed the immunology of thyroid autoimmunity with special reference to the importance of B lymphocytes (B cells) in thyroidal and extrathyroidal Graves' disease (GD), thus providing a framework for the hypothesis that B cell depletion may be beneficial in GD. Additionally, after...... reviewing the efficacy and safety in other autoimmune diseases, we propose that treatment with the B cell-depleting agent Rituximab may become a clinically relevant treatment option in selected cases of GD, particularly when complicated with thyroid-associated ophthalmopathy....

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

    Directory of Open Access Journals (Sweden)

    Hui Xu

    2010-11-01

    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.

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

    Science.gov (United States)

    Xu, Hui; Yan, Yaping; Williams, Mark S; Carey, Gregory B; Yang, Jingxian; Li, Hongmei; Zhang, Guang-Xian; Rostami, Abdolmohamad

    2010-11-01

    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.

  5. Peripheral T-Cell Lymphoma with Aberrant Expression of CD19, CD20, and CD79a: Case Report and Literature Review

    Science.gov (United States)

    Matnani, Rahul G.; Stewart, Rachel L.; Pulliam, Joseph; Jennings, Chester D.; Kesler, Melissa

    2013-01-01

    A case of lymphoma of T-cell derivation with aberrant expression of three B-cell lineage markers (CD19, CD20, and CD79a), which was diagnosed on a left axillary excision, is described. Immunohistochemical studies and flow cytometry analysis demonstrated neoplastic cells expressing CD3, CD19, CD20, and CD79a with absence of CD4, CD8, CD10, CD30, CD34, CD56, CD68, TDT, MPO, PAX-5, and surface immunoglobulin. Gene rearrangement studies performed on paraffin blocks demonstrated monoclonal T-cell receptor gamma chain rearrangement with no evidence of clonal heavy chain rearrangement. The neoplastic cells were negative for Epstein-Barr virus (EBV) or Human Herpes Virus 8 (HHV-8). At the time of diagnosis, the PET scan demonstrated hypermetabolic neoplastic cells involving the left axilla, bilateral internal jugular areas, mediastinum, right hilum, bilateral lungs, and spleen. However, bone marrow biopsy performed for hemolytic anemia revealed normocellular bone marrow with trilineage maturation. The patient had no evidence of immunodeficiency or infection with EBV or HHV-8. This is the first reported case of a mature T-cell lymphoma with aberrant expression of three B-cell lineage markers. The current report also highlights the need for molecular gene rearrangement studies to determine the precise lineage of ambiguous neoplastic clones. PMID:24066244

  6. Peripheral T-Cell Lymphoma with Aberrant Expression of CD19, CD20, and CD79a: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Rahul G. Matnani

    2013-01-01

    Full Text Available A case of lymphoma of T-cell derivation with aberrant expression of three B-cell lineage markers (CD19, CD20, and CD79a, which was diagnosed on a left axillary excision, is described. Immunohistochemical studies and flow cytometry analysis demonstrated neoplastic cells expressing CD3, CD19, CD20, and CD79a with absence of CD4, CD8, CD10, CD30, CD34, CD56, CD68, TDT, MPO, PAX-5, and surface immunoglobulin. Gene rearrangement studies performed on paraffin blocks demonstrated monoclonal T-cell receptor gamma chain rearrangement with no evidence of clonal heavy chain rearrangement. The neoplastic cells were negative for Epstein-Barr virus (EBV or Human Herpes Virus 8 (HHV-8. At the time of diagnosis, the PET scan demonstrated hypermetabolic neoplastic cells involving the left axilla, bilateral internal jugular areas, mediastinum, right hilum, bilateral lungs, and spleen. However, bone marrow biopsy performed for hemolytic anemia revealed normocellular bone marrow with trilineage maturation. The patient had no evidence of immunodeficiency or infection with EBV or HHV-8. This is the first reported case of a mature T-cell lymphoma with aberrant expression of three B-cell lineage markers. The current report also highlights the need for molecular gene rearrangement studies to determine the precise lineage of ambiguous neoplastic clones.

  7. Bendamustine/Mitoxantrone/Rituximab (BMR): a very effective, well tolerated outpatient chemoimmunotherapy for relapsed and refractory CD20-positive indolent malignancies. Final results of a pilot study.

    Science.gov (United States)

    Weide, Rudolf; Pandorf, Annette; Heymanns, Jochen; Köppler, Hubert

    2004-12-01

    We have developed a new chemoimmunotherapy for patients with relapsed or refractory CD20-positive indolent lymphomas and CLL by combining the chemotherapeutic agents Bendamustine (B) and Mitoxantrone (M) with the monoclonal antibody Rituximab. Treatment consisted of (B): 90 mg/m2 (80 mg/m2 in CLL) day 1 + 2, (M): 10 mg/m2 day 1 and (R): 375 mg/m2 day 8,15,22 and 29. BM was repeated 3 times starting on day 36, thereafter every 4 weeks. The maximal therapy consisted of 1 x BMR followed by 5 x BM. We have treated 54 patients with BMR. Median age was 68 years (36-82). Disease distribution was as follows: 21 B-CLL, 1 B-PLL, 8 lymphoplasmacytic, 14 follicular, 2 mantle cell, 2 marginal zone, 6 secondary high grade. Median number of previous treatments was 2 (1-7). ORR was 96% with 41% CR and 55% PR. Median time to progression is 17 months in CLL and has not been reached in indolent lymphomas with a median observation time of 27 months (3-60+). The time to next antilymphoma treatment is prolonged significantly by BMR. No therapy associated death or hospitalization occurred within the study period. BMR is a well tolerated very effective outpatient treatment for relapsed and refractory CD20-positive indolent lymphomas and CLL.

  8. Comparative study of CD4 and CD45RO T cells and CD20 B cells in cerebrospinal fluid of syphilitic meningitis and tuberculous meningitis patients.

    Science.gov (United States)

    Yu, Nian; Zhang, Qiao-Quan; Zhang, Kang; Xie, Yuan; Zhu, Hai-Qing; Lin, Xing-Jian; Di, Qing

    2016-09-01

    This study was to investigate the differences of lymphocyte in the cerebrospinal fluid (CSF) of patients with syphilis meningitis (SM) and tuberculous meningitis (TBM) for new diagnostic insights. Totally, 79 cases of SM and 45 cases of TBM were enrolled. In the CSF, the CD4, CD45RO or CD20 positive lymphocytes were detected by immunohistochemistry. The proportion of CD4 T cells in the CSF lymphocytes in patients with SM was significantly higher than that in patients with TBM (p CD4 T-cell proportion in both groups (p CD45RO T cells in CSF lymphocytes of patients with SM was less than that of patients with TBM (p CD45RO T cells was increased in the CSF of both group patients (p cells in the CSF lymphocytes was not obviously different between the two groups during every stage. In conclusion, there are strong differences of CD4 and CD45RO T-cell ratio, but not the CD20 B cells in the meningitis. CD4 and CD45RO T cells in CSF are a useful complement in differentially diagnosing SM and TBM; it contributes to further understand the pathogenesis and prognosis of SM and TBM. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  9. 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

  10. 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 ofatumu...

  11. Isolation and structure of a cDNA encoding the B1 (CD20) cell-surface antigen of human B lymphocytes

    International Nuclear Information System (INIS)

    Tender, T.F.; Streuli, M.; Schlossman, S.F.; Saito, H.

    1988-01-01

    The B1 (CD20) molecule is a M/sub r/ 33,000 phosphoprotein on the surface of human B lymphocytes that may serve a central role in the homoral immune response by regulating B-cell proliferation and differentiation. In this report, a cDNA clone that encodes the B1 molecule was isolated and the amino acid sequence of B1 was determined. B-cell-specific cDNA clones were selected from a human tonsillar cDNA library by differential hybridization with labeled cDNA derived from either size-fractionated B-cell mRNA or size-fractionated T-cell mRNA. Of the 261 cDNA clones isolated, 3 cross-hybridizing cDNA clones were chosen as potential candidates for encoding B1 based on their selective hybridization to RNA from B1-positive cell lines. The longest clone, pB1-21, contained a 2.8-kilobase insert with an 891-base-pair open reading frame that encodes a protein of 33 kDa. mRNA synthesized from the pB1-21 cDNA clone in vitro was translated into a protein of the same apparent molecular weight as B1. Limited proteinase digestion of the pB1-21 translation product and B1 generated peptides of the same sizes, indicating that the pB1-21 cDNA encodes the B1 molecule. Gel blot analysis indicated that pB1-21 hybridized with two mRNA species of 2.8 and 3.4 kilobases only in B1-positive cell lines. The amino acid sequence deduced from the pB1-21 nucleotide sequence apparently lacks a signal sequence and contains three extensive hydrophobic regions. The deduced B1 amino acid sequence shows no significant homology with other known patients

  12. Feasibility of abbreviated cycles of immunochemotherapy for completely resected limited-stage CD20+ diffuse large B-cell lymphoma (CISL 12-09).

    Science.gov (United States)

    Yoon, Dok Hyun; Sohn, Byeong Seok; Oh, Sung Yong; Lee, Won-Sik; Lee, Sang Min; Yang, Deok-Hwan; Huh, Jooryung; Suh, Cheolwon

    2017-02-21

    The appropriate number of chemotherapy cycles for limited stage diffuse large B-cell lymphoma (DLBCL) patients without gross residual lesions after complete resection, has not been specifically questioned. We performed a multicenter, single-arm, phase 2 study to investigate the feasibility of 3 cycles of abbreviated R-CHOP chemotherapy in low-risk patients with completely resected localized CD20+ DLBCL. Between December 2010 and May 2013, we recruited 23 patients. One was excluded due to ineligibility, and hence, 22 were included in the final analysis. The primary sites comprised the intestine (n = 15), cervical lymph nodes (n = 4), stomach (n = 1), tonsil (n = 1), and spleen (n = 1). All patients successfully completed the 3 cycles of planned R-CHOP chemotherapy. Over a median follow-up of 39.5 months (95% confidence interval, 29.9-47.1 months), both the estimated 2-year disease-free survival and overall survival rates was 95% confidence interval, 85.9-104.1%. Only one patient with an international prognostic index of 2 experienced relapse and died. The most common grade 3 or 4 toxicity condition included neutropenia (n = 8, 36.4%). Three patients experienced grade 3 febrile neutropenia, but no grade 3 or 4 non-hematologic toxicity was observed. DLBCL patients without residual lesions after resection were enrolled and R-CHOP chemotherapy was repeated at 3-week-intervals over 3 cycles. The primary endpoint was 2-year disease-free survival. Three cycles of abbreviated R-CHOP immunochemotherapy is feasible for completely resected low risk localized DLBCL.

  13. MS4A1 dysregulation in asbestos-related lung squamous cell carcinoma is due to CD20 stromal lymphocyte expression.

    Directory of Open Access Journals (Sweden)

    Casey M Wright

    Full Text Available Asbestos-related lung cancer accounts for 4-12% of lung cancers worldwide. We have previously identified ADAM28 as a putative oncogene involved in asbestos-related lung adenocarcinoma (ARLC-AC. We hypothesised that similarly gene expression profiling of asbestos-related lung squamous cell carcinomas (ARLC-SCC may identify candidate oncogenes for ARLC-SCC. We undertook a microarray gene expression study in 56 subjects; 26 ARLC-SCC (defined as lung asbestos body (AB counts >20AB/gram wet weight (gww and 30 non-asbestos related lung squamous cell carcinoma (NARLC-SCC; no detectable lung asbestos bodies; 0AB/gww. Microarray and bioinformatics analysis identified six candidate genes differentially expressed between ARLC-SCC and NARLC-SCC based on statistical significance (p2-fold. Two genes MS4A1 and CARD18, were technically replicated by qRT-PCR and showed consistent directional changes. As we also found MS4A1 to be overexpressed in ARLC-ACs, we selected this gene for biological validation in independent test sets (one internal, and one external dataset (2 primary tumor sets. MS4A1 RNA expression dysregulation was validated in the external dataset but not in our internal dataset, likely due to the small sample size in the test set as immunohistochemical (IHC staining for MS4A1 (CD20 showed that protein expression localized predominantly to stromal lymphocytes rather than tumor cells in ARLC-SCC. We conclude that differential expression of MS4A1 in this comparative gene expression study of ARLC-SCC versus NARLC-SCC is a stromal signal of uncertain significance, and an example of the rationale for tumor cell enrichment in preparation for gene expression studies where the aim is to identify markers of particular tumor phenotypes. Finally, our study failed to identify any strong gene candidates whose expression serves as a marker of asbestos etiology. Future research is required to determine the role of stromal lymphocyte MS4A1 dysregulation in

  14. A Phase I/II Study to Evaluate the Safety of Cellular Immunotherapy Using Autologous T Cells Engineered to Express a CD20-Specific Chimeric Antigen Receptor for Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphomas

    Science.gov (United States)

    2018-04-11

    CD20 Positive; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Transformed Indolent Non-Hodgkin Lymphoma

  15. Prototropic mu-H-8,H-9 and mu-H-9,H-10 Tautomers Derived from the [nido-5,6-C2B8H11](-) Anion

    Czech Academy of Sciences Publication Activity Database

    Tok, Oleg L.; Růžičková, Z.; Růžička, A.; Hnyk, Drahomír; Štíbr, Bohumil

    2016-01-01

    Roč. 55, č. 20 (2016), s. 10122-10124 ISSN 0020-1669 R&D Projects: GA ČR(CZ) GA16-01618S Institutional support: RVO:61388980 Keywords : tautomers Subject RIV: CA - Inorganic Chemistry Impact factor: 4.857, year: 2016

  16. 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.

    2014-01-01

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients with purine analogue 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 (PAR) designed to decrease the risk of treatment associated infections and limit 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 analogue 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 9.1 months, and overall survival 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 NK cells without a profound and sustained decrease in expression of CD20 by circulating CLL cells. We conclude that PAR 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

  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. © 2014 Wiley Periodicals, Inc.

  18. 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: 4.179, year: 2015

  19. Neurophysiological and clinical responses to rituximab in patients with anti-MAG polyneuropathy.

    Science.gov (United States)

    Zara, Gabriella; Zambello, Renato; Ermani, M

    2011-12-01

    Rituximab treatment has shown clinical improvement in anti-myelin associated glycoprotein (MAG) polyneuropathy. We analyzed scores of clinical scales and the most sensitive electrophysiological parameters before and after immunomodulating treatment with rituximab in a group of patients affected by anti-MAG demyelinating polyneuropathy. Clinical scores, the percentage of CD20 B-lymphocytes, anti-MAG antibody titers and electrophysiological data in 7 patients with anti-MAG polyneuropathy were analyzed. The patients were examined before a cycle with rituximab, 6, 12 and 24 months after the end of the treatment. Two patients were treated with rituximab additional cycles and re-evaluated 48 months after the first treatment. There were no evident correlation between anti-MAG serum antibody titers or clinical scales and electrodiagnostic data. Significant decrease in the proportion of CD20 B-lymphocytes was observed. Significant anti-MAG antibodies titers reduction was detected after re-treatment. At follow-up, pinprik sensation and two point discrimination presented a significant improvement compared with the score before treatment. In our patients, rituximab did not improve any electrophysiological data. No correlation with anti-MAG serum antibodies course was found. With rituximab only pin sensibility improved. Rituximab re-treatment significantly reduces anti-MAG serum antibodies titers but improves only small fibers sensibility. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  20. Acute neurological worsening after Rituximab treatment in patients with anti-MAG neuropathy.

    Science.gov (United States)

    Sala, Emilie; Robert-Varvat, Florence; Paul, Stéphane; Camdessanché, Jean-Philippe; Antoine, Jean-Christophe

    2014-10-15

    Patients with peripheral neuropathy and anti-MAG monoclonal IgM may respond to Rituximab, a humanized monoclonal anti-CD20 antibody. We report on three patients with peripheral neuropathy and anti-MAG monoclonal IgM who deteriorated under Rituximab and reviewed seven previously published cases. Worsening was acute and severe, and occurred during the treatment period. All the patients improved after deterioration but at final evaluation only one was improved comparatively to baseline, five were worsened and four were stabilized. Deterioration was not clearly associated with an increase of the anti-MAG antibody titer. Two patients received Rituximab prior or after the course which induced worsening without adverse reaction. Although rare, acute worsening of the neuropathy can occur after Rituximab. The deterioration is however reversible within some weeks to several months. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Imatinib treatment induces CD5+ B lymphocytes and IgM natural antibodies with anti-leukemic reactivity in patients with chronic myelogenous leukemia.

    Directory of Open Access Journals (Sweden)

    Silvia Catellani

    Full Text Available Imatinib mesylate is a first line treatment of Chronic Myelogenous Leukemia and of a rare form of gastrointestinal stromal cancer, where the response to the drug is also linked to the immune system activation with production of antineoplastic cytokines. In this study, forty patients in the chronic phase of disease, treated with imatinib mesylate, were analyzed. Bone marrow aspirates were drawn at diagnosis, after 3, 6, 12, 18 months for haematological, cytofluorimetric, cytogenetic, biomolecular evaluation and cytokine measurement. Responder and non responder patients were defined according to the European LeukemiaNet recommendations. In responder patients (n = 32, the percentage of bone marrow CD20(+CD5(+sIgM(+ lymphocytes, and the plasma levels of IgM, were significantly higher, at 3 months and up to 9 months, than in non responders. These IgM reacted with O-linked sugars expressed by leukemic cells and could induce tumor cell apoptosis. In responder patients the stromal-derived factor-1 and the B-lymphocyte-activating factor of the tumor necrosis factor family significantly raised in the bone marrow after imatinib administration, together with the bone morphogenetic proteins-2 and -7. All patients with high number of CD20(+CD5(+sIgM(+ cells and high stromal-derived factor-1 and B lymphocyte activating factor levels, underwent complete cytogenetic and/or molecular remission by 12 months. We propose that CD20(+CD5(+sIgM(+ lymphocytes producing anti-carbohydrate antibodies with anti-tumor activity, might contribute to the response to imatinib treatment. As in multivariate analysis bone marrow CD20(+CD5(+sIgM(+ cells and stromal-derived factor-1 and B-lymphocyte-activating factor levels were significantly related to cytogenetical and molecular changes, they might contribute to the definition of the pharmacological response.

  2. Efficacy of D- red blood cell transfusion and rituximab therapy in autoimmune hemolytic anemia with anti-D and panreactive autoantibodies arising after hematopoietic stem cell transplant.

    Science.gov (United States)

    Minakawa, Keiji; Ohto, Hitoshi; Yasuda, Hiroyasu; Saito, Shunichi; Kawabata, Kinuyo; Ogawa, Kazuei; Nollet, Kenneth E; Ikeda, Kazuhiko

    2018-04-17

    Autoimmune hemolytic anemia (AIHA) is caused by autoantibodies to red blood cells (RBCs), which can be panreactive and/or specific to Rh/other blood group antigens. We report a severe case of AIHA after bone marrow transplantation (BMT) due to autoanti-D triggered by reactivation of Epstein-Barr virus (EBV) infection. A combined strategy of D- RBC transfusion and administration of anti-CD20 monoclonal antibody (MoAb) resolved the hemolysis. A 33-year-old male underwent allogeneic BMT from an ABO-identical and HLA-matched unrelated male donor. Five months later, while having mild chronic graft-versus-host disease, he manifested AIHA, with a hemoglobin (Hb) level of 5.1 g/dL on AIHA Day 2 (Posttransplant Day 156) and was refractory to D+ RBCs, with a Hb level of 2.4 g/dL on AIHA Day 6. Anti-D-like autoantibodies (titer 1280, subclass immunoglobulin G 1 , monocyte monolayer assay 28.7%) and panreactive (titer 40) were identified. Changing the RBC transfusion strategy to D- increased his Hb level to 6.7 g/dL on Day 10. Administration of anti-CD20 MoAb mitigated EBV-related B-cell proliferation and reduced anti-D autoantibody titer to 320 by Day 16 with normalized Hb concentration after 6 months. In severe AIHA, when standard treatment and regular RBC transfusions are ineffective, transfusion of RBCs lacking the target antigen(s) of autoantibodies and administration of anti-CD20 MoAb should be considered. © 2018 AABB.

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

    Science.gov (United States)

    Klitgaard, Josephine L; Koefoed, Klaus; Geisler, Christian; Gadeberg, Ole V; Frank, David A; Petersen, Jørgen; Jurlander, Jesper; Pedersen, Mikkel W

    2013-10-01

    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 secondary effector functions represent an attractive opportunity for CLL treatment. Here, a repertoire of mAbs against human CD5 was generated and tested for ability to induce complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) both as single mAbs and combinations of two mAbs against non-overlapping epitopes on human CD5. The results demonstrated that combinations of two mAbs significantly increased the level of CDC compared to the single mAbs, while no enhancement of ADCC was seen with anti-CD5 mAb combinations. High levels of CDC and ADCC correlated with low levels of Ab-induced CD5 internalization and degradation. Importantly, an anti-CD5 mAb combination enhanced CDC of CLL cells when combined with the anti-CD20 mAbs rituximab and ofatumumab as well as with the anti-CD52 mAb alemtuzumab. These results suggest that an anti-CD5 mAb combination inducing CDC and ADCC may be effective alone, in combination with mAbs against other targets or combined with chemotherapy for CLL and other CD5-expressing haematological or lymphoid malignancies. © 2013 John Wiley & Sons Ltd.

  4. Membranous Nephropathy and Anti-Podocytes Antibodies: Implications for the Diagnostic Workup and Disease Management.

    Science.gov (United States)

    Pozdzik, Agnieszka; Brochériou, Isabelle; David, Cristina; Touzani, Fahd; Goujon, Jean Michel; Wissing, Karl Martin

    2018-01-01

    The discovery of circulating antibodies specific for native podocyte antigens has transformed the diagnostic workup and greatly improved management of idiopathic membranous nephropathy (iMN). In addition, their identification has clearly characterized iMN as a largely autoimmune disorder. Anti-PLA2R1 antibodies are detected in approximately 70% to 80% and anti-THSD7A antibodies in only 2% of adult patients with iMN. The presence of anti-THSD7A antibodies is associated with increased risk of malignancy. The assessment of PLA2R1 and THSD7A antigen expression in glomerular immune deposits has a better sensitivity than measurement of the corresponding autoantibodies. Therefore, in the presence of circulating anti-podocytes autoantibodies and/or enhanced expression of PLA2R1 and THSD7A antigens MN should be considered as primary MN (pMN). Anti-PLA2R1 or anti-THSD7A autoantibodies have been proposed as biomarkers of autoimmune disease activity and their blood levels should be regularly monitored in pMN to evaluate disease activity and predict outcomes. We propose a revised clinical workup flow for patients with MN that recommends assessment of kidney biopsy for PLA2R1 and THSD7A antigen expression, screening for circulating anti-podocytes antibodies, and assessment for secondary causes, especially cancer, in patients with THSD7A antibodies. Persistence of anti-podocyte antibodies for 6 months or their increase in association with nephrotic proteinuria should lead to the introduction of immunosuppressive therapies. Recent data have reported the efficacy and safety of new specific therapies targeting B cells (anti-CD20 antibodies, inhibitors of proteasome) in pMN which should lead to an update of currently outdated treatment guidelines.

  5. C anti c q anti q states

    Energy Technology Data Exchange (ETDEWEB)

    Chao, K T [Oxford Univ. (UK). Dept. of Theoretical Physics; Science Research Council, Chilton (UK). Rutherford and Appleton Labs.)

    1980-07-01

    Taking account of the colour magnetic and electric forces, we discuss the spectroscopy of various types of c anti c q anti q states. Their decay, hadronic production, production in e/sup +/e/sup -/ annihilation as well as photoproduction are also studied.

  6. Photon anti bunching versus phantom anti bunching?

    International Nuclear Information System (INIS)

    Miranowicz, A.; Ekert, A.; Ekert, A.; Bajer, J.; Leonski, W.

    1997-01-01

    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)

  7. Dgroup: DG02629 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ritumomab tiuxetan (genetical recombination) (JAN) ... ATC code: V10XX02 Antineoplastic, Radioactive agent, Anti-CD20 antibody... Monoclonal antibody CD20 [HSA:931] [KO:K06466] ... Genomic biomarker: CD20 [HSA:931

  8. Anti-Bubbles

    Science.gov (United States)

    Tufaile, Alberto; Sartorelli, José Carlos

    2003-08-01

    An anti-bubble is a striking kind of bubble in liquid that seemingly does not comply the buoyancy, and after few minutes it disappears suddenly inside the liquid. Different from a simple air bubble that rises directly to the liquid surface, an anti-bubble wanders around in the fluid due to its slightly lesser density than the surrounding liquid. In spite of this odd behavior, an anti-bubble can be understood as the opposite of a conventional soap bubble in air, which is a shell of liquid surrounding air, and an anti-bubble is a shell of air surrounding a drop of the liquid inside the liquid. Two-phase flow has been a subject of interest due to its relevance to process equipment for contacting gases and liquids applied in industry. A chain of bubbles rising in a liquid formed from a nozzle is a two-phase flow, and there are certain conditions in which spherical air shells, called anti-bubbles, are produced. The purpose of this work is mainly to note the existence of anti-bubbling regime as a sequel of a bubbling system. We initially have presented the experimental apparatus. After this we have described the evolution of the bubbling regimes, and emulated the effect of bubbling coalescence with simple maps. Then is shown the inverted dripping as a consequence of the bubble coalescence, and finally the conditions for anti-bubble formation.

  9. [Anti-angiogenic drugs].

    Science.gov (United States)

    Sato, Yasufumi

    2010-06-01

    Angiogenesis or neovascularization, the formation of neo-vessels, is a physiological phenomenon endued in vasculature, but is involved in various pathological conditions. Angiogenesis is required for tumor growth and metastasis, and thus constitutes an important target for the control of tumor progression. Indeed, the recent development of bevacizumab, a neutralizing anti-VEGF monoclonal antibody as the first anti-angiogenic drug, legalized the clinical merit of anti-angiogenesis in cancers. Thereafter, various drugs targeting VEGF-mediated signals have been developed to control tumor angiogenesis. Thus, anti-angiogenic drugs are now recognized in the clinic as a major step forward for the treatment of cancers. This review focuses on the current status of antiangiogenesis treatment in cancers.

  10. Pathogenetic and Clinical Aspects of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitides

    Directory of Open Access Journals (Sweden)

    Peter Lamprecht

    2018-04-01

    Full Text Available Anti-neutrophil cytoplasmic autoantibodies (ANCA targeting proteinase 3 (PR3 and myeloperoxidase expressed by innate immune cells (neutrophils and monocytes are salient diagnostic and pathogenic features of small vessel vasculitis, comprising granulomatosis with polyangiitis (GPA, microscopic polyangiitis, and eosinophilic GPA. Genetic studies suggest that ANCA-associated vasculitides (AAV constitute separate diseases, which share common immunological and pathological features, but are otherwise heterogeneous. The successful therapeutic use of anti-CD20 antibodies emphasizes the prominent role of ANCA and possibly other autoantibodies in the pathogenesis of AAV. However, to elucidate causal effects in AAV, a better understanding of the complex interplay leading to the emergence of B lymphocytes that produce pathogenic ANCA remains a challenge. Different scenarios seem possible; e.g., the break of tolerance induced by a shift from non-pathogenic toward pathogenic autoantigen epitopes in inflamed tissue. This review gives a brief overview on current knowledge about genetic and epigenetic factors, barrier dysfunction and chronic non-resolving inflammation, necro-inflammatory auto-amplification of cellular death and inflammation, altered autoantigen presentation, alternative complement pathway activation, alterations within peripheral and inflamed tissue-residing T- and B-cell populations, ectopic lymphoid tissue neoformation, the characterization of PR3-specific T-cells, properties of ANCA, links between autoimmune disease and infection-triggered pathology, and animal models in AAV.

  11. Anti pp interactions in anti p atoms

    International Nuclear Information System (INIS)

    Poth, H.

    1975-01-01

    The x-rays of anti p atoms were recorded to trace out a strong interaction shift and width to the electromagnetic energy and the radiation width of the low-lying levels. The energy of the levels and consequently the energy of the transitions was calculated by solving numerically the Dirac equation with an electromagnetic potential, taking into account the finite size of the nucleus and the vacuum polarization. Due to the lack of sufficient data, the antiproton-nucleon interaction was not well understood at low energies. In order to separate antiproton-proton from antiproton-neutron interactions, the studies of isotope effects were proposed. (L.M.K.)

  12. The experimental study on biodistribution and radioimmunoimaging of 131I labeled anti-lymphoma Fab antibody in nude mice bearing human B cell lymphoma

    International Nuclear Information System (INIS)

    Yang Xiaochun; Zhang Meihua; Shen Junkang; Shen Yongmei; Shi Yizhen; Liu Zengli

    2008-01-01

    Objective: Radioimmunoimaging is still an interesting study in the domain of nuclear medicine. The aim of this study was to evaluate the biodistribution and radioimmunoimaging of 131 I-Fab anti- body in nude mice beating human B cell lymphoma. Methods: The immunoreactivity of Fab antibody to Raji cells was analyzed by immunohistochemistry and flow cytometry. Fab antibody and CD20 monoclonal antibody (as control) were labeled with 131 I using Iodogen method. 131 I-Fab antibody or 131 I-CD20 was injected into nude mice bearing B cell lymphoma via tail veins. The biodistribution and radioimmunoimaging results were obtained at 2, 4, 8 and 24 h postinjection, respectively. Results: The results of immunohistochemistry and flow cytometry indicated that both Fab antibody and 131 I-Fab antibody could bind strongly with membrane antigens on Raji cells, and the binding rate reached above 87%. Clear tumor image was obtained at 8 h after injection with 131 I-Fab and elimination was observed at 24 h postinjection. The clear tumor image for 131 I-CD20 antibody was obtained at 24 h post injection. The biodistribution in vivo showed that the percentage activities of injection dose per gram of tumor (% ID/g) of 131 I-Fab group at 2, 4, 8 h postinjection were higher than that of 131 I-CD20 antibody [(1.37±0.28), (1.84±0.13), (2.21±0.15)% ID/g vs (0.33±0.06), (0.62±0.08), (1.46±0.24)% ID/g, respectively; F=52.22, 278.42 and 29.00, all P 131 I-Fad and 131 I-CD20 groups at 2, 4, 8 and 24 h were [(0.22±0.03)-(5.44± 0.31)] vs[(0.04±0.01)-(3.10±0.29)], [(0.43±0.11) - (21.01±3.97)] vs [(0.11±0.05) - (7.99±1.81)], [(1.09±0.07) -(20.28±2.77)] vs [(0.48±0.06) - (23.55±1.69)], [(1.12± 0.02) - (10.29±1.78)] vs [(2.32 ± 0.34) - (33.23±6.83)], respectively. Conclusion: 131 I-Fab anti- body has advantages of small molecular weight, excellent targeting characteristics, early imaging and fast elimination, which indicates the potential application value in diagnosing B cell

  13. 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.

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

    International Nuclear Information System (INIS)

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

    2004-01-01

    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 ( 9 0yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM ( 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

  15. 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.

  16. Herba Cistanches: Anti-aging

    OpenAIRE

    Wang, Ningqun; Ji, Shaozhen; Zhang, Hao; Mei, Shanshan; Qiao, Lumin; Jin, Xianglan

    2017-01-01

    The Cistanche species (“Rou Cong Rong” in Chinese) is an endangered wild species growing in arid or semi-arid areas. The dried fleshy stem of Cistanches has been used as a tonic in China for many years. Modern pharmacological studies have since demonstrated that Herba Cistanches possesses broad medicinal functions, especially for use in anti-senescence, anti-oxidation, neuroprotection, anti-inflammation, hepatoprotection, immunomodulation, anti-neoplastic, anti-osteoporosis and the promotion ...

  17. Discrete anti-gravity

    International Nuclear Information System (INIS)

    Noyes, H.P.; Starson, S.

    1991-03-01

    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

  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. Anti-smooth muscle antibody

    Science.gov (United States)

    ... gov/ency/article/003531.htm Anti-smooth muscle antibody To use the sharing features on this page, please enable JavaScript. Anti-smooth muscle antibody is a blood test that detects the presence ...

  20. 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.

  1. Insane anti-Membranes?

    International Nuclear Information System (INIS)

    Giecold, Gregory; Orsi, Francesco; Puhm, Andrea

    2014-01-01

    The backreactions of anti-branes on a variety of supergravity backgrounds have been shown in a recent series of papers to be riled by some unexplained flux singularities. All of the situations studied so far involve backgrounds with (close to) AdS-asymptotics. It is the purpose of this work to study the backreaction of anti-M2 branes on a background exhibiting a different UV behavior: the so-called A 8 regular solution of eleven-dimensional supergravity that we consider has “Taub-NUT type' asymptotics. As it turns out, some subleading infrared singularities are inevitable; they cannot be naturally ascribed to the anti-branes backreacting on this background. Moreover, our configuration does not involve smeared branes. This lends further credence to the work of Bena et al. http://dx.doi.org/10.1007/JHEP09(2013)142 suggesting that the singularities encountered are in no way remnants of smearing that would wash away once brane polarization is taken into account

  2. Hybrid mesons (Q anti Qg) in N anti N annihilation

    International Nuclear Information System (INIS)

    Dover, C.B.; Gutsche, T.; Faessler, A.

    1993-09-01

    N anti N annihilation reactions provide exciting possibilities to study mesonic resonances beyond the usual Q anti Q spectrum. Particularly the search for Q anti Qg mesons containing an explicit dynamical excitation of the gluon field is not promising, since hybrids are predicted to display unique features: exotic quantum numbers (J πC ) and dynamical selection rules for their decay modes. The authors have investigated the possibility of producing hybrids from p anti p atomic states in reactions of the type N anti N(L= 0,1) → π + Q anti Qg. Production rates for hybrid mesons are found to display a strong dependence on the quantum numbers and kinematical factors associated with the transition. The dependence on the orbital angular momentum L of the p anti p atomic state, accessible in p anti p annihilation at rest, would provide a striking signature for the production of hybrids. In estimating branching ratios for the formation of Q anti Qg hybrid mesons in N anti N annihilation reactions at rest, the authors have employed a microscopic model with constituent quarks and gluons in analogy to the annihilation model for the production of Q anti Q mesons

  3. Biological Treatments in Behçet’s Disease: Beyond Anti-TNF Therapy

    Directory of Open Access Journals (Sweden)

    Francesco Caso

    2014-01-01

    Full Text Available Behçet’s disease (BD is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molecules, chiefly tumor necrosis factor- (TNF- α, interleukin- (IL- 1β, and IL-6. However, although biological treatment with anti-TNF-α agents has been largely demonstrated to be effective in BD, not all patients are definite responders, and this beneficial response might drop off over time. Therefore, additional therapies for a subset of refractory patients with BD are inevitably needed. Different agents targeting various cytokines and their receptors or cell surface molecules have been studied: the IL-1 receptor has been targeted by anakinra, the IL-1 by canakinumab and gevokizumab, the IL-6 receptor by tocilizumab, the IL12/23 receptor by ustekinumab, and the B-lymphocyte antigen CD-20 by rituximab. The aim of this review is to summarize all current experiences and the most recent evidence regarding these novel approaches with biological drugs other than TNF-α blockers in BD, providing a valuable addition to the actually available therapeutic armamentarium.

  4. Biological treatments in Behçet's disease: beyond anti-TNF therapy.

    Science.gov (United States)

    Caso, Francesco; Costa, Luisa; Rigante, Donato; Lucherini, Orso Maria; Caso, Paolo; Bascherini, Vittoria; Frediani, Bruno; Cimaz, Rolando; Marrani, Edoardo; Nieves-Martín, Laura; Atteno, Mariangela; Raffaele, Carmela G L; Tarantino, Giusyda; Galeazzi, Mauro; Punzi, Leonardo; Cantarini, Luca

    2014-01-01

    Behçet's disease (BD) is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molecules, chiefly tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, and IL-6. However, although biological treatment with anti-TNF-α agents has been largely demonstrated to be effective in BD, not all patients are definite responders, and this beneficial response might drop off over time. Therefore, additional therapies for a subset of refractory patients with BD are inevitably needed. Different agents targeting various cytokines and their receptors or cell surface molecules have been studied: the IL-1 receptor has been targeted by anakinra, the IL-1 by canakinumab and gevokizumab, the IL-6 receptor by tocilizumab, the IL12/23 receptor by ustekinumab, and the B-lymphocyte antigen CD-20 by rituximab. The aim of this review is to summarize all current experiences and the most recent evidence regarding these novel approaches with biological drugs other than TNF-α blockers in BD, providing a valuable addition to the actually available therapeutic armamentarium.

  5. Triply heavy tetraquark states with the QQ anti Q anti q configuration

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Kan; Liu, Xiang [Lanzhou University, School of Physical Science and Technology, Lanzhou (China); Lanzhou University and Institute of Modern Physics of CAS, Research Center for Hadron and CSR Physics, Lanzhou (China); Liu, Yan-Rui; Wu, Jing [Shandong University, School of Physics and Key Laboratory of Particle Physics and Particle Irradiation (MOE), Jinan (China); Zhu, Shi-Lin [Peking University, School of Physics and State Key Laboratory of Nuclear Physics and Technology, Beijing (China); Collaborative Innovation Center of Quantum Matter, Beijing (China); Peking University, Center of High Energy Physics, Beijing (China)

    2017-01-15

    In the framework of the color-magnetic interaction, we systematically investigate the mass splittings of the QQ anti Q anti q tetraquark states and estimate their rough masses in this work. These systems include the explicitly exotic states cc anti b anti q and bb anti c anti q and the hidden exotic states cc anti c anti q, cb anti b anti q, bc anti c anti q, and bb anti b anti q. If a state around the estimated mass region can be observed, its nature as a genuine tetraquark is favored. The strong decay patterns shown here will be helpful to the experimental search for these exotic states. (orig.)

