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Sample records for pc61 mab induces

  1. Sorbitol crystallization-induced aggregation in frozen mAb formulations.

    Science.gov (United States)

    Piedmonte, Deirdre Murphy; Hair, Alison; Baker, Priti; Brych, Lejla; Nagapudi, Karthik; Lin, Hong; Cao, Wenjin; Hershenson, Susan; Ratnaswamy, Gayathri

    2015-02-01

    Sorbitol crystallization-induced aggregation of mAbs in the frozen state was evaluated. The effect of protein aggregation resulting from sorbitol crystallization was measured as a function of formulation variables such as protein concentration and pH. Long-term studies were performed on both IgG1 and IgG2 mAbs over the protein concentration range of 0.1-120 mg/mL. Protein aggregation was measured by size-exclusion HPLC (SE-HPLC) and further characterized by capillary-electrophoresis SDS. Sorbitol crystallization was monitored and characterized by subambient differential scanning calorimetry and X-ray diffraction. Aggregation due to sorbitol crystallization is inversely proportional to both protein concentration and formulation pH. At high protein concentrations, sorbitol crystallization was suppressed, and minimal aggregation by SE-HPLC resulted, presumably because of self-stabilization of the mAbs. The glass transition temperature (Tg ') and fragility index measurements were made to assess the influence of molecular mobility on the crystallization of sorbitol. Tg ' increased with increasing protein concentration for both mAbs. The fragility index decreased with increasing protein concentration, suggesting that it is increasingly difficult for sorbitol to crystallize at high protein concentrations. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  2. Electronic states of Ca/PC61BM: Mechanism of low work function metal as interfacial material

    Directory of Open Access Journals (Sweden)

    Ying-Ying Du

    2018-03-01

    Full Text Available We have studied the electronic states at Ca/PC61BM interface using photoemission spectroscopy. It is found that the state of unoccupied molecular orbitals of the top molecular layer (TML becomes occupied by the electrons transferred from the Ca atoms. The work function of the heavily doped TML of PC61BM film is smaller than that of metal Ca, and thus the contact between the TML and metal Ca is Ohmic. A transition layer (TL of several molecular layers forms beneath the TML due to the diffusion of the Ca atoms. The TL is conductive and aligns its Fermi level with the negative integer charge transfer level of the interior PC61BM. The built-in electric field in the TL facilitates the electron transport from the interior of the PC61BM film to the TML.

  3. Subnanosecond Charge Recombination Dynamics in P3HT/PC61BM Films

    Directory of Open Access Journals (Sweden)

    Jian-Ping Zhang

    2012-11-01

    Full Text Available Ultrafast near-infrared absorption spectroscopy was used to investigate the influence of film morphology and excitation photon energy on the charge recombination (CR dynamics in the initial nanosecond timescale in the P3HT/PC61BM blend films. With reference to the CS2-cast films, the solvent vapor annealed (SVA ones show 2–3-fold improvement in hole mobility and more than 5-fold reduction in the polymer-localized trap states of holes. At Dt = 70 ps, the hole mobility (mh and the bimolecular CR rate (gbi of the SVA films are mh = 8.7 × 10−4 cm2×s−1×V−1 and gbi = 4.5 × 10−10 cm3×s−1, whereas at Dt = 1 ns they drop to 8.7 × 10−5 cm2×s−1×V−1 and 4.6 × 10−11 cm3×s−1, respectively. In addition, upon increasing the hole concentration, the hole mobility increases substantially faster under the above-gap photoexcitation than it does under the band-gap photoexcitation, irrespective of the film morphologies. The results point to the importance of utilizing the photogenerated free charges in the early timescales.

  4. Anti-CD25 mAb administration prevents spontaneous liver transplant tolerance.

    Science.gov (United States)

    Li, W; Carper, K; Liang, Y; Zheng, X X; Kuhr, C S; Reyes, J D; Perkins, D L; Thomson, A W; Perkins, J D

    2006-12-01

    Liver allografts are accepted spontaneously in all mouse strain combinations without immunosuppressive therapy. The mechanisms underlying this phenomenon remain largely undefined. In this study, we examined the effect of CD4+ CD25+ T regulatory cells (Treg) on the induction of mouse liver transplant tolerance. Orthotopic liver transplantation was performed from B10 (H2b) to C3H (H2k) mice. Depleting rat anti-mouse CD25 mAb (PC61) was given to the donors or recipients (250 microg/d IP) pretransplant or to the recipients postoperatively. At day 5 posttransplantation, both effector T cells (mainly CD8) and CD4+ CD25+ Treg were increased in the liver allografts and host spleens compared to naïve mice. Anti-CD25 mAb administration, either pretransplantation or posttransplantation, reduced the ratio of CD4+ CD25+ Treg to the CD3 T cells of liver grafts and recipient spleens and induced liver allograft acute rejection compared to IgG treatment. Anti-CD25 mAb administration elevated anti-donor T-cell proliferative responses and CTL and NK activities of graft infiltrates and host splenocytes; reduced CTLA4, Foxp3, and IDO mRNA levels; increased IL-10 and IFN-gamma; and decreased IL-4 mRNA levels in the livers or host spleens. The number of apoptotic T cells was reduced significantly in the liver grafts and treated host spleens. Therefore, anti-CD25 mAb administration changed the balance of CD4+ CD25+ Treg to activated T cells of liver graft recipients, preventing liver transplant tolerance. This was associated with enhanced anti-donor immune reactivity, downregulated Treg gene expression, and reduced T cell apoptosis in the grafts and host spleens.

  5. Effects of anti-CD40 mAb on inducing malignant B cells proliferation arrest and apoptosis and its mechanism

    International Nuclear Information System (INIS)

    Tang Lin; Zhuang Yumei; Zhou Zhaohua; Yu Gehua; Pan Jianzhong; Zhang Xueguang

    2002-01-01

    Objective: To study the expression of CD 40 molecule and the biological effects mediated by CD 40 molecules on malignant B cells. Methods: Agonistic anti-human CD 40 monoclonal antibody (clone 5C11) was added to cell culture system. Cell counting, PI staining, Annexin-V staining and flow cytometric analysis were used to study the behavior of malignant B cell lines after treatment with mAb clone 5C11. Results: 5C11 induced homotypic aggregation and proliferation arrest and mediated apoptosis in multiple myeloma cell line XG2 that expressed CD 40 strongly; 5C11 induced B lymphoma cell line Daudi homotypic aggregation and proliferation arrest and apoptosis, the apoptosis of XG2 and Daudi by CD40 activation was not mediated by TNF. Conclusion: Agonistic anti-CD 40 mAb 5C11 can inhibit the proliferation of malignant B cells by inducing them to die apoplectically

  6. Static and Dynamic Energetic Disorders in the C 60 , PC 61 BM, C 70 , and PC 71 BM Fullerenes

    KAUST Repository

    Tummala, Naga Rajesh

    2015-09-17

    We use a combination of molecular dynamics simulations and density functional theory calculations to investigate the energetic disorder in fullerene systems. We show that the energetic disorder evaluated from an ensemble average contains contributions of both static origin (time-independent, due to loose packing) and dynamic origin (time-dependent, due to electron-vibration interactions). In order to differentiate between these two contributions, we compare the results obtained from an ensemble average approach with those derived from a time average approach. It is found that in both amorphous C60 and C70 bulk systems, the degrees of static and dynamic disorder are comparable, while in the amorphous PC61BM and PC71BM systems, static disorder is about twice as large as dynamic disorder. © 2015 American Chemical Society.

  7. Modified processing conditions for optimized organic solar cells with inkjet printed P3HT:PC61BM active layers

    International Nuclear Information System (INIS)

    Lange, Alexander; Hollaender, Andreas; Wegener, Michael

    2013-01-01

    Highlights: ► Inkjet printing was used to deposit P3HT:PC 61 BM solar cell active layers. ► The fill factor was dependent on the drying conditions used after printing. ► Fast drying at 100 °C and post-annealing resulted in good device performance. ► Devices with active layers which were slowly dried had high efficiencies without post-annealing. -- Abstract: Inkjet printing can be used to deposit the functional layers of organic solar cells and it offers advantages over spin coating such as the possibility to print films with user-defined patterns. In this study, inkjet printing was utilized to deposit polymer:fullerene solar cell active layers and different drying and annealing conditions were examined in order to optimize device performance. Low fill factors of approximately 30% were found for devices with printed active layers that were dried at 100 °C and a considerable shift in the fill factor of up to 60% was seen after post-annealing at 150 °C. Changes in the fill factor corresponded to an increase in device efficiency from ∼1.3% to ∼2.4% after post-annealing. An alternative active layer drying procedure was used based on solvent annealing which resulted in high fill factors of 60% and efficiencies of ∼2.4% without post-annealing. Blend films were examined with atomic force microscopy, ultra-violet visible spectroscopy and X-ray photoelectron spectroscopy. It was determined that solvent annealed, inkjet printed active layers are considerably rougher and show enhanced organization with respect to films that were dried at 100 °C. Two preparation routes are provided for devices with printed active layers with acceptable efficiencies based on quick drying and post-annealing or slow drying (solvent annealing)

  8. Interfacial and Electrode Modifications in P3HT:PC61BM based Organic Solar Cells: Devices, Processing and Characterization

    Science.gov (United States)

    Das, Sayantan

    The inexorable upsurge in world’s energy demand has steered the search for newer renewable energy sources and photovoltaics seemed to be one of the best alternatives for energy production. Among the various photovoltaic technologies that emerged, organic/polymer photovoltaics based on solution processed bulk-heterojunctions (BHJ) of semiconducting polymers has gained serious attention owing to the use of inexpensive light-weight materials, exhibiting high mechanical flexibility and compatibility with low temperature roll-to-roll manufacturing techniques on flexible substrates. The most widely studied material to date is the blend of regioregular P3HT and PC61BM used as donor and acceptor materials. The object of this study was to investigate and improve the performance/stability of the organic solar cells by use of inexpensive materials. In an attempt to enhance the efficiency of organic solar cells, we have demonstrated the use of hexamethyldisilazane (HMDS) modified indium tin oxide (ITO) electrode in bulk heterojunction solar cell structure The device studies showed a significant enhancement in the short-circuit current as well as in the shunt resistance on use of the hexamethyldisilazane (HMDS) layer. In another approach a p-type CuI hole-transport layer was utilized that could possibly replace the acidic PEDOT:PSS layer in the fabrication of high-efficiency solar cells. The device optimization was done by varying the concentration of CuI in the precursor solution which played an important role in the efficiency of the solar cell devices. Recently a substantial amount of research has been focused on identifying suitable interfacial layers in organic solar cells which has efficient charge transport properties. It was illustrated that a thin layer of silver oxide interfacial layer showed a 28% increase in power conversion efficiency in comparison to that of the control cell. The optoelectronic properties and morphological features of indium-free Zn

  9. Novel Monoclonal Antibody LpMab-17 Developed by CasMab Technology Distinguishes Human Podoplanin from Monkey Podoplanin.

    Science.gov (United States)

    Kato, Yukinari; Ogasawara, Satoshi; Oki, Hiroharu; Honma, Ryusuke; Takagi, Michiaki; Fujii, Yuki; Nakamura, Takuro; Saidoh, Noriko; Kanno, Hazuki; Umetsu, Mitsuo; Kamata, Satoshi; Kubo, Hiroshi; Yamada, Mitsuhiro; Sawa, Yoshihiko; Morita, Kei-Ichi; Harada, Hiroyuki; Suzuki, Hiroyoshi; Kaneko, Mika Kato

    2016-04-01

    Podoplanin (PDPN) is a type-I transmembrane sialoglycoprotein, which possesses a platelet aggregation-stimulating (PLAG) domain in its N-terminus. Among the three PLAG domains, O-glycan on Thr52 of PLAG3 is critical for the binding with C-type lectin-like receptor-2 (CLEC-2) and is essential for platelet-aggregating activity of PDPN. Although many anti-PDPN monoclonal antibodies (mAbs) have been established, almost all mAbs bind to PLAG domains. We recently established CasMab technology to produce mAbs against membranous proteins. Using CasMab technology, we produced a novel anti-PDPN mAb, LpMab-17, which binds to non-PLAG domains. LpMab-17 clearly detected endogenous PDPN of cancer cells and normal cells in Western-blot, flow cytometry, and immunohistochemistry. LpMab-17 recognized glycan-deficient PDPN in flow cytometry, indicating that the interaction between LpMab-17 and PDPN is independent of its glycosylation. The minimum epitope of LpMab-17 was identified as Gly77-Asp82 of PDPN using enzyme-linked immunosorbent assay. Of interest, LpMab-17 did not bind to monkey PDPN, whereas the homology is 94% between human PDPN and monkey PDPN, indicating that the epitope of LpMab-17 is unique compared with the other anti-PDPN mAbs. The combination of different epitope-possessing mAbs could be advantageous for the PDPN-targeting diagnosis or therapy.

  10. Antitumor activity of chLpMab-2, a human-mouse chimeric cancer-specific antihuman podoplanin antibody, via antibody-dependent cellular cytotoxicity.

    Science.gov (United States)

    Kaneko, Mika K; Yamada, Shinji; Nakamura, Takuro; Abe, Shinji; Nishioka, Yasuhiko; Kunita, Akiko; Fukayama, Masashi; Fujii, Yuki; Ogasawara, Satoshi; Kato, Yukinari

    2017-04-01

    Human podoplanin (hPDPN), a platelet aggregation-inducing transmembrane glycoprotein, is expressed in different types of tumors, and it binds to C-type lectin-like receptor 2 (CLEC-2). The overexpression of hPDPN is involved in invasion and metastasis. Anti-hPDPN monoclonal antibodies (mAbs) such as NZ-1 have shown antitumor and antimetastatic activities by binding to the platelet aggregation-stimulating (PLAG) domain of hPDPN. Recently, we developed a novel mouse anti-hPDPN mAb, LpMab-2, using the cancer-specific mAb (CasMab) technology. In this study we developed chLpMab-2, a human-mouse chimeric anti-hPDPN antibody, derived from LpMab-2. chLpMab-2 was produced using fucosyltransferase 8-knockout (KO) Chinese hamster ovary (CHO)-S cell lines. By flow cytometry, chLpMab-2 reacted with hPDPN-expressing cancer cell lines including glioblastomas, mesotheliomas, and lung cancers. However, it showed low reaction with normal cell lines such as lymphatic endothelial and renal epithelial cells. Moreover, chLpMab-2 exhibited high antibody-dependent cellular cytotoxicity (ADCC) against PDPN-expressing cells, despite its low complement-dependent cytotoxicity. Furthermore, treatment with chLpMab-2 abolished tumor growth in xenograft models of CHO/hPDPN, indicating that chLpMab-2 suppressed tumor development via ADCC. In conclusion, chLpMab-2 could be useful as a novel antibody-based therapy against hPDPN-expressing tumors. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  11. Analysis list: mab-5 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available mab-5 Embryo,Larvae + ce10 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/m...ab-5.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/mab-5.5.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/ce10/target/mab-5.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/mab-5.Embryo.tsv,http://dbarchive.bioscien...cedbc.jp/kyushu-u/ce10/colo/mab-5.Larvae.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/ce10/colo/Embryo.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/Larvae.gml ...

  12. The UC Davis/NIH NeuroMab Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The mission of the UC Davis/NIH NeuroMab facility is to generate and distribute high quality, validated mouse monoclonal antibodies against molecular targets found...

  13. The mAb against adipocyte fatty acid-binding protein 2E4 attenuates the inflammation in the mouse model of high-fat diet-induced obesity via toll-like receptor 4 pathway.

    Science.gov (United States)

    Miao, Xiaoliang; Wang, Ying; Wang, Wang; Lv, Xiaobo; Wang, Min; Yin, Hongping

    2015-03-05

    Adipocyte fatty acid-binding protein (A-FABP) plays an important role in fatty acid-mediated processes and related metabolic and inflammatory responses. In this study, we prepared a novel monoclonal antibody against A-FABP, designated 2E4. Our data showed that 2E4 specifically binded to the recombinant A-FABP and native A-FABP of mice adipose tissue. Furthermore, we investigated the effect of 2E4 on metabolic and inflammatory responses in C57BL/6J obese mice fed on a high fat diet. 2E4 administration improved glucose response in high-fat-diet induced obese mice. The 2E4 treated groups exhibited lower free fatty acids, cholesterol, and triglycerides in a concentration-dependent manner. These changes were accompanied by down-regulated expression of pro-inflammatory cytokines in adipose tissue, including tumor necrosis factor α, monocyte chemotactic protein-1, and interleukin-6. Meanwhile, our data demonstrated that 2E4 significantly decreased the mRNA and protein levels of A-FABP in adipose tissue of mice. Further experiments showed that 2E4 notably suppressed the phosphorylation of IκBα and jun-N-terminal kinase through toll-like receptor 4 signaling pathway. Taken together, 2E4 is an effective monoclonal antibody against A-FABP, which attenuated the inflammatory responses induced in the high-fat-diet mice. These findings may provide scientific insight into the treatment of chronic low-grade inflammation in obesity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Rapamycin combined with anti-CD45RB mAb and IL-10 or with G-CSF induces tolerance in a stringent mouse model of islet transplantation.

    Directory of Open Access Journals (Sweden)

    Nicola Gagliani

    Full Text Available BACKGROUND: A large pool of preexisting alloreactive effector T cells can cause allogeneic graft rejection following transplantation. However, it is possible to induce transplant tolerance by altering the balance between effector and regulatory T (Treg cells. Among the various Treg-cell types, Foxp3(+Treg and IL-10-producing T regulatory type 1 (Tr1 cells have frequently been associated with tolerance following transplantation in both mice and humans. Previously, we demonstrated that rapamycin+IL-10 promotes Tr1-cell-associated tolerance in Balb/c mice transplanted with C57BL/6 pancreatic islets. However, this same treatment was unsuccessful in C57BL/6 mice transplanted with Balb/c islets (classified as a stringent transplant model. We accordingly designed a protocol that would be effective in the latter transplant model by simultaneously depleting effector T cells and fostering production of Treg cells. We additionally developed and tested a clinically translatable protocol that used no depleting agent. METHODOLOGY/PRINCIPAL FINDINGS: Diabetic C57BL/6 mice were transplanted with Balb/c pancreatic islets. Recipient mice transiently treated with anti-CD45RB mAb+rapamycin+IL-10 developed antigen-specific tolerance. During treatment, Foxp3(+Treg cells were momentarily enriched in the blood, followed by accumulation in the graft and draining lymph node, whereas CD4(+IL-10(+IL-4(- T (i.e., Tr1 cells localized in the spleen. In long-term tolerant mice, only CD4(+IL-10(+IL-4(- T cells remained enriched in the spleen and IL-10 was key in the maintenance of tolerance. Alternatively, recipient mice were treated with two compounds routinely used in the clinic (namely, rapamycin and G-CSF; this drug combination promoted tolerance associated with CD4(+IL-10(+IL-4(- T cells. CONCLUSIONS/SIGNIFICANCE: The anti-CD45RB mAb+rapamycin+IL-10 combined protocol promotes a state of tolerance that is IL-10 dependent. Moreover, the combination of rapamycin+G-CSF induces

  15. LpMab-19 Recognizes Sialylated O-Glycan on Thr76 of Human Podoplanin.

    Science.gov (United States)

    Ogasawara, Satoshi; Kaneko, Mika K; Kato, Yukinari

    2016-08-26

    Human podoplanin (hPDPN) is expressed in lymphatic vessels, pulmonary type-I alveolar cells, and renal glomerulus. The hPDPN/C-type lectin-like receptor-2 (CLEC-2) interaction is involved in platelet aggregation and cancer metastasis. High expression of hPDPN in cancer cells or cancer-associated fibroblasts (CAFs) leads to a poor prognosis for cancer patients. In our previous research, we reported on several anti-hPDPN monoclonal antibodies (mAbs), including LpMab-2, LpMab-3, LpMab-7, LpMab-9, LpMab-12, LpMab-13, and LpMab-17 of mouse IgG 1 subclass, which were produced using CasMab technology. Here we produced a novel anti-hPDPN mAb LpMab-19 of mouse IgG 2b subclass. Flow cytometry revealed that the epitope of LpMab-19 includes O-glycan, which is attached to Thr76 of hPDPN. We further identified the minimum epitope of LpMab-19 as Thr76-Arg79 of hPDPN. Immunohistochemistry revealed that LpMab-19 is useful for detecting not only normal cells, including lymphatic vessels, but also glioblastoma and oral squamous cell carcinoma cells. LpMab-19 could be useful for investigating the physiological function of O-glycosylated hPDPN.

  16. Analysis of Japanese Municipalities With Geopark, MAB, and GIAHS Certification

    Directory of Open Access Journals (Sweden)

    Ryo Kohsaka

    2015-11-01

    Full Text Available We analyzed the discussions of Japanese municipalities in their process for obtaining certifications for the Geoparks by the United Nations Educational, Scientific and Cultural Organization (UNESCO, the Man and the Biosphere Programme (MAB by the UNESCO, and the Globally Important Agricultural Heritage systems (GIAHS by the Food and Agriculture Organization (FAO of the United Nations. The official records at the municipality diet were analyzed in a quantitative manner from 2011 to 2013. As the first step, we analyzed the eight municipalities of Noto and Sado for the GIAHS, the cities Itoigawa and Hakusan for the Geopark, and Katsuyama Yamanouchi village from Nagano for the MAB. As individual examples, we analyzed City of Suzu with GIAHS, Itoigawa (Geopark, and Yamanouchi town (MAB with the text-mining approach. For the GIAHS, it was clear that the larger municipalities with city status tended to discuss certification issues more frequently than the smaller towns and villages. Terms such as conservation and certification tended to be used with GIAHS at the Suzu City. The term brand was used with GIAHS and MAB but not for the Geopark. The findings using quantitative methods are at initial stage for analysis of municipality strategies and require further future research.

  17. Preparation for gluing of Carbon prototype MAB at INEGI, Porto

    CERN Multimedia

    Miguel Moreira, Porto, INEGI

    2001-01-01

    MAB's will assure the alignment of the CMS detector. It is equipped with muon cameras, measuring the position of the barrel muon stations and at the same time linking via the link elements, connecting the barrel muon detectors with the Tracker. In addition there is a connection with the endcap. More details can be found on the muon/alignment homepage on the web

  18. LpMab-12 Established by CasMab Technology Specifically Detects Sialylated O-Glycan on Thr52 of Platelet Aggregation-Stimulating Domain of Human Podoplanin.

    Directory of Open Access Journals (Sweden)

    Yukinari Kato

    Full Text Available Podoplanin (PDPN, also known as Aggrus, possesses three tandem repeat of platelet aggregation-stimulating (PLAG domains in its N-terminus. Among the PLAG domains, sialylated O-glycan on Thr52 of PLAG3 is essential for the binding to C-type lectin-like receptor-2 (CLEC-2 and the platelet-aggregating activity of human PDPN (hPDPN. Although various anti-hPDPN monoclonal antibodies (mAbs have been generated, no specific mAb has been reported to target the epitope containing glycosylated Thr52. We recently established CasMab technology to develop mAbs against glycosylated membrane proteins. Herein, we report the development of a novel anti-glycopeptide mAb (GpMab, LpMab-12. LpMab-12 detected endogenous hPDPN by flow cytometry. Immunohistochemical analyses also showed that hPDPN-expressing lymphatic endothelial and cancer cells were clearly labeled by LpMab-12. The minimal epitope of LpMab-12 was identified as Asp49-Pro53 of hPDPN. Furthermore, LpMab-12 reacted with the synthetic glycopeptide of hPDPN, corresponding to 38-54 amino acids (hpp3854: 38-EGGVAMPGAEDDVVTPG-54, which carries α2-6 sialylated N-acetyl-D-galactosamine (GalNAc on Thr52. LpMab-12 did not recognize non-sialylated GalNAc-attached glycopeptide, indicating that sialylated GalNAc on Thr52 is necessary for the binding of LpMab-12 to hPDPN. Thus, LpMab-12 could serve as a new diagnostic tool for determining whether hPDPN possesses the sialylation on Thr52, a site-specific post-translational modification critical for the hPDPN association with CLEC-2.

  19. Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs.

    Directory of Open Access Journals (Sweden)

    Marnie L Fusco

    2015-06-01

    Full Text Available The filoviruses, which include the marburg- and ebolaviruses, have caused multiple outbreaks among humans this decade. Antibodies against the filovirus surface glycoprotein (GP have been shown to provide life-saving therapy in nonhuman primates, but such antibodies are generally virus-specific. Many monoclonal antibodies (mAbs have been described against Ebola virus. In contrast, relatively few have been described against Marburg virus. Here we present ten mAbs elicited by immunization of mice using recombinant mucin-deleted GPs from different Marburg virus (MARV strains. Surprisingly, two of the mAbs raised against MARV GP also cross-react with the mucin-deleted GP cores of all tested ebolaviruses (Ebola, Sudan, Bundibugyo, Reston, but these epitopes are masked differently by the mucin-like domains themselves. The most efficacious mAbs in this panel were found to recognize a novel "wing" feature on the GP2 subunit that is unique to Marburg and does not exist in Ebola. Two of these anti-wing antibodies confer 90 and 100% protection, respectively, one hour post-exposure in mice challenged with MARV.

  20. Structural and biochemical characterization of the cell fate determining nucleotidyltransferase fold protein MAB21L1.

    Science.gov (United States)

    de Oliveira Mann, Carina C; Kiefersauer, Reiner; Witte, Gregor; Hopfner, Karl-Peter

    2016-06-08

    The exceptionally conserved metazoan MAB21 proteins are implicated in cell fate decisions and share considerable sequence homology with the cyclic GMP-AMP synthase. cGAS is the major innate immune sensor for cytosolic DNA and produces the second messenger 2'-5', 3'-5' cyclic GMP-AMP. Little is known about the structure and biochemical function of other proteins of the cGAS-MAB21 subfamily, such as MAB21L1, MAB21L2 and MAB21L3. We have determined the crystal structure of human full-length MAB21L1. Our analysis reveals high structural conservation between MAB21L1 and cGAS but also uncovers important differences. Although monomeric in solution, MAB21L1 forms a highly symmetric double-pentameric oligomer in the crystal, raising the possibility that oligomerization could be a feature of MAB21L1. In the crystal, MAB21L1 is in an inactive conformation requiring a conformational change - similar to cGAS - to develop any nucleotidyltransferase activity. Co-crystallization with NTP identified a putative ligand binding site of MAB21 proteins that corresponds to the DNA binding site of cGAS. Finally, we offer a structure-based explanation for the effects of MAB21L2 mutations in patients with eye malformations. The underlying residues participate in fold-stabilizing interaction networks and mutations destabilize the protein. In summary, we provide a first structural framework for MAB21 proteins.

  1. LpMab-23: A Cancer-Specific Monoclonal Antibody Against Human Podoplanin.

    Science.gov (United States)

    Yamada, Shinji; Ogasawara, Satoshi; Kaneko, Mika K; Kato, Yukinari

    2017-04-01

    Human podoplanin (hPDPN), the ligand of C-type lectin-like receptor-2, is involved in cancer metastasis. Until now, many monoclonal antibodies (mAbs) have been established against hPDPN. However, it is still difficult to develop a cancer-specific mAb (CasMab) against hPDPN because the protein sequence of hPDPN expressed in cancer cells is the same as that in normal cells. Herein, we report LpMab-23 of the mouse IgG 1 subclass, a novel CasMab against hPDPN. In an immunohistochemical analysis, LpMab-23 reacted with tumor cells of human oral cancer, but did not react with normal cells such as lymphatic endothelial cells (LECs). In contrast, LpMab-17, another anti-hPDPN mAb, reacted with both tumor cells and LECs. Furthermore, flow cytometric analysis revealed that LpMab-23 reacted with hPDPN-expressing cancer cell lines (LN319, RERF-LC-AI/hPDPN, Y-MESO-14/hPDPN, and HSC3/hPDPN) but showed little reaction with normal cells (LECs and HEK-293T), although another anti-hPDPN mAb, LpMab-7, reacted with both hPDPN-expressing cancer cells and normal cells, indicating that LpMab-23 is a CasMab against hPDPN.

  2. Generation, characterization and therapeutic potential of anti-feline TNF-alpha MAbs for feline infectious peritonitis.

    Science.gov (United States)

    Doki, Tomoyoshi; Takano, Tomomi; Nishiyama, Yuri; Nakamura, Michiyo; Hohdatsu, Tsutomu

    2013-12-01

    Feline infectious peritonitis (FIP) is a lethal infectious disease affecting domestic and wild cats. Several reports suggested that TNF-alpha is related to the progression of FIP. Thus, the administration of a feline TNF-alpha-neutralizing antibody to cats with FIP may reduce the disease progression. In this study, we have prepared nine monoclonal antibodies (MAbs) that recognize feline TNF-alpha. All MAbs neutralized recombinant TNF-alpha. The 50% inhibitory concentrations (IC50) of the MAbs for the cytotoxicity of recombinant TNF-alpha were 5-684 ng/ml. MAb 2-4 exhibited high neutralizing activity against natural TNF-alpha derived from FIPV-infected macrophages, and was confirmed to inhibit the following feline TNF-alpha-induced conditions in vitro: (i) an increase in the survival rate of neutrophils from cats with FIP, (ii) aminopeptidase N (APN) mRNA expression in macrophages, and (iii) apoptosis of a feline T-lymphocyte cell line. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Inhibition of the β-Lactamase BlaMab by Avibactam Improves the In Vitro and In Vivo Efficacy of Imipenem against Mycobacterium abscessus.

    Science.gov (United States)

    Lefebvre, Anne-Laure; Le Moigne, Vincent; Bernut, Audrey; Veckerlé, Carole; Compain, Fabrice; Herrmann, Jean-Louis; Kremer, Laurent; Arthur, Michel; Mainardi, Jean-Luc

    2017-04-01

    Mycobacterium abscessus pulmonary infections are treated with a macrolide (clarithromycin or azithromycin), an aminoglycoside (amikacin), and a β-lactam (cefoxitin or imipenem). The triple combination is used without any β-lactamase inhibitor, even though M abscessus produces the broad-spectrum β-lactamase Bla Mab We determine whether inhibition of Bla Mab by avibactam improves the activity of imipenem against M. abscessus The bactericidal activity of drug combinations was assayed in broth and in human macrophages. The in vivo efficacy of the drugs was tested by monitoring the survival of infected zebrafish embryos. The level of Bla Mab production in broth and in macrophages was compared by quantitative reverse transcription-PCR and Western blotting. The triple combination of imipenem (8 or 32 μg/ml), amikacin (32 μg/ml), and avibactam (4 μg/ml) was bactericidal in broth (imipenem was used at 8 and 32 μg/ml, respectively. The triple combination achieved significant intracellular killing, with the bacterial survival rates being 54% and 7% with the low (8 μg/ml) and high (32 μg/ml) dosages of imipenem, respectively. In vivo inhibition of Bla Mab by avibactam improved the survival of zebrafish embryos treated with imipenem. Expression of the gene encoding Bla Mab was induced (20-fold) in the infected macrophages. Inhibition of Bla Mab by avibactam improved the efficacy of imipenem against M. abscessus in vitro , in macrophages, and in zebrafish embryos, indicating that this β-lactamase inhibitor should be clinically evaluated. The in vitro evaluation of imipenem may underestimate the impact of Bla Mab , since the production of the β-lactamase is inducible in macrophages. Copyright © 2017 American Society for Microbiology.

  4. Controlling the Glycosylation Profile in mAbs Using Time-Dependent Media Supplementation

    Directory of Open Access Journals (Sweden)

    Devesh Radhakrishnan

    2017-12-01

    Full Text Available In order to meet desired drug product quality targets, the glycosylation profile of biotherapeutics such as monoclonal antibodies (mAbs must be maintained consistently during manufacturing. Achieving consistent glycan distribution profiles requires identifying factors that influence glycosylation, and manipulating them appropriately via well-designed control strategies. Now, the cell culture media supplement, MnCl2, is known to alter the glycosylation profile in mAbs generally, but its effect, particularly when introduced at different stages during cell growth, has yet to be investigated and quantified. In this study, we evaluate the effect of time-dependent addition of MnCl2 on the glycan profile quantitatively, using factorial design experiments. Our results show that MnCl2 addition during the lag and exponential phases affects the glycan profile significantly more than stationary phase supplementation does. Also, using a novel computational technique, we identify various combinations of glycan species that are affected by this dynamic media supplementation scheme, and quantify the effects mathematically. Our experiments demonstrate the importance of taking into consideration the time of addition of these trace supplements, not just their concentrations, and our computational analysis provides insight into what supplements to add, when, and how much, in order to induce desired changes.

  5. Structures and Stability of Metal Amidoboranes (MAB): Density Functional Calculations

    International Nuclear Information System (INIS)

    Li Cailin; Wu Chaoling; Chen Yungui; Zhou Jingjing; Zheng Xin; Pang Lijuan; Deng Gang

    2010-01-01

    Molecule geometry structures, frequencies, and energetic stabilities of ammonia borane (AB, NH 3 BH 3 ) and metal amidoboranes (MAB, MNH 2 BH 3 ), formed by substituting H atom in AB with one of main group metal atoms, have been investigated by density-functional theory and optimized at the B3LYP levels with 6-311G++ (3df, 3pd) basic set. Their structural parameters and infrared spectrum characteristic peaks have been predicted, which should be the criterion of a successfully synthesized material. Several parameters such as binding energies, vibrational frequencies, and the energy gaps between the HOMO and the LUMO have been adopted to characterize and evaluate their structure stabilities. It is also found that the binding energies and HOMO-LUMO energy gaps of the MAB obviously change with the substitution of the atoms. MgAB has the lowest binding energy and is easier to decompose than any other substitutional structures under same conditions, while CaAB has the highest chemical activity. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

  6. The anti-(+-methamphetamine monoclonal antibody mAb7F9 attenuates acute (+-methamphetamine effects on intracranial self-stimulation in rats.

    Directory of Open Access Journals (Sweden)

    Andrew C Harris

    Full Text Available Passive immunization with monoclonal antibodies (mAbs against (+-methamphetamine (METH is being evaluated for the treatment of METH addiction. A human/mouse chimeric form of the murine anti-METH mAb7F9 has entered clinical trials. This study examined the effects of murine mAb7F9 on certain addiction-related behavioral effects of METH in rats as measured using intracranial self-stimulation (ICSS. Initial studies indicated that acute METH (0.1-0.56 mg/kg, s.c. lowered the minimal (threshold stimulation intensity that maintained ICSS. METH (0.3 mg/kg, s.c. also blocked elevations in ICSS thresholds (anhedonia-like behavior during spontaneous withdrawal from a chronic METH infusion (10 mg/kg/day x 7 days. In studies examining effects of i.v. pretreatment with mAb7F9 (at 30, 100, or 200 mg/kg, 200 mg/kg blocked the ability of an initial injection of METH (0.3 mg/kg, s.c. to reduce baseline ICSS thresholds, but was less capable of attenuating the effect of subsequent daily injections of METH. MAb7F9 (200 mg/kg also produced a small but significant reduction in the ability of METH (0.3 mg/kg, s.c. to reverse METH withdrawal-induced elevations in ICSS thresholds. These studies demonstrate that mAb7F9 can partially attenuate some addiction-related effects of acute METH in an ICSS model, and provide some support for the therapeutic potential of mAb7F9 for the treatment of METH addiction.

  7. Immunoreactivity of the 14F7 Mab Raised against N-Glycolyl GM3 Ganglioside in Primary Lymphoid Tumors and Lymph Node Metastasis

    Science.gov (United States)

    Blanco, Rancés; Blanco, Damián; Quintana, Yisel; Escobar, Xiomara; Rengifo, Charles E.; Osorio, Marta; Gutiérrez, Zailí; Lamadrid, Janet; Cedeño, Mercedes; Frómeta, Milagros; Carr, Adriana; Rengifo, Enrique

    2013-01-01

    The reactivity of the 14F7 Mab, a highly specific IgG1 against N-glycolyl GM3 ganglioside (NeuGcGM3) in normal tissues, lymphomas, lymph node metastasis, and other metastatic sites was assessed by immunohistochemistry. In addition, the effect of chemical fixation on the 14F7 Mab staining using monolayers of P3X63Ag.653 cells was also evaluated. Moreover, the ability of 14F7 to bind NeuGcGM3 ganglioside inducing complement-independent cytotoxicity by a flow cytometry-based assay was measured. The 14F7 Mab was reactive in unfixed, 4% paraformaldehyde, 4% formaldehyde, and acetone fixed cells. Postfixation with acetone did not alter the localization of NeuGcGM3, while the staining with 14F7 Mab was significantly eliminated in both cells fixed and postfixed with methanol but only partially reduced with ethanol. The staining with 14F7 Mab was evidenced in the 89.2%, 89.4%, and 88.9% of lymphomas, lymph node metastasis, and other metastatic sites, respectively, but not in normal tissues. The treatment with 14F7 Mab affected both morphology and membrane integrity of P3X63Ag.653 cells. This cytotoxic activity was dose-dependent and ranged from 24.0 to 84.7% (10–1000 μg/mL) as compared to the negative control. Our data could support the possible use of NeuGcGM3 as target for both active and passive immunotherapy against malignancies expressing this molecule. PMID:24381785

  8. The UNC-4 homeobox protein represses mab-9 expression in DA motor neurons in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Jafari, Gholamali; Appleford, Peter J; Seago, Julian

    2011-01-01

    , an RNAi screen designed to identify upstream transcriptional regulators of mab-9 showed that silencing of unc-4 (encoding a paired-class homeodomain protein) increases mab-9::gfp expression in the nervous system, specifically in posterior DA motor neurons. Over-expression of unc-4 from a heat...

  9. Podocyte changes after induction of acute albuminuria in mice by anti-aminopeptidase A mAb.

    Science.gov (United States)

    Dijkman, Henry B P M; Gerlofs-Nijland, Miriam E; van der Laak, Jeroen A W M; Wetzels, Jack F M; Groenen, Patricia J T A; Assmann, Karel J M

    2003-01-01

    Administration of a specific combination of anti-aminopeptidase A (APA) mAb (ASD-37/41) in mice induces an acute albuminuria which is independent of angiotensin II, a well-known substrate of APA. In the present experiments, we examined whether binding of the mAb initiated changes in the podocytic expression of cytoskeleton (-associated), adhesion and slit-diaphragm proteins in relation to the time course of albuminuria. In addition, we measured ultrastructurally the extent of foot process retraction (the number of foot processes per microm GBM) and the width of the slit pore between the podocytes by morphometric methods. An injection of the mAb combination ASD-37/41 induced a massive but transient albuminuria that started at 6 h, and peaked at 8 h, after which it declined. However, even at day 7 after injection of the mAbs some albuminuria was present. Injection of the combination ASD-3/41 or saline did not induce an albuminuria. Notably, we observed changes in the staining of CD2AP and podocin, two slit-pore-associated proteins that coincided with the start of the albuminuria. Nephrin staining was reduced and podocytic actin staining became more granular only at a time albuminuria was declining (24 h). The number of foot processes per microm GBM was already decreased at 4 h with a further reduction thereafter. The width of the slit pore was unchanged at the time of peak albuminuria and gradually decreased thereafter. At day 7, podocytic foot process effacement was even more prominent although albuminuria was only slightly abnormal. Expression of CD2AP was still granular. We observed however a change toward normal in the expression of podocin. Injection of saline or ASD-3/41 had no effect on the expression of podocytic proteins, the number of foot processes or width of the slit pore. Our data show that the onset of albuminuria in the anti-APA model is related to alterations in CD2AP and podocin, proteins that are important for maintaining slit-diaphragm structure

  10. Neutron Reflection Study of Surface Adsorption of Fc, Fab, and the Whole mAb.

    Science.gov (United States)

    Li, Zongyi; Li, Ruiheng; Smith, Charles; Pan, Fang; Campana, Mario; Webster, John R P; van der Walle, Christopher F; Uddin, Shahid; Bishop, Steve M; Narwal, Rojaramani; Warwicker, Jim; Lu, Jian Ren

    2017-07-12

    Characterizing the influence of fragment crystallization (Fc) and antigen-binding fragment (Fab) on monoclonal antibody (mAb) adsorption at the air/water interface is an important step to understanding liquid mAb drug product stability during manufacture, shipping, and storage. Here, neutron reflection is used to study the air/water adsorption of a mAb and its Fc and Fab fragments. By varying the isotopic contrast, the adsorbed amount, thickness, orientation, and immersion of the adsorbed layers could be determined unambiguously. While Fc adsorption reached saturation within the hour, its surface adsorbed amount showed little variation with bulk concentration. In contrast, Fab adsorption was slower and the adsorbed amount was concentration dependent. The much higher Fc adsorption, as compared to Fab, was linked to its lower surface charge. Time and concentration dependence of mAb adsorption was dominated by Fab behavior, although both Fab and Fc behaviors contributed to the amount of mAb adsorbed. Changing the pH from 5.5 to 8.8 did not much perturb the adsorbed amount of Fc, Fab, or mAb. However, a small decrease in adsorption was observed for the Fc over pH 8-8.8 and vice versa for the Fab and mAb, consistent with a dominant Fab behavior. As bulk concentration increased from 5 to 50 ppm, the thicknesses of the Fc layers were almost constant at 40 Å, while Fab and mAb layers increased from 45 to 50 Å. These results imply that the adsorbed mAb, Fc, and Fab all retained their globular structures and were oriented with their short axial lengths perpendicular to the interface.

  11. First experiences with the AMERLEX-MAB FREE T4 assay

    International Nuclear Information System (INIS)

    Nijhof, W.A.; Penders, T.J.

    1989-01-01

    The new Amerlex-MAB FT 4 is a quick direct free T 4 assay with good reproducability. The correlation between the Amerlex-MAB FT 4 and the free T 4 of Byk is good. In the non-thyreoidal illness patient group no deviation for the values were found. Amerlex-MAB FT 4 is cheaper, because no total T4 has to be measured. More research has to be done for special patient sera. Disturbing influences as free fatty acids, heparin and auto-antibodies have to be checked. (R.B.). 3 refs.; 3 figs.; 4 tabs

  12. Dynamics of immature mAb glycoform secretion during CHO cell culture

    DEFF Research Database (Denmark)

    Jimenez del Val, Ioscani; Fan, Yuzhou; Weilguny, Dietmar

    2016-01-01

    Ensuring consistent glycosylation-associated quality of therapeutic monoclonal antibodies (mAbs) has become a priority in pharmaceutical bioprocessing given that the distribution and composition of the carbohydrates (glycans) bound to these molecules determines their therapeutic efficacy and immu......Ensuring consistent glycosylation-associated quality of therapeutic monoclonal antibodies (mAbs) has become a priority in pharmaceutical bioprocessing given that the distribution and composition of the carbohydrates (glycans) bound to these molecules determines their therapeutic efficacy...

  13. Monoclonal Antibody L1Mab-13 Detected Human PD-L1 in Lung Cancers.

    Science.gov (United States)

    Yamada, Shinji; Itai, Shunsuke; Nakamura, Takuro; Yanaka, Miyuki; Chang, Yao-Wen; Suzuki, Hiroyoshi; Kaneko, Mika K; Kato, Yukinari

    2018-04-01

    Programmed cell death ligand-1 (PD-L1) is a type I transmembrane glycoprotein expressed on antigen-presenting cells. It is also expressed in several tumor cells such as melanoma and lung cancer cells. A strong correlation has been reported between human PD-L1 (hPD-L1) expression in tumor cells and negative prognosis in cancer patients. Here, a novel anti-hPD-L1 monoclonal antibody (mAb) L 1 Mab-13 (IgG 1 , kappa) was produced using a cell-based immunization and screening (CBIS) method. We investigated hPD-L1 expression in lung cancer using flow cytometry, Western blot, and immunohistochemical analyses. L 1 Mab-13 specifically reacted hPD-L1 of hPD-L1-overexpressed Chinese hamster ovary (CHO)-K1 cells and endogenous hPD-L1 of KMST-6 (human fibroblast) in flow cytometry and Western blot. Furthermore, L 1 Mab-13 reacted with lung cancer cell lines (EBC-1, Lu65, and Lu99) in flow cytometry and stained lung cancer tissues in a membrane-staining pattern in immunohistochemical analysis. These results indicate that a novel anti-hPD-L1 mAb, L 1 Mab-13, is very useful for detecting hPD-L1 of lung cancers in flow cytometry, Western blot, and immunohistochemical analyses.

  14. Development of an Anti-HER2 Monoclonal Antibody H2Mab-139 Against Colon Cancer.

    Science.gov (United States)

    Kaneko, Mika K; Yamada, Shinji; Itai, Shunsuke; Kato, Yukinari

    2018-02-01

    Human epidermal growth factor receptor 2 (HER2) expression has been reported in several cancers, such as breast, gastric, lung, pancreatic, and colorectal cancers. HER2 is overexpressed in those cancers and is associated with poor clinical outcomes. Trastuzumab, a humanized anti-HER2 antibody, provides significant survival benefits for patients with HER2-overexpressing breast cancers and gastric cancers. In this study, we developed a novel anti-HER2 monoclonal antibody (mAb), H 2 Mab-139 (IgG 1 , kappa) and investigated it against colon cancers using flow cytometry, western blot, and immunohistochemical analyses. Flow cytometry analysis revealed that H 2 Mab-139 reacted with colon cancer cell lines, such as Caco-2, HCT-116, HCT-15, HT-29, LS 174T, COLO 201, COLO 205, HCT-8, SW1116, and DLD-1. Although H 2 Mab-139 strongly reacted with LN229/HER2 cells on the western blot, we did not observe a specific signal for HER2 in colon cancer cell lines. Immunohistochemical analyses revealed sensitive and specific reactions of H 2 Mab-139 against colon cancers, indicating that H 2 Mab-139 is useful in detecting HER2 overexpression in colon cancers using flow cytometry and immunohistochemical analyses.

  15. Determination of critical epitope of PcMab-47 against human podocalyxin

    Directory of Open Access Journals (Sweden)

    Shunsuke Itai

    2018-07-01

    Full Text Available Podocalyxin (PODXL is a type I transmembrane protein, which is highly glycosylated. PODXL is expressed in some types of human cancer tissues including oral, breast, and lung cancer tissues and may promote tumor growth, invasion, and metastasis. We previously produced PcMab-47, a novel anti-PODXL monoclonal antibody (mAb which reacts with endogenous PODXL-expressing cancer cell lines and normal cells independently of glycosylation in Western blot, flow cytometry, and immunohistochemical analysis. In this study, we used enzyme-linked immunosorbent assay (ELISA, flow cytometry, and immunohistochemical analysis to determine the epitope of PcMab-47. The minimum epitope of PcMab-47 was found to be Asp207, His208, Leu209, and Met210. A blocking peptide containing this minimum epitope completely neutralized PcMab-47 reaction against oral cancer cells by flow cytometry and immunohistochemical analysis. These findings could lead to the production of more functional anti-PODXL mAbs, which are advantageous for antitumor activities.

  16. Determination of critical epitope of PcMab-47 against human podocalyxin.

    Science.gov (United States)

    Itai, Shunsuke; Yamada, Shinji; Kaneko, Mika K; Kato, Yukinari

    2018-07-01

    Podocalyxin (PODXL) is a type I transmembrane protein, which is highly glycosylated. PODXL is expressed in some types of human cancer tissues including oral, breast, and lung cancer tissues and may promote tumor growth, invasion, and metastasis. We previously produced PcMab-47, a novel anti-PODXL monoclonal antibody (mAb) which reacts with endogenous PODXL-expressing cancer cell lines and normal cells independently of glycosylation in Western blot, flow cytometry, and immunohistochemical analysis. In this study, we used enzyme-linked immunosorbent assay (ELISA), flow cytometry, and immunohistochemical analysis to determine the epitope of PcMab-47. The minimum epitope of PcMab-47 was found to be Asp207, His208, Leu209, and Met210. A blocking peptide containing this minimum epitope completely neutralized PcMab-47 reaction against oral cancer cells by flow cytometry and immunohistochemical analysis. These findings could lead to the production of more functional anti-PODXL mAbs, which are advantageous for antitumor activities.

  17. Conservation Compromises: The MAB and the Legacy of the International Biological Program, 1964-1974.

    Science.gov (United States)

    Schleper, Simone

    2017-02-01

    This article looks at the International Biological Program (IBP) as the predecessor of UNESCO's well-known and highly successful Man and the Biosphere Programme (MAB). It argues that international conservation efforts of the 1970s, such as the MAB, must in fact be understood as a compound of two opposing attempts to reform international conservation in the 1960s. The scientific framework of the MAB has its origins in disputes between high-level conservationists affiliated with the International Union for the Conservation of Nature and Natural Resources (IUCN) about what the IBP meant for the future of conservation. Their respective visions entailed different ecological philosophies as much as diverging sets of political ideologies regarding the global implementation of conservation. Within the IBP's Conservation Section, one group propagated a universal systems approach to conservation with a centralized, technocratic management of nature and society by an elite group of independent scientific experts. Within IUCN, a second group based their notion of environmental expert roles on a more descriptive and local ecology of resource mapping as practiced by UNESCO. When the IBP came to an end in 1974, both groups' ecological philosophies played into the scientific framework underlying the MAB's World Network or Biosphere Reserves. The article argues that it is impossible to understand the course of conservation within the MAB without studying the dynamics and discourses between the two underlying expert groups and their respective visions for reforming conservation.

  18. Rituximab (MabThera) til behandling af aktiv reumatoid artritis

    DEFF Research Database (Denmark)

    El Fassi, Daniel; Nielsen, Claus Henrik; Bendtzen, Klaus

    2006-01-01

    Rituximab (RTX) is a murine/human monoclonal antibody to CD20, a protein expressed almost exclusively on human B-lymphocytes. RTX induces rapid and marked B-cell depletion with beneficial clinical effects in 1/3 to 1/2 of rheumatoid arthritis patients. Treatment is given as two iv. infusions with...

  19. SPECT scintigraphy with HDP and Mab BW 250/183 of loosened hip endoprothesis

    Energy Technology Data Exchange (ETDEWEB)

    Predic, P [Hospital Celje, Celje (Sierra Leone); Gregoric, E [Hospital Izola, Izola (Sierra Leone); Dodig, D [Clinical Hospital Centre, Zagreb (Croatia). Dept. of Nuclear Medicine and Radiation Protection

    1994-10-01

    Main problem of the loosened hip endoprothesis is in distinguishing between the aseptic and septic loosening of endoprothesis. The study involved 27 pts with a loosened hip; 15 pts with aseptic and 12 pts with septic loosening. The patients were injected 550-770 MBq Tc-99m-HDP and underwent SPECT scintigraphy of the hips to repeat then the examination with only 370 MBq Tc-99m-Mab Bw 230/183. HDP application evidenced positive accumulation at the endoprothesis in all patients with a loosened hip while Mab Bw 250/183 only in the patients with septic loosening. Conclusion: SPECT scintigraphy of hip endoprothesis with HDP and Mab BW 250/183 allows differential diagnosing between septic and aseptic hip loosening and hereby a correct therapeutical approach. (author).

  20. Development of at-line assay to monitor charge variants of MAbs during production.

    Science.gov (United States)

    St Amand, M M; Ogunnaike, B A; Robinson, A S

    2014-01-01

    One major challenge currently facing the biopharmaceutical industry is to understand how MAb microheterogeneity affects therapeutic efficacy, potency, immunogenicity, and clearance. MAb micro-heterogeneity can result from post-translational modifications such as sialylation, galactosylation, C-terminal lysine cleavage, glycine amidation, and tryptophan oxidation, each of which can generate MAb charge variants; such heterogeneity can affect pharmacokinetics (PK) considerably. Implementation of appropriate on-line quality control strategies may help to regulate bioprocesses, thus enabling more homogenous material with desired post-translational modifications and PK behavior. However, one major restriction to implementation of quality control strategies is the availability of techniques for obtaining on-line or at-line measurements of these attributes. In this work, we describe the development of an at-line assay to separate MAb charge variants in near real-time, which could ultimately be used to implement on-line quality control strategies for MAb production. The assay consists of a 2D-HPLC method with sequential in-line Protein A and WCX-10 HPLC column steps. To perform the 2D-HPLC assay at-line, the two columns steps were integrated into a single method using a novel system configuration that allowed parallel flow over column 1 or column 2 or sequential flow from column 1 to column 2. A bioreactor system was also developed such that media samples could be removed automatically from bioreactor vessels during production and delivered to the 2D-HPLC for analysis. With this at-line HPLC assay, we have demonstrated that MAb microheterogeneity occurs throughout the cell cycle whether the host cell line is grown under different or the same nominal culture conditions. © 2013 American Institute of Chemical Engineers.