  6. Herba Cistanches: Anti-aging.

    Science.gov (United States)

    Wang, Ningqun; Ji, Shaozhen; Zhang, Hao; Mei, Shanshan; Qiao, Lumin; Jin, Xianglan

    2017-12-01

    The Cistanche species ("Rou Cong Rong" in Chinese) is an endangered wild species growing in arid or semi-arid areas. The dried fleshy stem of Cistanches has been used as a tonic in China for many years. Modern pharmacological studies have since demonstrated that Herba Cistanches possesses broad medicinal functions, especially for use in anti-senescence, anti-oxidation, neuroprotection, anti-inflammation, hepatoprotection, immunomodulation, anti-neoplastic, anti-osteoporosis and the promotion of bone formation. This review summarizes the up-to-date and comprehensive information on Herba Cistanches covering the aspects of the botany, traditional uses, phytochemistry and pharmacology, to lay ground for fully elucidating the potential mechanisms of Herba Cistanches' anti-aging effect and promote its clinical application as an anti-aging herbal medicine.

  7. Synergistic anti-tumor therapy by a comb-like multifunctional antibody nanoarray with exceptionally potent activity

    Science.gov (United States)

    Li, Huafei; Sun, Yun; Chen, Di; Zhao, He; Zhao, Mengxin; Zhu, Xiandi; Ke, Changhong; Zhang, Ge; Jiang, Cheng; Zhang, Li; Zhang, Fulei; Wei, Huafeng; Li, Wei

    2015-10-01

    Simultaneously blocking multiple mediators offers new hope for the treatment of complex diseases. However, the curative potential of current combination therapy by chronological administration of separate monoclonal antibodies (mAbs) or multi-specific mAbs is still moderate due to inconvenient manipulation, low cooperative effectors, poor pharmacokinetics and insufficient tumor accumulation. Here, we describe a facile strategy that arms distinct mAbs with cooperative effectors onto a long chain to form a multicomponent comb-like nano mAb. Unlike dissociative parental mAbs, the multifunctional mAb nanoarray (PL-RB) constructed from type I/II anti-CD20 mAbs shows good pharmacokinetics. This PL-RB simultaneously targets distinct epitopes on a single antigen (Ag) and neighboring Ags on different lymphocytes. This unique intra- and intercellular Ag cross-linking endows the multifunctional mAb nanoarray with potent apoptosis activity. The exceptional apoptosis, complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) that are synchronously evoked by the nano PL-RB are further synergistically promoted via enhanced permeability and retention (EPR), which resulted in high intratumor accumulation and excellent anti-lymphoma efficiency.

  8. The Anti-Landscape

    DEFF Research Database (Denmark)

    There have always been some uninhabitable places, but in the last century human beings have produced many more of them. These anti-landscapes have proliferated to include the sandy wastes of what was once the Aral Sea, severely polluted irrigated lands, open pit mines, blighted nuclear zones...... that no 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...

  9. Anti-parallel triplexes

    DEFF Research Database (Denmark)

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

    2015-01-01

    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 and one...... of the phosphate groups in Watson-Crick strand. Also, it was shown that the nucleobase Y made a good stacking and binding with the other nucleobases in the TFO and Watson-Crick duplex, respectively. In contrast, the nucleobase Z with LNA moiety was forced to twist out of plane of Watson-Crick base pair which......The phosphoramidites of DNA monomers of 7-(3-aminopropyn-1-yl)-8-aza-7-deazaadenine (Y) and 7-(3-aminopropyn-1-yl)-8-aza-7-deazaadenine LNA (Z) are synthesized, and the thermal stability at pH 7.2 and 8.2 of anti-parallel triplexes modified with these two monomers is determined. When, the anti...

  10. B cells and ectopic follicular structures: novel players in anti-tumor programming with prognostic power for patients with metastatic colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Anastasia Meshcheryakova

    Full Text Available Remarkably limited information is available about biological mechanisms that determine the disease entity of metastatic colorectal cancer in the liver (CRCLM with no good clinical parameters to estimate prognosis. For the last few years, understanding the relationship between tumor characteristics and local immune response has gained increasing attention. Given the multifaceted roles of B-cell-driven responses, we aimed to elucidate the immunological imprint of B lymphocytes at the metastatic site, the interrelation with macrophages, and their prognostic relevance. Here we present novel algorithm allowing to assess a link between the local patient-specific immunological capacity and clinical outcome. The microscopy-based imaging platform was used for automated scanning of large-scale tissue sections and subsequent qualitative and quantitative analyses of immune cell subtypes using lineage markers and single-cell recognition strategy. Results indicate massive infiltration of CD45-positive leukocytes confined to the metastatic border. We report for the first time the accumulation of CD20-positive B lymphocytes at the tumor-liver interface comprising the major population within the large CD45-positive aggregates. Strikingly, functionally active, activation-induced cytidine deaminase (AID-positive ectopic lymphoid structures were found to be assembled within the metastatic margin. Furthermore, the CD20-based data set revealed a strong prognostic power: patients with high CD20 content and/or ectopic follicles had significantly lower risk for disease recurrence as revealed by univariate analysis (p<0.001 for both and in models adjusted for clinicopathological variables (p<0.001 and p = 0.01, respectively, and showed prolonged overall survival. In contrast, CD68 staining-derived data set did not show an association with clinical outcome. Taken together, we nominate the magnitude of B lymphocytes, including those organized in ectopic follicles, as

  11. [Anti-N-methyl-D aspartate receptor encephalitis - guideline to the challenges of diagnosis and therapy].

    Science.gov (United States)

    Hau, Lídia; Csábi, Györgyi; Tényi, Tamás

    2015-01-01

    Anti-N-methyl-D-Aspartate encephalitis is a recently diagnosed autoimmune disorder with increasing significance. During this disease antibodies are produced against the subunit of the NMDA receptor, which cause different symptoms, both psychiatric and neurological. The aim of this publication is to introduce this disease, to facilitate the diagnosis and to recommend therapeutical guideline. In this review we summarized the relevant literature published between 2007 and 2015 giving emphasis on etiopathogenesis, diagnosis, differential diagnosis, treatment and prognosis. In the etiology an underlying tumor or a viral agent should be considered. During the disease we can discern 3 periods: first prodromal viral infections-like symptoms can be seen, 1-2 weeks later psychiatric symptoms, such as aggression, sleep and behavior disturbances appear. After that neurological symptoms (tonic-clonic convulsions, aphasia, catatonia, orofacial dyskinesia, autonom lability, altered mental state) are typical, and the patient's condition deteriorates. For the correct diagnosis it is necessary to detect antibodies against the NMDA receptor from the serum and the liquor. Steroids, immunoglobulins and plasmaheresis are the first-line therapies. If the disease is unresponsive, then as a second-line therapy anti-CD 20 (Rituximab) and cyclophosphamid can be useful. Most of the patients are improving without any neurological sequale with prompt detection and appropriate therapy. It is important to be familiar with the symptoms, diagnosis and therapy of this disease as a practicing clinician, especially as a psychiatrist or neurologist. 75 percentage of the patients are admitted to psychiatric departments first because of the leading symptoms. Autoimmune NMDA encephalitis is a reversible disease after early diagnosis and treatment.

  12. Anti-vibration gloves?

    Science.gov (United States)

    Hewitt, Sue; Dong, Ren G; Welcome, Daniel E; McDowell, Thomas W

    2015-03-01

    For exposure to hand-transmitted vibration (HTV), personal protective equipment is sold in the form of anti-vibration (AV) gloves, but it remains unclear how much these gloves actually reduce vibration exposure or prevent the development of hand-arm vibration syndrome in the workplace. This commentary describes some of the issues that surround the classification of AV gloves, the assessment of their effectiveness and their applicability in the workplace. The available information shows that AV gloves are unreliable as devices for controlling HTV exposures. Other means of vibration control, such as using alternative production techniques, low-vibration machinery, routine preventative maintenance regimes, and controlling exposure durations are far more likely to deliver effective vibration reductions and should be implemented. Furthermore, AV gloves may introduce some adverse effects such as increasing grip force and reducing manual dexterity. Therefore, one should balance the benefits of AV gloves and their potential adverse effects if their use is considered. © Crown copyright 2014.

  13. anti p and anti Λ production in Si+Au collisions at the AGS

    International Nuclear Information System (INIS)

    Wu, Yuedong

    1996-01-01

    Anti p and anti Λ production in central Si + Au collisions has been measured by E589 at the BNL-AGS. Preliminary m perpendicular spectra are presented for anti p's and anti Λ's. The dn/dy distribution for anti p's is also presented. Based on the anti p and anti Λ measurements, anti Λ/anti p ratios are calculated in the rapidity range of 1.1-1.5

  14. Anti-arrythemic and anti-hyperlipidaemic potentials of aqueous ...

    African Journals Online (AJOL)

    Anti-arrythemic and anti-hyperlipidaemic potentials of aqueous garlic extract in hyper-cholesterolaemic rat. H U Nwanjo, G O Oze. Abstract. No Abstract. IJONAS Vol. 3 (2) 2007: pp. 214-221. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT.

  15. Anti-Bias Education: Reflections

    Science.gov (United States)

    Derman-Sparks, Louise

    2011-01-01

    It is 30 years since NAEYC published "Anti-Bias Curriculum Tools for Empowering Young Children" (Derman-Sparks & ABC Task Force, 1989). Since then, anti-bias education concepts have become part of the early childhood education (ECE) narrative in the United States and many other countries. It has brought a fresh way of thinking about…

  16. Charmed meson rescattering in the reaction anti pd→ anti DDN

    International Nuclear Information System (INIS)

    Haidenbauer, J.; Krein, G.; Meissner, U.G.; Sibirtsev, A.

    2008-01-01

    We examine the possibility to extract information about the DN and anti DN interactions from the anti pd→D 0 D - p reaction. We utilize the notion that the open-charm mesons are first produced in the annihilation of the antiproton on one nucleon in the deuteron and subsequently rescatter on the other (the spectator) nucleon. The latter process is then exploited for investigating the DN and anti DN interactions. We study different methods for isolating the contributions from the D 0 p and D - p rescattering terms. (orig.)

  17. Anti-nuclear movements

    International Nuclear Information System (INIS)

    Ruedig, W.

    1990-01-01

    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)

  18. What is it really? Anti-G or Anti-D plus Anti-C: Clinical Significance in Antenatal Mothers.

    Science.gov (United States)

    Das, Soumya; Shastry, Shamee; Murugesan, M; B, Poornima Baliga; Shastry, Shamee

    2017-06-01

    G antigen of Rh blood group system is present either along with D and/or C positive red cells. Hence, [serologically anti-G presents with the similar picture as that of multiple antibodies (anti-D + anti-C). Differentiating them is important as anti-D + anti-C causes severe hemolytic disease of the fetus and newborn than anti-G. In pregnancies with anti-G alone, alloimmunization due to D antigen could be prevented by prophylactic administration of RhIg. Differentiating between anti-D + C from anti-G in alloimmunized pregnant mothers becomes essential. Sera from antenatal mothers, whose antibody identification by 11-cell panel gave a pattern for anti-D and anti-C were selected. Extended phenotyping for Rh system was performed for these antenatal cases. Differential adsorption and elution testing using R 2 R 2 cells initially and r'r cells subsequently were performed to distinguish anit-G from anti-D + anti-C. Antibody titers of these antibodies were determined and their clinical outcome in the newborn was followed. A pattern suggestive of anti D and anti C on antibody identification were observed in six antenatal cases. On further workup 50 % of them confirmed to have anti G. Antibody titers of anti-G and anti-C were lower than that of Anti-D. All newborns were sensitized in vivo and the antibody specificity in them were confirmed with elution studies. The mothers who had only anti-G were subsequently administered with an appropriate dose of RhIg.Differential adsorption and elution studies help in identifying anti-G and distinguishing it from anti-D plus anti-C, thus helping in better patient management.

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

    International Nuclear Information System (INIS)

    Maher, C.J.

    1986-06-01

    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

  20. 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 ...

  1. anti K-nucleon interactions

    Energy Technology Data Exchange (ETDEWEB)

    Chand, Ramesh

    1963-10-15

    Total scattering and absorption cross sections for anti K-nucleon collisions in I = 1, p3/2 - channel are given as functions of the two sets of energy dependent anti KN scattering parameters solutions, called solution A' and solution B'. These scattering parameters are obtained by linear interpolations between Watson's amplitudes around 400 MeV/c and the amplitude at the position of the pole in the anti KN scattering amplitude corresponding to the p3/2-wave 1385 MeV Y1-resonance with 50 MeV width. The zero-range expansion for p-wave anti K-nucleon phase shift and the scattering parameters of Watson's solution B are found to be in violation of the requirements of causality and of positive definiteness of transition probabilities. (auth)

  2. 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...... 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 guide theory...

  3. Narrow n anti n resonances

    International Nuclear Information System (INIS)

    Bogdanova, L.N.; Dalkarov, O.D.; Kerbikov, B.O.; Shapiro, I.S.

    1975-01-01

    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

  4. SHORT COMMUNICATION SYNTHESIS AND ANTI ...

    African Journals Online (AJOL)

    THIADIAZOL DERIVATIVES OF MEFENAMIC ACID ... acid derivatives were synthesized and confirmed by spectroscopic data. ... evaluations indicate that these new compounds showed potent anti-inflammatory activities compare to .... intermediate compound (A) ,this intermediate has a good characteristics like carbonyl.

  5. Anti-C.Diff Pill

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Anand [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2018-01-30

    The anti- C.diff pill is being developed for patients who are at high risk for Clostridium difficile, a bacterium that causes diarrhea and serious intestinal conditions like colitis. C-diff is deadly, killing over 30,000 people a year in the United States and costing an average of $42,000 per treatment. The most common treatment is a fecal transplant (FT). The anti- C.diff replaces the invasive and messy FT practice with a pill.

  6. Approach to a Pregnant Woman with Anti D + Anti C Reactivity Pattern: A Diagnostic Conundrum.

    Science.gov (United States)

    Rai, Preeti; Sharma, Geetika; Singh, Deeksha; Garg, Jyoti

    2017-09-01

    The Rhesus G antigen is present on all RBCs that are C+ and also on most D+ RBCs. Due to this co-distribution of G with either C or D antigen, it mimics a reactivity pattern of anti C + anti D on Indirect Antiglobulin Test (IAT), though the role of Anti G in causing Hemolytic Disease of Newborn (HDN) is controversial. The differentiation of anti D, anti C, and anti G is essential particularly in pregnant females. We hereby report a rare case of anti G with anti D and anti C in a pregnant woman with emphasis on approach to identify anti D+C+G and its implications.

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

    International Nuclear Information System (INIS)

    Ishiura, Yoshihito; Kotani, Norihiro; Yamashita, Ryusuke; Yamamoto, Harumi; Kozutsumi, Yasunori; Honke, Koichi

    2010-01-01

    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.

  8. 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.

  9. Anti-human SIRPα antibody is a new tool for cancer immunotherapy.

    Science.gov (United States)

    Murata, Yoji; Tanaka, Daisuke; Hazama, Daisuke; Yanagita, Tadahiko; Saito, Yasuyuki; Kotani, Takenori; Oldenborg, Per-Arne; Matozaki, Takashi

    2018-02-23

    Interaction of signal regulatory protein α (SIRPα) expressed on the surface of macrophages with its ligand CD47 expressed on target cells negatively regulates phagocytosis of the latter cells by the former. We recently showed that blocking Abs to mouse SIRPα enhanced both the Ab-dependent cellular phagocytosis (ADCP) activity of mouse macrophages for Burkitt's lymphoma Raji cells opsonized with an Ab to CD20 (rituximab) in vitro as well as the inhibitory effect of rituximab on the growth of tumors formed by Raji cells in nonobese diabetic (NOD)/SCID mice. However, the effects of blocking Abs to human SIRPα in preclinical cancer models have remained unclear given that such Abs have failed to interact with endogenous SIRPα expressed on macrophages of immunodeficient mice. With the use of Rag2 -/- γ c -/- mice harboring a transgene for human SIRPα under the control of human regulatory elements (hSIRPα-DKO mice), we here show that a blocking Ab to human SIRPα significantly enhanced the ADCP activity of macrophages derived from these mice for human cancer cells. The anti-human SIRPα Ab also markedly enhanced the inhibitory effect of rituximab on the growth of tumors formed by Raji cells in hSIRPα-DKO mice. Our results thus suggest that the combination of Abs to human SIRPα with therapeutic Abs specific for tumor antigens warrants further investigation for potential application to cancer immunotherapy. In addition, humanized mice, such as hSIRPα-DKO mice, should prove useful for validation of the antitumor effects of checkpoint inhibitors before testing in clinical trials. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  10. Approach to a Pregnant Woman with Anti D + Anti C Reactivity Pattern: A Diagnostic Conundrum

    OpenAIRE

    Rai, Preeti; Sharma, Geetika; Singh, Deeksha; Garg, Jyoti

    2017-01-01

    The Rhesus G antigen is present on all RBCs that are C+ and also on most D+ RBCs. Due to this co-distribution of G with either C or D antigen, it mimics a reactivity pattern of anti C + anti D on Indirect Antiglobulin Test (IAT), though the role of Anti G in causing Hemolytic Disease of Newborn (HDN) is controversial. The differentiation of anti D, anti C, and anti G is essential particularly in pregnant females. We hereby report a rare case of anti G with anti D and anti C in a pregnant woma...

  11. Synovial features of patients with rheumatoid arthritis and psoriatic arthritis in clinical and ultrasound remission differ under anti-TNF therapy: a clue to interpret different chances of relapse after clinical remission?

    Science.gov (United States)

    Alivernini, Stefano; Tolusso, Barbara; Petricca, Luca; Bui, Laura; Di Sante, Gabriele; Peluso, Giusy; Benvenuto, Roberta; Fedele, Anna Laura; Federico, Franco; Ferraccioli, Gianfranco; Gremese, Elisa

    2017-07-01

    To define the synovial characteristics of patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in clinical and ultrasound remission achieved by combination therapy with methotrexate (MTX) and tumour necrosis factor (TNF) blockers. Patients with RA in remission (n=25) (disease activity score (DAS)<1.6 for at least 6 months), patients with RA in low disease activity (LDA) (n=10) (1.6anti-TNF (adalimumab 40 mg or etanercept 50 mg) with power Doppler (PDUS)-negative synovial hypertrophy underwent synovial tissue biopsy. Patients with RA with high/moderate disease naïve to treatment (n=50) were included as a comparison group. Immunostaining for cluster designation (CD)68, CD21, CD20, CD3, CD31 and collagen was performed. PDUS-negative patients with RA in remission showed lower histological scores for synovial CD68 + , CD20 + , CD3 + cells and CD31 + vessels and collagen deposition (p<0.05 for both lining and sublining) compared with PDUS-positive patients with RA with high/moderate disease. In addition, there was no significant difference in terms of lining and sublining CD68 + , CD20 + , CD3 + , CD31 + cells and collagen comparing PDUS-negative patients with RA in remission and in LDA, respectively. On the contrary, PDUS-negative patients with PsA in remission showed higher histological scores for sublining CD68 + (p=0.02) and CD3 + cells (p=0.04) as well as CD31 + vessels (p<0.001) than PDUS-negative patients with RA in remission. PDUS-negative patients with RA in remission have comparable synovial histological features than PDUS-negative patients with RA in LDA. However, patients with PsA in remission are characterised by a higher degree of residual synovial inflammation than patients with RA in remission, despite PDUS negativity under TNF inhibition. Published by the BMJ

  12. 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. Copyright © 2016 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  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 Fermilab anti pp collider

    International Nuclear Information System (INIS)

    Harrison, M.

    1984-01-01

    The goal of the Tevatron I project is to achieve anti pp collisions in the centre-of-mass energy range up to 2 TeV with a luminosity of at least 10 30 cm -2 sec -1 . The project involves adapting the Tevatron to function as a storage ring and modifying the lattice to provide low-beta interaction points; changes to the Main Ring to allow anti p transfers and the installation of experimental equipment; and the construction of a anti p source. Major experimental areas will be located in the socalled BO and DO straight sections together with smaller, more specialized experiments in several of the other interacting regions. (orig./HSI)

  15. Anti-regulatory T cells

    DEFF Research Database (Denmark)

    Andersen, Mads Hald

    2017-01-01

    responses to tumours or inhibiting autoimmunity development. However, recent studies report the discovery of self-reactive pro-inflammatory T cells—termed anti-regulatory T cells (anti-Tregs)—that target immune-suppressive cells. Thus, regulatory cells can now be defined as both cells that suppress immune...... reactions as well as effector cells that counteract the effects of suppressor cells and support immune reactions. Self-reactive anti-Tregs have been described that specifically recognize human leukocyte antigen-restricted epitopes derived from proteins that are normally expressed by regulatory immune cells......Our initial understanding of immune-regulatory cells was based on the discovery of suppressor cells that assure peripheral T-cell tolerance and promote immune homeostasis. Research has particularly focused on the importance of regulatory T cells (Tregs) for immune modulation, e.g. directing host...

  16. Anti-G with concomitant anti-C and anti-D: A case report in a pregnant woman

    Directory of Open Access Journals (Sweden)

    Rabeya Yousuf

    2017-01-01

    Full Text Available The G antigen of Rh blood group system is present in almost all D-positive or C-positive red cells but absent from red cells lacking D and C antigens. The differentiation of anti-D and anti-C from anti-G is not necessary for routine transfusion; however, during pregnancy, it is important because anti-G can masquerade as anti-D and anti-C with initial antibody testing. The false presence of anti-D will exclude the patient from receiving anti-D immunoglobulin (RhIG when the patient actually is a candidate for RhIG prophylaxis. Moreover, patients with positive anti-D or anti-G are at risk of developing hemolytic disease of the fetus and newborn and need close monitoring. Thus, proper identification allows the clinicians to manage patients properly. This case report highlights a rare case of anti-G together with anti-D and anti-C in a pregnant woman. This report disseminates knowledge on identification of anti-G and its importance in pregnant women.

  17. Anti-G with concomitant anti-C and anti-D: A case report in a pregnant woman.

    Science.gov (United States)

    Yousuf, Rabeya; Mustafa, Ahmad Nasirudin; Ho, Siew-Ling; Tang, Yee-Loong; Leong, Chooi-Fun

    2017-01-01

    The G antigen of Rh blood group system is present in almost all D-positive or C-positive red cells but absent from red cells lacking D and C antigens. The differentiation of anti-D and anti-C from anti-G is not necessary for routine transfusion; however, during pregnancy, it is important because anti-G can masquerade as anti-D and anti-C with initial antibody testing. The false presence of anti-D will exclude the patient from receiving anti-D immunoglobulin (RhIG) when the patient actually is a candidate for RhIG prophylaxis. Moreover, patients with positive anti-D or anti-G are at risk of developing hemolytic disease of the fetus and newborn and need close monitoring. Thus, proper identification allows the clinicians to manage patients properly. This case report highlights a rare case of anti-G together with anti-D and anti-C in a pregnant woman. This report disseminates knowledge on identification of anti-G and its importance in pregnant women.

  18. Interaction between anti-hypertensive and non-steroidal anti ...

    African Journals Online (AJOL)

    AKS Publication

    Department of Physiotherapy, College of Medicine, University College Hospital,. University of Ibadan, Nigeria. (Received 19 ... that NSAIDs diminish the effects of anti-hypertensive drugs and may lead to an ineffective hypertension therapy. ..... repair, regeneration and transplantation. Instr Course Lect. 1998;47:487-504. 15.

  19. Anti-inflammatory, anti-nociceptive and antipyretic potential of ...

    African Journals Online (AJOL)

    Materials and Methods: Extracts of Terminalia citrina fruits were evaluated at doses of 200mg/kg, 400mg/kg and 600mg/kg in albino mice for preventive effect in inflammatory edema, peripheral pain sensation and pyrexia. Carrageenan induced paw edema method was utilized to evaluate anti-inflammatory activity.

  20. 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.

  1. CP-25, a Novel Anti-inflammatory and Immunomodulatory Drug, Inhibits the Functions of Activated Human B Cells through Regulating BAFF and TNF-alpha Signaling and Comparative Efficacy with Biological Agents

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    2017-12-01

    Full Text Available Paeoniflorin-6′-O-benzene sulfonate (code: CP-25 was the chemistry structural modifications of Paeoniflorin (Pae. CP-25 inhibited B cells proliferation stimulated by B cell activating factor belonging to the TNF family (BAFF or Tumor necrosis factor alpha (TNF-alpha. CP-25, Rituximab and Etanercept reduced the percentage and numbers of CD19+ B cells, CD19+CD20+ B cells, CD19+CD27+ B cells and CD19+CD20+CD27+ B cells induced by BAFF or TNF-alpha. There was significant difference between CP-25 and Rituximab or CP-25 and Etanercept. CP-25 down-regulated the high expression of BAFFR, BCMA, and TACI stimulated by BAFF or TNF-alpha. The effects of Rituximab and Etanercept on BAFFR or BCMA were stronger than that of CP-25. CP-25, Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha. CP-25, Rituximab and Etanercept down-regulated the expression of MKK3, P-p38, P-p65, TRAF2, and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha. These results suggest that CP-25 regulated moderately activated B cells function by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway. This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.

  2. CP-25, a Novel Anti-inflammatory and Immunomodulatory Drug, Inhibits the Functions of Activated Human B Cells through Regulating BAFF and TNF-alpha Signaling and Comparative Efficacy with Biological Agents.

    Science.gov (United States)

    Zhang, Feng; Shu, Jin-Ling; Li, Ying; Wu, Yu-Jing; Zhang, Xian-Zheng; Han, Le; Tang, Xiao-Yu; Wang, Chen; Wang, Qing-Tong; Chen, Jing-Yu; Chang, Yan; Wu, Hua-Xun; Zhang, Ling-Ling; Wei, Wei

    2017-01-01

    Paeoniflorin-6'- O -benzene sulfonate (code: CP-25) was the chemistry structural modifications of Paeoniflorin (Pae). CP-25 inhibited B cells proliferation stimulated by B cell activating factor belonging to the TNF family (BAFF) or Tumor necrosis factor alpha (TNF-alpha). CP-25, Rituximab and Etanercept reduced the percentage and numbers of CD19 + B cells, CD19 + CD20 + B cells, CD19 + CD27 + B cells and CD19 + CD20 + CD27 + B cells induced by BAFF or TNF-alpha. There was significant difference between CP-25 and Rituximab or CP-25 and Etanercept. CP-25 down-regulated the high expression of BAFFR, BCMA, and TACI stimulated by BAFF or TNF-alpha. The effects of Rituximab and Etanercept on BAFFR or BCMA were stronger than that of CP-25. CP-25, Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha. CP-25, Rituximab and Etanercept down-regulated the expression of MKK3, P-p38, P-p65, TRAF2, and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha. These results suggest that CP-25 regulated moderately activated B cells function by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway. This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.

  3. Model independent calculation of B(anti B0→D(*)+τ- anti ν)/B(anti B0→D(*)+e- anti ν)

    International Nuclear Information System (INIS)

    Hwang, D.S.

    2000-01-01

    Using the formulas for the dΓ/dq 2 distribution with non-zero lepton mass and experimentally determined form factors, we calculate the dΓ(D (*)+ l - anti ν)/dq 2 spectra and branching fractions for l=e,μ and τ. We obtain the results B(anti B 0 →D + τ - anti ν)/B(anti B 0 →D + e - anti ν)=0.278 +0.049 -0.035 and B(anti B 0 →D *+ τ - anti ν)/B(anti B 0 →D *+ e - anti ν)=0.256 +0.014 -0.013 . Since we used the experimentally measured form factors, these results are independent of theoretical models of the form factors. (orig.)

  4. Equilibrated anti-Monge Matrices

    Czech Academy of Sciences Publication Activity Database

    Fiedler, Miroslav

    2001-01-01

    Roč. 335, - (2001), s. 151-156 ISSN 0024-3795 R&D Projects: GA ČR GA201/98/0222 Institutional research plan: AV0Z1030915 Keywords : Monge matrix * anti-Monge matrix Subject RIV: BA - General Mathematics Impact factor: 0.423, year: 2001

  5. Anti-osteoporosis drug use

    DEFF Research Database (Denmark)

    Hoff, M.; Skurtveit, S.; Meyer, H. E.

    2018-01-01

    Summary: Use of anti-osteoporotic drugs (AODs) was examined in a Norwegian population 50–85 years. Among them with Fracture Risk Assessment Tool (FRAX) score for major osteoporotic fracture ≥ 20, 25% of the women and 17% of the men received AODs. The strongest predictors for AODs were high age in...

  6. Pendidikan Anti Korupsi Berbasis Agama

    Directory of Open Access Journals (Sweden)

    Kasinyo Harto

    2016-03-01

    Full Text Available Tulisan ini memfokuskan pada pendidikan anti korupsi melalui perspektif agama dengan model rekonstruksi sosial. Pendekatan teoritis pendidikan  antikorupsi berbasis agama berupaya melihat sejauhmana realitas masyarakat religius dapat diakomodasi dalam aspek-aspek Pendidikan Anti-Korupsi, baik pada aspek materi, metode pembelajaran, evaluasi, dan sebagainya. Dengan pendekatan seperti itu, tulisan ini diharapkan mampu melakukan analisis-sintesis yang menghasilkan konsep-konsep teoritis PAK berbasis agama yang visibel untuk diterapkan dalam proses pembelajaran di kelas dan berhasil dalam implementasinya pada kehidupan sehari-hari. Jika konsep ini mungkin diterapkan, maka diharapkan akan terjadi perubahan dalam cara pandang peserta didik terhadap nilai agama yang dapat diterapkan dalam kehidupan empiris. Dampak lebih jauh dan jangka panjang diharapkan bahwa proses menuju masyarakat Indonesia yang bersih semakin  akan dapat diwujudkan. This paper focused on the anti-corruption education through religion perspective with social reconstruction model. The theoretical approach of anti-corruption education based religion sought to see how far the reality of religious communities could be accommodated in the aspects of Anti-Corruption Education, both in material aspects, teaching methods, evaluation, and so on. With that approach, this paper was expected to do the analysis-synthesis that produced theoretical concepts PAK-based religion that was visible to be applied in the learning process in the classroom and succeed in its implementation in daily life. If this concept might be applied, it was expected that there would be changes in learners' perspective on religion values that could be applied in empirical life. Further impacts and long-term it was expected that the process towards the Indonesian societies who clean more would be created.

  7. Impact of leptonic tau decays on the distribution of anti B → Dμ anti ν

    Energy Technology Data Exchange (ETDEWEB)

    Bordone, Marzia; Isidori, Gino; Dyk, Danny van [Physik-Institut, Universitaet Zuerich, Winterthurer Strasse 190, 8057 Zuerich (Switzerland)

    2016-07-01

    We present results for the decay rate of anti B → Dτ(→ μ anti νν) anti ν, which is a sizeable background to anti B → Dμ anti ν decays. In particular, we calculate analytically the differential decay rate with respect to all seven kinematic variables. We consider the impact of this decay on the distributions of anti B → Dμ anti ν in either the muon helicity angle or the muon energy in the anti B rest frame. Our numerical results are obtained from Monte Carlo pseudo events. Finally, we provide necessary information for cross checks of the experimental analyses.

  8. Production of d, t, 3He, anti d, anti t and anti 3He by 200 GeV protons

    International Nuclear Information System (INIS)

    Bozzoli, W.; Giacomelli, G.; Rimondi, F.; Zylberajch, S.; Lesquoy, E.; Meunier, R.; Moscoso, L.; Muller, A.; Bussiere, A.

    1978-01-01

    Data are presented on the yields of d, t, 3 He, anti d, anti t, and anti 3 He with laboratory momenta between 12 and 37 GeV/c produced by 200 GeV protons on beryllium and aluminium. The production yield of nuclei depends significantly on the target nucleus, while the anti d production is independent of target material. The mass dependence of the production cross section is exponential for both nuclei and antinuclei

  9. Anti-idiotypic antibodies directed against anti-HBs among the patients with chronic hepatitis B.

    Science.gov (United States)

    Kobayashi, K; Suzuki, H; Ueno, Y; Nagatomi, R; Kanno, A; Otsuki, M; Toyota, T

    1990-08-01

    Anti-idiotypic antibodies (anti-Id) against anti-HBs were found in the sera of patients with chronic hepatitis type B. Anti-idiotypic antibodies were detected by an enzyme-linked immunosorbent assay using horseradish peroxidase conjugated mouse monoclonal anti-HBs. Ten of 72 HBsAg positive sera contained anti-Id (13.9%). The prevalence of anti-Id did not appear to correlate with HBeAg/anti-HBe system. However, HB virus specific DNA polymerase activity was significantly higher in anti-Id positive sera. In the sera obtained from the patients treated with predonisolone before, anti-Id positive rate was higher than that in the patients without a history of predonisolone therapy. These results suggest that anti-Id may be related to the immunoregulatory mechanism of HB virus replication.

  10. Anti- versus Pro-Competitive Mergers

    OpenAIRE

    Fridolfsson, Sven-Olof

    2007-01-01

    In a framework where mergers are mutually excluding, I show that firms pursue anti- rather than (alternative) pro-competitive mergers. Potential outsiders to anti-competitive mergers refrain from pursuing pro-competitive mergers if the positive externalities from anti-competitive mergers are strong enough. Potential outsiders to pro-competitive mergers pursue anti-competitive mergers if the negative externalities from the pro-competitive mergers are strong enough. Potential participants in an...

  11. [Analytic study of dot blotting for the detection of anti-Jo-1, anti-M2, anti-ribosomes and anti-LKM].

    Science.gov (United States)

    Huguet, S; Sghiri, R; Ballot, E; Johanet, C

    2004-01-01

    The Cyto-Dot 4 HM043 kit commercialised by BMD, has replaced the Cyto-Dot HM010 kit that allowed three auto-antibodies detection (anti-Jo-1, anti-M2 and anti-ribosomal protein). Detection of anti-LKM1 auto-antibody was added. These four auto-antibodies have in common only the intracytoplasmic localisation of their respective antigen. The aim of our study was to evaluate this new kit using 104 sera and to compare our results with reference techniques (indirect immunofluorescence IF for anti-M2, anti-ribosomal protein and anti-LKM1, double immunodiffusion ID for anti-Jo-1 and anti-LKM1, western blotting WB for anti-M2) and with Cyto-Dot HM010. The one hundred and four sera were divided into five groups: Group I (n = 12) with anti-Jo-1 detected by ID; Group II (n = 28) with 26 anti-M2 positive by IF and WB, 2 anti-M2 positive only by WB; Group III (n = 10) with anti-ribosomal protein detected by IF 5 of which precipitated by ID; Group IV (n = 32) with anti-LKM1 by IF and ID divided into 18 AIH2 and 14 HCV; Group V (n = 22) consisting of 14 healthy individuals and 8 patients with hypergammaglobulinemia. Results of this study are similar to those of Cyto-Dot HM010 for the three auto-antibodies already in use. Cyto-Dot 4 is a very good anti-LKM1 confirmation method as it is ID. Copyright John Libbey Eurotext 2003.

  12. Anti-clogging filter system

    Science.gov (United States)

    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.

  13. Biological anti-TNF drugs

    DEFF Research Database (Denmark)

    Prado, Mônica Simon; Bendtzen, Klaus; Andrade, Luis Eduardo Coelho

    2017-01-01

    practice shows a significant percentage of individuals who do not exhibit the desired response. Loss of therapeutic benefit after initial successful response is designated secondary failure. Immune-biological agents are not self-antigens and are therefore potentially immunogenic. Secondary failure...... is frequently caused by antibodies against immune-biologicals, known as anti-drug antibodies (ADA). ADA that neutralize circulating immune-biologicals and/or promote their clearance can reduce treatment efficacy. Furthermore, ADA can induce adverse events by diverse immunological mechanisms. This review...... provides a comprehensive overview of ADA in rheumatoid arthritis patients treated with anti-TNF immune-biologicals, and explores the concept of therapeutic drug monitoring (TDM) as an effective strategy to improve therapeutic management. Expert opinion: Monitoring circulating ADA and therapeutic immune-biological...

  14. p anti p atom spectroscopy

    International Nuclear Information System (INIS)

    Kerbikov, B.O.

    1980-01-01

    A detailed investigation of the nuclear shifts of p anti p atom s levels is presented. The problem is discussed within the framework of a simple model assuming the existence of such an interaction radius R that strong interaction may be neglected for the range r>R and the Coulomb one for the range r< R. The analytic structure of the S matrix is taken into account. It is shown that the protonium spectrum may be completely rearranged due to the interaction in n anti n channel. A procedure has been developed for the localization of the instability domains of the multichannel system spectrum. The data on the nuclear shifts do not allow qualitative predictions on the position of the nuclear-like state near the threshold

  15. Anti-TNF-α biotherapies

    DEFF Research Database (Denmark)

    Bendtzen, Klaus

    2012-01-01

    This article discusses the rationale behind recommending immunopharmacological guidance of long-term therapies with genetically engineered anti-TNF-α immunoglobulin constructs. Arguments why therapeutic decision-making should not rely on clinical outcome alone are presented. Central...... to this is that the use of theranostics (i.e., monitoring circulating levels of functional anti-TNF-α drugs and antidrug antibodies) would markedly improve treatment because therapies can be tailored to individual patients and provide more effective and economical long-term therapies with minimal risk of side effects....... Large-scale immunopharmacological knowledge of how patients 'handle' TNF-α biopharmaceuticals would also help industry develop more effective and safer TNF-α inhibitors....

  16. 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...

  17. Adventures with the K anti K system

    International Nuclear Information System (INIS)

    Cason, N.M.

    1975-01-01

    The status of the new generation of K anti K experiments is reviewed. The reactions discussed are of the type πN → K anti KN. The general characteristics of the K anti K system which make it interesting and unique, the results of the first generation of experiments, and finally the status of the current experiments and some plans for future analyses

  18. Mimicking anti-correlations with classical interference

    International Nuclear Information System (INIS)

    Godoy, S; Seifert, B; Wallentowitz, S

    2013-01-01

    It is shown how classical laser light impinging on a beam splitter with internal reflections may mimic anti-correlations of the detected outputs, similar to those observed for anti-bunched light. The experimentally observed anti-correlation may be interpreted as a classical Hong–Ou–Mandel dip. (paper)

  19. Corruption and Anti-Corruption

    OpenAIRE

    Larmour, Peter; Wolanin, Nick

    2013-01-01

    There is new international attention being given to the old problem of corruption. It has been taken up by international organisations, and driven by economic analysis. It is impatient of cultural justifications, and suspicious of state action. It is concerned with corruption prevention as much as detection, investigation and prosecution. Corruption and Anti-Corruption deals with the international dimensions of corruption, including campaigns to recover the assets of former dictators, and...

  20. Anti-authoritarianism and school

    OpenAIRE

    Lah, Irena

    2016-01-01

    When looking for an answer to the question why the mankind , despite general democratization and access to public education in developed countries and despite rapid scientific and technological development so far, has been still encountering the most basic human issues, the roles of authority and anti-authority in relation to school at unsuccessful confrontation and solving mankind's problems have been researched. For this purpose, historical foundations of authority in the forms of tradit...

  1. EU Lobbying and Anti-Dumping Policy

    DEFF Research Database (Denmark)

    Nielsen, Jørgen Ulff-Møller; Svendsen, Gert Tinggaard

    2012-01-01

    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...... to the empirical pattern of EU country distribution in Council voting. Our results show a low petitioning intensity for anti-dumping investigations and a high voting intensity against anti-dumping measures in Northern Europe. Thus, it seems likely that domestic lobbying efforts have influenced the political...

  2. 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

    Directory of Open Access Journals (Sweden)

    Chao Lien Liu

    2016-06-01

    Full Text Available 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.

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

    International Nuclear Information System (INIS)

    Bienert, Maren; Reisinger, Ingrid; Humplik, Beatrice I.; Reim, Christel; Kroessin, Thomas; Avril, Norbert; Munz, Dieter L.; Srock, Stefanie; Pezzutto, Antonio

    2005-01-01

    The aim of this study was to evaluate the safety, toxicity and therapeutic response of non-myeloablative radioimmunotherapy using 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 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 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.)

  4. 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.

  5. Partial wave analysis of anti pp → anti ΛΛ

    International Nuclear Information System (INIS)

    Bugg, D.V.

    2004-01-01

    A partial wave analysis of PS185 data for anti pp → anti ΛΛ is presented. A 3 S 1 cusp is identified in the inverse process anti ΛΛ→ anti p p at threshold, using detailed balance to deduce cross sections from anti pp → anti ΛΛ. Partial wave amplitudes for anti pp 3 P 0 , 3 F 3 , 3 D 3 and 3 G 3 exhibit a behaviour very similar to resonances observed in Crystal Barrel data. With this identification, the anti pp → anti ΛΛ data then provide evidence for a new I=0, J PC =1 - resonance with mass M = 2290 ±20 MeV, Γ= 275 ±35 MeV, coupling to both 3 S 1 and 3 D 1 . (orig.)

  6. Exotic tetraquark states with the qq anti Q anti Q configuration

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Si-Qiang; Chen, Kan; Liu, Xiang [Lanzhou University, School of Physical Science and Technology, Lanzhou (China); Lanzhou University and Institute of Modern Physics, CAS, Research Center for Hadron and CSR Physics, Lanzhou (China); Liu, Yan-Rui [Shandong University, School of Physics and Key Laboratory of Particle Physics and Particle Irradiation (MOE), Jinan (China); Zhu, Shi-Lin [Peking University, School of Physics and State Key Laboratory of Nuclear Physics and Technology, Beijing (China); Collaborative Innovation Center of Quantum Matter, Beijing (China); Peking University, Center for High Energy Physics, Beijing (China)

    2017-10-15

    In this work, we study systematically the mass splittings of the qq anti Q anti Q (q = u, d, s and Q = c, b) tetraquark states with the color-magnetic interaction by considering color mixing effects and estimate roughly their masses. We find that the color mixing effect is relatively important for the J{sup P} = 0{sup +} states and possible stable tetraquarks exist in the nn anti Q anti Q (n = u, d) and ns anti Q anti Q systems either with J = 0 or with J = 1. Possible decay patterns of the tetraquarks are briefly discussed. (orig.)

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

    International Nuclear Information System (INIS)

    Albrecht, H.; Ehrlichmann, H.; Hamacher, T.; Hofmann, R.P.; Kirchhoff, T.; Nau, A.; Nowak, S.; Schroeder, H.; Schulz, H.D.; Walter, M.; Wurth, R.; Appuhn, R.D.; Hast, C.; Kolanoski, H.; Lange, A.; Lindner, A.; Mankel, R.; Schieber, M.; Siegmund, T.; Spaan, B.; Thurn, H.; Toepfer, D.; Walther, A.; Wegener, D.; Britton, D.I.; Charlesworth, C.E.K.; Edwards, K.W.; Hyatt, E.R.F.; Kapitza, H.; Krieger, P.; MacFarlane, D.B.; Patel, P.M.; Prentice, J.D.; Saull, P.R.B.; Tzamariudaki, K.; Van de Water, R.G.; Yoon, T.S.; Ressing, D.; Schmidtler, M.; Schneider, M.; Schubert, K.R.; Strahl, K.; Waldi, R.; Weseler, S.

    1993-01-01

    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 B 0 →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 B 0 →D *+ (→D 0 π + )l - anti ν the forward-backward asymmetry A FB and the D *+ polarization parameter α have been determined to be A FB =0.20±0.08±0.06 and α=1.1±0.4±0.2. (orig.)

  8. Anti-deuteron sensitivity studies at LHCb

    CERN Multimedia

    Baker, Sophie Katherine

    2018-01-01

    Measurements of anti-deuterons in collider experiments can help to reduce systematic uncertainties in indirect searches for dark matter. Two predominant unknowns in these searches are the production of secondary anti-deuterons in the cosmos from spallation processes, and anti-deuteron production from annihilating dark matter. LHCb is a forward spectrometer on the LHC ring, designed to measure b-hadron decays from high energy proton-proton collisions. With the detector's excellent particle identification capabilities, deuteron and anti-deuteron measurements at LHCb could help to parametrise the two cosmological processes. Recent studies of (anti-)deuteron identification at LHCb and the prospects for measuring prompt (anti-)deuterons from pp-collisions will be presented, as well as a working analysis of b-baryrons decaying to deuterons.

  9. 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...

  10. Anti-synchronization of chaotic oscillators

    International Nuclear Information System (INIS)

    Kim, Chil-Min; Rim, Sunghwan; Kye, Won-Ho; Ryu, Jung-Wan; Park, Young-Jai

    2003-01-01

    We have observed anti-synchronization phenomena in coupled identical chaotic oscillators. Anti-synchronization can be characterized by the vanishing of the sum of relevant variables. We have qualitatively analyzed its base mechanism by using the dynamics of the difference and the sum of the relevant variables in coupled chaotic oscillators. Near the threshold of the synchronization and anti-synchronization transition, we have obtained the novel characteristic relation

  11. Anti-VEGF drugs: evidence for effectiveness

    OpenAIRE

    Evans, Jennifer; Virgili, Gianni

    2014-01-01

    Anti-vascular endothelial growth factors (anti-VEGF) are targeted biological drugs (e.g. monoclonal antibodies) that prevent the growth of new vessels by inhibiting VEGF. VEGF is a cytokine (cell-signalling protein) that promotes the growth of, and leakage from, new vessels. Currently there are three anti-VEGF drugs licensed for use in eye disease: pegaptanib, aflibercept, ranibizumab and one that is not licensed but is commonly used off-label (bevacizumab).

  12. 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.

  13. 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.

  14. PERILAKU ANTI SOSIAL PADA ANAK SEKLOAH DASAR

    Directory of Open Access Journals (Sweden)

    Ratna Sari Dewi

    2015-09-01

    Full Text Available Perilaku Anti Sosial merupakan perilaku negatif atau perilaku yang menyimpang dari norma-norma, baik aturan keluarga, sekolah, masyarakat, maupun hukum. Jenis perilaku anti sosial pada anak sekolah dasar diantaranya perilaku negativisme, agresi dan tingkah laku menguasai. Faktor risiko yang menyebabkan perilaku anti sosial pada anak-anak dapat dikategorikan sebagai faktor pribadi (personal risk factors, keluarga (family risk factors, berkaitan dengan sekolah (school-related risk factors dan sosial (social risk factors. Upaya penanganan anak dengan anti sosial dapat dilakukan dengan upaya orang tua menerapkan pola asuh authoritative. Jika terlanjur berperilaku anti sosial pada taraf melanggar hukum negara, maka orang tua harus membawa anaknya untuk melakukan terapi gangguan kepribadian, yang disebut Terapi Perilaku Dialektikal. Sedangkan yang dapat diupayakan guru dalam menangani anak anti sosial adalah dengan menerapkan metode pembelajaran kooperatif serta memberikan perhatian Psikologi dan Perkembangan Multiple Intelegensi Anak. Selain itu masyarakat dapat memberikan kontribusi dalam penanganan anak anti sosial dengan cara menumbuhkan norma sosial yang baik serta tersedianya tayangan media massa yang memberikan tuntunan baik bagi anak.Kata Kunci : Anti – Sosial, Kooperatif, Multiple IntelegensiAnti-social behavior is a negative behavior or deviates behavior  from the norms, a good rule of family, school, community, or the law. The type of anti-social behavior in elementary school children including negativism behavior, aggression and behavioral controls. The risk factors that lead to anti-social behavior in children can be categorized as personal factors (personal risk factors, family (family risk factors, related to the school (school-related risk factors and social (social risk factors. Efforts to tackle anti-social child can do with the efforts of parents to apply parenting authoritative. If already at the level of anti-social behavior in

  15. Anti-neutrino disintegration of the deuteron

    International Nuclear Information System (INIS)

    Mueller, W.; Gari, M.; Max-Planck-Institut fuer Chemie

    1981-01-01

    The anti-neutrino disintegration of the deuteron (anti ν + D → anti ν + n + p and anti νsub(e) + D → + e + + n + n) is calculated using realistic two-body states. Meson-exchange currents are considered in the one-boson-exchange limit. The results are discussed as corrections to the cross sections obtained in effective range approximations. It is shown that the ratio of the cross sections (sigma - /sigma 0 ) for reactor antineutrinos is practically independent of the nuclear physics uncertainties. (orig.)

  16. Anti-inflammatory effects of exercise

    DEFF Research Database (Denmark)

    Pedersen, Bente Klarlund

    2017-01-01

    and IL-10 is provoked by exercise and exerts direct anti-inflammatory effects by an inhibition of TNF-α and by stimulating IL-1ra, thereby limiting IL-1β signalling. Moreover, muscle-derived IL-6 appears to have direct anti-inflammatory effects and serves as a mechanism to improve glucose tolerance....... In addition, indirect anti-inflammatory effects of long-term exercise are mediated via improvements in body composition. CONCLUSION: Physical activity represents a natural, strong anti-inflammatory strategy with minor side effects and should be integrated in the management of patients with cardiometabolic...

  17. 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...

  18. Configuring Symantec AntiVirus

    CERN Document Server

    Shimonski, Robert

    2003-01-01

    This is the only book that will teach system administrators how to configure, deploy, and troubleshoot Symantec Enterprise Edition in an enterprise network. The book will reflect Symantec''s philosophy of "Centralized Antivirus Management." For the same reasons that Symantec bundled together these previously separate products, the book will provide system administrators with a holistic approach to defending their networks from malicious viruses. This book will also serve as a Study Guide for those pursuing Symantec Product Specialist Certifications.Configuring Symantec AntiVirus Enterprise Edition contains step-by-step instructions on how to Design, implement and leverage the Symantec Suite of products in the enterprise.ØFirst book published on market leading product and fast-growing certification. Despite the popularity of Symantec''s products and Symantec Product Specialist certifications, there are no other books published or announced.ØLess expensive substitute for costly on-sight training. Symantec off...

  19. 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

  20. Anti-cancer Lead Molecule

    KAUST Repository

    Sagar, Sunil; Kaur, Mandeep; Esau, Luke E.

    2014-01-01

    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

  1. The anti-nuclear disinformation

    International Nuclear Information System (INIS)

    Gay, Michel

    2013-01-01

    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

  2. The Salivary Anti-A and Anti-B Isoantibody System in Group O Males.

    Science.gov (United States)

    agglutinins increased significantly in two individuals and anti-B in four, and parotid saliva anti-A agglutinins in one and anti-B in three. Both whole...and parotid saliva agglutinating activity were demonstrated to be primarily due to secretory IgA, both pre- and postimmunization. IgG coating activity

  3. Anti-oxidant and anti-inflammatory effects of rice bran and green tea ...

    African Journals Online (AJOL)

    Purpose: To investigate the anti-inflammatory and anti-oxidant properties of an enzyme bath of Oryza sativa (rice bran) and Camellia sinensis O. Kuntz (green tea) fermented with Bacillus subtilis (OCB). Methods: The anti-oxidant effects of OCB were assessed by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) assay and flow ...

  4. Theatrical language, narrative techniques and anti-anti-Gypsyism

    Directory of Open Access Journals (Sweden)

    Andrea Mochi Sismondi

    2017-07-01

    Full Text Available With this article based on his fieldwork in Šuto Orizari, a Municipality in the suburbs of Skopje (Macedonia, the author analyses how theatrical language and narrative techniques can be used to oppose the strengthening of anti-gypsyism in public opinion. Šuto Orizari is the only Municipality in the world where romanés is used as an official language, and the Mayor and the majority of the members of the assembly of the municipality come from the Roma community, thus enjoying a degree of effective self-government. Andrea Mochi Sismondi and Fiorenza Menni lived there for two years trying to understand the different visions of the world originating among Roma, while collecting dramaturgical materials later used in the production of two theatrical performances, a book and several public events where Roma and Gadžé can exchange their points of view on fundamental issues concerning political philosophy. Freedom, equality, the legitimate aspiration to a better life, freedom of movement: all values modern constitutions are based on, and on which the two artists focused their long interviews and conversations with Šuto Orizari citizens and Roma colleagues. The work has been presented all over Italy and its results reveal how literary non-fiction and performing arts can be successfully used to show the weakness of the arguments alleging the cultural distance that would make the dialogue between Roma and Gadžé impossible.

  5. Independence requirements for anti-corruption institutions

    African Journals Online (AJOL)

    The Court's approach and these apparent requirements are compared with current provisions for political 'independence' of anti-corruption agencies in Australia and Indonesia, raising, in particular, an assessment of the arguments for and against (a) the need for an anti-corruption investigative agency to be separate from ...

  6. Anti-malware software and medical devices.

    Science.gov (United States)

    2010-10-01

    Just as much as healthcare information systems, medical devices need protection against cybersecurity threats. Anti-malware software can help safeguard the devices in your facility-but it has limitations and even risks. Find out what steps you can take to manage anti-malware applications in your devices.

  7. Combined antiretroviral and anti- tuberculosis drug resistance ...

    African Journals Online (AJOL)

    these epidemics, many challenges remain.[3] Antiretroviral and anti-TB drug resistance pose considerable threats to the control of these epidemics.[4,5]. The breakdown in HIV/TB control within prisons is another emerging threat.[6,7] We describe one of the first reports of combined antiretroviral and anti-TB drug resistance ...

  8. Discrimination and Anti-discrimination in Denmark

    DEFF Research Database (Denmark)

    Olsen, Tore Vincents

    The purpose of this report is to describe and analyse Danish anti-discrimination legislation and the debate about discrimination in Denmark in order to identify present and future legal challenges. The main focus is the implementation of the EU anti-discrimination directives in Danish law...

  9. What's Missing? Anti-Racist Sex Education!

    Science.gov (United States)

    Whitten, Amanda; Sethna, Christabelle

    2014-01-01

    Contemporary sexual health curricula in Canada include information about sexual diversity and queer identities, but what remains missing is any explicit discussion of anti-racist sex education. Although there exists federal and provincial support for multiculturalism and anti-racism in schools, contemporary Canadian sex education omits crucial…

  10. Anti-emetic principles of Poria cocos.

    Science.gov (United States)

    Tai, T; Akita, Y; Kinoshita, K; Koyama, K; Takahashi, K; Watanabe, K

    1995-12-01

    The triterpenes isolated from P. cocos and their derivatives were examined for anti-emetic activity. Some of these triterpenes inhibited emetic action induced by oral administration of copper sulfate pentahydrate to leopard frog. The triterpenes having an exomethylene group at C-24 showed anti-emetic activity to frogs.

  11. Stabiliteit van drijvende lichamen; anti-slingertanks

    NARCIS (Netherlands)

    Bourgingnon, G.P.

    1980-01-01

    Het dempen van de slingerbewegingen (roll) van een drijvend lichaam door middel van tanks met een vrije vloeistofoppervlakte. In de scheepsbouwkunde is vrij veel bekend over het toepassen van anti-slingertanks. De anti-slingertank, die ook dempt bij een stilliggend schip (in tegenstelling tot

  12. Anti-influenza M2e antibody

    Science.gov (United States)

    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.

  13. Anti-inflammatory and neuropharmacological activities of ...

    African Journals Online (AJOL)

    The crude methanolic extracts of leaves of Caesalpinia pulcherrima were evaluated for its anti-inflammatory and neuropharmacological activities. When given orally to rats at dose of 200 and 400 mg/kg, the extract showed a significant (P<0.001) anti-inflammatory activity against carrageenin induced paw edema in rats ...

  14. An anti-inflammatory principle from cactus.

    Science.gov (United States)

    Park, E H; Kahng, J H; Lee, S H; Shin, K H

    2001-03-01

    In previous studies, the ethanol extract of cactus (Opuntia ficus-indica) showed potent anti-inflammatory action. In the present study, following fractionation of the methanol extract of cactus stems guided by adjuvant-induced chronic inflammation model in mice, an active anti-inflammatory principle has been isolated and identified as beta-sitosterol.

  15. Anti-mutated citrullinated vimentin (anti-MCV) and anti-65 kDa heat shock protein (anti-hsp65): new biomarkers in ankylosing spondylitis.

    Science.gov (United States)

    Bodnár, Nóra; Szekanecz, Zoltán; Prohászka, Zoltán; Kemény-Beke, Adám; Némethné-Gyurcsik, Zsuzsanna; Gulyás, Katalin; Lakos, Gabriella; Sipka, Sándor; Szántó, Sándor

    2012-01-01

    Citrullination as well as anti-citrullinated protein/peptide antibodies (ACPA) have been implicated in the pathogenesis of rheumatoid arthritis (RA). While ACPAs are specific and sensitive markers for RA, there have been hardly any reports regarding ACPAs in ankylosing spondylitis (AS). The possible role of antibodies to Mycobacterial 65 kDa heat shock protein (hsp65) has not been characterized in AS. As new laboratory biomarkers of AS are needed, we investigated the prevalence of anti-mutated citrullinated vimentin (MCV) and anti-hsp65 antibodies in AS. Altogether 43 AS and 44 healthy controls were included in the study. Anti-MCV and anti-hsp65 were determined in sera by commercial and in-house ELISA, respectively. Serum autoantibody levels were correlated with ESR, CRP, HLA-B27 status, smoking habits, pain intensity, BASDAI, BASFI and BASMI indices. Patients with AS had significantly higher serum anti-MCV levels (17.3 U/mL, range: 8.3-31.5 U/mL) in comparison to healthy subjects (8.9 U/mL, range: 5.4-13.3 U/mL) (p20 U/mL). The mean anti-hsp65 concentration in AS sera was 124.8 AU/mL (range: 27.2-1000 AU/mL), while controls exerted significantly lower anti-hsp65 levels (mean: 51.8 AU/mL; range: 22.5-88.5 AU/mL) (p<0.001). Correlation analysis revealed that both anti-MCV positivity (r=0.613; p=0.012) and absolute serum anti-MCV levels (r=0.553; p=0.021) correlated with anti-hsp65 levels. Anti-MCV positivity also correlated with ESR (r=0.437; p=0.03). Anti-MCV and anti-hsp65 may be novel biomarkers in AS. Copyright © 2011. Published by Elsevier SAS.

  16. 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.”

  17. Anti-atherosclerotic effects of tomatoes

    Directory of Open Access Journals (Sweden)

    Hidekatsu Yanai

    2017-06-01

    Full Text Available Tomatoes are rich in lycopene, which causes the red coloring of tomatoes. Several reports have suggested lycopene plays a role in the prevention of cardiovascular diseases. In this study, we systematically reviewed the interventional studies using tomatoes or tomato products to understandtheanti-atherosclerotic effects of the tomatoas a functional food. We found that a significantnumber of interventional studies reportedtheanti-atherosclerotic effects of tomatoes, includinganti-obesity effects, hypotensiveeffects, improvement of lipid/glucose metabolismand endothelial function, anti-oxidative and anti-inflammatory effect, and anti-platelet effect; however, the anti-platelet effect was disagreed uponby some studies. Furthermore, we discoveredcooking methods significantlyaffect anti-atherosclerotic effects of tomatoes.

  18. Intravenous Immunoglobulin therapy for anti-E hemolytic disease in the newborn.

    Science.gov (United States)

    Onesimo, Roberta; Rizzo, Daniela; Ruggiero, Antonio; Valentini, Piero

    2010-09-01

    Anti-E alloimmunisation is a less common cause of haemolytic disease in the newborn (HDN) and is usually associated with mild to moderate clinical manifestations, that are often less severe than anti-D immunisation. Conventional treatments for HDN are phototherapy and exchange transfusion, the latter still representing a high-risk procedure. Currently, intravenous immunoglobulin has been used as alternative treatment for HDN to reduce the need for exchange transfusion, as well as the length of phototherapy and hospitalisation. We report a case of anti-E HDN treated successfully with intravenous immunoglobulin, as adjuvant treatment to phototherapy.

  19. Pharmacological Experimental Study Of The Anti-Depressant Effect ...

    African Journals Online (AJOL)

    Pharmacological Experimental Study Of The Anti-Depressant Effect Of Total Saikosaponins. Y Liu, C Cao, H Ding. Abstract. Background: Chai Hu has the hepato-protective, choleretic, anti-tussive, analgesic, anti-inflammatory, anti-viral, hypotensive, hypolipidemic, and anti-tumor pharmacological effects. In this study, the ...

  20. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Identification of {2 anti 1 anti 10} and {10 anti 10} Laue patterns of hexagonal and rhombohedral silicon carbide polytypes

    International Nuclear Information System (INIS)

    Yoganathan, M.; Suttrop, W.; Devaty, R.P.; Choyke, W.J.

    1994-01-01

    The development of epitaxic and bulk-grown semiconductor SiC exhibiting uniform polytype phase homogeneity is critically dependent upon the accurate identification of crystallographic orientations corresponding to the desired polytype. In this paper, experimental transmission Laue photographs as well as computer-generated transmission Laue patterns are presented for {2 anti 1 anti 10} and {10 anti 10} faces of the 4H, 6H and 15R polytypes of silicon carbide. The transmission patterns permit easy recognition of polytypes and crystal orientations. (orig.)

  2. 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.

  3. IN-VITRO EVALUATION OF ANTI-TRICHOMONAL ACTIVITIES OF ...

    African Journals Online (AJOL)

    infective, has shown anti-malarial and antitrypanocidal activities. Therefore using bioactivity guided fractionation, anti-trichomonal activity of E. uniflora leaf was investigated. Anti-trichomonal activities of leaf methanol extract and its fractions against ...

  4. Anti-Seizure Medications: Relief from Nerve Pain

    Science.gov (United States)

    Anti-seizure medications: Relief from nerve pain Anti-seizure drugs often are used to help control the type of ... by damaged nerves. By Mayo Clinic Staff Anti-seizure medications were originally designed to treat people with ...

  5. Adaptive H∞ Chaos Anti-synchronization

    International Nuclear Information System (INIS)

    Ahn, Choon Ki

    2010-01-01

    A new adaptive H ∞ anti-synchronization (AHAS) method is proposed for chaotic systems in the presence of unknown parameters and external disturbances. Based on the Lyapunov theory and linear matrix inequality formulation, the AHAS controller with adaptive laws of unknown parameters is derived to not only guarantee adaptive anti-synchronization but also reduce the effect of external disturbances to an H ∞ norm constraint. As an application of the proposed AHAS method, the H ∞ anti-synchronization problem for Genesio–Tesi chaotic systems is investigated. (general)

  6. Physics of nuclear anti-shadowing

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, I. [Universidad Tecnica Federico Santa Maria, Dept. de Fisica, Valparaiso (Chile)

    2005-07-01

    Shadowing and anti-shadowing of the electromagnetic nuclear structure functions are produced by the coherence of multi-scattering quark nuclear processes. This picture leads to substantially different anti-shadowing for charged and neutral current processes, particularly in neutrino reactions, thus affecting the extraction of the weak-mixing angle sin{sup 2}({theta}{sub W}). We have found that the shadowing/anti-shadowing effect on the weak-mixing angle is approximately: {delta}sin{sup 2}({theta}{sub W}) = 0.001.

  7. 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

  8. Analysis of the QQ anti Q anti Q tetraquark states with QCD sum rules

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhi-Gang [North China Electric Power University, Department of Physics, Baoding (China)

    2017-07-15

    In this article, we study the J{sup PC} = 0{sup ++} and 2{sup ++} QQ anti Q anti Q tetraquark states with the QCD sum rules, and we obtain the predictions M{sub X(cc} {sub anti} {sub c} {sub anti} {sub c,0}{sup {sub +}{sub +)}} =5.99 ± 0.08 GeV, M{sub X(cc} {sub anti} {sub c} {sub anti} {sub c,2}{sup {sub +}{sub +)}} = 6.09 ± 0.08 GeV, M{sub X(bb} {sub anti} {sub b} {sub anti} {sub b,0}{sup {sub +}{sub +)}} = 18.84 ± 0.09 GeV and M{sub X(bb} {sub anti} {sub b} {sub anti} {sub b,2}{sup {sub +}{sub +)}} = 18.85 ± 0.09 GeV, which can be confronted to the experimental data in the future. Furthermore, we illustrate that the diquark-antidiquark type tetraquark state can be taken as a special superposition of a series of meson-meson pairs and that it embodies the net effects. (orig.)

  9. The prozone effect exerted by the complement-binding anti-Lea on anti-D.

    Science.gov (United States)

    Joshi, Sanmukh R; Parekh, Kamlesh H

    2017-01-01

    Prozone phenomenon is seen with very high-titer antibodies in an immune serum. The prozone effect on anti-D by a low-titer anti-Le a was investigated associated with neonatal jaundice. Standard methods were used in investigations. The child was born at full-term developed mild jaundice. With weak direct antiglobulin test+, her indirect serum bilirubin was progressed to 27.5 mg/dL in 48 h. Anti-D and anti-Le a were detected in the mother. Both these antibodies were detected in the child's serum though the eluate from red blood cells (RBCs) contained only anti-D. Mother's anti-D was masked by anti-Le a if the RBCs possessed both the antigens together. Anti-D was revealed only with D-positive RBCs lacking Le a or if the serum was modified by mixing with Le a+ saliva or was heated at 56°C or fortified with citrate solution. An anti-D showed prozone effect exerted by the complement-fixing anti-Le a in the test.

  10. Comments about anti-pp collisions

    International Nuclear Information System (INIS)

    Jung, M.

    1978-01-01

    A review concerning specific properties of anti-pp collisions has been done through the summary of several theoretical and experimental papers. Some new experimental measurements are suggested towards the analysis of different already known hadronic processes

  11. Laparoscopic Anti-Reflux (GERD) Surgery

    Science.gov (United States)

    ... and Humanitarian Efforts Login Laparoscopic Anti-Reflux (GERD) Surgery Patient Information from SAGES Download PDF Find a SAGES Surgeon Surgery for “Heartburn” If you suffer from moderate to ...

  12. EVALUATION OF ANTI-INFLAMMATORY, ANTIBACTERIAL AND ...

    African Journals Online (AJOL)

    User

    Anti-inflammatory activity was determined using a LOX-inhibitor screening assay kit according to the ... and the Ferric ion reducing antioxidant power (FRAP). Antimicrobial activities ..... the best of our knowledge this is the first report on the.

  13. National Health Care Anti-Fraud Association

    Science.gov (United States)

    ... a Glance Pre-Conference Programs Conference Sessions Registration Hotel & Travel Information Conference Tracks Credit Opportunities Anti-Fraud Expo Sponsors Programs Budget Adequately for 2018 Trainings NETS Webinars Launch Webinar ...

  14. Tomato leaves methanol extract possesses anti- inflammatory ...

    African Journals Online (AJOL)

    GREGORY

    2011-12-16

    Dec 16, 2011 ... demonstrated, the anti-inflammatory effect of tomato leaves and its associated molecular mechanisms have not yet .... dissolved in 10% of culture-grade dimethylsulfoxide (DMSO; Sigma-. Aldrich .... In Vitro Cell. Dev. Biol.

  15. 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....

  16. 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...

  17. Characterization of multilayer anti-fog coatings.

    Science.gov (United States)

    Chevallier, Pascale; Turgeon, Stéphane; Sarra-Bournet, Christian; Turcotte, Raphaël; Laroche, Gaétan

    2011-03-01

    Fog formation on transparent substrates constitutes a major challenge in several optical applications requiring excellent light transmission characteristics. Anti-fog coatings are hydrophilic, enabling water to spread uniformly on the surface rather than form dispersed droplets. Despite the development of several anti-fog coating strategies, the long-term stability, adherence to the underlying substrate, and resistance to cleaning procedures are not yet optimal. We report on a polymer-based anti-fog coating covalently grafted onto glass surfaces by means of a multistep process. Glass substrates were first activated by plasma functionalization to provide amino groups on the surface, resulting in the subsequent covalent bonding of the polymeric layers. The anti-fog coating was then created by the successive spin coating of (poly(ethylene-maleic anhydride) (PEMA) and poly(vinyl alcohol) (PVA) layers. PEMA acted as an interface by covalently reacting with both the glass surface amino functionalities and the PVA hydroxyl groups, while PVA added the necessary surface hydrophilicity to provide anti-fog properties. Each step of the procedure was monitored by XPS, which confirmed the successful grafting of the coating. Coating thickness was evaluated by profilometry, nanoindentation, and UV visible light transmission. The hydrophilic nature of the anti-fog coating was assessed by water contact angle (CA), and its anti-fog efficiency was determined visually and tested quantitatively for the first time using an ASTM standard protocol. Results show that the PEMA/PVA coating not only delayed the initial period required for fog formation but also decreased the rate of light transmission decay. Finally, following a 24 hour immersion in water, these PEMA/PVA coatings remained stable and preserved their anti-fog properties.

  18. Possible D(*) anti D(*) and B(*) anti B(*) molecular states in the extended constituent quark models

    International Nuclear Information System (INIS)

    Yang, You-Chang; Tan, Zhi-Yun; Ping, Jialun; Zong, Hong-Shi

    2017-01-01

    The possible neutral D (*) anti D (*) and B (*) anti B (*) molecular states are studied in the framework of the constituent quark models, which is extended by including the s-channel one-gluon exchange. Using different types of quark-quark potentials, we solve the four-body Schroedinger equation by means of the Gaussian expansion method. The bound states of D (*) anti D (*) with J PC = 1 ++ , 2 ++ and B (*) anti B (*) with J PC = 0 ++ , 1 +- , 1 ++ , 2 ++ are obtained. The molecular states D* anti D with J PC = 1 ++ and B* anti B with J PC = 1 +- are good candidates for X(3872) and Z 0 b (10610), respectively. The dependence of the results on the model parameters is also discussed. (orig.)

  19. Measurement of b anti b correlations at the CERN p anti p collider

    International Nuclear Information System (INIS)

    Albajar, C.; Ankoviak, K.; Bartha, S.; Bezaguet, A.; Boehrer, A.; Bos, K.; Buchanan, C.; Buschbeck, B.; Castilla-Valdez, H.; Cennini, P.; Cittolin, S.; Clayton, E.; Cline, D.; Caughlan, J.A.; Dau, D.; Daum, C.; Della Negra, M.; Demoulin, M.; Denegri, D.; Dibon, H.; Dorenbosch, J.; Dowell, J.D.; Eggert, K.; Eisenhandler, E.; Ellis, N.; Evans, H.; Faissner, H.; Fensome, I.F.; Fortson, L.; Garvey, J.; Geiser, A. Givernaud, A.; Gonidec, A.; Gonzalez, B.; Gronberg, J.; Holthuizen, D.J.; Jank, W.; Jorat, G.; Kalmus, P.I.P.; Karimaeki, V.; Kenyon, I.; Kinnunen, R.; Krammer, M.; Lammel, S.; Landon, M.P.J.; Lemoigne, Y.; Levegruen, S.; Lipa, P.; Markou, C.; Markytan, M.; Maurin, G.; McMahon, S.; Merlo, J.P.; Meyer, T.; Moers, T.; Mohammadi, M.; Morsch, A.; Moulin, A.; Norton, A.; Otwinowski, S.; Pancheri, G.; Pietarinen, E.; Pimiae, M.; Placci, A.; Porte, J.P.; Priem, R.; Prosi, R.; Radermacher, E.; Rauschkolb, M.; Reithler, H.; Revol, J.P.; Robinson, D.; Rubbia, C.; Samyn, D.; Schinzel, D.; Schleichert, R.; Schroeder, M.; Seez, C.; Shah, T.P.; Sphicas, P.; Sumorok, K.; Szoncso, F.; Tan, C.H.; Taurok, A.; Taylor, L.; Tether, S.; Teykal, H.; Thompson, G.; Tuchscherer, H.; Tuominiemi, J.; Van de Guchte, W.; Van Dijk, A.; Vargas, M.; Virdee, T.S.; Schlippe, W. von; Vuillemin, V.; Wacker, K.; Wagner, H.; Walzel, G.; Wulz, C.E.; Zotto, P.; NIKHEF-H, Amsterdam; Birmingham Univ.; CERN, Geneva; Helsinki Univ.; Kiel Univ.; Blackett Lab., Imperial Coll., London; Queen Mary and Westfield Coll., London; MIT, Cambridge, MA; Rutherford Appleton Lab., Chilton; DPHPE/SEPh, CEN Saclay, Gif-sur-Yvette; California Univ., Los Angeles, CA; Oesterreichische Akademie der Wissenschaften, Vienna

    1994-01-01

    We report on measurements of correlated b anti b production in p anti p at √s=630 GeV, using dimuon data to tag both the b and anti b quarks. Starting from an inclusive dimuon sample we obtain improved cross-sections for single inclusive beauty production and confirm our earlier results on B 0 - anti B 0 mixing. From a study of b anti b correlations we derive explicit cross-sections for semi-differential b anti b production. We compare the measured cross-sections and correlations to OMIKRON (α s 3 ) QCD predictions and find good quantitative agreement. From the measured angular distributions we establish a sizeable contribution from higher order QCD processes with a significance of about seven standard deviations. A large nonperturbative contribution to these higher order corrections is excluded. (orig.)

  20. Anti-foam System design description

    International Nuclear Information System (INIS)

    White, M.A.

    1994-01-01

    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

  1. DIALEKTIKA RADIKALISME DAN ANTI RADIKALISME DI PESANTREN

    Directory of Open Access Journals (Sweden)

    Thohir Yuli Kusmanto

    2015-06-01

    Upaya menentang segala bentuk radikalisme merupakan bagian dari reaksi anti radikalisme. Semangat anti radikalisme muncul sebagai bagian dari resistensi masyarakat. Radikalisme dan anti radikalisme saling berkaitan secara dialektis. Meski­pun keduanya merupakan sesuatu yang paradoks, namun selalu menyatu. Dialektika radikalisme dan anti radikalisme menarik ketika dilihat dalam kehidupan pesantren. Fenomena radikalisme Islam seringkali dihubungkan dengan masya­ra­kat pesantren di Indonesia. Beberapa kelompok masyarakat memahami radikal­isme tumbuh dari pesantren. Pandangan tersebut didasari oleh banyaknya pelaku radikalisme Islam dalam bentuk kekerasan alumni pesantren. Realitas tersebut bisa jadi benar dalam kasus tertentu, tetapi tidak bisa digeneralisasi. Penelitian ini ber­upaya menggali data pandangan pesantren tentang wacana dan praksis radikalisme dan anti radikalisme serta pola resistensinya. Hasil penelitian menunjukkan bahwa masyarakat pesantren menolak, menentang dan aktif membangun spirit anti radikalisme yang diwujud­kan dalam beberapa pola. Temuan penelitian tersebut merupakan sintesis dari tesis yang selama ini menjadi wacana masyarakat tentang radikalisme dan pesantren.