  1. Anti-NKG2D mAb

    DEFF Research Database (Denmark)

    Vadstrup, Kasper; Bendtsen, Flemming

    2017-01-01

    with a wide range of cell types and proteins involved. Natural Killer Group 2D (NKG2D) is an activating receptor constitutively expressed on human Natural Killer (NK), γδ T, mucosal-associated invariant T (MAIT), CD56⁺ T, and CD8⁺ T cells. Activation of NKG2D triggers cellular proliferation, cytokine...... production, and target cell killing. Research into the NKG2D mechanism of action has primarily been focused on cancer and viral infections where cytotoxicity evasion is a concern. In human inflammatory bowel disease (IBD) this system is less characterized, but the ligands have been shown to be highly...... expressed during intestinal inflammation and the following receptor activation may contribute to tissue degeneration. A recent phase II clinical trial showed that an antibody against NKG2D induced clinical remission of CD in some patients, suggesting NKG2D and its ligands to be of importance...

  2. Anti-GD2 mAb and Vorinostat synergize in the treatment of neuroblastoma

    NARCIS (Netherlands)

    Kroesen, M.; Bull, C.; Gielen, P.R.; Brok, I.C.; Armandari, I.; Wassink, M.; Looman, M.W.G.; Boon, L.; Brok, M.H.M.G.M. den; Hoogerbrugge, P.M.; Adema, G.J.

    2016-01-01

    Neuroblastoma (NBL) is a childhood malignancy of the sympathetic nervous system. For high-risk NBL patients, the mortality rate is still over 50%, despite intensive multimodal treatment. Anti-GD2 monoclonal antibody (mAB) in combination with systemic cytokine immunotherapy has shown clinical

  3. Multicapillary SDS-gel electrophoresis for the analysis of fluorescently labeled mAb preparations: a high throughput quality control process for the production of QuantiPlasma and PlasmaScan mAb libraries.

    Science.gov (United States)

    Székely, Andrea; Szekrényes, Akos; Kerékgyártó, Márta; Balogh, Attila; Kádas, János; Lázár, József; Guttman, András; Kurucz, István; Takács, László

    2014-08-01

    Molecular heterogeneity of mAb preparations is the result of various co- and post-translational modifications and to contaminants related to the production process. Changes in molecular composition results in alterations of functional performance, therefore quality control and validation of therapeutic or diagnostic protein products is essential. A special case is the consistent production of mAb libraries (QuantiPlasma™ and PlasmaScan™) for proteome profiling, quality control of which represents a challenge because of high number of mAbs (>1000). Here, we devise a generally applicable multicapillary SDS-gel electrophoresis process for the analysis of fluorescently labeled mAb preparations for the high throughput quality control of mAbs of the QuantiPlasma™ and PlasmaScan™ libraries. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Production and characterization of monoclonal antibodies (mAbs) against human serum albumin (HSA) for the development of an immunoaffinity system with oriented anti-HSA mAbs as immobilized ligand.

    Science.gov (United States)

    Rajak, Poonam; Vijayalakshmi, M A; Jayaprakash, N S

    2013-05-05

    Proteins present in human serum are of immense importance in the field of biomarker discovery. But, the presence of high-abundant proteins like albumin makes the analysis more challenging because of masking effect on low-abundant proteins. Therefore, removal of albumin using highly specific monoclonal antibodies (mAbs) can potentiate the discovery of low-abundant proteins. In the present study, mAbs against human serum albumin (HSA) were developed and integrated in to an immunoaffinity based system for specific removal of albumin from the serum. Hybridomas were obtained by fusion of Sp2/0 mouse myeloma cells with spleen cells from the mouse immunized with HSA. Five clones (AHSA1-5) producing mAbs specific to HSA were established and characterized by enzyme linked immunosorbent assay (ELISA) and immunoblotting for specificity, sensitivity and affinity in terms of antigen binding. The mAbs were able to bind to both native albumin as well as its glycated isoform. Reactivity of mAbs with different mammalian sera was tested. The affinity constant of the mAbs ranged from 10(8) to 10(9)M(-1). An approach based on oriented immobilization was followed to immobilize purified anti-HSA mAbs on hydrazine activated agarose gel and the dynamic binding capacity of the column was determined. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Germline-specific MATH-BTB substrate adaptor MAB1 regulates spindle length and nuclei identity in maize.

    Science.gov (United States)

    Juranič, Martina; Srilunchang, Kanok-orn; Krohn, Nádia Graciele; Leljak-Levanic, Dunja; Sprunck, Stefanie; Dresselhaus, Thomas

    2012-12-01

    Germline and early embryo development constitute ideal model systems to study the establishment of polarity, cell identity, and asymmetric cell divisions (ACDs) in plants. We describe here the function of the MATH-BTB domain protein MAB1 that is exclusively expressed in the germ lineages and the zygote of maize (Zea mays). mab1 (RNA interference [RNAi]) mutant plants display chromosome segregation defects and short spindles during meiosis that cause insufficient separation and migration of nuclei. After the meiosis-to-mitosis transition, two attached nuclei of similar identity are formed in mab1 (RNAi) mutants leading to an arrest of further germline development. Transient expression studies of MAB1 in tobacco (Nicotiana tabacum) Bright Yellow-2 cells revealed a cell cycle-dependent nuclear localization pattern but no direct colocalization with the spindle apparatus. MAB1 is able to form homodimers and interacts with the E3 ubiquitin ligase component Cullin 3a (CUL3a) in the cytoplasm, likely as a substrate-specific adapter protein. The microtubule-severing subunit p60 of katanin was identified as a candidate substrate for MAB1, suggesting that MAB1 resembles the animal key ACD regulator Maternal Effect Lethal 26 (MEL-26). In summary, our findings provide further evidence for the importance of posttranslational regulation for asymmetric divisions and germline progression in plants and identified an unstable key protein that seems to be involved in regulating the stability of a spindle apparatus regulator(s).

  6. Germline-Specific MATH-BTB Substrate Adaptor MAB1 Regulates Spindle Length and Nuclei Identity in Maize[W

    Science.gov (United States)

    Juranić, Martina; Srilunchang, Kanok-orn; Krohn, Nádia Graciele; Leljak-Levanić, Dunja; Sprunck, Stefanie; Dresselhaus, Thomas

    2012-01-01

    Germline and early embryo development constitute ideal model systems to study the establishment of polarity, cell identity, and asymmetric cell divisions (ACDs) in plants. We describe here the function of the MATH-BTB domain protein MAB1 that is exclusively expressed in the germ lineages and the zygote of maize (Zea mays). mab1 (RNA interference [RNAi]) mutant plants display chromosome segregation defects and short spindles during meiosis that cause insufficient separation and migration of nuclei. After the meiosis-to-mitosis transition, two attached nuclei of similar identity are formed in mab1 (RNAi) mutants leading to an arrest of further germline development. Transient expression studies of MAB1 in tobacco (Nicotiana tabacum) Bright Yellow-2 cells revealed a cell cycle–dependent nuclear localization pattern but no direct colocalization with the spindle apparatus. MAB1 is able to form homodimers and interacts with the E3 ubiquitin ligase component Cullin 3a (CUL3a) in the cytoplasm, likely as a substrate-specific adapter protein. The microtubule-severing subunit p60 of katanin was identified as a candidate substrate for MAB1, suggesting that MAB1 resembles the animal key ACD regulator Maternal Effect Lethal 26 (MEL-26). In summary, our findings provide further evidence for the importance of posttranslational regulation for asymmetric divisions and germline progression in plants and identified an unstable key protein that seems to be involved in regulating the stability of a spindle apparatus regulator(s). PMID:23250449

  7. H2Mab-77 is a Sensitive and Specific Anti-HER2 Monoclonal Antibody Against Breast Cancer.

    Science.gov (United States)

    Itai, Shunsuke; Fujii, Yuki; Kaneko, Mika K; Yamada, Shinji; Nakamura, Takuro; Yanaka, Miyuki; Saidoh, Noriko; Chang, Yao-Wen; Handa, Saori; Takahashi, Maki; Suzuki, Hiroyoshi; Harada, Hiroyuki; Kato, Yukinari

    2017-08-01

    Human epidermal growth factor receptor 2 (HER2) plays a critical role in the progression of breast cancers, and HER2 overexpression is associated with poor clinical outcomes. Trastuzumab is an anti-HER2 humanized antibody that leads to significant survival benefits in patients with HER2-positive metastatic breast cancers. In this study, we developed novel anti-HER2 monoclonal antibodies (mAbs) and characterized their efficacy in flow cytometry, Western blot, and immunohistochemical analyses. Initially, we expressed the full length or ectodomain of HER2 in LN229 glioblastoma cells and then immunized mice with ectodomain of HER2 or LN229/HER2, and performed the first screening by enzyme-linked immunosorbent assays using ectodomain of HER2. Subsequently, we selected mAbs according to their efficacy in flow cytometry (second screening), Western blot (third screening), and immunohistochemical analyses (fourth screening). Among 100 mAb clones, only three mAbs reacted with HER2 in Western blot, and clone H 2 Mab-77 (IgG 1 , kappa) was selected. Finally, immunohistochemical analyses with H 2 Mab-77 showed sensitive and specific reactions against breast cancer cells, warranting the use of H 2 Mab-77 to detect HER2 in pathological analyses of breast cancers.

  8. Administration of anti-CD25 mAb leads to impaired alpha-galactosylceramide-mediated induction of IFN-gamma production in a murine model

    Czech Academy of Sciences Publication Activity Database

    Rosalia, Rodney Alexander; Štěpánek, Ivan; Polláková, Veronika; Šímová, Jana; Bieblová, Jana; Indrová, Marie; Moravcová, Simona; Přibylová, Hana; Bontkes, H.; Bubeník, Jan; Sparwasser, T.; Reiniš, Milan

    2013-01-01

    Roč. 218, č. 6 (2013), s. 851-859 ISSN 0171-2985 R&D Projects: GA ČR GA301/07/1410; GA ČR GAP301/10/2174 Institutional research plan: CEZ:AV0Z50520514 Institutional support: RVO:68378050 Keywords : cancer immunotherapy * DEREG mice * interferon γ * natural killer T cells * PC61 monoclonal antibody * T regulatory cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.180, year: 2013

  9. TGF-beta Sma/Mab signaling mutations uncouple reproductive aging from somatic aging.

    Directory of Open Access Journals (Sweden)

    Shijing Luo

    2009-12-01

    Full Text Available Female reproductive cessation is one of the earliest age-related declines humans experience, occurring in mid-adulthood. Similarly, Caenorhabditis elegans' reproductive span is short relative to its total life span, with reproduction ceasing about a third into its 15-20 day adulthood. All of the known mutations and treatments that extend C. elegans' reproductive period also regulate longevity, suggesting that reproductive span is normally linked to life span. C. elegans has two canonical TGF-beta signaling pathways. We recently found that the TGF-beta Dauer pathway regulates longevity through the Insulin/IGF-1 Signaling (IIS pathway; here we show that this pathway has a moderate effect on reproductive span. By contrast, TGF-beta Sma/Mab signaling mutants exhibit a substantially extended reproductive period, more than doubling reproductive span in some cases. Sma/Mab mutations extend reproductive span disproportionately to life span and act independently of known regulators of somatic aging, such as Insulin/IGF-1 Signaling and Dietary Restriction. This is the first discovery of a pathway that regulates reproductive span independently of longevity and the first identification of the TGF-beta Sma/Mab pathway as a regulator of reproductive aging. Our results suggest that longevity and reproductive span regulation can be uncoupled, although they appear to normally be linked through regulatory pathways.

  10. ChLpMab-23: Cancer-Specific Human-Mouse Chimeric Anti-Podoplanin Antibody Exhibits Antitumor Activity via Antibody-Dependent Cellular Cytotoxicity.

    Science.gov (United States)

    Kaneko, Mika K; Nakamura, Takuro; Kunita, Akiko; Fukayama, Masashi; Abe, Shinji; Nishioka, Yasuhiko; Yamada, Shinji; Yanaka, Miyuki; Saidoh, Noriko; Yoshida, Kanae; Fujii, Yuki; Ogasawara, Satoshi; Kato, Yukinari

    2017-06-01

    Podoplanin is expressed in many cancers, including oral cancers and brain tumors. The interaction between podoplanin and its receptor C-type lectin-like receptor 2 (CLEC-2) has been reported to be involved in cancer metastasis and tumor malignancy. We previously established many monoclonal antibodies (mAbs) against human podoplanin using the cancer-specific mAb (CasMab) technology. LpMab-23 (IgG 1 , kappa), one of the mouse anti-podoplanin mAbs, was shown to be a CasMab. However, we have not shown the usefulness of LpMab-23 for antibody therapy against podoplanin-expressing cancers. In this study, we first determined the minimum epitope of LpMab-23 and revealed that Gly54-Leu64 peptide, especially Gly54, Thr55, Ser56, Glu57, Asp58, Arg59, Tyr60, and Leu64 of podoplanin, is a critical epitope of LpMab-23. We further produced human-mouse chimeric LpMab-23 (chLpMab-23) and investigated whether chLpMab-23 exerts antibody-dependent cellular cytotoxicity (ADCC) and antitumor activity. In flow cytometry, chLpMab-23 showed high sensitivity against a podoplanin-expressing glioblastoma cell line, LN319, and an oral cancer cell line, HSC-2. chLpMab-23 also showed ADCC activity against podoplanin-expressing CHO cells (CHO/podoplanin). In xenograft models with HSC-2 and CHO/podoplanin, chLpMab-23 exerts antitumor activity using human natural killer cells, indicating that chLpMab-23 could be useful for antibody therapy against podoplanin-expressing cancers.

  11. Antiglycopeptide Mouse Monoclonal Antibody LpMab-21 Exerts Antitumor Activity Against Human Podoplanin Through Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity.

    Science.gov (United States)

    Kato, Yukinari; Kunita, Akiko; Fukayama, Masashi; Abe, Shinji; Nishioka, Yasuhiko; Uchida, Hiroaki; Tahara, Hideaki; Yamada, Shinji; Yanaka, Miyuki; Nakamura, Takuro; Saidoh, Noriko; Yoshida, Kanae; Fujii, Yuki; Honma, Ryusuke; Takagi, Michiaki; Ogasawara, Satoshi; Murata, Takeshi; Kaneko, Mika K

    2017-02-01

    The interaction between podoplanin (PDPN) and C-type lectin-like receptor 2 (CLEC-2) is involved in tumor malignancy. We have established many monoclonal antibodies (mAbs) against human podoplanin using the cancer-specific mAb (CasMab) technology. LpMab-21, one of the mouse antipodoplanin mAbs, is of the IgG 2a subclass, and its minimum epitope was determined to be Thr76-Arg79 of the human podoplanin. Importantly, sialic acid is linked to Thr76; therefore, LpMab-21 is an antiglycopeptide mAb (GpMab). In this study, we investigated whether LpMab-21 shows antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against human podoplanin-expressing cancer cell lines in vitro and also studied its antitumor activities using a xenograft model. LpMab-21 showed high ADCC and CDC activities against not only podoplanin-expressing Chinese hamster ovary cells but also LN319 glioblastoma cells and PC-10 lung cancer cells, both of which endogenously express podoplanin. Furthermore, LpMab-21 decreased tumor growth in vivo, indicating that LpMab-21 could be useful for antibody therapy against human podoplanin-expressing cancers.

  12. In vitro and in vivo comparison of binding of 99m-Tc-labeled anti-CEA MAb F33-104 with 99m-Tc-labeled anti-CEA MAb BW431/26

    International Nuclear Information System (INIS)

    Watanabe, N.; Gunma Univ. School of Medicine; Oriuchi, N.; Inoue, T.; Sugiyama, S.; Kuroki, M.; Matsuoka, Y.; Tanada, S.; Murata, H.; Sasaki, Y.

    1999-01-01

    Aim: The purpose of this study was to assess the potential for radioimmunodetection (RAID) of murine anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb) F33-104 labeled with technetium-99m (99m-Tc) by a reduction-mediated labeling method. Methods: The binding capacity of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA by means of in vitro procedures such as immunoradiometric assay and cell binding assay and the biodistribution of 99m-Tc-labeled anti-CEA MAb F33-104 in normal nude mice and nude mice bearing human colon adenocarcinoma LS180 tumor were investigated and compared with 99m-Tc-labeled anti-CEA MAb BW431/26. Results: The in vitro binding rate of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA in solution and attached to the cell membrane was significantly higher than 99m-Tc-labeled anti-CEA MAb BW431/261 (31.4 ± 0.95% vs. 11.9 ± 0.55% at 100 ng/mL of soluble CEA, 83.5 ± 2.84% vs. 54.0 ± 2.54% at 10 7 of LS 180 cells). In vivo, accumulation of 99m-Tc-labeled anti-CEA MAb F33-104 was higher at 18 h postinjection than 99m-Tc-labeled anti-CEA MAb BW431/26 (20.1 ± 3.50% ID/g vs. 14.4 ± 3.30% ID/g). 99m-Tc-activity in the kidneys of nude mice bearing tumor was higher at 18 h postinjection than at 3 h (12.8 ± 2.10% ID/g vs. 8.01 ± 2.40% ID/g of 99m-Tc-labeled anti-CEA MAb F33-104, 10.7 ± 1.70% ID/g vs. 8.10 ± 1.75% ID/g of 99m-Tc-labeled anti-CEA MAb BW431/26). Conclusion: 99m-Tc-labeled anti-CEA MAb F33-104 is a potential novel agent for RAID of recurrent colorectal cancer. (orig.) [de

  13. Detection of high PD-L1 expression in oral cancers by a novel monoclonal antibody L1Mab-4.

    Science.gov (United States)

    Yamada, Shinji; Itai, Shunsuke; Kaneko, Mika K; Kato, Yukinari

    2018-03-01

    Programmed cell death-ligand 1 (PD-L1), which is a ligand of programmed cell death-1 (PD-1), is a type I transmembrane glycoprotein that is expressed on antigen-presenting cells and several tumor cells, including melanoma and lung cancer cells. There is a strong correlation between human PD-L1 (hPD-L1) expression on tumor cells and negative prognosis in cancer patients. In this study, we produced a novel anti-hPD-L1 monoclonal antibody (mAb), L 1 Mab-4 (IgG 2b , kappa), using cell-based immunization and screening (CBIS) method and investigated hPD-L1 expression in oral cancers. L 1 Mab-4 reacted with oral cancer cell lines (Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4) in flow cytometry and stained oral cancers in a membrane-staining pattern. L 1 Mab-4 stained 106/150 (70.7%) of oral squamous cell carcinomas, indicating the very high sensitivity of L 1 Mab-4. These results indicate that L 1 Mab-4 could be useful for investigating the function of hPD-L1 in oral cancers.

  14. Detection of high PD-L1 expression in oral cancers by a novel monoclonal antibody L1Mab-4

    Directory of Open Access Journals (Sweden)

    Shinji Yamada

    2018-03-01

    Full Text Available Programmed cell death-ligand 1 (PD-L1, which is a ligand of programmed cell death-1 (PD-1, is a type I transmembrane glycoprotein that is expressed on antigen-presenting cells and several tumor cells, including melanoma and lung cancer cells. There is a strong correlation between human PD-L1 (hPD-L1 expression on tumor cells and negative prognosis in cancer patients. In this study, we produced a novel anti-hPD-L1 monoclonal antibody (mAb, L1Mab-4 (IgG2b, kappa, using cell-based immunization and screening (CBIS method and investigated hPD-L1 expression in oral cancers. L1Mab-4 reacted with oral cancer cell lines (Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4 in flow cytometry and stained oral cancers in a membrane-staining pattern. L1Mab-4 stained 106/150 (70.7% of oral squamous cell carcinomas, indicating the very high sensitivity of L1Mab-4. These results indicate that L1Mab-4 could be useful for investigating the function of hPD-L1 in oral cancers. Keywords: Programmed cell death-ligand 1, Monoclonal antibody, Oral cancer

  15. Establishment of H2Mab-119, an Anti-Human Epidermal Growth Factor Receptor 2 Monoclonal Antibody, Against Pancreatic Cancer.

    Science.gov (United States)

    Yamada, Shinji; Itai, Shunsuke; Nakamura, Takuro; Chang, Yao-Wen; Harada, Hiroyuki; Suzuki, Hiroyoshi; Kaneko, Mika K; Kato, Yukinari

    2017-12-01

    Human epidermal growth factor receptor 2 (HER2) is overexpressed in breast cancer and is associated with poor clinical outcomes. In addition, HER2 expression has been reported in other cancers, such as gastric, colorectal, lung, and pancreatic cancers. An anti-HER2 humanized antibody, trastuzumab, leads to significant survival benefits in patients with HER2-overexpressing breast cancers and gastric cancers. Herein, we established a novel anti-HER2 monoclonal antibody (mAb), H 2 Mab-119 (IgG 1 , kappa), and characterized its efficacy against pancreatic cancers using flow cytometry, Western blot, and immunohistochemical analyses. H 2 Mab-119 reacted with pancreatic cancer cell lines, such as KLM-1, Capan-2, and MIA PaCa-2, but did not react with PANC-1 in flow cytometry analysis. Western blot analysis also revealed a moderate signal for KLM-1 and a weak signal for MIA PaCa-2, although H 2 Mab-119 reacted strongly with LN229/HER2 cells. Finally, immunohistochemical analyses with H 2 Mab-119 revealed sensitive and specific reactions against breast and colon cancers but did not react with pancreatic cancers, indicating that H 2 Mab-119 is useful for detecting HER2 overexpression in pancreatic cancers using flow cytometry and Western blot analyses.

  16. Glucosidase trimming inhibitors preferentially perturb T cell activation induced by CD2 mAb

    NARCIS (Netherlands)

    van Kemenade, F. J.; Rotteveel, F. T.; van den Broek, L. A.; Baars, P. A.; van Lier, R. A.; Miedema, F.

    1994-01-01

    Glycosidase trimming inhibitors may be used to study contribution of N-linked glycan moieties in T cell function. We have studied the effects of castanospermine (Cas), swainsonine (Swain), 1-deoxynojirimycin (dNM), and 1-deoxymannojirimycin (dMM) on T cell activation and differentiation. Our

  17. Technical Note: PLASTIMATCH MABS, an open source tool for automatic image segmentation

    International Nuclear Information System (INIS)

    Zaffino, Paolo; Spadea, Maria Francesca; Raudaschl, Patrik; Fritscher, Karl; Sharp, Gregory C.

    2016-01-01

    Purpose: Multiatlas based segmentation is largely used in many clinical and research applications. Due to its good performances, it has recently been included in some commercial platforms for radiotherapy planning and surgery guidance. Anyway, to date, a software with no restrictions about the anatomical district and image modality is still missing. In this paper we introduce PLASTIMATCH MABS, an open source software that can be used with any image modality for automatic segmentation. Methods: PLASTIMATCH MABS workflow consists of two main parts: (1) an offline phase, where optimal registration and voting parameters are tuned and (2) an online phase, where a new patient is labeled from scratch by using the same parameters as identified in the former phase. Several registration strategies, as well as different voting criteria can be selected. A flexible atlas selection scheme is also available. To prove the effectiveness of the proposed software across anatomical districts and image modalities, it was tested on two very different scenarios: head and neck (H&N) CT segmentation for radiotherapy application, and magnetic resonance image brain labeling for neuroscience investigation. Results: For the neurological study, minimum dice was equal to 0.76 (investigated structures: left and right caudate, putamen, thalamus, and hippocampus). For head and neck case, minimum dice was 0.42 for the most challenging structures (optic nerves and submandibular glands) and 0.62 for the other ones (mandible, brainstem, and parotid glands). Time required to obtain the labels was compatible with a real clinical workflow (35 and 120 min). Conclusions: The proposed software fills a gap in the multiatlas based segmentation field, since all currently available tools (both for commercial and for research purposes) are restricted to a well specified application. Furthermore, it can be adopted as a platform for exploring MABS parameters and as a reference implementation for comparing against

  18. Technical Note: PLASTIMATCH MABS, an open source tool for automatic image segmentation

    Energy Technology Data Exchange (ETDEWEB)

    Zaffino, Paolo; Spadea, Maria Francesca [Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, Catanzaro 88100 (Italy); Raudaschl, Patrik; Fritscher, Karl [Institute for Biomedical Image Analysis, Private University of Health Sciences, Medical Informatics and Technology, Hall in Tirol 6060 (Austria); Sharp, Gregory C. [Department for Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114 (United States)

    2016-09-15

    Purpose: Multiatlas based segmentation is largely used in many clinical and research applications. Due to its good performances, it has recently been included in some commercial platforms for radiotherapy planning and surgery guidance. Anyway, to date, a software with no restrictions about the anatomical district and image modality is still missing. In this paper we introduce PLASTIMATCH MABS, an open source software that can be used with any image modality for automatic segmentation. Methods: PLASTIMATCH MABS workflow consists of two main parts: (1) an offline phase, where optimal registration and voting parameters are tuned and (2) an online phase, where a new patient is labeled from scratch by using the same parameters as identified in the former phase. Several registration strategies, as well as different voting criteria can be selected. A flexible atlas selection scheme is also available. To prove the effectiveness of the proposed software across anatomical districts and image modalities, it was tested on two very different scenarios: head and neck (H&N) CT segmentation for radiotherapy application, and magnetic resonance image brain labeling for neuroscience investigation. Results: For the neurological study, minimum dice was equal to 0.76 (investigated structures: left and right caudate, putamen, thalamus, and hippocampus). For head and neck case, minimum dice was 0.42 for the most challenging structures (optic nerves and submandibular glands) and 0.62 for the other ones (mandible, brainstem, and parotid glands). Time required to obtain the labels was compatible with a real clinical workflow (35 and 120 min). Conclusions: The proposed software fills a gap in the multiatlas based segmentation field, since all currently available tools (both for commercial and for research purposes) are restricted to a well specified application. Furthermore, it can be adopted as a platform for exploring MABS parameters and as a reference implementation for comparing against

  19. Russian biosphere reserves at the youth MAB-2017 Forum in Italy

    Directory of Open Access Journals (Sweden)

    Elena A. Shuyskaya

    2018-02-01

    Full Text Available Russia was represented by 9 participants from Biosphere Reserves at the MAB Youth Forum in Italy. The main question of the Forum was «How to involve the young in the work of biosphere reserves?» The debate resulted in a Declaration, elaborated by participants from around the world (282 delegates from 85 countries. Measures to improve scientific cooperation, data exchange in the sphere of educational tourism and administrative management, development of joint projects in environmental education were formulated. The article contains a number of recommendations for the network of biosphere reserves in Russia, based on Seville strategy and Lima Action Plan.

  20. Identification and quantification of predominant metabolites of synthetic cannabinoid MAB-CHMINACA in an authentic human urine specimen.

    Science.gov (United States)

    Hasegawa, Koutaro; Minakata, Kayoko; Gonmori, Kunio; Nozawa, Hideki; Yamagishi, Itaru; Watanabe, Kanako; Suzuki, Osamu

    2018-02-01

    An autopsy case in which the cause of death was judged as drug poisoning by two synthetic cannabinoids, including MAB-CHMINACA, was investigated. Although unchanged MAB-CHMINACA could be detected from solid tissues, blood and stomach contents in the case, the compound could not be detected from a urine specimen. We obtained six kinds of reference standards of MAB-CHMINACA metabolites from a commercial source. The MAB-CHMINACA metabolites from the urine specimen of the abuser were extracted using a QuEChERS method including dispersive solid-phase extraction, and analyzed by liquid chromatography-tandem mass spectrometry with or without hydrolysis with β-glucuronidase. Among the six MAB-CHMINACA metabolites tested, two predominant metabolites could be identified and quantified in the urine specimen of the deceased. After hydrolysis with β-glucuronidase, an increase of the two metabolites was not observed. The metabolites detected were a 4-monohydroxycyclohexylmethyl metabolite M1 (N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-((4-hydroxycyclohexyl)methyl)-1H-indazole-3-carboxamide) and a dihydroxyl (4-hydroxycyclohexylmethyl and tert-butylhydroxyl) metabolite M11 (N-(1-amino-4-hydroxy-3,3-dimethyl-1-oxobutan-2-yl)-1-((4-hydroxycyclohexyl)methyl)-1H-indazole-3-carboxamide). Their concentrations were 2.17 ± 0.15 and 10.2 ± 0.3 ng/mL (n = 3, each) for M1 and M11, respectively. Although there is one previous in vitro study showing the estimation of metabolism of MAB-CHMINACA using human hepatocytes, this is the first report dealing with in vivo identification and quantification of MAB-CHMINACA metabolites in an authentic human urine specimen. Copyright © 2017 John Wiley & Sons, Ltd.

  1. Experimental Treatment of Bladder Cancer with Bi-213-anti-EGFR MAb

    International Nuclear Information System (INIS)

    Seidl, Christof; Pfost, Birgit; Müller, Felix

    2013-01-01

    Therapy of non-muscle-invasive bladder cancer (carcinoma in situ) comprises transurethral resection of the tumour and subsequent instillation of the chemotherapeutic drug mitomycin C in order to eradicate remaining tumour cells. Yet 15 – 40% of treated patients relapse within 5 years. Therefore, new therapeutic strategies to combat tumour recurrence are needed. Alpha-particle emitting radionuclides efficiently kill single tumour cells or small tumour cell clusters. Because the epidermal growth factor receptor (EGFR) is overexpressed on bladder cancer cells, conjugates composed of the alpha-emitter Bi-213 and the anti-EGFR antibody matuzumab should provide a powerful drug to eliminate disseminated bladder cancer cells. Therefore, the aims of our study were (i) to analyse the cytotoxic effects of Bi-213-anti-EGFR radioimmunoconjugates at the cellular level, (ii) to evaluate therapeutic efficacy of intravesically applied Bi-213- anti-EGFR-Mab in a nude mouse model with intravesical human bladder cancer xenografts, (iii) to compare Bi- 213-anti-EGFR-Mab efficacy with chemotherapy using mitomycin C and (iv) to demonstrate that radioimmunotherapy is not toxic to cells of the bladder wall and of the kidneys

  2. Detection of high CD44 expression in oral cancers using the novel monoclonal antibody, C44Mab-5

    Directory of Open Access Journals (Sweden)

    Shinji Yamada

    2018-07-01

    Full Text Available CD44 is a transmembrane glycoprotein that regulates a variety of genes related to cell-adhesion, migration, proliferation, differentiation, and survival. A large number of alternative splicing isoforms of CD44, containing various combinations of alternative exons, have been reported. CD44 standard (CD44s, which lacks variant exons, is widely expressed on the surface of most tissues and all hematopoietic cells. In contrast, CD44 variant isoforms show tissue-specific expression patterns and have been extensively studied as both prognostic markers and therapeutic targets in cancer and other diseases. In this study, we immunized mice with CHO-K1 cell lines overexpressing CD44v3-10 to obtain novel anti-CD44 mAbs. One of the clones, C44Mab-5 (IgG1, kappa, recognized both CD44s and CD44v3-10. C44Mab-5 also reacted with oral cancer cells such as Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4 using flow cytometry. Moreover, immunohistochemical analysis revealed that C44Mab-5 detected 166/182 (91.2% of oral cancers. These results suggest that the C44Mab-5 antibody may be useful for investigating the expression and function of CD44 in various cancers.

  3. Detection of high CD44 expression in oral cancers using the novel monoclonal antibody, C44Mab-5.

    Science.gov (United States)

    Yamada, Shinji; Itai, Shunsuke; Nakamura, Takuro; Yanaka, Miyuki; Kaneko, Mika K; Kato, Yukinari

    2018-07-01

    CD44 is a transmembrane glycoprotein that regulates a variety of genes related to cell-adhesion, migration, proliferation, differentiation, and survival. A large number of alternative splicing isoforms of CD44, containing various combinations of alternative exons, have been reported. CD44 standard (CD44s), which lacks variant exons, is widely expressed on the surface of most tissues and all hematopoietic cells. In contrast, CD44 variant isoforms show tissue-specific expression patterns and have been extensively studied as both prognostic markers and therapeutic targets in cancer and other diseases. In this study, we immunized mice with CHO-K1 cell lines overexpressing CD44v3-10 to obtain novel anti-CD44 mAbs. One of the clones, C 44 Mab-5 (IgG 1 , kappa), recognized both CD44s and CD44v3-10. C 44 Mab-5 also reacted with oral cancer cells such as Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4 using flow cytometry. Moreover, immunohistochemical analysis revealed that C 44 Mab-5 detected 166/182 (91.2%) of oral cancers. These results suggest that the C 44 Mab-5 antibody may be useful for investigating the expression and function of CD44 in various cancers.

  4. Immunohistochemical Analysis Using Antipodocalyxin Monoclonal Antibody PcMab-47 Demonstrates Podocalyxin Expression in Oral Squamous Cell Carcinomas.

    Science.gov (United States)

    Itai, Shunsuke; Yamada, Shinji; Kaneko, Mika K; Harada, Hiroyuki; Kato, Yukinari

    2017-10-01

    Podocalyxin is a CD34-related type I transmembrane protein that is highly glycosylated with N-glycan, O-glycan, and keratan sulfate. Podocalyxin was originally found in the podocytes of rat kidney and is reportedly expressed in many types of tumors, including brain tumors, colorectal cancers, and breast cancers. Overexpression of podocalyxin is an independent predictor of progression, metastasis, and poor outcome. We recently immunized mice with recombinant human podocalyxin, which was produced using LN229 glioblastoma cells, and produced a novel antipodocalyxin monoclonal antibody (mAb), PcMab-47, which reacts with endogenous podocalyxin-expressing cancer cell lines and normal cell lines independent of glycosylation in Western blot, flow cytometry, and immunohistochemical analyses. In this study, we performed immunohistochemical analysis against oral cancers using PcMab-47. PcMab-47-stained oral squamous cell carcinoma cells in a cytoplasmic pattern and detected 26/38 (68.4%) of oral squamous cell carcinoma cells on tissue microarrays. These results indicate that PcMab-47 is useful in detecting podocalyxin of oral cancers for immunohistochemical analysis.

  5. Monoclonal antibody proteomics: use of antibody mimotope displaying phages and the relevant synthetic peptides for mAb scouting.

    Science.gov (United States)

    Hajdú, István; Flachner, Beáta; Bognár, Melinda; Végh, Barbara M; Dobi, Krisztina; Lőrincz, Zsolt; Lázár, József; Cseh, Sándor; Takács, László; Kurucz, István

    2014-08-01

    Monoclonal antibody proteomics uses nascent libraries or cloned (Plasmascan™, QuantiPlasma™) libraries of mAbs that react with individual epitopes of proteins in the human plasma. At the initial phase of library creation, cognate protein antigen and the epitope interacting with the antibodies are not known. Scouting for monoclonal antibodies (mAbs) with the best binding characteristics is of high importance for mAb based biomarker assay development. However, in the absence of the identity of the cognate antigen the task represents a challenge. We combined phage display, and surface plasmon resonance (Biacore) experiments to test whether specific phages and the respective mimotope peptides obtained from large scale studies are applicable to determine key features of antibodies for scouting. We show here that mAb captured phage-mimotope heterogeneity that is the diversity of the selected peptide sequences, is inversely correlated with an important binding descriptor; the off-rate of the antibodies and that represents clues for driving the selection of useful mAbs for biomarker assay development. Carefully chosen synthetic mimotope peptides are suitable for specificity testing in competitive assays using the target proteome, in our case the human plasma. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Structural rearrangements occurring upon cofactor binding in the Mycobacterium smegmatis β-ketoacyl-acyl carrier protein reductase MabA.

    Science.gov (United States)

    Küssau, Tanja; Flipo, Marion; Van Wyk, Niel; Viljoen, Albertus; Olieric, Vincent; Kremer, Laurent; Blaise, Mickaël

    2018-05-01

    In mycobacteria, the ketoacyl-acyl carrier protein (ACP) reductase MabA (designated FabG in other bacteria) catalyzes the NADPH-dependent reduction of β-ketoacyl-ACP substrates to β-hydroxyacyl-ACP products. This first reductive step in the fatty-acid biosynthesis elongation cycle is essential for bacteria, which makes MabA/FabG an interesting drug target. To date, however, very few molecules targeting FabG have been discovered and MabA remains the only enzyme of the mycobacterial type II fatty-acid synthase that lacks specific inhibitors. Despite the existence of several MabA/FabG crystal structures, the structural rearrangement that occurs upon cofactor binding is still not fully understood. Therefore, unlocking this knowledge gap could help in the design of new inhibitors. Here, high-resolution crystal structures of MabA from Mycobacterium smegmatis in its apo, NADP + -bound and NADPH-bound forms are reported. Comparison of these crystal structures reveals the structural reorganization of the lid region covering the active site of the enzyme. The crystal structure of the apo form revealed numerous residues that trigger steric hindrance to the binding of NADPH and substrate. Upon NADPH binding, these residues are pushed away from the active site, allowing the enzyme to adopt an open conformation. The transition from an NADPH-bound to an NADP + -bound form is likely to facilitate release of the product. These results may be useful for subsequent rational drug design and/or for in silico drug-screening approaches targeting MabA/FabG.

  7. Mobility field and mobility temperature dependence in PC61BM: A kinetic Monte-Carlo study

    Science.gov (United States)

    Sousa, Leonardo; Volpi, Riccardo; da Silva Filho, Demétrio Antônio; Linares, Mathieu

    2017-12-01

    A study of electron mobility in a PCBM system is performed by means of analytical considerations and Kinetic Monte Carlo simulations. Orbital energies are calculated at the ZINDO level of theory and successively corrected considering contributions from permanent charges and polarization interactions. The relative importance of these environmental effects is analyzed in details, furthermore the predicted mobilities are compared with experimental results and similar simulations performed in C60.

  8. Rapid desensitization of mice with anti-FcγRIIb/FcγRIII mAb safely prevents IgG-mediated anaphylaxis.

    Science.gov (United States)

    Khodoun, Marat V; Kucuk, Zeynep Yesim; Strait, Richard T; Krishnamurthy, Durga; Janek, Kevin; Clay, Corey D; Morris, Suzanne C; Finkelman, Fred D

    2013-12-01

    Stimulatory IgG receptors (FcγRs) on bone marrow-derived cells contribute to the pathogenesis of several autoimmune and inflammatory disorders. Monoclonal antibodies that block FcγRs might suppress these diseases, but they can induce anaphylaxis. We wanted to determine whether a rapid desensitization approach can safely suppress IgG/FcγR-mediated anaphylaxis. Mice were injected with serially increasing doses of 2.4G2, a rat mAb that blocks the inhibitory FcγR, FcγRIIb, and the stimulatory receptor, FcγRIII. Rectal temperature was used to detect the development of anaphylaxis. Passive and active IgG-mediated anaphylaxis were evaluated in mice that had been rapidly desensitized with 2.4G2 or mock-desensitized in mice in which monocyte/macrophages, basophils, or neutrophils had been depleted or desensitized and in mice in which FcγRI, FcγRIII, and/or FcγRIV had been deleted or blocked. Rapid desensitization with 2.4G2 prevented 2.4G2-induced shock and completely suppressed IgG-mediated anaphylaxis. Rapid desensitization of ovalbumin-sensitized mice with 2.4G2 was safer and more effective than rapid desensitization with ovalbumin. 2.4G2 treatment completely blocked FcγRIII and removed most FcγRI and FcγRIV from nucleated peripheral blood cells. Because IgG(2a)-mediated anaphylaxis was partially FcγRI and FcγRIV dependent, the effects of 2.4G2 on FcγRI and FcγRIV were probably crucial for its complete inhibition of IgG(2a)-mediated anaphylaxis. IgG(2a)-mediated anaphylaxis was partially inhibited by depletion or desensitization of monocyte/macrophages, basophils, or neutrophils. IgG-mediated anaphylaxis can be induced by ligation of FcγRI, FcγRIII, or FcγRIV on monocycte/macrophages, basophils, or neutrophils and can be safely suppressed by rapid desensitization with anti-FcγRII/RIII mAb. A similar approach may safely suppress other FcγR-dependent immunopathology. Published by Mosby, Inc.

  9. Production, Characterization and Antioxidant Potential of Protease from Streptomyces sp. MAB18 Using Poultry Wastes

    Directory of Open Access Journals (Sweden)

    Panchanathan Manivasagan

    2013-01-01

    Full Text Available Poultry waste is an abundant renewable source for the recovery of several value-added metabolites with potential industrial applications. This study describes the production of protease on poultry waste, with the subsequent use of the same poultry waste for the extraction of antioxidants. An extracellular protease-producing strain was isolated from Cuddalore coast, India, and identified as Streptomyces sp. MAB18. Its protease was purified 17.13-fold with 21.62% yield with a specific activity of 2398.36 U/mg and the molecular weight was estimated as 43 kDa. The enzyme was optimally active at pH 8–10 and temperature 50–60°C and it was most stable up to pH 12 and 6–12% of NaCl concentration. The enzyme activity was reduced when treated with Hg2+, Pb2+, and SDS and stimulated by Fe2+, Mg2+, Triton X-100, DMSO (dimethyl sulfoxide, sodium sulphite, and β-mercaptoethanol. Furthermore, the antioxidant activities of protease were evaluated using in vitro antioxidant assays, such as DPPH radical-scavenging activity, O2 scavenging activity, NO scavenging activity, Fe2+ chelating activity, and reducing power. The enzyme showed important antioxidant potential with an IC50 value of 78±0.28 mg/mL. Results of the present study indicate that the poultry waste-derived protease may be useful as supplementary protein and antioxidant in the animal feed formulations.

  10. 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.

  11. IL-2/anti-IL-2 mAb immunocomplexes: A renascence of IL-2 in cancer immunotherapy?

    Czech Academy of Sciences Publication Activity Database

    Tomala, Jakub; Kovář, Marek

    2016-01-01

    Roč. 5, č. 3 (2016), e1102829 ISSN 2162-402X R&D Projects: GA ČR GA13-12885S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61388971 Keywords : Anti-IL-2 mAb * cancer immunotherapy * IL-2 Subject RIV: EE - Microbiology, Virology Impact factor: 7.719, year: 2016

  12. Aree Protette del Po e della Collina Torinese: studi propedeutici alla Candidatura MAB - Man and the Biosphere

    Directory of Open Access Journals (Sweden)

    Cimnaghi Elisabetta

    2014-03-01

    Full Text Available Il programma MAB fu lanciato dall’UNESCO negli anni ’70 al fine di migliorare il rapporto tra uomo e ambiente. Negli anni il programma ha portato al riconoscimento di Riserve della Biosfera che gli Stati Membri si impegnano a gestire nella prospettiva della conservazione delle risorse. L’Organismo Gestore dell’Area Protetta, partendo, da un lato, dalla consapevolezza della ricchezza ambientale che caratterizza il suo territorio e, dall’altro, del contesto di sviluppo antropico elevato in cui essa è situata, ha riconosciuto nel programma MAB un’opportunità per incrementare le sue attività di protezione e potenziamento delle risorse. Questo articolo descrive i primi risultati ottenuti negli studi preliminari per la Designazione al MAB, con particolare attenzione sia alle opportunità di implementazione di progetti legati al marchio “Collina Po”, creato dall’Organo di Gestione del Parco, si ain termini di scambio di ‘best practices’ con altre Riserve di Biosfera.

  13. 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

  14. Inhibition of Helicobacter pylori CagA-Induced Pathogenesis by Methylantcinate B from Antrodia camphorata

    Directory of Open Access Journals (Sweden)

    Chun-Jung Lin

    2013-01-01

    Full Text Available The bacterial pathogen Helicobacter pylori (Hp is the leading risk factor for the development of gastric cancer. Hp virulence factor, cytotoxin-associated gene A (CagA interacted with cholesterol-enriched microdomains and leads to induction of inflammation in gastric epithelial cells (AGS. In this study, we identified a triterpenoid methylantcinate B (MAB from the medicinal mushroom Antrodia camphoratawhich inhibited the translocation and phosphorylation of CagA and caused a reduction in hummingbird phenotype in HP-infected AGS cells. Additionally, MAB suppressed the Hp-induced inflammatory response by attenuation of NF-κB activation, translocation of p65 NF-κB, and phosphorylation of IκB-α, indicating that MAB modulates CagA-mediated signaling pathway. Additionally, MAB also suppressed the IL-8 luciferase activity and its secretion in HP-infected AGS cells. On the other hand, molecular structure simulations revealed that MAB interacts with CagA similarly to that of cholesterol. Moreover, binding of cholesterol to the immobilized CagA was inhibited by increased levels of MAB. Our results demonstrate that MAB is the first natural triterpenoid which competes with cholesterol bound to CagA leading to attenuation of Hp-induced pathogenesis of epithelial cells. Thus, this study indicates that MAB may have a scope to develop as a therapeutic candidate against Hp CagA-induced inflammation.

  15. A fully human IgG1 anti-PD-L1 MAb in an in vitro assay enhances antigen-specific T-cell responses

    OpenAIRE

    Grenga, Italia; Donahue, Renee N; Lepone, Lauren M; Richards, Jacob; Schlom, Jeffrey

    2016-01-01

    Monoclonal antibodies (MAbs) that interfere with checkpoint molecules are being investigated for the treatment of infectious diseases and cancer, with the aim of enhancing the function of an impaired immune system. Avelumab (MSB0010718C) is a fully human IgG1 MAb targeting programmed death-ligand 1 (PD-L1), which differs from other checkpoint-blocking antibodies in its ability to mediate antibody-dependent cell-mediated cytotoxicity. These studies were conducted to define whether avelumab cou...

  16. A targeted complement-dependent strategy to improve the outcome of mAb therapy, and characterization in a murine model of metastatic cancer

    Science.gov (United States)

    Elvington, Michelle; Huang, Yuxiang; Morgan, B. Paul; Qiao, Fei; van Rooijen, Nico; Atkinson, Carl

    2012-01-01

    Complement inhibitors expressed on tumor cells provide an evasion mechanism against mAb therapy and may modulate the development of an acquired antitumor immune response. Here we investigate a strategy to amplify mAb-targeted complement activation on a tumor cell, independent of a requirement to target and block complement inhibitor expression or function, which is difficult to achieve in vivo. We constructed a murine fusion protein, CR2Fc, and demonstrated that the protein targets to C3 activation products deposited on a tumor cell by a specific mAb, and amplifies mAb-dependent complement activation and tumor cell lysis in vitro. In syngeneic models of metastatic lymphoma (EL4) and melanoma (B16), CR2Fc significantly enhanced the outcome of mAb therapy. Subsequent studies using the EL4 model with various genetically modified mice and macrophage-depleted mice revealed that CR2Fc enhanced the therapeutic effect of mAb therapy via both macrophage-dependent FcγR-mediated antibody-dependent cellular cytotoxicity, and by direct complement-mediated lysis. Complement activation products can also modulate adaptive immunity, but we found no evidence that either mAb or CR2Fc treatment had any effect on an antitumor humoral or cellular immune response. CR2Fc represents a potential adjuvant treatment to increase the effectiveness of mAb therapy of cancer. PMID:22442351

  17. Immuno-PET of undifferentiated thyroid carcinoma with radioiodine-labelled antibody cMAb U36: application to antibody tumour uptake studies

    Energy Technology Data Exchange (ETDEWEB)

    Fortin, Marc-Andre [Centre Hospitalier Universitaire de Quebec and Laval University, Laboratory for Biomaterials and Bioengineering, Quebec City (Canada); Uppsala University, Biomedical Radiation Sciences, Department of Oncology, Radiology, and Clinical Immunology, Rudbeck Laboratory, Uppsala (Sweden); Salnikov, Alexei V. [Uppsala University, BMC, Department of Medical Biochemistry and Microbiology, Uppsala (Sweden); German Cancer Research Center, Division of Molecular Immunology, Heidelberg (Germany); Nestor, Marika [Uppsala University, Division of Otolaryngology and Head and Neck Surgery, Department of Surgical Sciences, Uppsala (Sweden); Heldin, Nils-Erik [Uppsala University, Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala (Sweden); Rubin, Kristofer [Uppsala University, BMC, Department of Medical Biochemistry and Microbiology, Uppsala (Sweden); Lundqvist, Hans [Uppsala University, Biomedical Radiation Sciences, Department of Oncology, Radiology, and Clinical Immunology, Rudbeck Laboratory, Uppsala (Sweden)

    2007-09-15

    We tested the suitability of the chimeric monoclonal anti-human CD44 splice version 6 antibody (cMAb U36) for targeting and visualising human anaplastic thyroid carcinoma with PET. We also performed experiments aimed at elucidating the relation between tumour interstitial fluid pressure (TIFP) and the tumour uptake of antibodies. The affinity and specificity of the cMAb U36 for KAT-4 cells were evaluated in vitro, as was the Na{sup +}/I{sup -} symporter (NIS) expression. Biodistribution studies were performed on KAT-4 carcinoma-bearing mice injected with {sup 124}I-cMAb U36 or free iodine. Biodistribution studies were also performed in animals treated with the specific TGF-{beta}1 and -{beta}3 inhibitor Fc:T{beta}RII, which lowers TIFP. Treated and non-treated animals were scanned by microPET. Cultured human undifferentiated/anaplastic thyroid carcinoma KAT-4 cells expressed low levels of NIS and uptake of free iodine was insignificant. The cMAb U36 expressed an affinity (K{sub D}) of 11 {+-} 2 nM. Tumour radioactivity uptake reached maximum values 48 h after injection of {sup 124}I-cMAb U36 ({proportional_to}22%IA/g). KAT-4 carcinomas were readily identified in all {sup 124}I-immuno-PET images. Radioactivity tumour uptake in Fc:T{beta}RII-treated animals was significantly lower at 24 and 48 h after injection, and five times higher thyroid uptake was also noted. We successfully used {sup 124}I-cMAb U36 to visualise CD44v6-expressing human anaplastic thyroid carcinoma. Given the lack of NIS expression in KAT-4, tumour visualisation is not due to free iodine uptake. Lowering the TIFP in KAT-4 carcinomas did not increase the uptake of mAbs into tumour tissue. (orig.)

  18. Reliable LC-MS quantitative glycomics using iGlycoMab stable isotope labeled glycans as internal standards.

    Science.gov (United States)

    Zhou, Shiyue; Tello, Nadia; Harvey, Alex; Boyes, Barry; Orlando, Ron; Mechref, Yehia

    2016-06-01

    Glycans have numerous functions in various biological processes and participate in the progress of diseases. Reliable quantitative glycomic profiling techniques could contribute to the understanding of the biological functions of glycans, and lead to the discovery of potential glycan biomarkers for diseases. Although LC-MS is a powerful analytical tool for quantitative glycomics, the variation of ionization efficiency and MS intensity bias are influencing quantitation reliability. Internal standards can be utilized for glycomic quantitation by MS-based methods to reduce variability. In this study, we used stable isotope labeled IgG2b monoclonal antibody, iGlycoMab, as an internal standard to reduce potential for errors and to reduce variabililty due to sample digestion, derivatization, and fluctuation of nanoESI efficiency in the LC-MS analysis of permethylated N-glycans released from model glycoproteins, human blood serum, and breast cancer cell line. We observed an unanticipated degradation of isotope labeled glycans, tracked a source of such degradation, and optimized a sample preparation protocol to minimize degradation of the internal standard glycans. All results indicated the effectiveness of using iGlycoMab to minimize errors originating from sample handling and instruments. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Physico-chemical Stability of MabThera Drug-product Solution for Subcutaneous Injection under in-use Conditions with Different Administration Materials.

    Science.gov (United States)

    Mueller, Claudia; Dietel, Elke; Heynen, Severin R; Nalenz, Heiko; Goldbach, Pierre; Mahler, Hanns-Christian; Schmidt, Johannes; Grauschopf, Ulla; Schoenhamnmer, Karin

    2015-01-01

    MabThera is an essential component of the standard-of-care regimens in the treatment of non-Hodgkin lymphoma and Chronic Lymphatic Leukemia. MabThera for subcutaneous injection is a novel line extension that has been approved by the European Medicines Agency for the treatment of patients with follicular lymphoma and diffuse large B-cell lymphoma. This study aimed to evaluate in-use stability data of MabThera subcutaneous drug-product solution in single-use syringes for subcutaneous administration according to the European Medicines Agency guideline. The drug-product solution was exposed to material contact surfaces of five different administration setups commonly used in subcutaneous drug delivery. MabThera subcutaneous was transferred under aseptic conditions into polypropylene and polycarbonate syringes and stored for 1, 2, and 4 weeks at 2°C to 8°C followed by 24 hours at 30°C. After storage, subcutaneous administration was simulated and MabThera subcutaneous drug-product solution quality attributes were evaluated by using compendial physico-chemical tests, as well as suitable and validated molecule- and formulation-specific analytical methods. MabThera subcutaneous vials were treated and analyzed in parallel. The physico-chemical results of MabThera subcutaneous in the different setups were comparable to the control for all timepoints. No change in drug-product quality after storage and simulated administration was found compared to the control. However, since single-dose products do not contain preservatives, microbial contamination and growth needs to be avoided and product sterility needs to be ensured. The results showed that MabThera subcutaneous remains compatible and stable, from a physico-chemical perspective, for up to 4 weeks at 2°C to 8°C followed by 24 hours at 30°C with the contact materials tested in this study. In order to avoid and minimize microbial growth, MabThera subcutaneous should be used immediately after removal from the original

  20. System visualization of integrated biofuels and high value chemicals developed within the MacroAlgaeBiorefinery (MAB3) project

    DEFF Research Database (Denmark)

    Seghetta, Michele; Hasler, Berit; Bastianoni, Simone

    MacroAlgaeBiorefinery (MAB3) may functions as production platform and raw material supplier for future sustainable production chains of biofuels and high value chemicals. Biofuels are interesting energy source but challenges in terms of the composition of the biomass and resulting energy...... efficiencies has to be compensated for to make the biofuel prices competitive in replacing fossil fuel. Since it is difficult to increase the yield of the single biorefinery, the overall system productivity can be improved integrating different sub-systems. In this study, macroalgae cultivation in Denmark...... is integrated with a biogas biorefinery, a bioethanol biorefinery and a fish feed industry. The modeled system is able to adapt itself to different amount and quality of feedstock and to maximize valuable outputs (e.g. bio-fuels and chemical). Macroalgae are harvested and utilized as feedstock in bioethanol...