  2. The Superheavy Elements and Anti-Gravity

    International Nuclear Information System (INIS)

    Anastasovski, Petar K.

    2004-01-01

    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 < 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

  3. Anti-Inflammatory Iridoids of Botanical Origin

    Science.gov (United States)

    Viljoen, A; Mncwangi, N; Vermaak, I

    2012-01-01

    Inflammation is a manifestation of a wide range of disorders which include; arthritis, atherosclerosis, Alzheimer’s disease, inflammatory bowel syndrome, physical injury and infection amongst many others. Common treatment modalities are usually non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, paracetamol, indomethacin and ibuprofen as well as corticosteroids such as prednisone. These however, may be associated with a host of side effects due to non-selectivity for cyclooxygenase (COX) enzymes involved in inflammation and those with selectivity may be highly priced. Thus, there is a continuing search for safe and effective anti-inflammatory molecules from natural sources. Research has confirmed that iridoids exhibit promising anti-inflammatory activity which may be beneficial in the treatment of inflammation. Iridoids are secondary metabolites present in various plants, especially in species belonging to the Apocynaceae, Lamiaceae, Loganiaceae, Rubiaceae, Scrophulariaceae and Verbenaceae families. Many of these ethnobotanicals have an illustrious history of traditional use alluding to their use to treat inflammation. Although iridoids exhibit a wide range of pharmacological activities such as cardiovascular, hepatoprotection, hypoglycaemic, antimutagenic, antispasmodic, anti-tumour, antiviral, immunomodulation and purgative effects this review will acutely focus on their anti-inflammatory properties. The paper aims to present a summary for the most prominent iridoid-containing plants for which anti-inflammatory activity has been demonstrated in vitro and / or in vivo. PMID:22414102

  4. PRODUKSI ANTIBODI KUNING TELUR (IGY ANTI STREPTOCOCCUS MUTANS SEBAGAI ANTI KARIES GIGI

    Directory of Open Access Journals (Sweden)

    Okti Nadia Poetri

    2006-12-01

    Full Text Available The aim of this study was to explore IgY anti Streptococcus mutan production and the ability of Igy Streptococcus mutans blocking adhesion process. The eggs was collected from Single Comb Brown Leghorn which have been immunized by S. mutan. Agar gel precipitation test was done to detect IgY anti S. mutans in serum and egg. Egg which Countain IgY anti S. mutans was collected. IgY anti S. mutans extracted from egg yolk by mean s PEG-Amonium sulfat and purified using fast protein liquid chromatography. The purity of Igy anti S. mutans was determined by UV spectropometer. Biological activities of Igy anti S. mutans to inhibit adhession process was learned by anti adhesion test. We use two dose of IgY, which is 100 ug and 500 ug. Igy anti S. mutans formen in serum five weeks after the first immunization while it formed in egg nine weeks after the first immunization. Igy anti S. mutanss still present in serum andegg until twelve weeks from the first immunization. Igy anti S. mutanss could decrease the amount of bacteria which attach the epithelial cell surface. The amount of sticky bacteria on epithelial cell (without IgY are 40 cell bacteria/epithelial cell. After blocked by IgY anti S. mutanss the amount of bacteria turn into 30 cell bacteria/epithelial cell (for dose of 100 ug IgY and 28 cell bacteria/epitheelial cell (for dose of 500 ug IgY. This research concluded that hens were capable producing IgY anti S. mutanss in egg yolk and it can be used to solve dental caries problem which caused by S. mutanss.

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

    Science.gov (United States)

    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 measured using the griess method. iNOS and proteins regulating NF-κB and ERK1/2 signaling were analyzed by Western blot. In anti-cancer activity, cell growth was measured by MTT assay. Cleaved PARP, ATF3 and cyclin D1 were analyzed by Western blot. Results In anti-inflammatory effect, MRBE blocked NO production via suppressing iNOS over-expression in LPS-stimulated RAW264.7 cells. In addition, MRBE inhibited NF-κB activation through p65 nuclear translocation via blocking IκB-α degradation and ERK1/2 activation via its hyper-phosphorylation. In anti-cancer activity, MRBE deos-dependently induced cell growth arrest and apoptosis in human colorectal cancer cells, SW480. MRBE treatment to SW480 cells activated ATF3 expression and down-regulated cyclin D1 level. We also observed that MRBE-induced ATF3 expression was dependent on ROS and GSK3β. Moreover, MRBE-induced cyclin D1 down-regulation was mediated from cyclin D1 proteasomal degradation, which was dependent on ROS. Conclusions These findings suggest that mulberry root bark exerts anti-inflammatory and anti-cancer activity. PMID:24962785

  6. Anti Ma2-associated myeloradiculopathy: expanding the phenotype of anti-Ma2 associated paraneoplastic syndromes

    OpenAIRE

    Murphy, Sinead M; Khan, Usman; Alifrangis, Constantine; Hazell, Steven; Hrouda, David; Blake, Julian; Ball, Joanna; Gabriel, Carolyn; Markarian, Pierre; Rees, Jeremy; Karim, Abid; Seckl, Michael J; Lunn, Michael P; Reilly, Mary M

    2011-01-01

    Anti-Ma2 associated paraneoplastic syndrome usually presents as limbic encephalitis in association with testicular tumours.1, 2 Only four patients have been reported with involvement outside the CNS, two of whom also had limbic or brainstem encephalitis.2, 3 We report a man with anti- Ma2 associated myeloradiculopathy and previous testicular cancer whose neurological syndrome stabilised and anti-Ma2 titres fell following orchidectomy of a microscopically normal testis.

  7. Study of phytochemical, anti-microbial, anti-oxidant, and anti-cancer properties of Allium wallichii.

    Science.gov (United States)

    Bhandari, Jaya; Muhammad, BushraTaj; Thapa, Pratiksha; Shrestha, Bhupal Govinda

    2017-02-08

    There is growing interest in the use of plants for the treatment and prevention of cancer. Medicinal plants are currently being evaluated as source of promising anticancer agents. In this paper, we have investigated the anticancer potential of plant Allium wallichii, a plant native to Nepal and growing at elevations of 2300-4800 m. This is the first study of its kind for the plant mentioned. The dried plant was extracted in aqueous ethanol. Phytochemical screening, anti-microbial assay, anti-oxidant assay, cytotoxicity assay and the flow-cytometric analysis were done for analyzing different phytochemicals present, anti-microbial activity, anti-oxidant activity and anti-cancer properties of Allium wallichii. We observed the presence of steroids, terpenoids, flavonoids, reducing sugars and glycosides in the plant extract and the plant showed moderate anti-microbial and anti-oxidant activity. The IC 50 values of Allium wallichii in different cancer cell lines are 69.69 μg/ml for Prostate cancer (PC3) cell line, 55.29 μg/ml for Breast Cancer (MCF-7) cell line and 46.51 μg/ml for cervical cancer (HeLa) cell line as compared to Doxorubicin (0.85 μg/ml). The cell viability assay using FACS showed that the IC 50 value of Allium wallichii for Burkitt's lymphoma (B-Lymphoma) cell line was 3.817 ± 1.99 mg/ml. Allium wallichii can be an important candidate to be used as an anticancer agent. Separation of pure compounds with bioassay guided extraction, spectrometric analysis and subsequent cytotoxicity assay of the pure bioactive compounds from Allium wallichii is highly recommended as the crude extract itself showed promising cytotoxicity.

  8. Poly herbal formulation with anti-elastase and anti-oxidant properties for skin anti-aging.

    Science.gov (United States)

    Kalyana Sundaram, Induja; Sarangi, Deepika Deeptirekha; Sundararajan, Vignesh; George, Shinomol; Sheik Mohideen, Sahabudeen

    2018-01-29

    Skin forms an important part of human innate immune system. Wrinkles, thinning and roughening of skin are some of the symptoms that affect the skin as it ages. Reactive oxygen species induced oxidative stress plays a major role in skin aging by modulating the elastase enzyme level in the skin. Extrinsic factors that affect skin aging such as UV radiation can also cause malignant melanoma. Here we selected four medicinal plant materials, namely, leaves of Nyctanthes arbor-tristis, unripe and ripe Aegle marmelos fruit pulp and the terminal meristem of Musa paradisiaca flower and investigated their anti-aging properties and cytotoxicity in vitro individually as well as in a poly herbal formulation containing the four plant extracts in different ratios. The phytochemical contents of the plant extracts were investigated for radical scavenging activity and total reducing power. Based upon its anti-oxidant properties, a poly herbal formulation containing leaves of Nyctanthes arbor-tristis, unripe and ripe fruit pulp of Aegle marmelos, and the terminal meristem of Musa paradisiaca flower in the ratio 6:2:1:1 (Poly Herbal Formulation 1) and 1:1:1:1 (Poly Herbal Formulation 2), respectively were formulated. It has been observed that the Poly Herbal Formulation 1 was more potent than Poly Herbal Formulation 2 due to better anti-oxidant and anti-elastase activities in NIH3T3 fibroblast cells. In addition Poly Herbal formulation 1 also had better anti-cancer activity in human malignant melanoma cells. Based on these results these beneficial plant extracts were identified for its potential application as an anti-aging agent in skin creams as well as an anti-proliferation compound against cancer cells.

  9. Explicit and implicit effects of anti-marijuana and anti-tobacco TV advertisements.

    Science.gov (United States)

    Czyzewska, Maria; Ginsburg, Harvey J

    2007-01-01

    Effects of anti-tobacco and anti-marijuana TV advertisements on explicit (i.e., semantic differential ratings) and implicit (i.e. Implicit Association Test, IAT) attitudes toward tobacco and marijuana were compared. Two hundred twenty nine, 18- to 19-year-old U.S. college students were randomly assigned to anti-tobacco or anti-marijuana PSA viewing conditions. Participants completed a short survey on attitudes to tobacco and marijuana. Afterwards they watched 15 PSAs embedded in a 15-min science program. At the end, all participants completed IAT for marijuana, IAT for tobacco and the assessment of explicit attitudes. Results of ANCOVA revealed a significant interaction between type of TV PSAs watched and implicit attitudes, F(1,223)=7.12, padvertisements watched (i.e., anti-tobacco or anti-marijuana). However, analogical analysis on explicit measures showed that attitudes to marijuana became less negative among students that watched anti-marijuana ads than the group with anti-tobacco ads, F(1,222)=5.79, p<0.02. The discussion focused on the practical and theoretical implications of the observed dissociation between implicit and explicit attitudes to marijuana after the exposure to anti-marijuana PSAs.

  10. Production of light (anti-)nuclei and (anti-)hypernuclei with ALICE at the LHC

    CERN Multimedia

    CERN. Geneva

    2017-01-01

    The measurements in smaller collision systems may also provide an input to cosmological searches for segregated primordial anti-matter and dark matter, since anti-nuclei produced in pp and p--A collisions in interstellar space represent a background source in these measurements. Thanks to its excellent particle identification and tracking capabilities, the ALICE detector allows for the measurement of deuterons, tritons, 3He, 4He and their corresponding anti-nuclei. Moreover, the secondary vertices from the mesonic decays of (anti-)hypernuclei can ...

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

    OpenAIRE

    Usman, Adiyyatu Sa?idu; Mustaffa, Rapiaah; Ramli, Noraida; 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...

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

    International Nuclear Information System (INIS)

    Elazar, Z.; Kanety, H.; Schreiber, M.; Fuchs, S.

    1988-01-01

    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 [ 3 H]-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 D 2 -dopamine receptors

  13. Polysaccharides from Sargassum thunbergii: Monthly variations and anti-complement and anti-tumour activities.

    Science.gov (United States)

    Jin, Weihua; Liu, Ge; Zhong, Weihong; Sun, Chaomin; Zhang, Quanbin

    2017-12-01

    Monthly variations of polysaccharides from Sargassum thunbergii and their anti-complement and anti-tumour activities were investigated. It was observed that an increase in fucose and total sugar contents occurred during the growth period (from early April to mid-June), accompanied by a decrease in molar ratios of other monosaccharides to fucose. The highest yields were obtained from early July to early September, which was in accordance with the significant increase in molar ratio of glucose to fucose and decrease in molar ratio of other monosaccharides to fucose. And the above results suggested that S. Thunbergii synthesized large amount of laminaran, the storage substance of brown algae, during the senescence period. However, sulfate contents were relatively stable in the life cycle of S. thunbergii. These results suggested that S. thunbergii synthesized complex sulfated heteropolysacchairdes during inactive period, while during other periods, it synthesized more sulfated galactofucan. All polysaccharides showed anti-complement activity, suggesting that the harvesting time did not influence the anti-complement activities. In the anti-tumour assay in vitro, the polysaccharides taken during the senescence period had much lower anti-tumour activity, suggesting that fucoidan, but not laminaran, determined the anti-tumour activities. Therefore, polysaccharides from S. thunbergii might have great potential in anti-complement and anti-tumour application. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Dynamics of Anti-Proton -- Protons and Anti-Proton -- Nucleus Reactions

    CERN Document Server

    Galoyan, A; Uzhinsky, V

    2016-01-01

    A short review of simulation results of anti-proton-proton and anti-proton-nucleus interactions within the framework of Geant4 FTF (Fritiof) model is presented. The model uses the main assumptions of the Quark-Gluon-String Model or Dual Parton Model. The model assumes production and fragmentation of quark-anti-quark and diquark-anti-diquark strings in the mentioned interactions. Key ingredients of the model are cross sections of string creation processes and an usage of the LUND string fragmentation algorithm. They allow one to satisfactory describe a large set of experimental data, especially, a strange particle production, Lambda hyperons and K mesons.

  15. Anti-Ma and anti-Ma2-associated paraneoplastic neurological syndromes.

    Science.gov (United States)

    Ortega Suero, G; Sola-Valls, N; Escudero, D; Saiz, A; Graus, F

    Analyse the clinical profile, associated tumour types, and response to treatment of paraneoplastic neurological syndromes associated with antibodies against Ma proteins. A retrospective study of patients with antibodies against Ma proteins identified in a neuroimmunology laboratory of reference. Of the 32 patients identified, 20 showed reactivity against Ma2 only (anti-Ma2 antibodies), 11 against Ma1 and Ma2 (anti-Ma antibodies), and 1 with reactivity against Ma1 only (anti-Ma1 antibodies). The most common clinical presentations were limbic encephalopathy, diencephalic dysfunction, or brainstem encephalopathy, frequently appearing as a combination of these features. Three patients had isolated cerebellar dysfunction with anti-Ma antibodies, and 2 exhibited peripheral nervous system syndrome with anti-Ma2 antibodies. Testicular tumours were the most common neoplasms (40%) in the anti-Ma2 cases. In the group associated with anti-Ma1 antibodies, the most common were lung tumours (36%), followed by testicular tumours. All idiopathic cases were reactive to Ma2. The clinical outcome was significantly better in the anti-Ma2 group. The patient with anti-Ma1 presented with limbic encephalitis and brainstem dysfunction associated with lymphoepithelioma of the bladder. Specifically determining the different reactivities of anti-Ma protein antibodies in order to differentiate between Ma1 and Ma2 antibodies is important because anti-Ma2-associated paraneoplastic syndromes have a better outcome. Lastly, this study is the first to confirm that there may be cases that react exclusively to antibodies against Ma1. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Bioassay guided isolation and identification of anti-inflammatory and ...

    African Journals Online (AJOL)

    The present study describes the anti-inflammatory, anti-microbial activity and lipophilic profile with acute toxicological studies of Urtica dioica. Successive extraction of the leaves with organic solvents of increasing polarity and their screening for anti-inflammatory and anti-microbial activity was assessed. Hexane extract ...

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

    International Nuclear Information System (INIS)

    Senft, Christian; Polacin, Margareth; Priester, Maike; Seifert, Volker; Kögel, Donat; Weissenberger, Jakob

    2010-01-01

    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

  18. Biological activities (anti-inflammatory and anti-oxidant) of fractions ...

    African Journals Online (AJOL)

    Biological activities (anti-inflammatory and anti-oxidant) of fractions and methanolic extract of Philonotis hastate (Duby Wijk & MargaDant). ... The fractions and methanolic extract exhibited moderate antioxidant potentials with various models. The flavonoid contents of the methanol extract and fractions ranged between 1.70 ...

  19. Single phase semipolar (11 anti 22) GaN on (10 anti 10) sapphire

    Energy Technology Data Exchange (ETDEWEB)

    Ploch, S.; Stellmach, J.; Schwaner, T.; Frentrup, M.; Wernicke, T.; Pristovsek, M.; Kneissl, M. [Institute of Solid States Physics, (Germany); Park, J.B.; Niermann, T.; Lehmann, M. [Institute of Optics and Atomic Physics, TU Berlin, Hardenbergstr. 36, 10623 Berlin (Germany)

    2011-07-01

    InGaN quantum well based light emitters grown on (0001) GaN suffer from poor quantum efficiencies with increasing indium mole fraction due to strong polarization fields along the polar crystal orientation. This effect can be greatly reduced by growing on semi- and non-polar GaN orientations. Semipolar (11 anti 22) GaN layers were deposited by metalorganic vapour phase epitaxy on (10 anti 10) sapphire. After sapphire substrate nitridation at 1000 C, a GaN nucleation layer was deposited at high temperature, followed by the deposition of 1.5 nm thick GaN buffer layers. The samples show predominantly (11 anti 22) orientation with a small fraction of (10 anti 13) oriented domains. With increasing nitridation layer thickness the (10 anti 13) phase is suppressed leading to a very smooth surface morphology (rms roughness < 4nm). PL measurements show dominant basel plane stacking fault (BSF) I{sub 1} luminescence without any other defects. Transmission electron microscopy measurements reveal a high BSF density. The FWHM of the X-ray diffraction rocking curve measurements of the (1122) reflection decreases to 1193 arcsec and 739 arcsec along [1 anti 100] and [11 anti 23] respectively with increasing nucleation temperature. Using high temperature nucleation smooth and homogeneous (11 anti 22) phase GaN layers have been obtained.

  20. The Meaning of Anti-Americanism: A Performative Approach to Anti-American Prejudice

    Directory of Open Access Journals (Sweden)

    Felix Knappertsbusch

    2013-06-01

    Full Text Available A contribution to the ongoing debate on how anti-Americanism can be adequately conceptualized and how such prejudice can be distinguished from legitimate criticism, arguing that part of these conceptual problems arise from a too narrow focus on defining anti-Americanism and the use of standardized empirical operationalizations. Such approaches exhibit severe limitations in grasping the flexibility of the phenomenon in everyday discourse and often underestimate or ignore the interpretive aspect involved in identifying utterances as anti-American prejudice. Alternatively, a performative approach is proposed, understanding anti-Americanism as a network of speech acts bound by family resemblance rather than identical features. In combination with qualitative empirical research methods such a conceptualization is especially suited to account for the flexible, situated use of anti-American utterances. At the same time it grants reflexivity to the research concept, in the sense of a close description of the scientific application of the notion of anti-Americanism. Two empirical examples from an interview study on anti-American speech in Germany illustrate the potential of such an approach, providing an insight into how anti-Americanism is incorporated into the construction and expression of racist and revisionist national identifications in everyday discourse.

  1. Anti-nociceptive and anti-inflammatory properties of the ethanolic ...

    African Journals Online (AJOL)

    Anti-nociceptive and anti-inflammatory properties of the ethanolic extract of Lagenaria breviflora whole fruit in rat and mice. ... Its effect was comparable especially at 200mg/kg body weight to those of diclofenac, indomethacin and ibuprofen. It could be suggested from the findings of this experiment that the extract may be ...

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

    NARCIS (Netherlands)

    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

  3. Anti-inflammatory and anti-oxidant activities of Secamone afzelii ...

    African Journals Online (AJOL)

    . This study re-ports the anti-inflammatory and antioxidant properties of S. afzelii. The anti-inflammatory activity was determined by the carrageenan-induced paw oedema method in 7 day old chicks and antioxi-dant property by the 2 ...

  4. Sero-Prevalence of anti-sperm anti-bodies in infertile males in Port ...

    African Journals Online (AJOL)

    Background: Infertility is a serious health challenge which causes distress to the couples especially; in Africa. The cause of infertility is multifactorial. Immunological infertility is said to be one of the major causes of unexplained infertility in men. Anti-sperm anti-bodies can be used as an immunological marker of infertility.

  5. Synthesis, structure analysis, anti-bacterial and in vitro anti-cancer ...

    Indian Academy of Sciences (India)

    DOI 10.1007/s12039-015-0824-z. Synthesis, structure analysis, anti-bacterial and in vitro anti-cancer activity of new Schiff base and its copper complex derived from sulfamethoxazole. I RAMA∗ and R SELVAMEENA. PG and Research Department of Chemistry, Seethalakshmi Ramaswami College,. Tiruchirappalli 620 002 ...

  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. The Efficacy of Anti-vibration Gloves

    Science.gov (United States)

    Hewitt, Sue; Dong, Ren; McDowell, Tom; Welcome, Daniel

    2016-01-01

    Anyone seeking to control the risks from vibration transmitted to the hands and arms may contemplate the use of anti-vibration gloves. To make an informed decision about any type of personal protective equipment, it is necessary to have performance data that allow the degree of protection to be estimated. The information provided with an anti-vibration glove may not be easy to understand without some background knowledge of how gloves are tested and does not provide any clear route for estimating likely protection. Some of the factors that influence the potential efficacy of an anti-vibration glove include how risks from hand–arm vibration exposure are assessed, how the standard test for a glove is carried out, the frequency range and direction of the vibration for which protection is sought, how much hand contact force or pressure is applied and the physical limitations due to glove material and construction. This paper reviews some of the background issues that are useful for potential purchasers of anti-vibration gloves. Ultimately, anti-vibration gloves cannot be relied on to provide sufficient and consistent protection to the wearer and before their use is contemplated all other available means of vibration control ought first to be implemented. PMID:27582615

  8. Marine Microalgae with Anti-Cancer Properties.

    Science.gov (United States)

    Martínez Andrade, Kevin A; Lauritano, Chiara; Romano, Giovanna; Ianora, Adrianna

    2018-05-15

    Cancer is the leading cause of death globally and finding new therapeutic agents for cancer treatment remains a major challenge in the pursuit for a cure. This paper presents an overview on microalgae with anti-cancer activities. Microalgae are eukaryotic unicellular plants that contribute up to 40% of global primary productivity. They are excellent sources of pigments, lipids, carotenoids, omega-3 fatty acids, polysaccharides, vitamins and other fine chemicals, and there is an increasing demand for their use as nutraceuticals and food supplements. Some microalgae are also reported as having anti-cancer activity. In this review, we report the microalgal species that have shown anti-cancer properties, the cancer cell lines affected by algae and the concentrations of compounds/extracts tested to induce arrest of cell growth. We also report the mediums used for growing microalgae that showed anti-cancer activity and compare the bioactivity of these microalgae with marine anticancer drugs already on the market and in phase III clinical trials. Finally, we discuss why some microalgae can be promising sources of anti-cancer compounds for future development.

  9. Performative Pedagogy in Teaching Anti-Racism

    Directory of Open Access Journals (Sweden)

    Nena Močnik

    2015-06-01

    Full Text Available The paper deals with the issue of effective anti-racism teaching in everyday contexts, where the traditional forms of racism are replaced by more sophisticated, subtle practices of exlusion, hatred and violence. Historical connotations of terms such as racism, xenophobia, homophobia, etc. specifically characterize certain groups of people and somehow further deepen divisions between the hegemonic majority and the oppressed minority; therefore, several indicators of inefficience in teaching anti-racism have appeared, particularly in applying theories into practices. Teaching anti-racism is presented through new attitudes towards performative pedagogy, for a long time understood in the context of the teacher as the actor who engage his/her students as spectators through variety of acting techniques and performative practies. Along with the theoretical and applied development of the field, more and more the performative pedagogy is recognized as a critical teaching approach, based on artistic expression, improvisation, continuous dialogue, and the body as an ideologically inscribed product.

  10. Anti-nuclear movement and art

    International Nuclear Information System (INIS)

    Go, Seung Woo; Yun, Beom Mo

    1989-08-01

    This book goes into in detail of nuclear weapon and independent unification in the Korean peninsula. So it describes how to build of peace of circumstances both inside and outside the Korean peninsula, how to deal with nuclear crisis of the Korean peninsula and to overcome nuclear crisis. Especially, this book deals with art which is used to resist nuclear and war including art activity for unity, anti-nuclear war, Kollwitz's etching as a connecting tool with public and a painting about atom bomb pictured by Maruky in Japan who worked for anti-nuclear war.

  11. 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.

  12. PENDIDIKAN ANTI KORUPSI; UPAYA PREVENTIF MEMBERANTAS KORUPSI

    Directory of Open Access Journals (Sweden)

    Mohammad Kosim Mohammad Kosim

    2012-03-01

    Full Text Available AbstractThis writing will describe corruption that up to now still become big problem for a number of countries, especially for the poor and developing ones. The negative effect of corruption is  both from the material side and immaterial. Therefore, with any reasons, corruption cannot be accepted and must be eliminated. The elimination of corruption must be done repressively and preventively. One of the preventive ways proposed in this writing is trough education anti corruption, especially trough family and school.Kata-kata kuncikorupsi, pendidikan anti korupsi

  13. In defense of anti-matter

    International Nuclear Information System (INIS)

    Rogers, S.; Thompson, W.B.

    1980-01-01

    There appears to be a prejudice in the astronomical world against an obvious high-energy source - the mutual annihilation of matter and anti-matter. In favor of this prejudice is the lack of any convincing evidence of the presence of naturally occurring anti-matter. Only recently have cosmic-ray antiprotons been detected (cf. Golden et al., 1979), and then in numbers consistent with secondary production in flight, while annihilation X-rays have also been detected, but again in circumstances where they might well be attributed to secondary effects of some other high-energy process. (orig.)

  14. Immunogenicity of Anti-TNF-α Biotherapies

    DEFF Research Database (Denmark)

    Bendtzen, Klaus

    2015-01-01

    % of 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...... 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....

  15. 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.

  16. Quantitation of anti-tetanus and anti-diphtheria antibodies by enzymoimmunoassay: methodology and applications.

    Science.gov (United States)

    Virella, G; Hyman, B

    1991-01-01

    We have developed enzymoimmunoassays (EIA) for the quantitation of antibodies (Ab) to tetanus and diphtheria toxoids (TT, DT) using Immulon I plates coated with the appropriate toxoid. A preparation of human tetanus immunoglobulin with a known concentration of anti-TT Ab was used as calibrator of the anti-TT antibody assay. The assay of anti-DT Ab is calibrated with a pool of human sera whose anti-DT Ab concentration was determined by quantitative immunoelectrophoresis, using a horse anti-DT with known Ab concentration as calibrator. A peroxidase-conjugated anti-human IgG was used in both assays. ABTS was used as substrate, and the reaction was stopped after 1 min incubation with citric acid and the OD measured at 414 nm on a Vmax reader. The assays have been applied to a variety of clinical situations. In patients suspected of having tetanus, the quantitation of antibodies has been helpful in establishing a diagnosis. In patients with a history of hypersensitivity to tetanus toxoid, verification of the levels of anti-TT antibody may prevent unnecessary and potentially harmful immunizations. The assays have also been used for the diagnostic evaluation of the humoral immune response to TT and DT, both in pediatric patients and in immunosuppressed patients. Several non-responders have been detected, and we have recently used the assay to monitor the effects of fish oil administration on the humoral immune response.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. The anti-proliferative and anti-angiogenic effect of the methanol extract from brittle star.

    Science.gov (United States)

    Baharara, Javad; Amini, Elaheh; Mousavi, Marzieh

    2015-04-01

    Anti-angiogenic therapy is a crucial step in cancer treatment. The discovery of new anti-angiogenic compounds from marine organisms has become an attractive concept in anti-cancer therapy. Because little data correlated to the pro- and anti-angiogenic efficacies of Ophiuroidea, which include brittle star, the current study was designed to explore the anti-angiogenic potential of brittle star methanol extract in vitro and in vivo. The anti-proliferative effect of brittle star extract on A2780cp cells was examined by MTT assays, and transcriptional expression of VEGF and b-FGF was evaluated by RT-PCR. In an in vivo model, 40 fertilized Ross eggs were divided into control and three experimental groups. The experimental groups were incubated with brittle star extract at concentrations of 25, 50 and 100 µg/ml, and photographed by photo-stereomicroscopy. Ultimately, numbers and lengths of vessels were measured by Image J software. Data were analyzed with SPSS software (pstar extract exerted a dose- and time-dependent anti-proliferative effect on A2780cp cancer cells. In addition, VEGF and b-FGF expression decreased with brittle star methanol extract treatment. Macroscopic evaluations revealed significant changes in the second and third experimental group compared to controls (pstar methanol extract in vitro and in vivo confer novel insight into the application of natural marine products in angiogenesis-related pathologies.

  18. The anti-aging and anti-oxidation effects of tea water extract in Caenorhabditis elegans.

    Science.gov (United States)

    Fei, Tianyi; Fei, Jian; Huang, Fang; Xie, Tianpei; Xu, Jifeng; Zhou, Yi; Yang, Ping

    2017-10-15

    Tea includes puer tea, black tea, green tea and many others. By using model organism Caenorhabditis elegans, the anti-aging and anti-oxidation effects of tea water extract were systemically examined in this study. We found that water extract of puer tea, black tea and green tea all increased the lifespan of worms, postponed Aβ-induced progressive paralysis in Alzheimer's disease transgenic worms, and improved the tolerance of worms to the oxidative stress induced by heavy metal Cr 6+ . Moreover, the anti-oxidation effects of tea water extract at low concentration were different among 4 kinds of brands of green tea. The underlying mechanisms were further explored using genetically manipulated-mutant worms. The anti-oxidative stress effects of green tea water extract depend on the dietary restriction and germline signaling pathways, but not the FOXO and mitochondrial respiratory chain signals. Therefore, tea water extract provides benefits of anti-aging, anti-AD and anti-oxidation. Copyright © 2017. Published by Elsevier Inc.

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

    International Nuclear Information System (INIS)

    Chekanov, S.; Derrick, M.; Magill, S.

    2007-05-01

    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 0.3 T /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.)

  20. 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.

  1. Poisoning by anti-malarial drugs

    African Journals Online (AJOL)

    had taken chloroquine: no other anti-malarial drugs were involved [1]. ... and angio-oedema have been described. Itching without a ... 15mg/L the risk of permanent visual damage and cardiac dysrhythmias is ... to use an alternative method.

  2. 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…

  3. Λ(anti Λ) beams at FNAL

    International Nuclear Information System (INIS)

    Overseth, O.

    1977-01-01

    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

  4. Quantum Zeno and anti-Zeno paradoxes

    Indian Academy of Sciences (India)

    Abstract. 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.

  5. Predictive Mapping of Anti-Social Behaviour

    NARCIS (Netherlands)

    Smit, S.K.; Vecht, B. van der; Lebesque, L.H.E.M.

    2014-01-01

    Predictive mapping of crime and anti-social behaviour is becoming more and more popular as a tool to support police and policy makers. Important ingredients of such models are often demographic and economic characteristics of the area. Since those are hard to influence, we propose to use the

  6. Anti-early pregnancy by PDT

    Science.gov (United States)

    Ding, Ai-Hua; Chen, Hui-Ling

    1993-03-01

    The effect of laser on anti-early pregnancy in rabbits showed that laser in combination with HPD could induce necrosis of blastocysts and complete absorption. The anti-fertility efficiency of the combined treatment was more effective than that of the He-Ne laser or the HPD treatment alone. The fluorescence spectrum of HPD determined by PNQ3 showed that its affinity to embryonic tissue was about 4 times greater than that to uterine tissue. This may underlie the mechanisms of anti-early pregnancy of the laser. The operation of artificial abortion is a routine method to terminate early pregnancy. Though it is simple and easy, its syndrome and complications can not be absolutely avoided. Many antifertility drugs have been reported, however, they often bring in general reaction. Our present work is to explore a new way of anti-early pregnancy in rabbits by means of the light inhibitory and light sensitive effects of laser. It is a quite safe and painless treatment without expanding and scraping of the uterus.

  7. Anti-inflammatory drugs and psychosis

    NARCIS (Netherlands)

    Laan, W.

    2008-01-01

    This thesis focuses on the disorder we know as schizophrenia. Although there is treatment for schizophrenia in the form of anti-psychotic drugs, not all patients respond well to this treatment. A large part of patients will have remaining symptoms for the rest of their lives. A number of hypotheses

  8. 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, meliorism,…

  9. Reconciling Anti-essentialism and Quantitative Methodology

    DEFF Research Database (Denmark)

    Jensen, Mathias Fjællegaard

    2017-01-01

    Quantitative methodology has a contested role in feminist scholarship which remains almost exclusively qualitative. Considering Irigaray’s notion of mimicry, Spivak’s strategic essentialism, and Butler’s contingent foundations, the essentialising implications of quantitative methodology may prove...... the potential to reconcile anti-essentialism and quantitative methodology, and thus, to make peace in the quantitative/qualitative Paradigm Wars....

  10. 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

  11. Random Walks with Anti-Correlated Steps

    OpenAIRE

    Wagner, Dirk; Noga, John

    2005-01-01

    We conjecture the expected value of random walks with anti-correlated steps to be exactly 1. We support this conjecture with 2 plausibility arguments and experimental data. The experimental analysis includes the computation of the expected values of random walks for steps up to 22. The result shows the expected value asymptotically converging to 1.

  12. Anti-angiogenic treatment of gastrointestinal malignancies.

    Science.gov (United States)

    Salmon, J Stuart; Lockhart, A Craig; Berlin, Jordan

    2005-01-01

    The scientific rationale to block angiogenesis as a treatment strategy for human cancer has been developed over the last 30 years, but is only now entering the clinical arena. Preclinical studies have demonstrated the importance of the vascular endothelial growth factor (VEGF) pathways in both physiologic and pathologic angiogenesis, and have led to the development of approaches to block its role in tumor angiogenesis. Bevacizumab is an antibody to VEGF and has been shown to prolong survival when given with chemotherapy in the treatment of metastatic colorectal cancer (CRC). Although this is the first anti-angiogenic treatment to be approved for the treatment of human epithelial malignancy, a number of other approaches currently are in development. Soluble chimeric receptors to sequester serum VEGF and monoclonal antibodies against VEGF receptors have both shown considerable promise in the laboratory and are being brought into clinical investigation. A number of small-molecule tyrosine kinase inhibitors that have activity against VEGF receptors also are in clinical trials. Although these novel treatments are being pioneered in CRC, anti-angiogenic approaches also are being tested in the treatment of other gastrointestinal malignancies. Anti-VEGF therapy has shown promise in such traditionally resistant tumors as pancreatic cancer and hepatocellular carcinoma. This review will examine the preclinical foundation and then focus on the clinical studies of anti-VEGF therapy in gastrointestinal cancers.

  13. 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...

  14. Centauro- and anti-Centauro-type events

    International Nuclear Information System (INIS)

    Martinis, M.; Mikuta-Martinis, V.; Svarc, A.; Crnugelj, J.

    1995-01-01

    Assuming that leading particles in high-energy hadronic and nuclear collisions become sources of a classical pion field, we show that the direct production of pions favors Centauro (mainly charged) events and that the production of pions through the ρ-type channel favors anti-Centauro (mainly neutral) events. We also observe a strong negative neutral-charged correlation in both cases

  15. Anti-glucagon antibodies in diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Gergely, A; Koranyi, L; Halmos, T; Zsombok, M; Peterfy, F; Csizer, Z; Salamon, F; Tako, J

    1973-01-01

    Anti-insulin antibodies appear in the sera of patients treated with insulin lastingly. A high anti-insulin antibody level results in the development of insulin resistance. Most of the insulin preparations available on the market contain also glucagon as an impurity. It was therefore to be expected that in part of the patients, who had been treated with insulin lastingly, antibodies would be produced also against glucagon, and the presence of these was actually demonstrated. It is to be assumed that the anti-glucagon antibodies play a role in the pathomechanism of diabetes mellitus, mainly in its labile form. The possible presence of anti-glucagon antibodies must be taken into account when the glucagon concentration in the sera of diabetics is to be determined by means of radioimmunoassay (RIA). The specific antibodies in the serum give false results in the quantitative determination of glucagon. We have tested the sera of 10 diabetics who had been treated with insulin for at least 6 years. All patients were given protamine zinc and crystalline insulin preparations.

  16. Protecting Anti-virus Programs From Viral Attacks

    OpenAIRE

    Mishra, Umakant

    2013-01-01

    During a fight between viruses and anti-viruses it is not always predictable that the anti-virus is going to win. There are many malicious viruses which target to attack and paralyze the anti-viruses. It is necessary for an anti-virus to detect and destroy the malware before its own files are detected and destroyed by the malware. The anti-virus may follow thorough testing and auditing procedures to fix all its bugs before releasing the software in the market. Besides the anti-virus may use a...

  17. Brief History of Anti-Doping.

    Science.gov (United States)

    Ljungqvist, Arne

    2017-01-01

    The fight against doping in sport as we know it today commenced by the creation of the International Olympic Committee (IOC) Medical Commission in 1961 following the death of a Danish cyclist during the Rome Olympic Games the year before. After a slow start, the fight got under way as from the early 1970s under the leadership of the IOC and of the International Association of Athletics Federations. Despite a lack of understanding and weak support even from the sports community, a series of measures were taken during the 1970s and 1980s which still form cornerstones of today's anti-doping strategy. In addition to information and education campaigns, the most important examples are the introduction of procedural rules for doping controls, the establishment and follow-up of a list of prohibited substances and methods, the accreditation of doping control laboratories, the introduction of in- and out-of-competition testing, rules for therapeutic use exemption, and the introduction of blood sampling. During the 1990s, the anti-doping fight gained increasing support both inside and outside the sport community. In order to harmonize the wide variety of rules that had developed both in sport organizations and at the domestic level and to promote anti-doping activities, the World Anti-Doping Agency (WADA) was jointly created by the Olympic movement and the public authorities in 1999. WADA is today carrying on the fight supported by the universally accepted WADA Code and an International Anti-Doping Convention under UNESCO. © 2017 S. Karger AG, Basel.

  18. Future of anti-addiction vaccines.

    Science.gov (United States)

    Kosten, Thomas R

    2005-01-01

    The medical rational for using anti-drug antibodies in the serum as a treatment is to reduce drug levels in the brain and to bind drug before it enters the brain. Drugs of abuse are small molecules that can readily cross the blood brain barrier, while antibodies are larger molecules that cannot get into the brain. Thus, any drug that is bound to antibody also cannot cross the blood brain barrier and cannot enter the brain. Active anti-drug vaccines stimulate the body to makes its own antibodies, but the small size of abused drugs prevents them from stimulating an immune response. Thus, individuals do not ordinarily produce antibodies to abused drugs, and vaccines to stimulate antibodies are made by chemically linking these abused drugs to toxins such as cholera toxin. Alternatively, passive immunotherapy uses monoclonal antibodies that are generated in a laboratory and then administered via intravenous injection. Antibodies can be used to treat drug overdose; to reduce drug use relapse; or to protect certain at risk populations who have not yet become drug dependent. The advantages of anti-addiction vaccines are that antibodies target the drug, not the drug's sites of action in the brain and antibody binding inactivates the drug. These vaccines can complement behavioral and other medical therapies with minimal side effects and are not addictive like some chemical agonists. Technology advances in manufacturing and delivery systems will improve future anti-addiction vaccines, but social acceptance of anti-addiction vaccines will depend on substance abuse program staff and the families of substance abusers, who have some values that oppose medical solutions to addictive diseases and view addictions as moral problems.

  19. CD20-Specific Immunoligands Engaging NKG2D Enhance γδ T Cell-Mediated Lysis of Lymphoma Cells

    DEFF Research Database (Denmark)

    Peipp, M.; Wesch, D.; Oberg, H. H.

    2017-01-01

    Human γδ T cells are innate-like T cells which are able to kill a broad range of tumour cells and thus may have potential for cancer immunotherapy. The activating receptor natural killer group 2 member D (NKG2D) plays a key role in regulating immune responses driven by γδ T cells. Here, we explor...

  20. 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.

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

    Science.gov (United States)

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

    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, anti-microbial 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. PMID:19701969

  2. Anti-inflammatory, anti-cholinergic and cytotoxic effects of Sida rhombifolia.

    Science.gov (United States)

    Mah, Siau Hui; Teh, Soek Sin; Ee, Gwendoline Cheng Lian

    2017-12-01

    Sida (Malvaceae) has been used as a traditional remedy for the treatment of diarrhoea, malarial, gastrointestinal dysentery, fevers, asthma and inflammation. This study evaluates the anti-inflammatory, cytotoxic and anti-cholinergic activities of Sida rhombifolia Linn. whole plant for the first time. S. rhombifolia whole plant was extracted by n-hexane, ethyl acetate and methanol using Soxhlet apparatus. The plant extracts were evaluated for their antioxidant (DPPH, FIC and FRAP), anti-inflammatory (NO and protein denaturation inhibitions), cytotoxic (MTT) and anti-cholinesterase (AChE) properties in a range of concentrations to obtain IC 50 values. GC-MS analysis was carried out on the n-hexane extract. The ethyl acetate extract exhibited the most significant antioxidant activities by scavenging DPPH radicals and ferrous ions with EC 50 of 380.5 and 263.4 μg/mL, respectively. In contrast, the n-hexane extract showed the strongest anti-inflammatory activity with IC 50 of 52.16 and 146.03 μg/mL for NO and protein denaturation inhibition assays, respectively. The same extract also revealed the strongest effects in anti-cholinesterase and cytotoxic tests at the concentration of 100 μg/mL, AChE enzyme inhibition was 58.55% and human cancer cells, SNU-1 and Hep G2 inhibition was 68.52% and 47.82%, respectively. The phytochemicals present in the n-hexane extract are palmitic acid, linoleic acid and γ-sitosterol. The present study revealed that the n-hexane extract possessed relatively high pharmacological activities in anti-inflammation, cytotoxicity and anti-cholinesterase assays. Thus, further work on the detail mechanism of the bioactive phytochemicals which contribute to the biological properties are strongly recommended.

  3. Recherche et Titrage des Hémolysines Anti-A et Anti-B Chez Les ...

    African Journals Online (AJOL)

    Les hémolysines apparaissent suite à une immunisation ABO et peuvent causer, à titre élevé, une hémolyse chez le receveur de sang ou chez le nouveau-né. ... Mots Clés: Hémolysines anti-A et anti-A, Incompatibilité foeto-maternelle ABO, Maladie hémolytique du nouveau-né, Période du post-partum immédiate ...

  4. Anti-neuronal anti-bodies in patients with early psychosis.

    Science.gov (United States)

    Mantere, O; Saarela, M; Kieseppä, T; Raij, T; Mäntylä, T; Lindgren, M; Rikandi, E; Stoecker, W; Teegen, B; Suvisaari, J

    2018-02-01

    It may be challenging to distinguish autoimmune encephalitis associated with anti-neuronal autoantibodies from primary psychiatric disorders. Here, serum was drawn from patients with a first-episode psychosis (n=70) or a clinical high-risk for psychosis (n=6) and controls (n=34). We investigated the serum prevalence of 24 anti-neuronal autoantibodies: IgG antibodies for anti-N-methyl-d-aspartate-type glutamate receptor (anti-NMDAR), glutamate and γ-aminobutyric acid alpha and beta receptors (GABA-a, GABA-b), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA), glycine receptor (GlyR), metabotropic glutamate receptor 1 and 5 (mGluR1, mGluR5), anti-Tr/Delta/notch-like epidermal growth factor-related receptor (DNER), contactin-associated protein-like 2 (CASPR2), myelin oligodendrocyte glycoprotein (MOG), glutamic acid decarboxylase-65 (GAD65), collapsin response mediator protein 5/crossveinless-2 (CV2), aquaporin-4 (AQP4), anti-dipeptidyl-peptidase-like protein-6 (DPPX), type 1 anti-neuronal nuclear antibody (ANNA-1, Hu), Ri, Yo, IgLON5, Ma2, zinc finger protein 4 (ZIC4), Rho GTPase-activating protein 26, amphiphysin, and recoverin, as well as IgA and IgM for dopamine-2-receptor (DRD2). Anti-NMDA IgG antibodies were positive with serum titer 1:320 in one patient with a clinical high risk for psychosis. He did not receive a diagnosis of encephalitis after comprehensive neurological evaluation. All other antineuronal autoantibodies were negative and there were no additional findings with immunohistochemistry of brain issues. Copyright © 2017 Elsevier B.V. All rights reserved.

  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. 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.

  7. Differential requirement for nitric oxide in IGF-1-induced anti-apoptotic, anti-oxidant and anti-atherosclerotic effects

    Science.gov (United States)

    Sukhanov, Sergiy; Higashi, Yusuke; Shai, Shaw-Yung; Blackstock, Christopher; Galvez, Sarah; Vaughn, Charlotte; Titterington, Jane; Delafontaine, Patrick

    2011-01-01

    We have shown previously that insulin like-growth factor I (IGF-1) suppressed atherosclerosis in Apoe−/− mice and activated endothelial nitric oxide (NO) synthase. To determine whether IGF-1-induced atheroprotection depends on NO, IGF-1- or saline-infused mice were treated with L-NAME, the pan-NO synthase inhibitor or with D-NAME (control). IGF-1 reduced atherosclerosis in both the D-NAME and L-NAME groups suggesting that IGF-1’s anti-atherogenic effect was NO-independent. IGF-1 increased plaque smooth muscle cells, suppressed cell apoptosis and downregulated lipoprotein lipase and these effects were also NO-independent. On the contrary, IGF-1 decreased oxidative stress and suppressed TNF-α levels and these effects were blocked by L-NAME. Thus IGF-1’s anti-oxidant effect is dependent on its ability to increase NO but is distinct from its anti-atherosclerotic effect which is NO-independent. PMID:21872589

  8. Systemic Effects of Anti-Angiogenic Therapy

    International Nuclear Information System (INIS)

    Starlinger, P.

    2011-01-01

    Anti-angiogenic cancer therapy has gained importance within the past decades. In this context, Bevacizumab, a monoclonal antibody neutralizing vascular endothelial growth factor, has been approved for clinical use. The combination of chemotherapy with Bevacizumab has shown a remarkable benefit in several neoplastic entities. However, a notable number of patients do not respond to this therapy. Furthermore, response to therapy seems to be short-lived. The primary topic of this PhD thesis was to characterize systemic effects of anti-angiogenic therapy to possibly identify mechanisms that could explain this heterogeneity in therapy response. To this end, a carefully selected subset of angiogenesis factors were monitored in detail in the course of a clinical study of pancreatic cancer receiving gemcitabine based anti-angiogenic therapy with Bevacizumab. To enable the reliable monitoring of angiogenesis parameters, we initially defined an optimized procedure to evaluate angiogenesis factors in blood. During these investigations a remarkable association of circulating angiogenic growth factors with platelet counts and activation was observed. Strikingly, we were able to confirm this association in the clinical setting. In particular, the anti-angiogenic factor thrombospondin-1 (TSP-1) correlated with platelet counts. We further showed that the highly myelosuppressive chemotherapeutic agent gemcitabine resulted in a decrease of platelet counts and circulating TSP-1 levels. As a result, we hypothesized that the choice of chemotherapy might affect the angiogenic balance and counteract the therapeutic effect of bevacizumab. This notion was further supported by a careful evaluation of other studies reporting on the combination of Bevacizumab with thrombocytopenic chemotherapies which were generally of minor therapeutic benefit for cancer patients. To further focus on TSP-1 as an essential modulator of neovascularization and anti-angiogenic therapy we investigated TSP-1

  9. Lectins with Anti-HIV Activity: A Review

    Directory of Open Access Journals (Sweden)

    Ouafae Akkouh

    2015-01-01

    Full Text Available 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 algal lectins comprise Boodlea coacta lectin, Griffithsin, Oscillatoria agardhii agglutinin. The anti-HIV cyanobacterial lectins are cyanovirin-N, scytovirin, Microcystis viridis lectin, and microvirin. Actinohivin is an anti-HIV actinomycete lectin. The anti-HIV worm lectins include Chaetopterus variopedatus polychaete marine worm lectin, Serpula vermicularis sea worm lectin, and C-type lectin Mermaid from nematode (Laxus oneistus. The anti-HIV nonpeptidic lectin mimics comprise pradimicins and benanomicins. Their anti-HIV mechanisms are discussed.

  10. Heavy meson decays and p anti p collisions

    International Nuclear Information System (INIS)

    Berger, E.L.; Damgaard, P.H.; Tsokos, K.

    1985-01-01

    We use the formalism of exclusive processes at high momentum transfer, to give predictions for the decay of the 2 ++ chi state into a p anti p pair and the production cross section for chi in p anti p collisions

  11. Anti-retroviral therapy induced diabetes in a Nigerian | Bakari ...

    African Journals Online (AJOL)

    African Health Sciences ... Background:Anti-retroviral therapy (ART) using Highly Active Anti-retroviral Therapy (HAART) has led to ... HIV infected individuals on one hand, and side effects of chronic administration of these drugs on the other.

  12. Optimization and anti-optimization of structures under uncertainty

    National Research Council Canada - National Science Library

    Elishakoff, Isaac; Ohsaki, Makoto

    2010-01-01

    .... The necessity of anti-optimization approach is first demonstrated, then the anti-optimization techniques are applied to static, dynamic and buckling problems, thus covering the broadest possible set of applications...

  13. The production of anti-matter in our galaxy

    Energy Technology Data Exchange (ETDEWEB)

    Chardonnet, P.; Orloff, J.; Salati, P. [Grenoble-1 Univ., 74 - Annecy (France). Lab. de Physique Theorique

    1997-12-31

    A coalescence model is applied to assess the amount of anti-deuterium and anti-helium {sup 3}He present in cosmic rays together with anti-protons. The propagation of cosmic rays in the galaxy is described through a two-zone diffusion model which correctly describes the observed abundances. The {sup 3}He/p abundance does not exceed {approx} 4 x 10{sup -13}. Heavier anti-nuclei are even further suppressed. (author). 12 refs.

  14. fJ(2220) and hadronic anti Bs0 decays

    International Nuclear Information System (INIS)

    Hsiao, Y.K.; Geng, C.Q.

    2015-01-01

    We study the hadronic anti B s 0 decays based on the existence of the resonant state f J (2220). In particular,we are able to explain the unexpected large experimental result of B(anti B s 0 → J/ψp anti p) = (3.0 -1.1 +1.2 ± 0.52 ± 0.03) x 10 -6 measured recently by the LHCb collaboration due to the resonant contribution in anti B s 0 → J/ψf J (2220) with f J (2220) → p anti p, while it is estimated to be at most of order 10 -9 in terms of the OZI rule without the resonance. In addition, we find that B(anti B s 0 → D *0 (f J →)p anti p) = (4.70 ± 2.89) x 10 -7 , B(anti B s 0 → J/ψ(f J →)ππ) = (15.6 ± 15.2) x 10 -6 , and B(anti B s 0 → D *0 (f J →)ππ) = (24.5 ± 24.4) x 10 -7 , while B(anti B s 0 → J/ψ(f J →)K anti K) < 1.6 x 10 -5 and B(anti B s 0 → D *0 (f J →)K anti K) < 2.5 x 10 -6 . Moreover, we predict that the decay branching ratios of anti B s 0 → (J/ψ, D *0 )Λ anti Λ are (2.68 ± 1.23) x 10 -7 and (2.25 ± 0.80) x 10 -6 . Some of the predicted anti B s 0 decays are accessible to the experiments at the LHCb. (orig.)

  15. The production of anti-matter in our galaxy

    International Nuclear Information System (INIS)

    Chardonnet, P.; Orloff, J.; Salati, P.

    1997-01-01

    A coalescence model is applied to assess the amount of anti-deuterium and anti-helium 3 He present in cosmic rays together with anti-protons. The propagation of cosmic rays in the galaxy is described through a two-zone diffusion model which correctly describes the observed abundances. The 3 He/p abundance does not exceed ∼ 4 x 10 -13 . Heavier anti-nuclei are even further suppressed. (author)

  16. 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...... 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....

  17. Camellia sinensis L. Extract and Its Potential Beneficial Effects in Antioxidant, Anti-Inflammatory, Anti-Hepatotoxic, and Anti-Tyrosinase Activities

    Directory of Open Access Journals (Sweden)

    Surached Thitimuta

    2017-03-01

    Full Text Available The aims of this study were to investigate the potential benefits of antioxidant, anti-inflammatory, anti-hepatotoxic, and anti-tyrosinase activities of a methanolic extract of fresh tea leaves (FTE (Camellia sinensis L.. The antioxidant capacity was investigated using three different methods at different temperatures. The anti-inflammatory activity was studied in vitro by the inhibition of 5-lipoxygenase assay. The anti-hepatotoxic effect was investigated in CCl4-induced liver injury in rats. The anti-tyrosinase activities of the FTE and its principal phenolic compounds were investigated in l-3,4-dihydroxyphenylalanine (l-DOPA oxidation by a mushroom tyrosinase. A molecular docking study was conducted to determine how the FTE’s principal catechins interact with the tyrosinase. The FTE exhibited the best shelf life at low temperatures and demonstrated concentration-dependent antioxidant, anti-inflammatory, anti-hepatotoxic, and anti-tyrosinase effects compared to positive references. Treatment of rats with the FTE at 2000 mg/kg/day for 28 consecutive days reversed CCl4-induced oxidative damage in hepatic tissues by lowering the levels of alanine aminotransferase by 69% and malondialdehyde by 90%. Our findings suggest that the FTE has the capacity to scavenge free radicals and can protect against oxidative stress induced by CCl4 intoxication. The docking results were consistent with our in vitro data, indicating the anti-tyrosinase potency of the principal catechins.

  18. Camellia sinensis L. Extract and Its Potential Beneficial Effects in Antioxidant, Anti-Inflammatory, Anti-Hepatotoxic, and Anti-Tyrosinase Activities.

    Science.gov (United States)

    Thitimuta, Surached; Pithayanukul, Pimolpan; Nithitanakool, Saruth; Bavovada, Rapepol; Leanpolchareanchai, Jiraporn; Saparpakorn, Patchreenart

    2017-03-04

    The aims of this study were to investigate the potential benefits of antioxidant, anti-inflammatory, anti-hepatotoxic, and anti-tyrosinase activities of a methanolic extract of fresh tea leaves (FTE) ( Camellia sinensis L.). The antioxidant capacity was investigated using three different methods at different temperatures. The anti-inflammatory activity was studied in vitro by the inhibition of 5-lipoxygenase assay. The anti-hepatotoxic effect was investigated in CCl₄-induced liver injury in rats. The anti-tyrosinase activities of the FTE and its principal phenolic compounds were investigated in l-3,4-dihydroxyphenylalanine (l-DOPA) oxidation by a mushroom tyrosinase. A molecular docking study was conducted to determine how the FTE's principal catechins interact with the tyrosinase. The FTE exhibited the best shelf life at low temperatures and demonstrated concentration-dependent antioxidant, anti-inflammatory, anti-hepatotoxic, and anti-tyrosinase effects compared to positive references. Treatment of rats with the FTE at 2000 mg/kg/day for 28 consecutive days reversed CCl₄-induced oxidative damage in hepatic tissues by lowering the levels of alanine aminotransferase by 69% and malondialdehyde by 90%. Our findings suggest that the FTE has the capacity to scavenge free radicals and can protect against oxidative stress induced by CCl₄ intoxication. The docking results were consistent with our in vitro data, indicating the anti-tyrosinase potency of the principal catechins.

  19. Anti-Romani Terrorism in Europe

    Directory of Open Access Journals (Sweden)

    Mareš Miroslav

    2016-12-01

    Full Text Available This article analyzes terrorism against the Roma in Europe. It identifies acts of terrorism in violence that targets the largest stateless nation on the continent and categorizes this terrorism according to current research methods. Focusing on events in both Western and Eastern Europe, the article analyses and compares the most significant terrorist acts against the Roma of recent years. It concludes that anti-Romani terrorism is heterogeneous in terms of tactics, strategies, and ideological justification, yet can usually be subsumed into the broadly conceived category of far-right terrorism. The variety of attacks suggests that terrorist acts are an offshoot of the broad spectrum of anti-Romani activity, and are influenced by contemporary trends in inter-ethnic violence.

  20. Anti-Infectious Agents against MRSA

    Directory of Open Access Journals (Sweden)

    Nobuhiro Koyama

    2012-12-01

    Full Text Available Clinically useful antibiotics, β-lactams and vancomycin, are known to inhibit bacterial cell wall peptidoglycan synthesis. Methicillin-resistant Staphylococcus aureus (MRSA has a unique cell wall structure consisting of peptidoglycan and wall teichoic acid. In recent years, new anti-infectious agents (spirohexaline, tripropeptin C, DMPI, CDFI, cyslabdan, 1835F03, and BPH-652 targeting MRSA cell wall biosynthesis have been discovered using unique screening methods. These agents were found to inhibit important enzymes involved in cell wall biosynthesis such as undecaprenyl pyrophosphate (UPP synthase, FemA, flippase, or UPP phosphatase. In this review, the discovery, the mechanism of action, and the future of these anti-infectious agents are described.

  1. Anti-inflammatory actions of acupuncture

    Directory of Open Access Journals (Sweden)

    Freek J. Zijlstra

    2003-01-01

    Full Text Available Acupuncture has a beneficial effect when treating many diseases and painful conditions, and therefore is thought to be useful as a complementary therapy or to replace generally accepted pharmacological intervention. The attributive effect of acupuncture has been investigated in inflammatory diseases, including asthma, rhinitis, inflammatory bowel disease, rheumatoid arthritis, epicondylitis, complex regional pain syndrome type 1 and vasculitis. Large randomised trials demonstrating the immediate and sustained effect of acupuncture are missing. Mechanisms underlying the ascribed immunosuppressive actions of acupuncture are reviewed in this communication. The acupuncture-controlled release of neuropeptides from nerve endings and subsequent vasodilative and anti-inflammatory effects through calcitonine gene-related peptide is hypothesised. The complex interactions with substance P, the analgesic contribution of β-endorphin and the balance between cell-specific pro-inflammatory and anti-inflammatory cytokines tumour necrosis factor-α and interleukin-10 are discussed.

  2. [Anti-ageing therapies in Alzheimer's disease].

    Science.gov (United States)

    Alonso Abreu, Gara S; Brito Armas, José M; Castro Fuentes, Rafael

    Alzheimer's disease is the most common cause of dementia in the elderly population. Currently, there are no effective treatments to prevent or delay the natural course of the disease. Numerous studies have provided information about the molecular processes underlying biological ageing and, perhaps more importantly, potential interventions to slow ageing and promote healthy longevity in laboratory model systems. The main issue addressed in this review is whether an intervention that has anti-ageing properties can alter the appearance and/or progression of Alzheimer's disease, a disease in which age is the biggest risk factor. Different anti-ageing interventions have been shown to prevent (and in some cases possibly restore) several parameters recognised as central symptoms to the development of Alzheimer's disease. In addition, they are taking the first steps towards translating these laboratory discoveries into clinical applications. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. A Switching Anti-windup Design Using Multiple Lyapunov Functions

    NARCIS (Netherlands)

    Lu, L.; Lin, Z.; Chen, J.

    2009-01-01

    This paper proposes a switching anti-windup design, which aims to enlarge the domain of attraction of the closed-loop system. Multiple anti-windup gains along with an index function that orchestrates the switching among these anti-windup gains are designed based on the min function of multiple

  4. Striking the Right Balance : Effectiveness of Anti-Doping Policies

    NARCIS (Netherlands)

    de Hon, O.M.

    2016-01-01

    Doping, and anti-doping, is in the news on a continuous basis. At the core of these stories and discussions is the question how effective anti-doping policies are to curb the use of doping in sports. Anti-doping policies are based on ethical values, a juridical framework, laboratory analyses,

  5. 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 is...

  6. 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 items...

  7. 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 has...

  8. The Phytochemical Constituents, Analgesic and Anti-inflammatory ...

    African Journals Online (AJOL)

    This effect was comparable to the observed effect with Piroxicam (0.5mg/kg) which was used as a standard. The effect was also dose- dependent. Furthermore, Jatropha ... This also supports its use traditionally as an anti-snake bite, rheumatism and anti- cancer or anti-tumor agent. Further study is on the way to find out the ...

  9. Rhesus anti-D immunoglobulin in chronic autoimmune neuropathy

    NARCIS (Netherlands)

    de Jager, AEJ; van der Hoeven, JH

    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

  10. Anti-prothrombin antibodies are associated with adverse pregnancy outcome.

    Science.gov (United States)

    Marozio, Luca; Curti, Antonella; Botta, Giovanni; Canuto, Emilie M; Salton, Loredana; Tavella, Anna Maria; Benedetto, Chiara

    2011-11-01

    Women with antiphospholipid antibodies (aPL) such as lupus anticoagulant, anticardiolipin antibodies, and anti-β(2) glycoprotein-1 antibodies are at high risk of late pregnancy complications, such as severe pre-eclampsia, placental insufficiency, and fetal loss. It has been observed that aPL consists of a heterogeneous group of antibodies targeting several phospholipid-binding plasma proteins, including also anti-prothrombin (anti-PT), anti-protein S (anti-PS), and anti-protein C (anti-PC) antibodies. Their potential role in late pregnancy complications is not known. The aim of this work was to investigate the association between those autoantibodies and histories for adverse pregnancy outcome. Anti-PT, anti-PS, and anti-PC antibodies were evaluated in 163 patients with previous severe pre-eclampsia, fetal death, and/or placental abruption and in as many women with previous uneventful pregnancies, negative for aPL. The prevalence of anti-PT antibodies was higher in cases than in controls (OR, 95% CI: 10.92, 4.52-26.38). The highest prevalence was observed in subjects with fetal death. Anti-PT antibodies appear to be associated with adverse pregnancy outcome, irrespectively of aPL. © 2011 John Wiley & Sons A/S.

  11. 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.

  12. Ship Anti Ballistic Missile Response (SABR)

    OpenAIRE

    Johnson, Allen P.; Breeden, Bryan; Duff, Willard Earl; Fishcer, Paul F.; Hornback, Nathan; Leiker, David C.; Carlisle, Parker; Diersing, Michael; Devlin, Ryan; Glenn, Christopher; Hoffmeister, Chris; Chong, Tay Boon; Sing, Phang Nyit; Meng, Low Wee; Meng, Fann Chee

    2006-01-01

    Includes supplementary material. Based on public law and Presidential mandate, ballistic missile defense development is a front-burner issue for homeland defense and the defense of U.S. and coalition forces abroad. Spearheaded by the Missile Defense Agency, an integrated ballistic missile defense system was initiated to create a layered defense composed of land-, air-, sea-, and space-based assets. The Ship Anti-Ballistic Response (SABR) Project is a systems engineering approach t...

  13. La disciplina anti-riciclaggio in Germania

    Directory of Open Access Journals (Sweden)

    Verena Zoppei

    2016-11-01

    Full Text Available Questo testo contribuisce alla discussione sull’efficacia del reato di riciclaggio nel far fronte al fenomeno dell’infiltrazione dei flussi di denaro sporco nell’economia lecita. Sebbene la pratica di nascondere i proventi di reato in modo da evitare la persecuzione giudiziaria risalga a molto tempo addietro, il concetto giuridico di riciclaggio è relativamente recente ed è stato introdotto nei codici penali nella maggior parte del mondo a partire dalla fine degli anni ‘80. Nel frattempo, nonostante le innumerevoli novità introdotte e i cospicui emendamenti che hanno in larga parte espanso il campo di applicazione della normativa, la disciplina anti-riciclaggio è stata oggetto di un dibattito acceso a causa dell’incapacità di impedire il reinvestimento nel processo produttivo dei capitali di provenienza illecita. Questo lavoro propone un approccio critico alla questione dell’efficacia, sulla base di un caso di studio nazionale. Parole chiave: Riciclaggio di denaro sporco; disciplina anti-riciclaggio; Germania; efficacia; flussi di denaro sporco This paper contributes to the discussion on the effectiveness of the money laundering offence in tackling the infiltration of illicit financial flows in the licit economy. Despite the practice of concealing proceeds of crime to avoid prosecution dates back long time, the legal concept of money laundering is relatively recent. It has been introduced in criminal laws from the beginning of the 80ies. So far, the scope of the anti-money laundering regime has been expanded. Yet, the regulations are object of a controversial debate due to their incapacity of impeding the reinvestment of ill-gotten gains into the legitimate economy. This work proposes an alternative approach to the question of the effectiveness, on the basis of a national case study. Keywords: Money laundering - anti-money laundering regime - Germany - effectiveness - illicit financial flows

  14. Proteomics of anti-cancer drugs

    Czech Academy of Sciences Publication Activity Database

    Kovářová, Hana; Martinková, Jiřina; Hrabáková, Rita; Skalníková, Helena; Novák, Petr; Hajdůch, M.; Gadher, S. J.

    2009-01-01

    Roč. 276, Supplement 1 (2009), s. 84-84 E-ISSN 1742-4658. [34th FEBS Congress. 04.07.2009-09.07.2009, Praha] R&D Projects: GA MŠk LC07017 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50200510 Keywords : proteomics * anti-cancer drugs * biomarkers Subject RIV: FD - Oncology ; Hematology

  15. Gravitational collapse in anti de Sitter space

    International Nuclear Information System (INIS)

    Garfinkle, David

    2004-01-01

    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

  16. ANTI INFLAMMATORY ACTIVITY OF MORINGA OLIEFERA. LAM

    Science.gov (United States)

    Rao, K.N. Venkataswera; Gopalakrishnan, V.; Loganathan, V.; Nathan, S. Shanmuganathan

    1999-01-01

    The aqueous and ethanolic (90%) extract of the leaves of M.Oliera Lam (Fam: Moringaceae) were studied for their anti inflammatory action in ale albino rats. Two extracts exhibited maximum action within two hours of challenge. The aqueous extract sowed significant (P<0.01) odema suppression similar to that of Ibuprofen at the first hour of carrageenan injection. The results confirms the folkers claim of the plant. PMID:22556890

  17. Association between anti-thyroid peroxidase and anti-cytokeratin 18 autoantibodies and bronchial asthma in women

    Directory of Open Access Journals (Sweden)

    Hala A. Mohammad

    2016-01-01

    Conclusion: Positive anti-TPO autoantibodies and anti-CK18 autoantibodies in asthmatic patients and their higher level in the non-allergic asthma group may strengthen the presence of a hidden autoimmune phenomenon in non-allergic asthma.

  18. Anti-inflammatory effects of insulin.

    Science.gov (United States)

    Dandona, Paresh; Chaudhuri, Ajay; Mohanty, Priya; Ghanim, Husam

    2007-07-01

    This review deals with the recent observations on the pro-inflammatory effects of glucose and the anti-inflammatory actions of insulin. Apart from being novel, they are central to our understanding of why hyperglycemia is a prognosticator of bad clinical outcomes including patients with acute coronary syndromes, stroke and in patients in the intensive care unit. The pro-inflammatory effect of glucose as well as that of other macronutrients including fast food meals provides the basis of chronic oxidative stress and inflammation in the obese and their propensity to atherosclerotic disease. The anti-inflammatory action of insulin provides a neutralizing effect to balance macronutrient induced inflammation on the one hand and the possibility of using insulin as an anti-inflammatory drug on the other. The actions of macronutrients and insulin described above explain why insulin resistant states like obesity and type 2 diabetes are associated with oxidative stress, inflammation and atherosclerosis. They also suggest that insulin may be antiatherogenic.

  19. Anti- Sporothrix spp. activity of medicinal plants

    Directory of Open Access Journals (Sweden)

    Stefanie Bressan Waller

    Full Text Available ABSTRACT Cases of sporotrichosis in humans and animals without satisfactory clinical response have increased, a warning sign of strains resistant to conventional antifungal agents. The urgent search for alternative therapies was an incentive for research on medicinal plants with anti-Sporothrix spp. properties. A bibliographic survey was performed based on scientific papers about in vitro and in vivo antifungal activity of essential oils and extracts of plants in differents solvents against the fungal of the Sporothrix schenckii complex. The study methodology consisted of a literature review in Google Scholar, Science Direct, Pubmed, Bireme and Springer link with papers from 1986 to 2015. We found 141 species of plants that were investigated, of which 100 species were concentrated in 39 botanical families that had confirmed anti-Sporothrix activity. Combretaceae, Asteraceae and Lamiaceae represented the botanical families with the greatest number of plants species with antifungal potential, using different methodologies. However, there are few studies with medicinal plants in experimental infection in animals that prove their activity in the treatment of sporotrichosis. It reinforces the need for further research related to standardization of in vitro methodologies and in vivo studies related to safety and to toxicity potential of these plants with anti-Sporothrix spp. activity.

  20. Cannabis in sport: anti-doping perspective.

    Science.gov (United States)

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

    2011-11-01

    Since 2004, when the World Anti-Doping Agency assumed the responsibility 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 cannabis to enhance sports performance, the risk it poses to the athlete's health and its violation of the spirit of sport. Although these compounds are prohibited in-competition only, we explain why the pharmacokinetics of their main psychoactive compound, Δ(9)-tetrahydrocannabinol, may complicate the results management of adverse analytical findings. Passive inhalation does not appear to be a plausible explanation for a positive test. Although the prohibition of cannabinoids in sports is one of the most controversial issues in anti-doping, in this review we stress the reasons behind this prohibition, with strong emphasis on the evolving knowledge of cannabinoid pharmacology.

  1. News exposure predicts anti-Muslim prejudice.

    Science.gov (United States)

    Shaver, John H; Sibley, Chris G; Osborne, Danny; Bulbulia, Joseph

    2017-01-01

    News coverage of Islamic extremism is reigniting debates about the media's role in promoting prejudice toward Muslims. Psychological theories of media-induced prejudice date to the 1950's, and find support from controlled experiments. However, national-scale studies of media effects on Muslim prejudice are lacking. Orthogonal research investigating media-induced prejudice toward immigrants has failed to establish any link. Moreover, it has been found that people interpret the news in ways that confirm pre-existing attitudes, suggesting that media induced Muslim prejudice in liberal democracies is unlikely. Here, we test the association between news exposure and anti-Muslim prejudice in a diverse national sample from one of the world's most tolerant societies, where media effects are least likely to hold (N = 16,584, New Zealand). In support of media-induced Islamophobia, results show that greater news exposure is associated with both increased anger and reduced warmth toward Muslims. Additionally, the relationship between media exposure and anti-Muslim prejudice does not reliably vary with political ideology, supporting claims that it is widespread representations of Muslims in the news, rather than partisan media biases, that drives anti-Muslim prejudice.

  2. Anti-oxidant and anti-inflammatory activity of leaf extracts and fractions of Mangifera indica.

    Science.gov (United States)

    Mohan, C G; Deepak, M; Viswanatha, G L; Savinay, G; Hanumantharaju, V; Rajendra, C E; Halemani, Praveen D

    2013-04-13

    To evaluate the anti-oxidant and anti-inflammatory activity of leaf extracts and fractions of Mangifera indica in in vitro conditions. 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. In in vitro DPPH radical scavenging activity, the MEMI, EMEMI and BMEMI have offered significant antioxidant activity with IC(50) values of 13.37, 3.55 and 14.19 μg/mL respectively. Gallic acid, a reference standard showed significant antioxidant activity with IC(50) 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 IC(50) 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 IC(50) 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. These findings suggest that the MEMI and EMEMI possess potent anti-oxidant and anti-inflammatory activities in in vitro conditions. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  3. Direct anti-atherosclerotic therapy; development of natural anti-atherosclerotic drugs preventing cellular cholesterol retention.

    Science.gov (United States)

    Orekhov, Alexander N

    2013-01-01

    The results of numerous clinical trials with statins and other drugs have demonstrated the principal possibility of the prevention and regression of atherosclerosis by pharmacotherapy. This review describes the use of cultured human arterial cells for the mass screening of anti-atherosclerotic substances, the investigation of the mechanisms responsible for their atherosclerosis-related effects, and the optimization of anti-atherosclerotic and anti-atherogenic drug and dietary therapies. Natural products can be considered promising drugs for anti-atherosclerotic therapy. Our basic studies have shown that cellular lipidosis is the principal event in the genesis of atherosclerotic lesions. Using cellular models and natural products, we have developed an approach to prevent lipid accumulation in arterial cells. Based on our knowledge of atherosclerosis, we developed drugs that possess direct anti-atherosclerotic activity. Two-year treatment with allicor (garlic powder) has a direct anti-atherosclerotic effect on carotid atherosclerosis in asymptomatic men. Inflaminat (calendula, elder, and violet), which possesses anti-cytokine activity, has been shown to cause the regression of carotid atherosclerosis following the treatment of asymptomatic men for one year. The phytoestrogen-rich drug karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid) prevents the development of carotid atherosclerosis in postmenopausal women. Thus, our basic findings were successfully translated into clinical practice. Because of this translation, a novel approach to antiatherosclerotic therapy was developed. Our clinical trial confirmed the efficacy of both the novel approach and the novel drugs.

  4. Tropical fruit camu-camu (Myrciaria dubia) has anti-oxidative and anti-inflammatory properties.

    Science.gov (United States)

    Inoue, Teruo; Komoda, Hiroshi; Uchida, Toshihiko; Node, Koichi

    2008-10-01

    Oxidative stress as well as inflammation plays a pivotal role in the pathogenesis of atherosclerosis. Although, various anti-oxidative dietary supplements have been evaluated for their ability to prevent atherosclerosis, no effective ones have been determined at present. "Camu-camu" (Myrciaria dubia) is an Amazonian fruit that offers high vitamin C content. However, its anti-oxidative property has not been evaluated in vivo in humans. To assess the anti-oxidative and anti-inflammatory properties of camu-camu in humans, 20 male smoking volunteers, considered to have an accelerated oxidative stress state, were recruited and randomly assigned to take daily 70 ml of 100% camu-camu juice, corresponding to 1050 mg of vitamin C (camu-camu group; n=10) or 1050 mg of vitamin C tablets (vitamin C group; n=10) for 7 days. After 7 days, oxidative stress markers such as the levels of urinary 8-hydroxy-deoxyguanosine (P<0.05) and total reactive oxygen species (P<0.01) and inflammatory markers such as serum levels of high sensitivity C reactive protein (P<0.05), interleukin (IL)-6 (P<0.05), and IL-8 (P<0.01) decreased significantly in the camu-camu group, while there was no change in the vitamin C group. Our results suggest that camu-camu juice may have powerful anti-oxidative and anti-inflammatory properties, compared to vitamin C tablets containing equivalent vitamin C content. These effects may be due to the existence of unknown anti-oxidant substances besides vitamin C or unknown substances modulating in vivo vitamin C kinetics in camu-camu.