  1. Development of monoclonal antibodies (MAbs) to feline interferon (fIFN)-γ as tools to evaluate cellular immune responses to feline infectious peritonitis virus (FIPV).

    Science.gov (United States)

    Satoh, Ryoichi; Kaku, Ayumi; Satomura, Megumi; Kohori, Michiyo; Noura, Kanako; Furukawa, Tomoko; Kotake, Masako; Takano, Tomomi; Hohdatsu, Tsutomu

    2011-06-01

    Feline infectious peritonitis virus (FIPV) can cause a lethal disease in cats, feline infectious peritonitis (FIP). The antibody-dependent enhancement (ADE) of FIPV infection has been recognised in experimentally infected cats, and cellular immunity is considered to play an important role in preventing the onset of FIP. To evaluate the importance of cellular immunity for FIPV infection, monoclonal antibodies (MAbs) against feline interferon (fIFN)-γ were first created to establish fIFN-γ detection systems using the MAbs. Six anti-fIFN-γ MAbs were created. Then, the difference in epitope which those MAbs recognise was demonstrated by competitive enzyme-linked immunosorbent assay (ELISA) and IFN-γ neutralisation tests. Detection systems for fIFN-γ (sandwich ELISA, ELISpot assay, and two-colour flow cytometry) were established using anti-fIFN-γ MAbs that recognise different epitopes. In all tests, fIFN-γ production from peripheral blood mononuclear cells (PBMCs) obtained from cats experimentally infected with an FIPV isolate that did not develop the disease was significantly increased by heat-inactivated FIPV stimulation in comparison with medium alone. Especially, CD8(+)fIFN-γ(+) cells, but not CD4(+)fIFN-γ(+) cells, were increased. In contrast, fIFN-γ production from PBMCs isolated from cats that had developed FIP and specific pathogen-free (SPF) cats was not increased by heat-inactivated FIPV stimulation. These results suggest that cellular immunity plays an important role in preventing the development of FIP. Measurement of fIFN-γ production with the anti-fIFN-γ MAbs created in this study appeared to be useful in evaluating cellular immunity in cats. Copyright © 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

  2. Immunoreactivity of the 14F7 Mab Raised against N-Glycolyl GM3 Ganglioside in Epithelial Malignant Tumors from Digestive System

    OpenAIRE

    Blanco, Rancés; Rengifo, Enrique; Cedeño, Mercedes; Rengifo, Charles E.; Alonso, Daniel F.; Carr, Adriana

    2011-01-01

    The limited expression of N-Glycolyl GM3 (NeuGcGM3) ganglioside in human normal tissues, as well as its presence in melanoma and breast carcinoma using 14F7 Mab (anti-NeuGcGM3), has been previously reported. In this work we evaluated for the first time the 14F7 Mab immunorecognition in some digestive system tumors. Immunohistochemical assays were made with 14F7, followed by anti-mouse biotinylated antibody and ABC/HRP system in normal and pathological human tissues were made. No immunoreactio...

  3. Monoclonal antibodies protect from Staphylococcal Enterotoxin K (SEK) induced toxic shock and sepsis by USA300 Staphylococcus aureus.

    Science.gov (United States)

    Aguilar, Jorge L; Varshney, Avanish K; Pechuan, Ximo; Dutta, Kaushik; Nosanchuk, Joshua D; Fries, Bettina C

    2017-08-18

    Staphylococcus aureus is a leading infectious cause of life-threatening disease in humans, yet there is currently no vaccine to combat this bacterium. The pathogenesis of S. aureus is mediated by a diverse array of protein toxins including a large family of secreted pyrogenic superantigens. Neutralization of superantigens, including SEB and TSST-1, has proven to be protective in several animal models of toxic shock and sepsis. We demonstrate, for the first time, that a far more prevalent staphylococcal superantigen, SEK, can also induce lethal shock in mice. Additionally, we describe monoclonal antibodies (mAbs) that inhibit SEK-induced mitogenicity as well as protect against SEK-induced lethality, and enhance survival from S. aureus septicemia in murine models. MAb-4G3 (IgG2b), mAb-5G2 (IgG1), and mAb-9H2 (IgG1), all inhibit SEK-induced proliferation and cytokine production of human immune cells. We then demonstrate that passive immunization with a combination of mAb-4G3 and mAb-5G4, 2 mAbs that do not compete for epitope(s) on SEK, significantly enhance survival in a murine model of SEK-induced toxic shock (p = 0.006). In the setting of sepsis, passive immunization with this combination of mAbs also significantly enhances survival in mice after challenge with CA-MRSA strain USA300 (p = 0.03). Furthermore, septic mice that received mAb treatment in conjunction with vancomycin exhibit less morbidity than mice treated with vancomycin alone. Taken together, these findings suggest that the contribution of SEK to S. aureus pathogenesis may be greater than previously appreciated, and that adjunctive therapy with passive immunotherapy against SEs may be beneficial.

  4. Tissue Reactivity of the 14F7 Mab Raised against N-Glycolyl GM3 Ganglioside in Tumors of Neuroectodermal, Mesodermal, and Epithelial Origin

    Science.gov (United States)

    Blanco, Rancés; Quintana, Yisel; Blanco, Damián; Cedeño, Mercedes; Rengifo, Charles E.; Frómeta, Milagros; Ríos, Martha; Rengifo, Enrique; Carr, Adriana

    2013-01-01

    The expression of N-glycolylneuraminic acid forming the structure of gangliosides and/or other glycoconjugates (Hanganutziu-Deicher antigen) in human has been considered as a tumor-associated antigen. Specifically, some reports of 14F7 Mab (a highly specific Mab raised against N-glycolyl GM3 ganglioside) reactivity in human tumors have been recently published. Nevertheless, tumors of epithelial origin have been mostly evaluated. The goal of the present paper was to evaluate the immunohistochemical recognition of 14F7 Mab in different human tumors of neuroectodermal, mesodermal, and epithelial origins using an immunoperoxidase staining method. Samples of fetal, normal, and reactive astrocytosis of the brain were also included in the study. In general, nontumoral tissues, as well as, low-grade brain tumors showed no or a limited immunoreaction with 14F7 Mab. Nevertheless, high-grade astrocytomas (III-IV) and neuroblastomas, as well as, sarcomas and thyroid carcinomas were mostly reactive with 14F7. No reaction was evidenced in medulloblastomas and ependymoblastomas. Our data suggest that the expression of N-glycolyl GM3 ganglioside could be related to the aggressive behavior of malignant cells, without depending on the tumor origin. Our data could also support the possible use of N-glycolyl GM3 as a target for both active and passive immunotherapies of malignancies expressing this molecule. PMID:26317019

  5. Freeze-dried formulation for direct {sup 99m}Tc-labeling ior-egf/r3 MAb: additives, biodistribution, and stability

    Energy Technology Data Exchange (ETDEWEB)

    Morales, Alejo A. Morales; Nunez-Gandolff, Gilda; Perez, Niuvis Perez; Veliz, Belkis Chico; Caballero-Torres, Idania; Duconge, Jorge; Fernandez, Eduardo; Crespo, Francisco Zayas; Veloso, Ana; Iznaga-Escobar, Normando E-mail: normando@ict.sld.cu

    1999-08-01

    Monoclonal antibodies (MAbs) have been useful for immunoscintigraphic applications in clinical diagnosis since they were introduced in nuclear medicine practice. The MAb ior egf/r3 developed at the Center of Molecular Immunology (Havana, Cuba) is a murine antibody that recognizes the human epidermal growth factor receptor (EGF-R) and has been used widely in the radioimmunodiagnosis of tumors of epithelial origin. Based on the direct Schwarz method, the present report describes the preparation of a freeze-dried formulation for radiolabeling the MAb ior egf/r3 with {sup 99m}Tc for immunoscintigraphic applications. Radiolabeling efficiency, effects on immunoreactivity, biodistribution, pharmacokinetic, and stability of the formulation are reported. The study demonstrated that the freeze-dried formulation can be labeled with {sup 99m}Tc at high yield. The resulting {sup 99m}Tc-labeled ior egf/r3 MAb can be used to visualize in vivo human tumors of epithelial origin by immunoscintigraphy studies. The kit does not need any other addition or purification at the time of tagging other than the requisite amount of pertechnetate (40-50 mCi). Because the contents of the kit are lyophilized, no special storage or transportation is required.

  6. Freeze-dried formulation for direct 99mTc-labeling ior-egf/r3 MAb: additives, biodistribution, and stability

    International Nuclear Information System (INIS)

    Morales, Alejo A. Morales; Nunez-Gandolff, Gilda; Perez, Niuvis Perez; Veliz, Belkis Chico; Caballero-Torres, Idania; Duconge, Jorge; Fernandez, Eduardo; Crespo, Francisco Zayas; Veloso, Ana; Iznaga-Escobar, Normando

    1999-01-01

    Monoclonal antibodies (MAbs) have been useful for immunoscintigraphic applications in clinical diagnosis since they were introduced in nuclear medicine practice. The MAb ior egf/r3 developed at the Center of Molecular Immunology (Havana, Cuba) is a murine antibody that recognizes the human epidermal growth factor receptor (EGF-R) and has been used widely in the radioimmunodiagnosis of tumors of epithelial origin. Based on the direct Schwarz method, the present report describes the preparation of a freeze-dried formulation for radiolabeling the MAb ior egf/r3 with 99m Tc for immunoscintigraphic applications. Radiolabeling efficiency, effects on immunoreactivity, biodistribution, pharmacokinetic, and stability of the formulation are reported. The study demonstrated that the freeze-dried formulation can be labeled with 99m Tc at high yield. The resulting 99m Tc-labeled ior egf/r3 MAb can be used to visualize in vivo human tumors of epithelial origin by immunoscintigraphy studies. The kit does not need any other addition or purification at the time of tagging other than the requisite amount of pertechnetate (40-50 mCi). Because the contents of the kit are lyophilized, no special storage or transportation is required

  7. Differential expression of Meis2, Mab21l2 and Tbx3 during limb development associated with diversification of limb morphology in mammals.

    Science.gov (United States)

    Dai, Mengyao; Wang, Yao; Fang, Lu; Irwin, David M; Zhu, Tengteng; Zhang, Junpeng; Zhang, Shuyi; Wang, Zhe

    2014-01-01

    Bats are the only mammals capable of self-powered flight using wings. Differing from mouse or human limbs, four elongated digits within a broad wing membrane support the bat wing, and the foot of the bat has evolved a long calcar that spread the interfemoral membrane. Our recent mRNA sequencing (mRNA-Seq) study found unique expression patterns for genes at the 5' end of the Hoxd gene cluster and for Tbx3 that are associated with digit elongation and wing membrane growth in bats. In this study, we focused on two additional genes, Meis2 and Mab21l2, identified from the mRNA-Seq data. Using whole-mount in situ hybridization (WISH) we validated the mRNA-Seq results for differences in the expression patterns of Meis2 and Mab21l2 between bat and mouse limbs, and further characterize the timing and location of the expression of these two genes. These analyses suggest that Meis2 may function in wing membrane growth and Mab21l2 may have a role in AP and DV axial patterning. In addition, we found that Tbx3 is uniquely expressed in the unique calcar structure found in the bat hindlimb, suggesting a role for this gene in calcar growth and elongation. Moreover, analysis of the coding sequences for Meis2, Mab21l2 and Tbx3 showed that Meis2 and Mab21l2 have high sequence identity, consistent with the functions of genes being conserved, but that Tbx3 showed accelerated evolution in bats. However, evidence for positive selection in Tbx3 was not found, which would suggest that the function of this gene has not been changed. Together, our findings support the hypothesis that the modulation of the spatiotemporal expression patterns of multiple functional conserved genes control limb morphology and drive morphological change in the diversification of mammalian limbs.

  8. Aeroallergen analyses and their clinical relevance. I. Immunochemical quantification of allergens by RAST-inhibition, Mab-ELISA, basophil histamine release, and counter current immuno electrophoresis

    DEFF Research Database (Denmark)

    Johnsen, C R; Abrahamsen, L; Stahl Skov, P

    1991-01-01

    The aim was to compare IgE and IgG4 RAST-inhibition assay (RI), monoclonal antibody ELISA (Mab-ELISA), counter current immuno electrophoresis (CCIE) and histamine release from basophil leukocytes (HR) for allergen quantification with special reference to aeroallergen detection. As components......-U/ml) than IgE-RI (2*10(3) SQ-U/ml). The ranges of allergen detection limits for the Mab-ELISA were equal for cat and Derm. pter. (10-10(2) SQ-U/ml). The range of allergen detection limits for CCIE, assaying dog were 10(4)-10(5) SQ-U/ml. The ranges of allergen detection limits for HR were equal for cat...

  9. Static and Dynamic Energetic Disorders in the C 60 , PC 61 BM, C 70 , and PC 71 BM Fullerenes

    KAUST Repository

    Tummala, Naga Rajesh; Zheng, Zilong; Aziz, Saadullah G.; Coropceanu, Veaceslav; Bré das, Jean Luc

    2015-01-01

    We use a combination of molecular dynamics simulations and density functional theory calculations to investigate the energetic disorder in fullerene systems. We show that the energetic disorder evaluated from an ensemble average contains

  10. Solid-state mAbs and ADCs subjected to heat-stress stability conditions can be covalently modified with buffer and excipient molecules.

    Science.gov (United States)

    Valliere-Douglass, John F; Lewis, Patsy; Salas-Solano, Oscar; Jiang, Shan

    2015-02-01

    We report that a unique type of chemical modification occurs on lyophilized proteins. Freeze-dried mAbs and antibody-drug conjugates (ADCs) can be covalently modified with buffer and excipient molecules on the side chains of Glu, Asp, Thr, and Ser amino acids when subjected to temperature stress. The reaction occurs primarily via condensation of common buffers and excipients such as histidine, tris, trehalose and sucrose, with Glu and Asp carboxylates in the primary sequence of proteins. The reaction was also found to proceed through condensation of carboxylate containing buffers such as citrate, with Thr and Ser hydroxyls in the primary sequence of proteins. Based on the mass of the covalent adducts observed on mAbs and ADCs, it is apparent that the reaction produces water as a product and is thus favored in a low moisture environments such as a lyophilized protein cake. Herein, we present the evidence for the covalent modification of proteins drawn from case studies of in-depth characterization of heat-stressed mAbs and ADCs in the solid state. We also demonstrate how common charge variant assays such as imaged capillary isoelectric focusing and mass spectrometry can be used to monitor this specific class of protein modification. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  11. Monoclonal antibodies (MAb) made against insect-derived metacyclic trypomastigotes (IMT) of Trypanosoma cruzi (TC) cross-react with other parasite forms

    International Nuclear Information System (INIS)

    Kirchhoff, L.V.; Gilliam, F.C.

    1986-01-01

    Considerable information has been generated in recent years about stage-specific surface membrane antigens of a number of protozoa, and this phenomenon has been observed among several stages of TC as well. However, little is known about the surface antigens of IMT, the true infective stage of TC, because of the difficulty of obtaining sufficient numbers of these organisms for analysis. The Tulahuen strain of TC was maintained in the reduviid vector Dipetalogaster maximus by repeated feeding on mice with high parasitemias. IMT collected with insect urine were irradiated (150 krad) and used to immunize a BALB/c mouse for hybridoma production. Supernatants were screened by immunofluorescence assay for the presence of IgG MAb that react with methanol-fixed IMT, epimastogotes (EPI) and culture-derived metacyclic trypomastigoes (CMT). Of 41 MAb obtained, 40 reacted with IMT, 37 with EPI and 38 with CMT. Four MAb immunoprecipitated radioiodinated proteins or protein conjugates of M/sub r/ 80, 72, 45 and 45 from lysates of 125 I surface-labeled EPI. These results indicate that, at least at the epitopic level, there is considerable overlap among IMT, EPI and CMT surface antigens. This finding suggests that analysis of surface proteins of the latter 2 parasite forms may lead to identification of molecules useful for vaccine development

  12. 64Cu-DOTA-Anti-CTLA-4 mAb Enabled PET Visualization of CTLA-4 on the T-Cell Infiltrating Tumor Tissues

    Science.gov (United States)

    Higashikawa, Kei; Yagi, Katsuharu; Watanabe, Keiko; Kamino, Shinichiro; Ueda, Masashi; Hiromura, Makoto; Enomoto, Shuichi

    2014-01-01

    Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) targeted therapy by anti-CTLA-4 monoclonal antibody (mAb) is highly effective in cancer patients. However, it is extremely expensive and potentially produces autoimmune-related adverse effects. Therefore, the development of a method to evaluate CTLA-4 expression prior to CTLA-4-targeted therapy is expected to open doors to evidence-based and cost-efficient medical care and to avoid adverse effects brought about by ineffective therapy. In this study, we aimed to develop a molecular imaging probe for CTLA-4 visualization in tumor. First, we examined CTLA-4 expression in normal colon tissues, cultured CT26 cells, and CT26 tumor tissues from tumor-bearing BALB/c mice and BALB/c nude mice by reverse transcription polymerase chain reaction (RT-PCR) analysis and confirmed whether CTLA-4 is strongly expressed in CT26 tumor tissues. Second, we newly synthesized 64Cu-1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid-anti-mouse CTLA-4 mAb (64Cu-DOTA-anti-CTLA-4 mAb) and evaluated its usefulness in positron emission tomography (PET) and ex-vivo biodistribution analysis in CT26-bearing BALB/c mice. High CTLA-4 expression was confirmed in the CT26 tumor tissues of tumor-bearing BALB/c mice. However, CTLA-4 expression was extremely low in the cultured CT26 cells and the CT26 tumor tissues of tumor-bearing BALB/c nude mice. The results suggested that T cells were responsible for the high CTLA-4 expression. Furthermore, 64Cu-DOTA-anti-CTLA-4 mAb displayed significantly high accumulation in the CT26 tumor, thereby realizing non-invasive CTLA-4 visualization in the tumor. Together, the results indicate that 64Cu-DOTA-anti-CTLA-4 mAb would be useful for the evaluation of CTLA-4 expression in tumor. PMID:25365349

  13. The Role of Interleukin-6 in Lipopolysaccharide-Induced Weight Loss, Hypoglycemia and Fibrinogen Production, in Vivo

    Science.gov (United States)

    1994-07-01

    result in chronic wasting or cachexia. In neoplastic severe weight loss in syngeneic hosts.6 In this model, diseases, the presence of wasting of muscle...48 h post-endotoxin). Anti-TNF MAb tribution of TNF and IL-6 in several metabolic changes reduced by c. 50% the LPS-induced weight loss, but...similar results. Also, the addi- hypertriglyceridemia , hypoglycemia as well as stimu- tion of fresh 20F3 MAb to diluted serum sample from late the

  14. Radioimmunoscintigraphy with monoclonal antibody Technetium-99m-Anti-EGF-Receptor (R3-MAB) for the detection of head and neck tumours, metastasis and recurrence. Final report for the period 15 April 1995 - 15 April 1997

    International Nuclear Information System (INIS)

    Oliva Gonzalez, J.P.

    1998-03-01

    A clinical study was carried out to determine the sensitivity of radioimmunoscintigraphy (RIS) using indigenously produced mouse monoclonal antibody (MAB) against epidermal growth factor receptor in the detection of primary, recurrent and metastatic malignant epithelial tumours of the head and neck region in 13 patients. The MAB was labelled with 99m Tc and imaging was carried out using gamma camera and SPECT. The results were correlated with histopathological findings. RIS gave a sensitivity of 76.9%. This study showed that the indigenously produced MAB can be used for the detection of malignant epithelial tumours in the head and neck region but the MAB will be further characterized to improve its sensitivity in the detection of the neoplasia. (author)

  15. Myeloablative radioimmunotherapy with 188Re-CD66mAb before stem cell transplantation. No increase of proinflammatory cytokine levels of TNF-α

    International Nuclear Information System (INIS)

    Mutschler, J.; Reske, S.N.; Steinbach, G.; Bunjes, D.; Buchmann, I.

    2009-01-01

    Tumour necrosis factor-α (TNF-α) serum levels may increase due to intensive conditioning regimes with high-dose chemotherapy and total body irradiation (TBI) before stem cell transplantation. This increases the risk for developing acute graft versus host disease (aGvHD) after stem cell transplantation. In this prospective study we investigated the influence of radioimmunotherapy with 188 Re-CD-66-mAb on changes on TNF-α serum levels. Patients, methods: In 18 patients we measured TNF-α before and up to 96 hours after radioimmunotherapy, in 2 patients in addition following TBI, in 9 patients also following chemotherapy. For measuring TNF-α we used an automated immunochemiluminescence assay (Immulite 1000 DPC Biermann, Bad Nauheim). The mean follow up period to record incidence of aGVHD was 100 days after stem cell transplantation. Compared to the basal levels before, the levels of TNF-α after conditioning with 188 Re-CD-66-mAb did not increase significantly and remained in the physiological range. In contrast, these initial physiological cytokine levels increased and became pathological following 48 h after total body irradiation (13.2 ± 6.6 pg/ml) and chemotherapy (10.8 ± 15.7 pg/ml). In our study we found a low incidence of aGvHD (22.2%, n = 4/18). Conclusion: These results demonstrate that additional conditioning therapy with 188 Re-CD-66-mAb does not increase proinflammatory cytokine levels of TNF-α. This finding may indicate that additive radioimmunotherapy may not be a significant factor for increasing the rate of conditioning- associated aGvHD. (orig.)

  16. Anti-osteopontin monoclonal antibody prevents ovariectomy-induced osteoporosis in mice by promotion of osteoclast apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Bo [International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433 (China); PLA General Hospital Cancer Center and PLA Cancer Research Institute, PLA Postgraduate School of Medicine, 28 Fuxing Road, Beijing (China); Dai, Jianxin [International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433 (China); PLA General Hospital Cancer Center and PLA Cancer Research Institute, PLA Postgraduate School of Medicine, 28 Fuxing Road, Beijing (China); National Engineering Research Center for Antibody Medicine and Shanghai Key Lab. of Cell Engineering and Antibody, 399 Libing Road, Shanghai 201203 (China); Wang, Huaqing [International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433 (China); Wei, Huafeng [International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433 (China); PLA General Hospital Cancer Center and PLA Cancer Research Institute, PLA Postgraduate School of Medicine, 28 Fuxing Road, Beijing (China); Zhao, Jian [International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433 (China); National Engineering Research Center for Antibody Medicine and Shanghai Key Lab. of Cell Engineering and Antibody, 399 Libing Road, Shanghai 201203 (China); Guo, Yajun, E-mail: yguo_smmu@163.com [International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433 (China); PLA General Hospital Cancer Center and PLA Cancer Research Institute, PLA Postgraduate School of Medicine, 28 Fuxing Road, Beijing (China); National Engineering Research Center for Antibody Medicine and Shanghai Key Lab. of Cell Engineering and Antibody, 399 Libing Road, Shanghai 201203 (China); and others

    2014-09-26

    Highlight: • We first report that anti-osteopontin mAb could protect osteoporosis in mice. • Anti-osteopontin mAb could promote the osteoclast apoptosis. • Targeting osteopontin might have therapeutic potentials for osteoporosis. - Abstract: Osteopontin (OPN) is abundant in mineralized tissues and has long been implicated in bone remodeling. However, the therapeutic effect of targeting OPN in bone loss diseases and the underlying molecular mechanism remain largely unknown. Here, we reported that anti-OPN mAb (23C3) could protect against ovariectomy-induced osteoporosis in mice, demonstrated by microcomputed tomography analysis and histopathology evaluation. In vitro assay showed that 23C3 mAb reduced osteoclasts (OCs)-mediated bone resorption through promotion of mature OC apoptosis. Thus, the study has important implications for understanding the role of OPN in OC bone resorption and survival, and OPN antagonists may have therapeutic potential for osteoporosis and other osteopenic diseases.

  17. Anti-osteopontin monoclonal antibody prevents ovariectomy-induced osteoporosis in mice by promotion of osteoclast apoptosis

    International Nuclear Information System (INIS)

    Zhang, Bo; Dai, Jianxin; Wang, Huaqing; Wei, Huafeng; Zhao, Jian; Guo, Yajun

    2014-01-01

    Highlight: • We first report that anti-osteopontin mAb could protect osteoporosis in mice. • Anti-osteopontin mAb could promote the osteoclast apoptosis. • Targeting osteopontin might have therapeutic potentials for osteoporosis. - Abstract: Osteopontin (OPN) is abundant in mineralized tissues and has long been implicated in bone remodeling. However, the therapeutic effect of targeting OPN in bone loss diseases and the underlying molecular mechanism remain largely unknown. Here, we reported that anti-OPN mAb (23C3) could protect against ovariectomy-induced osteoporosis in mice, demonstrated by microcomputed tomography analysis and histopathology evaluation. In vitro assay showed that 23C3 mAb reduced osteoclasts (OCs)-mediated bone resorption through promotion of mature OC apoptosis. Thus, the study has important implications for understanding the role of OPN in OC bone resorption and survival, and OPN antagonists may have therapeutic potential for osteoporosis and other osteopenic diseases

  18. Elucidating the weak protein-protein interaction mechanisms behind the liquid-liquid phase separation of a mAb solution by different types of additives.

    Science.gov (United States)

    Wu, Guoliang; Wang, Shujing; Tian, Zhou; Zhang, Ning; Sheng, Han; Dai, Weiguo; Qian, Feng

    2017-11-01

    Liquid-liquid phase separation (LLPS) has long been observed during the physical stability investigation of therapeutic protein formulations. The buffer conditions and the presence of various excipients are thought to play important roles in the formulation development of monoclonal antibodies (mAbs). In this study, the effects of several small-molecule excipients (histidine, alanine, glycine, sodium phosphate, sodium chloride, sorbitol and sucrose) with diverse physical-chemical properties on LLPS of a model IgG1 (JM2) solutions were investigated by multiple techniques, including UV-vis spectroscopy, circular dichroism, differential scanning calorimetry/fluorimetry, size exclusion chromatography and dynamic light scattering. The LLPS of JM2 was confirmed to be a thermodynamic equilibrium process with no structural changes or irreversible aggregation of proteins. Phase diagrams of various JM2 formulations were constructed, suggesting that the phase behavior of JM2 was dependent on the solution pH, ionic strength and the presence of other excipients such as glycine, alanine, sorbitol and sucrose. Furthermore, we demonstrated that for this mAb, the interaction parameter (k D ) determined at low protein concentration appeared to be a good predictor for the occurrence of LLPS at high concentration. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Small scale affinity purification and high sensitivity reversed phase nanoLC-MS N-glycan characterization of mAbs and fusion proteins.

    Science.gov (United States)

    Higel, Fabian; Seidl, Andreas; Demelbauer, Uwe; Sörgel, Fritz; Frieß, Wolfgang

    2014-01-01

    N-glycosylation is a complex post-translational modification with potential effects on the efficacy and safety of therapeutic proteins and known influence on the effector function of biopharmaceutical monoclonal antibodies (mAbs). Comprehensive characterization of N-glycosylation is therefore important in biopharmaceutical development. In early development, e.g. during pool or clone selection, however, only minute protein amounts of multiple samples are available for analytics. High sensitivity and high throughput methods are thus needed. An approach based on 96-well plate sample preparation and nanoLC-MS of 2- anthranilic acid or 2-aminobenzoic acid (AA) labeled N-glycans for the characterization of biopharmaceuticals in early development is reported here. With this approach, 192 samples can be processed simultaneously from complex matrices (e.g., cell culture supernatant) to purified 2-AA glycans, which are then analyzed by reversed phase nanoLC-MS. Attomolar sensitivity has been achieved by use of nanoelectrospray ionization, resulting in detailed glycan maps of mAbs and fusion proteins that are exemplarily shown in this work. Reproducibility, robustness and linearity of the approach are demonstrated, making use in a routine manner during pool or clone selection possible. Other potential fields of application, such as glycan biomarker discovery from serum samples, are also presented.

  20. Susceptibility of different subsets of immature thymocytes to apoptosis induced by anti-TCRmAb

    International Nuclear Information System (INIS)

    Li Hongmei; Zhong Renqian; Yu Jiaping; Kong Xiantao; Chen Weifeng

    2003-01-01

    To analysis the susceptibility of different subsets of immature mice thymocytes to apoptosis induced by anti-TCRmAbs in vitro apoptosis was induced in unfractionated mice thymocytes by anti-TCRmAb. In Vivo apoptosis was induced in BALB/c mice by anti-TCR mAb, and thymocytes were examined by FACS. Results showed that CD4 + CD8 + DP thymocytes and CD4 - CD8 + CD3 - thymocytes were equally sensitive to apoptosis after treatment with the anti-TCR mAb. In sharp contrast, the early migrants or precursor containing thymocytes which are CD4 - CD8 - CD3 - TN have a lower spontaneous apoptosis rate and were relatively resistant to the anti-TCR mAb. The findings showed a breakpoint in thymocyte sensitivity to apoptosis which occurs after the onset of CD4 - CD8 + CD3 expression, suggesting that susceptibility of thymocytes to apoptosis is developmentally regulated

  1. A monoclonal antibody against PDGF B-chain inhibits PDGF-induced DNA synthesis in C3H fibroblasts and prevents binding of PDGF to its receptor.

    Science.gov (United States)

    Vassbotn, F S; Langeland, N; Hagen, I; Holmsen, H

    1990-09-01

    A monoclonal antibody (MAb 6D11) against platelet-derived growth factor (PDGF) was studied. We found that the MAb 6D11 in concentrations equimolar to PDGF blocked the [3H]thymidine incorporation in C3H/10T1/2 C18 fibroblasts stimulated by PDGF B-B and PDGF A-B. This inhibition was overcome by high doses of PDGF. The [3H]thymidine incorporation stimulated by other growth factors (aFGF, bFGF and bombesin) was not inhibited by the antibody. The MAb 6D11 blocked receptor binding of PDGF B-B, but not PDGF A-A. These findings suggest that the MAb 6D11 abolishes PDGF-induced DNA synthesis by blocking PDGF receptor binding. In this communication we demonstrate an isoform-specific monoclonal antibody against PDGF.

  2. Chemical changes demonstrated in cartilage by synchrotron infrared microspectroscopy in an antibody-induced murine model of rheumatoid arthritis

    Science.gov (United States)

    Croxford, Allyson M.; Selva Nandakumar, Kutty; Holmdahl, Rikard; Tobin, Mark J.; McNaughton, Don; Rowley, Merrill J.

    2011-06-01

    Collagen antibody-induced arthritis develops in mice following passive transfer of monoclonal antibodies (mAbs) to type II collagen (CII) and is attributed to effects of proinflammatory immune complexes, but transferred mAbs may react directly and damagingly with CII. To determine whether such mAbs cause cartilage damage in vivo in the absence of inflammation, mice lacking complement factor 5 that do not develop joint inflammation were injected intravenously with two arthritogenic mAbs to CII, M2139 and CIIC1. Paws were collected at day 3, decalcified, paraffin embedded, and 5-μm sections were examined using standard histology and synchrotron Fourier-transform infrared microspectroscopy (FTIRM). None of the mice injected with mAb showed visual or histological evidence of inflammation but there were histological changes in the articular cartilage including loss of proteoglycan and altered chondrocyte morphology. Findings using FTIRM at high lateral resolution revealed loss of collagen and the appearance of a new peak at 1635 cm-1 at the surface of the cartilage interpreted as cellular activation. Thus, we demonstrate the utility of synchrotron FTIRM for examining chemical changes in diseased cartilage at the microscopic level and establish that arthritogenic mAbs to CII do cause cartilage damage in vivo in the absence of inflammation.

  3. Evaluation of anti-IL-6 monoclonal antibody therapy using murine type II collagen-induced arthritis

    Directory of Open Access Journals (Sweden)

    Shealy David

    2009-04-01

    Full Text Available Abstract Interleukin-6 is a multifunctional cytokine that is critical for T/B-cell differentiation and maturation, immunoglobulin secretion, acute-phase protein production, and macrophage/monocyte functions. Extensive research into the biology of IL-6 has implicated IL-6 in the pathophysiology and pathogenesis of RA. An anti-murine IL-6 mAb that neutralizes mouse IL-6 activities was tested in animal model of collagen-induced arthritis. Prophylactic treatment with anti-IL-6 mAb significantly reduced the incidence and severity of arthritis compared to control mAb treated mice. The mitogenic response of B and T cells isolated from the lymph nodes of anti-IL-6 treated mice was significantly reduced compared to cells isolated from control mAb treated mice. The overall histopathology score for paws from the anti-IL-6 treated mice was significantly reduced when compared to paws from mice treated with control mAb, including both inflammatory (synovitis and pannus and erosive (erosions and architecture parameters. Reduced loss of cartilage matrix components was also observed in the anti-IL-6 treated mice. Collectively, these data suggest that IL-6 plays a major role in the pathophysiology of rheumatoid arthritis, and thus support the potential benefit of anti-IL-6 mAb treatment in rheumatoid arthritis patients.

  4. Establishment of novel mAb to human ERC/mesothelin useful for study and diagnosis of ERC/mesothelin-expressing cancers.

    Science.gov (United States)

    Ishikawa, Kiyoshi; Segawa, Tatsuya; Hagiwara, Yoshiaki; Maeda, Masahiro; Abe, Masaaki; Hino, Okio

    2009-03-01

    Malignant mesothelioma is a highly aggressive tumor of the serosal cavity that arises from the mesothelial cells of the pleura, peritoneum, or pericardium. The immunohistochemical diagnosis of epithelioid mesothelioma from biopsy or surgically resected specimens has been actively pursued, using markers such as mesothelin. Several markers have indeed been helpful for confirming the diagnosis of mesothelioma and distinguishing between mesothelioma and adenocarcinoma. The authors have developed a novel mAb to human C-ERC/mesothelin, which performed well when used in western blotting, fluorescence-activated cell sorting, immunocytochemistry and immunohistochemistry, and which therefore will be useful in studying the molecular biology of mesothelin, in addition to improving the diagnosis and therapy of mesothelin-expressing cancers.

  5. The expression analysis of ICOS-L on activated T cells and immature dendritic cells as well as malignant B cells and Grave's-disease-derived thyroid tissues by two novel mAbs against human ICOS-L.

    Science.gov (United States)

    Wang, F; Zhu, W; Liu, T; Sun, Z; Ju, S; Ju, S; Yu, G; Xie, W; Deng, Z; Lu, B; Zhang, X

    2007-01-01

    ICOS-L, a newly identified member of B7 superfamily, plays an important role in immune responses. In this article, we report on two novel mouse anti-human ICOS-L monoclonal antibodies (mAbs) named as 11C4 and 12B11, whose specificities were verified by methods of flow cytometry, western blotting, and epitope competition assay. The two mAbs bound to distinct ICOS-L epitopes on B cells. Interestingly, mAb 11C4 could well recognize ICOS-L molecule on activated T cells and Jurkat cell lines, which is different from commercial anti-ICOS-L mAb (clone number MIH12) and the other mAb 12B11. In addition, we found that the expression of ICOS-L molecule was only detected on the surface of immature monocyte-derived dendritic cells (Mo-DCs) and was sharply decreased after induction of mature Mo-DCs activated by tumor necrosis factor-alpha or CD40. Furthermore, we showed that 11C4 could effectively suppress the maturation of Mo-DCs in vitro as evidenced by the low expression of CD80, CD86, CD83, and human leukocyte antigen-DR, which suggested that ICOS-L may be involved in the maturation of Mo-DCs. Using immunohistochemistry staining with mAb 11C4, the expression of ICOS-L was found in B lymphoma tissues and thyroid tissues from the Grave's disease but not in thyroid adenoma and normal thyroid tissues.

  6. Life‐cycle and cost of goods assessment of fed‐batch and perfusion‐based manufacturing processes for mAbs

    Science.gov (United States)

    Bunnak, Phumthep; Allmendinger, Richard; Ramasamy, Sri V.; Lettieri, Paola

    2016-01-01

    Life‐cycle assessment (LCA) is an environmental assessment tool that quantifies the environmental impact associated with a product or a process (e.g., water consumption, energy requirements, and solid waste generation). While LCA is a standard approach in many commercial industries, its application has not been exploited widely in the bioprocessing sector. To contribute toward the design of more cost‐efficient, robust and environmentally‐friendly manufacturing process for monoclonal antibodies (mAbs), a framework consisting of an LCA and economic analysis combined with a sensitivity analysis of manufacturing process parameters and a production scale‐up study is presented. The efficiency of the framework is demonstrated using a comparative study of the two most commonly used upstream configurations for mAb manufacture, namely fed‐batch (FB) and perfusion‐based processes. Results obtained by the framework are presented using a range of visualization tools, and indicate that a standard perfusion process (with a pooling duration of 4 days) has similar cost of goods than a FB process but a larger environmental footprint because it consumed 35% more water, demanded 17% more energy, and emitted 17% more CO2 than the FB process. Water consumption was the most important impact category, especially when scaling‐up the processes, as energy was required to produce process water and water‐for‐injection, while CO2 was emitted from energy generation. The sensitivity analysis revealed that the perfusion process can be made more environmentally‐friendly than the FB process if the pooling duration is extended to 8 days. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1324–1335, 2016 PMID:27390260

  7. Growth suppression of colorectal cancer by plant-derived multiple mAb CO17-1A × BR55 via inhibition of ERK1/2 phosphorylation.

    Science.gov (United States)

    Kwak, Dong Hoon; Moussavou, Ghislain; Lee, Ju Hyoung; Heo, Sung Youn; Ko, Kisung; Hwang, Kyung-A; Jekal, Seung-Joo; Choo, Young-Kug

    2014-11-14

    We have generated the transgenic Tabaco plants expressing multiple monoclonal antibody (mAb) CO7-1A × BR55 by cross-pollinating with mAb CO17-1A and mAb BR55. We have demonstrated the anti-cancer effect of plant-derived multiple mAb CO17-1A × BR55. We find that co-treatment of colorectal mAbs (anti-epithelial cellular adhesion molecule (EpCAM), plant-derived monoclonal antibody (mAb(P)) CO17-1A and mAb(P) CO17-1A × BR55) with RAW264.7 cells significantly inhibited the cell growth in SW620 cancer cells. In particular, multi mAb(P) CO17-1A × BR55 significantly and efficiently suppressed the growth of SW620 cancer cells compared to another mAbs. Apoptotic death-positive cells were significantly increased in the mAb(P) CO17-1A × BR55-treated. The mAb(P) CO17-1A × BR55 treatment significantly decreased the expression of B-Cell lymphoma-2 (BCl-2), but the expression of Bcl-2-associated X protein (Bax), and cleaved caspase-3 were markedly increased. In vivo, the mAb(P) CO17-1A × BR55 significantly and efficiently inhibited the growth of colon tumors compared to another mAbs. The apoptotic cell death and inhibition of pro-apoptotic proteins expression were highest by treatment with mAb(P) CO17-1A × BR55. In addition, the mAb(P) CO17-1A × BR55 significantly inhibited the extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation in cancer cells and tumors. Therefore, this study results suggest that multiple mAb(P) CO17-1A × BR55 has a significant effect on apoptosis-mediated anticancer by suppression of ERK1/2 phosphorylation in colon cancer compared to another mAbs. In light of these results, further clinical investigation should be conducted on mAb(P) CO17-1A × BR55 to determine its possible chemopreventive and/or therapeutic efficacy against human colon cancer.

  8. Myeloablative radioimmunotherapy with {sup 188}Re-CD66mAb before stem cell transplantation. No increase of proinflammatory cytokine levels of TNF-{alpha}; Myeloablative Radioimmuntherapie mit {sup 188}Re-CD66mAb vor Stammzelltransplantation. Kein Anstieg proinflammatorischer Zytokinspiegel von TNF-{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Mutschler, J.; Reske, S.N. [Universitaetsklinik Ulm (Germany). Klinik fuer Nuklearmedizin; Steinbach, G. [Universitaetsklinik Ulm (Germany). Abt. Klinische Chemie; Bunjes, D. [Universitaetsklinik Ulm (Germany). Medizinische Klinik III; Buchmann, I. [Universitaetsklinik Heidelberg (Germany). Abt. fuer Nuklearmedizin

    2009-07-01

    Tumour necrosis factor-{alpha} (TNF-{alpha}) serum levels may increase due to intensive conditioning regimes with high-dose chemotherapy and total body irradiation (TBI) before stem cell transplantation. This increases the risk for developing acute graft versus host disease (aGvHD) after stem cell transplantation. In this prospective study we investigated the influence of radioimmunotherapy with {sup 188}Re-CD-66-mAb on changes on TNF-{alpha} serum levels. Patients, methods: In 18 patients we measured TNF-{alpha} before and up to 96 hours after radioimmunotherapy, in 2 patients in addition following TBI, in 9 patients also following chemotherapy. For measuring TNF-{alpha} we used an automated immunochemiluminescence assay (Immulite 1000 DPC Biermann, Bad Nauheim). The mean follow up period to record incidence of aGVHD was 100 days after stem cell transplantation. Compared to the basal levels before, the levels of TNF-{alpha} after conditioning with {sup 188}Re-CD-66-mAb did not increase significantly and remained in the physiological range. In contrast, these initial physiological cytokine levels increased and became pathological following 48 h after total body irradiation (13.2 {+-} 6.6 pg/ml) and chemotherapy (10.8 {+-} 15.7 pg/ml). In our study we found a low incidence of aGvHD (22.2%, n = 4/18). Conclusion: These results demonstrate that additional conditioning therapy with {sup 188}Re-CD-66-mAb does not increase proinflammatory cytokine levels of TNF-{alpha}. This finding may indicate that additive radioimmunotherapy may not be a significant factor for increasing the rate of conditioning- associated aGvHD. (orig.)

  9. A novel anti-CD 18 mAb recognizes an activation-related epitope and induces a high-affinity conformation in leukocyte integrins

    Czech Academy of Sciences Publication Activity Database

    Drbal, Karel; Angelisová, Pavla; Hilgert, Ivan; Hořejší, Václav

    2001-01-01

    Roč. 203, č. 4 (2001), s. 687-698 ISSN 0171-2985 R&D Projects: GA ČR GA310/99/0349; GA AV ČR IAA7052904 Institutional research plan: CEZ:AV0Z5052915 Keywords : adhesion * integrin * LFA-1 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.648, year: 2001

  10. A comparison of targeting of neuroblastoma with mIBG and anti L1-CAM antibody mAb chCE7: therapeutic efficacy in a neuroblastoma xenograft model and imaging of neuroblastoma patients

    NARCIS (Netherlands)

    Hoefnagel, C. A.; Rutgers, M.; Buitenhuis, C. K.; Smets, L. A.; de Kraker, J.; Meli, M.; Carrel, F.; Amstutz, H.; Schubiger, P. A.; Novak-Hofer, I.

    2001-01-01

    Iodine-131 labelled anti L1-CAM antibody mAb chCE7 was compared with the effective neuroblastoma-seeking agent 131I-labelled metaiodobenzylguanidine (MIBG) with regard to (a) its therapeutic efficacy in treating nude mice with neuroblastoma xenografts and (b) its tumour targeting ability in

  11. Development of an ErbB4 monoclonal antibody that blocks neuregulin-1-induced ErbB4 activation in cancer cells

    International Nuclear Information System (INIS)

    Okazaki, Shogo; Nakatani, Fumi; Masuko, Kazue; Tsuchihashi, Kenji; Ueda, Shiho; Masuko, Takashi; Saya, Hideyuki; Nagano, Osamu

    2016-01-01

    The use of monoclonal antibodies (mAbs) for cancer therapy is one of the most important strategies for current cancer treatment. The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, which regulates cancer cell proliferation, survival, and migration, is a major molecular target for antibody-based therapy. ErbB4/HER4, which contains a ligand-binding extracellular region, is activated by several ligands, including neuregulins (NRGs), heparin-binding EGF-like growth factor, betacellulin and epiregulin. Although there are clinically approved antibodies for ErbB1 and ErbB2, there are no available therapeutic mAbs for ErbB4, and it is not known whether ErbB4 is a useful target for antibody-based cancer therapy. In this study, we developed an anti-ErbB4 mAb (clone P6-1) that suppresses NRG-dependent activation of ErbB4 and examined its effect on breast cancer cell proliferation in the extracellular matrix. - Highlights: • We newly generated four clones of human ErbB4 specific mAb. • ErbB4 mAb clone P6-1 blocks ErbB4 phosphorylation induced by NRG-1. • ErbB4 mAb clone P6-1 suppresses NRG-1-promoted breast cancer cells proliferation on three dimensional culture condition.

  12. Development of an ErbB4 monoclonal antibody that blocks neuregulin-1-induced ErbB4 activation in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Okazaki, Shogo [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Nakatani, Fumi [Cell Biology Laboratory, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kinki University, Higashiosaka, Osaka 577-8502 Japan (Japan); Masuko, Kazue; Tsuchihashi, Kenji [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Ueda, Shiho; Masuko, Takashi [Cell Biology Laboratory, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kinki University, Higashiosaka, Osaka 577-8502 Japan (Japan); Saya, Hideyuki [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Nagano, Osamu, E-mail: osmna@sb3.so-net.ne.jp [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan)

    2016-01-29

    The use of monoclonal antibodies (mAbs) for cancer therapy is one of the most important strategies for current cancer treatment. The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, which regulates cancer cell proliferation, survival, and migration, is a major molecular target for antibody-based therapy. ErbB4/HER4, which contains a ligand-binding extracellular region, is activated by several ligands, including neuregulins (NRGs), heparin-binding EGF-like growth factor, betacellulin and epiregulin. Although there are clinically approved antibodies for ErbB1 and ErbB2, there are no available therapeutic mAbs for ErbB4, and it is not known whether ErbB4 is a useful target for antibody-based cancer therapy. In this study, we developed an anti-ErbB4 mAb (clone P6-1) that suppresses NRG-dependent activation of ErbB4 and examined its effect on breast cancer cell proliferation in the extracellular matrix. - Highlights: • We newly generated four clones of human ErbB4 specific mAb. • ErbB4 mAb clone P6-1 blocks ErbB4 phosphorylation induced by NRG-1. • ErbB4 mAb clone P6-1 suppresses NRG-1-promoted breast cancer cells proliferation on three dimensional culture condition.

  13. Kinetics of platelets in dogs with thrombocytopenia induced by antiglycoprotein IIb/IIIa receptor monoclonal antibody

    International Nuclear Information System (INIS)

    Hosono, Makoto; Sone, Naoaki; Endo, Keigo; Saga, Tsuneo; Kobayashi, Hisataka; Hosono, Masako N.; Sakahara, Harumi; Yasunaga, Kojiro; Konishi, Junji

    1995-01-01

    To experimentally assess the kinetics of platelets in thrombocytopenia, we constructed a canine model using 111 In-oxine labeled autologous platelets and an intact antiplatelet monoclonal antibody (MAb) NNKY2-11 (IgG2a). With the infusion of radiolabeled autologous platelets into dogs, the peripheral platelet count and blood radioactivity level were examined, and the radioactivity in the liver, spleen and heart was determined with scintigraphic analysis. Thereafter, i.v. injection of 100 μg/kg of NNKY2-11 had no effect on platelet counts or the biodistribution of radiolabeled platelets. However, 200 and 300 μg/kg of MAb reduced the platelets, and the radioactivity of the liver and spleen augmented clearly after injection of MAb. Platelet radioactivity in serum, which had decreased after MAb infusion, did not recover, even when peripheral platelet counts returned to the normal levels, indicating that these new platelets might be derived from the platelet-storage pool or new thrombocytogenesis. This model of antiplatelet MAb induced thrombocytopenia seems to be useful for analyzing the kinetics of platelets in thrombocytopenia

  14. The Role of Biosphere Reserves in Environmental Education and Training = Le Role des reserves de la biosphere dans l'education et la formation environnementales. Report of the Unesco/MAB Symposium Held During the Unesco/UNEP International Congress on Environmental Education and Training (Moscow, USSR, August 17-21, 1987). Report 20.

    Science.gov (United States)

    Francis, George, Ed.

    Environmental education and training have been key elements of Unesco's Program on Man and the Biosphere (MAB) since its inception in 1971. The MAB Program is an intergovernmental program of research, training, demonstration and distribution of information, aimed at providing the scientific background and the trained personnel to deal with…

  15. Different signaling pathways induced by alpha-CD3 monoclonal antibody versus alloantigen on the basis of differential ornithine sensitivity.

    Science.gov (United States)

    Mehrotra nee Tandon, P; Lind, D S; Bear, H D; Susskind, B M

    1992-08-01

    Previously we reported that 10 mM ornithine (Orn) selectively inhibits the development of CD8+ CTL in MLC. Herein we show that induction by alpha-CD3 mAb of CD8+ killer cells which manifest antibody-redirected cytotoxicity (ARC) of FcR+ targets is not Orn sensitive. Orn resistance was independent of activation kinetics or alpha-CD3 mAb concentration. alpha-CD3 mAb added to the cytotoxicity assay did not reveal a cytolytic potential in CTL from an Orn-treated MLC when the target cells bore both the inducing alloantigen and FcR. Addition of alpha-CD3 mAb to MLC failed to overcome Orn inhibition of CTL and yet induced ARC activity in the same culture. Expression of mRNA for pore-forming proteins (PFP) and granzyme B was inhibited by Orn in CTL but not in ARC killer cells. Our results demonstrate differences in the T cell activation process stimulated by alloantigen or alpha-CD3 mAb.

  16. Inhibition of rotavirus replication by a non-neutralizing, rotavirus VP6–specific IgA mAb

    Science.gov (United States)

    Feng, Ningguo; Lawton, Jeffrey A.; Gilbert, Joana; Kuklin, Nelly; Vo, Phuoc; Prasad, B.V. Venkataram; Greenberg, Harry B.

    2002-01-01

    Rotaviruses are the leading cause of severe diarrheal disease in young children. Intestinal mucosal IgA responses play a critical role in protective immunity against rotavirus reinfection. Rotaviruses consist of three concentric capsid layers surrounding a genome of 11 segments of double-stranded RNA. The outer layer proteins, VP4 and VP7, which are responsible for viral attachment and entry, are targets for protective neutralizing antibodies. However, IgA mAb’s directed against the intermediate capsid protein VP6, which do not neutralize the virus, have also been shown to protect mice from rotavirus infection and clear chronic infection in SCID mice. We investigated whether the anti-VP6 IgA (7D9) mAb could inhibit rotavirus replication inside epithelial cells and found that 7D9 acted at an early stage of infection to neutralize rotavirus following antibody lipofection. Using electron cryomicroscopy, we determined the three-dimensional structure of the virus-antibody complex. The attachment of 7D9 IgA to VP6 introduces a conformational change in the VP6 trimer, rendering the particle transcriptionally incompetent and preventing the elongation of initiated transcripts. Based on these observations, we suggest that anti-VP6 IgA antibodies confers protection in vivo by inhibiting viral transcription at the start of the intracellular phase of the viral replication cycle. PMID:11994409

  17. Immunoreactivity of the 14F7 Mab (Raised against N-Glycolyl GM3 Ganglioside as a Positive Prognostic Factor in Non-Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Rancés Blanco

    2012-01-01

    Full Text Available Lung carcinoma is the leading cause of cancer-related mortality worldwide. Therefore, numerous studies are focusing on the assessment of other biological and molecular prognostic factors in these tumors. We evaluated the relationship between 14F7 Mab reactivity, pathological features, DNA-content and S-phase fraction (SPF, and their impact in the survival of NSCLC patients. Hematoxylin and eosin staining and immunohistochemistry optical microscopy assays as well as DNA content and SPF measuring using flow cytometry were performed. The 14F7 reactivity was widely observed in NSCLC sections, no depending of the clinicopathological characteristics. We also obtained differences in the intensity of reaction with 14F7 as well as in the SPF between diploid and aneuploid carcinomas. Patients with diploid tumors showing higher SPF and 14F7 reaction joint to a low mitotic index displayed higher survival rates. Our results are in agreement with the assumption of the possible positive prognostic value of 14F7 staining in NSCLC.