  5. Specificity of anti-phospholipid antibodies in infectious mononucleosis: a role for anti-cofactor protein antibodies

    Science.gov (United States)

    Sorice, M; Pittoni, V; Griggi, T; Losardo, A; Leri, O; Magno, M S; Misasi, R; Valesini, G

    2000-01-01

    The antigen specificity of anti-phospholipid antibodies in infectious mononucleosis (IM) was studied using ELISA for the detection of anti-β2-glycoprotein I (β2-GPI), anti-annexin V, anti-protein S and anti-prothrombin antibodies and TLC immunostaining for the detection of anti-phospholipid antibodies. This technique enabled us to look at antibodies reacting to ‘pure’ phospholipid antigens in the absence of protein contamination. Sera from 46 patients with IM, 18 with systemic lupus erythematosus (SLE), 21 with primary anti-phospholipid antibody syndrome (PAPS), 50 with Helicobacter pylori infection and 30 healthy blood donors were tested. This study highlights anti-phospholipid antibodies in patients with IM as specific ‘pure’ anti-cardiolipin antibodies, while in PAPS and SLE patients anti-phosphatidylserine and anti-phosphatidylethanolamine antibodies were also found. This investigation also shows that the anti-cardiolipin antibodies found in IM can be present with anti-cofactor protein antibodies. The higher prevalence of anti-cofactor antibodies found in IM sera than in Helicobacter pylori sera may be due to the immunostimulatory effect and/or the polyclonal activation often observed in course of Epstein–Barr virus infection. However, anti-β2-GPI and, to a lesser extent, anti-prothrombin antibodies occur with a significantly lower prevalence in IM than in PAPS patients. This finding suggests that these antibodies should be regarded as the expression of the broad autoimmune syndrome involving the phospholipid-binding plasma proteins. PMID:10792380

  6. Anti-nucleosome antibodies in systemic lupus erythematosus patients: Relation to anti-double stranded deoxyribonucleic acid and disease activity

    Directory of Open Access Journals (Sweden)

    Mayada Ali Abdalla

    2018-01-01

    Conclusion: Anti-NCS antibodies could play a role in the pathogenesis of SLE and is related to disease activity. Its association with anti-dsDNA antibodies and its presence in those with negative anti-ds DNA may aid in the diagnosis of SLE.

  7. Anti-inflammatory and anti-oxidative effects of herbal preparation EM 1201 in adjuvant arthritic rats

    Directory of Open Access Journals (Sweden)

    Laimis Akramas

    2015-01-01

    Conclusions: The present study suggests that EM 1201 has protective activity against arthritis and demonstrated its potential beneficiary effect analogical to diclofenac. Anti-inflammatory and anti-oxidative effect of EM 1201 in rats with AA support the need of further investigations by using it as supplementary agent alone or together with other anti-arthritic drugs in the treatment of rheumatoid arthritis.

  8. B0 → D0 anti D0K0, B+ → D0 anti D0K+, and the scalar D anti D bound state

    International Nuclear Information System (INIS)

    Dai, L.R.; Xie, Ju-Jun; Oset, E.

    2016-01-01

    We study the B 0 decay to D 0 anti D 0 K 0 based on the chiral unitary approach, which generates the X(3720) resonance, and we make predictions for the D 0 anti D 0 invariant mass distribution. From the shape of the distribution, the existence of the resonance below threshold could be induced. We also predict the rate of production of the X(3720) resonance to the D 0 anti D 0 mass distribution with no free parameters. (orig.)

  9. In vitro anti-inflammatory and anti-cancer activities of Cuscuta reflexa Roxb.

    Science.gov (United States)

    Suresh, V; Sruthi, V; Padmaja, B; Asha, V V

    2011-04-12

    To determine anti-inflammatory and anti-cancer activities of Cuscuta reflexa in cell lines (in vitro). Anti-inflammatory activity of the water extract was analysed in vitro using lipopolysaccharide (LPS) induced inflammatory reactions in murine macrophage cell line RAW264.7. The expression of COX-2 and TNF-α genes involved in inflammation was analysed by SQ RT-PCR. EMSA was conducted to analyse the influence of the extract on NF-κB signalling. Anti-cancer activity was analysed on Hep3B cells by MTT assay, DAPI staining, annexin V staining and SQ-RT PCR analysis of BAX, Bcl-2, p53 and survivin. The extract down regulated LPS induced over expression of TNF-α and COX-2 in RAW264.7 cells; blocked NF-κB binding to its motifs and induced apoptosis in Hep3B cells as evidenced from MTT, DAPI staining and annexin V staining assays. The extract up regulated pro-apoptotic factors BAX and p53, and down regulated anti-apoptotic factors Bcl-2 and survivin. The study showed that Cuscuta reflexa inhibits LPS induced inflammatory responses in RAW264.7 cells through interplay of TNF-α, COX-2 and NF-κB signalling. It induced apoptosis in Hep3B cells through the up regulation of p53, BAX and down regulation of Bcl-2 and survivin. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. 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.

  11. 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.

  12. Different conceptions of anti-discrimination: an analytical framework

    DEFF Research Database (Denmark)

    Olsen, Tore Vincents

    2011-01-01

    In social science and legal studies there is a lack of clarity in the categorisation of different national anti-discrimination policies. To remedy this situation, the article develops an analytical framework for categorising anti-discrimination policies. It suggests that it is useful to distinguish...... between assimilationist, liberal and multiculturalist anti-discrimination policies and demonstrates the usefulness of the analytical framework by analysing the Danish anti-discrimination policy. The categorisation of anti-discrimination policies as assimilationist, liberal or multiculturalist depends...

  13. 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...... 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 exerts...... its activity by suppressing stroma cell recruitment to the site of the growing tumor. Our epitope mapping studies suggested that the antibody recognition site overlaps with the target binding interface of human S100A4. We conclude here that this antibody could serve as a solid basis for development...

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

    Energy Technology Data Exchange (ETDEWEB)

    Chekanov, S.; Derrick, M.; Magill, S. [Argonne National Laboratory, Argonne, IL (US)] (and others)

    2007-05-15

    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{sup -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. (orig.)

  15. Anti-carbamylated Protein Antibody Levels Correlate with Anti-Sa (Citrullinated Vimentin) Antibody Levels in Rheumatoid Arthritis.

    Science.gov (United States)

    Challener, Gregory J; Jones, Jonathan D; Pelzek, Adam J; Hamilton, B JoNell; Boire, Gilles; de Brum-Fernandes, Artur José; Masetto, Ariel; Carrier, Nathalie; Ménard, Henri A; Silverman, Gregg J; Rigby, William F C

    2016-02-01

    The presence of anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) indicates a breach in immune tolerance. Recent studies indicate that this breach extends to homocitrullination of lysines with the formation of anti-carbamylated protein (anti-CarP) antibodies. We analyzed the clinical and serologic relationships of anti-CarP in 2 RA cohorts. Circulating levels of immunoglobulin G anti-CarP antibodies were determined by ELISA in established (Dartmouth-Hitchcock Medical Center) and early (Sherbrooke University Hospital Center) cohorts and evaluated for anticyclic citrullinated peptide antibodies (anti-CCP), specific ACPA, and rheumatoid factor (RF) levels using the Student t test and correlation analysis. We identified elevated anti-CarP antibodies titers in 47.0% of seropositive patients (Dartmouth, n = 164), with relationships to anti-CCP (p < 0.0001) and IgM-RF (p = 0.001). Similarly, 38.2% of seropositive patients from the Sherbrooke cohort (n = 171) had elevated anti-CarP antibodies; titers correlated to anti-CCP (p = 0.01) but not IgM-RF (p = 0.09). A strong correlation with anti-Sa was observed: 47.9% anti-Sa+ patients were anti-CarP antibodies+ versus only 25.4% anti-Sa- in the Sherbrooke cohort (p = 0.0002), and 62.6% anti-Sa+ patients versus 26.9% anti-Sa- were anti-CarP antibodies+ in Dartmouth (p < 0.0001). We found a more variable response for reactivity to citrullinated fibrinogen or to citrullinated peptides from fibrinogen and α enolase. In 2 North American RA cohorts, we observed a high prevalence of anti-CarP antibody positivity. We also describe a surprising and unexpected association of anti-CarP with anti-Sa antibodies that could not be explained by cross-reactivity. Further, considerable heterogeneity exists between anti-CarP reactivity and other citrullinated peptide reactivity, raising the question of how the pathogenesis of antibody responses for carbamylated proteins and citrullinated proteins may be linked in vivo.

  16. Prophylactic anti-D preparations display variable decreases in Fc-fucosylation of anti-D.

    Science.gov (United States)

    Kapur, Rick; Della Valle, Luciana; Verhagen, Onno J H M; Hipgrave Ederveen, Agnes; Ligthart, Peter; de Haas, Masja; Kumpel, Belinda; Wuhrer, Manfred; van der Schoot, C Ellen; Vidarsson, Gestur

    2015-03-01

    RhIG is obtained from hyperimmunized healthy anti-D donors (HIDs) boosted with D+ red blood cells (RBCs). One hypothesis for its mechanism of action is fast clearance of opsonized D+ RBCs through Fcγ receptor (FcγR)III. Levels of immunoglobulin (Ig)G Fc-fucosylation influence interactions with FcγRIII, with less Fc-fucosylation strengthening the interaction. Anti-D IgG1 Fc-glycosylation patterns in 93 plasma samples from 28 male and 28 female Dutch HIDs and RhIG were analyzed with mass spectrometry. The Fc-glycosylation profiles of HIDs were evaluated with regard to their immunization history. HID sera demonstrated clearly lowered anti-D Fc-fucosylation compared to normal IgG fucosylation (93%); this was more pronounced for female than for male HIDs (47% vs. 65%, p = 0.001). RhIG preparations from seven manufacturers varied greatly in the level of Fc-fucosylation (56%-91%). The level of fucosylation slightly increased upon repeated immunization, although it remained fairly constant over time. The RhIG from the different manufacturers all demonstrated increased Fc-galactosylation (64%-82%) compared to total IgG (38%-51%). RhIG preparations vary in Fc-fucosylation and all demonstrate increased galactosylation. Despite not knowing the exact working mechanism, immunoprophylaxis could perhaps be optimized by selection of donors whose anti-D have low amounts of Fc-fucose, to increase the clearance activity of anti-D preparations, as well as high amounts of galactosylation, for anti-inflammatory effects. Implementing a biologic assay in the standardization of RhIG preparations might be considered. © 2014 AABB.

  17. 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

  18. Dual anti-inflammatory and anti-parasitic action of topical ivermectin 1% in papulopustular rosacea.

    Science.gov (United States)

    Schaller, M; Gonser, L; Belge, K; Braunsdorf, C; Nordin, R; Scheu, A; Borelli, C

    2017-11-01

    Recently, therapy of rosacea with inflammatory lesions (papulopustular) has improved substantially with the approval of topical ivermectin 1% cream. It is assumed to have a dual mode of action with anti-inflammatory capacities and anti-parasitic effects against Demodex, which however has not yet been demonstrated in vivo. To find scientific rationale for the dual anti-inflammatory and anti-parasitic mode of action of topical ivermectin 1% cream in patients with rosacea. A monocentric pilot study was performed including 20 caucasion patients with moderate to severe rosacea, as assessed by investigator global assessment (IGA score ≥3) and a Demodex density ≥15/cm 2 . Patients were treated with topical ivermectin 1% cream once daily (Soolantra ® ) for ≥12 weeks. The density of Demodex mites was assessed with skin surface biopsies. Expression of inflammatory and immune markers was evaluated with RT-PCR and by immunofluorescence staining. The mean density of mites was significantly decreased at week 6 and week 12 (P < 0.001). The gene expression levels of IL-8, LL-37, HBD3, TLR4 and TNF-α were downregulated at both time points. Reductions in gene expression were significant for LL-37, HBD3 and TNF-α at both follow-up time points and at week 12 for TLR4 (all P < 0.05). Reduced LL-37 expression (P < 0.05) and IL-8 expression were confirmed on the protein level by immunofluorescence staining. All patients improved clinically, and 16 of 20 patients reached therapeutic success defined as IGA score ≤1. Topical ivermectin 1% cream acts by a dual, anti-inflammatory and anti-parasitic mode of action against rosacea by killing Demodex spp. in vivo, in addition to significantly improving clinical signs and symptoms in the skin. © 2017 European Academy of Dermatology and Venereology.

  19. Analgesic, anti-inflammatory and anti-platelet activities of Buddleja crispa.

    Science.gov (United States)

    Bukhari, Ishfaq A; Gilani, Anwar H; Meo, Sultan Ayoub; Saeed, Anjum

    2016-02-25

    Buddleja crispa Benth (Buddlejaceae) is a dense shrub; several species of genus Buddleja have been used in the management of various health conditions including pain and inflammation. The present study was aimed to investigate the analgesic, anti-inflammatory and anti-platelet properties of B. crispa. Male rats (220-270 gm,) and mice (25-30 gm) were randomly divided into different groups (n = 6). Various doses of plant extract of B. crispa, its fractions and pure compounds isolated from the plant were administered intraperitoneally (i.p). The analgesic, anti-inflammatory and anti-platelet activities were assessed using acetic acid and formalin-induced nociception in mice, carrageenan-induced rat paw edema and arachidonic acid-induced platelets aggregation tests. The intraperitoneal administration of the methanolic extract (50 and 100 mg/kg), hexane fraction (10 and 25 mg/kg i.p) exhibited significant inhibition (P < 0.01) of the acetic acid-induced writhing in mice and attenuated formalin-induced reaction time of animals in second phase of the test. Pure compounds BdI-2, BdI-H3 and BH-3 isolated from B. crispa produced significant (P < 0.01) analgesic activity in acetic acid-induced and formalin tests. The crude extract of B. crispa (50-200 mg/kg i.p.) and its hexane fraction inhibited carrageenan-induced rat paw edema with maximum inhibition of 65 and 71% respectively (P < 0.01). The analgesic and anti-inflammatory effect of the plant extract and isolated pure compounds were comparable to diclofenac sodium. B. crispa plant extract (0.5-2.5 mg/mL) produced significant anti-platelet effect (P < 0.01) with maximum inhibition of 78% at 2.5 mg/ml. The findings from our present study suggest that B. crispa possesses analgesic, anti-inflammatory and anti-platelet properties. B. crispa could serve a potential novel source of compounds effective in pain and inflammatory conditions.

  20. Synthesis and characterization of anti-bacterial and anti-fungal citrate-based mussel-inspired bioadhesives

    Science.gov (United States)

    Guo, Jinshan; Wang, Wei; Hu, Jianqing; Xie, Denghui; Gerhard, Ethan; Nisic, Merisa; Shan, Dingying; Qian, Guoying; Zheng, Siyang; Yang, Jian

    2016-01-01

    Bacterial and fungal infections in the use of surgical devices and medical implants remain a major concern. Traditional bioadhesives fail to incorporate anti-microbial properties, necessitating additional anti-microbial drug injection. Herein, by the introduction of the clinically used and inexpensive anti-fungal agent, 10-undecylenic acid (UA), into our recently developed injectable citrate-based mussel-inspired bioadhesives (iCMBAs), a new family of anti-bacterial and anti-fungal iCMBAs (AbAf iCs) was developed. AbAf iCs not only showed strong wet tissue adhesion strength, but also exhibited excellent in vitro cyto-compatibility, fast degradation, and strong initial and considerable long-term anti-bacterial and anti-fungal ability. For the first time, the biocompatibility and anti-microbial ability of sodium metaperiodate (PI), an oxidant used as a cross-linking initiator in the AbAf iCs system, was also thoroughly investigated. Our results suggest that the PI-based bioadhesives showed better anti-microbial properties compared to the unstable silver-based bioadhesive materials. In conclusion, AbAf iCs family can serve as excellent anti-bacterial and anti-fungal bioadhesive candidates for tissue/wound closure, wound dressing, and bone regeneration, especially when bacterial or fungal infections are a major concern. PMID:26874283

  1. Evaluation of Iowa's anti-bullying law.

    Science.gov (United States)

    Ramirez, Marizen; Ten Eyck, Patrick; Peek-Asa, Corinne; Onwuachi-Willig, Angela; Cavanaugh, Joseph E

    2016-12-01

    Bullying is the most common form of youth aggression. Although 49 of all 50 states in the U.S. have an anti-bullying law in place to prevent bullying, little is known about the effectiveness of these laws. Our objective was to measure the effectiveness of Iowa's anti-bullying law in preventing bullying and improving teacher response to bullying. Sixth, 8th, and 11th grade children who completed the 2005, 2008 and 2010 Iowa Youth Survey were included in this study (n = 253,000). Students were coded according to exposure to the law: pre-law for 2005 survey data, one year post-law for 2008 data, and three years post-law for 2010 data. The outcome variables were: 1) being bullied (relational, verbal, physical, and cyber) in the last month and 2) extent to which teachers/adults on campus intervened with bullying. Generalized linear mixed models were constructed with random effects. The odds of being bullied increased from pre-law to one year post-law periods, and then decreased from one year to three years post-law but not below 2005 pre-law levels. This pattern was consistent across all bullying types except cyberbullying. The odds of teacher intervention decreased 11 % (OR = 0.89, 95 % CL = 0.88, 0.90) from 2005 (pre-law) to 2010 (post-law). Bullying increased immediately after Iowa's anti-bullying law was passed, possibly due to improved reporting. Reductions in bullying occurred as the law matured. Teacher response did not improve after the passage of the law.

  2. Superfield approach to anti de Sitter supersymmetry

    International Nuclear Information System (INIS)

    Ivanov, E.A.

    1979-01-01

    A self-contained superfield approach to global supersymmetry in anti de Sitter space (OSp(1.4)) is developed. General transformation laws for OSp(1.4)-superfields are established, and all basic elements of the OSp(1.4)-covariant formalism in the real basis, such as covariant superfield derivatives, invariant integration measure over the superspace OSp(1.4)/O(1.3), etc., are explicitly given. The reducibility questions are analyzed and realizations of OSp(1.4) in the left- and right-handed chiral superspaces are found

  3. Structures in anti pp → π π

    International Nuclear Information System (INIS)

    Martin, B.R.; Morgan, D.

    1980-03-01

    A Barrelet-zero analysis is presented of data on anti pp → π π in the momentum range 1 to 2 GeV/c. With π - π + data alone, the scope for ambiguity is very large but the addition of π 0 π 0 information enables the number of solutions to be reduced to just a few. Although the alternative solutions differ considerably, they have significant common features, in particular, with plausible extra assumptions, all solutions appear to be dominated by resonance in all spin states from J = 1 to 5

  4. Anti-sound and Acoustical Cloaks

    Directory of Open Access Journals (Sweden)

    Veturia CHIROIU

    2016-12-01

    Full Text Available The principles by which the acoustics can be mimicked in order to reduce or cancel the vibrational field are based on anti-sound concept which can be materialized by acoustic cloaks. Geometric transformations open an elegant way towards the unconstrained control of sound through acoustic metamaterials. Acoustic cloaks can be achieved through geometric transformations which bring exotic metamaterial properties into the acoustic equations. Our paper brings new ideas concerning the technological keys for manufacturing of novel metamaterials based on the spatial compression of Cantor structures, and the architecture of 3D acoustic cloaks in a given frequency band, with application to architectural acoustics.

  5. p anti p collider physics: summary talk

    International Nuclear Information System (INIS)

    Bjorken, J.D.

    1985-06-01

    Progress is very briefly summarized in these areas: Drell-Yan production of W and Z; inclusive spectra of jets; angular distribution of two jet final states; Dalitz plot analysis of three jet final states; interior structure of jets; minijets; issues and relevent data in soft-collision physics; structure of the pomeron; W, Z, and electroweak theory; heavy quark physics; extinct exotica; extant exotica, including monojets, the top quark, and possibly anomalous same-sign isolated dimuons. Future directions are anticipated for the Sp anti pS, Tevatron I, instrumentation and detectors, group theory, and the physics at SSC energies. 39 refs., 18 figs

  6. Anti-inflammatory activity of Lippia dulcis.

    Science.gov (United States)

    Pérez, S; Meckes, M; Pérez, C; Susunaga, A; Zavala, M A

    2005-10-31

    Lippia dulcis hexane and ethanol extracts were tested for its anti-inflammatory activity in several animal models. Hexane extract showed to be inactive, but the ethanol extract at doses of 400 mg/kg produced significant inhibition of carrageenan-induced paw oedema and reduced the weight of cotton pellet-induced granuloma, moreover, the topical application of 0.5 mg/ear of this extract inhibited the edema induced with TPA by 49.13%, an effect which is of less intensity than that produced by indomethacine at the same dose.

  7. RAY TRACING RENDER MENGGUNAKAN FRAGMENT ANTI ALIASING

    Directory of Open Access Journals (Sweden)

    Febriliyan Samopa

    2008-07-01

    Full Text Available Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin-top:0cm; mso-para-margin-right:0cm; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0cm; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} Rendering is generating surface and three-dimensional effects on an object displayed on a monitor screen. Ray tracing as a rendering method that traces ray for each image pixel has a drawback, that is, aliasing (jaggies effect. There are some methods for executing anti aliasing. One of those methods is OGSS (Ordered Grid Super Sampling. OGSS is able to perform aliasing well. However, this method requires more computation time since sampling of all pixels in the image will be increased. Fragment Anti Aliasing (FAA is a new alternative method that can cope with the drawback. FAA will check the image when performing rendering to a scene. Jaggies effect is only happened at curve and gradient object. Therefore, only this part of object that will experience sampling magnification. After this sampling magnification and the pixel values are computed, then downsample is performed to retrieve the original pixel values. Experimental results show that the software can implement ray tracing well in order to form images, and it can implement FAA and OGSS technique to perform anti aliasing. In general, rendering using FAA is faster than using OGSS

  8. Mass in anti-de Sitter spaces

    International Nuclear Information System (INIS)

    Liu, James T.; Sabra, W.A.

    2005-01-01

    The boundary stress tensor approach has proven extremely useful in defining mass and angular momentum in asymptotically anti-de Sitter spaces with CFT duals. An integral part of this method is the use of boundary counterterms to regulate the gravitational action and stress tensor. In the presence of matter, however, ambiguities may arise that are related to the addition of possible finite counterterms. We demonstrate this explicitly for R-charged black holes in AdS 5 , where introduction of a finite counterterm proportional to φ 2 is necessary to properly reproduce the expected mass/charge relation for the black holes

  9. Anti-Ageing Cultures, Biopolitics and Globalisation

    Directory of Open Access Journals (Sweden)

    Brett Neilson

    2011-11-01

    Full Text Available In March 2004, the author attended the Inaugural International Conference on Longevity at the Sydney Exhibition and Convention Centre in Darling Harbour. As a cultural researcher interested in the interactions between demographic shifts, capitalist globalisation and changing forms of political power, the prospect of a direct encounter with the debates and practices surrounding the burgeoning field of anti-ageing medicine promised a means to observe the complex cultural dynamics of population ageing at play. This article explores the discord the atuhor witnessed; a quarrel that, despite the march of technological advance, attests the ongoing conflict in the nexus where politics meets life.

  10. Nanotag luminescent fingerprint anti-counterfeiting technology

    DEFF Research Database (Denmark)

    Radziwon, Michal Jędrzej; Rubahn, Horst-Günter; Johansen, Stefan

    2012-01-01

    We describe a method to fabricate, transfer and validate via image processing nanofibre- based, unique security marks (“nanotags”) for anti-counterfeiting purposes. Epitaxial surface growth of oligophenylenes on a heated muscovite mica crystal results in a thin film of mutually aligned nanofibres....... This fingerprint can be transferred on an adhesive tape as a label of a product, imaged using low magnification microscopy, digitalised and stored in a database. Infrared surface heating, enforced cooling and load lock transfer makes the fabrication process fast and scalable to mass production....

  11. 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...... on these strategies exist at the moment. A third potential approach involves novel agents whose mechanism of action is closely related to COPD mechanisms and pathophysiology. Such novel treatments are of great interest since they may treat both COPD and co-morbidities. Several novel agents are currently under...

  12. Experimental Study on Anti-body effects of Anti-BV on the Bee Venom Herbal Acupuncture

    Directory of Open Access Journals (Sweden)

    Ki Rok Kwon

    2005-02-01

    Full Text Available Objectives : To observe physiological anti-body effects of anti-BV, acute toxic response, measurement of LD50, and the effects of anti-body were evaluated. Methods : LD50 of Anti-Bee Venom were measured, and to analyze acute toxic responses, weight, and the anti-body effects various concentrations of Anti-BV were diluted and the survival rate was measured. Cell blood count (CBC, liver, spleen, and kidney pathologies were observed from the histological aspects. Results : Experiment was conducted to observe Anti-BV as the anti-body to the bee venom and the following results were obtained: 1. Anti-BV was injected intraperitoneally and no toxic responses were witnessed. All of the experiment subjects stayed alive during the experiment, making LD50 analysis impossible. 2. Anti-BV was injected intraperitoneally in mice and no significant weight changes were measured between the control group and the experiment groups. 3. Measuring the concentration dependent survival rate, the highest survival rate was at the concentration of 1.25×102mg/kg(1/2.000 for Anti-BV. 4. No particular results were shown in the CBC test. 5. Observation of changes in the organ tissues, Anti-BV was found to suppress blood stasis in the liver and inhibit necrosis of the cells. Conclusion : Above results suggest that Anti-BV doesn't cause any toxic responses in the body and works as an anti-body to the bee venom. Further studies must be followed to secure the findings.

  13. Anti-Diabetic, Anti-Oxidant and Anti-Hyperlipidemic Activities of Flavonoids from Corn Silk on STZ-Induced Diabetic Mice.

    Science.gov (United States)

    Zhang, Yan; Wu, Liying; Ma, Zhongsu; Cheng, Jia; Liu, Jingbo

    2015-12-23

    Corn silk is a well-known ingredient frequently used in traditional Chinese herbal medicines. This study was designed to evaluate the anti-diabetic, anti-oxidant and anti-hyperlipidemic activities of crude flavonoids extracted from corn silk (CSFs) on streptozotocin (STZ)-induced diabetic mice. The results revealed that treatment with 300 mg/kg or 500 mg/kg of CSFs significantly reduced the body weight loss, water consumption, and especially the blood glucose (BG) concentration of diabetic mice, which indicated their potential anti-diabetic activities. Serum total superoxide dismutase (SOD) and malondialdehyde (MDA) assays were also performed to evaluate the anti-oxidant effects. Besides, several serum lipid values including total cholesterol (TC), triacylglycerol (TG), low density lipoprotein cholesterol (LDL-C) were reduced and the high density lipoprotein cholesterol level (HDL-C) was increased. The anti-diabetic, anti-oxidant and anti-hyperlipidemic effect of the CSFs suggest a potential therapeutic treatment for diabetic conditions.

  14. Anti-Diabetic, Anti-Oxidant and Anti-Hyperlipidemic Activities of Flavonoids from Corn Silk on STZ-Induced Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    2015-12-01

    Full Text Available Corn silk is a well-known ingredient frequently used in traditional Chinese herbal medicines. This study was designed to evaluate the anti-diabetic, anti-oxidant and anti-hyperlipidemic activities of crude flavonoids extracted from corn silk (CSFs on streptozotocin (STZ-induced diabetic mice. The results revealed that treatment with 300 mg/kg or 500 mg/kg of CSFs significantly reduced the body weight loss, water consumption, and especially the blood glucose (BG concentration of diabetic mice, which indicated their potential anti-diabetic activities. Serum total superoxide dismutase (SOD and malondialdehyde (MDA assays were also performed to evaluate the anti-oxidant effects. Besides, several serum lipid values including total cholesterol (TC, triacylglycerol (TG, low density lipoprotein cholesterol (LDL-C were reduced and the high density lipoprotein cholesterol level (HDL-C was increased. The anti-diabetic, anti-oxidant and anti-hyperlipidemic effect of the CSFs suggest a potential therapeutic treatment for diabetic conditions.

  15. 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.

  16. Therapeutic effects of date fruits (Phoenix dactylifera) in the prevention of diseases via modulation of anti-inflammatory, anti-oxidant and anti-tumour activity.

    Science.gov (United States)

    Rahmani, Arshad H; Aly, Salah M; Ali, Habeeb; Babiker, Ali Y; Srikar, Sauda; Khan, Amjad A

    2014-01-01

    The current mode of treatment of various diseases based on synthetic drugs is expensive, alters genetic and metabolic pathways and also shows adverse side effects. Thus, safe and effective approach is needed to prevent the diseases development and progression. In this vista, Natural products are good remedy in the treatment/management of diseases and they are affordable and effective without any adverse effects. Dates are main fruit in the Arabian Peninsula and are considered to be one of the most significant commercial crops and also have been documented in Holy Quran and modern scientific literatures. Earlier studies have shown that constituents of dates act as potent antioxidant, anti-tumour as well as anti-inflammatory, provide a suitable alternative therapy in various diseases cure. In this review, dates fruits has medicinal value are summarized in terms of therapeutic implications in the diseases control through anti-oxidant, anti-inflammatory, anti-tumour and ant-diabetic effect.

  17. [Anti-TNF alpha in dermatology].

    Science.gov (United States)

    Mahe, E; Descamps, V

    2002-12-01

    The discovery of the major role of TNF alpha in the physiopathology of certain inflammatory diseases and notably in rheumatoid arthritis and Crohn's disease has led to the development of anti-TNF alpha drugs. These new therapeutic arms issued from bio-technology have rapidly demonstrated their efficacy in the treatment of these two diseases. The anti-TNF alpha arsenal is currently dominated by etanercept, a fusion protein composed of a soluble TNF alpha receptor, and infliximab, a chimeric monoclonal antibody. However, new molecules will soon enrich this arsenal. TNF alpha is a major cytokine of inflammatory diseases of the skin. Many dermatological diseases will probably benefit from these new treatments. Two studies have already demonstrated their interest in cutaneous and articular psoriasis. Encouraging sporadic results suggest other potential indications (Behcet's disease, bullous dermatitis, neutrophilic dermatitis, toxic epidermal necrolysis, systemic vascularitis,.). These promising new treatments, although expensive, and with yet unknown long term side effects, justify rigorous assessment of their efficacy and tolerance in each indication. Here again the dermatologist has a major role to play in post-marketing pharmacovigilance.

  18. 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.

    2017-06-27

    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.

  19. Anti-idling campaign : Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-11-01

    The efficient use of transportation fuels and other petroleum products is being promoted by the Canadian Petroleum Products Institute. The Institute was busy during the past year in attempting to gain an understanding of the measures that could be adopted to assist motorists clearly identify the relationship between fuel consumption, personal transportation spending, and environmental impacts. The Institute undertook these efforts with Natural Resources Canada (NRCan) Office of Energy Efficiency (which both provided funding) and the Public Policy Forum. A first step proposed was the development of an anti-idling public awareness campaign. It was recognized that idling a vehicle for more than ten seconds costs money and wastes fuel, while simultaneously contributing to air pollution, greenhouse gas emissions, and climate change. The campaign also involved Esso, Shell, Petro-Canada, Canadian Tire and Sunoco for the development and implementation phases over the last two weeks of August 2002. A pilot campaign was tested in Mississauga, Ontario. Various materials were used for this campaign, such as posters, banners, cling vinyl window decals, air fresheners and information cards. The main successes of the campaign were: testing the methods of communicating the anti-idling message to drivers at gasoline retailing sites, increasing awareness among the driving public concerning the problems resulting from excessive idling, and encouraging the reduction of idling whenever and wherever it takes place. 1 tab.

  20. 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.

  1. Continuous anti-Stokes Raman laser operation

    International Nuclear Information System (INIS)

    Feitisch, A.; Muller, T.; Welling, H.; Wellegehausen, B.

    1988-01-01

    The anti-Stokes Raman laser (ASRL) process has proved to be a method that works well for frequency upconversion and for the generation of powerful tunable narrowband (pulsed) laser radiation in the UV and VUV spectral range. This conversion process allows large-frequency shifts in single step, high output energies, and high efficiencies. A basic requirement is population inversion on a two-photon transition, where, in general, the upper level of the transition should be metastable. Up to now the ASRL technique has only been demonstrated for the pulsed regime, where the necessary population inversion was generated by photodissociation or inner shell photoionization. These inversion techniques, however, cannot be transferred to cw operation of an ASRL, and, therefore, other inversion techniques have to be developed. Here a novel approach for the creation of the necessary population inversion is proposed, that uses well-known cw gas lasers as the active material for the conversion process. The basic idea is to use either existing two-photon population inversions in a cw laser material or to generate the necessary population inversion by applying a suitable population transfer process to the material. A natural two-photon inversion situation in a laser material is evident whenever a cascade laser can be operated. Cascade laser-based anti-Stokes schemes are possible in a He-Ne laser discharge, and investigations of these schemes are discussed

  2. [Omalizumab: Beyond anti-IgE properties].

    Science.gov (United States)

    Perotin, J-M; Barnig, C

    2017-02-01

    Omalizumab is used as a treatment for severe allergic asthma. Its intended mechanism of action is based on its anti-IgE proprieties. However, recent studies have highlighted other mechanisms of action. Omalizumab treatment is associated with a decrease in the number of dendritic cells, T and B lymphocytes and eosinophils. This anti-inflammatory activity is characterized by a decrease in the levels of several cytokines involved in the recruitment, activation and survival of eosinophils and mastocytes, and in a Th2 orientation of the immune response. A modulation of bronchial remodeling by omalizumab has recently been shown. A decrease in the production of extracellular matrix components and in the proliferation of smooth muscle cells could be involved in this modulation. These mechanisms of action could explain in part the clinical efficiency of omalizumab in non-allergic conditions such as non-allergic asthma, non-allergic urticaria or nasal polyposis. A precise knowledge of the mechanisms of action of omalizumab could allow the identification of biomarkers predictive of efficacy of this treatment. These could be useful tools in the phenotyping of severe asthma. Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  3. Violation of Particle Anti-particle Symmetry

    CERN Multimedia

    CERN. Geneva

    2001-01-01

    Symmetry is a fundamental concept which can be found in the whole range of human activities e. g. from arts to science. The beauty of a statues is often related to its symmetric form. In physics, all the laws are related to some sort of symmetry. Equally important is a small breakdown ofsymmetry. Even for the case of a statue, its beauty might be enhanced by introducing small distortions. In this course, we investigate the role symmetry in the world of elementary particles. Some symmetries found there are very similar to those which can be seen in our daily life, while others are more exotic and related to the quantum nature of the elementary particles. Our particular focus ismade on symmetry and its violation between the matter and anti-matter, known as CP violation. It is experimentally well established that particleand anti-particle behave a tiny bit differently in the world of elementary particles. We discuss how this would be explained and how we can extendour knowledge. Evolution of our universe is stro...

  4. Origins of anti-DNA autoantibodies

    International Nuclear Information System (INIS)

    Schwartz, R.S.

    1985-01-01

    The direction of research in autoimmunity was strongly influenced by three notable discoveries made more than 25 year ago: anti-DNA anti-bodies in lupus serum, the immunofluorescent antinuclar antibody test and the NZB mouse. Now another turning point has been reached for three new reasons: the discovery of the hybridoma technic, advances in cellular immunology and the use of molecular biology to solve immunological problems. These developments have motivated fresh approaches to questions about the origins and pathogenic mechanisms of autoantibodies. Systemic lupus erythematosus (SLE) has a conspicuous position in the field of autoimmunity for several reasons. Its diverse manifestations have attracted a correspondingly diverse group of investigators whose interests range from molecular biology to therapeutic trials; superb models of the disease occur spontaneously in animals; and the extensive variety of autoantibodies in SLE provides an abundance of investigative reagents. An explanation of the origins of these autoantibodies is one of the major goals of research in the disease. The autoantibodies that bind to DNA are of central interest. They occur in almost all patients with active SLE, they often fluctuate with its clinical activity, and they participate in forming its lesions

  5. 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. Copyright © 2013. Published by Elsevier B.V.

  6. Pharmacogenetics of Anti-Diabetes Drugs

    Directory of Open Access Journals (Sweden)

    Johanna K. DiStefano

    2010-08-01

    Full Text Available A variety of treatment modalities exist for individuals with type 2 diabetes mellitus (T2D. In addition to dietary and physical activity interventions, T2D is also treated pharmacologically with nine major classes of approved drugs. These medications include insulin and its analogues, sulfonylureas, biguanides, thiazolidinediones (TZDs, meglitinides, α-glucosidase inhibitors, amylin analogues, incretin hormone mimetics, and dipeptidyl peptidase 4 (DPP4 inhibitors. Pharmacological treatment strategies for T2D are typically based on efficacy, yet favorable responses to such therapeutics are oftentimes variable and difficult to predict. Characterization of drug response is expected to substantially enhance our ability to provide patients with the most effective treatment strategy given their individual backgrounds, yet pharmacogenetic study of diabetes medications is still in its infancy. To date, major pharmacogenetic studies have focused on response to sulfonylureas, biguanides, and TZDs. Here, we provide a comprehensive review of pharmacogenetics investigations of these specific anti-diabetes medications. We focus not only on the results of these studies, but also on how experimental design, study sample issues, and definition of ‘response’ can significantly impact our interpretation of findings. Understanding the pharmacogenetics of anti-diabetes medications will provide critical baseline information for the development and implementation of genetic screening into therapeutic decision making, and lay the foundation for “individualized medicine” for patients with T2D.

  7. 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.

  8. 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

  9. Anti-leishmanial and Anti-cancer Activities of a Pentacyclic ...

    African Journals Online (AJOL)

    Erah

    against promastigotes of Leishmania donovani, and anti-cancer activity on K562 leukaemic cell line. Results: A .... crisis of chronic myeloid leukemia was used for this test. The cells ... containing 1×106 cells/ml, 2 mM L-glutamine and 50 µg/ml ...

  10. Anti-cyclic Citrullinated Peptide Antibody (Anti-CCP and Diagnostic Value for Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Mehmet Agilli

    2014-02-01

    Full Text Available Rheumatoid arthritis (RA is an inflammatory multisystem disease of unknown etiology characterized by chronic destructive synovitis. It and #8217;s prevalence is about 1% all over the world. Serologic markers are also important beside some clinical situations upon RA diagnosis. Today, the most commonly used laboratory test is rheumatoid factor (RF in patients with suspected RA. RF is sensitive but not a specific biomarker for diagnosing RA. Early diagnosis of RA is essential to prevent of progressive joint damage. In recent years, anticyclic citrullinated peptide/protein antibody (anti-CCP attracts the attention as a remarkable biomarker for early diagnosis. Anti-CCP which is a family of anti-citrullinated protein antibodies (ACPA family, showed quite satisfactory specificity in the diagnosis of RA. Due to the prescence of ACPA was included to 2010 RA diagnostic criteria, in a manner of speaking, importance of anti-CCP was registered. [TAF Prev Med Bull 2014; 13(1.000: 83-88

  11. Assessment of the anti-angiogenic, anti-inflammatory and antinociceptive properties of ethyl vanillin.

    Science.gov (United States)

    Jung, Hyun-Joo; Song, Yun Seon; Kim, Kyunghoon; Lim, Chang-Jin; Park, Eun-Hee

    2010-02-01

    The present work aimed to assess novel pharmacological properties of ethyl vanillin (EVA) which is used as a flavoring agent for cakes, dessert, confectionary, etc. EVA exhibited an inhibitory activity in the chorioallantoic membrane angiogenesis. Anti-inflammatory activity of EVA was convinced using the two in vivo models, such as vascular permeability and air pouch models in mice. Antinociceptive activity of EVA was assessed using acetic acid-induced writhing model in mice. EVA suppressed production of nitric oxide and induction of inducible nitric oxide synthase in the lipopolysaccharide (LPS)-activated RAW264.7 macrophage cells. However, EVA could not suppress induction of cyclooxygenase-2 in the LPS-activated macrophages. EVA diminished reactive oxygen species level in the LPS-activated macrophages. EVA also suppressed enhanced matrix metalloproteinase-9 gelatinolytic activity in the LPSactivated RAW264.7 macrophage cells. EVA at the used concentrations couldn't diminish viability of the macrophage cells. Taken together, the anti-angiogenic, anti-inflammatory and anti-nociceptive properties of EVA are based on its suppressive effect on the production of nitric oxide possibly via decreasing the reactive oxygen species level.

  12. 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

  13. Prophylactic anti-D preparations display variable decreases in Fc-fucosylation of anti-D.

    NARCIS (Netherlands)

    Kapur, R.; Della Valle, L.; Verhagen, O.J.; Hipgrave Ederveen, A.; Ligthart, P.; de Haas, M.; Kumpel, B.; Wuhrer, M.; van der Schoot, C.E.; Vidarsson, G.

    2015-01-01

    Background RhIG is obtained from hyperimmunized healthy anti-D donors (HIDs) boosted with D+ red blood cells (RBCs). One hypothesis for its mechanism of action is fast clearance of opsonized D+ RBCs through Fcγ receptor (FcγR)III. Levels of immunoglobulin (Ig)G Fc-fucosylation influence interactions

  14. Prophylactic anti-D preparations display variable decreases in Fc-fucosylation of anti-D

    NARCIS (Netherlands)

    Kapur, Rick; Della Valle, Luciana; Verhagen, Onno J. H. M.; Hipgrave Ederveen, Agnes; Ligthart, Peter; de Haas, Masja; Kumpel, Belinda; Wuhrer, Manfred; van der Schoot, C. Ellen; Vidarsson, Gestur

    2015-01-01

    RhIG is obtained from hyperimmunized healthy anti-D donors (HIDs) boosted with D+ red blood cells (RBCs). One hypothesis for its mechanism of action is fast clearance of opsonized D+ RBCs through Fcγ receptor (FcγR)III. Levels of immunoglobulin (Ig)G Fc-fucosylation influence interactions with

  15. Four anti-protozoal and anti-bacterial compounds from Tapirira guianensis.

    Science.gov (United States)

    Roumy, Vincent; Fabre, Nicolas; Portet, Bénédicte; Bourdy, Geneviève; Acebey, Lucia; Vigor, Claire; Valentin, Alexis; Moulis, Claude

    2009-01-01

    Tapirira guianensis is a common tree used in traditional medicine in French Guiana against several infectious diseases (malaria, leishmaniasis, bacteria, etc.). The bioassay-guided purification of CH(2)Cl(2) bark extract led to the isolation of four cyclic alkyl polyol derivatives: 4,6,2'-trihydroxy-6-[10'(Z)-heptadecenyl]-1-cyclohexen-2-one (1a), 1,4,6-trihydroxy-1,2'-epoxy-6-[10'(Z)-heptadecenyl]-2-cyclohexene (1b), 1,4,5,2'-tetrahydroxy-1-[10'(Z)-heptadecenyl]-2-cyclohexene (2), and 1,3,4,6-tetrahydroxy-1,2'-epoxy-6-[10'(Z)-heptadecenyl]-cyclohexane (3). The structures were established on the basis of 1D and 2D NMR analyses. The anti-leishmanial, anti-plasmodial, anti-bacterial (on Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli), and anti-fungal (on Candida albicans) activities of the extracts and of these original compounds were evaluated. Two showed medicinal interest supporting the traditional uses of the plant. The structures were established through spectral analyses of the isolates and their derivatives.

  16. Anti-oxidant and anti-inflammatory effects of rice bran and green tea ...

    African Journals Online (AJOL)

    assay and flow cytometry. The anti-inflammatory effects of OCB were assessed by a nitric oxide (NO) assay ... (DOAJ), African Journal Online, Bioline International, Open-J-Gate and Pharmacy Abstracts ... officially used at the 11th Winter Olympics Games of 1972 in ... well known for its beneficial properties on body condition ...

  17. Anti-diabetic and anti-oxidant effects of Zingiber Officinale on ...

    African Journals Online (AJOL)

    This study was designed to investigate the hypoglycaemic and anti-oxidant effects of Zingiber officinale on experimentally induced diabetes mellitus using alloxan and insulin resistance. Aqueous extracts of raw ginger was administered orally at a chosen dose of 500mg/ml for a period of 4 weeks to alloxan-induced diabetic ...

  18. Anti-plasmodial and anti-inflammatory activities of cyclotide-rich ...

    African Journals Online (AJOL)

    2017-09-03

    Sep 3, 2017 ... orthodox anti-malarial treatments, and in search of relief, people living in ... the world today are still derived from natural sources.5. An important role in ..... each assay plate. Effect of CRF on LPS-evoked tumor necrosis factor ..... to contribute to the inflammatory cascade by increasing vascular permeability.

  19. Anti-tumor and anti-angiogenic ergosterols from Ganoderma lucidum

    Science.gov (United States)

    Chen, Shaodan; Yong, Tianqiao; Zhang, Yifang; Su, Jiyan; Jiao, Chunwei; Xie, Yizhen

    2017-10-01

    This study was carried out to isolate chemical constituents from the lipid enriched fraction of Ganoderma lucidum extract and to evaluate their anti-proliferative effect on cancer cell lines and human umbilical vein endothelial cells. Ergosterol derivatives (1-14) were isolated from the lipid enriched fraction of G. lucidum. Their structures were established on the basis of spectroscopic analyses or by comparison of mass and NMR spectral data with those reported previously. Amongst, compound 1 was isolated and identified as a new compound. All the compounds were evaluated for their inhibitory effect on tumor cells and human umbilical vein endothelial cells in vitro. Compounds 9-13 displayed inhibitory activity against two tumor cell lines and human umbilical vein endothelial cells, which indicated that these four compounds had both anti-tumor and anti-angiogenesis activities. Compound 2 had significant selective inhibition against two tumor cell lines, while 3 exhibited selective inhibition against human umbilical vein endothelial cells. The structure–activity relationships for inhibiting human HepG2 cells were revealed by 3D-QASR. Ergosterol content in different parts of the raw material and products of G. lucidum was quantified. This study provides a basis for further development and utilization of ergosterol derivatives as natural nutraceuticals and functional food ingredients, or as source of new potential antitumor or anti-angiogenesis chemotherapy agent.

  20. Macrolide Hybrid Compounds: Drug Discovery Opportunities in Anti- Infective and Anti-inflammatory Area.

    Science.gov (United States)

    Paljetak, Hana Cipcic; Tomaskovic, Linda; Matijasic, Mario; Bukvic, Mirjana; Fajdetic, Andrea; Verbanac, Donatella; Peric, Mihaela

    2017-01-01

    Macrolides, polyketide natural products, and their 15-membered semi-synthetic derivatives are composed of substituted macrocyclic lactone ring and used primarily as potent antibiotics. Recently their usefulness was extended to antimalarial and anti-inflammatory area. Hybrid macrolides presented in this article are the next generation semi-synthetic compounds that combine pharmacophores from antibacterial, antimalarial and anti-inflammatory area with 14- and 15-membered azalide scaffolds. Antibacterial azalide hybrids with sulphonamides showed improved activity against resistant streptococci while quinolone conjugates demonstrated full coverage of respiratory pathogens including macrolide resistant strains and their efficacy was confirmed in mouse pneumonia model. Antimalarial macrolide hybrids, mainly involving (chloro)quinoline pharmacophores, showed outstanding activity against chloroquine resistant strains, favourable pharmacokinetics, promising in vivo efficacy as well as encouraging developmental potential. Anti-inflammatory hybrids were obtained by combining macrolides with corticosteroid and non-steroidal anti-inflammatory drugs. They were found active in in vivo animal models of locally induced inflammation, asthma, inflammatory bowel disease and rheumatoid arthritis and demonstrated improved safety over parent steroid drugs. Overall, macrolide hybrids possess significant potential to be developed as potent novel medicines in therapeutic areas of utmost pharmaceutical interest. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Clinico-laboratory aspects of anti-nuclear and anti-native DNA antibody tests.

    Science.gov (United States)

    Webb, J

    1978-01-01

    Available techniques for detection of anti-nuclear antibodies are here briefly reviewed. The relatively insensitive LE cell test has been largely supplanted by the indirect immunofluorescent ANA test which should be reported in terms of titre and pattern. Specific measurement of nDNA antibodies is now a regular technique in SLE diagnosis and management.

  2. [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.

  3. Anti-leukemic activity and tolerability of anti-human CD47 monoclonal antibodies

    Science.gov (United States)

    Pietsch, E C; Dong, J; Cardoso, R; Zhang, X; Chin, D; Hawkins, R; Dinh, T; Zhou, M; Strake, B; Feng, P-H; Rocca, M; Santos, C Dos; Shan, X; Danet-Desnoyers, G; Shi, F; Kaiser, E; Millar, H J; Fenton, S; Swanson, R; Nemeth, J A; Attar, R M

    2017-01-01

    CD47, a broadly expressed cell surface protein, inhibits cell phagocytosis via interaction with phagocyte-expressed SIRPα. A variety of hematological malignancies demonstrate elevated CD47 expression, suggesting that CD47 may mediate immune escape. We discovered three unique CD47-SIRPα blocking anti-CD47 monoclonal antibodies (mAbs) with low nano-molar affinity to human and cynomolgus monkey CD47, and no hemagglutination and platelet aggregation activity. To characterize the anti-cancer activity elicited by blocking CD47, the mAbs were cloned into effector function silent and competent Fc backbones. Effector function competent mAbs demonstrated potent activity in vitro and in vivo, while effector function silent mAbs demonstrated minimal activity, indicating that blocking CD47 only leads to a therapeutic effect in the presence of Fc effector function. A non-human primate study revealed that the effector function competent mAb IgG1 C47B222-(CHO) decreased red blood cells (RBC), hematocrit and hemoglobin by >40% at 1 mg/kg, whereas the effector function silent mAb IgG2σ C47B222-(CHO) had minimal impact on RBC indices at 1 and 10 mg/kg. Taken together, our findings suggest that targeting CD47 is an attractive therapeutic anti-cancer approach. However, the anti-cancer activity observed with anti-CD47 mAbs is Fc effector dependent as are the side effects observed on RBC indices. PMID:28234345

  4. Anti-oxidative and anti-inflammatory effects of Tagetes minuta essential oil in activated macrophages

    Science.gov (United States)

    Karimian, Parastoo; Kavoosi, Gholamreza; Amirghofran, Zahra

    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-α mRNA 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-α mRNA 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. PMID:25182441

  5. Anti-inflammatory effects and anti-oxidant capacity of Myrathius arboreus (Cecropiaceae) in experimental models.

    Science.gov (United States)

    Oluwole, Oluwafemi Gabriel; Ologe, Olufunmilayo; Alabi, Akinyinka; Tunde Yusuf, Ganiyu; Umukoro, Solomon

    2017-11-27

    Inflammation is involved in various diseases; search for safe treatments is warranted. Anti-inflammatory effects of ethanol extract of Myrathius arboreus (EEMa) were studied in carrageenan-induced model, formaldehyde sub-acute-induced model, and in 48 h lipopolysaccharide-induced air pouch model of inflammation. EEMa membrane-stabilizing activities and anti-oxidant capacity were determined in vitro. In the carrageenan model EEMa (125, 250, or 500 mg/kg), indomethacin (5 mg/kg), or vehicle 3 mL/kg was administered orally in rats (n=5). After 1 h, 0.1 mL of 1% carrageenan was injected into the right hind paw of rats. Change in edema sizes was measured for 3 h with plethysmometer. One-tenth milliliter (0.1 mL) of 2.5% formaldehyde was injected into the rat paw on the first day and the third day to induce sub-acute inflammation; changes in the edema sizes were determined, and percentages of inhibitions were calculated. Anti-inflammatory effects of EEMa were further examined in lipopolysaccharide (LPS)-induced air-pouch based on leukocytes count, volume of exudates, levels of malondialdehyde, glutathione, superoxide dismutase, nitric oxides, and tumor necrosis factor released into the inflammatory fluids. EEMa-free radicals scavenging activities were studied in DPPH and reducing power tests. Membrane-stabilizing activities of EEMa were evaluated in the red blood cell lysis induced by thermal and hypotonic solution. EEMa (250, 500 mg/kg) produced significant (p<0.001; p<0.05) inhibition of inflammation when compared with vehicle. Also, EEMa (250, 500, or 1000 μg/mL) significantly stabilized membrane and produced free radical scavenging activities. M. arboreus possesses anti-inflammatory and the anti-oxidant properties that might benefit translational medicine.

  6. Nature is the best source of anti-inflammatory drugs: indexing natural products for their anti-inflammatory bioactivity.

    Science.gov (United States)

    Aswad, Miran; Rayan, Mahmoud; Abu-Lafi, Saleh; Falah, Mizied; Raiyn, Jamal; Abdallah, Ziyad; Rayan, Anwar

    2018-01-01

    The aim was to index natural products for less expensive preventive or curative anti-inflammatory therapeutic drugs. A set of 441 anti-inflammatory drugs representing the active domain and 2892 natural products representing the inactive domain was used to construct a predictive model for bioactivity-indexing purposes. The model for indexing the natural products for potential anti-inflammatory activity was constructed using the iterative stochastic elimination algorithm (ISE). ISE is capable of differentiating between active and inactive anti-inflammatory molecules. By applying the prediction model to a mix set of (active/inactive) substances, we managed to capture 38% of the anti-inflammatory drugs in the top 1% of the screened set of chemicals, yielding enrichment factor of 38. Ten natural products that scored highly as potential anti-inflammatory drug candidates are disclosed. Searching the PubMed revealed that only three molecules (Moupinamide, Capsaicin, and Hypaphorine) out of the ten were tested and reported as anti-inflammatory. The other seven phytochemicals await evaluation for their anti-inflammatory activity in wet lab. The proposed anti-inflammatory model can be utilized for the virtual screening of large chemical databases and for indexing natural products for potential anti-inflammatory activity.

  7. Walloons as General or Specific Others? A Comparison of anti-Walloon and anti-immigrant Attitudes in Flanders

    Directory of Open Access Journals (Sweden)

    Bart Meuleman

    2017-11-01

    Full Text Available This study attempts to shed light on the structure, the prevalence and the determinants of anti-Walloon attitudes in Flanders. For this purpose, we contrast anti-Walloon prejudice with prejudice against a relatively well-understood and archetypical out-group, namely immigrants. Our theoretical approach draws on insights from two paradigms of intergroup relations: the Group-Focused Enmity approach stressing that specific prejudices have a strong common denominator, and the Differentiated Threat model arguing that specific prejudices are contingent on the context of intergroup relations as well as the involved types of threat. To assess the (dissimilarities in anti-Walloon and anti-immigrant prejudice, we use the Flemish dataset of the Belgian National Election Study (BNES 2010. Comparable measurement instruments for both forms of prejudice are analyzed by means of structural equation modeling. Our results reveal a nuanced picture regarding the similarities and differences between anti-Walloon and anti-immigrant attitudes in Flanders. One the one hand, anti-Walloon and anti-immigration attitudes are strongly correlated and rooted in economic threat perceptions. On the other hand, anti-Walloon attitudes are less outspoken in the Flemish population than anti-immigrant attitudes, are less founded on cultural threat perceptions and are more closely linked to feelings of identification with the Flemish in-group.

  8. 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.)

  9. Phase I/II 90Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) radioimmunotherapy dosimetry results in relapsed or refractory non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Wiseman, G.A.; Dunn, W.L.; White, C.A.; Berlfein, J.R.; Ding, E.; Grillo-Lopez, A.J.; Stabin, M.; Erwin, W.; Spies, S.; Dahlbom, M.; Silverman, D.H.S.; Raubitschek, A.; Karvelis, K.; Schultheiss, T.; Witzig, T.E.; Belanger, R.

    2000-01-01

    Dosimetry studies in patients with non-Hodgkin's lymphoma were performed to estimate the radiation absorbed dose to normal organs and bone marrow from 90 Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) treatment in this phase I/II, multicenter trial. The trial was designed to determine the dose of Rituximab (chimeric anti-CD20, Rituxan, IDEC-C2B8, MabThera), the unlabeled antibody given prior to the radioconjugate to clear peripheral blood B cells and optimize distribution, and to determine the maximum tolerated dose of 90 Y-Zevalin [7.4, 11, or 15 MBq/kg (0.2, 0.3, or 0.4 mCi/kg)]. Patients received 111 In-Zevalin (indium-111 ibritumomab tiuxetan, IDEC-In2B8) on day 0 followed by a therapeutic dose of 90 Y-Zevalin on day 7. Both doses were preceded by an infusion of the chimeric, unlabeled antibody Rituximab. Following administration of 111 In-Zevalin, serial anterior/posterior whole-body scans were acquired. Major-organ radioactivity versus time estimates were calculated using regions of interest. Residence times were computed and entered into the MIRDOSE3 computer software program to calculate estimated radiation absorbed dose to each organ. Initial analyses of estimated radiation absorbed dose were completed at the clinical site. An additional, centralized dosimetry analysis was performed subsequently to provide a consistent analysis of data collected from the seven clinical sites. In all patients with dosimetry data (n=56), normal organ and red marrow radiation absorbed doses were estimated to be well under the protocol-defined upper limit of 20 Gy and 3 Gy, respectively. Median estimated radiation absorbed dose was 3.4 Gy to liver (range 1.2-7.8 Gy), 2.6 Gy to lungs (range 0.72-4.4 Gy), and 0.38 Gy to kidneys (range 0.07-0.61 Gy). Median estimated tumor radiation absorbed dose was 17 Gy (range 5.8-67 Gy). No correlation was noted between hematologic toxicity and the following variables: red marrow radiation absorbed dose, blood T 1/2 , blood AUC

  10. LEMBAGA PENDIDIKAN ISLAM SEBAGAI WAHANA IMPLEMENTASI PENDIDIKAN ANTI KORUPSI

    Directory of Open Access Journals (Sweden)

    Much. Arif Saiful Anam

    2015-11-01

    Full Text Available It has widely spread among either central or local government officials. Hence, it is crucial to build the awareness of all parties to combat, eliminate, and fight any kinds of corruption The spirit of anti-corruption that should be studied are building a mindset, an attitude, and anti-corruption behavior through school where a civilizing prosess occurs. Thus, formal education sector in Indonesia can play a role in meeting the needs of the prevention of corruption. There are two indirect preventive approaches. Firstly, set the learners as a target, and secondly empower learners to influence the society against corruption. Implementation of anti-corruption education in Madrasah should be able to create a conducive situation to reach a free of corruption environment and build generations of anti corruption. It can break the corruption chain. The main strategy of anti-corruption education in Indonesia can be run through implenting anti-corruption action in Madrasah.

  11. ASACUSA: the first beam of anti-hydrogen atoms

    International Nuclear Information System (INIS)

    2014-01-01

    The ASACUSA experiment at CERN has produced for the first time a beam of anti-hydrogen atoms, 80 atoms of anti-hydrogen have been detected at a distance of 2.7 meters away from their production place which is the true achievement of this experiment. The ASACUSA team has developed an innovative device that allows the transfer of the anti-hydrogen atoms in a place where they can be studied in flight, away from the intense magnetic field that was necessary to produce them but affect their spectroscopic properties. Anti-hydrogen atoms are made up of anti-electrons and anti-protons, according to the theory their spectrum must be identical to that of hydrogen atoms and any difference that might be detected by the ASACUSA experiment may shed light on the matter-antimatter asymmetry issue. (A.C.)

  12. [A spectrum of neurological diseases with anti-VGKC antibody].

    Science.gov (United States)

    Arimura, Kimiyoshi; Watanabe, Osamu; Nagado, Tatsui

    2007-11-01

    Anti-VGKC antibody causing peripheral nerve hyperexcitability is already an established clinical entity. Recently, many patients with non-herpetic limbic encephalitis (NHLE) with anti-VGKC antibody have been reported. The characteristic clinical features are low serum Na+ concentration and good response to immunotherapy. Anti-VGK antibody positive NHLE is relatively frequent among immune-mediated NHLE. It is important to know that this disease is responsive to immunotherapy. Furthermore, anti-VGKC antibody is also positive in some intractable epilepsies. These findings suggest that anti-VGKC is correlated with hyperexcitability in both the peripheral and central nervous system and that the spectrum of anti-VGKC antibody syndrome is now expanding.

  13. The automotive anti-collision system based on Ultrasonic

    Directory of Open Access Journals (Sweden)

    Qi Qinqin

    2017-08-01

    Full Text Available In the existing system of automobile anti-collision,the radar is mainly used for ranging.However,it can't be widely used because of its high cost.In this paper,based on the existing system of automobile anti-collision,the ultrasonic sensor is used to measure the distance and establish relevant anti-collision model.The experimental results show that the alarming information is accurate within a certain range.

  14. 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 to...

  15. EU Anti-Circumvention Rules: Do They Beat the Alternative?

    OpenAIRE

    Edwin Vermulst

    2015-01-01

    This article discusses EU law and practice with regard to tackling circumvention of trade defence instruments, notably anti-dumping measures. The author considers that, while strong legal arguments can be made that anti-circumvention rules are WTO-illegal, as a practical matter transparent and predictable anti-circumvention rules are to be preferred over vague and multi-interpretable non-preferential origin rules that vary from country to country. Furthermore, the many findings of transhipmen...

  16. What are the anti-particles of KL,S

    International Nuclear Information System (INIS)

    Mathur, V.S.; Rajeev, S.G.

    1991-01-01

    The authors study the consequences of an anti-unitary symmetry such as CPT for an unstable quantum system described by a non-self-adjoint Hamiltonian. In this paper it is shown that CPT invariance by itself does not imply that every particle has an anti-particle of equal mass and life-time. In particular, the neutral kaons K L and K S do not have anti-particles even when CPT is conserved

  17. Anti-Money Laundering Requirements – Perceived Effectiveness

    OpenAIRE

    C. C. Huang; M. S. Amirrudin; N. A. Ahamad Noruddin; R. Othman

    2013-01-01

    Anti-money laundering is commonly recognized as a set of procedures, laws or regulations designed to reduce the practice of generating income through illegal actions. In Malaysia, the government and law enforcement agencies have stepped up their capacities and efforts to curb money laundering since 2001. One of these measures was the enactment of the Anti-Money Laundering Act (AMLA) in 2001. The implementation costs on anti-money laundering requirements (AMLR) can be burd...

  18. Medicinal herbs as possible sources of anti-inflammatory products

    Directory of Open Access Journals (Sweden)

    Andreia Corciovă

    2017-12-01

    Full Text Available Plants constitute an inexhaustible source of bioactive compounds that can be valuable for research in the chemistry field of anti-inflammatory compounds. This review describes several plants from international and national flora that have been shown to have anti-inflammatory activity in various clinical trials. The paper includes: general aspects regarding the vegetal source, compounds responsible for anti-inflammatory activity, mechanism of action and clinical trials carried out with extracts or products containing standardized extracts.

  19. Test Production of Anti-Corrosive Paint in Laboratory Scale

    International Nuclear Information System (INIS)

    Thein Thein Win, Daw; Khin Aye Tint, Daw; Wai Min Than, Daw

    2003-02-01

    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

  20. Mediale Zukunft : die Erreichbarkeit des (Anti-)Utopischen

    OpenAIRE

    Orth, Dominik

    2009-01-01

    Während die Erforschung der politischen und literarischen Utopien und Anti-Utopien im wissenschaftlichen Diskurs nach wie vor eine große Rolle spielt, wurde die Analyse von utopischen und anti-utopischen Aspekten im Medium Film bislang vernachlässigt. Eine mögliche Ursache könnte sein, dass die Existenz von genuinen filmischen (Anti-)Utopien bezweifelt werden kann. Seit der Verlagerung der literarischen (Anti-)Utopien vom Raum in die Zeit ist die Darstellung von Gesellschaftsmodellen zumeist ...

  1. Optimization and anti-optimization of structures under uncertainty

    National Research Council Canada - National Science Library

    Elishakoff, Isaac; Ohsaki, Makoto

    2010-01-01

    The volume presents a collaboration between internationally recognized experts on anti-optimization and structural optimization, and summarizes various novel ideas, methodologies and results studied over 20 years...

  2. Design of vehicle intelligent anti-collision warning system

    Science.gov (United States)

    Xu, Yangyang; Wang, Ying

    2018-05-01

    This paper mainly designs a low cost, high-accuracy, micro-miniaturization, and digital display and acousto-optic alarm features of the vehicle intelligent anti-collision warning system that based on MCU AT89C51. The vehicle intelligent anti-collision warning system includes forward anti-collision warning system, auto parking systems and reversing anti-collision radar system. It mainly develops on the basis of ultrasonic distance measurement, its performance is reliable, thus the driving safety is greatly improved and the parking security and efficiency enhance enormously.

  3. Terrorism, Anti-Terrorism, and the Copycat Effect

    DEFF Research Database (Denmark)

    Jensen, Thomas

    that 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...

  4. Weight Gain and Hair Loss during Anti-TNF Therapy

    Directory of Open Access Journals (Sweden)

    Abdo Lutf

    2012-01-01

    Full Text Available Objectives. To investigate the incidence of weight gain and hair loss as adverse effects of anti-TNF therapy in rheumatic diseases. Methods. Patients using anti-TNF therapy, who are followed in rheumatology clinic, were interviewed using a questionnaire to investigate the side effects of anti-TNF therapy. Patients who complained of hair loss and weight gain were asked additional questions concerning the relationship of these adverse effects to anti-TNF use, whether therapy was stopped because of these adverse effects and if the adverse effects reversed after stopping therapy. The files were reviewed to follow the weight change before, during, and after discontinuation of anti-TNF. Results. One hundred fifty consecutive patients (82 RA, 34 ankylosing spondylitis, 32 psoriatic arthritis, and 4 for other indications were interviewed .Weight gain was observed in 20 patients (13.3% with average gain of 5.5 Kg. Anti-TNF was stopped in five patients because of this adverse effect. Hair loss during anti-TNf therapy was reported in five females (3.3% and anti-TNF therapy was stopped in all of them. Conclusion. Weight gain and hair loss appear to be associated with anti-TNF therapy and may be one reason for discontinuing the therapy.

  5. Anti-Kählerian Geometry on Lie Groups

    Science.gov (United States)

    Fernández-Culma, Edison Alberto; Godoy, Yamile

    2018-03-01

    Let G be a Lie group of even dimension and let ( g, J) be a left invariant anti-Kähler structure on G. In this article we study anti-Kähler structures considering the distinguished cases where the complex structure J is abelian or bi-invariant. We find that if G admits a left invariant anti-Kähler structure ( g, J) where J is abelian then the Lie algebra of G is unimodular and ( G, g) is a flat pseudo-Riemannian manifold. For the second case, we see that for any left invariant metric g for which J is an anti-isometry we obtain that the triple ( G, g, J) is an anti-Kähler manifold. Besides, given a left invariant anti-Hermitian structure on G we associate a covariant 3-tensor 𝜃 on its Lie algebra and prove that such structure is anti-Kähler if and only if 𝜃 is a skew-symmetric and pure tensor. From this tensor we classify the real 4-dimensional Lie algebras for which the corresponding Lie group has a left invariant anti-Kähler structure and study the moduli spaces of such structures (up to group isomorphisms that preserve the anti-Kähler structures).

  6. Anti-Aliasing filter for reverse-time migration

    KAUST Repository

    Zhan, Ge

    2012-01-01

    We develop an anti-aliasing filter for reverse-time migration (RTM). It is similar to the traditional anti-aliasing filter used for Kirchhoff migration in that it low-pass filters the migration operator so that the dominant wavelength in the operator is greater than two times the trace sampling interval, except it is applied to both primary and multiple reflection events. Instead of applying this filter to the data in the traditional RTM operation, we apply the anti-aliasing filter to the generalized diffraction-stack migration operator. This gives the same migration image as computed by anti-aliased RTM. Download

  7. Anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis patients

    International Nuclear Information System (INIS)

    Fakhr, A.; Ahmed, M.; Bashir, M.; Hakim, F.; Basri, R.

    2017-01-01

    Objective: To detect the anti cyclic citrullinated peptide (Anti-CCP) antibody in rheumatoid arthritis (RA) patients to determine its diagnostic value in Pakistani patients. Study Design: Cross sectional study. Place and Duration of Study: Military Hospital (MH) Rawalpindi, from January 2013 to June 2015. Material and Methods: A total of 58 patients with complications of rheumatoid arthritis were recruited in the study using convenient sampling technique after their informed consent. Age and gender of the patients were recorded. Blood was collected from the patients subjected to ELISA based detection of anti-CCP and latex agglutination test for detection of Rheumatoid Factor (RF). Data obtained were analyzed using Microsoft excel 2010. Results: Among the fifty eight RA patients, 40 percent were males and 60 percent were females. Age ranged between 12 to 80 years (mean age 49.74 +- 16.81 years) of the males RA patients and was higher as compared to females (mean age 43.2 +-16.70 years). ELISA based detection of anti-CCP antibody showed that about 91 percent of RA patients were positive for anti CCP antibody. About 72 percent were positive for anti CCP antibody alone, 19 percent were positive for both anti-CCP and RF and 9 percent were positive for RF. Conclusion: The results concluded that a higher percentage of the RA patients are positive for anti-CCP antibody marking its importance as a diagnostic marker. Anti-CCP has more sensitivity as compared to RF in RA patients. (author)

  8. Anti-vibration bars for nuclear steam generators

    International Nuclear Information System (INIS)

    Gowda, B.V.; Wilson, R.M.; Wepfer, R.M.

    1986-01-01

    A method of installing tubular anti-vibration bars into a tube bundle of a steam generator wherein the tube bundle comprises rows of tubes, with the anti-vibration bars received between adjacent rows of the tube bundle for stabilizing the tubes against vibration. The anti-vibration bars are first inserted between adjacent rows of the tube bundle and a pressurized fluid is then introduced into the anti-vibration bars which are thus expanded into contact with the tubes of the adjacent rows for support

  9. Anti-Saccharomyces cerevisiae and perinuclear anti-neutrophil cytoplasmic antibodies in coeliac disease before and after gluten-free diet.

    Science.gov (United States)

    Granito, A; Zauli, D; Muratori, P; Muratori, L; Grassi, A; Bortolotti, R; Petrolini, N; Veronesi, L; Gionchetti, P; Bianchi, F B; Volta, U

    2005-04-01

    Anti-Saccharomyces cerevisiae and perinuclear anti-neutrophil cytoplasmic autoantibodies are markers of Crohn's disease and ulcerative colitis respectively. To determine the prevalence of anti-S. cerevisiae and perinuclear anti-neutrophil cytoplasmic autoantibodies in a large series of coeliac disease patients before and after gluten free diet, and to correlate anti-S. cerevisiae-positivity with intestinal mucosal damage. One hundred and five consecutive coeliac disease patients and 141 controls (22 ulcerative colitis, 24 Crohn's disease, 30 primary sclerosing cholangitis, 15 postenteritis syndrome, 50 blood donors) were tested for anti-S. cerevisiae by enzyme-linked immunosorbent assay and for perinuclear anti-neutrophil cytoplasmic autoantibodies by indirect immunofluorescence. In coeliac disease anti-S. cerevisiae (immunoglobulin G and/or immunoglobulin A) were slightly less frequent (59%) than in Crohn's disease (75%, P = 0.16) and significantly more frequent than in ulcerative colitis (27%), primary sclerosing cholangitis (30%), postenteritis syndrome (26%) and blood donors (4%) (P = 0.009, P = 0.0002, P = 0.025, P < 0.0001). No correlation was found between anti-S. cerevisiae and degree of mucosal damage. Perinuclear anti-neutrophil cytoplasmic autoantibodies were detected only in one coeliac. After gluten free diet the disappearance of anti-S. cerevisiae-immunoglobulin A (93%) was more frequent than that of immunoglobulin G (17%, P = 0.0001); perinuclear anti-neutrophil cytoplasmic autoantibodies disappeared in the only coeliac positive at diagnosis. More than half of untreated coeliacs are anti-S. cerevisiae-positive irrespective of the severity of mucosal damage. Differently from immunoglobulin A, anti-S. cerevisiae-immunoglobulin G persisted in more than 80% after gluten free diet. The high prevalence of anti-S. cerevisiae in coeliac disease suggests that they may be the effect of a non-specific immune response in course of chronic small bowel disease.

  10. Rituximab for the treatment of refractory simultaneous anti-glomerular basement membrane (anti-GBM) and membranous nephropathy.

    Science.gov (United States)

    Bandak, Ghassan; Jones, Bruce A; Li, Jian; Yee, Jerry; Umanath, Kausik

    2014-02-01

    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 disease, yet responded to an alternative treatment of rituximab. This B-cell directed, monoclonal, chimeric antibody treatment substantially reduced anti-GBM antibody titers and led to discontinuation of plasmapheresis, while maintaining the remission of membranous nephropathy and anti-GBM disease.

  11. anti p and anti d production in relativistic heavy ion collisions: Results of BNL-E858

    Energy Technology Data Exchange (ETDEWEB)

    Stankus, P; Nagamiya, S [Columbia Univ., Nevis Labs., Irvington, NY (United States); Aoki, M; Hayano, R S; Shimizu, Y [Tokyo Univ. (Japan); Beatty, J [Boston Univ., MA (United States); Beavis, D; Debbe, R [Brookhaven National Lab., Upton, NY (United States); Carroll, J B [California Univ., Los Angeles, CA (United States); Chiba, J; Tanaka, K H [National Lab. for High Energy Physics (KEK), Tsukuba (Japan); Doke, T; Kashiwagi, T; Kikuchi, J [Waseda Univ., Tokyo (Japan); Hallman, T J [Johns Hopkins Univ., Baltimore, MD (United States); Heckman, H H; Lindstrom, P J [Lawrence Berkeley Lab., CA (United States); Kirk, P N; Wang, Z F [Louisiana State Univ., Baton Rouge, LA (United States); Crawford, H J; Engelage, J; Greiner, L [Space Sciences Lab., California Univ., Berkeley, CA (United States); E858 Collaboration

    1992-07-20

    The production of long-lived negative secondaries, including [pi][sup -], K[sup -], antiprotons (anti p) and antideuterons (anti d) at 0deg in Si+Au, Si+Cu, and Si+Al collisions at the BNL-AGS has been measured using a double-bend, double-focussing spectrometer. The anti p rapidity spectra from all three targets are well fit by Gaussians centered (anti y = 1.7 - 1.8) at mid-rapidity, and are consistent with production in nucleon-nucleon first collisions. The anti d/anti p[sup 2] ratio in Si+Al collisions is lower by a factor of 10 than that seen in p+p and p+A collisions. (orig.).

  12. ETHICS in GOVERNMENT: ANTI-CORRUPTION MEASURES

    Directory of Open Access Journals (Sweden)

    Coskun Can Aktan

    2015-07-01

    Full Text Available Unethicalbehavior in government is viewed as a situation where there isfraudulent or dishonest conduct or improper behaviour by people who are in aposition or power. Bribery, extortion, embezzlement,the use of legislated powersby government officials for illegitimate private gain, nepotism, rent seeking etc.are some examples forunethical behavior in government.How to deal with unethical behavior in government?. How to curb corruption?Experience demonstrates that establishing an ethical government is not an easytask. There is no single approach to curb (political corruption effectively. Instead,controlling (political corruption requires a wide range of strategies.Thisdescriptive survey aims to explore the anti-corruptions measures in general.