  18. Immunoreactivity of the 14F7 Mab (Raised against N-Glycolyl GM3 Ganglioside) as a Positive Prognostic Factor in Non-Small-Cell Lung Cancer

    Science.gov (United States)

    Blanco, Rancés; Rengifo, Charles E.; Cedeño, Mercedes; Frómeta, Milagros; Rengifo, Enrique; Carr, Adriana

    2012-01-01

    Lung carcinoma is the leading cause of cancer-related mortality worldwide. Therefore, numerous studies are focusing on the assessment of other biological and molecular prognostic factors in these tumors. We evaluated the relationship between 14F7 Mab reactivity, pathological features, DNA-content and S-phase fraction (SPF), and their impact in the survival of NSCLC patients. Hematoxylin and eosin staining and immunohistochemistry optical microscopy assays as well as DNA content and SPF measuring using flow cytometry were performed. The 14F7 reactivity was widely observed in NSCLC sections, no depending of the clinicopathological characteristics. We also obtained differences in the intensity of reaction with 14F7 as well as in the SPF between diploid and aneuploid carcinomas. Patients with diploid tumors showing higher SPF and 14F7 reaction joint to a low mitotic index displayed higher survival rates. Our results are in agreement with the assumption of the possible positive prognostic value of 14F7 staining in NSCLC. PMID:22482082

  19. Computational identification of epitopes in the glycoproteins of novel bunyavirus (SFTS virus) recognized by a human monoclonal antibody (MAb 4-5)

    Science.gov (United States)

    Zhang, Wenshuai; Zeng, Xiaoyan; Zhang, Li; Peng, Haiyan; Jiao, Yongjun; Zeng, Jun; Treutlein, Herbert R.

    2013-06-01

    In this work, we have developed a new approach to predict the epitopes of antigens that are recognized by a specific antibody. Our method is based on the "multiple copy simultaneous search" (MCSS) approach which identifies optimal locations of small chemical functional groups on the surfaces of the antibody, and identifying sequence patterns of peptides that can bind to the surface of the antibody. The identified sequence patterns are then used to search the amino-acid sequence of the antigen protein. The approach was validated by reproducing the binding epitope of HIV gp120 envelop glycoprotein for the human neutralizing antibody as revealed in the available crystal structure. Our method was then applied to predict the epitopes of two glycoproteins of a newly discovered bunyavirus recognized by an antibody named MAb 4-5. These predicted epitopes can be verified by experimental methods. We also discuss the involvement of different amino acids in the antigen-antibody recognition based on the distributions of MCSS minima of different functional groups.

  20. Aeroallergen analyses and their clinical relevance. I. Immunochemical quantification of allergens by RAST-inhibition, Mab-ELISA, basophil histamine release, and counter current immuno electrophoresis

    DEFF Research Database (Denmark)

    Johnsen, C R; Abrahamsen, L; Stahl Skov, P

    1991-01-01

    of indoor aeroallergens, cat, dog, and Derm. pter. allergen extracts were selected for the experiments. To evaluate unspecific interference, these allergens were compared mutually and with Cladosporium herbarum. Allergen extracts in varying dilutions were mixed with crushed glass fibre filter materials......, eluted, recovered by centrifugation, and allergen concentration quantified by the assays. Equal sensitivity was found for both IgE- and IgG4-RI assaying cat allergen (in the range 5-50 SQ-U/ml) and dog allergen (in the range 10(2)-10(3) SQ-U/ml). The IgG4-RI assaying Derm. pter. was more sensitive (50 SQ......-U/ml) than IgE-RI (2*10(3) SQ-U/ml). The ranges of allergen detection limits for the Mab-ELISA were equal for cat and Derm. pter. (10-10(2) SQ-U/ml). The range of allergen detection limits for CCIE, assaying dog were 10(4)-10(5) SQ-U/ml. The ranges of allergen detection limits for HR were equal for cat...

  1. Evolving GIS technologies in nature conservation and the spatial planning strategy of Tara NP (Serbia as a potential UNECSO MAB reserve

    Directory of Open Access Journals (Sweden)

    Radović Dejan

    2008-01-01

    Full Text Available Mt. Tara NP was nominated in 2004 within the UNESCO - ROSTE programme, for Man and the Biosphere (MAB Reserve status in Serbia as transboundary 'Peace Park' status between Serbia and Bosnia & Herzegovina. Mt. Tara is one of the most important centres of Balkans and European ecosystems and species diversity. They represent a unique example of well preserved forests in south eastern Europe with numerous endemic and relict species of flora and fauna. In this floristic diversity of Mt Tara of the greatest interest is the Serbian (Pančić's spruce Picea omorika. Mt. Tara NP is characterized by specific geomorphologic, hydrologic, geologic, soil and climatic features. The geographical information system (GIS that we have created has proved an excellent tool for the spatial planning strategy in assessment and conservation of all natural characteristics of Mt. Tara NP, and is helpful to Park management for sustainable use of landscape resources. GIS of Mt. Tara NP includes data on natural, artificial and management themes.

  2. MHC class II ligation induces CD58 (LFA-3)-mediated adhesion in human T cells

    DEFF Research Database (Denmark)

    Nielsen, M; Gerwien, J; Geisler, C

    1998-01-01

    ligation induces homotypic adhesion in both beta2-integrin-positive and negative, CD4-positive T cell lines. Anti-CD18 monoclonal antibody (mAb) weakly inhibited the adhesion response in beta2-integrin-positive T cells and had no effect on beta2-integrin-negative T cells. In contrast, an anti-CD58 (LFA-3...

  3. A 44 bp intestine-specific hermaphrodite-specific enhancer from the C. elegans vit-2 vitellogenin gene is directly regulated by ELT-2, MAB-3, FKH-9 and DAF-16 and indirectly regulated by the germline, by daf-2/insulin signaling and by the TGF-β/Sma/Mab pathway.

    Science.gov (United States)

    Goszczynski, Barbara; Captan, Vasile V; Danielson, Alicia M; Lancaster, Brett R; McGhee, James D

    2016-05-01

    The Caenorhabditis elegans vitellogenin genes are transcribed in the intestine of adult hermaphrodites but not of males. A 44-bp region from the vit-2 gene promoter is able largely to reconstitute this tissue-, stage- and sex-specific-expression. This "enhancer" contains a binding site for the DM-domain factor MAB-3, the male-specific repressor of vitellogenesis, as well as an activator site that we show is the direct target of the intestinal GATA factor ELT-2. We further show that the enhancer is directly activated by the winged-helix/forkhead-factor FKH-9, (whose gene has been shown by others to be a direct target of DAF-16), by an unknown activator binding to the MAB-3 site, and by the full C. elegans TGF-β/Sma/Mab pathway acting within the intestine. The vit-2 gene has been shown by others to be repressed by the daf-2/daf-16 insulin signaling pathway, which so strongly influences aging and longevity in C. elegans. We show that the activity of the 44 bp vit-2 enhancer is abolished by loss of daf-2 but is restored by simultaneous loss of daf-16. DAF-2 acts from outside of the intestine but DAF-16 acts both from outside of the intestine and from within the intestine where it binds directly to the same non-canonical target site that interacts with FKH-9. Activity of the 44 bp vit-2 enhancer is also inhibited by loss of the germline, in a manner that is only weakly influenced by DAF-16 but that is strongly influenced by KRI-1, a key downstream effector in the pathway by which germline loss increases C. elegans lifespan. The complex behavior of this enhancer presumably allows vitellogenin gene transcription to adjust to demands of body size, germline proliferation and nutritional state but we suggest that the apparent involvement of this enhancer in aging and longevity "pathways" could be incidental. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Comparison between anti-CEA and anti-HER2 212Pb-labeled mAbs during α-RIT of small volume peritoneal carcinomatosis - Role of activity distribution on therapeutic efficacy and toxicity?

    International Nuclear Information System (INIS)

    Elgqvist, J.; Boudousq, V.; Bobyk, L.; Busson, M.; Lozza, C.; Navarro-Teulon, I.; Pouget, J.P.; Maquaire, P.; Torgue, J.

    2015-01-01

    Full text of publication follows. Objectives: we investigated the role of internalizing/non-internalizing monoclonal antibodies (mAbs) on the final outcome (efficacy/toxicity) of mice treated with alpha radioimmunotherapy (α- RIT) using 212 Pb-labeled mAbs. The relationship between distribution of radioactivity at the tissue level and biological parameters was also assessed. Methods: nude mice bearing 2-3 mm peritoneal nodules obtained by xenograft of A-431 tumor cells, expressing low and high level of HER2 and CEA receptors, respectively, were intraperitoneally (i.p.) injected with increasing activities (370-1480 kBq; 37 MBq/mg) of either 35A7 (non-internalising anti-CEA), Trastuzumab (internalizing anti-HER2) or PX (non-specific) 212 Pb-labeled mAbs. Control groups were injected with corresponding amount of unlabeled mAbs or with NaCl. Tumor growth was followed by bioluminescence and median survival (MS) of control and treated mice was determined. 212 Pb-35A7 and 212 Pb-Trastuzumab biodistribution was used to determine the cumulative uptake of radioactivity (UOR) in organs and tumors. Mean absorbed doses were calculated using the MIRD formalism. Haematological, liver and kidney toxicities were also assessed. Distribution of radioactivity at the tissue level was determined by digital micro-autoradiography and the relationship with biological markers of tissue damage was investigated using immunohistochemistry. Results: a mild and transient haematological toxicity in groups treated with the highest amount of activity was observed. MS of the groups treated either with internalizing or non-internalizing 212 Pb-labeled mAbs was significantly improved compared to those treated with non-specific 212 Pb-PX or those only given unlabeled mAbs or just NaCl. MS ranged from 42 days to 94 days using various activity levels of anti-CEA 212 Pb-35A7 while MS was not reached over the follow-up period of 130 days for mice treated with anti-HER2 212 Pb-Trastuzumab. However, UOR and

  5. Prevention of Herpes Simplex Virus Induced Stromal Keratitis by a Glycoprotein B-Specific Monoclonal Antibody

    Science.gov (United States)

    Krawczyk, Adalbert; Dirks, Miriam; Kasper, Maren; Buch, Anna; Dittmer, Ulf; Giebel, Bernd; Wildschütz, Lena; Busch, Martin; Goergens, Andre; Schneweis, Karl E.; Eis-Hübinger, Anna M.; Sodeik, Beate; Heiligenhaus, Arnd; Roggendorf, Michael; Bauer, Dirk

    2015-01-01

    The increasing incidence of acyclovir (ACV) and multidrug-resistant strains in patients with corneal HSV-1 infections leading to Herpetic Stromal Keratitis (HSK) is a major health problem in industrialized countries and often results in blindness. To overcome this obstacle, we have previously developed an HSV-gB-specific monoclonal antibody (mAb 2c) that proved to be highly protective in immunodeficient NOD/SCID-mice towards genital infections. In the present study, we examined the effectivity of mAb 2c in preventing the immunopathological disease HSK in the HSK BALB/c mouse model. Therefore, mice were inoculated with HSV-1 strain KOS on the scarified cornea to induce HSK and subsequently either systemically or topically treated with mAb 2c. Systemic treatment was performed by intravenous administration of mAb 2c 24 h prior to infection (pre-exposure prophylaxis) or 24, 40, and 56 hours after infection (post-exposure immunotherapy). Topical treatment was performed by periodical inoculations (5 times per day) of antibody-containing eye drops as control, starting at 24 h post infection. Systemic antibody treatment markedly reduced viral loads at the site of infection and completely protected mice from developing HSK. The administration of the antiviral antibody prior or post infection was equally effective. Topical treatment had no improving effect on the severity of HSK. In conclusion, our data demonstrate that mAb 2c proved to be an excellent drug for the treatment of corneal HSV-infections and for prevention of HSK and blindness. Moreover, the humanized counterpart (mAb hu2c) was equally effective in protecting mice from HSV-induced HSK when compared to the parental mouse antibody. These results warrant the future development of this antibody as a novel approach for the treatment of corneal HSV-infections in humans. PMID:25587898

  6. Prevention of herpes simplex virus induced stromal keratitis by a glycoprotein B-specific monoclonal antibody.

    Directory of Open Access Journals (Sweden)

    Adalbert Krawczyk

    Full Text Available The increasing incidence of acyclovir (ACV and multidrug-resistant strains in patients with corneal HSV-1 infections leading to Herpetic Stromal Keratitis (HSK is a major health problem in industrialized countries and often results in blindness. To overcome this obstacle, we have previously developed an HSV-gB-specific monoclonal antibody (mAb 2c that proved to be highly protective in immunodeficient NOD/SCID-mice towards genital infections. In the present study, we examined the effectivity of mAb 2c in preventing the immunopathological disease HSK in the HSK BALB/c mouse model. Therefore, mice were inoculated with HSV-1 strain KOS on the scarified cornea to induce HSK and subsequently either systemically or topically treated with mAb 2c. Systemic treatment was performed by intravenous administration of mAb 2c 24 h prior to infection (pre-exposure prophylaxis or 24, 40, and 56 hours after infection (post-exposure immunotherapy. Topical treatment was performed by periodical inoculations (5 times per day of antibody-containing eye drops as control, starting at 24 h post infection. Systemic antibody treatment markedly reduced viral loads at the site of infection and completely protected mice from developing HSK. The administration of the antiviral antibody prior or post infection was equally effective. Topical treatment had no improving effect on the severity of HSK. In conclusion, our data demonstrate that mAb 2c proved to be an excellent drug for the treatment of corneal HSV-infections and for prevention of HSK and blindness. Moreover, the humanized counterpart (mAb hu2c was equally effective in protecting mice from HSV-induced HSK when compared to the parental mouse antibody. These results warrant the future development of this antibody as a novel approach for the treatment of corneal HSV-infections in humans.

  7. A comparison of targetting of neuroblastoma with MIBG and anti L1-CAM antibody mAb chCE7: therapeutic efficacy in a neuroblastoma xenograft model and imaging of neuroblastoma patients

    International Nuclear Information System (INIS)

    Hoefnagel, C.A.; Rutgers, M.; Buitenhuis, C.K.M.; Smets, L.A.; Kraker, J. de; Meli, M.; Carrel, F.; Schubiger, P.A.; Novak-Hofer, I.; Amstutz, H.

    2001-01-01

    Modine-131 labelled anti L1-CAM antibody mAb chCE7 was compared with the effective neuroblastoma-seeking agent 131 I-labelled metaiodobenzylguanidine (MIBG) with regard to (a) its therapeutic efficacy in treating nude mice with neuroblastoma xenografts and (b) its tumour targetting ability in neuroblastoma patients. The SK-N-SH tumour cells used in the mouse experiments show good MIBG uptake and provide a relatively low number of 6,300 binding sites/cell for mAb chCE7. Tumours were treated with single injections of 131 I-MIBG (110 MBq) and with 131 I-labelled mAb chCE7 (17 MBq) and both agents showed antitumour activity. After therapy with 131 I-chCE7, the subcutaneous tumours nearly disappeared; treatment with 131 I-MIBG was somewhat less effective, resulting in a 70% reduction in tumour volume. A calculated tumour regrowth delay of 9 days occurred with a radioactivity dose of 17 MBq of an irrelevant control antibody mAb 35, which does not bind to SK-N-SH cells, compared with a regrowth delay of 34 days with 131 I-mAb chCE7 and of 24 days with 131 I-MIBG. General toxicity appeared to be mild, as assessed by a transient, approximate 10% maximum decrease in body weight during the treatments. The superior growth inhibition achieved by 131 I-chCE7 compared with 131 I-MIBG can be explained by its prolonged retention in the tumours, due to slower normal tissue and plasma clearance. Cross-reaction of mAb chCE7 with L1-CAM present in normal human tissues was investigated by direct binding of radioiodinated mAb to frozen tissue sections. Results showed a strong reaction with normal human brain tissue and weak but detectable binding to normal adult kidney sections. Seven patients with recurrent neuroblastoma were sequentially imaged with 131 I-MIBG and 131 I-chCE7. The results underlined the heterogeneity of neuroblastoma and showed the two imaging modalities to be complementary. 131 I-chCE7 scintigraphy may have clinical utility in detecting metastases which do not

  8. A literatura como resistência política: traços neorrealistas na produção literária do Movimento dos Atingidos por Barragens (MAB

    Directory of Open Access Journals (Sweden)

    Carolina Alves Pereira

    2018-04-01

    Full Text Available Este trabalho busca analisar as relações existentes entre as produções literárias do inicio do século XX, com o surgimento da corrente neo-realista, e a literatura produzida pelo Movimento dos Atingidos por Barragens (MAB, como manifestação de resistência à cultura elitista, no que tange ao espaço das criações artísticas. Para tanto, discute-se a característica do neo-realismo como expressão literária definidora dos aspectos sociais e políticos representados nas obras da época. Analisa-se, também, o conceito de resistência como determinante para a definição da literatura marginalizada do movimento campesino (MAB. Por fim, a seguinte pesquisa ratifica a importância da literatura e das artes produzida para além das universidades e dos cânones habituais. Palavras-chave: Literatura de resistência, Neorrealismo, Movimento dos Atingidos por Barragens (MAB. _________________________ This paper analyzes the relationship between the literary productions of the early twentieth century, with the rise of neo-realist current, and the literature produced by the Brazilian social group called Movimento do Atingidos por Barragens (MAB as a manifestation of resistance to elitist culture in terms the space of artistic creations. To this aim, I discuss the characteristic of neorealism as the defining literary expression of social and political represented in the works of the time aspects. In addition, I analyze the concept of resistance as a determinant for defining the literature of marginalized campesino movement (MAB. Finally, the following research confirms the importance of literature and the arts produced in excess of the usual canons and universities. Keywords: Literature of Resistance, Neorealism, Movimento dos Atingidos por Barragens (MAB.

  9. Protein A affinity chromatography of Chinese hamster ovary (CHO) cell culture broths containing biopharmaceutical monoclonal antibody (mAb): Experiments and mechanistic transport, binding and equilibrium modeling.

    Science.gov (United States)

    Grom, Matic; Kozorog, Mirijam; Caserman, Simon; Pohar, Andrej; Likozar, Blaž

    2018-04-15

    Protein A-based affinity chromatography is a highly-efficient separation method to capture, purify and isolate biosimilar monoclonal antibodies (mAb) - an important medical product of biopharmaceutical industrial manufacturing. It is considered the most expensive step in purification downstream operations; therefore, its performance optimization offers a great cost saving in the overall production expenditure. The biochemical mixture-separating specific interaction experiments with Chinese hamster ovary (CHO) cell culture harvest, containing glycosylated extracellular immunoglobulins (Ig), were made using five different state-of-the-art commercial resins. Packing breakthrough curves were recorded at an array of prolonged residence times. A mathematical simulation model was developed, applied and validated in combination with non-linear regression algorithms on bed effluent concentrations to determine the previously-unknown binding properties of stationary phase materials. Apart from the columns' differential partitioning, the whole external system was also integrated. It was confirmed that internal pore diffusion is the global rate-limiting resistance of the compound retention process. Immobilizing substrate characteristics, obtained in this engineering study, are indispensable for the scale-up of the periodic counter-current control with mechanistic load, elution and wash reduction. Furthermore, unit's volumetric flow screening measurements revealed dynamic effect correlation to eluate quality parameters, like the presence of aggregates, the host cell-related impurities at supernatant's extended feeding, and titre. Numerical sensitivity outputs demonstrated the impacts of fluidics (e.g. axial dispersion coefficient), thermodynamics (Langmuir adsorption) and mass transfer fluxes. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. 47-mG2a: A Mouse IgG2a-Type of PcMab-47 Useful for Detecting Podocalyxin in Esophageal Cancers by Immunohistochemistry.

    Science.gov (United States)

    Kaneko, Mika K; Itai, Shunsuke; Yamada, Shinji; Kato, Yukinari

    2018-04-09

    Esophageal cancer is one of the highly malignant cancers. It comprises two of the most common histological tumor types: squamous cell carcinoma (SCC) and adenocarcinoma. SCC accounts for about 90% of esophageal cancers. Despite developments in treatment strategies, the prognosis and survival rate remain poor. Podocalyxin (PODXL) is a highly glycosylated type-I transmembrane protein. It is expressed in normal tissues such as kidney, heart, breast, and pancreas. Upregulation of PODXL correlates with tumor progression, invasion, and metastasis. Therefore, this glycoprotein could be a potential biomarker for predicting the prognosis of some cancers, for instance, brain, colorectal, oral, lung, bladder, prostate, and ovarian cancers. We previously developed a specific and sensitive anti-PODXL monoclonal antibody (mAb), PcMab-47 (mouse IgG 1 , kappa) and its mouse IgG 2a -type (47-mG 2a ). We showed their utility in immunohistochemical analysis of oral cancers. Herein, we demonstrate that PcMab-47 and 47-mG 2a can also be used to detect esophageal squamous cell carcinoma (ESCC) with this technique. These two antibodies, respectively, stained 123/130 (94.6%) and 127/130 (97.7%) ESCC cases, indicating that they can detect PODXL with high sensitivity in this carcinoma. Of more than 3+ cases, 47-mG 2a was more effective than PcMab-47, respectively, staining 56/127 (44.1%) and 41/123 (33.3%). Therefore, 47-mG 2a can be used for the detection of PODXL in ESCC using immunohistochemical analysis.

  11. Preparation of monoclonal antibodies against radiation-induced protein

    International Nuclear Information System (INIS)

    Nozawa, R.; Tanaka, A.; Watanabe, H.; Kitayama, S.

    1992-01-01

    We obtained the 6 monoclonal antibodies against gamma-induced proteins of Deinococcus radiodurans, and these antibodies were designated as Mab-3F, 4B, 4D, 4F, 4G and 12G. Using these antibodies, we investigated the relations between gamma-induced proteins and other stress protein in strain R1, and the induction of proteins were compared among strain R1, resistant mutant (rec1) and radiosensitive mutant (rec30). We found new 6 proteins recognized by these monoclonal antibodies which were induced after gamma-irradiation especially in strain R1 and rec 1, but not induced in strain rec30. We suppose that these proteins participate in repair of DNA damages including double strand breaks caused by gamma-irradiation. One of them was around 46kDa protein band recognized by Mab-12G, and this protein was so induced in a large quantity after irradiation that the protein could detect by gold staining. In addition to this observation, we found some proteins which were induced in R1 and rec 1 by gamma-irradiation and other stress, but not in strain rec30, such as 31kDa protein band recognized by Mab-3F, 4B and 4G, and other 11 proteins which were especially induced in irradiated strain R1. The latter proteins might be reinforcement factor to radioresistance such as GroE and DnaK, or participant in repair of damage by gamma-irradiation in strain R1. (author)

  12. Polysome profiling of mAb producing CHO cell lines links translational control of cell proliferation and recombinant mRNA loading onto ribosomes with global and recombinant protein synthesis.

    Science.gov (United States)

    Godfrey, Charlotte L; Mead, Emma J; Daramola, Olalekan; Dunn, Sarah; Hatton, Diane; Field, Ray; Pettman, Gary; Smales, C Mark

    2017-08-01

    mRNA translation is a key process determining growth, proliferation and duration of a Chinese hamster ovary (CHO) cell culture and influences recombinant protein synthesis rate. During bioprocessing, CHO cells can experience stresses leading to reprogramming of translation and decreased global protein synthesis. Here we apply polysome profiling to determine reprogramming and translational capabilities in host and recombinant monoclonal antibody-producing (mAb) CHO cell lines during batch culture. Recombinant cell lines with the fastest cell specific growth rates were those with the highest global translational efficiency. However, total ribosomal capacity, determined from polysome profiles, did not relate to the fastest growing or highest producing mAb cell line, suggesting it is the ability to utilise available machinery that determines protein synthetic capacity. Cell lines with higher cell specific productivities tended to have elevated recombinant heavy chain transcript copy numbers, localised to the translationally active heavy polysomes. The highest titre cell line was that which sustained recombinant protein synthesis and maintained high recombinant transcript copy numbers in polysomes. Investigation of specific endogenous transcripts revealed a number that maintained or reprogrammed into heavy polysomes, identifying targets for potential cell engineering or those with 5' untranslated regions that might be utilised to enhance recombinant transcript translation. © 2017 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. The humanized anti-human AMHRII mAb 3C23K exerts an anti-tumor activity against human ovarian cancer through tumor-associated macrophages.

    Science.gov (United States)

    Bougherara, Houcine; Némati, Fariba; Nicolas, André; Massonnet, Gérald; Pugnière, Martine; Ngô, Charlotte; Le Frère-Belda, Marie-Aude; Leary, Alexandra; Alexandre, Jérôme; Meseure, Didier; Barret, Jean-Marc; Navarro-Teulon, Isabelle; Pèlegrin, André; Roman-Roman, Sergio; Prost, Jean-François; Donnadieu, Emmanuel; Decaudin, Didier

    2017-11-21

    Müllerian inhibiting substance, also called anti-Müllerian hormone (AMH), inhibits proliferation and induces apoptosis of AMH type II receptor-positive tumor cells, such as human ovarian cancers (OCs). On this basis, a humanized glyco-engineered monoclonal antibody (3C23K) has been developed. The aim of this study was therefore to experimentally confirm the therapeutic potential of 3C23K in human OCs. We first determined by immunofluorescence, immunohistochemistry and cytofluorometry analyses the expression of AMHRII in patient's tumors and found that a majority (60 to 80% depending on the detection technique) of OCs were positive for this marker. We then provided evidence that the tumor stroma of OC is enriched in tumor-associated macrophages and that these cells are responsible for 3C23K-induced killing of tumor cells through ADCP and ADCC mechanisms. In addition, we showed that 3C23K reduced macrophages induced-T cells immunosuppression. Finally, we evaluated the therapeutic efficacy of 3C23K alone and in combination with a carboplatin-paclitaxel chemotherapy in a panel of OC Patient-Derived Xenografts. In those experiments, we showed that 3C23K significantly increased the proportion and the quality of chemotherapy-based in vivo responses. Altogether, our data support the potential interest of AMHRII targeting in human ovarian cancers and the evaluation of 3C23K in further clinical trials.

  14. Oregovomab: anti-CA-125 monoclonal antibody B43.13--AltaRex, B43.13, MAb B43.13, monoclonal antibody B43.13.

    Science.gov (United States)

    2006-01-01

    ViRexx Medical Corp is developing the murine monoclonal antibody oregovomab [OvaRex, MAb B43.13] for the treatment of ovarian cancer. Oregovomab targets the circulating tumour-associated antigen CA 125, which is shed from the surface of human ovarian cancer cells; the antibodies induce broad cellular and humoral immune responses against CA 125 via complex formation. Unlike free CA 125, CA 125-oregovomab complexes can prime dendritic cells, leading to downstream activation of T cells. The antibody is undergoing advanced clinical development. AltaRex, the originator of oregovomab, was acquired by, and merged into, ViRexx Medical Corp in December 2004. AltaRex (now ViRexx Medical Corp) has established several strategic corporate alliances for the development and/or commercialisation of oregovomab. Unither Pharmaceuticals, a subsidiary of United Therapeutics Corporation, entered into a licensing agreement with ViRexx in April 2002. The agreement covers most territories worldwide, except Europe and the Middle East, which are covered by other agreements (see below); ViRexx did retain the rights to most member nations of the EU and certain other countries. In August 2003, the agreement was extended, granting United Therapeutics Corporation development rights for Germany. AltaRex and Dompe entered into a distribution agreement for oregovomab in July 2004. Territories included in the agreement are Italy, Spain, Portugal, Hungary, Poland, Czech Republic, Switzerland, Austria and certain other Eastern European countries. Under the terms of the agreement, ViRexx retains responsibility for product development and registration of the antibody, upon commercialisation in the agreed territory. The two companies will work closely to achieve product registration throughout Europe. In June 2001, Dompe entered into a sublicensing agreement with FAES for the commercialisation of oregovomab in Spain and Portugal. ViRexx is also seeking collaboration partners for Northern European markets

  15. Aggregate complexes of HIV-1 induced by multimeric antibodies.

    Science.gov (United States)

    Stieh, Daniel J; King, Deborah F; Klein, Katja; Liu, Pinghuang; Shen, Xiaoying; Hwang, Kwan Ki; Ferrari, Guido; Montefiori, David C; Haynes, Barton; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Rerks-Ngarm, Supachai; Michael, Nelson L; Robb, Merlin L; Kim, Jerome H; Denny, Thomas N; Tomaras, Georgia D; Shattock, Robin J

    2014-10-02

    Antibody mediated viral aggregation may impede viral transfer across mucosal surfaces by hindering viral movement in mucus, preventing transcytosis, or reducing inter-cellular penetration of epithelia thereby limiting access to susceptible mucosal CD4 T cells and dendritic cells. These functions may work together to provide effective immune exclusion of virus from mucosal tissue; however little is known about the antibody characteristics required to induce HIV aggregation. Such knowledge may be critical to the design of successful immunization strategies to facilitate viral immune exclusion at the mucosal portals of entry. The potential of neutralizing and non-neutralizing IgG and IgA monoclonals (mAbs) to induce HIV-1 aggregation was assessed by Dynamic light scattering (DLS). Although neutralizing and non-neutralizing IgG mAbs and polyclonal HIV-Ig efficiently aggregated soluble Env trimers, they were not capable of forming viral aggregates. In contrast, dimeric (but not monomeric) IgA mAbs induced stable viral aggregate populations that could be separated from uncomplexed virions. Epitope specificity influenced both the degree of aggregation and formation of higher order complexes by dIgA. IgA purified from serum of uninfected RV144 vaccine trial responders were able to efficiently opsonize viral particles in the absence of significant aggregation, reflective of monomeric IgA. These results collectively demonstrate that dIgA is capable of forming stable viral aggregates providing a plausible basis for testing the effectiveness of aggregation as a potential protection mechanism at the mucosal portals of viral entry.

  16. Interleukin-12 promotes activation of effector cells that induce a severe destructive granulomatous form of murine experimental autoimmune thyroiditis.

    OpenAIRE

    Braley-Mullen, H.; Sharp, G. C.; Tang, H.; Chen, K.; Kyriakos, M.; Bickel, J. T.

    1998-01-01

    Granulomatous inflammatory lesions are a major histopathological feature of a wide spectrum of human infectious and autoimmune diseases. Experimental autoimmune thyroiditis (EAT) with granulomatous histopathological features can be induced by mouse thyroglobulin (MTg)-sensitized spleen cells activated in vitro with MTg and anti-interleukin-2 receptor (anti-IL-2R), anti-IL-2, or anti-interferon-gamma (anti-IFN-gamma) monoclonal antibody (MAb). These studies suggested that IFN-gamma-producing T...

  17. Oxidative Stress-Responsive Apoptosis Inducing Protein (ORAIP) Plays a Critical Role in High Glucose-Induced Apoptosis in Rat Cardiac Myocytes and Murine Pancreatic β-Cells.

    Science.gov (United States)

    Yao, Takako; Fujimura, Tsutomu; Murayama, Kimie; Okumura, Ko; Seko, Yoshinori

    2017-10-18

    We previously identified a novel apoptosis-inducing humoral factor in the conditioned medium of hypoxic/reoxygenated-cardiac myocytes. We named this novel post-translationally-modified secreted-form of eukaryotic translation initiation factor 5A Oxidative stress-Responsive Apoptosis-Inducing Protein (ORAIP). We confirmed that myocardial ischemia/reperfusion markedly increased plasma ORAIP levels and rat myocardial ischemia/reperfusion injury was clearly suppressed by neutralizing anti-ORAIP monoclonal antibodies (mAbs) in vivo. In this study, to investigate the mechanism of cell injury of cardiac myocytes and pancreatic β-cells involved in diabetes mellitus (DM), we analyzed plasma ORAIP levels in DM model rats and the role of ORAIP in high glucose-induced apoptosis of cardiac myocytes in vitro. We also examined whether recombinant-ORAIP induces apoptosis in pancreatic β-cells. Plasma ORAIP levels in DM rats during diabetic phase were about 18 times elevated as compared with non-diabetic phase. High glucose induced massive apoptosis in cardiac myocytes (66.2 ± 2.2%), which was 78% suppressed by neutralizing anti-ORAIP mAb in vitro. Furthermore, recombinant-ORAIP clearly induced apoptosis in pancreatic β-cells in vitro. These findings strongly suggested that ORAIP plays a pivotal role in hyperglycemia-induced myocardial injury and pancreatic β-cell injury in DM. ORAIP will be a biomarker and a critical therapeutic target for cardiac injury and progression of DM itself.

  18. A study of the use of radioimmunoscintigraphy (RIA) with the monoclonal antibody MAb-170, and fluorine-18 flurodeoxyglucose positron emission tomography (18FDG-PET) for the preoperative imaging of complex ovarian masses and their ability to identify ovarian cancer

    Science.gov (United States)

    Lieberman, Gidon

    The hypothesis for this study is whether the newer diagnostic techniques of radioimmunoscintigraphy (RIS) utilising radiolabelled monoclonal antibodies and 2-[[18]F] fluoro-2-deoxy-D-glucose ([18]FDG) imaging using a double headed gamma camera offer improvements in preoperative selection for referral of patients to Cancer Centres. Monoclonal antibody radioimmunoscintigraphy (RIS) is hindered by several factors including false positive results due to physiological excretion, concern over production of human anti-mouse antibodies (HAMA) that would prevent repeated doses and difficulty in precisely relating areas of accumulation and anatomy. [18]FDG imaging relies on the accumulation of radiolabelled sugars, and subsequent breakdown products within tumour. [18]FDG imaging with dedicated positron emission tomography has real potential, but its use is limited by large capital outlay. Newer techniques involving "dual headed cameras" (DHC) offer PET capability at a lower cost. Chapter two describes the evaluation of a monoclonal antibody (MAb-170) in 27 women who presented with suspicious pelvic masses. The preoperative clinical, radiological and radioimmunoscintigraphy findings are compared to those at surgery and subsequent histology. All 18 patients with malignant or borderline ovarian cancer were correctly identified using RIS. The overall sensitivity and specificity for all sites were 100% and 38%. RIS was particularly useful in the identification of (intra-abdominal) serosal deposits. Enzyme linked immunosorbant assay (ELISA) was used to quantify the HAMA. A strong HAMA production was seen in at least 3 patients, however HAMA response was independent of clinical parameters. Chapter three describes the immunohistochemical staining of paraffin embedded biopsy specimens from the 27 patients who underwent RIS with MAb-170. The original research into the cellular location of the specific epitope to which the antibody interacts was performed on isopentane frozen biopsies

  19. CD99 triggering induces methuosis of Ewing sarcoma cells through IGF-1R/RAS/Rac1 signaling.

    Science.gov (United States)

    Manara, Maria Cristina; Terracciano, Mario; Mancarella, Caterina; Sciandra, Marika; Guerzoni, Clara; Pasello, Michela; Grilli, Andrea; Zini, Nicoletta; Picci, Piero; Colombo, Mario P; Morrione, Andrea; Scotlandi, Katia

    2016-11-29

    CD99 is a cell surface molecule that has emerged as a novel target for Ewing sarcoma (EWS), an aggressive pediatric bone cancer. This report provides the first evidence of methuosis in EWS, a non-apoptotic form of cell death induced by an antibody directed against the CD99 molecule. Upon mAb triggering, CD99 induces an IGF-1R/RAS/Rac1 complex, which is internalized into RAB5-positive endocytic vacuoles. This complex is then dissociated, with the IGF-1R recycling to the cell membrane while CD99 and RAS/Rac1 are sorted into immature LAMP-1-positive vacuoles, whose excessive accumulation provokes methuosis. This process, which is not detected in CD99-expressing normal mesenchymal cells, is inhibited by disruption of the IGF-1R signaling, whereas enhanced by IGF-1 stimulation. Induction of IGF-1R/RAS/Rac1 was also observed in the EWS xenografts that respond to anti-CD99 mAb, further supporting the role of the IGF/RAS/Rac1 axis in the hyperstimulation of macropinocytosis and selective death of EWS cells. Thus, we describe a vulnerability of EWS cells, including those resistant to standard chemotherapy, to a treatment with anti-CD99 mAb, which requires IGF-1R/RAS signaling but bypasses the need for their direct targeting. Overall, we propose CD99 targeting as new opportunity to treat EWS patients resistant to canonical apoptosis-inducing agents.

  20. Enhancement of CD147 on M1 macrophages induces differentiation of Th17 cells in the lung interstitial fibrosis.

    Science.gov (United States)

    Geng, Jie-jie; Zhang, Kui; Chen, Li-na; Miao, Jin-lin; Yao, Meng; Ren, Ying; Fu, Zhi-guang; Chen, Zhi-nan; Zhu, Ping

    2014-09-01

    Lung interstitial fibrosis is a chronic lung disease, and few effective therapies are available to halt or reverse the progression of the disease. In murine and human lung fibrosis, the expression of CD147 is increased. However, the role of CD147 in lung fibrosis has not been identified, and it remains to be determined whether lung fibrosis would be improved by decreasing the expression of CD147. A murine bleomycin-induced lung interstitial fibrosis model was used in the experiments, and HAb18 mAbs and CsA were administered during the induction of lung fibrosis. In our study, we found that the HAb18 mAbs markedly reduced the collagen score and down-regulated M1 macrophages and Th17 cells. In vitro, flow cytometry analysis showed that M1 macrophages induced higher Th17 differentiation than M2 macrophages. After treatment with HAb18 mAbs or after reducing the expression of CD147 by lentivirus interference in M1 macrophages, the level of Th17 cells were significantly inhibited. In conclusion, HAb18 mAbs or CsA treatment ameliorates lung interstitial fibrosis. CD147 promoted M1 macrophage and induced the differentiation of Th17 cells in lung interstitial fibrosis, perhaps by regulating some cytokines such as IL-6, IL-1β, IL-12 and IL-23. These results indicated that CD147 may play an important role in the development of lung interstitial fibrosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Canakinumab (ACZ885, a fully human IgG1 anti-IL-1β mAb) induces sustained remission in pediatric patients with cryopyrin-associated periodic syndrome (CAPS).

    Science.gov (United States)

    Kuemmerle-Deschner, Jasmin B; Ramos, Eduardo; Blank, Norbert; Roesler, Joachim; Felix, Sandra D; Jung, Thomas; Stricker, Kirstin; Chakraborty, Abhijit; Tannenbaum, Stacey; Wright, Andrew M; Rordorf, Christiane

    2011-02-28

    Cryopyrin-associated periodic syndrome (CAPS) represents a spectrum of three auto-inflammatory syndromes, familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease/chronic infantile neurological cutaneous and articular syndrome (NOMID/CINCA) with etiology linked to mutations in the NLRP3 gene resulting in elevated interleukin-1β (IL-1β) release. CAPS is a rare hereditary auto-inflammatory disease, which may start early in childhood and requires a life-long treatment. Canakinumab, a fully human anti-IL-1β antibody, produces sustained selective inhibition of IL-1β. This study was conducted to assess the efficacy, safety, and pharmacokinetics of canakinumab in the treatment of pediatric CAPS patients. Seven pediatric patients (five children and two adolescents) with CAPS were enrolled in a phase II, open-label study of canakinumab in patients with CAPS. Canakinumab was administered at a dose of 2 mg/kg subcutaneously (s.c.) (for patients with body weight ≤ 40 kg) or 150 mg s.c. (for patients with body weight > 40 kg) with re-dosing upon each relapse. The primary efficacy variable was time to relapse following achievement of a complete response (defined as a global assessment of no or minimal disease activity and no or minimal rash and values for serum C-reactive protein (CRP) and/or serum amyloid A (SAA) within the normal range, CAPS. ClinicalTrials.gov: NCT00487708.

  2. CD99 triggering induces methuosis of Ewing sarcoma cells through IGF-1R/RAS/Rac1 signaling

    OpenAIRE

    Manara, Maria Cristina; Terracciano, Mario; Mancarella, Caterina; Sciandra, Marika; Guerzoni, Clara; Pasello, Michela; Grilli, Andrea; Zini, Nicoletta; Picci, Piero; Colombo, Mario P.; Morrione, Andrea; Scotlandi, Katia

    2016-01-01

    CD99 is a cell surface molecule that has emerged as a novel target for Ewing sarcoma (EWS), an aggressive pediatric bone cancer. This report provides the first evidence of methuosis in EWS, a non-apoptotic form of cell death induced by an antibody directed against the CD99 molecule. Upon mAb triggering, CD99 induces an IGF-1R/RAS/Rac1 complex, which is internalized into RAB5-positive endocytic vacuoles. This complex is then dissociated, with the IGF-1R recycling to the cell membrane while CD9...

  3. Immunization of chickens with an agonistic monoclonal anti-chicken CD40 antibody-hapten complex: rapid and robust IgG response induced by a single subcutaneous injection.

    Science.gov (United States)

    Chen, Chang-Hsin; Abi-Ghanem, Daad; Waghela, Suryakant D; Chou, Wen-Ko; Farnell, Morgan B; Mwangi, Waithaka; Berghman, Luc R

    2012-04-30

    Producing diagnostic antibodies in chicken egg yolk represents an alternate animal system that offers many advantages including high productivity at low cost. Despite being an excellent counterpart to mammalian antibodies, chicken IgG from yolk still represents an underused resource. The potential of agonistic monoclonal anti-CD40 antibodies (mAb) as a powerful immunological adjuvant has been demonstrated in mammals, but not in chickens. We recently reported an agonistic anti-chicken CD40 mAb (designated mAb 2C5) and showed that it may have potential as an immunological adjuvant. In this study, we examined the efficacy of targeting a short peptide to chicken CD40 [expressed by the antigen-presenting cells (APCs)] in enhancing an effective IgG response in chickens. For this purpose, an immune complex consisting of one streptavidin molecule, two directionally biotinylated mAb 2C5 molecules, and two biotinylated peptide molecules was produced. Chickens were immunized subcutaneously with doses of this complex ranging from 10 to 90 μg per injection once, and relative quantification of the peptide-specific IgG response showed that the mAb 2C5-based complex was able to elicit a strong IgG response as early as four days post-immunization. This demonstrates that CD40-targeting antigen to chicken APCs can significantly enhance antibody responses and induce immunoglobulin isotype-switching. This immunization strategy holds promise for rapid production of hapten-specific IgG in chickens. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Protective Effect of CXCR3+CD4+CD25+Foxp3+ Regulatory T Cells in Renal Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Cao Jun

    2015-01-01

    Full Text Available Regulatory T cells (Tregs suppress excessive immune responses and are potential therapeutic targets in autoimmune disease and organ transplantation rejection. However, their role in renal ischemia-reperfusion injury (IRI is unclear. Levels of Tregs and expression of CXCR3 in Tregs were analyzed to investigate their function in the early phase of renal IRI. Mice were randomly divided into Sham, IRI, and anti-CD25 (PC61 + IRI groups. The PC61 + IRI group was established by i.p. injection of PC61 monoclonal antibody (mAb to deplete Tregs before renal ischemia. CD4+CD25+Foxp3+ Tregs and CXCR3 on Tregs were analyzed by flow cytometry. Blood urea nitrogen (BUN, serum creatinine (Scr levels, and tubular necrosis scores, all measures of kidney injury, were greater in the IRI group than in the Sham group. Numbers of Tregs were increased at 72 h after reperfusion in kidney. PC61 mAb preconditioning decreased the numbers of Tregs and aggravated kidney injury. There was no expression of CXCR3 on Tregs in normal kidney, while it expanded at 72 h after reperfusion and inversely correlated with BUN, Scr, and kidney histology score. This indicated that recruitment of Tregs into the kidney was related to the recovery of renal function after IRI and CXCR3 might be involved in the migration of Tregs.

  5. Induced Abortion

    Science.gov (United States)

    ... Education & Events Advocacy For Patients About ACOG Induced Abortion Home For Patients Search FAQs Induced Abortion Page ... Induced Abortion FAQ043, May 2015 PDF Format Induced Abortion Special Procedures What is an induced abortion? What ...

  6. The therapeutic CD38 monoclonal antibody daratumumab induces programmed cell death via fcg receptor-mediated cross-linking

    DEFF Research Database (Denmark)

    Overdijk, Marije B.; Jansen, J. H. Marco; Nederend, Maaike

    2016-01-01

    RIIb as well as activating FcgRs induce DARA cross-linking-mediated PCD. In conclusion, our in vitro and in vivo data show that FcgRmediated cross-linking of DARA induces PCD of CD38-expressing multiple myeloma tumor cells, which potentially contributes to the depth of response observed in DARA......Emerging evidence suggests that FcgR-mediated cross-linking of tumor-bound mAbs may induce signaling in tumor cells that contributes to their therapeutic activity. In this study, we show that daratumumab (DARA), a therapeutic human CD38 mAb with a broad-spectrum killing activity, is able to induce...... programmed cell death (PCD) of CD38+ multiple myeloma tumor cell lines when cross-linked in vitro by secondary Abs or via an FcgR. By comparing DARA efficacy in a syngeneic in vivo tumor model using FcRg-chain knockout or NOTAM mice carrying a signaling-inactive FcRg-chain, we found that the inhibitory Fcg...

  7. Interleukin-2 induces tyrosine phosphorylation and nuclear translocation of stat3 in human T lymphocytes

    DEFF Research Database (Denmark)

    Nielsen, M; Svejgaard, A; Skov, S

    1994-01-01

    that stimulation through the IL-2R induced tyrosine phosphorylation and subsequent nuclear translocation of stat3, a newly identified member of the signal transducers and activators of transcription (STAT) family of proteins. In contrast, stat1 proteins were not tyrosine phosphorylated after IL-2 ligation, whereas...... an apparent molecular mass of 84 kDa and was not recognized by stat3 or stat1 mAb or antisera. Since IL-2 induced nuclear translocation of the 84 kDa protein and stat3 followed identical kinetics, p84 is a candidate for a new, yet undefined, member of the STAT family. Taken together, we report that IL-2...... induces tyrosine phosphorylation and subsequent nuclear translocation of stat3 and an as yet undefined 84-kDa protein in antigen-specific human T cell lines....

  8. An antibody that prevents serpin polymerisation acts by inducing a novel allosteric behaviour.

    Science.gov (United States)

    Motamedi-Shad, Neda; Jagger, Alistair M; Liedtke, Maximilian; Faull, Sarah V; Nanda, Arjun Scott; Salvadori, Enrico; Wort, Joshua L; Kay, Christopher W M; Heyer-Chauhan, Narinder; Miranda, Elena; Perez, Juan; Ordóñez, Adriana; Haq, Imran; Irving, James A; Lomas, David A

    2016-10-01

    Serpins are important regulators of proteolytic pathways with an antiprotease activity that involves a conformational transition from a metastable to a hyperstable state. Certain mutations permit the transition to occur in the absence of a protease; when associated with an intermolecular interaction, this yields linear polymers of hyperstable serpin molecules, which accumulate at the site of synthesis. This is the basis of many pathologies termed the serpinopathies. We have previously identified a monoclonal antibody (mAb4B12) that, in single-chain form, blocks α1-antitrypsin (α1-AT) polymerisation in cells. Here, we describe the structural basis for this activity. The mAb4B12 epitope was found to encompass residues Glu32, Glu39 and His43 on helix A and Leu306 on helix I. This is not a region typically associated with the serpin mechanism of conformational change, and correspondingly the epitope was present in all tested structural forms of the protein. Antibody binding rendered β-sheet A - on the opposite face of the molecule - more liable to adopt an 'open' state, mediated by changes distal to the breach region and proximal to helix F. The allosteric propagation of induced changes through the molecule was evidenced by an increased rate of peptide incorporation and destabilisation of a preformed serpin-enzyme complex following mAb4B12 binding. These data suggest that prematurely shifting the β-sheet A equilibrium towards the 'open' state out of sequence with other changes suppresses polymer formation. This work identifies a region potentially exploitable for a rational design of ligands that is able to dynamically influence α1-AT polymerisation. © 2016 The Author(s).

  9. TWEAK induces liver progenitor cell proliferation

    Science.gov (United States)

    Jakubowski, Aniela; Ambrose, Christine; Parr, Michael; Lincecum, John M.; Wang, Monica Z.; Zheng, Timothy S.; Browning, Beth; Michaelson, Jennifer S.; Baestcher, Manfred; Wang, Bruce; Bissell, D. Montgomery; Burkly, Linda C.

    2005-01-01

    Progenitor (“oval”) cell expansion accompanies many forms of liver injury, including alcohol toxicity and submassive parenchymal necrosis as well as experimental injury models featuring blocked hepatocyte replication. Oval cells can potentially become either hepatocytes or biliary epithelial cells and may be critical to liver regeneration, particularly when hepatocyte replication is impaired. The regulation of oval cell proliferation is incompletely understood. Herein we present evidence that a TNF family member called TWEAK (TNF-like weak inducer of apoptosis) stimulates oval cell proliferation in mouse liver through its receptor Fn14. TWEAK has no effect on mature hepatocytes and thus appears to be selective for oval cells. Transgenic mice overexpressing TWEAK in hepatocytes exhibit periportal oval cell hyperplasia. A similar phenotype was obtained in adult wild-type mice, but not Fn14-null mice, by administering TWEAK-expressing adenovirus. Oval cell expansion induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) was significantly reduced in Fn14-null mice as well as in adult wild-type mice with a blocking anti-TWEAK mAb. Importantly, TWEAK stimulated the proliferation of an oval cell culture model. Finally, we show increased Fn14 expression in chronic hepatitis C and other human liver diseases relative to its expression in normal liver, which suggests a role for the TWEAK/Fn14 pathway in human liver injury. We conclude that TWEAK has a selective mitogenic effect for liver oval cells that distinguishes it from other previously described growth factors. PMID:16110324

  10. Detection of irradiation-induced, membrane heat shock protein 70 (Hsp70) in mouse tumors using Hsp70 Fab fragment

    International Nuclear Information System (INIS)

    Stangl, Stefan; Themelis, George; Friedrich, Lars; Ntziachristos, Vasilis; Sarantopoulos, Athanasios; Molls, Michael; Skerra, Arne; Multhoff, Gabriele

    2011-01-01

    Background and purpose: The major stress-inducible heat shock protein 70 (Hsp70) is frequently overexpressed in highly aggressive tumors, and elevated intracellular Hsp70 levels mediate protection against apoptosis. Following therapeutic intervention, such as ionizing irradiation, translocation of cytosolic Hsp70 to the plasma membrane is selectively increased in tumor cells and therefore, membrane Hsp70 might serve as a therapy-inducible, tumor-specific target structure. Materials and methods: Based on the IgG1 mouse monoclonal antibody (mAb) cmHsp70.1, we produced the Hsp70-specific recombinant Fab fragment (Hsp70 Fab), as an imaging tool for the detection of membrane Hsp70 positive tumor cells in vitro and in vivo. Results: The binding characteristics of Hsp70 Fab towards mouse colon (CT26) and pancreatic (1048) carcinoma cells at 4 deg. C were comparable to that of cmHsp70.1 mAb, as determined by flow cytometry. Following a temperature shift to 37 deg. C, Hsp70 Fab rapidly translocates into subcellular vesicles of mouse tumor cells. Furthermore, in tumor-bearing mice Cy5.5-conjugated Hsp70 Fab, but not unrelated IN-1 control Fab fragment (IN-1 ctrl Fab), gradually accumulates in CT26 tumors between 12 and 55 h after i.v. injection. Conclusions: In summary, the Hsp70 Fab provides an innovative, low immunogenic tool for imaging of membrane Hsp70 positive tumors, in vivo.

  11. Feasibility and toxicity of concomitant radio/immunotherapy with MabThera (Rituximab {sup registered}) for patients with non-Hodgkin's lymphoma. Results of a prospective phase I/II study

    Energy Technology Data Exchange (ETDEWEB)

    Haidenberger, Alfred; Popper, Bela-Andre; Skvortsova, Ira; Lukas, Peter [Medical Univ. Innsbruck (Austria). Dept. of Radiotherapy/Radiooncology; Fromm-Haidenberger, Sabine [Hospital Gmunden (Austria). Inst. of Radiology; Vries, Alexander de [Hospital Feldkirch (Austria). Dept. of Radiotherapy/Radiooncology; Steurer, Michael; Kantner, Johanna; Gunsilius, Eberhard [Medical Univ. Innsbruck (Austria). Dept. of Hematology

    2011-05-15

    Purpose: Non-Hodgkin's lymphomas (NHL) have a high radio- and chemosensitivity. Although initially responsive, approximately 50% of low grade B-cell lymphomas relapse after 10-15 years. Besides chemo- and radiotherapy, rituximab, a mouse/human chimeric antibody targeting CD20 antigen on the surface of B-cell lymphoma cells, is another treatment approach. In vitro data showed potentiation of radiation-induced apoptosis by addition of rituximab. The purpose of this study was to evaluate the feasibility and toxicity of radiotherapy with concomitant application of rituximab in NHL patients. Patients and Methods: A total of 21 patients with B-cell lymphoma (stage I: n = 11; II: n = 5; III: n = 1; IV: n = 4) were included in this study, treated with radiotherapy of 30-40 Gy and weekly application of rituximab (375 mg/m{sup 2}). Nine patients had R-CHOP chemotherapy previously, 1 patient leuceran chemotherapy, and 2 patients an initial treatment with 6 cycles of rituximab. Mean time of follow-up was 41.7 months. Results: No grade 4 toxicity or treatment-related death was observed. In 1 patient, rituximab application had to be stopped after 3 cycles due to radiation-induced side effects. No late toxicities were reported. All patients were in complete remission after treatment. Progression or relapse was observed in 6 patients (28%); the mean time to progression was 27 months. The mean overall survival (OS) was 53 months. Conclusion: Combined radio/immunotherapy is feasible and safe. Treatment was well tolerated, no late toxicities were observed, and treatment outcome is promising. Randomized trials are necessary to clarify the benefit of this treatment approach and its applicability. (orig.)