  13. Anti-adhesive properties of fish tropomyosins

    DEFF Research Database (Denmark)

    Vejborg, Rebecca Munk; Bernbom, Nete; Gram, Lone

    2008-01-01

    Aims: We have recently found that preconditioning of stainless steel surfaces with an aqueous fish muscle extract can significantly impede bacterial adhesion. The purpose of this study was to identify and characterize the primary components associated with this bacteria-repelling effect. Methods...... to the formation of a proteinaceous conditioning film composed primarily of fish tropomyosins. These fibrous proteins formed a considerable anti-adhesive conditioning layer on and reduced bacterial adhesion to several different materials including polystyrene, vinyl plastic, stainless steel and glass. The protein...... the importance of substratum's physiochemical properties and exposure time with regards to protein adsorption/elution efficiency and subsequent bacterial adhesion. Significance and Impact of the Study: Fish tropomyosin-coatings could potentially offer a nontoxic and relatively inexpensive measure of reducing...

  14. The Anti-Ballistic Missile Treaty

    International Nuclear Information System (INIS)

    Platt, A.

    1991-01-01

    This paper reports that in late May 1972 former President Richard M. Nixon went to Moscow and signed, among other documents, a Treaty to Limit Anti-Ballistic Missile (ABM) Systems. Under this agreement, both the United States and the Soviet Union made a commitment not to build nationwide ABM defenses against the other's intercontinental and submarine-launched ballistic missiles. They agreed to limit ABM deployments to a maximum of two sites, with no more than 100 launchers per site. Thirteen of the treaty's sixteen articles are intended to prevent any deviation from this. In addition, a joint Standing Consultative Commission to monitor compliance was created. National technical means --- sophisticated monitoring devices on land, sea, and in space --- were to be the primary instruments used to monitor compliance with the treaty. The ABM Treaty was signed in conjunction with an Interim Agreement to Limit Strategic Offensive Arms

  15. Review of Anti-Inflammatory Herbal Medicines

    Directory of Open Access Journals (Sweden)

    Mona Ghasemian

    2016-01-01

    Full Text Available Medicinal plants and their secondary metabolites are progressively used in the treatment of diseases as a complementary medicine. Inflammation is a pathologic condition that includes a wide range of diseases such as rheumatic and immune-mediated conditions, diabetes, cardiovascular accident, and etcetera. We introduce some herbs which their anti-inflammatory effects have been evaluated in clinical and experimental studies. Curcuma longa, Zingiber officinale, Rosmarinus officinalis, Borago officinalis, evening primrose, and Devil’s claw are some of the introduced medicinal herbs in this review. Since the treatment of inflammation is not a one-dimensional remedy, this review tries to reach a multidimensional therapeutic approach to inflammation with the help of herbal medicine and modification in lifestyle.

  16. The Business of Anti-Aging Science.

    Science.gov (United States)

    de Magalhães, João Pedro; Stevens, Michael; Thornton, Daniel

    2017-11-01

    Age-related conditions are the leading causes of death and health-care costs. Reducing the rate of aging would have enormous medical and financial benefits. Myriad genes and pathways are known to regulate aging in model organisms, fostering a new crop of anti-aging companies. Approaches range from drug discovery efforts to big-data methods and direct-to-consumer (DTC) strategies. Challenges and pitfalls of commercialization include reliance on findings from short-lived model organisms, poor biological understanding of aging, and hurdles in performing clinical trials for aging. A large number of potential aging-associated interventions and targets exist, but given the long validation times only a small fraction can be explored for clinical applications. If even one company succeeds, however, the impact will be huge. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Preparing Teachers for Anti-oppressive Education

    DEFF Research Database (Denmark)

    Baber, Sikunder Ali

    2004-01-01

    While theories and recommendations continue to proliferate in the educational research literature on what it means to teach towards social justice and to prepare teachers for such teaching, so do concerns that these theories and recommendations fail to account for the ways that the contexts...... of teaching cultural contexts, national contexts, political contexts always affect teaching in idiosyncratic, unpredictable and even contradictory ways. Given that much educational research fails to trouble the US-centric nature of prevailing conceptions of social justice and teacher education......, it is 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...

  18. ANEMIA DAN LAMA KONSUMSI OBAT ANTI TUBERCULOSIS

    Directory of Open Access Journals (Sweden)

    Anny Thuraidah

    2017-12-01

    Full Text Available Tuberkulosis adalah penyakit infeksi akibat kuman Mycobacterium tuberculosis yang dapat menginfeksi beberapa organ tubuh, diantaranya paru-paru, ginjal, dan tulang.Tujuan pengobatan tuberkulosis adalah memusnahkan basil tuberkulosis dengan cepat dan mencegah kekambuhan. Obat anti tuberkulosis (OAT dapat diterima dalam terapi, namun mempunyai efek toksik seperti agranulositosis, eosinofilia, trombositopenia dan anemia. Penelitian ini bertujuan untuk mengetahui hubungan lama konsumsi OAT pada pasien TB paru terhadap anemia. Penelitian ini bersifat Survey Analitic dengan rancangan Cross Sectional. Hasil penelitian rata-rata hitung sel darah merah 0 bulan 5,16 106/uL, 2 bulan 4,39 106/uL dan 6 bulan 4,61 106/uL, rata-rata kadar hemoglobin 0 bulan 15,17 g/dL, 2 bulan 12,73 g/dL dan 6 bulan 13,28 g/dL serta ratarata nilai hematokrit 0 bulan 44,26 %, 2 bulan 38,24 % dan 6 bulan 39,04 %. Dari hasil uji Spearman diperoleh nilai signifikan sebesar hitung sel darah merah 0,004 < α (0,05, kadar hemoglobin 0,007 < α (0,05 dan nilai hematokrit 0,015 < α (0,05 sehingga dapat disimpulkan ada hubungan antara lama konsumsi obat anti tuberkulosis pada pasien TB paru terhadap anemia dan nilai correlation coefficient hitung sel darah merah -0,531, kadar hemoglobin -0,479 serta nilai hematokrit -0,440 berarti memiliki kekuatan hubungan yang sedang. Disarankan untuk penelitian selanjutnya menggunakan parameter yang berbeda seperti jumlah trombosit, kadar AST/ALT dan sebaiknya menggunakan sampel atau pasien yang sama dari 0 bulan sampai 6 bulan.

  19. ANTI-CORRUPTION MEASURES FOR CORPORATE SECURITY

    Directory of Open Access Journals (Sweden)

    Natasha Georgieva Hadji Krsteski

    2017-04-01

    Full Text Available Corporate security should commit to ethical management and raising the quality of companies and markets through improving cooperation and transparency by applying anticorruption measures such as accepting a code of ethics; respect and follow international business principles for dealing with bribery; improve their transparency - via access to information; involvement in politics to protect persons who disclose corruption cases; and improving corporate governance - through active mutual discussions on adjustment of legal regulations. Research methods used in the paper are: qualitative analysis of secondary data obtained from relevant institutions. Results obtained from the survey include fighting corruption in corporations must find a unique solution that is long-term strategy developed transparent society crucial criteria and principles to meet the political criteria by the fulfillment of anti-corruption standards; it requires continuous cooperation of public and private sector, NGOs and the general corpus of all stakeholders in the country against corruption; the lack of a legal framework or platform for establishing public and private partnerships, is an important factor for anti-corruption measures to improve corporate governance; mechanisms for cooperation does not seem sufficiently developed between the public, private, political and civil society; the most important factor to tackle corruption is to adopt a law on public prosecutors and determination of higher norms and standards. Conclusions drawn from the survey: in the area of pre-trial procedure requires shifting responsibilities of Interior Ministry body training in the area of the judicial system; it is necessary to change the Criminal Code and Criminal Procedure Code by changing certain legal provisions which refer to the Agency for money laundering SCCP, a financial police and overall legislation.

  20. Anti-Halal and Anti-Animal Slaughtering Campaigns and Their Impact in Post-War Sri Lanka

    Directory of Open Access Journals (Sweden)

    Mohammad Agus Yusoff

    2017-03-01

    Full Text Available This paper aims to examine the overall impact of anti-halal and anti-slaughtering campaigns in the context of post-war Sri Lanka. The reemergence of majoritarian ethno-religious anti-minority nationalist forces and their intensified anti-minority hatred and violence have made it challenging for ethno-religious minorities in Sri Lanka to engage in religious norms and duties. This is especially true for the Muslim community. Numerous Islamic fundamentals have been criticized and opposed. Muslims have had to endure threats and acts of violence. These campaigns and violent oppositions, imposed by the Buddhist-nationalist forces, have caused concern for Muslims performing their obligatory religious duties and norms. In Sri Lanka, the Muslim community has been allowed to produce halal food and slaughter animals for human consumption and religious rituals for a long period without disturbance. Unfortunately, retaliation and hatred in the post-civil war era in the country have threatened these rights. Thus, it has become imperative to investigate the motivating factors of the anti-halal and anti-animal slaughtering campaigns and violence, as well as their related impact, which is lacking in the existing literature on ethno-religious politics in the context of Sri Lanka. This study found that the anti-halal and anti-animal slaughtering campaigns and oppositions that have been intensified by the Buddhist nationalist forces were part of anti-Muslim sentiments intended to sabotage the economic pride of Muslims and undermine their religious renaissance. The study also found that these campaigns have been facilitated by the state and that continuous facilitation of the anti-Muslim sentiments and campaigns, including the anti-halal and anti-animal slaughter campaigns, would challenge the country’s economic prosperity and the rebuilding of ethno-religious harmony.

  1. Analysis of "anti-crisis strategy" definition essence and its role in enterprise anti-crisis management

    Directory of Open Access Journals (Sweden)

    Тетяна Олександрівна Ставерська

    2016-12-01

    Full Text Available The analysis of existing research of the category essence of "anti-crisis strategy" is given, the main essential features are revealed. These features are best matching its content. Existing approaches to determine the definition of "anti-crisis strategy" are systematized and summarized. Based on the allocation of essential features of anti-crisis strategy, the author’s generalized definition of this category is formulated considering the trajectory of the turbulent processes in environment

  2. Expression of BAFF receptors in muscle tissue of myositis patients with anti-Jo-1 or anti-Ro52/anti-Ro60 autoantibodies.

    Science.gov (United States)

    Kryštůfková, Olga; Barbasso Helmers, Sevim; Venalis, Paulius; Malmström, Vivianne; Lindroos, Eva; Vencovský, Jiří; Lundberg, Ingrid E

    2014-10-10

    Anti-Jo-1 and anti-Ro52 autoantibodies are common in patients with myositis, but the mechanisms behind their production are not known. Survival of autoantibody-producing cells is dependent on B-cell-activating factor of the tumour necrosis factor family (BAFF). BAFF levels are elevated in serum of anti-Jo-1-positive myositis patients and are influenced by type-I interferon (IFN). IFN-producing cells and BAFF mRNA expression are present in myositis muscle. We investigated expression of the receptors for BAFF in muscle tissue in relation to anti-Jo-1 and anti-Ro52/anti-Ro60 autoantibodies and type-I IFN markers. Muscle biopsies from 23 patients with myositis selected based on autoantibody profile and 7 healthy controls were investigated for expression of BAFF receptor (BAFF-R), B-cell maturation antigen (BCMA) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). Nineteen samples were assessed for plasma (CD138) and B-cell (CD19) markers. The numbers of positive cells per area were compared with the expression of plasmacytoid dendritic cell (pDC) marker blood dendritic cell antigen-2 (BDCA-2) and IFNα/β-inducible myxovirus resistance-1 protein (MX-1). BAFF-R, BCMA and TACI were expressed in five, seven and seven patients, respectively, and more frequently in anti-Jo-1-positive and/or anti-Ro52/anti-Ro60-positive patients compared to controls and to patients without these autoantibodies (P = BAFF-R: 0.007, BCMA: 0.03 and TACI: 0.07). A local association of receptors with B and plasma cells was confirmed by confocal microscopy. The numbers of CD138-positive and BCMA-positive cells were correlated (r = 0.79; P = 0.001). Expression of BDCA-2 correlated with numbers of CD138-positive cells and marginally with BCMA-positive cells (r = 0.54 and 0.42, respectively; P = 0.04 and 0.06, respectively). There was a borderline correlation between the numbers of positively stained TACI cells and MX-1 areas (r = 0.38, P = 0.08). The expression

  3. Comparison of q anti qg and q anti qγ events in e+e- annihilation at PEP

    International Nuclear Information System (INIS)

    Hofmann, W.

    1986-07-01

    In comparing the particle flow in the event plane of three-jet (q anti qg) events and of radiative annihilation events (q anti qγ) for similar kinematic configurations, two PEP experiments find a significant decrease in particle density in the angular region opposite to the gluon jet in q anti qg events, relative to the particle density in the region opposite to the photon in q anti qγ events. The effect is predicted both by QCD and by phenomenological string models. 5 refs., 5 figs

  4. Enzyme-linked immunosorbent assay for total sennosides using anti-sennside A and anti-sennoside B monoclonal antibodies.

    Science.gov (United States)

    Morinaga, Osamu; Uto, Takuhiro; Sakamoto, Seiichi; Tanaka, Hiroyuki; Shoyama, Yukihiro

    2009-01-01

    Total sennosides concentration is a very important factor when rhubarb and senna will be used as crude drugs. However, one-step analytical technique for total sennosides has not been reported except HPLC. An enzyme-linked immunosorbent assay (ELISA) for total sennosides concentration by using the combination of anti-sennoside A (SA) and anti-sennoside B (SB) monoclonal antibodies (MAbs) in a single assay has been investigated. Total sennosides concentration in rhubarb and senna samples determined by newly developed assay system showed good agreement with those analyzed by ELISA using anti-SA MAb and anti-SB MAb, respectively.

  5. Polarized antiquark flavor asymmetry DELTA anti u(x)-DELTA anti d(x) and the pion cloud

    CERN Document Server

    Fries, R J; Weiss, C

    2003-01-01

    The flavor asymmetry of the unpolarized antiquark distributions in the proton, anti u(x)- anti d(x)0. Using a simple chiral linear sigma model as an example, we demonstrate that in the meson cloud picture a large positive DELTA anti u(x)-DELTA anti d(x) can be obtained from pi-sigma interference contributions. This calls into question previous estimates based on rho-meson contributions alone, and indicates how the results of the meson cloud picture may be reconciled with those of quark-based models. (orig.)

  6. Glutamic acid decarboxylase (anti-GAD & tissue transglutaminase (anti-TTG antibodies in patients with thyroid autoimmunity

    Directory of Open Access Journals (Sweden)

    R K Marwaha

    2013-01-01

    Full Text Available Background & objectives: Several autoimmune disorders have been reported to be associated with autoimmune thyroiditis and may coexist with other organ-specific autoantibodies. The aim of the present study was to evaluate the presence of tissue transglutaminase (anti-TTG and glutamic acid decarboxylase (anti-GAD antibodies in patients suffering from autoimmune thyroiditis as diagnosed by anti-thyroid peroxidase (anti-TPO antibodies, which may indicate high risk for developing celiac disease or type 1 diabetes mellitus. Methods: Five thousand children and 2800 adults were screening as part of a general health examination done on a voluntary basis in four different parts of Delhi. A total of 577 subjects positive for anti-TPO antibody constituted the cases. Equal number of age and sex matched anti-TPO antibody negative controls were randomly selected from the same cohort to form paired case control study. The cases and controls were further divided into two groups as follows: group-1 (children and adolescent 18 yr. Serum samples of cases and controls were analysed for thyroid function test (FT3, FT4, and TSH, anti-TTG and anti-GAD antibodies. Results: A total of 1154 subjects (577 cases and 577 controls were included in this study. Hypothyroidism was present in 40.2 per cent (232 cases compared to only 4.7 per cent (27 in controls (P<0.001. Anti-TTG and anti-GAD antibodies were present in 6.9 and 12.5 per cent subjects among cases compared to 3.5 per cent (P=0.015 and 4.3 per cent (P=0.001 in controls, respectively. Only anti-GAD antibody were significantly positive in cases among children and adolescents (P =0.0044 and adult (P=0.001 compared to controls. Levels of anti-TTG and anti-GAD antibodies increased with increasing titre of anti-TPO antibody. Interpretation & conclusions: Our findings showed high positivity of anti-GAD and anti-TTG antibodies among subjects with thyroid autoimmunity. It is, therefore, important to have high clinical index

  7. Diagnosis and classification of Goodpasture's disease (anti-GBM).

    Science.gov (United States)

    Hellmark, Thomas; Segelmark, Mårten

    2014-01-01

    Goodpasture's 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 autoantibodies. The disease is a prototype of autoimmune disease, where the patients develop autoantibodies that bind to the basement membranes and activate the classical pathway of the complement system, which start a neutrophil dependent inflammation. The diagnosis of anti-GBM disease relies on the detection of anti-GBM antibodies in conjunction with glomerulonephritis and/or alveolitis. Overt clinical symptoms are most prominent in the glomeruli where the inflammation usually results in a severe rapidly progressive glomerulonephritis. Despite modern treatment less than one third of the patients survive with a preserved kidney function after 6 months follow-up. Frequencies vary from 0.5 to 1 cases per million inhabitants per year and there is a strong genetic linkage to HLA-DRB1(∗)1501 and DRB1(∗)1502. Essentially, anti-GBM disease is now a preferred term for what was earlier called Goodpasture's syndrome or Goodpasture's disease; anti-GBM disease is now classified as small vessel vasculitis caused by in situ immune complex formation; the diagnosis relies on the detection of anti-GBM in tissues or circulation in conjunction with alveolar or glomerular disease; therapy is effective only when detected at an early stage, making a high degree of awareness necessary to find these rare cases; 20-35% have anti-GBM and MPO-ANCA simultaneously, which necessitates testing for anti-GBM whenever acute test for ANCA is ordered in patients with renal disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Anti-NMDA receptor encephalitis and nonencephalitic HSV-1 infection.

    Science.gov (United States)

    Salovin, Amy; Glanzman, Jason; Roslin, Kylie; Armangue, Thais; Lynch, David R; Panzer, Jessica A

    2018-07-01

    To determine whether there is an association between nonencephalitic herpes simplex virus 1 (HSV-1) infection and anti-NMDA receptor encephalitis (anti-NMDARE). Antibody testing was performed using samples from 2 cohorts in a case-control observational study. The cohort "Philadelphia" included 16 serum samples of pediatric anti-NMDARE cases and 42 age-matched controls with other neuroinflammatory disorders studied at the Children's Hospital of Philadelphia and University of Pennsylvania. The cohort "Barcelona" contained 23 anti-NMDARE patient samples and 26 age-matched participants with other neuroinflammatory disorders studied at IDIBAPS-Hospital Clinic, University of Barcelona. The presence of HSV-1 IgG antibodies was examined by ELISA. As an additional control, IgG antibodies to cytomegalovirus (CMV) and Epstein-Barr virus viral capsid antigen (EBV-VCA) were determined. In each cohort, more participants with anti-NMDARE than controls had anti-HSV-1 IgG antibodies. In the Philadelphia cohort (58 participants), 44% of anti-NMDARE cases had antibodies to HSV-1 compared with 14% controls (OR 4.67, 95% CI 1.3-17.3, p = 0.031). In the Barcelona cohort (49 participants), 52% of participants with anti-NMDARE had antibodies to HSV-1 compared with 31% of controls (OR 2.45, 95% CI 0.7-7.9, p = 0.155). Overall, 49% of anti-NMDARE cases have antibodies to HSV-1 in these 2 combined cohorts compared with 21% of controls (Mantel-Haenszel OR 3.21, 95% CI 1.3-7.7, p = 0.007). Past HSV-1 infection was found in significantly more anti-NMDARE cases than controls. This suggests a meaningful association between nonencephalitic HSV-1 infection and development of anti-NMDARE.

  9. Mechanisms Underlying the Anti-Aging and Anti-Tumor Effects of Lithocholic Bile Acid

    Directory of Open Access Journals (Sweden)

    Anthony Arlia-Ciommo

    2014-09-01

    Full Text Available Bile acids are cholesterol-derived bioactive lipids that play essential roles in the maintenance of a heathy lifespan. These amphipathic molecules with detergent-like properties display numerous beneficial effects on various longevity- and healthspan-promoting processes in evolutionarily distant organisms. Recent studies revealed that lithocholic bile acid not only causes a considerable lifespan extension in yeast, but also exhibits a substantial cytotoxic effect in cultured cancer cells derived from different tissues and organisms. The molecular and cellular mechanisms underlying the robust anti-aging and anti-tumor effects of lithocholic acid have emerged. This review summarizes the current knowledge of these mechanisms, outlines the most important unanswered questions and suggests directions for future research.

  10. THE ART OF AN ANTI-ROMANTIC AND AN ANTI-MODERNIST: LARKIN ABOUT MODERN REALITY

    Directory of Open Access Journals (Sweden)

    Leman DEMİRBAŞ

    2017-06-01

    Full Text Available In the early 1950s a group of young English poets formed a literary circle called The Movement, as a correspondent to Angry Young Man in theatre. Philip Larkin is a perfect representative of the Movement and post-war generation. He interpreted modern reality from his own perspective with a realistic, simple, clear, colloquial style that discarded both Romanticism and Modernism. He was the follower of a clearly English line, with provincialism in theme, traditionalism in form, blunt representations of modern reality, refusal of idealization of the self or nature, and a kind of simplicity, and accessibility. Thus in this paper Larkin’s anti-romantic and anti-modernist style of poetry will be discussed with his involvement of the Movement, and analyzed through several of his poems.

  11. Curcumin: An age-old anti-inflammatory and anti-neoplastic agent

    Directory of Open Access Journals (Sweden)

    Matthew C. Fadus

    2017-07-01

    Full Text Available Curcumin is a natural anti-inflammatory agent that has been used for treating medical conditions for many years. Several experimental and pharmacologic trials have demonstrated its efficacy in the role as an anti-inflammatory agent. Curcumin has been shown to be effective in treating chronic conditions like rheumatoid arthritis, inflammatory bowel disease, Alzheimer's and common malignancies like colon, stomach, lung, breast, and skin cancers. As treatments in medicine become more and more complex, the answer may be something simpler. This is a review article written with the objective to systematically analyze the wealth of information regarding the medical use of curcumin, the “curry spice”, and to understand the existent gaps which have prevented its widespread application in the medical community.

  12. Terpaan Pesan Iklan Anti Kekerasan Radio PRAMBORS dan Interaksi Peer Group terhadap Sikap Anti Kekerasan Remaja

    Directory of Open Access Journals (Sweden)

    Ayang Fitrianti

    2017-07-01

    Full Text Available Characteristic teen expressive, always curious and receptive to new values in this era of globalization should be directed and escorted on positive things like Prambors Radio which serve Ad Links anti Violence. Therefore, this study aims to determine the extent of Exposure to Violence Ad Links Prambors Radio and Peer Group of the Attitudes of Teen Violence. The method used in this research is quantitative method, explanatory paradigm of positivistic. The theory used in this study is the Social Learning Theory by Bandura and the theory of Hierarchy Effect Model. This study uses survey respondents were 116 respondents who are listeners Prambors Radio. Based on this research, it can be concluded that the inundation Ad Links Anti Violence positively related to Attitude Teen Violence. In addition the results also showed that interaction with the Peer Group also showed a significant positive correlation to the attitude of Teen Violence.

  13. Detecting the anti-hypertriton and anti-helium-4 from the RHIC

    Directory of Open Access Journals (Sweden)

    Ma Yu-Gang

    2014-03-01

    Full Text Available Recent progress on the dectection of antimatter particles at RHIC is briefly reviewed. The observations of the anti-hypertriton (H¯⊼3${}_ \\mathbin{\\buildrel\\relbar \\over{\\smash{\\scriptstyle\\wedge}\\vphantom{_x}}} ^3\\overline {\\rm{H}} $and anti-helium-4 nuclei ( (4He¯, or α¯$\\left( {^4\\overline {{\\rm{He}}} ,\\,{\\rm{or}}\\,\\overline {\\rm{\\alpha }} } \\right$, or ᾱ from the RHIC-STAR Collaboration are highlighted. In addition, preliminary lifetime measurement of H¯Λ3${}_\\Lambda ^3\\overline {\\rm{H}} $ and energy dependence of strangeness population factor are presented. The mechanism of light antinuclei production is also discussed.

  14. Anti-wrinkle and anti-whitening effects of jucá (Libidibia ferrea Mart.) extracts.

    Science.gov (United States)

    Pedrosa, Tatiana do Nascimento; Barros, Aline Oliveira; Nogueira, Jéssica Rodrigues; Fruet, Andréa Costa; Rodrigues, Isis Costa; Calcagno, Danielle Queiroz; Smith, Marilia de Arruda Cardoso; de Souza, Tatiane Pereira; Barros, Silvia Berlanga de Moraes; de Vasconcellos, Marne Carvalho; Silva, Felipe Moura Araújo da; Koolen, Hector Henrique Ferreira; Maria-Engler, Silvya Stuchi; Lima, Emerson Silva

    2016-11-01

    Skin aging is a natural process of the human body that may be accelerated due to extrinsic causes. Libidibia ferrea, popularly known as jucá, is a small tree, which possesses an abundant phenolic composition with potential antioxidant and enzymatic inhibition activities. Thus, this work aimed to investigate the anti-wrinkle and anti-whitening potentials of jucá trunk bark (LFB) and pod (LFP) extracts. A comprehensive analysis of LFB and LFP phenolic composition was accomplished by means of liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Effects on skin degradation were assessed by inhibitory enzymatic activity against elastase, hyaluronidase and collagenase through colorimetric assays. Cellular viability in B16F10 and primary fibroblasts were determined by Trypan Blue exclusion assay. Anti-melanogenic effects on B16F10 cells were evaluated using cellular tyrosinase, melanin content, western blot, and RT-qPCR analyses. Inhibition of matrix metalloproteinase-2 and metalloproteinase-9 (MMP-2 and MMP-9) was determined by gelatin zymography and western blot methodologies. LC-MS/MS analyses of LFB and LFP extracts allowed the characterization of 18 compounds, among them, flavonoids, phenolic acids, and secoridoids. Additionally the pod and trunk bark compositions were compared. Hyaluronidase inhibitory activity for both extracts, LFB (IC 50  = 8.5 ± 0.8 µg/mL) and LFP (IC 50  = 16 ± 0.5 µg/mL), was stronger than standard rutin (IC 50  = 27.6 ± 0.06). Pro-MMP-2 was significantly inhibited by both extracts. LFB and LFP decreased the melanin content in B16F10 due to tyrosinase inhibitory activity. L. ferrea extracts has high potential as a cosmetic ingredient due to its anti-wrinkle and depigmentant effects.

  15. Methanol extract of Xanthium strumarium L. possesses anti-inflammatory and anti-nociceptive activities.

    Science.gov (United States)

    Kim, In-Tae; Park, Young-Mi; Won, Jong-Heon; Jung, Hyun-Ju; Park, Hee-Juhn; Choi, Jong-Won; Lee, Kyung-Tae

    2005-01-01

    As an attempt to identify bioactive natural products with anti-inflammatory activity, we evaluated the effects of the methanol extract of the semen of Xanthium strumarium L. (MEXS) on lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2) and tumor necrosis factor-alpha (TNF-alpha) production in RAW 264.7 cells. Our data indicate that MEXS is a potent inhibitor of NO, PGE2 and TNF-alpha production. Consistent with these findings, the expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and iNOS, COX-2 and TNF-alpha mRNA were down-regulated in a concentration-dependent manner. Furthermore, MEXS inhibited nuclear factor kappa B (NF-kappaB) DNA binding activity and the translocation of NF-kappaB to the nucleus by blocking the degradation of inhibitor of kappa B-alpha (IkappaB-alpha). We further evaluated the anti-inflammatory and anti-nociceptive activities of MEXS in vivo. MEXS (100, 200 mg/kg/d, p.o.) reduced acute paw edema induced by carrageenin in rats, and showed analgesic activities in an acetic acid-induced abdominal constriction test and a hot plate test in mice. Thus, our study suggests that the inhibitions of iNOS, COX-2 expression, and TNF-alpha release by the methanol extract of the semen of Xanthium strumarium L. are achieved by blocking NF-kappaB activation, and that this is also responsible for its anti-inflammatory effects.

  16. Anti-hyperglycemic and anti-hyperlipidaemic effect of Arjunarishta in high-fat fed animals

    Directory of Open Access Journals (Sweden)

    Sushant A. Shengule

    2018-01-01

    Full Text Available Background: Arjunarishta (AA, a formulation used as cardiotonic is a hydroalcoholic formulation of Terminalia arjuna (Roxb. Wight and Arn. (TA belonging to family Combretaceae. Objective: To evaluate the anti-hyperglycemic and anti-hyperlipidemic effect of Arjunarishta on high-fat diet fed animals. Materials and methods: High-fat diet fed (HFD Wistar rats were randomly divided into three groups and treated with phytochemically standardized Arjunarishta (1.8 ml/kg, and hydroalcoholic extract of T. arjuna (TAHA (250 mg/kg and rosuvastatin (10 mg/kg, for 3 months. Intraperitoneal glucose tolerance test, blood biochemistry, liver triglyceride and systolic blood pressure were performed in all the groups. Effect of these drugs on the expression of tumor necrosis factor-α (TNF-α and insulin receptor substrate-1 (IRS-1 and peroxisome proliferators activated receptor γ coactivator 1-α (PGC-1α were studied in liver tissue using Quantitative Real-time PCR. Results: HFD increased fasting blood glucose, liver triglyceride, systolic blood pressure and gene expression of TNF-α, IRS-1 and PGC-1α. Treatment of AA and TAHA significantly reduced fasting blood glucose, systolic blood pressure, total cholesterol and triglyceride levels. These treatments significantly decreased gene expression of TNF-α (2.4, 2.2 and 2.6 fold change; increased IRS-1 (2.8, 2.9 and 2.8 fold change and PGC-1α (2.9, 3.7 and 3.3 fold change as compared to untreated HFD. Conclusion: Anti-hyperglycemic, anti-hyperlipidemic effect of Arjunarishta may be mediated by decreased TNF-α and increased PGC-1α and IRS-1. Keywords: Rosuvastatin, Type 2 diabetes, Insulin sensitizer genes, Arjunarishta

  17. Anti-allergic and anti-microbial activities of some Thai crops

    Directory of Open Access Journals (Sweden)

    Supinya Tewtrakul

    2008-07-01

    Full Text Available Thirteen Thai crops including banana, okra, jackfruit, germinated rice, rambutan, durian, jampadah, huasa potato,tamarind, coconut, mango, fan palm fruit and dioscorea tuber were tested for anti-allergic effect using RBL-2H3 cells andanti-microbial activity. These 13 crops, some of which included different parts, e.g. skin, flesh, and seed, were extracted withfour solvents separately [(95% ethanol (EtOH, 50% EtOH, water (W and hot water (HW], respectively, to obtain 112extracts. Among these extracts, mango seed in 50% EtOH possessed the highest anti-allergic activity against antigen-inducedb-hexosaminidase release as a marker of degranulation in RBL-2H3 cells with an IC50 value of 7.5±0.8 mg/ml, followed bybanana (W, IC50 = 13.5±2.4 mg/ml, okra (W, IC50 = 13.6±3.1 mg/ml, jampadah skin (HW, IC50 = 13.8±3.9 mg/ml, tamarindseed coat (HW, IC50 = 14.2±3.1 mg/ml, jampadah flesh (W, IC50 = 14.6±3.1 mg/ml; whereas other crops possessed IC50values from 21.5->100 mg/ml. Moreover, the plants showing high anti-allergic effects were also possessed marked antibacterialactivity. Rambutan peel, mango peel, mango seed and tamarind seed coat exhibited appropriate anti-bacterialactivity against Staphylococcus aureus, Bacillus subtilis and Pseudomonas aeruginosa with MIC values ranging from 250-2,000 mg/ml, but did not show any effect towards Escherichia coli and Candida albicans. This study indicates that these Thaicrops may have potential as functional foods and neutraceuticals for treatment of allergy, allergy-related diseases and somebacterial infections.

  18. Antibacterial, anti-swarming and anti-biofilm formation activities of Chamaemelum nobile against Pseudomonas aeruginosa.

    Science.gov (United States)

    Kazemian, Hossein; Ghafourian, Sobhan; Heidari, Hamid; Amiri, Pouya; Yamchi, Jalil Kardan; Shavalipour, Aref; Houri, Hamidreza; Maleki, Abbas; Sadeghifard, Nourkhoda

    2015-01-01

    Chamomile (Chamaemelum nobile) is widely used throughout the world, and has anti-inflammatory, deodorant, bacteriostatic, antimicrobial, carminative, sedative, antiseptic, anti-catarrhal, and spasmolytic properties. Because of the increasing incidence of drug-resistant bacteria, the development of natural antibacterial sources such as medical herbs for the treatment of infectious diseases is necessary. Extracts from different plant parts such as the leaves, flowers, fruit, and bark of Combretum albiflorum, Laurus nobilis , and Sonchus oleraceus were found to possess anti-quorum sensing (QS) activities. In this study, we evaluated the effect of C. nobile against Pseudomonas aeruginosa biofilm formation. The P. aeruginosa samples were isolated from patients with different types of infection, including wound infection, septicemia, and urinary tract infection. The flowers of C. nobile were dried and the extract was removed using a rotary device and then dissolved in dimethyl sulfoxide at pH 7.4. The microdilution method was used to evaluate the minimum inhibitory concentration (MIC) of this extract on P. aeruginosa , and biofilm inhibition was assayed. Eighty percent of the isolated samples (16/20) could form a biofilm, and most of these were isolated from wound infections. The biofilm inhibitory concentration of the C. nobile extract was 6.25-25mg/ml, whereas the MIC was 12.5-50mg/ml. The anti-QS property of C. nobile may play an important role in its antibacterial activity, thus offering an additional strategy in the fight against bacterial infections. However, molecular investigation is required to explore the exact mechanisms of the antibacterial action and functions of this phytocompound.

  19. Antibacterial, anti-swarming and anti-biofilm formation activities of Chamaemelum nobile against Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Hossein Kazemian

    2015-08-01

    Full Text Available AbstractINTRODUCTION:Chamomile ( Chamaemelum nobile is widely used throughout the world, and has anti-inflammatory, deodorant, bacteriostatic, antimicrobial, carminative, sedative, antiseptic, anti-catarrhal, and spasmolytic properties. Because of the increasing incidence of drug-resistant bacteria, the development of natural antibacterial sources such as medical herbs for the treatment of infectious diseases is necessary. Extracts from different plant parts such as the leaves, flowers, fruit, and bark of Combretum albiflorum, Laurus nobilis , and Sonchus oleraceus were found to possess anti-quorum sensing (QS activities. In this study, we evaluated the effect of C. nobile against Pseudomonas aeruginosa biofilm formationMETHODS:The P. aeruginosa samples were isolated from patients with different types of infection, including wound infection, septicemia, and urinary tract infection. The flowers of C. nobile were dried and the extract was removed using a rotary device and then dissolved in dimethyl sulfoxide at pH 7.4. The microdilution method was used to evaluate the minimum inhibitory concentration (MIC of this extract on P. aeruginosa , and biofilm inhibition was assayed.RESULTS:Eighty percent of the isolated samples (16/20 could form a biofilm, and most of these were isolated from wound infections. The biofilm inhibitory concentration of the C. nobile extract was 6.25-25mg/ml, whereas the MIC was 12.5-50mg/ml.CONCLUSIONS:The anti-QS property of C. nobile may play an important role in its antibacterial activity, thus offering an additional strategy in the fight against bacterial infections. However, molecular investigation is required to explore the exact mechanisms of the antibacterial action and functions of this phytocompound.

  20. Bovine lactoferricin is anti-inflammatory and anti-catabolic in human articular cartilage and synovium.

    Science.gov (United States)

    Yan, Dongyao; Chen, Di; Shen, Jie; Xiao, Guozhi; van Wijnen, Andre J; Im, Hee-Jeong

    2013-02-01

    Bovine lactoferricin (LfcinB) is a multi-functional peptide derived from proteolytic cleavage of bovine lactoferrin. LfcinB was found to antagonize the biological effects mediated by angiogenic growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) in endothelial cells. However, the effect of LfcinB on human articular cartilage remained unknown. Here, our findings demonstrate that LfcinB restored the proteoglycan loss promoted by catabolic factors (interleukin-1β) IL-1β and FGF-2 in vitro and ex vivo. Mechanistically, LfcinB attenuated the effects of IL-1β and FGF-2 on the expression of cartilage-degrading enzymes (MMP-1, MMP-3, and MMP-13), destructive cytokines (IL-1β and IL-6), and inflammatory mediators (iNOS and TLR2). LfcinB induced protective cytokine expression (IL-4 and IL-10), and downregulated aggrecanase basal expression. LfcinB specifically activated ERK MAPK and Akt signaling pathways, which may account for its anti-inflammatory activity. We also revealed that LfcinB exerted similar protective effects on human synovial fibroblasts challenged by IL-1β, with minimal cytotoxicity. Collectively, our results suggest that LfcinB possesses potent anti-catabolic and anti-inflammatory bioactivities in human articular tissues, and may be utilized for the prevention and/or treatment of OA in the future. Copyright © 2012 Wiley Periodicals, Inc.