  12. Role of tumor necrosis factor-alpha and platelet-activating factor in neoangiogenesis induced by synovial fluids of patients with rheumatoid arthritis.

    Science.gov (United States)

    Lupia, E; Montrucchio, G; Battaglia, E; Modena, V; Camussi, G

    1996-08-01

    The aim of the present study was to investigate in vivo in a mouse model the stimulation of neoangiogenesis by synovial fluids of patients with rheumatoid arthritis (RA) and to determine the role of tumor necrosis factor (TNF)-alpha and platelet-activating factor (PAF) in the formation of new vessels. Angiogenesis was studied in a mouse model in which Matrigel, injected subcutaneously, was used as a vehicle for the delivery of potential angiogenic stimuli. Synovial fluids of patients with RA but not with osteoarthritis (OA) were shown to induce neoangiogenesis. Since synovial fluid of patients with RA contained significantly higher levels of TNF-alpha-like bioactivity and of PAF than that of patients with OA, the role of these mediators was evaluated by using an anti-TNF-alpha neutralizing monoclonal antibody (mAb) and a PAF receptor antagonist, WEB 2170. When added to Matrigel, anti-TNF-alpha mAb and particularly WEB 2170 significantly reduced neoangiogenesis induced by synovial fluids of RA patients. Moreover, PAF extracted and purified from synovial fluid induced angiogenesis. These results suggest that the neoangiogenesis observed in rheumatoid synovitis may be due, at least in part, to the angiogenic effect of locally produced TNF-alpha and PAF.

  13. Antibody-Induced Internalization of the Human Respiratory Syncytial Virus Fusion Protein.

    Science.gov (United States)

    Leemans, A; De Schryver, M; Van der Gucht, W; Heykers, A; Pintelon, I; Hotard, A L; Moore, M L; Melero, J A; McLellan, J S; Graham, B S; Broadbent, L; Power, U F; Caljon, G; Cos, P; Maes, L; Delputte, P

    2017-07-15

    Respiratory syncytial virus (RSV) infections remain a major cause of respiratory disease and hospitalizations among infants. Infection recurs frequently and establishes a weak and short-lived immunity. To date, RSV immunoprophylaxis and vaccine research is mainly focused on the RSV fusion (F) protein, but a vaccine remains elusive. The RSV F protein is a highly conserved surface glycoprotein and is the main target of neutralizing antibodies induced by natural infection. Here, we analyzed an internalization process of antigen-antibody complexes after binding of RSV-specific antibodies to RSV antigens expressed on the surface of infected cells. The RSV F protein and attachment (G) protein were found to be internalized in both infected and transfected cells after the addition of either RSV-specific polyclonal antibodies (PAbs) or RSV glycoprotein-specific monoclonal antibodies (MAbs), as determined by indirect immunofluorescence staining and flow-cytometric analysis. Internalization experiments with different cell lines, well-differentiated primary bronchial epithelial cells (WD-PBECs), and RSV isolates suggest that antibody internalization can be considered a general feature of RSV. More specifically for RSV F, the mechanism of internalization was shown to be clathrin dependent. All RSV F-targeted MAbs tested, regardless of their epitopes, induced internalization of RSV F. No differences could be observed between the different MAbs, indicating that RSV F internalization was epitope independent. Since this process can be either antiviral, by affecting virus assembly and production, or beneficial for the virus, by limiting the efficacy of antibodies and effector mechanism, further research is required to determine the extent to which this occurs in vivo and how this might impact RSV replication. IMPORTANCE Current research into the development of new immunoprophylaxis and vaccines is mainly focused on the RSV F protein since, among others, RSV F-specific antibodies are

  14. POLÍTICAS PÚBLICAS PARA INCENTIVAR EL ACCESO A LA FINANCIACIÓN DE LAS PYMES EN ESPAÑA: EL MERCADO ALTERNATIVO BURSÁTIL (MAB / PUBLIC POLICY TO PROMOTE ACCESS TO FINANCING OF SMES IN SPAIN: THE ALTERNATIVE INVESTMENT MARKET (AIM

    Directory of Open Access Journals (Sweden)

    Álvaro GONZÁLEZ LORENTE

    2012-09-01

    Full Text Available La crisis económica actual ha afectado a las posibilidades de captación de financiación de las pequeñas y medianas empresas españolas. Al endurecimiento de las condiciones crediticias hay que sumarle también el aumento del riesgo debido, por un lado, al incremento de la morosidad y, por otro, a la caída del volumen de ventas provocado tanto por la notable pérdida de poder adquisitivo de los consumidores como por el aumento de su desconfianza. En este contexto el Mercado Alternativo Bursátil –en adelante MAB-, surge como un mercado de valores creado y destinado a proveer de financiación a empresas de menor capitalización que, no obstante, desean expandirse y poder llegar a más mercados de lo que su propia estructura financiera podría permitir. El principal objetivo del MAB es dotar de recursos financieros, mediante la aportación de recursos propios, a empresas en fase de expansión, tanto nacional como internacional. En el presente trabajo se analizarán las principales características de este novedoso mercado, así como las ventajas fiscales que incorpora tanto para los inversores como para las empresas. / The current economic crisis has affected the chances of attracting financing of small and medium-sized Spanish companies. To the tightening of credit conditions we must add also the increased risk because, on the one hand, the increase in defaults and, secondly, the fall in sales volume caused both by the significant loss of purchasing power of consumers as by increasing distrust. In this context the Alternative Investment Market (AIM, emerges as an alternative stock exchange market to provide financing to smaller companies, that however, want to expand and reach more markets than its own financial structure could afford. The main objective of the AIM is to provide financial resources, by increasing equity to companies undergoing expansion, both nationally and internationally. In this paper we analyze the main characteristics

  15. An oncolytic adenovirus regulated by a radiation-inducible promoter selectively mediates hSulf-1 gene expression and mutually reinforces antitumor activity of I131-metuximab in hepatocellular carcinoma.

    Science.gov (United States)

    Zhang, Yan; Fang, Lin; Zhang, Quan'an; Zheng, Qin; Tong, Jinlong; Fu, Xiaohui; Jiang, Xiaoqing; Su, Changqing; Zheng, Junnian

    2013-06-01

    Gene therapy and antibody approaches are crucial auxiliary strategies for hepatocellular carcinoma (HCC) treatment. Previously, we established a survivin promoter-regulated oncolytic adenovirus that has inhibitory effect on HCC growth. The human sulfatase-1 (hSulf-1) gene can suppress the growth factor signaling pathways, then inhibit the proliferation of cancer cells and enhance cellular sensitivity to radiotherapy and chemotherapy. I(131)-metuximab (I(131)-mab) is a monoclonal anti-HCC antibody that conjugated to I(131) and specifically recognizes the HAb18G/CD147 antigen on HCC cells. To integrate the oncolytic adenovirus-based gene therapy and the I(131)-mab-based radioimmunotherapy, this study combined the CArG element of early growth response-l (Egr-l) gene with the survivin promoter to construct a radiation-inducible enhanced promoter, which was used to recombine a radiation-inducible oncolytic adenovirus as hSulf-1 gene vector. When I(131)-mab was incorporated into the treatment regimen, not only could the antibody produce radioimmunotherapeutic effect, but the I(131) radiation was able to further boost adenoviral proliferation. We demonstrated that the CArG-enhanced survivin promoter markedly improved the proliferative activity of the oncolytic adenovirus in HCC cells, thereby augmenting hSulf-1 expression and inducing cancer cell apoptosis. This novel strategy that involved multiple, synergistic mechanisms, including oncolytic therapy, gene therapy and radioimmunotherapy, was demonstrated to exert an excellent anti-cancer outcome, which will be a promising approach in HCC treatment. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  16. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) enhances vascular and renal damage induced by hyperlipidemic diet in ApoE-knockout mice.

    Science.gov (United States)

    Muñoz-García, Begoña; Moreno, Juan Antonio; López-Franco, Oscar; Sanz, Ana Belén; Martín-Ventura, José Luis; Blanco, Julia; Jakubowski, Aniela; Burkly, Linda C; Ortiz, Alberto; Egido, Jesús; Blanco-Colio, Luis Miguel

    2009-12-01

    Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily of cytokines. TWEAK binds and activates the Fn14 receptor, and may regulate apoptosis, inflammation, and angiogenesis, in different pathological conditions. We have evaluated the effect of exogenous TWEAK administration as well as the role of endogenous TWEAK on proinflammatory cytokine expression and vascular and renal injury severity in hyperlipidemic ApoE-knockout mice. ApoE(-/-) mice were fed with hyperlipidemic diet for 4 to 10 weeks, then randomized and treated with saline (controls), TWEAK (10 microg/kg/d), anti-TWEAK neutralizing mAb (1000 microg/kg/d), TWEAK plus anti-TWEAK antibody (10 microg TWEAK +1000 microg anti-TWEAK/kg/d), or nonspecific IgG (1000 microg/kg/d) daily for 9 days. In ApoE(-/-) mice, exogenous TWEAK administration in ApoE(-/-) mice induced activation of NF-kappaB, a key transcription factor implicated in the regulation of the inflammatory response, in vascular and renal lesions. Furthermore, TWEAK treatment increased chemokine expression (RANTES and MCP-1), as well as macrophage infiltration in atherosclerotic plaques and renal lesions. These effects were associated with exacerbation of vascular and renal damage. Conversely, treatment of ApoE(-/-) mice with an anti-TWEAK blocking mAb decreased NF-kappaB activation, proinflammatory cytokine expression, macrophage infiltration, and vascular and renal injury severity, indicating a pathological role for endogenous TWEAK. Finally, in murine vascular smooth muscle cells or tubular cells, either ox-LDL or TWEAK treatment increased expression and secretion of both RANTES and MCP-1. Furthermore, ox-LDL and TWEAK synergized for induction of MCP-1 and RANTES expression and secretion. Our results suggest that TWEAK exacerbates the inflammatory response associated with a high lipid-rich diet. TWEAK may be a novel therapeutic target to prevent vascular and renal damage associated with

  17. A receptor tyrosine kinase ROR1 inhibitor (KAN0439834 induced significant apoptosis of pancreatic cells which was enhanced by erlotinib and ibrutinib.

    Directory of Open Access Journals (Sweden)

    Amir Hossein Daneshmanesh

    Full Text Available There is a great unmet medical need in pancreatic carcinoma (PC for novel drugs with other mechanisms of action than existing. PC cells express the onco-fetal RTK ROR1, absent on most normal post-partem cells. ROR1 is involved in proliferation, survival, EMT and metastasis of tumor cells in various malignancies. A small molecule inhibitor (KAN0439834 (530 Da targeting the TK domain of ROR1 was developed and the activity in ROR1 expressing human PC cell lines (n = 8 evaluated. The effects were compared to a murine mAb against the external part of ROR1, gemcitabine, erlotinib and ibrutinib. KAN0439834 induced significant apoptosis of the tumor cells. EC50 values for KAN0439834 varied between 250-650 nM depending on the cell line. The corresponding values for erlotinib and ibrutinib were 10-40 folds higher. KAN0439834 was much more effective in inducing tumor cell death than the ROR1 mAb although both inhibited ROR1 phosphorylation and downstream non-canonical Wnt pathway molecules. Combination of KAN0439834 with erlotinib or ibrutinib had significant additive effects on tumor cell death. A first-in-class small molecule ROR1 inhibitor (KAN0439834 showed promising in vitro activity against a number of human PC cell lines. Interesting is the additive effects of erlotinib and ibrutinib which warrants further studies as both these agents are in clinical trials for pancreatic carcinoma.

  18. Imiquimod induced ApoE-deficient mice might be a composite animal model for the study of psoriasis and dyslipideamia comorbidity.

    Science.gov (United States)

    Xie, Xinran; Zhang, Lei; Lin, Yan; Wang, Yan; Liu, Weihong; Li, Xue; Li, Ping

    2017-10-01

    Psoriasis patients are at increased risk of developing lipid metabolism disturbances. Both psoriasis and dyslipideamia not only closely interact in disease development, but occur as mutual side effects in some medicine treatment. The interactive mechanism of the two diseases is complicated and still unclear. Here, we proposed applying imiquimod on the dorsal skin of ApoE -/- mice to establish a composite animal model which formed psoriasiform skin lesions under hyperlipidemic condition. By comparison with corresponding wild-type(C57BL/6) mice, the composite mice model was evaluated by skin pathological features, lipid levels, immune inflammatory factors in order to clarify the diseases interplay mechanism. In addition, IL-17 mAb treatment was applied to observe the effect of IL-17 antibody on the composite animal model. The results verified that imiquimod-induced ApoE -/- mice model presented keratinocyte hyperplasia, parakeratosis, inflammatory cells infiltration and elevated serum lipid levels, and also reflected the complex interaction between inflammation and lipid metabolism. IL-17 mAb could inhibit psoriasis skin lesions with lipid accumulation via STAT3 pathway, but no influence on elevated serum cholesterol. Imiquimod-induced ApoE -/- mice model presented the pathological features of psoriasis and dyslipideamia, which could be an ideal composite animal model for the study of pathogenesis and pharmacotherapeutics of psoriasis and dyslipideamia comorbidity. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Gram-negative periodontal bacteria induce the activation of Toll-like receptors 2 and 4, and cytokine production in human periodontal ligament cells.

    Science.gov (United States)

    Sun, Ying; Shu, Rong; Li, Chao-Lun; Zhang, Ming-Zhu

    2010-10-01

    Periodontitis is a bacterially induced chronic inflammatory disease. Toll-like receptors (TLRs), which could recognize microbial pathogens, are important components in the innate and adaptive immune systems. Both qualitatively and quantitatively distinct immune responses might result from different bacteria stimulation and the triggering of different TLRs. This study explores the interaction of Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) with TLR2 and TLR4. We studied the gene expression changes of TLR2 and TLR4 and cytokine production (interleukin-1β, -6, -8, -10, and tumor necrosis factor-alpha) in human periodontal ligament cells (HPDLCs) stimulated with heat-killed bacteria or P. gingivalis lipopolysaccharide (LPS) in the presence or absence of monoclonal antibodies to TLR2 or TLR4 (anti-TLR2/4 mAb). Both test bacteria and 10 microg/ml P. gingivalis LPS treatment increased the gene expression of TLR2 and TLR4 and cytokine production in HPDLCs. In addition, these upregulations could be blocked by anti-TLR2/4 mAb. However, the expression of TLR4 mRNA in HPDLCs stimulated with 1 microg/ml P. gingivalis LPS was not increased. No differences were found in the cytokine production caused by 1 microg/ml P. gingivalis LPS treatment in the presence or absence of anti-TLR4 mAb. These patterns of gene expression and cytokine production indicate that Gram-negative periodontal bacteria or their LPS might play a role in triggering TLR2 and/or TLR4, and be of importance for the immune responses in periodontitis.

  20. Qualification and application of a surface plasmon resonance-based assay for monitoring potential HAHA responses induced after passive administration of a humanized anti Lewis-Y antibody.

    Science.gov (United States)

    Szolar, O H J; Stranner, S; Zinoecker, I; Mudde, G C; Himmler, G; Waxenecker, G; Nechansky, A

    2006-06-16

    A sensitive, surface plasmon resonance (SPR)-based assay monitoring potential human-anti-human antibody (HAHA) reactions against the monoclonal antibody (mAb) IGN311 is presented. The latter is a fully humanized Lewis-Y carbohydrate specific mAb that is currently tested in a passive immune therapy approach in a clinical phase I trial. For the SPR experiments a BIACORE 3000 analyzer was used. The ligand IGN311 was covalently coupled to the carboxy-methylated dextran matrix of a CM5 research grade chip (BIACORE). In the course of a fully nested experimental design, a four parameter logistic equation was identified as appropriate calibration model ranging from 0.3 microg/mL (lower limit of quantitation, LLOQ) to 200 microg/mL (upper limit of quantitation, ULOQ) using an anti-idiotypic mAb ('HAHA mimic') as calibrator. The bias ranged from -2.4% to 5.5% and the intermediate precision expressed as 95% CI revealed values from 5.6% to 8.3%. Specificity was evaluated using six human serum matrices from healthy donors spiked with calibrator at the limit of quantitation (LOQ) with >80% of values being recovered with less than 25% relative error. The qualified assay was applied to monitor potentially induced HAHA reactivity in 11 patients from a clinical phase I trial with passively administered IGN311. Of the 11 patients, one high HAHA responder and several low responders were identified. Protein-G depletion experiments with human serum samples revealed that the observed response is predominantly caused by IgG binding to the ligand. The characteristics of these HAHA responses were all of the so-called 'Type I' which is defined by a peak response around day 15 that decreases from this point steadily suggesting that some kind of tolerance is established. Therefore, this type of HAHA response is regarded as non critical for the patient's safety.

  1. Induced Seismicity

    Science.gov (United States)

    Keranen, Katie M.; Weingarten, Matthew

    2018-05-01

    The ability of fluid-generated subsurface stress changes to trigger earthquakes has long been recognized. However, the dramatic rise in the rate of human-induced earthquakes in the past decade has created abundant opportunities to study induced earthquakes and triggering processes. This review briefly summarizes early studies but focuses on results from induced earthquakes during the past 10 years related to fluid injection in petroleum fields. Study of these earthquakes has resulted in insights into physical processes and has identified knowledge gaps and future research directions. Induced earthquakes are challenging to identify using seismological methods, and faults and reefs strongly modulate spatial and temporal patterns of induced seismicity. However, the similarity of induced and natural seismicity provides an effective tool for studying earthquake processes. With continuing development of energy resources, increased interest in carbon sequestration, and construction of large dams, induced seismicity will continue to pose a hazard in coming years.

  2. Valitsus hämab liikluskindlustuse seadusega / Marika Tuus

    Index Scriptorium Estoniae

    Tuus, Marika, 1951-

    2004-01-01

    Ilmunud ka: Vooremaa, 12. veebr. 2004, lk. 2; Elva Postipoiss, 14. veebr. 2004, lk. 4; Meie Maa, 20. veebr. 2004, lk. 2; Vali Uudised, 20. veebr. 2004, lk. 2; Põhjarannik, 21. veebr. 2004, lk. 2; Severnoje Poberezhje, 21. veebr. 2004, lk. 2; Kesknädal, 25. veebr. 2004, lk. 2; Valgamaalane, 16. märts 2004, lk. 6. Kriitiliselt liikluskindlustuse seaduse eelnõust. Liikluskindlustuse seaduse eelnõu arutelust Riigikogus

  3. Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

    Directory of Open Access Journals (Sweden)

    Xiaolin He

    Full Text Available BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS. Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859 were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v. attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

  4. VEGF induces proliferation of human hair follicle dermal papilla cells through VEGFR-2-mediated activation of ERK

    International Nuclear Information System (INIS)

    Li, Wei; Man, Xiao-Yong; Li, Chun-Ming; Chen, Jia-Qi; Zhou, Jiong; Cai, Sui-Qing; Lu, Zhong-Fa; Zheng, Min

    2012-01-01

    Vascular endothelial growth factor (VEGF) is one of the strongest regulators of physiological and pathological angiogenesis. VEGF receptor 2 (VEGFR-2), the primary receptor for VEGF, is thought to mediate major functional effects of VEGF. Previously, we have localized both VEGF and VEGFR-2 in human hair follicles. In this study, we further defined the expression and roles of VEGFR-2 on human hair follicle dermal papilla (DP) cells. The expression of VEGFR-2 on DP cells was examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis separately, and localization of VEGFR-2 was defined by immunofluorescence. The effect of VEGF on DP cells was analyzed by MTT assays and specific inhibitors. Finally, the role of VEGF involved in the signaling pathways was investigated by Western blot. RT-PCR and Western blot analysis demonstrated the expression of VEGFR-2 on DP cells. Immunostaining for VEGFR-2 showed strong signal on cultured human DP cells in vitro. Exogenous VEGF 165 stimulated proliferation of DP cells in a dose-dependent manner. Furthermore, this stimulation was blocked by a VEGFR-2 neutralizing antibody (MAB3571) and an ERK inhibitor (PD98059). VEGF 165 -induced phosphorylation of ERK1/2 was abolished by MAB3571 and PD98059, while the phosphorylation of p38, JNK and AKT were not changed by VEGF 165 . Taken together, VEGFR-2 is expressed on primary human hair follicle DP cells and VEGF induces proliferation of DP cells through VEGFR-2/ERK pathway, but not p38, JNK or AKT signaling. -- Highlights: ► We examine the expression of VEGFR-2 on cultured human dermal papilla (DP) cells. ► VEGF 165 stimulated proliferation of human DP cells in a dose-dependent manner. ► This stimulation was through VEGFR-2-mediated activation of ERK.

  5. Acute Ethanol Intake Induces NAD(P)H Oxidase Activation and Rhoa Translocation in Resistance Arteries.

    Science.gov (United States)

    Simplicio, Janaina A; Hipólito, Ulisses Vilela; Vale, Gabriel Tavares do; Callera, Glaucia Elena; Pereira, Camila André; Touyz, Rhian M; Tostes, Rita de Cássia; Tirapelli, Carlos R

    2016-11-01

    The mechanism underlying the vascular dysfunction induced by ethanol is not totally understood. Identification of biochemical/molecular mechanisms that could explain such effects is warranted. To investigate whether acute ethanol intake activates the vascular RhoA/Rho kinase pathway in resistance arteries and the role of NAD(P)H oxidase-derived reactive oxygen species (ROS) on such response. We also evaluated the requirement of p47phox translocation for ethanol-induced NAD(P)H oxidase activation. Male Wistar rats were orally treated with ethanol (1g/kg, p.o. gavage) or water (control). Some rats were treated with vitamin C (250 mg/kg, p.o. gavage, 5 days) before administration of water or ethanol. The mesenteric arterial bed (MAB) was collected 30 min after ethanol administration. Vitamin C prevented ethanol-induced increase in superoxide anion (O2-) generation and lipoperoxidation in the MAB. Catalase and superoxide dismutase activities and the reduced glutathione, nitrate and hydrogen peroxide (H2O2) levels were not affected by ethanol. Vitamin C and 4-methylpyrazole prevented the increase on O2- generation induced by ethanol in cultured MAB vascular smooth muscle cells. Ethanol had no effect on phosphorylation levels of protein kinase B (Akt) and eNOS (Ser1177 or Thr495 residues) or MAB vascular reactivity. Vitamin C prevented ethanol-induced increase in the membrane: cytosol fraction ratio of p47phox and RhoA expression in the rat MAB. Acute ethanol intake induces activation of the RhoA/Rho kinase pathway by a mechanism that involves ROS generation. In resistance arteries, ethanol activates NAD(P)H oxidase by inducing p47phox translocation by a redox-sensitive mechanism. O mecanismo da disfunção vascular induzido pelo consumo de etanol não é totalmente compreendido. Justifica-se, assim a identificação de mecanismos bioquímicos e moleculares que poderiam explicar tais efeitos. Investigar se a ingestão aguda de etanol ativa a via vascular RhoA/Rho quinase

  6. Lung cancer induced in mice by the envelope protein of jaagsiekte sheep retrovirus (JSRV closely resembles lung cancer in sheep infected with JSRV

    Directory of Open Access Journals (Sweden)

    York Denis

    2006-12-01

    Full Text Available Abstract Background Jaagsiekte sheep retrovirus (JSRV causes a lethal lung cancer in sheep and goats. Expression of the JSRV envelope (Env protein in mouse lung, by using a replication-defective adeno-associated virus type 6 (AAV6 vector, induces tumors resembling those seen in sheep. However, the mouse and sheep tumors have not been carefully compared to determine if Env expression alone in mice can account for the disease features observed in sheep, or whether additional aspects of virus replication in sheep are important, such as oncogene activation following retrovirus integration into the host cell genome. Results We have generated mouse monoclonal antibodies (Mab against JSRV Env and have used these to study mouse and sheep lung tumor histology. These Mab detect Env expression in tumors in sheep infected with JSRV from around the world with high sensitivity and specificity. Mouse and sheep tumors consisted mainly of well-differentiated adenomatous foci with little histological evidence of anaplasia, but at long times after vector exposure some mouse tumors did have a more malignant appearance typical of adenocarcinoma. In addition to epithelial cell tumors, lungs of three of 29 sheep examined contained fibroblastic cell masses that expressed Env and appeared to be separate neoplasms. The Mab also stained nasal adenocarcinoma tissue from one United States sheep, which we show was due to expression of Env from ovine enzootic nasal tumor virus (ENTV, a virus closely related to JSRV. Systemic administration of the AAV6 vector encoding JSRV Env to mice produced numerous hepatocellular tumors, and some hemangiomas and hemangiosarcomas, showing that the Env protein can induce tumors in multiple cell types. Conclusion Lung cancers induced by JSRV infection in sheep and by JSRV Env expression in mice have similar histologic features and are primarily characterized by adenomatous proliferation of peripheral lung epithelial cells. Thus it is

  7. A chimeric antigen receptor for TRAIL-receptor 1 induces apoptosis in various types of tumor cells.

    Science.gov (United States)

    Kobayashi, Eiji; Kishi, Hiroyuki; Ozawa, Tatsuhiko; Hamana, Hiroshi; Nakagawa, Hidetoshi; Jin, Aishun; Lin, Zhezhu; Muraguchi, Atsushi

    2014-10-31

    Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and its associated receptors (TRAIL-R/TR) are attractive targets for cancer therapy because TRAIL induces apoptosis in tumor cells through TR while having little cytotoxicity on normal cells. Therefore, many agonistic monoclonal antibodies (mAbs) specific for TR have been produced, and these induce apoptosis in multiple tumor cell types. However, some TR-expressing tumor cells are resistant to TR-specific mAb-induced apoptosis. In this study, we constructed a chimeric antigen receptor (CAR) of a TRAIL-receptor 1 (TR1)-specific single chain variable fragment (scFv) antibody (TR1-scFv-CAR) and expressed it on a Jurkat T cell line, the KHYG-1 NK cell line, and human peripheral blood lymphocytes (PBLs). We found that the TR1-scFv-CAR-expressing Jurkat cells killed target cells via TR1-mediated apoptosis, whereas TR1-scFv-CAR-expressing KHYG-1 cells and PBLs killed target cells not only via TR1-mediated apoptosis but also via CAR signal-induced cytolysis, resulting in cytotoxicity on a broader range if target cells than with TR1-scFv-CAR-expressing Jurkat cells. The results suggest that TR1-scFv-CAR could be a new candidate for cancer gene therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Beta3 subunits promote expression and nicotine-induced up-regulation of human nicotinic alpha6* nicotinic acetylcholine receptors expressed in transfected cell lines.

    Science.gov (United States)

    Tumkosit, Prem; Kuryatov, Alexander; Luo, Jie; Lindstrom, Jon

    2006-10-01

    Nicotinic acetylcholine receptors (AChRs) containing alpha6 subunits are typically found at aminergic nerve endings where they play important roles in nicotine addiction and Parkinson's disease. alpha6* AChRs usually contain beta3 subunits. beta3 subunits are presumed to assemble only in the accessory subunit position within AChRs where they do not participate in forming acetylcholine binding sites. Assembly of subunits in the accessory position may be a critical final step in assembly of mature AChRs. Human alpha6 AChRs subtypes were permanently transfected into human tsA201 human embryonic kidney (HEK) cell lines. alpha6beta2beta3 and alpha6beta4beta3 cell lines were found to express much larger amounts of AChRs and were more sensitive to nicotine-induced increase in the amount of AChRs than were alpha6beta2 or alpha6beta4 cell lines. The increased sensitivity to nicotine-induced up-regulation was due not to a beta3-induced increase in affinity for nicotine but probably to a direct effect on assembly of AChR subunits. HEK cells express only a small amount of mature alpha6beta2 AChRs, but many of these subunits are on the cell surface. This contrasts with Xenopus laevis oocytes, which express a large amount of incorrectly assembled alpha6beta2 subunits that bind cholinergic ligands but form large amorphous intracellular aggregates. Monoclonal antibodies (mAbs) were made to the alpha6 and beta3 subunits to aid in the characterization of these AChRs. The alpha6 mAbs bind to epitopes C-terminal of the extracellular domain. These data demonstrate that both cell type and the accessory subunit beta3 can play important roles in alpha6* AChR expression, stability, and up-regulation by nicotine.

  9. Interferon-γ induces expression of MHC class II on intestinal epithelial cells and protects mice from colitis.

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    Christoph Thelemann

    Full Text Available Immune responses against intestinal microbiota contribute to the pathogenesis of inflammatory bowel diseases (IBD and involve CD4(+ T cells, which are activated by major histocompatibility complex class II (MHCII molecules on antigen-presenting cells (APCs. However, it is largely unexplored how inflammation-induced MHCII expression by intestinal epithelial cells (IEC affects CD4(+ T cell-mediated immunity or tolerance induction in vivo. Here, we investigated how epithelial MHCII expression is induced and how a deficiency in inducible epithelial MHCII expression alters susceptibility to colitis and the outcome of colon-specific immune responses. Colitis was induced in mice that lacked inducible expression of MHCII molecules on all nonhematopoietic cells, or specifically on IECs, by continuous infection with Helicobacter hepaticus and administration of interleukin (IL-10 receptor-blocking antibodies (anti-IL10R mAb. To assess the role of interferon (IFN-γ in inducing epithelial MHCII expression, the T cell adoptive transfer model of colitis was used. Abrogation of MHCII expression by nonhematopoietic cells or IECs induces colitis associated with increased colonic frequencies of innate immune cells and expression of proinflammatory cytokines. CD4(+ T-helper type (Th1 cells - but not group 3 innate lymphoid cells (ILCs or Th17 cells - are elevated, resulting in an unfavourably altered ratio between CD4(+ T cells and forkhead box P3 (FoxP3(+ regulatory T (Treg cells. IFN-γ produced mainly by CD4(+ T cells is required to upregulate MHCII expression by IECs. These results suggest that, in addition to its proinflammatory roles, IFN-γ exerts a critical anti-inflammatory function in the intestine which protects against colitis by inducing MHCII expression on IECs. This may explain the failure of anti-IFN-γ treatment to induce remission in IBD patients, despite the association of elevated IFN-γ and IBD.

  10. Molecular characterization of Trypanosoma cruzi SAP proteins with host-cell lysosome exocytosis-inducing activity required for parasite invasion.

    Science.gov (United States)

    Zanforlin, Tamiris; Bayer-Santos, Ethel; Cortez, Cristian; Almeida, Igor C; Yoshida, Nobuko; da Silveira, José Franco

    2013-01-01

    To invade target cells, Trypanosoma cruzi metacyclic forms engage distinct sets of surface and secreted molecules that interact with host components. Serine-, alanine-, and proline-rich proteins (SAP) comprise a multigene family constituted of molecules with a high serine, alanine and proline residue content. SAP proteins have a central domain (SAP-CD) responsible for interaction with and invasion of mammalian cells by metacyclic forms. Using a 513 bp sequence from SAP-CD in blastn analysis, we identified 39 full-length SAP genes in the genome of T. cruzi. Although most of these genes were mapped in the T. cruzi in silico chromosome TcChr41, several SAP sequences were spread out across the genome. The level of SAP transcripts was twice as high in metacyclic forms as in epimastigotes. Monoclonal (MAb-SAP) and polyclonal (anti-SAP) antibodies produced against the recombinant protein SAP-CD were used to investigate the expression and localization of SAP proteins. MAb-SAP reacted with a 55 kDa SAP protein released by epimastigotes and metacyclic forms and with distinct sets of SAP variants expressed in amastigotes and tissue culture-derived trypomastigotes (TCTs). Anti-SAP antibodies reacted with components located in the anterior region of epimastigotes and between the nucleus and the kinetoplast in metacyclic trypomastigotes. In contrast, anti-SAP recognized surface components of amastigotes and TCTs, suggesting that SAP proteins are directed to different cellular compartments. Ten SAP peptides were identified by mass spectrometry in vesicle and soluble-protein fractions obtained from parasite conditioned medium. Using overlapping sequences from SAP-CD, we identified a 54-aa peptide (SAP-CE) that was able to induce host-cell lysosome exocytosis and inhibit parasite internalization by 52%. This study provides novel information about the genomic organization, expression and cellular localization of SAP proteins and proposes a triggering role for extracellular SAP

  11. Uncarinic Acid C Isolated from Uncaria rhynchophylla Induces Differentiation of Th1-Promoting Dendritic Cells Through TLR4 Signaling.

    Science.gov (United States)

    Kim, Kyu Sik; Pham, Thanh Nhan Nguyen; Jin, Chun-Ji; Umeyama, Akemi; Shoji, Noboru; Hashimoto, Toshihiro; Lee, Je-Jung; Takei, Masao

    2011-02-28

    Uncarinic acid C (URC) is triterpene isolated from Uncaria rhynchophylla and is a pharmacologically active substance. The induction of dendritic cells (DC) is critical for the induction of Ag-specific T lymphocyte responses and may be essential for the development of human vaccines relying on T cell immunity. DC might be a potential target for URC. We demonstrate that URC activates human DC as documented by phenotypic and functional maturation, and altered cytokine production. The expression of CD1a, CD38, CD40, CD54, CD80, CD83, CD86, HLA-DR and CCR7 on URC-primed DC was enhanced. The production of IL-12p70 by URC-primed DC was higher than that of lipopolysaccharide (LPS)-primed DC. The production of IL-12p70 by URC-primed DC was inhibited by the anti-Toll-like receptor 4 (TLR4) monoclonal antibody (mAb), but partially abolished by anti-TLR2 mAb. mRNA coding for TLR2 and TLR4 was expressed in URC-primed DC. URC-primed DC induced the NF-κB transcription factor. Naïve T cells co-cultured with URC-primed DC turned into typical Th1 cells that produced large quantities of IFN-γ depending on IL-12 secretion. URC enhanced the T cell stimulatory capacity in an allo MLR. In the cytotoxic T-lymphocyte assay (CTL) assay, DNA fragmentation assay and (51)Cr release on URC-primed DC were more augmented than that of TNF-α-primed DC. DC matured with URC had an intermediate migratory capacity towards CCL19 and CCL21. These results suggest that URC modulates DC function in a fashion that favors Th1 polarization via the activation of IL-12p70 dependent on TLR4 signaling, and may be used on DC-based vaccine for cancer immunotherapy.

  12. Inducing autophagy

    DEFF Research Database (Denmark)

    Harder, Lea M; Bunkenborg, Jakob; Andersen, Jens S.

    2014-01-01

    catabolism, which has recently been found to induce autophagy in an MTOR independent way and support cancer cell survival. In this study, quantitative phosphoproteomics was applied to investigate the initial signaling events linking ammonia to the induction of autophagy. The MTOR inhibitor rapamycin was used...... as a reference treatment to emphasize the differences between an MTOR-dependent and -independent autophagy-induction. By this means 5901 phosphosites were identified of which 626 were treatment-specific regulated and 175 were coregulated. Investigation of the ammonia-specific regulated sites supported that MTOR...

  13. Sensitization to Gliadin Induces Moderate Enteropathy and Insulitis in Nonobese Diabetic-DQ8 Mice

    Science.gov (United States)

    Galipeau, Heather J.; Rulli, Nestor E.; Jury, Jennifer; Huang, Xianxi; Araya, Romina; Murray, Joseph A.; David, Chella S.; Chirdo, Fernando G.; McCoy, Kathy D.; Verdu, Elena F.

    2012-01-01

    Celiac disease (CD) is frequently diagnosed in patients with type 1 diabetes (T1D), and T1D patients can exhibit Abs against tissue transglutaminase, the auto-antigen in CD. Thus, gliadin, the trigger in CD, has been suggested to have a role in T1D pathogenesis. The objective of this study was to investigate whether gliadin contributes to enteropathy and insulitis in NOD-DQ8 mice, an animal model that does not spontaneously develop T1D. Gliadin-sensitized NOD-DQ8 mice developed moderate enteropathy, intraepithelial lymphocytosis, and barrier dysfunction, but not insulitis. Administration of anti-CD25 mAbs before gliadin-sensitization induced partial depletion of CD25+Foxp3+ T cells and led to severe insulitis, but did not exacerbate mucosal dysfunction. CD4+ T cells isolated from pancreatic lymph nodes of mice that developed insulitis showed increased proliferation and proinflammatory cytokines after incubation with gliadin but not with BSA. CD4+ T cells isolated from nonsensitized controls did not response to gliadin or BSA. In conclusion, gliadin sensitization induced moderate enteropathy in NOD-DQ8 mice. However, insulitis development required gliadin-sensitization and partial systemic depletion of CD25+Foxp3+ T cells. This humanized murine model provides a mechanistic link to explain how the mucosal intolerance to a dietary protein can lead to insulitis in the presence of partial regulatory T cell deficiency. PMID:21911598

  14. Mixed chimerism and permanent specific transplantation tolerance induced by a nonlethal preparative regimen

    International Nuclear Information System (INIS)

    Sharabi, Y.; Sachs, D.H.

    1989-01-01

    The use of allogeneic bone marrow transplantation as a means of inducing donor-specific tolerance across MHC barriers could provide an immunologically specific conditioning regimen for organ transplantation. However, a major limitation to this approach is the toxicity of whole body irradiation as currently used to abrogate host resistance and permit marrow engraftment. The present study describes methodology for abrogating host resistance and permitting marrow engraftment without lethal irradiation. Our preparative protocol involves administration of anti-CD4 and anti-CD8 mAbs in vivo, 300-rad WBI, 700-rad thymic irradiation, and unmanipulated fully MHC-disparate bone marrow. B10 mice prepared by this regimen developed stable mixed lymphohematopoetic chimerism without any clinical evidence of graft-vs.-host disease. Engraftment was accompanied by induction of specific tolerance to donor skin grafts (B10.D2), while third-party skin grafts (B10.BR) were promptly rejected. Mice treated with the complete regimen without bone marrow transplantation appeared healthy and enjoyed long-term survival. This study therefore demonstrates that stable mixed chimerism with donor-specific tolerance can be induced across an MHC barrier after a nonlethal preparative regimen, without clinical GVHD and without the risk of aplasia

  15. Lipopolysaccharide (LPS)-binding protein stimulates CD14-dependent Toll-like receptor 4 internalization and LPS-induced TBK1-IKKϵ-IRF3 axis activation.

    Science.gov (United States)

    Tsukamoto, Hiroki; Takeuchi, Shino; Kubota, Kanae; Kobayashi, Yohei; Kozakai, Sao; Ukai, Ippo; Shichiku, Ayumi; Okubo, Misaki; Numasaki, Muneo; Kanemitsu, Yoshitomi; Matsumoto, Yotaro; Nochi, Tomonori; Watanabe, Kouichi; Aso, Hisashi; Tomioka, Yoshihisa

    2018-05-14

    Toll-like receptor 4 (TLR4) is an indispensable immune receptor for lipopolysaccharide (LPS), a major component of the Gram-negative bacterial cell wall. Following LPS stimulation, TLR4 transmits the signal from the cell surface and becomes internalized in an endosome. However, the spatial regulation of TLR4 signaling is not fully understood. Here, we investigated the mechanisms of LPS-induced TLR4 internalization and clarified the roles of the extracellular LPS-binding molecules, LPS-binding protein (LBP), and glycerophosphatidylinositol-anchored protein (CD14). LPS stimulation of CD14-expressing cells induced TLR4 internalization in the presence of serum, and an inhibitory anti-LBP mAb blocked its internalization. Addition of LBP to serum-free cultures restored LPS-induced TLR4 internalization to comparable levels of serum. The secretory form of the CD14 (sCD14) induced internalization but required a much higher concentration than LBP. An inhibitory anti-sCD14 mAb was ineffective for serum-mediated internalization. LBP lacking the domain for LPS transfer to CD14 and a CD14 mutant with reduced LPS binding both attenuated TLR4 internalization. Accordingly, LBP is an essential serum molecule for TLR4 internalization, and its LPS transfer to membrane-anchored CD14 (mCD14) is a prerequisite. LBP induced the LPS-stimulated phosphorylation of TBK1, IKKϵ, and IRF3, leading to IFN-β expression. However, LPS-stimulated late activation of NFκB or necroptosis were not affected. Collectively, our results indicate that LBP controls LPS-induced TLR4 internalization, which induces TLR adaptor molecule 1 (TRIF)-dependent activation of the TBK1-IKKϵ-IRF3-IFN-β pathway. In summary, we showed that LBP-mediated LPS transfer to mCD14 is required for serum-dependent TLR4 internalization and activation of the TRIF pathway. Copyright © 2018, The American Society for Biochemistry and Molecular Biology.

  16. Identification of anti-CD98 antibody mimotopes for inducing antibodies with antitumor activity by mimotope immunization.

    Science.gov (United States)

    Saito, Misa; Kondo, Masahiro; Ohshima, Motohiro; Deguchi, Kazuki; Hayashi, Hideki; Inoue, Kazuyuki; Tsuji, Daiki; Masuko, Takashi; Itoh, Kunihiko

    2014-04-01

    A mimotope is an antibody-epitope-mimicking peptide retrieved from a phage display random peptide library. Immunization with antitumor antibody-derived mimotopes is promising for inducing antitumor immunity in hosts. In this study, we isolated linear and constrained mimotopes from HBJ127, a tumor-suppressing anti-CD98 heavy chain mAb, and determined their abilities for induction of antitumor activity equal to that of the parent antibody. We detected elevated levels of antipeptide responses, but failed to detect reactivity against native CD98-expressing HeLa cells in sera of immunized mice. Phage display panning and selection of mimotope-immunized mouse spleen-derived antibody Fab library showed that HeLa cell-reactive Fabs were successfully retrieved from the library. This finding indicates that native antigen-reactive Fab clones represented an undetectable minor population in mimotope-induced antibody repertoire. Functional and structural analysis of retrieved Fab clones revealed that they were almost identical to the parent antibody. From these results, we confirmed that mimotope immunization was promising for retrieving antitumor antibodies equivalent to the parent antibody, although the co-administration of adjuvant compounds such as T-cell epitope peptides and Toll-like receptor 4 agonist peptides is likely to be necessary for inducing stronger antitumor immunity than mimotope injection alone. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  17. Cirmtuzumab inhibits Wnt5a-induced Rac1 activation in chronic lymphocytic leukemia treated with ibrutinib.

    Science.gov (United States)

    Yu, J; Chen, L; Cui, B; Wu, Christina; Choi, M Y; Chen, Y; Zhang, L; Rassenti, L Z; Widhopf Ii, G F; Kipps, T J

    2017-06-01

    Signaling via the B cell receptor (BCR) plays an important role in the pathogenesis and progression of chronic lymphocytic leukemia (CLL). This is underscored by the clinical effectiveness of ibrutinib, an inhibitor of Bruton's tyrosine kinase (BTK) that can block BCR-signaling. However, ibrutinib cannot induce complete responses (CR) or durable remissions without continued therapy, suggesting alternative pathways also contribute to CLL growth/survival that are independent of BCR-signaling. ROR1 is a receptor for Wnt5a, which can promote activation of Rac1 to enhance CLL-cell proliferation and survival. In this study, we found that CLL cells of patients treated with ibrutinib had activated Rac1. Moreover, Wnt5a could induce Rac1 activation and enhance proliferation of CLL cells treated with ibrutinib at concentrations that were effective in completely inhibiting BTK and BCR-signaling. Wnt5a-induced Rac1 activation could be blocked by cirmtuzumab (UC-961), an anti-ROR1 mAb. We found that treatment with cirmtuzumab and ibrutinib was significantly more effective than treatment with either agent alone in clearing leukemia cells in vivo. This study indicates that cirmtuzumab may enhance the activity of ibrutinib in the treatment of patients with CLL or other ROR1 + B-cell malignancies.

  18. The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein.

    Directory of Open Access Journals (Sweden)

    Dianyuan Zhao

    2016-03-01

    Full Text Available Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP is involved in this process through activating dendritic cells (DCs and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12 and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.

  19. Interferon-β-induced activation of c-Jun NH2-terminal kinase mediates apoptosis through up-regulation of CD95 in CH31 B lymphoma cells

    International Nuclear Information System (INIS)

    Takada, Eiko; Shimo, Kuniaki; Hata, Kikumi; Abiake, Maira; Mukai, Yasuo; Moriyama, Masami; Heasley, Lynn; Mizuguchi, Junichiro

    2005-01-01

    Type I interferon (IFN)-induced antitumor action is due in part to apoptosis, but the molecular mechanisms underlying IFN-induced apoptosis remain largely unresolved. In the present study, we demonstrate that IFN-β induced apoptosis and the loss of mitochondrial membrane potential (ΔΨm) in the murine CH31 B lymphoma cell line, and this was accompanied by the up-regulation of CD95, but not CD95-ligand (CD95-L), tumor necrosis factor (TNF), or TNF-related apoptosis-inducing ligand (TRAIL). Pretreatment with anti-CD95-L mAb partially prevented the IFN-β-induced loss of ΔΨm, suggesting that the interaction of IFN-β-up-regulated CD95 with CD95-L plays a crucial role in the induction of fratricide. IFN-β induced a sustained activation of c-Jun NH 2 -terminal kinase 1 (JNK1), but not extracellular signal-regulated kinases (ERKs). The IFN-β-induced apoptosis and loss of ΔΨm were substantially compromised in cells overexpressing a dominant-negative form of JNK1 (dnJNK1), and it was slightly enhanced in cells carrying a constitutively active JNK construct, MKK7-JNK1 fusion protein. The IFN-β-induced up-regulation of CD95 together with caspase-8 activation was also abrogated in the dnJNK1 cells while it was further enhanced in the MKK7-JNK1 cells. The levels of cellular FLIP (c-FLIP), competitively interacting with caspase-8, were down-regulated by stimulation with IFN-β but were reversed by the proteasome inhibitor lactacystin. Collectively, the IFN-β-induced sustained activation of JNK mediates apoptosis, at least in part, through up-regulation of CD95 protein in combination with down-regulation of c-FLIP protein

  20. A role for CD4+ but not CD8+ T cells in immunity to Schistosoma mansoni induced by 20 krad-irradiated and Ro 11-3128-terminated infections

    International Nuclear Information System (INIS)

    Vignali, D.A.A.; Bickle, Q.D.; Taylor, M.G.; Crocker, P.; Cobbold, S.; Waldmann, H

    1989-01-01

    The role of CD4 + (L3/T4 + ) and CD8 + (Lyt-2 + ) T cells in immunity to Schistosoma mansoni induced by 20 krad-irradiated and Ro 11-terminated infections in mice was investigated directly by in vivo depletion of these subsets with cytotoxic rat monoclonal antibodies (mAb). Effective physical depletion was demonstrated by flow cytometric analysis and immunohistochemical staining. Functional depletion of helper activity following anti-CD4 treatment was indicated by an abrogation of concanavalin A(Con A)-induced colony-stimulating factor (CSF) release, while anti-CD8 treatment had no effect in these assays. Pre-existing S. mansoni-specific antibody levels were unaffected by anti-CD4 and anti-CD8 treatment. In vivo depletion of CD4 + T cells resulted in a dramatic reduction in immunity induced by one (up to 100%) and two (up to 70%) vaccinations with 20 krad-irradiated cercariae and also of resistance induced by Ro 11-attenuated infections (up to 100%). Depletion of CD8 + T cells had no effect on resistance induced by any of the vaccination protocols investigated. A correlation was observed between resistance and T cell-induced, macrophage-mediated killing of schistosomula in vitro, both of which were abrogated following anti-CD4 treatment but were unaffected by CD8 + T-cell depletion. The possible role of CD4 + T cells in vivo and the implications for vaccine development are discussed. (author)

  1. CXC chemokine receptor 3 expression on CD34(+) hematopoietic progenitors from human cord blood induced by granulocyte-macrophage colony-stimulating factor

    DEFF Research Database (Denmark)

    Jinquan, T; Quan, S; Jacobi, H H

    2000-01-01

    -induced CD34(+) progenitor chemotaxis. These chemotactic attracted CD34(+) progenitors are colony-forming units-granulocyte-macrophage. gamma IP-10 and Mig also induced GM-CSF-stimulated CD34(+) progenitor adhesion and aggregation by means of CXCR3, a finding confirmed by the observation that anti-CXCR3 m......Ab blocked these functions of gammaIP-10 and Mig but not of chemokine stromal cell-derived factor 1 alpha. gamma IP-10-induced and Mig-induced up-regulation of integrins (CD49a and CD49b) was found to play a crucial role in adhesion of GM-CSF-stimulated CD34(+) progenitors. Moreover, gamma IP-10 and Mig...... stimulated CXCR3 redistribution and cellular polarization in GM-CSF-stimulated CD34(+) progenitors. These results indicate that CXCR3-gamma IP-10 and CXCR3-Mig receptor-ligand pairs, as well as the effects of GM-CSF on them, may be especially important in the cytokine/chemokine environment...

  2. Dimerization of glycoprotein Ibα is not sufficient to induce platelet clearance.

    Science.gov (United States)

    Liang, X; Syed, A K; Russell, S R; Ware, J; Li, R

    2016-02-01

    ESSENTIALS: Many anti-glycoprotein (GP)Ibα antibodies induce platelet clearance in a dimer-dependent manner. Characterization of monoclonal antibodies that bind the mechanosensitive domain (MSD) of GPIbα. An anti-MSD antibody binds two copies of GPIbα in platelets but does not induce platelet clearance. The prevailing clustering model of GPIbα signaling is incorrect or needs revision. The mechanism of platelet clearance is not clear. Many antibodies binding the membrane-distal ligand-binding domain of glycoprotein (GP)Ibα induce rapid clearance of platelets and acute thrombocytopenia, which requires the bifurcated antibody structure. It was thought that binding of these antibodies induced lateral dimerization or clustering of GPIbα in the plasma membrane, which leads to downstream signaling and platelet clearance. However, many antibodies targeting GPIbβ and GPIX, which are associated with GPIbα in the GPIb-IX complex, do not induce platelet clearance, which is in contradiction to the clustering model. To test whether dimerization or clustering of GPIbα is sufficient to transmit the signal that leads to platelet clearance. We have recently raised several mAbs targeting the mechanosensitive domain (MSD) of GPIbα. Binding of these anti-MSD antibodies was characterized with biochemical methods. Their ability to stimulate platelets and induce platelet clearance in mice was assessed. Infusion of anti-MSD antibodies does not cause thrombocytopenia in mice. These antibodies show no detectable effects on platelet activation and aggregation in vitro. Further biochemical investigation showed that the anti-MSD antibody 3D1 binds two copies of GPIbα on the platelet surface. Therefore, lateral dimerization of GPIbα induced by antibody binding is not sufficient to initiate GPIb-IX signaling and induce platelet clearance. Our results suggest that a factor other than or in addition to clustering of GPIbα is required to induce platelet clearance. © 2015 International

  3. Glycoconjugates reveal diversity of human neural stem cells (hNSCs) derived from human induced pluripotent stem cells (hiPSCs).

    Science.gov (United States)

    Kandasamy, Majury; Roll, Lars; Langenstroth, Daniel; Brüstle, Oliver; Faissner, Andreas

    2017-06-01

    Neural stem cells (NSCs) have the ability to self-renew and to differentiate into various cell types of the central nervous system. This potential can be recapitulated by human induced pluripotent stem cells (hiPSCs) in vitro. The differentiation capacity of hiPSCs is characterized by several stages with distinct morphologies and the expression of various marker molecules. We used the monoclonal antibodies (mAbs) 487 LeX , 5750 LeX and 473HD to analyze the expression pattern of particular carbohydrate motifs as potential markers at six differentiation stages of hiPSCs. Mouse ESCs were used as a comparison. At the pluripotent stage, 487 LeX -, 5750 LeX - and 473HD-related glycans were differently expressed. Later, cells of the three germ layers in embryoid bodies (hEBs) and, even after neuralization of hEBs, subpopulations of cells were labeled with these surface antibodies. At the human rosette-stage of NSCs (hR-NSC), LeX- and 473HD-related epitopes showed antibody-specific expression patterns. We also found evidence that these surface antibodies could be used to distinguish the hR-NSCs from the hSR-NSCs stages. Characterization of hNSCs FGF-2/EGF derived from hSR-NSCs revealed that both LeX antibodies and the 473HD antibody labeled subpopulations of hNSCs FGF-2/EGF . Finally, we identified potential LeX carrier molecules that were spatiotemporally regulated in early and late stages of differentiation. Our study provides new insights into the regulation of glycoconjugates during early human stem cell development. The mAbs 487 LeX , 5750 LeX and 473HD are promising tools for identifying distinct stages during neural differentiation.

  4. Exercise-Induced Asthma

    Science.gov (United States)

    ... Videos for Educators Search English Español Exercise-Induced Asthma KidsHealth / For Parents / Exercise-Induced Asthma What's in ... Exercise-Induced Asthma Print What Is Exercise-Induced Asthma? Most kids and teens with asthma have symptoms ...

  5. Drug-induced thrombocytopenia

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U; Andersen, M; Hansen, P B

    1997-01-01

    induced by non-cytotoxic drugs is characterised by heterogeneous clinical picture and recovery is generally rapid. Although corticosteroids seem inefficient, we still recommend that severe symptomatic cases of drug-induced thrombocytopenia are treated as idiopathic thrombocytopenic purpura due...

  6. CD1 molecule expression on human monocytes induced by granulocyte-macrophage colony-stimulating factor.

    Science.gov (United States)

    Kasinrerk, W; Baumruker, T; Majdic, O; Knapp, W; Stockinger, H

    1993-01-15

    In this paper we demonstrate that granulocyte-macrophage CSF (GM-CSF) specifically induces the expression of CD1 molecules, CD1a, CD1b and CD1c, upon human monocytes. CD1 molecules appeared upon monocytes on day 1 of stimulation with rGM-CSF, and expression was up-regulated until day 3. Monocytes cultured in the presence of LPS, FMLP, PMA, recombinant granulocyte-CSF, rIFN-gamma, rTNF-alpha, rIL-1 alpha, rIL-1 beta, and rIL-6 remained negative. The induction of CD1 molecules by rGM-CSF was restricted to monocytes, since no such effect was observed upon peripheral blood granulocytes, PBL, and the myeloid cell lines Monomac1, Monomac6, MV4/11, HL60, U937, THP1, KG1, and KG1A. CD1a mRNA was detectable in rGM-CSF-induced monocytes but not in those freshly isolated. SDS-PAGE and immunoblotting analyses of CD1a mAb VIT6 immunoprecipitate from lysate of rGM-CSF-activated monocytes revealed an appropriate CD1a polypeptide band of 49 kDa associated with beta 2-microglobulin. Expression of CD1 molecules on monocytes complements the distribution of these structures on accessory cells, and their specific induction by GM-CSF strengthens the suggestion that CD1 is a family of crucial structures required for interaction between accessory cells and T cells.

  7. Ursolic acid isolated from Uncaria rhynchophylla activates human dendritic cells via TLR2 and/or TLR4 and induces the production of IFN-gamma by CD4+ naïve T cells.

    Science.gov (United States)

    Jung, Tae-Young; Pham, Thanh Nhan Nguyen; Umeyama, Akemi; Shoji, Noboru; Hashimoto, Toshihiro; Lee, Je-Jung; Takei, Masao

    2010-09-25

    Ursolic acid is triterpene isolated from Uncaria rhynchophylla and is a pharmacologically active substance. The induction of dendritic cell maturation is critical for the induction of Ag-specific T-lymphocyte response and may be essential for the development of human vaccine relying on T cell immunity. In this study, we investigated that the effect of Ursolic acid on the phenotypic and functional maturation of human monocyte-derived dendritic cells in vitro. Dendritic cells harvested on day 8 were examined using functional assay. The expression levels of CD1a, CD80, CD83, CD86, HLA-DR and CCR7 on Ursolic acid-primed dendritic cells was slightly enhanced. Ursolic acid dose-dependently enhanced the T cell stimulatory capacity in an allogeneic mixed lymphocyte reaction, as measured by T cell proliferation. The production of IL-12p70 induced by Ursolic acid-primed dendritic cells was inhibited by the anti-Toll-like receptor-2 (TLR2) mAb and anti-TLR4 mAb. Moreover, Ursolic acid-primed dendritic cells expressed levels of mRNA coding for both TLR2 and TLR4. The majority of cells produced considerable interferon-gamma (IFN-gamma), but also small amounts of interleukin (IL-4)-4. Ursolic acid-primed dendritic cells have an intermediate migratory capacity towards CCL19 and CCL21. These results suggest that Ursolic acid modulates human dendritic cells function in a fashion that favors Th1 polarization via the activation of IL-12p70 dependent on TLR2 and/or TLR4, and may be used on dendritic cells-based vaccines for cancer immunotherapy. 2010 Elsevier B.V. All rights reserved.

  8. Broad-spectrum inhibition of HIV-1 by a monoclonal antibody directed against a gp120-induced epitope of CD4.

    Science.gov (United States)

    Burastero, Samuele E; Frigerio, Barbara; Lopalco, Lucia; Sironi, Francesca; Breda, Daniela; Longhi, Renato; Scarlatti, Gabriella; Canevari, Silvana; Figini, Mariangela; Lusso, Paolo

    2011-01-01

    To penetrate susceptible cells, HIV-1 sequentially interacts with two highly conserved cellular receptors, CD4 and a chemokine receptor like CCR5 or CXCR4. Monoclonal antibodies (MAbs) directed against such receptors are currently under clinical investigation as potential preventive or therapeutic agents. We immunized Balb/c mice with molecular complexes of the native, trimeric HIV-1 envelope (Env) bound to a soluble form of the human CD4 receptor. Sera from immunized mice were found to contain gp120-CD4 complex-enhanced antibodies and showed broad-spectrum HIV-1-inhibitory activity. A proportion of MAbs derived from these mice preferentially recognized complex-enhanced epitopes. In particular, a CD4-specific MAb designated DB81 (IgG1Κ) was found to preferentially bind to a complex-enhanced epitope on the D2 domain of human CD4. MAb DB81 also recognized chimpanzee CD4, but not baboon or macaque CD4, which exhibit sequence divergence in the D2 domain. Functionally, MAb DB81 displayed broad HIV-1-inhibitory activity, but it did not exert suppressive effects on T-cell activation in vitro. The variable regions of the heavy and light chains of MAb DB81 were sequenced. Due to its broad-spectrum anti-HIV-1 activity and lack of immunosuppressive effects, a humanized derivative of MAb DB81 could provide a useful complement to current preventive or therapeutic strategies against HIV-1.

  9. Broad-spectrum inhibition of HIV-1 by a monoclonal antibody directed against a gp120-induced epitope of CD4.

    Directory of Open Access Journals (Sweden)

    Samuele E Burastero

    Full Text Available To penetrate susceptible cells, HIV-1 sequentially interacts with two highly conserved cellular receptors, CD4 and a chemokine receptor like CCR5 or CXCR4. Monoclonal antibodies (MAbs directed against such receptors are currently under clinical investigation as potential preventive or therapeutic agents. We immunized Balb/c mice with molecular complexes of the native, trimeric HIV-1 envelope (Env bound to a soluble form of the human CD4 receptor. Sera from immunized mice were found to contain gp120-CD4 complex-enhanced antibodies and showed broad-spectrum HIV-1-inhibitory activity. A proportion of MAbs derived from these mice preferentially recognized complex-enhanced epitopes. In particular, a CD4-specific MAb designated DB81 (IgG1Κ was found to preferentially bind to a complex-enhanced epitope on the D2 domain of human CD4. MAb DB81 also recognized chimpanzee CD4, but not baboon or macaque CD4, which exhibit sequence divergence in the D2 domain. Functionally, MAb DB81 displayed broad HIV-1-inhibitory activity, but it did not exert suppressive effects on T-cell activation in vitro. The variable regions of the heavy and light chains of MAb DB81 were sequenced. Due to its broad-spectrum anti-HIV-1 activity and lack of immunosuppressive effects, a humanized derivative of MAb DB81 could provide a useful complement to current preventive or therapeutic strategies against HIV-1.

  10. Anti-human CD73 monoclonal antibody inhibits metastasis formation in human breast cancer by inducing clustering and internalization of CD73 expressed on the surface of cancer cells

    DEFF Research Database (Denmark)

    Terp, Mikkel G; Olesen, Kristina A; Christensen, Eva Arnspang

    2013-01-01

    -linking of CD73, because both whole IgG anti-CD73 AD2 mAb and Fab' fragments thereof exhibited this effect. Ex vivo treatment of different breast cancer cell lines with anti-CD73 AD2 mAb before i.v. injection into mice inhibited extravasation/colonization of circulating tumor cells and significantly reduced...

  11. Exposure of Human CD8+ T Cells to Type-2 Cytokines Impairs Division and Differentiation and Induces Limited Polarization

    Directory of Open Access Journals (Sweden)

    Annette Fox

    2018-05-01

    Full Text Available Effector CD8+ T cells generally produce type-1 cytokines and mediators of the perforin/granzyme cytolytic pathway, yet type-2-polarized CD8+ cells (Tc2 are detected in type-2 (T2 cytokine-driven diseases such as asthma. It is unclear whether T2 cytokine exposure during activation is sufficient to polarize human CD8+ T cells. To address this question, a protocol was developed for high-efficiency activation of human CD8+ T cells in which purified single cells or populations were stimulated with plate-bound anti-CD3 and anti-CD11a mAb for up to 8 days in T2 polarizing or neutral conditions, before functional analysis. Activation of CD8+ naïve T cells (TN in T2 compared with neutral conditions decreased the size of single-cell clones, although early division kinetics were equivalent, indicating an effect on overall division number. Activation of TN in T2 conditions followed by brief anti-CD3 mAb restimulation favored expression of T2 cytokines, GATA3 and Eomes, and lowered expression of type-1 cytokines, Prf1, Gzmb, T-BET, and Prdm1. However, IL-4 was only weakly expressed, and PMA and ionomycin restimulation favored IFN-γ over IL-4 expression. Activation of TN in T2 compared with neutral conditions prevented downregulation of costimulatory (CD27, CD28 and lymph-node homing receptors (CCR7 and CD95 acquisition, which typically occur during differentiation into effector phenotypes. CD3 was rapidly and substantially induced after activation in neutral, but not T2 conditions, potentially contributing to greater division and differentiation in neutral conditions. CD8+ central memory T cells (TCM were less able to enter division upon reactivation in T2 compared with neutral conditions, and were more refractory to modulating IFN-γ and IL-4 production than CD8+ TN. In summary, while activation of TN in T2 conditions can generate T2 cytokine-biased cells, IL-4 expression is weak, T2 bias is lost upon strong restimulation, differentiation, and division

  12. Exercise-Induced Bronchoconstriction (EIB)

    Science.gov (United States)

    ... Conditions & Treatments ▸ Conditions Dictionary ▸ Exercise-Induced Bronchoconstriction Share | Exercise-Induced Bronchoconstriction (EIB) « Back to A to Z Listing Exercise-Induced Bronchoconstriction, (EIB), often known as exercise-induced ...

  13. CD36 participates in PrP(106-126-induced activation of microglia.

    Directory of Open Access Journals (Sweden)

    Mohammed Kouadir

    Full Text Available Microglial activation is a characteristic feature of the pathogenesis of prion diseases. The molecular mechanisms that underlie prion-induced microglial activation are not very well understood. In the present study, we investigated the role of the class B scavenger receptor CD36 in microglial activation induced by neurotoxic prion protein (PrP fragment 106-126 (PrP(106-126. We first examined the time course of CD36 mRNA expression upon exposure to PrP(106-126 in BV2 microglia. We then analyzed different parameters of microglial activation in PrP(106-126-treated cells in the presence or not of anti-CD36 monoclonal antibody (mAb. The cells were first incubated for 1 h with CD36 monoclonal antibody to block the CD36 receptor, and were then treated with neurotoxic prion peptides PrP(106-126. The results showed that PrP(106-126 treatment led to a rapid yet transitory increase in the mRNA expression of CD36, upregulated mRNA and protein levels of proinflammatory cytokines (IL-1β, IL-6 and TNF-α, increased iNOS expression and nitric oxide (NO production, stimulated the activation of NF-κB and caspase-1, and elevated Fyn activity. The blockade of CD36 had no effect on PrP(106-126-stimulated NF-κB activation and TNF-α protein release, abrogated the PrP(106-126-induced iNOS stimulation, downregulated IL-1β and IL-6 expression at both mRNA and protein levels as well as TNF-α mRNA expression, decreased NO production and Fyn phosphorylation, reduced caspase-1 cleavage induced by moderate PrP(106-126-treatment, but had no effect on caspase-1 activation after treatment with a high concentration of PrP(106-126. Together, these results suggest that CD36 is involved in PrP(106-126-induced microglial activation and that the participation of CD36 in the interaction between PrP(106-126 and microglia may be mediated by Src tyrosine kinases. Our findings provide new insights into the mechanisms underlying the activation of microglia by neurotoxic prion peptides

  14. Cyr61 induces IL-6 production by fibroblast-like synoviocytes promoting Th17 differentiation in rheumatoid arthritis.

    Science.gov (United States)

    Lin, Jinpiao; Zhou, Zhou; Huo, Rongfen; Xiao, Lianbo; Ouyang, Guilin; Wang, Li; Sun, Yue; Shen, Baihua; Li, Dangsheng; Li, Ningli

    2012-06-01

    Cysteine-rich protein 61 (Cyr61)/CCN1 is a product of an immediate early gene and functions in mediating cell adhesion and inducing cell migration. We previously showed that increased production of Cyr61 by fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) promotes FLS proliferation and participates in RA pathogenesis with the IL-17-dependent pathway. However, whether Cyr61 in turn regulates Th17 cell differentiation and further enhances inflammation of RA remained unknown. In the current study, we explored the potential role of Cyr61 as a proinflammatory factor in RA pathogenesis. We found that Cyr61 treatment dramatically induced IL-6 production in FLS isolated from RA patients. Moreover, IL-6 production was attenuated by Cyr61 knockdown in FLS. Mechanistically, we showed that Cyr61 activated IL-6 production via the αvβ5/Akt/NF-κB signaling pathway. Further, using a coculture system consisting of purified CD4(+) T cells and RA FLS, we found that RA FLS stimulated Th17 differentiation, and the pro-Th17 differentiation effect of RA FLS can be attenuated or stimulated by Cyr61 RNA interference or addition of exogenous Cyr61, respectively. Finally, using the collagen-induced arthritis animal model, we showed that treatment with the anti-Cyr61 mAb led to reduction of IL-6 levels, decrease of Th17 response, and attenuation of inflammation and disease progression in vivo. Taken together, our results reveal a novel role of Cyr61 in promoting Th17 development in RA via upregulation of IL-6 production by FLS, thus adding a new layer into the functional interplay between FLS and Th17 in RA pathogenesis. Our study also suggests that targeting of Cyr61 may represent a novel strategy in RA treatment.

  15. A sea urchin lectin, SUL-1, from the Toxopneustid sea urchin induces DC maturation from human monocyte and drives Th1 polarization in vitro

    International Nuclear Information System (INIS)

    Takei, Masao; Nakagawa, Hideyuki

    2006-01-01

    The sea urchin Toxopneustes pileolus belonging to the family Toxopneustidae, they have well-developed globiferous pedicellariae with pharmacologically active substances. We have purified a novel sea urchin lectin-1 (SUL-1) from the large globiferous pedicellariae of T. pileolus. Dendritic cells (DC) are professional APC and play a pivotal role in controlling immune responses. This study investigated whether SUL-1 can drive DC maturation from human immature monocyte-derived DC in vitro. Human monocytes were cultured with GM-CSF and IL-4 for 6 days followed by another 1 day in the presence of SUL-1 or LPS. DC harvested on day 7 were examined using functional assays. The expression levels of CD1a, CD80, CD83, CD86 and HLA-DR as expressed by mean fluorescence intensity (MFI) on DC differentiated from immature DC after culture with 1.0 μg/ml of SUL-1 for 1 day were enhanced and decreased endocytic activity. SUL-1-treated DC also displayed enhanced T cell stimulatory capacity in an MLR, as measured by T cell proliferation. Cell surface expression of CD80, CD83 and CD86 on SUL-1-treated DC was inhibited by anti-DC-SIGN mAb, while anti-DC-SIGN mAb had no influence on allogeneic T cell proliferation by SUL-1-treated DC. DC differentiated with SUL-1 induced the differentiation of naive T cell towards a helper T cell type 1 (Th1) response at DC/T (1:5) cells ratio depending on IL-12 secretion. In CTL assay, the production of IFN-γ and 51 Cr release on SUL-1-treated DC were more augmented than of immature DC or LPS-treated DC. SUL-1-treated DC expressed CCR7 and had a high migration to MIP-3β. Intracellular Ca 2+ mobilization in SUL-1-treated DC was also induced by MIP-3β. These results suggest that SUL-1 bindings to DC-SIGN on surface of immature DC may lead to differentiate DC from immature DC. Moreover, it suggests that SUL-1 may be used on DC-based vaccines for cancer immunotherapy

  16. An Antigen-Presenting and Apoptosis-Inducing Polymer Microparticle Prolongs Alloskin Graft Survival by Selectively and Markedly Depleting Alloreactive CD8+ T Cells

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2017-06-01

    Full Text Available Selectively depleting the pathogenic T cells is a fundamental strategy for the treatment of allograft rejection and autoimmune disease since it retains the overall immune function of host. The concept of killer artificial antigen-presenting cells (KaAPCs has been developed by co-coupling peptide–major histocompatibility complex (pMHC multimer and anti-Fas monoclonal antibody (mAb onto the polymeric microparticles (MPs to induce the apoptosis of antigen-specific T cells. But little information is available about its in vivo therapeutic potential and mechanism. In this study, polyethylenimine (PEI-coated poly lactic-co-glycolic acid microparticle (PLGA MP was fabricated as a cell-sized scaffold to covalently co-couple H-2Kb-Ig dimer and anti-Fas mAb for the generation of alloantigen-presenting and apoptosis-inducing MPs. Intravenous infusions of the biodegradable KaAPCs prolonged the alloskin graft survival for 43 days in a single MHC-mismatched murine model, depleted the most of H-2Kb-alloreactive CD8+ T cells in peripheral blood, spleen, and alloskin graft in an antigen-specific manner and anti-Fas-dependent fashion. The cell-sized KaAPCs circulated throughout vasculature into liver, kidney, spleen, lymph nodes, lung, and heart, but few ones into local allograft at early stage, with a retention time up to 36 h in vivo. They colocalized with CD8+ T cells in secondary lymphoid organs while few ones contacted with CD4+ T cells, B cells, macrophage, and dendritic cells, or internalized by phagocytes. Importantly, the KaAPC treatment did not significantly impair the native T cell repertoire or non-pathogenic immune cells, did not obviously suppress the overall immune function of host, and did not lead to visible organ toxicity. Our results strongly document the high potential of PLGA MP-based KaAPCs as a novel antigen-specific immunotherapy for allograft rejection and autoimmune disorder. The in vivo mechanism of alloinhibition, tissue

  17. Induced pluripotency with endogenous and inducible genes

    International Nuclear Information System (INIS)

    Duinsbergen, Dirk; Eriksson, Malin; Hoen, Peter A.C. 't; Frisen, Jonas; Mikkers, Harald

    2008-01-01

    The recent discovery that two partly overlapping sets of four genes induce nuclear reprogramming of mouse and even human cells has opened up new possibilities for cell replacement therapies. Although the combination of genes that induce pluripotency differs to some extent, Oct4 and Sox2 appear to be a prerequisite. The introduction of four genes, several of which been linked with cancer, using retroviral approaches is however unlikely to be suitable for future clinical applications. Towards developing a safer reprogramming protocol, we investigated whether cell types that express one of the most critical reprogramming genes endogenously are predisposed to reprogramming. We show here that three of the original four pluripotency transcription factors (Oct4, Klf4 and c-Myc or MYCER TAM ) induced reprogramming of mouse neural stem (NS) cells exploiting endogenous SoxB1 protein levels in these cells. The reprogrammed neural stem cells differentiated into cells of each germ layer in vitro and in vivo, and contributed to mouse development in vivo. Thus a combinatorial approach taking advantage of endogenously expressed genes and inducible transgenes may contribute to the development of improved reprogramming protocols

  18. Diet induced thermogenesis

    Directory of Open Access Journals (Sweden)

    Westerterp KR

    2004-08-01

    Full Text Available Objective Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet. Methods Measuring conditions include nutritional status of the subject, physical activity and duration of the observation. Diet characteristics are energy content and macronutrient composition. Results Most studies measure diet-induced thermogenesis as the increase in energy expenditure above basal metabolic rate. Generally, the hierarchy in macronutrient oxidation in the postprandial state is reflected similarly in diet-induced thermogenesis, with the sequence alcohol, protein, carbohydrate, and fat. A mixed diet consumed at energy balance results in a diet induced energy expenditure of 5 to 15 % of daily energy expenditure. Values are higher at a relatively high protein and alcohol consumption and lower at a high fat consumption. Protein induced thermogenesis has an important effect on satiety. In conclusion, the main determinants of diet-induced thermogenesis are the energy content and the protein- and alcohol fraction of the diet. Protein plays a key role in body weight regulation through satiety related to diet-induced thermogenesis.

  19. Induced quantum conformal gravity

    International Nuclear Information System (INIS)

    Novozhilov, Y.V.; Vassilevich, D.V.

    1988-11-01

    Quantum gravity is considered as induced by matter degrees of freedom and related to the symmetry breakdown in the low energy region of a non-Abelian gauge theory of fundamental fields. An effective action for quantum conformal gravity is derived where both the gravitational constant and conformal kinetic term are positive. Relation with induced classical gravity is established. (author). 15 refs

  20. Induced radioactivity at CERN

    CERN Multimedia

    1970-01-01

    A description of some of the problems and some of the advantages associated with the phenomenon of induced radioactivity at accelerator centres such as CERN. The author has worked in this field for several years and has recently written a book 'Induced Radioactivity' published by North-Holland.

  1. Diet induced thermogenesis

    NARCIS (Netherlands)

    Westerterp, K.R.

    2004-01-01

    OBJECTIVE: Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet. METHODS: Measuring

  2. Bleomycin-induced pneumonitis

    NARCIS (Netherlands)

    S. Sleijfer (Stefan)

    2001-01-01

    textabstractThe cytotoxic agent bleomycin is feared for its induction of sometimes fatal pulmonary toxicity, also known as bleomycin-induced pneumonitis (BIP). The central event in the development of BIP is endothelial damage of the lung vasculature due to bleomycin-induced

  3. NKT cells contribute to basal IL-4 production but are not required to induce experimental asthma.

    Science.gov (United States)

    McKnight, Christopher G; Morris, Suzanne C; Perkins, Charles; Zhu, Zhenqi; Hildeman, David A; Bendelac, Albert; Finkelman, Fred D

    2017-01-01

    CD1d-deficiency results in a selective deletion of NKT cells in mice that is reported to prevent murine allergic airway disease (AAD). Because we find 2-3 fold lower basal IL-4 production in CD1d- mice than in wild-type (WT) mice, we hypothesized that the contribution made by NKT cells to AAD would depend on the strength of the stimulus used to induce the disease. Consequently, we compared CD1d-deficient mice to WT mice in the development of AAD, using several models of disease induction that differed in the type and dose of allergen, the site of sensitization and the duration of immunization. Surprisingly we found equivalent allergic inflammation and airway disease in WT and CD1d- mice in all models investigated. Consistent with this, NKT cells constituted only ~2% of CD4+ T cells in the lungs of mice with AAD, and IL-4-transcribing NKT cells did not expand with disease induction. Concerned that the congenital absence of NKT cells might have caused a compensatory shift within the immune response, we administered an anti-CD1d monoclonal Ab (mAb) to block NKT function before airway treatments, before or after systemic sensitization to antigen. Such Ab treatment did not affect disease severity. We suggest that the differences reported in the literature regarding the significance of NKT cells in the induction of allergic airway disease may have less to do with the methods used to study the disease and more to do with the animals themselves and/or the facilities used to house them.

  4. NKT cells contribute to basal IL-4 production but are not required to induce experimental asthma.

    Directory of Open Access Journals (Sweden)

    Christopher G McKnight

    Full Text Available CD1d-deficiency results in a selective deletion of NKT cells in mice that is reported to prevent murine allergic airway disease (AAD. Because we find 2-3 fold lower basal IL-4 production in CD1d- mice than in wild-type (WT mice, we hypothesized that the contribution made by NKT cells to AAD would depend on the strength of the stimulus used to induce the disease. Consequently, we compared CD1d-deficient mice to WT mice in the development of AAD, using several models of disease induction that differed in the type and dose of allergen, the site of sensitization and the duration of immunization. Surprisingly we found equivalent allergic inflammation and airway disease in WT and CD1d- mice in all models investigated. Consistent with this, NKT cells constituted only ~2% of CD4+ T cells in the lungs of mice with AAD, and IL-4-transcribing NKT cells did not expand with disease induction. Concerned that the congenital absence of NKT cells might have caused a compensatory shift within the immune response, we administered an anti-CD1d monoclonal Ab (mAb to block NKT function before airway treatments, before or after systemic sensitization to antigen. Such Ab treatment did not affect disease severity. We suggest that the differences reported in the literature regarding the significance of NKT cells in the induction of allergic airway disease may have less to do with the methods used to study the disease and more to do with the animals themselves and/or the facilities used to house them.

  5. In vivo effects of monoclonal anti-L3T4 antibody on immune responsiveness of mice infected with Schistosoma mansoni. Reduction of irradiated cercariae-induced resistance

    International Nuclear Information System (INIS)

    Kelly, E.A.; Colley, D.G.

    1988-01-01

    Mice can be partially protected against challenge infections of Schistosoma mansoni cercariae by either single or multiple exposure to irradiated cercariae (x-cerc). The participation of L3T4+ lymphocytes on this resistance phenomenon was evaluated by selectively depleting this cell population through in vivo administration of mAb anti-L3T4 at three different times in relationship to the challenge infections. Treatment with anti-L3T4 before challenge such that depletion was effective during the time of cercarial skin penetration and dermal/s.c. residence significantly reduced the level of resistance induced by x-cerc sensitization. When treatment was delayed until after challenge, depletion of L3T4+ cells coincided with either the lung or post-lung/liver phases of schistosomular migration, and normal levels of x-cerc-induced resistance were induced. In contrast to once-immunized mice, mice hyperimmunized by five exposures to x-cerc and then depleted of L3T4+ cells at the time of challenge still expressed resistance to the challenge. These data suggest that when mice are sensitized only once with x-cerc the challenge infection provides a necessary immunologic boost which requires L3T4+ cells for effective expression of resistance. The requirement for this anamnestic effect by the challenge infection can be circumvented by hyperimmunization. Evaluation of the immune response of one-time sensitized or hyperimmunized mice demonstrated that cellular Ag-specific proliferative responses and mitogen-induced lymphokine production were abrogated after any of the various in vivo regimens of anti-L3T4 antibody. In contrast, immunoblot analysis of humoral responsiveness revealed a correlation between the expression of resistance and the ability of sera from immunized and anti-L3T4 treated mice to recognize a 75-kDa parasite antigenic component

  6. Induced abortion in Taiwan.

    Science.gov (United States)

    Wang, P D; Lin, R S

    1995-04-01

    Induced abortion is widely practised in Taiwan; however, it had been illegal until 1985. It was of interest to investigate induced abortion practices in Taiwan after its legalization in 1985 in order to calculate the prevalence rate and ratio of induced abortion to live births and to pregnancies in Taiwan. A study using questionnaires through personal interviews was conducted on more than seventeen thousand women who attended a family planning service in Taipei metropolitan areas between 1991 and 1992. The reproductive history and sexual behaviour of the subjects were especially focused on during the interviews. Preliminary findings showed that 46% of the women had a history of having had an induced abortion. Among them, 54.8% had had one abortion, 29.7% had had two, and 15.5% had had three or more. The abortion ratio was 379 induced abortions per 1,000 live births and 255 per 1,000 pregnancies. The abortion ratio was highest for women younger than 20 years of age, for aboriginal women and for nulliparous women. When logistic regression was used to control for confounding variables, we found that the number of previous live births is the strongest predictor relating to women seeking induced abortion. In addition, a significant positive association exists between increasing number of induced abortions and cervical dysplasia.

  7. Photon induced reactions

    International Nuclear Information System (INIS)

    Mecking, B.A.

    1982-04-01

    Various aspects of medium energy nuclear reactions induced by real photons are reviewed. Special emphasis is put on high accuracy experiments that will become possible with the next generation of electron accelerators. (orig.)

  8. Induced Noise Control

    National Research Council Canada - National Science Library

    Maidanik, G

    2002-01-01

    The induced noise control parameter is defined in terms of the ratio of the stored energy in a master dynamic system, when it is coupled to an adjunct dynamic system, to that stored energy when the coupling is absent...

  9. Beam induced RF heating

    CERN Document Server

    Salvant, B; Arduini, G; Assmann, R; Baglin, V; Barnes, M J; Bartmann, W; Baudrenghien, P; Berrig, O; Bracco, C; Bravin, E; Bregliozzi, G; Bruce, R; Bertarelli, A; Carra, F; Cattenoz, G; Caspers, F; Claudet, S; Day, H; Garlasche, M; Gentini, L; Goddard, B; Grudiev, A; Henrist, B; Jones, R; Kononenko, O; Lanza, G; Lari, L; Mastoridis, T; Mertens, V; Métral, E; Mounet, N; Muller, J E; Nosych, A A; Nougaret, J L; Persichelli, S; Piguiet, A M; Redaelli, S; Roncarolo, F; Rumolo, G; Salvachua, B; Sapinski, M; Schmidt, R; Shaposhnikova, E; Tavian, L; Timmins, M; Uythoven, J; Vidal, A; Wenninger, J; Wollmann, D; Zerlauth, M

    2012-01-01

    After the 2011 run, actions were put in place during the 2011/2012 winter stop to limit beam induced radio frequency (RF) heating of LHC components. However, some components could not be changed during this short stop and continued to represent a limitation throughout 2012. In addition, the stored beam intensity increased in 2012 and the temperature of certain components became critical. In this contribution, the beam induced heating limitations for 2012 and the expected beam induced heating limitations for the restart after the Long Shutdown 1 (LS1) will be compiled. The expected consequences of running with 25 ns or 50 ns bunch spacing will be detailed, as well as the consequences of running with shorter bunch length. Finally, actions on hardware or beam parameters to monitor and mitigate the impact of beam induced heating to LHC operation after LS1 will be discussed.

  10. Vitiligo, drug induced (image)

    Science.gov (United States)

    ... this person's face have resulted from drug-induced vitiligo. Loss of melanin, the primary skin pigment, occasionally ... is the case with this individual. The typical vitiligo lesion is flat and depigmented, but maintains the ...

  11. Tanezumab: a selective humanized mAb for chronic lower back pain

    Directory of Open Access Journals (Sweden)

    Webb MP

    2018-02-01

    Full Text Available Michael P Webb,1 Erik M Helander,2 Bethany L Menard,2 Richard D Urman,3 Alan D Kaye2 1Department of Anesthesiology, North Shore Hospital, Auckland, New Zealand; 2Department of Anesthesiology, LSU School of Medicine, New Orleans, LA, USA; 3Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Abstract: Chronic lower back pain is a significant disease that affects nearly 20% of the worldwide population. Along with hindering patients’ quality of life, chronic lower back pain is considered to be the second most common cause of disability among Americans. Treating chronic lower back pain is often a challenge for providers, especially in light of our current opioid epidemic. With this epidemic and an increased aging population, there is an imminent need for development of new pharmacologic therapeutic options, which are not only effective but also pose minimal adverse effects to the patient. With these considerations, a novel therapeutic agent called tanezumab has been developed and studied. Tanezumab is a humanized monoclonal immunoglobulin G2 antibody that works by inhibiting the binding of NGF to its receptors. NGF is involved in the function of sensory neurons and fibers involved in nociceptive transduction. It is commonly seen in excess in inflammatory joint conditions and in chronic pain patients. Nociceptors are dependent on NGF for growth and ongoing function. The inhibition of NGF binding to its receptors is a mechanism by which pain pathways can be interrupted. In this article, a number of recent randomized controlled trials are examined relating to the efficacy and safety of tanezumab in the treatment of chronic lower back pain. Although tanezumab was shown to be an effective pain modulator in major trials, several adverse effects were seen among different doses of the medication, one of which led to a clinical hold placed by the US Food and Drug Administration. In summary, tanezumab is a promising agent that warrants further investigation into its analgesic properties and safety profile. Keywords: tanezumab, monoclonal antibody, chronic lower back pain, neurotrophin nerve growth factor (NGF, tropomyosin receptor A (TrkA, treatment 

  12. Valge Maja hämab USA vägede tulevikust Iraagis / Neeme Raud

    Index Scriptorium Estoniae

    Raud, Neeme, 1969-

    2006-01-01

    Kuigi USA president George W. Bush on kõnelenud ja USA vägede ülemjuhataja Iraagis George Casey esitanud konkreetse plaani USA vägede väljatoomisest Iraagist, pole Valge Maja konkreetset plaani ametlikult kinnitanud. Lisa: Sõjatandrilt lahkumine

  13. Prevalence of mabDAS-1 positivity in biopsy specimens from the esophagogastric junction

    NARCIS (Netherlands)

    Rogge-Wolf, Claudia; Seldenrijk, Cornelis A.; Das, Kiron M.; Timmer, Robin; Breumelhof, Ronald; Smout, André J. P. M.; Amenta, Peter S.; Griffel, Louis H.

    2002-01-01

    OBJECTIVE: Intestinal metaplasia (IM) is a precursor for malignancies at the esophagogastric junction. A monoclonal antibody, mAbDAS-1, can probably identify cellular characteristics of IM before the appearance of goblet cells. The aim of this study was to examine the prevalence of mAbDAS-1

  14. Prevalence of mabDAS-1 positivity in biopsy specimens from the esophagogastric junction.

    Science.gov (United States)

    Rogge-Wolf, Claudia; Seldenrijk, Cornelis A; Das, Kiron M; Timmer, Robin; Breumelhof, Ronald; Smout, André J P M; Amenta, Peter S; Griffel, Louis H

    2002-12-01

    Intestinal metaplasia (IM) is a precursor for malignancies at the esophagogastric junction. A monoclonal antibody, mAbDAS-1, can probably identify cellular characteristics of IM before the appearance of goblet cells. The aim of this study was to examine the prevalence of mAbDAS-1 positivity in biopsies from the squamocolumnar junction (SCJ) and to correlate this positivity with the presence of IM and clinical findings. In 559 patients, reflux symptoms were scored, and the presence of reflux esophagitis and hiatus hernia was evaluated during endoscopy. Two biopsy specimens were obtained from the SCJ. In a subset of patients (n = 99), biopsies from the endoscopically defined cardiac region (2 cm distal to proximal margin of gastric folds) were available. Biopsy specimens were stained with hematoxylin and eosin, Alcian Blue, modified Giemsa, and mAbDAS-1. mAbDAS-1 positivity was observed in the SCJ biopsies of 201 of 486 (41.4%) patients without IM and in 64 of 73 (87.7%) patients with IM. Patients without IM but with antibody positivity showed similar histological characteristics as patients with IM at the SCJ. Biopsies of 123 of 559 patients (22%) revealed a columnar-cuboidal epithelium, which was found to be mAbDAS-1 positive in 64.2% (77 of 123). Tissue specimens from the cardiac region without IM stained positive in 14.2% (13 of 91), 12 of those also stained at the SCJ. In patients without IM, a high prevalence of mAbDAS-1 positivity was observed. Biopsies of these patients showed similar histological characteristics as patients with IM. Although not all patients exhibiting this reactivity may develop IM, mAbDAS-1 reactivity may help in the understanding of the histogenesis of IM at the SCJ.

  15. HER2 specific delivery of methotrexate by dendrimer conjugated anti-HER2 mAb

    International Nuclear Information System (INIS)

    Shukla, Rameshwer; Thomas, Thommey P; Desai, Ankur M; Kotlyar, Alina; Park, Steve J; Baker, James R Jr

    2008-01-01

    Herceptin, a humanized monoclonal antibody that binds to human growth factor receptor-2 (HER2), was covalently attached to a fifth-generation (G5) polyamidoamine dendrimer containing the cytotoxic drug methotrexate. The specific binding and internalization of this conjugate labeled with FITC was clearly demonstrated in cell lines overexpressing HER2 by flow cytometry as well as confocal microscopic analysis. In addition, binding and uptake of antibody conjugated dendrimers was completely blocked by excess non-conjugated herceptin. The dendrimer conjugate was also shown to inhibit the dihydrofolate reductase with similar activity to methotrexate. Co-localization experiments with lysotracker red indicate that antibody conjugate, although internalized efficiently into cells, has an unusually long residence time in the lysosome. Somewhat lower cytotoxicity of the conjugate in comparison to free methotrexate was attributed to the slow release of methotrexate from the conjugate and its long retention in the lysosomal pocket

  16. Intercomparison of radionuclide measurements in marine fish flesh sample MA-B-3

    International Nuclear Information System (INIS)

    1987-08-01

    This final report presents results of the laboratory intercomparison of the activity concentration determination of 40 K, 90 Sr, 137 Cs, 210 Pb, 210 Po, 226 Ra, 228 Th, 230 Th, 232 Th, 238 U, 239 Pu, 240 Pu and 241 Am in the sample of garpike fish organized by the IAEA's Analytical Quality Control Service. The forty-three laboratories from twenty-three countries have reported results established by different analytical techniques. This sample is intended as a reference material for the measurement of 40 K and 137 Cs in marine biological samples and other similar matrices. 4 refs, 9 tabs

  17. International Co-ordinating Council of the Programme on Man and the Biosphere (MAB). Final Report.

    Science.gov (United States)

    United Nations Educational, Scientific, and Cultural Organization, Paris (France).

    Man and the Biosphere Program is an interdisciplinary program of research which emphasizes an ecological approach to the study of interrelationships between man and the environment. It is concerned with subjects of global or major regional significance which require international cooperation. This final report discusses areas in which…

  18. Terahertz Induced Electromigration

    DEFF Research Database (Denmark)

    Strikwerda, Andrew; Zalkovskij, Maksim; Iwaszczuk, Krzysztof

    2014-01-01

    We report the first observation of THz-field-induced electromigration in subwavelength metallic gap structures after exposure to intense single-cycle, sub-picosecond electric field transients of amplitude up to 400 kV/cm.......We report the first observation of THz-field-induced electromigration in subwavelength metallic gap structures after exposure to intense single-cycle, sub-picosecond electric field transients of amplitude up to 400 kV/cm....

  19. Diet induced thermogenesis

    OpenAIRE

    Westerterp KR

    2004-01-01

    Objective Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet. Methods Measuring conditions include nutritional status of the subject, physical activity and duration of the observation. Diet characteristics are energy content and macronutrient composition. Resu...

  20. Laser-induced interactions

    International Nuclear Information System (INIS)

    Green, W.R.

    1979-01-01

    This dissertation discusses some of the new ways that lasers can be used to control the energy flow in a medium. Experimental and theoretical considerations of the laser-induced collision are discussed. The laser-induced collision is a process in which a laser is used to selectively transfer energy from a state in one atomic or molecular species to another state in a different species. The first experimental demonstration of this process is described, along with later experiments in which lasers were used to create collisional cross sections as large as 10 - 13 cm 2 . Laser-induced collisions utilizing both a dipole-dipole interaction and dipole-quadrupole interaction have been experimentally demonstrated. The theoretical aspects of other related processes such as laser-induced spin-exchange, collision induced Raman emission, and laser-induced charge transfer are discussed. Experimental systems that could be used to demonstrate these various processes are presented. An experiment which produced an inversion of the resonance line of an ion by optical pumping of the neutral atom is described. This type of scheme has been proposed as a possible method for constructing VUV and x-ray lasers

  1. Radiation-induced apoptosis

    International Nuclear Information System (INIS)

    Ohyama, Harumi

    1995-01-01

    Apoptosis is an active process of gene-directed cellular self-destruction that can be induced in many cell types via numerous physiological and pathological stimuli. We found that interphasedeath of thymocytes is a typical apoptosis showing the characteristic features of apoptosis including cell shrinkage, chromatin condensation and DNA degradation. Moderate dose of radiation induces extensive apoptosis in rapidly proliferating cell population such as the epithelium of intestinal crypt. Recent reports indicate that the ultimate form of radiation-induced mitotic death in several cells is also apoptosis. One of the hallmarks of apoptosis is the enzymatic internucleosomal degradation of chromatin DNA. We identified an endonuclease responsible for the radiation-induced DNA degradation in rat thymocytes. The death-sparing effects of interrupting RNA and protein synthesis suggested a cell genetic program for apoptosis. Apoptosis of thymocytes initiated by DNA damage, such as radiation and radio mimetic substance, absolutely requires the protein of p53 cancer suppresser gene. The cell death induced by glucocorticoid, or aging, has no such requirement. Expression of oncogene bcl-2 rescues cells from the apoptosis. Massive apoptosis in radiosensitive cells induced by higher dose radiation may be fatal. It is suggested that selective apoptotic elimination of cells would play an important role for protection against carcinogenesis and malformation through removal of cells with unrepaired radiation-induced DNA damages. Data to evaluate the significance of apoptosis in the radiation risk are still poor. Further research should be done in order to clarify the roles of the cell death on the acute and late effects of irradiation. (author)

  2. Neutralization of TSLP inhibits airway remodeling in a murine model of allergic asthma induced by chronic exposure to house dust mite.

    Directory of Open Access Journals (Sweden)

    Zhuang-Gui Chen

    Full Text Available Chronic allergic asthma is characterized by Th2-typed inflammation, and contributes to airway remodeling and the deterioration of lung function. However, the initiating factor that links airway inflammation to remodeling is unknown. Thymic stromal lymphopoietin (TSLP, an epithelium-derived cytokine, can strongly activate lung dendritic cells (DCs through the TSLP-TSLPR and OX40L-OX40 signaling pathways to promote Th2 differentiation. To determine whether TSLP is the underlying trigger of airway remodeling in chronic allergen-induced asthma, we induced allergic airway inflammation in mice by intranasal administration of house dust mite (HDM extracts for up to 5 consecutive weeks. We showed that repeated respiratory exposure to HDM caused significant airway eosinophilic inflammation, peribronchial collagen deposition, goblet cell hyperplasia, and airway hyperreactivity (AHR to methacholine. These effects were accompanied with a salient Th2 response that was characterized by the upregulation of Th2-typed cytokines, such as IL-4 and IL-13, as well as the transcription factor GATA-3. Moreover, the levels of TSLP and transforming growth factor beta 1 (TGF-β1 were also increased in the airway. We further demonstrated, using the chronic HDM-induced asthma model, that the inhibition of Th2 responses via neutralization of TSLP with an anti-TSLP mAb reversed airway inflammation, prevented structural alterations, and decreased AHR to methacholine and TGF-β1 level. These results suggest that TSLP plays a pivotal role in the initiation and persistence of airway inflammation and remodeling in the context of chronic allergic asthma.

  3. Chemical-induced Vitiligo

    Science.gov (United States)

    Harris, John E.

    2016-01-01

    Synopsis Chemical-induced depigmentation of the skin has been recognized for over 75 years, first as an occupational hazard but then extending to those using household commercial products as common as hair dyes. Since their discovery, these chemicals have been used therapeutically in patients with severe vitiligo to depigment their remaining skin and improve their appearance. The importance of recognizing this phenomenon was highlighted during an outbreak of vitiligo in Japan during the summer of 2013, when over 16,000 users of a new skin lightening cosmetic cream developed skin depigmentation at the site of contact with the cream and many in remote areas as well. Depigmenting chemicals appear to be analogs of the amino acid tyrosine that disrupt melanogenesis and result in autoimmunity and melanocyte destruction. Because chemical-induced depigmentation is clinically and histologically indistinguishable from non-chemically induced vitiligo, and because these chemicals appear to induce melanocyte autoimmunity, this phenomenon should be known as “chemical-induced vitiligo”, rather than less accurate terms that have been previously used. PMID:28317525

  4. CD3 directed bispecific antibodies induce increased lymphocyte-endothelial cell interactions in vitro

    NARCIS (Netherlands)

    Molema, G; Tervaert, JWC; Kroesen, BJ; Helfrich, W; Meijer, DKF; de Leij, LFMH

    Bispecific antibody (BsMAb) BIS-1 has been developed to redirect the cytolytic activity of cytotoxic T lymphocytes (CTL) to epithelial glycoprotein-2 (EGP-2) expressing tumour cells; intravenous administration of BIS-1 F(ab')(2) to carcinoma patients in a phase I/II clinical trial, caused

  5. [Drug induced diarrhea].

    Science.gov (United States)

    Morard, Isabelle; Hadengue, Antoine

    2008-09-03

    Diarrhea is a frequent adverse event involving the most frequently antibiotics, laxatives and NSAI. Drug induced diarrhea may be acute or chronic. It may be due to expected, dose dependant properties of the drug, to immuno-allergic or bio-genomic mechanisms. Several pathophysiological mechanisms have been described resulting in osmotic, secretory or inflammatory diarrhea, shortened transit time, or malabsorption. Histopathological lesions sometimes associated with drug induced diarrhea are usually non specific and include ulcerations, inflammatory or ischemic lesions, fibrous diaphragms, microscopic colitis and apoptosis. The diagnosis of drug induced diarrhea, sometimes difficult to assess, relies on the absence of other obvious causes and on the rapid disappearance of the symptoms after withdrawal of the suspected drug.

  6. Rosuvastatin-induced pemphigoid.

    LENUS (Irish Health Repository)

    Murad, Aizuri A

    2012-01-01

    Statins are widely prescribed medications and very well tolerated. Rosuvastatin is another member of this drug used to treat dyslipidaemia. It is a competitive inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase. Immunobullous disease is usually idiopathic but can be drug-induced. Both idiopathic and iatrogenic forms share common clinical and immunohistological features. The authors report a case of pemphigoid induced by rosuvastatin, a commonly prescribed medication. To our knowledge, there is limited report on rosuvastatin associated with pemphigoid in the literature.

  7. Cervical osteophyte induced dysphagia

    International Nuclear Information System (INIS)

    Davies, R.P.; Sage, M.R.; Brophy, B.P.

    1989-01-01

    Although cervical spondylosis is a common disorder, dysphagia induced by osteophyte formation is uncommon. Fewer than one hundred cases of cervical osteophyte induced dysphagia have been reported, with little attention to the diagnosis by barium swallow. The radiological features of two cases treated surgically with good results are described. Both cases complained of dysphagia while one had associated respiratory obstruction on forward flexion of his neck. The features on barium study of cervical osteophytes causing dysphagia include deformity at the level of osteophyte formation, in both AP and lateral projections. Tracheal aspirations due to deformity at the laryngeal inlet and interference with epiglottic retroversion may be present. 8 refs., 3 figs

  8. Exercise-induced rhabdomyolysis.

    Science.gov (United States)

    Lee, George

    2014-11-03

    Exercise-induced rhabdomyolysis, or exertional rhabdomyolysis (ER), is a clinical entity typically considered when someone presents with muscle stiffness, swelling, and pain out of proportion to the expected fatigue post exercise. The diagnosis is confirmed by myoglobinuria, and an elevated serum Creatinine Phosphokinase (CPK) level, usually 10 times the normal range. However, an elevation in CPK is seen in most forms of strenuous exercise, up to 20 times the upper normal range. Therefore, there is no definitive pathologic CPK cut-off. Fortunately the dreaded complication of acute renal failure is rare compared to other forms rhabdomyolysis. We review the risks, diagnosis, clinical course and treatment for exercise- induced rhabdomyolysis.

  9. Migraine induced by hypoxia

    DEFF Research Database (Denmark)

    Arngrim, Nanna; Schytz, Henrik Winther; Britze, Josefine

    2016-01-01

    in the visual cortex were measured by proton magnetic resonance spectroscopy. The circumference of cranial arteries was measured by 3 T high-resolution magnetic resonance angiography. Hypoxia induced migraine-like attacks in eight patients compared to one patient after sham (P = 0.039), aura in three...... and possible aura in 4 of 15 patients. Hypoxia did not change glutamate concentration in the visual cortex compared to sham, but increased lactate concentration (P = 0.028) and circumference of the cranial arteries (P ... suggests that hypoxia may provoke migraine headache and aura symptoms in some patients. The mechanisms behind the migraine-inducing effect of hypoxia should be further investigated....

  10. Airbag induced corneal ectasia.

    Science.gov (United States)

    Mearza, Ali A; Koufaki, Fedra N; Aslanides, Ioannis M

    2008-02-01

    To report a case of airbag induced corneal ectasia. Case report. A patient 3 years post-LASIK developed bilateral corneal ectasia worse in the right eye following airbag deployment in a road traffic accident. At last follow up, best corrected vision was 20/40 with -4.00/-4.00 x 25 in the right eye and 20/25 with -1.25/-0.50 x 135 in the left eye. This is a rare presentation of trauma induced ectasia in a patient post-LASIK. It is possible that reduction in biomechanical integrity of the cornea from prior refractive surgery contributed to this presentation.

  11. Sleep-inducing factors.

    Science.gov (United States)

    García-García, Fabio; Acosta-Peña, Eva; Venebra-Muñoz, Arturo; Murillo-Rodríguez, Eric

    2009-08-01

    Kuniomi Ishimori and Henri Piéron were the first researchers to introduce the concept and experimental evidence for a chemical factor that would presumably accumulate in the brain during waking and eventually induce sleep. This substance was named hypnotoxin. Currently, the variety of substances which have been shown to alter sleep includes peptides, cytokines, neurotransmitters and some substances of lipidic nature, many of which are well known for their involvement in other biological activities. In this chapter, we describe the sleep-inducing properties of the vasoactive intestinal peptide, prolactin, adenosine and anandamide.

  12. Inducible laryngeal obstruction

    DEFF Research Database (Denmark)

    Halvorsen, Thomas; Walsted, Emil Schwarz; Bucca, Caterina

    2017-01-01

    Inducible laryngeal obstruction (ILO) describes an inappropriate, transient, reversible narrowing of the larynx in response to external triggers. ILO is an important cause of a variety of respiratory symptoms and can mimic asthma. Current understanding of ILO has been hampered by imprecise nomenc...

  13. Drug-induced apnea.

    Science.gov (United States)

    Boutroy, M J

    1994-01-01

    Drugs have been in the past and will in the future still be liable to induce apnea in neonates, infants and older children. At these different stages of development, the child may be abnormally vulnerable to respiratory disorders and apnea, and doses of drugs, without any abnormal side effects in adult patients, can be harmful in younger subjects. Drugs responsible for apnea during development are numerous, but more than half of the problems are induced by sedatives and hypnotics, among which phenothiazines, barbiturates, benzodiazepines (included transplacentally acquired) and general anesthetics are a few. Other pharmacological families are apnea inducers in the neonatal period and childhood: analgesics and opioid narcotics, agents acting at the levels of neuromuscular function and autonomic ganglia, and cardiovascular agents. The pathogenesis of these apneas depends on the disturbance of any mechanism responsible for the respiratory activity: medullary centers and brain stem structures, afferent influx to CNS, sleep stages, upper airways, lungs and respiratory muscles. At key stages such as birth and infancy, drugs may emphasize the particular sensitivity of the mechanisms responsible for inducing apnea. This might explain unexpected respiratory disorders during development.

  14. Metronidazole-Induced Pancreatitis

    Directory of Open Access Journals (Sweden)

    E. O'Halloran

    2010-01-01

    Conclusion. This case provides the eighth report of Metronidazole induced pancreatitis. All of the cases were reported in females and ran a benign course.Early diagnosis, discontinuation of the drug and supportive care will lead to a successful recovery in the majority of cases.

  15. XTC-induced hepatitis

    NARCIS (Netherlands)

    Oranje, W.A.; van Pol, V.; van der Wurff, A.A.; Zeijen, R.N.; Stockbrügger, R.W.; Arends, J.W.

    1994-01-01

    XTC-induced hepatitis. Oranje WA, von Pol P, vd Wurff A, Zeijen RN, Stockbrugger RW, Arends JW. Department of Internal Medicine, University Hospital, Maastricht, Netherlands. An increasing number of severe complications associated with the use of XTC is being reported. After 11 earlier case reports

  16. Bowthruster-induced damage

    NARCIS (Netherlands)

    Schokking, L.A.; Janssen, P.C.; Verhagen, H.J.

    2003-01-01

    The stability of stones in propeller-induced jet wash is still difficult to predict. Especially the trend of bowthrusters increasing in size and power in sea going ships (especially ferries) over the last years may be a reason for concern when dealing with the protection of slopes and beds. But also

  17. Muon-induced fission

    International Nuclear Information System (INIS)

    Polikanov, S.

    1980-01-01

    A review of recent experimental results on negative-muon-induced fission, both of 238 U and 232 Th, is given. Some conclusions drawn by the author are concerned with muonic atoms of fission fragments and muonic atoms of the shape isomer of 238 U. (author)

  18. Calotropis procera -induced keratitis

    Directory of Open Access Journals (Sweden)

    Pandey Nidhi

    2009-01-01

    Full Text Available Calotropis procera produces copious amounts of latex, which has been shown to possess several pharmacological properities. Its local application produces intense inflammatory response. In the 10 cases of Calotropis procera -induced keratitis reported here, the clinical picture showed corneal edema with striate keratopathy without any evidence of intraocular inflammation. The inflammation was reversed by the local application of steroid drops.

  19. Induced nuclear beta decay

    International Nuclear Information System (INIS)

    Reiss, H.R.

    1986-01-01

    Certain nuclear beta decay transitions normally inhibited by angular momentum or parity considerations can be induced to occur by the application of an electromagnetic field. Such decays can be useful in the controlled production of power, and in fission waste disposal

  20. Hyperthermia-induced apoptosis

    NARCIS (Netherlands)

    Nijhuis, E.H.A.

    2008-01-01

    This thesis describes a number of studies that investigated several aspects of heat-induced apoptosis in human lymphoid malignancies. Cells harbour both pro- and anti-apoptotic proteins and the balance between these proteins determines whether a cell is susceptible to undergo apoptosis. In this

  1. Drug induced aseptic meningitis

    African Journals Online (AJOL)

    PROF. EZECHUKWU

    2013-09-29

    Sep 29, 2013 ... Abstract. Drug-induced aseptic meningitis (DIAM) is a rare but important and often challenging diagnosis for the physician. Intake of antimicrobials, steroids, anal- gesics amongst others has been implicated. Signs and symptoms generally develop within 24-48 hours of drug ingestion. The pa- tient often ...

  2. Contrast induced nephropathy

    DEFF Research Database (Denmark)

    Stacul, Fulvio; van der Molen, Aart J; Reimer, Peter

    2011-01-01

    PURPOSE: The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 1999 guidelines on contrast medium-induced nephropathy (CIN). AREAS COVERED: Topics reviewed include the definition of CIN, the choice of contrast medium, the prophylactic me...

  3. Radiation-induced pneumothorax

    International Nuclear Information System (INIS)

    Epstein, D.M.; Littman, P.; Gefter, W.B.; Miller, W.T.; Raney, R.B. Jr.

    1983-01-01

    Pneumothorax is an uncommon complication of radiation therapy to the chest. The proposed pathogenesis is radiation-induced fibrosis promoting subpleural bleb formation that ruptures resulting in pneumothorax. We report on two young patients with primary sarcomas without pulmonary metastases who developed spontaneous pneumothorax after irradiation. Neither patient had antecedent radiographic evidence of pulmonary fibrosis

  4. Irradiation-Induced Nanostructures

    Energy Technology Data Exchange (ETDEWEB)

    Birtcher, R.C.; Ewing, R.C.; Matzke, Hj.; Meldrum, A.; Newcomer, P.P.; Wang, L.M.; Wang, S.X.; Weber, W.J.

    1999-08-09

    This paper summarizes the results of the studies of the irradiation-induced formation of nanostructures, where the injected interstitials from the source of irradiation are not major components of the nanophase. This phenomena has been observed by in situ transmission electron microscopy (TEM) in a number of intermetallic compounds and ceramics during high-energy electron or ion irradiations when the ions completely penetrate through the specimen. Beginning with single crystals, electron or ion irradiation in a certain temperature range may result in nanostructures composed of amorphous domains and nanocrystals with either the original composition and crystal structure or new nanophases formed by decomposition of the target material. The phenomenon has also been observed in natural materials which have suffered irradiation from the decay of constituent radioactive elements and in nuclear reactor fuels which have been irradiated by fission neutrons and other fission products. The mechanisms involved in the process of this nanophase formation are discussed in terms of the evolution of displacement cascades, radiation-induced defect accumulation, radiation-induced segregation and phase decomposition, as well as the competition between irradiation-induced amorphization and recrystallization.

  5. Lupus induced by medicaments

    International Nuclear Information System (INIS)

    Canas D, Carlos Alberto; Perafan B, Pablo Eduardo

    2001-01-01

    We describe a 55 years old female patient who consulted by fever syndrome, artralgias and the presence of high tittles positives antinuclear antibodies. She had arterial hypertension in treatment with captopril. We suspected the clinical diagnoses of drug-induced lupus; the withdraw of captopril was associated with the remission of the clinical and laboratory manifestations

  6. Glucocorticoid-induced hyperglycaemia

    NARCIS (Netherlands)

    Gerards, M.C.

    2018-01-01

    This thesis contains studies on current practice, clinical implications and treatment of excess glucocorticoid receptor (GCR) stimulation, with a focus on glucocorticoid-induced hyperglycaemia (GCIH). Chapter 1 is a general introduction to the glucocorticoid hormone. In chapter 2 , we have

  7. Understanding induced seismicity

    NARCIS (Netherlands)

    Elsworth, Derek; Spiers, Christopher J.|info:eu-repo/dai/nl/304829323; Niemeijer, Andre R.|info:eu-repo/dai/nl/370832132

    2016-01-01

    Fluid injection–induced seismicity has become increasingly widespread in oil- and gas-producing areas of the United States (1–3) and western Canada. It has shelved deep geothermal energy projects in Switzerland and the United States (4), and its effects are especially acute in Oklahoma, where

  8. Geomagnetism and Induced Voltage

    Science.gov (United States)

    Abdul-Razzaq, W.; Biller, R. D.

    2010-01-01

    Introductory physics laboratories have seen an influx of "conceptual integrated science" over time in their classrooms with elements of other sciences such as chemistry, biology, Earth science, and astronomy. We describe a laboratory to introduce this development, as it attracts attention to the voltage induced in the human brain as it…

  9. INDUCED ABORTION IN NIGERIA

    African Journals Online (AJOL)

    2014-06-01

    Jun 1, 2014 ... 95% of women would have had an induced abortion. (10), which ... who were fluent in both English and the local language were chosen ... the woman and society. The Muslims ... that “traditional methods are only effective at the early stages of ... modern and traditional family planning services. However ...

  10. Advertising-Induced Embarrassment

    NARCIS (Netherlands)

    Puntoni, S.; Hooge, de I.E.; Verbeke, W.J.M.I.

    2015-01-01

    Abstract Consumer embarrassment is a concern for many advertisers. Yet little is known about ad-induced embarrassment. The authors investigate when and why consumers experience embarrassment as a result of exposure to socially sensitive advertisements. The theory distinguishes between viewing

  11. Uterine contraction induced by Tanzanian plants used to induce abortion

    DEFF Research Database (Denmark)

    Nikolajsen, Tine; Nielsen, Frank; Rasch, Vibeke

    2011-01-01

    Women in Tanzania use plants to induce abortion. It is not known whether the plants have an effect.......Women in Tanzania use plants to induce abortion. It is not known whether the plants have an effect....

  12. Anti-idiotypic antibodies against UV-induced tumor-specific CTL clones. Preparation in syngeneic combination

    International Nuclear Information System (INIS)

    Kuribayashi, K.; Tanaka, C.; Matsubayashi, Y.; Masuda, T.; Udono, H.; Abe, M.; Nakayama, E.; Shiku, H.

    1988-01-01

    In this study, we first established several CTL clones of (BALB/c x C57BL/6)F1 origin that were specific for either syngeneic UV female 1 or UV male 1 fibrosarcoma cell lines. All the CTL clones had Thy-1+ Lyt-2+ L3T4- phenotypes and showed Kd restriction when lysing the corresponding target cells. Sera obtained from syngeneic animals immunized with three CTL clones, 10B-5 for UV female 1, and CTL9 and CTL10 for UV male 1, showed specific inhibition of target cell lysis with the corresponding CTL clones. The inhibitory activities were found in sera of the majority of immunized animals. Because the inhibitory activity resides in protein A-binding fraction, mAb were produced by hybridizing spleen cells of hyperimmune animals. N1-56 was thus obtained from a mouse immunized with 10B-5 CTL clone reactive with UV female 1. N1-56 was clonotype specific, reacting with 10B-5 but not with other CTL lines or leukemia cell lines. No N1-56+ cells were detectable in thymocytes, lymph node cells, or spleen cells of either naive or UV female 1-immune CB6F1 mice. Immunoprecipitation showed that N1-56 reacts with 90,000 Mr molecules on 10B-5 CTL clone under nonreducing conditions and 45,000 Mr molecules under reducing conditions, indicating its reactivities with idiotypic determinants of TCR on the CTL clone. N1-56 inhibited lytic activity of 10B-5, but neither N1-56 nor alpha-10B-5 hyperimmune serum inhibited that of alpha-UV female 1 mixed lymphocyte tumor cell culture cells. N1-56 induced proliferation of 10B-5 without addition of Ag

  13. [Hydroxyurea-induced pneumonia].

    Science.gov (United States)

    Girard, A; Ricordel, C; Poullot, E; Claeyssen, V; Decaux, O; Desrues, B; Delaval, P; Jouneau, S

    2014-05-01

    Hydroxyurea is an antimetabolite drug used in the treatment of myeloproliferative disorders. Common adverse effects include haematological, gastrointestinal cutaneous manifestations, and fever. Hydroxyurea-induced pneumonitis is unusual. A female patient was treated with hydroxyurea for polycythemia vera. She was admitted 20 days after commencing treatment with a high fever, productive cough, clear sputum and nausea. A chest CT-scan showed diffuse ground-glass opacities. Microbiological investigations were negative. The symptoms disappeared a few days after discontinuation of the drug and rechallenge led to a relapse of symptoms. Our case and 15 earlier cases of hydroxyurea-induced pneumonitis are reviewed. Two patterns of this disease may exist: an acute febrile form occurring within 1 month of introduction of hydroxyurea and a subacute form without fever. Even if uncommon, one should be aware of this complication of hydroxyurea. Copyright © 2013. Published by Elsevier Masson SAS.

  14. Hydroxychloroquine-induced erythroderma.

    Science.gov (United States)

    Pai, Sunil B; Sudershan, Bhuvaneshwari; Kuruvilla, Maria; Kamath, Ashwin; Suresh, Pooja K

    2017-01-01

    Erythroderma is characterized by diffuse erythema and scaling of the skin involving more than 90% of the total body skin surface area. Drug-induced erythroderma has rarely been reported with hydroxychloroquine. We report a case of a 50-year-old female patient, with systemic lupus erythematosus, who developed itchy lesions all over the body 1 month after starting treatment with hydroxychloroquine. Drug-induced erythroderma was suspected. Hydroxychloroquine was withdrawn and the patient was treated with emollients, mid-potency corticosteroids, and oral antihistamines. A biopsy was done which confirmed the diagnosis of erythroderma. She recovered with treatment and was discharged. A careful history and clinical examination to search for potential causative factors will help prevent disabling sequelae in erythroderma.

  15. Mild induced hypothermia

    DEFF Research Database (Denmark)

    Johansen, Maria E; Jensen, Jens-Ulrik; Bestle, Morten H

    2014-01-01

    INTRODUCTION: Coagulopathy associates with poor outcome in sepsis. Mild induced hypothermia has been proposed as treatment in sepsis but it is not known whether this intervention worsens functional coagulopathy. MATERIALS AND METHODS: Interim analysis data from an ongoing randomized controlled...... trial; The Cooling And Surviving Septic shock (CASS) study. Patients suffering severe sepsis/septic shock are allocated to either mild induced hypothermia (cooling to 32-34°C for 24hours) or control (uncontrolled temperature). TRIAL REGISTRATION: NCT01455116. Thrombelastography (TEG) is performed three....... At enrollment, 3%, 38%, and 59% had a hypocoagulable, normocoagulable, and hypercoagulable TEG clot strength (MA), respectively. In the hypothermia group, functional coagulopathy improved during the hypothermia phase, measured by R and MA, in patients with hypercoagulation as well as in patients...

  16. Time Domain Induced Polarization

    DEFF Research Database (Denmark)

    Fiandaca, Gianluca; Auken, Esben; Christiansen, Anders Vest

    2012-01-01

    Time-domain-induced polarization has significantly broadened its field of reference during the last decade, from mineral exploration to environmental geophysics, e.g., for clay and peat identification and landfill characterization. Though, insufficient modeling tools have hitherto limited the use...... of time-domaininduced polarization for wider purposes. For these reasons, a new forward code and inversion algorithm have been developed using the full-time decay of the induced polarization response, together with an accurate description of the transmitter waveform and of the receiver transfer function......, to reconstruct the distribution of the Cole-Cole parameters of the earth. The accurate modeling of the transmitter waveform had a strong influence on the forward response, and we showed that the difference between a solution using a step response and a solution using the accurate modeling often is above 100...

  17. Topiramate Induced Excessive Sialorrhea

    Directory of Open Access Journals (Sweden)

    Ersel Dag

    2015-11-01

    Full Text Available It is well-known that drugs such as clozapine and lithium can cause sialorrhea. On the other hand, topiramate has not been reported to induce sialorrhea. We report a case of a patient aged 26 who was given antiepileptic and antipsychotic drugs due to severe mental retardation and intractable epilepsy and developed excessive sialorrhea complaint after the addition of topiramate for the control of seizures. His complaints continued for 1,5 years and ended after giving up topiramate. We presented this case since it was a rare sialorrhea case induced by topiramate. Clinicians should be aware of the possibility of sialorrhea development which causes serious hygiene and social problems when they want to give topiramate to the patients using multiple drugs.

  18. Noise-Induced Hearing Loss

    Science.gov (United States)

    ... Home » Health Info » Hearing, Ear Infections, and Deafness Noise-Induced Hearing Loss On this page: What is ... I find additional information about NIHL? What is noise-induced hearing loss? Every day, we experience sound ...

  19. Induced quantum torsion

    International Nuclear Information System (INIS)

    Denardo, G.; Spallucci, E.

    1985-07-01

    We study pregeometry in the framework of a Poincare gauge field theory. The Riemann-Cartan space-time is shown to be an ''effective geometry'' for this model in the low energy limit. By using Heat Kernel techniques we find the induced action for curvature and torsion. We obtain in this way the usual Einstein-Hilbert action plus an axial Maxwell term describing the propagation of a massless, axial vector torsion field. (author)

  20. Cisplatin Induced Nephrotoxicity

    Directory of Open Access Journals (Sweden)

    Seyed Seifollah Beladi Mousavi

    2014-02-01

    The standard approach to prevent cisplatin-induced nephrotoxicity is the administration of lower doses of cisplatin in combination with the administration of full intravenous isotonic saline before and after cisplatin administration. Although a number of pharmacologic agents including sodium thiosulfate, N-acetylcysteine, theophylline and glycine have been evaluated for prevention of nephrotoxicity, none have proved to have an established role, thus, additional clinical studies will be required to confirm their probable effects.

  1. Amitriptyline induced cervical dystonia

    Directory of Open Access Journals (Sweden)

    Shivanand B Hiremath

    2016-01-01

    Full Text Available Tricyclic antidepressants (TCAs, such as amitriptyline, have many side effects. But extrapyramidal tract symptom is an uncommon side effect of these drugs. Here, we report a case of a 28-year-old male who is suffering from amitriptyline induced cervical dystonia. Though rare, this side effect is an uncomfortable condition and may influence drug compliance. So clinicians should be aware of this side effect while treating a patient with amitriptyline.

  2. Polycation induced actin bundles

    OpenAIRE

    Muhlrad, Andras; Grintsevich, Elena E.; Reisler, Emil

    2011-01-01

    Three polycations, polylysine, the polyamine spermine and the polycationic protein lysozyme were used to study the formation, structure, ionic strength sensitivity and dissociation of polycation-induced actin bundles. Bundles form fast, simultaneously with the polymerization of MgATP-G-actins, upon addition of polycations to solutions of actins at low ionic strength conditions. This indicates that nuclei and/or nascent filaments bundle due to attractive, electrostatic effect of polycations an...

  3. Induced current heating probe

    International Nuclear Information System (INIS)

    Thatcher, G.; Ferguson, B.G.; Winstanley, J.P.

    1984-01-01

    An induced current heating probe is of thimble form and has an outer conducting sheath and a water flooded flux-generating unit formed from a stack of ferrite rings coaxially disposed in the sheath. The energising coil is made of solid wire which connects at one end with a coaxial water current tube and at the other end with the sheath. The stack of ferrite rings may include non-magnetic insulating rings which help to shape the flux. (author)

  4. Induced QCD I: theory

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, Bastian B. [Institute for Theoretical Physics, Goethe-University of Frankfurt,60438 Frankfurt (Germany); Institute for Theoretical Physics, University of Regensburg,93040 Regensburg (Germany); Lohmayer, Robert; Wettig, Tilo [Institute for Theoretical Physics, University of Regensburg,93040 Regensburg (Germany)

    2016-11-14

    We explore an alternative discretization of continuum SU(N{sub c}) Yang-Mills theory on a Euclidean spacetime lattice, originally introduced by Budzcies and Zirnbauer. In this discretization the self-interactions of the gauge field are induced by a path integral over N{sub b} auxiliary boson fields, which are coupled linearly to the gauge field. The main progress compared to earlier approaches is that N{sub b} can be as small as N{sub c}. In the present paper we (i) extend the proof that the continuum limit of the new discretization reproduces Yang-Mills theory in two dimensions from gauge group U(N{sub c}) to SU(N{sub c}), (ii) derive refined bounds on N{sub b} for non-integer values, and (iii) perform a perturbative calculation to match the bare parameter of the induced gauge theory to the standard lattice coupling. In follow-up papers we will present numerical evidence in support of the conjecture that the induced gauge theory reproduces Yang-Mills theory also in three and four dimensions, and explore the possibility to integrate out the gauge fields to arrive at a dual formulation of lattice QCD.

  5. Laser induced energy transfer

    International Nuclear Information System (INIS)

    Falcone, R.W.

    1979-01-01

    Two related methods of rapidly transferring stored energy from one excited chemical species to another are described. The first of these, called a laser induced collision, involves a reaction in which the energy balance is met by photons from an intense laser beam. A collision cross section of ca 10 - 17 cm 2 was induced in an experiment which demonstrated the predicted dependence of the cross section on wavelength and power density of the applied laser. A second type of laser induced energy transfer involves the inelastic scattering of laser radiation from energetically excited atoms, and subsequent absorption of the scattered light by a second species. The technique of producing the light, ''anti-Stokes Raman'' scattering of visible and infrared wavelength laser photons, is shown to be an efficient source of narrow bandwidth, high brightness, tunable radiation at vacuum ultraviolet wavelengths by using it to excite a rare gas transition at 583.7 A. In addition, this light source was used to make the first measurement of the isotopic shift of the helium metastable level at 601 A. Applications in laser controlled chemistry and spectroscopy, and proposals for new types of lasers using these two energy transfer methods are discussed

  6. Radiation-induced myelopathy

    Energy Technology Data Exchange (ETDEWEB)

    Gaenshirt, H [Heidelberg Univ. (F.R. Germany). Neurologische Klinik

    1975-10-01

    12 cases of radiation-induced myelopathy after /sup 60/Co teletherapy are reported on. Among these were 10 thoracal lesions, one cerviothoracal lesion, and one lesion of the medulla oblongata. In 9 cases, Hodgkin's disease had been the primary disease, tow patients had been irradiated because of suspected vertebral metastases of cancer of the breast, and one patient had suffered from a glomus tumour of the petrous bone. The spinal doses had exceeded the tolerance doses recommended in the relevant literature. There was no close correlation between the radiation dose and the course of the disease. The latency periods between the end of the radiotherapy and the onset of the neurological symptons varied from 6 to 16 mouths and were very constant in 7 cases with 6 to 9 months. The segmental height of the lesion corresponded to the level of irradiation. The presenting symptons of radiation-induced myelopathy are buruing dysaesthesias and Brown-Sequard's paralysis which may develop into transverse lesion of the cord with paraplegia still accompanied by dissociated perception disorders. The disease developed intermittently. Disturbances of the bladder function are frequent. The fluid is normal in most cases. Myelographic examinations were made in 8 cases. 3 cases developed into stationary cases exhibiting. Brown-Sequard syndrome, while 9 patients developed transverse lesion of the cord with paraplegia. 3 patients have died; antopsy findings are given for two of these. In the pathogenesis of radiation-induced myelopathy, the vascular factor is assumed to be of decisive importance.

  7. Baby universes with induced gravity

    International Nuclear Information System (INIS)

    Gao Yihong; Gao Hongbo

    1989-01-01

    In this paper some quantum effects of baby universes with induced gravity are discussed. It is proved that the interactions between the baby-parent universes are non-local, and argue that the induced low-energy cosmological constant is zero. This argument does not depend on the detail of the induced potential

  8. Efek ekstrak daun singkong (Manihot utilissima terhadap ekspresi COX-2 pada monosit yang dipapar LPS E.coli (The effect of Manihot utilissima extracts on COX-2 expression of monocytes induced by LPS E. coli

    Directory of Open Access Journals (Sweden)

    Zahara Meilawaty

    2013-12-01

    Full Text Available Background: Periodontal disease is a common and widespread disease in the community. Gram negative bacteria have a role inperiodontitis. These bacteria secrete a variety of products such as endotoxin lipopolysaccharide (LPS, which causes the occurrenceof inflammation or infection. The body defense responses are neutrophils and mononuclear cells (monocytes and macrophages. Inresponse to defense mechanism, the body will be expressed enzyme cyclooxygenase (COX which functions convert arachidonic acidto prostaglandins. Cassava leaf cells known to play a role in reducing inflammation, but the mechanism for inhibiting COX-2, is notknown. Purpose: The study was aimed to determine the effect of cassava leaf extract (Manihot utilissima on expression of enzyme COX-2 in monocytes which were exposed by LPS E. coli. Methods: This study was in vitro experimental studies with the design of posttestonly control group design. The sample was the cassava leaves extract (Manihot utilissima at concentration of 12.5 % and 25 %. Theexpression of COX-2 was determined by immunocytochemistry method. Isolated monocytes were incubated in cassava leaf extract, andthen exposed to LPS, after washing imunostaning procedure was performed using a monoclonal antibody (MAb anti-human COX-2.The research data was the number of monocytes that express COX-2. Results: Expression of COX-2 in the group cassava leaf extractwas higher than the group that induced by LPS E. coli only. Conclusion: Cassava leaf extract did not inhibit the expression of COX-2in monocytes which were exposed by LPS E. coli.Latar belakang: Penyakit periodontal merupakan penyakit umum dan tersebar luas di masyarakat. Bakteri yang banyak berperanpada periodontitis adalah Gram negatif. Bakteri ini mengeluarkan berbagai produk antara lain endotoksin lipopolisakarida (LPS yangmenyebabkan inflamasi atau infeksi. Respon pertahanan tubuh pertama adalah netrofil dan sel mononuklear (monosit dan makrofag.Pada respon

  9. Polycation induced actin bundles.

    Science.gov (United States)

    Muhlrad, Andras; Grintsevich, Elena E; Reisler, Emil

    2011-04-01

    Three polycations, polylysine, the polyamine spermine and the polycationic protein lysozyme were used to study the formation, structure, ionic strength sensitivity and dissociation of polycation-induced actin bundles. Bundles form fast, simultaneously with the polymerization of MgATP-G-actins, upon the addition of polycations to solutions of actins at low ionic strength conditions. This indicates that nuclei and/or nascent filaments bundle due to attractive, electrostatic effect of polycations and the neutralization of repulsive interactions of negative charges on actin. The attractive forces between the filaments are strong, as shown by the low (in nanomolar range) critical concentration of their bundling at low ionic strength. These bundles are sensitive to ionic strength and disassemble partially in 100 mM NaCl, but both the dissociation and ionic strength sensitivity can be countered by higher polycation concentrations. Cys374 residues of actin monomers residing on neighboring filaments in the bundles can be cross-linked by the short span (5.4Å) MTS-1 (1,1-methanedyl bismethanethiosulfonate) cross-linker, which indicates a tight packing of filaments in the bundles. The interfilament cross-links, which connect monomers located on oppositely oriented filaments, prevent disassembly of bundles at high ionic strength. Cofilin and the polysaccharide polyanion heparin disassemble lysozyme induced actin bundles more effectively than the polylysine-induced bundles. The actin-lysozyme bundles are pathologically significant as both proteins are found in the pulmonary airways of cystic fibrosis patients. Their bundles contribute to the formation of viscous mucus, which is the main cause of breathing difficulties and eventual death in this disorder. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Induced mutations in citrus

    International Nuclear Information System (INIS)

    Spiegel-Roy, P.; Vardi, Aliza

    1990-01-01

    Full text: Parthenocarpic tendency is an important prerequisite for successful induction of seedlessness in breeding and especially in mutation breeding. A gene for asynapsis and accompanying seedless fruit has been found by us in inbred progeny of cv. 'Wilking'. Using budwood irradiation by gamma rays, seedless mutants of 'Eureka' and 'Villafranca' lemon (original clone of the latter has 25 seeds) and 'Minneola' tangelo have been obtained. Ovule sterility of the three mutants is nearly complete, with some pollen fertility still remaining. A semi-compact mutant of Shamouti orange has been obtained by irradiation. A programme for inducing seedlessness in easy peeling citrus varieties and selections has been initiated. (author)

  11. Shear-induced chaos

    International Nuclear Information System (INIS)

    Lin, Kevin K; Young, Lai-Sang

    2008-01-01

    Guided by a geometric understanding developed in earlier works of Wang and Young, we carry out numerical studies of shear-induced chaos in several parallel but different situations. The settings considered include periodic kicking of limit cycles, random kicks at Poisson times and continuous-time driving by white noise. The forcing of a quasi-periodic model describing two coupled oscillators is also investigated. In all cases, positive Lyapunov exponents are found in suitable parameter ranges when the forcing is suitably directed

  12. Shear-induced chaos

    Science.gov (United States)

    Lin, Kevin K.; Young, Lai-Sang

    2008-05-01

    Guided by a geometric understanding developed in earlier works of Wang and Young, we carry out numerical studies of shear-induced chaos in several parallel but different situations. The settings considered include periodic kicking of limit cycles, random kicks at Poisson times and continuous-time driving by white noise. The forcing of a quasi-periodic model describing two coupled oscillators is also investigated. In all cases, positive Lyapunov exponents are found in suitable parameter ranges when the forcing is suitably directed.

  13. Xerostomia induced by radiotherapy

    Directory of Open Access Journals (Sweden)

    Alimi D

    2015-08-01

    Full Text Available David Alimi Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USAWe read with great interest the excellent review on xerostomia induced by radiotherapy, by Pinna et al.1 The authors should be congratulated for a very detailed review of the physiopathology, clinical symptoms, and therapeutic management of an extremely difficult condition. Although we agree that the use of anticholinergic medication represents treatment, it requires the patient to have residual salivary gland function. Unfortunately, it is well established that in most cases radiotherapy destroys most of the salivary gland and associated salivary secretions.     

  14. Cannabis induced asystole.

    Science.gov (United States)

    Brancheau, Daniel; Blanco, Jessica; Gholkar, Gunjan; Patel, Brijesh; Machado, Christian

    2016-01-01

    Cannabis or marijuana is the most used recreational, and until recently illegal, drug in the United States. Although cannabis has medicinal use, its consumption has been linked to motor vehicle accidents in dose dependent fashion. Marijuana and other cannabinoids produce a multitude of effects on the human body that may result in these motor vehicle accidents. Some of the effects that marijuana has been known to cause include altered sensorium, diminished reflexes, and increased vagal tone. We present a case of cannabis induced asystole from hypervagotonia. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Pacing-induced Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Alex Koo

    2017-10-01

    Full Text Available We present a case of pacing-induced cardiomyopathy. The patient presented with clinical symptoms of dyspnea, leg swelling, and orthopnea several months after a dual-chambered pacemaker was placed for third-degree heart block. The echocardiogram demonstrated a depressed ejection fraction. Coronary angiography was performed, which showed widely patent vessels. Single- and dual-chambered pacemakers create ventricular dyssynchrony, which in turn can cause structural, molecular changes leading to cardiomyopathy. With early intervention of biventricular pacemaker replacement, these changes can be reversible; thus, a timely diagnosis and awareness is warranted.

  16. Induced skeletal mutations

    International Nuclear Information System (INIS)

    Selby, P.B.

    1979-01-01

    This paper describes a large-scale experiment that, by means of breeding tests, confirmed that many dominant skeletal mutations are induced by large-dose radiation exposure. The author also discusses: (1) the major advantages and disadvantages of the skeletal method in improving estimates of genetic hazard to man; (2) future uses of the skeletal method; (3) direct estimation of risk beyond the first generation using the skeletal method; and (4) the possibility of using the skeletal method as a quick and easy screen for chemical mutagens

  17. Trauma Induced Coagulopathy

    DEFF Research Database (Denmark)

    Genét, Gustav Folmer; Johansson, Per; Meyer, Martin Abild Stengaard

    2013-01-01

    It remains debated whether traumatic brain injury (TBI) induces a different coagulopathy compared to non-TBI. This study investigated traditional coagulation tests, biomarkers of coagulopathy and endothelial damage in trauma patients with and without TBI. Blood from 80 adult trauma patients were...... sampled (median of 68 min (IQR 48-88) post-injury) upon admission to our trauma centre. Plasma/serum were retrospectively analysed for biomarkers reflecting sympathoadrenal activation (adrenaline, noradrenaline), coagulation activation/inhibition and fibrinolysis (protein C, activated protein C, tissue...

  18. Trastuzumab-induced cardiomyopathy.

    Science.gov (United States)

    Guglin, Maya; Cutro, Raymond; Mishkin, Joseph D

    2008-06-01

    Trastuzumab is a recombinant humanized monoclonal antibody used for the treatment of advanced breast cancer. It improves survival and increases response to chemotherapy. The major side effect of trastuzumab is cardiotoxicity manifesting as a reduction in left ventricular systolic function, either asymptomatic or with signs and symptoms of heart failure. Although reversible in most cases, cardiotoxicity frequently results in the discontinuation of trastuzumab. The objective of this review is to summarize facts about trastuzumab-induced cardiotoxicity and to highlight the areas of future investigations. We searched PubMed for trials involving trastuzumab used as an adjuvant therapy for breast cancer, including the metastatic breast cancer setting, and focused on cardiotoxicity.

  19. Docetaxel-induced neuropathy

    DEFF Research Database (Denmark)

    Eckhoff, Lise; Feddersen, Søren; Knoop, Ann

    2015-01-01

    Background. Docetaxel is a highly effective treatment of a wide range of malignancies but is often associated with peripheral neuropathy. The genetic variability of genes involved in the transportation or metabolism of docetaxel may be responsible for the variation in docetaxel-induced peripheral...... neuropathy (DIPN). The main purpose of this study was to investigate the impact of genetic variants in GSTP1 and ABCB1 on DIPN. Material and methods. DNA was extracted from whole blood from 150 patients with early-stage breast cancer who had received adjuvant docetaxel from February 2011 to May 2012. Two...

  20. Chemotherapy-induced polyneuropathy

    DEFF Research Database (Denmark)

    Zedan, Ahmed; Vilholm, Ole Jakob

    2014-01-01

    Chemotherapy-induced polyneuropathy (CIPN) is a common, but underestimated, clinical challenge. Incidence varies depending on many factors that are equally as important as the type of chemotherapeutic agent itself. Moreover, the assessment of CIPN is still uncertain, as several of the most...... frequently used scales do not rely on a formal neurological evaluation and depend on patients' reports and examiners' interpretations. Therefore, the aim of this MiniReview was to introduce the most common chemotherapies that cause neuropathy, and in addition to this, highlight the most significant...

  1. Contrast induced nephropathy

    DEFF Research Database (Denmark)

    Stacul, Fulvio; van der Molen, Aart J; Reimer, Peter

    2011-01-01

    PURPOSE: The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 1999 guidelines on contrast medium-induced nephropathy (CIN). AREAS COVERED: Topics reviewed include the definition of CIN, the choice of contrast medium, the prophylactic me....../min/1.73 m (2) is CIN risk threshold for intravenous contrast medium. • Hydration with either saline or sodium bicarbonate reduces CIN incidence. • Patients with eGFR = 60 ml/min/1.73 m (2) receiving contrast medium can continue metformin normally....

  2. Ion induced Auger spectroscopy

    International Nuclear Information System (INIS)

    Thomas, E.W.; Legg, K.O.; Metz, W.A.

    1980-01-01

    Auger electron spectra are induced by impact of heavy ions (e.g. Ar + ) on surfaces; it has been suggested that analysis of such spectra would be a useful technique for surface analysis. We have examined the Auger spectra for various projectile-target combinations and present as representative data the spectra for 100 keV Ar + impact on Al, Cr, Mn, Fe and Co. For a projectile incident on a species of higher nuclear charge the spectrum is dominated by Auger lines from the projectile, broadened considerably by the Doppler effect due to the projectile's motion. The spectra are not characteristic of the target and therefore offer no opportunity for surface analysis. For a projectile incident on a target of lower nuclear charge the spectrum is that of the target species but the spectrum is consistent with the source being sputtered excited atoms; the Auger electrons do not come from the surface. We conclude that the ion induced Auger spectra are in general not a convenient method for surface analysis. (orig.)

  3. Induced Seismicity Monitoring System

    Science.gov (United States)

    Taylor, S. R.; Jarpe, S.; Harben, P.

    2014-12-01

    There are many seismological aspects associated with monitoring of permanent storage of carbon dioxide (CO2) in geologic formations. Many of these include monitoring underground gas migration through detailed tomographic studies of rock properties, integrity of the cap rock and micro seismicity with time. These types of studies require expensive deployments of surface and borehole sensors in the vicinity of the CO2 injection wells. Another problem that may exist in CO2 sequestration fields is the potential for damaging induced seismicity associated with fluid injection into the geologic reservoir. Seismic hazard monitoring in CO2 sequestration fields requires a seismic network over a spatially larger region possibly having stations in remote settings. Expensive observatory-grade seismic systems are not necessary for seismic hazard deployments or small-scale tomographic studies. Hazard monitoring requires accurate location of induced seismicity to magnitude levels only slightly less than that which can be felt at the surface (e.g. magnitude 1), and the frequencies of interest for tomographic analysis are ~1 Hz and greater. We have developed a seismo/acoustic smart sensor system that can achieve the goals necessary for induced seismicity monitoring in CO2 sequestration fields. The unit is inexpensive, lightweight, easy to deploy, can operate remotely under harsh conditions and features 9 channels of recording (currently 3C 4.5 Hz geophone, MEMS accelerometer and microphone). An on-board processor allows for satellite transmission of parameter data to a processing center. Continuous or event-detected data is kept on two removable flash SD cards of up to 64+ Gbytes each. If available, data can be transmitted via cell phone modem or picked up via site visits. Low-power consumption allows for autonomous operation using only a 10 watt solar panel and a gel-cell battery. The system has been successfully tested for long-term (> 6 months) remote operations over a wide range

  4. Traffic forecasts ignoring induced demand

    DEFF Research Database (Denmark)

    Næss, Petter; Nicolaisen, Morten Skou; Strand, Arvid

    2012-01-01

    the model calculations included only a part of the induced traffic, the difference in cost-benefit results compared to the model excluding all induced traffic was substantial. The results show lower travel time savings, more adverse environmental impacts and a considerably lower benefitcost ratio when...... induced traffic is partly accounted for than when it is ignored. By exaggerating the economic benefits of road capacity increase and underestimating its negative effects, omission of induced traffic can result in over-allocation of public money on road construction and correspondingly less focus on other...... performance of a proposed road project in Copenhagen with and without short-term induced traffic included in the transport model. The available transport model was not able to include long-term induced traffic resulting from changes in land use and in the level of service of public transport. Even though...

  5. Paliperidone palmitate-induced sialorrhoea

    Directory of Open Access Journals (Sweden)

    Cengiz Cengisiz

    2016-03-01

    Full Text Available Extrapyramidal, metabolic, and cardiac side effects were reported for atypical antipsychotics; although a few resources show paliperidone-induced sialorrhea, there are no resources that show paliperidone palmitate-induced sialorrhea. In this paper, we present the paliperidone palmitate-induced sialorrhea side effects of a patient who applied on our clinic [Cukurova Med J 2016; 41(0.100: 8-13

  6. Radiation-induced cancer

    International Nuclear Information System (INIS)

    Dutrillaux, B.; CEA Fontenay-aux-Roses, 92

    1998-01-01

    The induction of malignant diseases is one of the most concerning late effects of ionising radiation. A large amount of information has been collected form atomic bomb survivors, patients after therapeutic irradiation, occupational follow-up and accidentally exposed populations. Major uncertainties persist in the (very) low range i.e, population and workers radioprotection. A review of the biological mechanisms leading to cancer strongly suggests that the vast majority of radiation-induced malignancies arise as a consequence of recessive mutations can be unveiled by ageing, this process being possibly furthered by constitutional or acquired genomic instability. The individual risk is likely to be very low, probably because of the usual dose level. However, the magnitude of medical exposure and the reliance of our societies on nuclear industry are so high that irreproachable decision-making processes and standards for practice are inescapable. (author)

  7. Radiation-induced nondisjunction

    International Nuclear Information System (INIS)

    Uchida, I.A.

    1979-01-01

    The methodology and results of epidemiological studies of the effects of preconception diagnostic x-rays of the abdomen on chromosome segregation in humans are described. The vast majority of studies show the same positive, though not significant, trend to increased nondisjunction among the offspring of irradiated women. The results of the various studies, however, cannot be pooled because of differing methodologies used. Abnormal chromosome segregation during mitotic division has been inducted experimentally by the in vitro exposure of human lymphocytes to a low dose of 50 R gamma irradiation. First meiotic nondisjunction has been successfully induced by whole body exposure of female mice to a low dose of radiation. The question of time-related repair of the mechanism involved in chromosome segregation is raised

  8. Radiation induced oral mucositis

    Directory of Open Access Journals (Sweden)

    P S Satheesh Kumar

    2009-01-01

    Full Text Available Patients receiving radiotherapy or chemotherapy will receive some degree of oral mucositis The incidence of oral mucositis was especially high in patients: (i With primary tumors in the oral cavity, oropharynx, or nasopharynx; (ii who also received concomitant chemotherapy; (iii who received a total dose over 5,000 cGy; and (iv who were treated with altered fractionation radiation schedules. Radiation-induced oral mucositis affects the quality of life of the patients and the family concerned. The present day management of oral mucositis is mostly palliative and or supportive care. The newer guidelines are suggesting Palifermin, which is the first active mucositis drug as well as Amifostine, for radiation protection and cryotherapy. The current management should focus more on palliative measures, such as pain management, nutritional support, and maintenance, of good oral hygiene

  9. Laser induced nuclear reactions

    International Nuclear Information System (INIS)

    Ledingham, Ken; McCanny, Tom; Graham, Paul; Fang Xiao; Singhal, Ravi; Magill, Joe; Creswell, Alan; Sanderson, David; Allott, Ric; Neely, David; Norreys, Peter; Santala, Marko; Zepf, Matthew; Watts, Ian; Clark, Eugene; Krushelnick, Karl; Tatarakis, Michael; Dangor, Bucker; Machecek, Antonin; Wark, Justin

    1998-01-01

    Dramatic improvements in laser technology since 1984 have revolutionised high power laser technology. Application of chirped-pulse amplification techniques has resulted in laser intensities in excess of 10 19 W/cm 2 . In the mid to late eighties, C. K. Rhodes and K. Boyer discussed the possibility of shining laser light of this intensity onto solid surfaces and to cause nuclear transitions. In particular, irradiation of a uranium target could induce electro- and photofission in the focal region of the laser. In this paper it is shown that μCi of 62 Cu can be generated via the (γ,n) reaction by a laser with an intensity of about 10 19 Wcm -2

  10. Radiation induced pesticidal microbes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ki Yup; Lee, Y. K.; Kim, J. S.; Kim, J. K.; Lee, S. J.; Lim, D. S

    2001-01-01

    To isolate pesticidal microbes against plant pathogenic fungi, 4 strains of bacteria(K1. K3, K4, YS1) were isolated from mushroom compost and hot spring. K4, K1, K3, YS1 strain showed wide antifungal spectrum and high antifungal activities against 12 kinds of fungi. Specific proteins and the specific transcribed genes were found from the YS1 and its radiation-induced mutants. And knock-out mutants of antifungal activity were derived by transposon mutagenesis. From these knock-out mutants, the antifungal activity related genes and its modification by gamma-ray radiation are going to be studied. These results suggested that radiation could be an useful tool for the induction of functional mutants.

  11. Radiation induced microbial pesticide

    International Nuclear Information System (INIS)

    Kim, Ki Yup; Lee, Young Keun; Kim, Jae Sung; Kim, Jin Kyu; Lee, Sang Jae

    2000-01-01

    To control plant pathogenic fungi, 4 strains of bacteria (K1, K3, K4, YS1) were isolated from mushroom compost and hot spring. K4, K1, K3, YS1 strain showed wide antifungal spectrum and high antifungal activities against 13 kinds of fungi. Mutants of K1 and YS1 strains were induced by gamma-ray radiation and showed promising antifungal activities. These wild type and mutants showed resistant against more than 27 kinds of commercial pesticides among 30 kinds of commercial pesticides test particularly, YS1-1006 mutant strain showed resistant against hydrogen oxide. And mutants had increased antifungal activity against Botryoshaeria dothidea. These results suggested that radiation could be an useful method for the induction of functional mutants. (author)

  12. Aripiprazole-induced priapism

    Directory of Open Access Journals (Sweden)

    Satya K Trivedi

    2016-01-01

    Full Text Available Priapism is a urologic emergency representing a true disorder of penile erection that persists beyond or is unrelated to sexual interest or stimulation. A variety of psychotropic drugs are known to produce priapism, albeit rarely, through their antagonistic action on alpha-1 adrenergic receptors. We report such a case of priapism induced by a single oral dose of 10 mg aripiprazole, a drug with the least affinity to adrenergic receptors among all atypical antipsychotics. Polymorphism of alpha-2A adrenergic receptor gene in schizophrenia patients is known to be associated with sialorrhea while on clozapine treatment. Probably, similar polymorphism of alpha-1 adrenergic receptor gene could contribute to its altered sensitivity and resultant priapism. In future, pharmacogenomics-based approach may help in personalizing the treatment and effectively prevent the emergence of such side effects.

  13. [Cannabis-induced disorders].

    Science.gov (United States)

    Soyka, M; Preuss, U; Hoch, E

    2017-03-01

    Use and misuse of cannabis and marihuana are frequent. About 5% of the adult population are current users but only 1.2% are dependent. The medical use of cannabis is controversial but there is some evidence for improvement of chronic pain and spasticity. The somatic toxicity of cannabis is well proven but limited and psychiatric disorders induced by cannabis are of more relevance, e.g. cognitive disorders, amotivational syndrome, psychoses and delusional disorders as well as physical and psychological dependence. The withdrawal symptoms are usually mild and do not require pharmacological interventions. To date there is no established pharmacotherapy for relapse prevention. Psychosocial interventions include psychoeducation, behavioral therapy and motivational enhancement. The CANDIS protocol is the best established German intervention among abstinence-oriented therapies.

  14. Induced seismicity. Final report

    International Nuclear Information System (INIS)

    Segall, P.

    1997-01-01

    The objective of this project has been to develop a fundamental understanding of seismicity associated with energy production. Earthquakes are known to be associated with oil, gas, and geothermal energy production. The intent is to develop physical models that predict when seismicity is likely to occur, and to determine to what extent these earthquakes can be used to infer conditions within energy reservoirs. Early work focused on earthquakes induced by oil and gas extraction. Just completed research has addressed earthquakes within geothermal fields, such as The Geysers in northern California, as well as the interactions of dilatancy, friction, and shear heating, on the generation of earthquakes. The former has involved modeling thermo- and poro-elastic effects of geothermal production and water injection. Global Positioning System (GPS) receivers are used to measure deformation associated with geothermal activity, and these measurements along with seismic data are used to test and constrain thermo-mechanical models

  15. Macroscopic Optomechanically Induced Transparency

    Science.gov (United States)

    Pate, Jacob; Castelli, Alessandro; Martinez, Luis; Thompson, Johnathon; Chiao, Ray; Sharping, Jay

    Optomechanically induced transparency (OMIT) is an effect wherein the spectrum of a cavity resonance is modified through interference between coupled excitation pathways. In this work we investigate a macroscopic, 3D microwave, superconducting radio frequency (SRF) cavity incorporating a niobium-coated, silicon-nitride membrane as the flexible boundary. The boundary supports acoustic vibrational resonances, which lead to coupling with the microwave resonances of the SRF cavity. The theoretical development and physical understanding of OMIT for our macroscopic SRF cavity is the same as that for other recently-reported OMIT systems despite vastly different optomechanical coupling factors and device sizes. Our mechanical oscillator has a coupling factor of g0 = 2 π . 1 ×10-5 Hz and is roughly 38 mm in diameter. The Q = 5 ×107 for the SRF cavity allows probing of optomechanical effects in the resolved sideband regime.

  16. [Glucocorticoid induced osteoporosis].

    Science.gov (United States)

    Anić, Branimir; Mayer, Miroslav

    2014-01-01

    Secondary osteoporosis most often develops due to glucocorticoid therapy. Glucocorticoids affect all stages of the bone remodeling cycle, its formation and resorption. Osteoblasts are primarily affected, decreasing their activity and enhancing apoptosis. Patients treated with glucocorticoids have lower bone mineral density and increased fracture risk. Glucocorticoid-induced osteoporosis can be prevented by administering the minimal effective dose of glucocorticoids, calcium and vitamin D supplementation or, if possible, by hormone replace- ment therapy. Moreover, appropriate physical activity should be encouraged. Patients who are at higher risk for low-energy fractures (for example post-menopausal women) have to be actively treated, usually with antiresorptive drugs among which bisphosphonates are currently the first line therapy.

  17. Radiation induced genomic instability

    International Nuclear Information System (INIS)

    Morgan, W.

    2003-01-01

    This presentation will focus on delayed genetic effects occurring in the progeny of cells after exposure to ionizing radiation. We have developed a model system for investigating those genetic effects occurring multiple generations after radiation exposure. The presentation will describe some of the delayed effects observed after radiation exposures including delayed chromosomal rearrangements, and recombination events as determined by a plasmid based assay system. We will present new data on how changes in gene expression as measured by differential display and DNA microarray analysis provides a mechanism by which cells display a memory of irradiation, and introduce candidate genes that may play a role in initiating and perpetuation the unstable phenotype. These results will be discussed in terms of the recently described non-targeted Death Inducing Effect (DIE) where by secreted factors from clones of unstable cells can elicit effects in non irradiated cells and may serve to perpetuate the unstable phenotype in cells that themselves were not irradiated

  18. Radiation induced pesticidal microbes

    International Nuclear Information System (INIS)

    Kim, Ki Yup; Lee, Y. K.; Kim, J. S.; Kim, J. K.; Lee, S. J.; Lim, D. S.

    2001-01-01

    To isolate pesticidal microbes against plant pathogenic fungi, 4 strains of bacteria(K1. K3, K4, YS1) were isolated from mushroom compost and hot spring. K4, K1, K3, YS1 strain showed wide antifungal spectrum and high antifungal activities against 12 kinds of fungi. Specific proteins and the specific transcribed genes were found from the YS1 and its radiation-induced mutants. And knock-out mutants of antifungal activity were derived by transposon mutagenesis. From these knock-out mutants, the antifungal activity related genes and its modification by gamma-ray radiation are going to be studied. These results suggested that radiation could be an useful tool for the induction of functional mutants

  19. Alcohol-Induced Blackout

    Directory of Open Access Journals (Sweden)

    Dai Jin Kim

    2009-11-01

    Full Text Available For a long time, alcohol was thought to exert a general depressant effect on the central nervous system (CNS. However, currently the consensus is that specific regions of the brain are selectively vulnerable to the acute effects of alcohol. An alcohol-induced blackout is the classic example; the subject is temporarily unable to form new long-term memories while relatively maintaining other skills such as talking or even driving. A recent study showed that alcohol can cause retrograde memory impairment, that is, blackouts due to retrieval impairments as well as those due to deficits in encoding. Alcoholic blackouts may be complete (en bloc or partial (fragmentary depending on severity of memory impairment. In fragmentary blackouts, cueing often aids recall. Memory impairment during acute intoxication involves dysfunction of episodic memory, a type of memory encoded with spatial and social context. Recent studies have shown that there are multiple memory systems supported by discrete brain regions, and the acute effects of alcohol on learning and memory may result from alteration of the hippocampus and related structures on a cellular level. A rapid increase in blood alcohol concentration (BAC is most consistently associated with the likelihood of a blackout. However, not all subjects experience blackouts, implying that genetic factors play a role in determining CNS vulnerability to the effects of alcohol. This factor may predispose an individual to alcoholism, as altered memory function during intoxication may affect an individual‟s alcohol expectancy; one may perceive positive aspects of intoxication while unintentionally ignoring the negative aspects. Extensive research on memory and learning as well as findings related to the acute effects of alcohol on the brain may elucidate the mechanisms and impact associated with the alcohol- induced blackout.

  20. Radiation induced nano structures

    International Nuclear Information System (INIS)

    Ibragimova, E.M.; Kalanov, M.U.; Khakimov, Z.

    2006-01-01

    Full text: Nanometer-size silicon clusters have been attracting much attention due to their technological importance, in particular, as promising building blocks for nano electronic and nano photonic systems. Particularly, silicon wires are of great of interest since they have potential for use in one-dimensional quantum wire high-speed field effect transistors and light-emitting devices with extremely low power consumption. Carbon and metal nano structures are studied very intensely due to wide possible applications. Radiation material sciences have been dealing with sub-micron objects for a long time. Under interaction of high energy particles and ionizing radiation with solids by elastic and inelastic mechanisms, at first point defects are created, then they form clusters, column defects, disordered regions (amorphous colloids) and finally precipitates of another crystal phase in the matrix. Such irradiation induced evolution of structure defects and phase transformations was observed by X-diffraction techniques in dielectric crystals of quartz and corundum, which exist in and crystal modifications. If there is no polymorphism, like in alkali halide crystals, then due to radiolysis halogen atoms are evaporated from the surface that results in non-stoichiometry or accumulated in the pores formed by metal vacancies in the sub-surface layer. Nano-pores are created by intensive high energy particles irradiation at first chaotically and then they are ordered and in part filled by inert gas. It is well-known mechanism of radiation induced swelling and embrittlement of metals and alloys, which is undesirable for construction materials for nuclear reactors. Possible solution of this problem may come from nano-structured materials, where there is neither swelling nor embrittlement at gas absorption due to very low density of the structure, while strength keeps high. This review considers experimental observations of radiation induced nano-inclusions in insulating

  1. Development of a mouse-feline chimeric antibody against feline tumor necrosis factor-alpha

    Science.gov (United States)

    DOKI, Tomoyoshi; TAKANO, Tomomi; HOHDATSU, Tsutomu

    2016-01-01

    Feline infectious peritonitis (FIP) is a fatal inflammatory disease caused by FIP virus infection. Feline tumor necrosis factor (fTNF)-alpha is closely involved in the aggravation of FIP pathology. We previously described the preparation of neutralizing mouse anti-fTNF-alpha monoclonal antibody (mAb 2–4) and clarified its role in the clinical condition of cats with FIP using in vitro systems. However, administration of mouse mAb 2–4 to cat may lead to a production of feline anti-mouse antibodies. In the present study, we prepared a mouse-feline chimeric mAb (chimeric mAb 2–4) by fusing the variable region of mouse mAb 2–4 to the constant region of feline antibody. The chimeric mAb 2–4 was confirmed to have fTNF-alpha neutralization activity. Purified mouse mAb 2–4 and chimeric mAb 2–4 were repeatedly administered to cats, and the changes in the ability to induce feline anti-mouse antibody response were investigated. In the serum of cats treated with mouse mAb 2–4, feline anti-mouse antibody production was induced, and the fTNF-alpha neutralization effect of mouse mAb 2–4 was reduced. In contrast, in cats treated with chimeric mAb 2–4, the feline anti-mouse antibody response was decreased compared to that of mouse mAb 2–4-treated cats. PMID:27264736

  2. Effects of Thy-1+ cell depletion on the capacity of donor lymphoid cells to induce tolerance across an entire MHC disparity in sublethally irradiated adult hosts

    International Nuclear Information System (INIS)

    Pierce, G.E.; Watts, L.M.

    1989-01-01

    Thy-1+ cell depletion with anti-Thy-1.2 mAb and complement markedly reduced the capacity of C57BL/6J, H-2b bone marrow to establish mixed lymphoid chimerism and induce tolerance to C57BL/6J skin grafts across an entire MHC disparity in BALB/c, H-2d hosts conditioned with sublethal, fractionated 7.5 Gy total-body irradiation. In this model tolerance can be transferred to secondary irradiated BALB/c hosts only by cells of C57BL/6J donor, not host, genotype isolated from the spleens of tolerant hosts. Thy-1+ cell depletion abolished the capacity of C57BL/6J donor cells from tolerant BALB/c host spleens to transfer tolerance. The capacity of semiallogeneic BALB/c x C57BL/6J F1, H-2d/b donor BM and spleen cells to induce chimerism and tolerance to C57BL/6J skin grafts in BALB/c parental hosts was also reduced by Thy-1+ cell depletion. Thus the requirement for donor Thy-1+ cells cannot be explained simply on the basis of alloaggression. It is unlikely that the requisite Thy-1+ cells are nonspecific suppressor cells: Thy-1+ cell depletion had no effect on the slight but significant prolongation of third-party C3H/HeJ, H-2k skin grafts in irradiated BALB/c hosts injected with allogeneic C57BL/6J or semiallogeneic BALB/c x C57BL/6J F1 BM compared to irradiated controls injected with medium only. Furthermore, injections of semiallogeneic F1 spleen cells had no significant effect on the survival of the third-party grafts, although these cells were fully capable of inducing tolerance, and their capacity to induce tolerance was significantly reduced by Thy-1+ cell depletion. The requirement for a specific population of lymphoid cells, i.e. Thy-1+, remains unexplained but suggests that donor cells might play a role in the induction or maintenance of tolerance in this model other than merely providing a circulating source of donor antigens

  3. Prolactin induces adrenal hypertrophy

    Directory of Open Access Journals (Sweden)

    E.J. Silva

    2004-02-01

    Full Text Available Although adrenocorticotropic hormone is generally considered to play a major role in the regulation of adrenal glucocorticoid secretion, several reports have suggested that other pituitary hormones (e.g., prolactin also play a significant role in the regulation of adrenal function. The aim of the present study was to measure the adrenocortical cell area and to determine the effects of the transition from the prepubertal to the postpubertal period on the hyperprolactinemic state induced by domperidone (4.0 mg kg-1 day-1, sc. In hyperprolactinemic adult and young rats, the adrenals were heavier, as determined at necropsy, than in the respective controls: adults (30 days: 0.16 ± 0.008 and 0.11 ± 0.007; 46 days: 0.17 ± 0.006 and 0.12 ± 0.008, and 61 days: 0.17 ± 0.008 and 0.10 ± 0.004 mg for treated and control animals, respectively; P < 0.05, and young rats (30 days: 0.19 ± 0.003 and 0.16 ± 0.007, and 60 days: 0.16 ± 0.006 and 0.13 ± 0.009 mg; P < 0.05. We selected randomly a circular area in which we counted the nuclei of adrenocortical cells. The area of zona fasciculata cells was increased in hyperprolactinemic adult and young rats compared to controls: adults: (61 days: 524.90 ± 47.85 and 244.84 ± 9.03 µm² for treated and control animals, respectively; P < 0.05, and young rats: (15 days: 462.30 ± 16.24 and 414.28 ± 18.19; 60 days: 640.51 ± 12.91 and 480.24 ± 22.79 µm²; P < 0.05. Based on these data we conclude that the increase in adrenal weight observed in the hyperprolactinemic animals may be due to prolactin-induced adrenocortical cell hypertrophy.

  4. Congruence properties of induced representations

    DEFF Research Database (Denmark)

    Mayer, Dieter; Momeni, Arash; Venkov, Alexei

    In this paper we study representations of the projective modular group induced from the Hecke congruence group of level 4 with Selberg's character. We show that the well known congruence properties of Selberg's character are equivalent to the congruence properties of the induced representations...

  5. Laser-induced nuclear fusion

    International Nuclear Information System (INIS)

    Jablon, Claude

    1977-01-01

    Research programs on laser-induced thermonuclear fusion in the United States, in Europe and in USSR are reviewed. The principle of the fusion reactions induced is explained, together with the theoretical effects of the following phenomena: power and type of laser beams, shape and size of the solid target, shock waves, and laser-hydrodynamics coupling problems [fr

  6. Preclinical Studies of Induced Pluripotent Stem Cell-Derived Astrocyte Transplantation in ALS

    Science.gov (United States)

    2014-12-01

    antibodies used: Human nuclear antigen (HuNA) (Millipore #MAB1281, 1:100), Tuj1 ( Covance #MRB-435P, 1:500), Glial Fibrillary Acidic Protein (GFAP...Nicholas J. Maragakis, M.D. CONTRACTING ORGANIZATION : Johns Hopkins University School of Medicine REPORT DATE: December 2014 TYPE OF REPORT: Final...Hongjun Song, Ph.D. 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS

  7. Force induced DNA melting

    International Nuclear Information System (INIS)

    Santosh, Mogurampelly; Maiti, Prabal K

    2009-01-01

    When pulled along the axis, double-strand DNA undergoes a large conformational change and elongates by roughly twice its initial contour length at a pulling force of about 70 pN. The transition to this highly overstretched form of DNA is very cooperative. Applying a force perpendicular to the DNA axis (unzipping), double-strand DNA can also be separated into two single-stranded DNA, this being a fundamental process in DNA replication. We study the DNA overstretching and unzipping transition using fully atomistic molecular dynamics (MD) simulations and argue that the conformational changes of double-strand DNA associated with either of the above mentioned processes can be viewed as force induced DNA melting. As the force at one end of the DNA is increased the DNA starts melting abruptly/smoothly above a critical force depending on the pulling direction. The critical force f m , at which DNA melts completely decreases as the temperature of the system is increased. The melting force in the case of unzipping is smaller compared to the melting force when the DNA is pulled along the helical axis. In the case of melting through unzipping, the double-strand separation has jumps which correspond to the different energy minima arising due to sequence of different base pairs. The fraction of Watson-Crick base pair hydrogen bond breaking as a function of force does not show smooth and continuous behavior and consists of plateaus followed by sharp jumps.

  8. Chemotherapy-induced hypocalcemia.

    Science.gov (United States)

    Ajero, Pia Marie E; Belsky, Joseph L; Prawius, Herbert D; Rella, Vincent

    2010-01-01

    To present a unique case of transient, asymptomatic chemotherapy-induced hypocalcemia not attributable to hypomagnesemia or tumor lysis syndrome and review causes of hypocalcemia related to cancer with and without use of chemotherapy. We present a case detailing the clinical and laboratory findings of a patient who had severe hypocalcemia during chemotherapy and discuss causes of hypocalcemia with an extensive literature review of chemotherapeutic agents associated with this biochemical abnormality. In a 90-year-old man, hypocalcemia developed during 2 courses of chemotherapy for Hodgkin lymphoma, with partial recovery between courses and normal serum calcium 10 months after completion of treatment. Magnesium, vitamin D, and parathyroid hormone levels were low normal. There was no evidence of tumor lysis syndrome. Of the various agents administered, vinca alkaloids seemed the most likely cause. Serial testing suggested that the underlying mechanism may have been acquired, reversible hypoparathyroidism. No other similar case was found in the published literature. The severe hypocalcemia in our patient could not be attributed to hypomagnesemia or tumor lysis syndrome, and it was clearly associated with the timing of his chemotherapeutic regimen. Possibilities include direct parathyroid hormone suppression or alteration of calcium sensing by the chemotherapeutic drugs. Serum calcium surveillance before and during chemotherapeutic management of cancer patients may reveal more instances and provide insight into the exact mechanism of this lesser known yet striking complication.

  9. Collision-induced coherence

    International Nuclear Information System (INIS)

    Bloembergen, N.

    1985-01-01

    Collision-induced coherence is based on the elimination of phase correlations between coherent Feynman-type pathways which happen to interfere destructively in the absence of damping for certain nonlinear processes. One consequence is the appearance of the extra resonances in four-wave light mixing experiments, for which the intensity increases with increasing buffer gas pressure. These resonances may occur between a pair of initially unpopulated excited states, or between a pair of initially equally populated ground states. The pair of levels may be Zeeman substrates which became degenerate in zero magnetic field. The resulting collision-enhanced Hanle resonances can lead to very sharp variations in the four-wave light mixing signal as the external magnetic field passes through zero. The theoretical description in terms of a coherence grating between Zeeman substrates is equivalent to a description in terms of a spin polarization grating obtained by collision-enhanced transverse optical pumping. The axis of quantization in the former case is taken perpendicular to the direction of the light beams; in the latter case is taken parallel to this direction

  10. Linezolid induced retinopathy.

    Science.gov (United States)

    Park, Dae Hyun; Park, Tae Kwann; Ohn, Young-Hoon; Park, Jong Sook; Chang, Jee Ho

    2015-12-01

    While optic neuropathy is a well-known cause of visual disturbances in linezolid-treated patients, the possibility of linezolid-related retinopathy has not been investigated. Here, we report a case of retinopathy demonstrated by multifocal electroretinogram (mfERG) in a linezolid-treated patient. A 61-year-old man with extensively drug-resistant pulmonary tuberculosis treated with linezolid for 5 months presented with painless loss of vision in both eyes. The patient's best corrected visual acuity was 20/50 in the right eye and 20/100 in the left eye. Fundus examination revealed mild disc edema, and color vision was defective in both eyes. Humphrey visual field tests showed a superotemporal field defect in the right eye and central and pericentral field defect in the left eye. Optical coherence tomography (OCT) revealed only mild optic disc swelling. In mfERG, central amplitudes were depressed in both eyes. Four months after the cessation of linezolid, visual acuity was restored to 20/20 right eye and 20/25 left eye. The color vision and visual field had improved. The OCT and mfEFG findings improved as well. Although the clinical features were similar to linezolid-induced optic neuropathy, the mfERG findings suggest the possibility of a retinopathy through cone dysfunction.

  11. Food-induced anaphylaxis.

    Science.gov (United States)

    Järvinen, Kirsi M

    2011-06-01

    Food-induced anaphylaxis is the leading single cause of anaphylaxis treated in emergency departments and increasing in prevalence. Food allergy is an increasing problem in westernized countries around the world, with a cumulative prevalence of 3-6%. Peanut, tree nuts, and shellfish are the most commonly implicated foods in anaphylaxis, although milk is a common trigger in children. Asthmatics, adolescents, and those with a prior reaction are at increased risk for more severe reactions. Most first reactions and reactions in children most commonly occur at home, whereas most subsequent reactions and reactions in adults occur outside home. Studies on schools have identified inadequate management plans and symptom recognition whereas those on restaurants report lack of prior notification by allergic individuals and lack in staff education. Epinephrine, although underutilized is the drug of choice with multiple doses needed in up to one-fifth of reactions. Diagnosis is currently based on convincing history and allergy testing supported by elevated serum tryptase, if available. Long-term management includes strict avoidance and emergency action plan. With a growing population of food-allergic children and adults, markers to predict which individuals are at increased risk for anaphylaxis as well as new therapies are vigorously sought.

  12. Methaemoglobinemia Induced by MDMA?

    Directory of Open Access Journals (Sweden)

    L. L. W. Verhaert

    2011-01-01

    Full Text Available Case. A 45-year-old man with a blank medical history presented at the emergency room with dizziness and cyanosis. Physical examination showed cyanosis with a peripheral saturation (SpO2 of 85%, he did not respond to supplemental oxygen. Arterial blood gas analysis showed a striking chocolate brown colour. Based on these data, we determined the arterial methaemoglobin concentration. This was 32%. We gave 100% oxygen and observed the patient in a medium care unit. The next day, patient could be discharged in good condition. Further inquiry about exhibitions and extensive history revealed that the patient used MDMA (3,4- methylenedioxymethamphetamine, the active ingredient of ecstasy. Conclusion. Acquired methaemoglobinemia is a condition that occurs infrequently, but is potentially life threatening. Different nutrients, medications, and chemicals can induce methaemoglobinemia by oxidation of haemoglobin. The clinical presentation of a patient with methaemoglobinemia is due to the impossibility of O2 binding and transport, resulting in tissue hypoxia. Important is to think about methaemoglobin in a patient who presents with cyanosis, a peripheral saturation of 85% that fails to respond properly to the administration of O2. Because methaemoglobin can be reduced physiologically, it is usually sufficient to remove the causative agent, to give O2, and to observe the patient.

  13. Induced mutations in castor

    International Nuclear Information System (INIS)

    Ganesan, K.; Javad Hussain, H.S.; Vindhiyavarman, P.

    2001-01-01

    Castor (Ricinus communis L.) is an important oilseed crop in India. To create variability mutations were induced in two cultivars 'TMV5' (maturing in 130-140 days) and 'CO1' (perennial type). Gamma rays and diethyl sulphate and ethidium bromide were used for seed treatment. Ten doses, from 100 to 1000 Gy were employed. For chemical mutagenesis five concentrations of mutagenes from 10 to 50 mM were tried. No economic mutants could be isolated after treatment with the chemical mutagens. The following economic mutants were identified in the dose 300 Gy of gamma rays. Annual types from perennial CO 1 castor CO 1 is a perennial variety (8-10 years) with bold seeds (100 seed weight 90 g) and high oil content (57%). Twenty-one lines were isolated with annual types (160-180 days) with high yield potential as well as bold seeds and high oil content. These mutants, identified in M 3 generation were bred true in subsequent generations up to M 8 generation. Critical evaluation of the mutants in yield evaluation trials is in progress

  14. Laughter-induced syncope.

    Science.gov (United States)

    Kim, Alexander J; Frishman, William H

    2012-01-01

    Reported cases of syncope caused directly by laughter are rare. The common scenario described in a few reports involved episodes of fortuitous laughter, sometimes followed by a short prodrome of lightheadedness, facial flushing, and dizziness, followed by an episode of definite syncope. There were no seizure-like movements, automatisms, or bladder or bowel incontinence. After the syncopal episodes that were seconds in length, the patients regained consciousness, and at that point were fully oriented. These episodes could recur in a similar situation with such laughter. Many of these patients subsequently underwent full syncope workups, without elucidating a primary cardiac or neurologic cause. In this review of laughter-induced syncope, we describe a patient of ours who fit these descriptions. This phenomenon is likely a subtype of benign Valsalva-related syncope, with autonomic reflex arcs coming into play that ultimately result in global cerebral hypoperfusion. Besides the Valsalva produced by a great fit of laughter, laughter itself has its own neuroendocrine and vasculature effects that may play a role.

  15. Radiation-induced cerebrovasculopathy

    International Nuclear Information System (INIS)

    Ikeyama, Yukihide; Abiko, Seisho; Kurokawa, Yasushi; Okamura, Tomomi; Watanabe, Kohsaku; Inoue, Shinichi; Fujii, Yasuhiro.

    1993-01-01

    We reported a patient who suffered from cerebrovasculopathy after irradiation therapy for astrocytoma located at the left temporal lobe. An eleven year-old boy who presented with headache and vomiting received partial removal of a tumor. Histological diagnosis of the tumor was astrocytoma (grade II). His preoperative cerebral angiograms showed mass sign solely, without stenosis or occlusion of the cerebral vessel. Postoperatively, he was treated with irradiation therapy involving the whole brain with a total of 30 Gy, and gamma knife therapy. Six months after irradiation, he started suffering from frequent cerebral ischemic attacks, but there was no regrowth of the tumor visible on CT scans. Cerebral angiograms were made again, and revealed multifocal stenoses in the bilateral internal carotid arteries, middle cerebral arteries, and the anterior cerebral artery. His symptoms did not improve after conservative treatment with steroids, calcium antagonist, or low molecular weight dextran. Although he received a superficial temporal artery-middle cerebral artery (STA-MCA) anastomoses bilaterally, multiple cerebral infarctions appeared. Although irradiation therapy is acceptable in patients with brain tumor, cerebrovasculopathy after irradiation should be considered as one of the most important complications, and the risk incurred by irradiation therapy should lead to more careful consideration and caution when treating intracranial brain tumors, especially in children. From our experience, the usefulness of bypass surgery for radiation-induced cerebrovasculopathy is still controversial. (author)

  16. Temozolomide-Induced Myelodysplasia

    Directory of Open Access Journals (Sweden)

    Ethan A. Natelson

    2010-01-01

    Full Text Available A patient who had received temozolomide (TMZ as a single agent in treatment of malignant glioma developed therapy-induced myelodysplasia (T-MDS. TMZ is an orally active imidazotetrazine which methylates guanine residues in DNA, ultimately causing single and double-strand DNA breaks leading to apoptotic cell death. TMZ does not chemically cross-link DNA and is considered a nonclassical alkylating agent, similar in structure and activity to dacarbazine. Observations on this patient, and on similarly treated others, suggest that the cumulative dose threshold (CDT for TMZ that predisposes to T-MDS and which may potentially lead to acute myeloid leukemia (T-AML is around 18000 to 20000 mg/sq m. Although the incidence of T-MDS and the predisposing CDT of TMZ may differ from that of other potentially leukemogenic compounds currently and formerly used as chemotherapeutic agents, all alkylating agents, including TMZ, should be considered potentially leukemogenic when administered long term.

  17. Microbiologically induced corrosion

    International Nuclear Information System (INIS)

    Stein, A.A.

    1988-01-01

    Biological attack is a problem that can affect all metallic materials in a variety of environments and systems. In the power industry, corrosion studies have focused on condensers and service water systems where slime, barnacles, clams, and other macro-organisms are easily detected. Efforts have been made to eliminate the effect of these organisms through the use of chlorination, backflushing, organic coating, or thermal shock. The objective is to maintain component performance by eliminating biofouling and reducing metallic corrosion. Recently, corrosion of power plant components by micro-organisms (bacteria) has been identified even in very clean systems. A system's first exposure to microbiologically induced corrosion (MIC) occurs during its first exposure to an aqueous environment, such as during hydrotest or wet layup. Corrosion of buried pipelines by sulfate-reducing bacteria has been studied by the petrochemical industry for years. This paper discusses various methods of diagnosing, monitoring, and controlling MIC in a variety of systems, as well as indicates areas where further study is needed

  18. Doxycycline induced Esophagitis

    Directory of Open Access Journals (Sweden)

    Banu Karakus Yilmaz

    2014-02-01

    Full Text Available Esophagitis is a hazardous condition such as acid reflux of esophageal mucosa, infection, systemic diseases, radiation, drugs and trauma. Drug- induced esophagial injury (DIEI is a disease with the use of variety of drugs that caused serious damage and ulcer in the mucosa of the esophagus. The most commonly implicated drugs are non-steroidal anti-inflammatory drugs (NSAIDs, chloride and especially antibiotics. Thirty-six year-old female patient presented to the emergency department with odynophagia during swallowing and complaining of retrosternal pain. One week before 100 mg doxycycline (2x1 PO for therapeutic abortion were prescribed. It was learned that in the third day of the initiation of medication, the patient\\'s symptoms began and stopped using drug by the fourth day due to advers effect of drugs, but her symptoms didn’t regressed although she didn’t use them. Endoscopy appointment was taken, proton pump inhibitor and antiacid treatment was given, than patient was discharged from the emergency department. In the endoscopy, 20 mm segment esophageal ulcer was seen approximately in the 30.th cm of the esophagius. DIEI is a relatively common, although under-recognized, so this case was presented for remainding DIEI to emergency medicine personals and reweiving its diagnosis, treatment and follow-up.

  19. Ceftazidime-induced thrombocytopenia.

    Science.gov (United States)

    Domingo-Chiva, E; Díaz-Rangel, M; Monsalve-Naharro, J Á; Cuesta-Montero, P; Catalá-Ripoll, J V; García-Martínez, E M

    2017-12-01

    Ceftazidime is an antibiotic belonging to the group of third generation cephalosporins, frequently used in clinical practice for its broad antibacterial spectrum. A case report is presented on a 78-year-old man who entered the intensive care unit due to respiratory failure secondary to nosocomial pneumonia in the postoperative period of a laparoscopic hepatic bisegmentectomy for a hepatocarcinoma. It required invasive mechanical ventilation and was treated with ceftazidime, developing a progressive decrease in platelet count after the onset of this drug and after re-exposure to it, not coinciding with the introduction of other drugs. The adverse reaction was reported to the Spanish pharmacosurveillance system and according to the Naranjo algorithm the causal relationship was probable. Since no case of ceftazidime-induced thrombocytopenia was found in the literature, we consider knowledge of it relevant as an adverse effect to be taken into account given its potential severity, especially when it cannot be explained by other causes. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Neutron induced electron radiography

    International Nuclear Information System (INIS)

    Andrade, Marcos Leandro Garcia

    2008-01-01

    In the present paper a new radiography technique, the 'Neutron Induced Electron Radiography' - NIER, to inspect low thickness samples on the order of micra, has been developed. This technique makes use of low energy electrons as penetrating radiation generated from metallic gadolinium screens when irradiated by thermal neutrons. The conditions to obtain the best image for the conventional X-ray film Kodak-AA were determined by using a digital system to quantify the darkening level of the film. The irradiations have been performed at a radiography equipment installed at the beam-hole no. 8 of the 5 MW IEA-R1 nuclear research reactor of IPEN-CNEN/SP. The irradiation time to obtain the best radiography was 100 seconds and for such condition the technique was able to discern 1 μm in 24 μm of aluminum at a resolution of 32 μm. By visual comparison the images obtained by the NIER shown a higher quality when compared with the ones from other usual techniques the make use of electrons a penetrating radiation and films for image registration. Furthermore the use of the digital system has provided a smaller time for data acquisition and data analysis as well as an improvement in the image visualization. (author)

  1. Ion-induced sputtering

    International Nuclear Information System (INIS)

    Yamamura, Yasumichi; Shimizu, Ryuichi; Shimizu, Hazime; Ito, Noriaki.

    1983-01-01

    The research on ion-induced sputtering has been continued for a long time, since a hundred or more years ago. However, it was only in 1969 by Sigmund that the sputtering phenomena were theoretically arranged into the present form. The reason why the importance of sputtering phenomena have been given a new look recently is the application over wide range. This paper is a review centering around the mechanism of causing sputtering and its characteristics. Sputtering is such a phenomenon that the atoms in the vicinity of a solid surface are emitted into vacuum by receiving a part of ion energy, or in other words, it is a kind of irradiation damage in the vicinity of a solid surface. In this meaning, it can be considered that the sputtering based on the ions located on the clean surface of a single element metal is simple, and has already been basically understood. On the contrary, the phenomena can not be considered to be fully understood in the case of alloys and compounds, because these surface conditions under irradiation are not always clear due to segregation and others. In the paper, the physical of sputtering, single element sputtering, the sputtering in alloys and compounds, and the behaviour of emitted particles are explained. Finally, some recent topics of the sputtering measurement by laser resonant excitation, the sputtering by electron excitation, chemical sputtering, and the sputtering in nuclear fusion reactors are described. (Wakatsuki, Y.)

  2. Tumor-induced osteomalacia

    Science.gov (United States)

    Chong, William H; Molinolo, Alfredo A; Chen, Clara C; Collins, Michael T

    2012-01-01

    Tumor-induced osteomalacia (TIO) is a rare and fascinating paraneoplastic syndrome in which patients present with bone pain, fractures, and muscle weakness. The cause is high blood levels of the recently identified phosphate and vitamin D-regulating hormone, fibroblast growth factor 23 (FGF23). In TIO, FGF23 is secreted by mesenchymal tumors that are usually benign, but are typically very small and difficult to locate. FGF23 acts primarily at the renal tubule and impairs phosphate reabsorption and 1α-hydroxylation of 25-hydroxyvitamin D, leading to hypophosphatemia and low levels of 1,25-dihydroxy vitamin D. A step-wise approach utilizing functional imaging (F-18 fluorodeoxyglucose positron emission tomography and octreotide scintigraphy) followed by anatomical imaging (computed tomography and/or magnetic resonance imaging), and, if needed, selective venous sampling with measurement of FGF23 is usually successful in locating the tumors. For tumors that cannot be located, medical treatment with phosphate supplements and active vitamin D (calcitriol or alphacalcidiol) is usually successful; however, the medical regimen can be cumbersome and associated with complications. This review summarizes the current understanding of the pathophysiology of the disease and provides guidance in evaluating and treating these patients. Novel imaging modalities and medical treatments, which hold promise for the future, are also reviewed. PMID:21490240

  3. Laxative-induced rhabdomyolysis

    Directory of Open Access Journals (Sweden)

    Alfonso Merante

    2010-03-01

    Full Text Available Alfonso Merante1, Pietro Gareri2,3, Norma Maria Marigliano2, Salvatore De Fazio2, Elvira Bonacci1, Carlo Torchia1, Gaetano Russo1, Pasquale Lacroce1, Roberto Lacava3, Alberto Castagna3, Giovambattista De Sarro2, Giovanni Ruotolo11Geriatrist, Geriatric Unit “Pugliese-Ciaccio” Hospital, Catanzaro, Italy; 2Department of Experimental and Clinical Medicine, Faculty of Medicine and Surgery, University Magna Graecia of Catanzaro, Clinical Pharmacology and Pharmacovigilance Unit, Mater Domini University Hospital, Catanzaro, Italy; 3Geriatrist, Operative Unit Elderly Health Care, Catanzaro, ItalyAbstract: The present study describes a case of laxative-induced rhabdomyolysis in an elderly patient. An 87-year-old woman was hospitalized for the onset of confusion, tremors, an inability to walk, and a fever that she had been experiencing for 36 hours. She often took high dosages of lactulose and sorbitol syrup as a laxative (about 70 g/day. During her physical examination, the patient was confused, drowsy, and she presented hyposthenia in her upper and lower limbs, symmetric and diffuse moderate hyporeflexia, and her temperature was 37.8°C. Laboratory tests revealed severe hyponatremia with hypokalemia, hypocalcemia, hypochloremia, and metabolic alkalosis. Moreover, rhabdomyolysis markers were found. The correction of hydroelectrolytic imbalances with saline, potassium and sodium chlorure, calcium gluconate was the first treatment. During her hospitalization the patient presented acute delirium, treated with haloperidol and prometazine chloridrate intramuscularly. She was discharged 12 days later, after resolution of symptoms, and normalized laboratory tests. Over-the-counter drugs such as laxatives are usually not considered dangerous; on the other hand, they may cause serum electrolytic imbalance and rhabdomyolysis. A careful monitoring of all the drugs taken by the elderly is one of the most important duties of a physician since drug interactions and

  4. Tumour-induced osteomalacia.

    Science.gov (United States)

    Minisola, Salvatore; Peacock, Munro; Fukumoto, Seijii; Cipriani, Cristiana; Pepe, Jessica; Tella, Sri Harsha; Collins, Michael T

    2017-07-13

    Tumour-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is a rare paraneoplastic disorder caused by tumours that secrete fibroblast growth factor 23 (FGF23). Owing to the role of FGF23 in renal phosphate handling and vitamin D synthesis, TIO is characterized by decreased renal tubular reabsorption of phosphate, by hypophosphataemia and by low levels of active vitamin D. Chronic hypophosphataemia ultimately results in osteomalacia (that is, inadequate bone mineralization). The diagnosis of TIO is usually suspected when serum phosphate levels are chronically low in the setting of bone pain, fragility fractures and muscle weakness. Locating the offending tumour can be very difficult, as the tumour is often very small and can be anywhere in the body. Surgical removal of the tumour is the only definitive treatment. When the tumour cannot be located or when complete resection is not possible, medical treatment with phosphate salts or active vitamin D is necessary. One of the most promising emerging treatments for unresectable tumours that cause TIO is the anti-FGF23 monoclonal antibody KRN23. The recent identification of a fusion of fibronectin and fibroblast growth factor receptor 1 (FGFR1) as a molecular driver in some tumours not only sheds light on the pathophysiology of TIO but also opens the door to a better understanding of the transcription, translocation, post-translational modification and secretion of FGF23, as well as suggesting approaches to targeted therapy. Further study will reveal if the FGFR1 pathway is also involved in tumours that do not harbour the translocation.

  5. Catecholamine induced cardiomyopathy in pheochromocytoma

    Directory of Open Access Journals (Sweden)

    Ron Thomas Varghese

    2013-01-01

    Full Text Available Catecholamine induced cardiomyopathy in the setting of pheochromocytoma is an unusual clinical entity. Earlier studies have reported left ventricular dysfunction in around 10% of subjects with pheochromocytoma. [1] Catecholamine induced vasoconstriction, direct toxic effect of byproducts of catecholamine degradation and direct receptor-mediated mechanisms are thought to contribute to cardiomyopathy in subjects with pheochromocytoma. The presentation remains a diagnostic challenge as patients may already have hypertensive heart disease and acute coronary syndrome on account of uncontrolled secondary hypertension. We report a case of a 42-year-old male, who presented with features of pheochromocytoma induced cardiomyopathy.

  6. Cisplatin-Induced Eosinophilic Pneumonia

    Directory of Open Access Journals (Sweden)

    Hideharu Ideguchi

    2014-01-01

    Full Text Available A 67-year-old man suffering from esophageal cancer was admitted to our hospital complaining of dyspnea and hypoxemia. He had been treated with cisplatin, docetaxel, and fluorouracil combined with radiotherapy. Chest computed tomography revealed bilateral ground-glass opacity, and bronchoalveolar lavage fluid showed increased eosinophils. Two episodes of transient eosinophilia in peripheral blood were observed after serial administration of anticancer drugs before the admission, and drug-induced lymphocyte stimulation test to cisplatin was positive. Thus cisplatin-induced eosinophilic pneumonia was suspected, and corticosteroid was effectively administered. To our knowledge, this is the first reported case of cisplatin-induced eosinophilic pneumonia.

  7. Systemic resistance induced by rhizosphere bacteria

    NARCIS (Netherlands)

    Loon, L.C. van; Bakker, P.A.H.M.; Pieterse, C.M.J.

    1998-01-01

    Nonpathogenic rhizobacteria can induce a systemic resistance in plants that is phenotypically similar to pathogen-induced systemic acquired resistance (SAR). Rhizobacteria-mediated induced systemic resistance (ISR) has been demonstrated against fungi, bacteria, and viruses in Arabidopsis, bean,

  8. Tumor-induced osteomalacia

    Directory of Open Access Journals (Sweden)

    Pablo Florenzano

    2017-12-01

    Full Text Available Tumor-induced osteomalacia (TIO is a rare paraneoplastic syndrome clinically characterized by bone pain, fractures and muscle weakness. It is caused by tumoral overproduction of fibroblast growth factor 23 (FGF23 that acts primarily at the proximal renal tubule, decreasing phosphate reabsorption and 1α-hydroxylation of 25 hydroxyvitamin D, thus producing hypophosphatemia and osteomalacia. Lesions are typically small, benign mesenchymal tumors that may be found in bone or soft tissue, anywhere in the body. In up to 60% of these tumors, a fibronectin-1(FN1 and fibroblast growth factor receptor-1 (FGFR1 fusion gene has been identified that may serve as a tumoral driver. The diagnosis is established by the finding of acquired chronic hypophosphatemia due to isolated renal phosphate wasting with concomitant elevated or inappropriately normal blood levels of FGF23 and decreased or inappropriately normal 1,25-OH2-Vitamin D (1,25(OH2D. Locating the tumor is critical, as complete removal is curative. For this purpose, a step-wise approach is recommended, starting with a thorough medical history and physical examination, followed by functional imaging. Suspicious lesions should be confirmed by anatomical imaging, and if needed, selective venous sampling with measurement of FGF23. If the tumor is not localized, or surgical resection is not possible, medical therapy with phosphate and active vitamin D is usually successful in healing the osteomalacia and reducing symptoms. However, compliance is often poor due to the frequent dosing regimen and side effects. Furthermore, careful monitoring is needed to avoid complications such us secondary/tertiary hyperparathyroidism, hypercalciuria, and nephrocalcinosis. Novel therapeutical approaches are being developed for TIO patients, such as image-guided tumor ablation and medical treatment with the anti-FGF23 monoclonal antibody KRN23 or anti FGFR medications. The case of a patient with TIO is presented to

  9. Infrasonic induced ground motions

    Science.gov (United States)

    Lin, Ting-Li

    On January 28, 2004, the CERI seismic network recorded seismic signals generated by an unknown source. Our conclusion is that the acoustic waves were initiated by an explosive source near the ground surface. The meteorological temperature and effective sound speed profiles suggested existence of an efficient near-surface waveguide that allowed the acoustic disturbance to propagate to large distances. An explosion occurring in an area of forest and farms would have limited the number of eyewitnesses. Resolution of the source might be possible by experiment or by detailed analysis of the ground motion data. A seismo-acoustic array was built to investigate thunder-induced ground motions. Two thunder events with similar N-wave waveforms but different horizontal slownesses are chosen to evaluate the credibility of using thunder as a seismic source. These impulsive acoustic waves excited P and S reverberations in the near surface that depend on both the incident wave horizontal slowness and the velocity structure in the upper 30 meters. Nineteen thunder events were chosen to further investigate the seismo-acoustic coupling. The consistent incident slowness differences between acoustic pressure and ground motions suggest that ground reverberations were first initiated somewhat away from the array. Acoustic and seismic signals were used to generate the time-domain transfer function through the deconvolution technique. Possible non-linear interaction for acoustic propagation into the soil at the surface was observed. The reverse radial initial motions suggest a low Poisson's ratio for the near-surface layer. The acoustic-to-seismic transfer functions show a consistent reverberation series of the Rayleigh wave type, which has a systematic dispersion relation to incident slownesses inferred from the seismic ground velocity. Air-coupled Rayleigh wave dispersion was used to quantitatively constrain the near-surface site structure with constraints afforded by near-surface body

  10. [Medical induced abortion].

    Science.gov (United States)

    Bettahar, K; Pinton, A; Boisramé, T; Cavillon, V; Wylomanski, S; Nisand, I; Hassoun, D

    2016-12-01

    Updated clinical recommendations for medical induced abortion procedure. A systematic review of French and English literature, reviewing the evidence relating to the provision of medical induced abortion was carried out on PubMed, Cochrane Library and international scientific societies recommendations. The effectiveness of medical abortion is higher than 95% when the protocols are adjusted to gestational age (EL1). Misoprostol alone is less effective than a combination of mifepristone and misoprostol (EL1). Gemeprost is less effective than misoprostol (EL2). The dose of 200mg of mifepristone should be preferred to 600mg (NP1, Rank A). Mifepristone can be taken at home (professional agreement). The optimum interval between mifepristone and misoprostol intake should be 24 to 48 hours (EL1, grade A). Before 7 weeks LMP, the dose of 400μg misoprostol should be given orally (EL1, grade A) eventually repeated after 3hours if no bleeding occurs. For optimal effectiveness between 7 and 14 LMP, the interval between mifepristone and misoprostol should not be shortened to less than 8hours (grade 1). An interval of 24 to 48hours will not affect the effectiveness of the method provided misoprostol dosage is 800μg (EL1). Vaginal, sublingual or buccal routes of administration are more effective and better tolerated than the oral route, which should be abandoned (EL1). An amount of 800μg sublingual or buccal misoprostol route has the same effectiveness than the vaginal route but more gastrointestinal side effects (EL1, grade A). Between 7 and 9 LMP, it does not seem necessary to repeat misoprostol dose whereas it should be repeated beyond 9 SA (grade B). Between 9 and 14 LMP, the dose of 400μg misoprostol given either vaginally, buccally or sublingually should be repeated every 3hours if needed (with a maximum of 5 doses) (EL2, grade B). There is no strong evidence supporting routine antibiotic prophylaxis for medical abortion (professional agreement). Rare contraindications

  11. Solid lipid nanoparticles carrying chemotherapeutic drug across the blood-brain barrier through insulin receptor-mediated pathway.

    Science.gov (United States)

    Kuo, Yung-Chih; Shih-Huang, Chun-Yuan

    2013-09-01

    Carmustine (BCNU)-loaded solid lipid nanoparticles (SLNs) were grafted with 83-14 monoclonal antibody (MAb) (83-14 MAb/BCNU-SLNs) and applied to the brain-targeting delivery. Human brain-microvascular endothelial cells (HBMECs) incubated with 83-14 MAb/BCNU-SLNs were stained to demonstrate the interaction between the nanocarriers and expressed insulin receptors (IRs). The results revealed that the particle size of 83-14 MAb/BCNU-SLNs decreased with an increasing weight percentage of Dynasan 114 (DYN). Storage at 4 °C for 6 weeks slightly deformed the colloidal morphology. In addition, poloxamer 407 on 83-14 MAb/BCNU-SLNs induced cytotoxicity to RAW264.7 cells and inhibited phagocytosis by RAW264.7 cells. An increase in the weight percentage of DYN from 0% to 67% slightly reduced the viability of RAW264.7 cells and promoted phagocytosis. Moreover, the transport ability of 83-14 MAb/BCNU-SLNs across the blood-brain barrier (BBB) in vitro enhanced with an increasing weight percentage of Tween 80. 83-14 MAb on MAb/BCNU-SLNs stimulated endocytosis by HBMECs via IRs and enhanced the permeability of BCNU across the BBB. 83-14 MAb/BCNU-SLNs can be a promising antitumor drug delivery system for transporting BCNU to the brain.

  12. Mutations induced in plant breeding

    International Nuclear Information System (INIS)

    Barriga B, P.

    1984-01-01

    The most significant aspects of the use of ionizing radiations in plant breeding are reviewed. Aspects such as basic principles of mutation, expression and selection in obtention of mutants, methods for using induced mutations and sucess achieved with this methodology in plant breeding are reviewed. Results obtained in a program of induced mutation on wheat for high content of protein and lysine at the Universidad Austral de Chile are presented. (Author)

  13. Mutations induced in plant breeding

    Energy Technology Data Exchange (ETDEWEB)

    Barriga B, P. (Universidad Austral de Chile, Valdivia. Inst. de Produccion y Sanidad Vegetal)

    1984-10-01

    The most significant aspects of the use of ionizing radiations in plant breeding are reviewed. Aspects such as basic principles of mutation, expression and selection in obtention of mutants, methods for using induced mutations and sucess achieved with this methodology in plant breeding are reviewed. Results obtained in a program of induced mutation on wheat for high content of protein and lysine at the Universidad Austral de Chile are presented.

  14. Holographic Two-Photon Induced Photopolymerization

    Data.gov (United States)

    Federal Laboratory Consortium — Holographic two-photon-induced photopolymerization (HTPIP) offers distinct advantages over conventional one-photon-induced photopolymerization and current techniques...

  15. Mitochondrial Swelling Induced by Glutathione

    Science.gov (United States)

    Lehninger, Albert L.; Schneider, Marion

    1959-01-01

    Reduced glutathione, in concentrations approximating those occurring in intact rat liver, causes swelling of rat liver mitochondria in vitro which is different in kinetics and extent from that yielded by L-thyroxine. The effect is also given by cysteine, which is more active, and reduced coenzyme A, but not by L-ascorbate, cystine, or oxidized glutathione. The optimum pH is 6.5, whereas thyroxine-induced swelling is optimal at pH 7.5. The GSH-induced swelling is not inhibited by DNP or dicumarol, nor by high concentrations of sucrose, serum albumin, or polyvinylpyrrolidone, in contrast to thyroxine-induced swelling. ATP inhibits the GSH swelling, but ADP and AMP are ineffective. Mn-+ is a very potent inhibitor, but Mg++ is ineffective. Ethylenediaminetetraacetate is also an effective inhibitor of GSH-induced swelling. The respiratory inhibitors amytal and antimycin A do not inhibit the swelling action of GSH, but cyanide does; these findings are consistent with the view that the oxidation-reduction state of the respiratory chain between cytochrome c and oxygen is a determinant of GSH-induced swelling. Reversal of GSH-induced swelling by osmotic means or by ATP in KCl media could not be observed. Large losses of nucleotides and protein occur during the swelling by GSH, suggesting that the action is irreversible. The characteristically drastic swelling action of GSH could be prevented if L-thyroxine was also present in the medium. PMID:13630941

  16. Induced mutations in sesame breeding

    International Nuclear Information System (INIS)

    Ashri, A.

    2001-01-01

    The scope of induced mutations in sesame (Sesamum indicum L.) breeding is reviewed. So far in Egypt, India, Iraq, Rep. of Korea, and Sri Lanka, 14 officially released varieties have been developed through induced mutations: 12 directly and 2 through cross breeding (one using the 'dt45' induced mutant from Israel). For another variety released in China there are no details. The induced mutations approach was adopted primarily in order to obtain genetic variability that was not available in the germplasm collection. The mutagens commonly applied have been gamma rays, EMS and sodium azide. Sesame seeds can withstand high mutagen doses, and there are genotypic differences in sensitivity between varieties. The mutants induced in the above named countries and others include better yield, improved seed retention, determinate habit, modified plant architecture and size, more uniform and shorter maturation period, earliness, resistance to diseases, genic male sterility, seed coat color, higher oil content and modified fatty acids composition. Some of the induced mutants have already given rise to improved varieties, the breeding value of other mutants is now being assessed and still others can serve as useful markers in genetic studies and breeding programmes. (author)

  17. Victim-induced criminality.

    Science.gov (United States)

    Fooner, M

    1966-09-02

    about the probable effects on the administration of criminal justice. These are pragmatic problems; there is a third problem which may at this time seem speculative, but is, nevertheless, quite important. 3) To what extent will a particular proposal for victim compensation contribute to a temptation-opportunity pattern in victim behavior? In previous studies it has been pointed out that large numbers of our fellow Americans have tended to acquire casual money-handling habits-generically designated "carelessness"-which contribute to the national growth of criminality. How the victim helps the criminal was sketched in reports of those studies (10). It was made abundantly clear that human beings in our affluent society cannot be assumed to be prudent or self-protective against the hazards of crime. Even when the "victim" is not overtly acting to commit a crime-as in the case of the property owner who hires an arsonist-he often tempts the offender. Among the victims of burglary-statistically the most prevalent crime in the United States-are a substantial number of Americans who keep cash, jewelry, and other valuables carelessly at home or in hotel rooms to which the burglar has easy access through door or window. Victims of automobile theft-one of the fastest growing classes of crime-include drivers who leave the vehicle or its contents invitingly accessible to thieves. And so on with other classes of crime. As pointed out in previous studies, when victim behavior follows a temptation-opportunity pattern, it (i) contributes to a "climate of criminal inducements," (ii) adds to the economic resources available to criminal societies, and (iii) detracts from the ability of lawenforcement agencies to suppress the growth of crime.

  18. Chimera of IL-2 Linked to Light Chain of anti-IL-2 mAb Mimics IL-2/anti-IL-2 mAb Complexes Both Structurally and Functionally

    Czech Academy of Sciences Publication Activity Database

    Tomala, Jakub; Kovářová, Jiřina; Kabešová, Martina; Votavová, Petra; Chmelová, Helena; Dvořáková, Barbora; Říhová, Blanka; Kovář, Marek

    2013-01-01

    Roč. 8, č. 5 (2013), s. 871-876 ISSN 1554-8929 R&D Projects: GA ČR GAP301/11/0325 Institutional support: RVO:61388971 Keywords : IN-VIVO EXPANSION * IL-2 * ANTIBODY Subject RIV: CE - Biochemistry Impact factor: 5.356, year: 2013

  19. Diet-induced obesity attenuates fasting-induced hyperphagia.

    Science.gov (United States)

    Briggs, D I; Lemus, M B; Kua, E; Andrews, Z B

    2011-07-01

    Obesity impairs arcuate (ARC) neuropeptide Y (NPY)/agouti-releated peptide (AgRP) neuronal function and renders these homeostatic neurones unresponsive to the orexigenic hormone ghrelin. In the present study, we investigated the effect of diet-induced obesity (DIO) on feeding behaviour, ARC neuronal activation and mRNA expression following another orexigenic stimulus, an overnight fast. We show that 9 weeks of high-fat feeding attenuates fasting-induced hyperphagia by suppressing ARC neuronal activation and hypothalamic NPY/AgRP mRNA expression. Thus, the lack of appropriate feeding responses in DIO mice to a fast is caused by failure ARC neurones to recognise and/or respond to orexigenic cues. We propose that fasting-induced hyperphagia is regulated not by homeostatic control of appetite in DIO mice, but rather by changes in the reward circuitry. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

  20. Pur-Alpha Induces JCV Gene Expression and Viral Replication by Suppressing SRSF1 in Glial Cells.

    Directory of Open Access Journals (Sweden)

    Ilker Kudret Sariyer

    Full Text Available PML is a rare and fatal demyelinating disease of the CNS caused by the human polyomavirus, JC virus (JCV, which occurs in AIDS patients and those on immunosuppressive monoclonal antibody therapies (mAbs. We sought to identify mechanisms that could stimulate reactivation of JCV in a cell culture model system and targeted pathways which could affect early gene transcription and JCV T-antigen production, which are key steps of the viral life cycle for blocking reactivation of JCV. Two important regulatory partners we have previously identified for T-antigen include Pur-alpha and SRSF1 (SF2/ASF. SRSF1, an alternative splicing factor, is a potential regulator of JCV whose overexpression in glial cells strongly suppresses viral gene expression and replication. Pur-alpha has been most extensively characterized as a sequence-specific DNA- and RNA-binding protein which directs both viral gene transcription and mRNA translation, and is a potent inducer of the JCV early promoter through binding to T-antigen.Pur-alpha and SRSF1 both act directly as transcriptional regulators of the JCV promoter and here we have observed that Pur-alpha is capable of ameliorating SRSF1-mediated suppression of JCV gene expression and viral replication. Interestingly, Pur-alpha exerted its effect by suppressing SRSF1 at both the protein and mRNA levels in glial cells suggesting this effect can occur independent of T-antigen. Pur-alpha and SRSF1 were both localized to oligodendrocyte inclusion bodies by immunohistochemistry in brain sections from patients with HIV-1 associated PML. Interestingly, inclusion bodies were typically positive for either Pur-alpha or SRSF1, though some cells appeared to be positive for both proteins.Taken together, these results indicate the presence of an antagonistic interaction between these two proteins in regulating of JCV gene expression and viral replication and suggests that they play an important role during viral reactivation leading to

  1. Sociocultural determinants of induced abortion.

    Science.gov (United States)

    Korejo, Razia; Noorani, Khurshid Jehan; Bhutta, Shereen

    2003-05-01

    To determine the frequency of induced abortion and identify the role of sociocultural factors contributing to termination of pregnancy and associated morbidity and mortality in hospital setting. Prospective observational study. The study was conducted in the Department of Obstetrics and Gynaecology, Jinnah Postgraduate Medical Centre, Karachi from January 1999 to June 2001. The patients who were admitted for induced abortion were interviewed in privacy. On condition of anonymity they were asked about the age, parity, family setup and relationships, with particular emphasis on sociocultural reasons and factors contributing to induction of abortion. Details of status of abortionist and methods used for termination of pregnancy, the resulting complications and their severity were recorded. Out of total admissions, 57(2.35%) gave history of induced abortion. All women belonged to low socioeconomic class and 59.6% of them were illiterate. Forty-three (75.5%) of these women had never practiced contraception. Twenty-four (42%) were grandmultiparae and did not want more children. In 29 women (50.9%) the decision for abortion had been supported by the husband. In 25 women (43.8%) abortion was carried out by Daiyan (traditional midwives). Serious complications like uterine perforation with or without bowel injury were encountered in 25 (43.8%) of these women. During the study period illegally induced abortion accounted for 6 (10.5%) maternal deaths. Prevalence of poverty, illiteracy, grand multiparity and non-practice of contraception are strong determinants of induced abortion.

  2. Sociocultural determinants of induced abortion

    International Nuclear Information System (INIS)

    Korejo, R.; Noorani, K.J.; Bhutta, S.

    2003-01-01

    Objective: To determine the frequency of induced abortion and identity the role of sociocultural factors contributing to termination of pregnancy and associated morbidity and mortality in hospital setting. Subjects and Methods: The patients who were admitted for induced abortion were interviewed in privacy. On condition of anonymity they were asked about the age, parity, family setup and relationships, with particular emphasis on sociocultural reasons and factors contributing to induction of abortion. Details of status of abortionist and methods used for termination of pregnancy, the resulting complications and their severity were recorded. Results: Out of total admissions, 57(2.35%) gave history of induced abortion. All women belonged to low socioeconomic class and 59.6% of them were illiterate. Forty-three (75.5%) of these women had never practiced concentration. Twenty-four (42%) were grandmultiparae and did not want more children. In 29 women (50.9%) the decision for abortion had been supported by the husband. In 25 (43.8%) abortion was carried out by Daiyan (traditional midwives). Serious complications like uterine perforation with or without bowel injury were encouraged in 25 (43.8%) of these women. During the study period illegally induced abortion accounted for 6 (10.5%) maternal deaths. Conclusion: Prevalence of poverty, illiteracy, grand multiparity and non-practice of contraception are strong determinants of induced abortion. (author)

  3. Pharmacokinetics of radiolabelled anti-fibrin MAb DD-3B6/22 and factors effecting its localization to thrombi

    International Nuclear Information System (INIS)

    Boniface, G.R.; Lee, F.T.; Milner, L.J.; Walker, K.Z.

    1990-01-01

    The monoclonal antibody DD-3B6/22 recognizes the D-dimer (DD) epitope of human cross-linked fibrin and is currently being investigated as a potential thrombosis imaging agent. The pharmacokinetic profiles of 99m Tc labelled intact and Fab' fragments of DD-3B6/22 were determined in rabbits and gave whole body clearance estimates of 0.06 ± 0.01 and 1.61 ± 0.24 mL/min/kg respectively. The effect of heparin, radiological contrast media and free DD antigen levels on in vitro binding of 99m Tc-DD-3B6/22 Fab' was determined by inhibition assays to immobilized antigen and human clots. No effect on binding was demonstrated with heparin or contrast media at clinically significant concentrations. DD supernata concentrations of between 8-20 μg/mL were required to inhibit the in vitro binding 99m Tc-DD-3B6/22 Fab' to immobilized antigen or blood clot by 50%. Localisation studies of 99m Tc-DD-3B6/22 Fab' in a rabbit jugular vein clot model were carried out in animals co-administered free DD antigen. Results indicated minimal inhibition of 99m Tc-DD-3B6/22 Fab' clot localization after 4 hours up to a level of 16 μg/mL DD plasma concentration. These results suggest that thrombosis imaging with radiolabelled DD-3B6/22 should be unduly affected by the co-administration of heparin or venographic contrast media in the clinical setting, whilst free antigen effect should not occur within clinically relevant titres. 21 refs., 2 tabs., 4 figs

  4. Exploiting mAb structure characteristics for a directed QbD implementation in early process development.

    Science.gov (United States)

    Karlberg, Micael; von Stosch, Moritz; Glassey, Jarka

    2018-03-07

    In today's biopharmaceutical industries, the lead time to develop and produce a new monoclonal antibody takes years before it can be launched commercially. The reasons lie in the complexity of the monoclonal antibodies and the need for high product quality to ensure clinical safety which has a significant impact on the process development time. Frameworks such as quality by design are becoming widely used by the pharmaceutical industries as they introduce a systematic approach for building quality into the product. However, full implementation of quality by design has still not been achieved due to attrition mainly from limited risk assessment of product properties as well as the large number of process factors affecting product quality that needs to be investigated during the process development. This has introduced a need for better methods and tools that can be used for early risk assessment and predictions of critical product properties and process factors to enhance process development and reduce costs. In this review, we investigate how the quantitative structure-activity relationships framework can be applied to an existing process development framework such as quality by design in order to increase product understanding based on the protein structure of monoclonal antibodies. Compared to quality by design, where the effect of process parameters on the drug product are explored, quantitative structure-activity relationships gives a reversed perspective which investigates how the protein structure can affect the performance in different unit operations. This provides valuable information that can be used during the early process development of new drug products where limited process understanding is available. Thus, quantitative structure-activity relationships methodology is explored and explained in detail and we investigate the means of directly linking the structural properties of monoclonal antibodies to process data. The resulting information as a decision tool can help to enhance the risk assessment to better aid process development and thereby overcome some of the limitations and challenges present in QbD implementation today.

  5. Influence of connection tubing in modern size exclusion chromatography and its impact on the characterization of mAbs.

    Science.gov (United States)

    Fekete, Szabolcs; Guillarme, Davy

    2018-02-05

    The goal of the study was to evaluate the impact of connection tubing in modern size exclusion chromatography (SEC), since it may strongly impact the apparent column efficiency, as the compounds are not retained in SEC. For this purpose, a reference SEC column of 150×4.6mm, 1.8μm was considered, and various proteins were tested as model compounds. Different tube geometries (lengths and internal diameters) and materials (stainless steel and PEEK) were evaluated in a systematic way. Large proteins always showed larger tube dispersion vs. small molecules, especially when the residence time in the tube was long (at low flow rate). This confirms the need to drastically reduce the tube volume (using the shortest and narrowest connector tubing) to attain the full benefits of UHPSEC columns. In addition, PEEK tubing were found to be more appropriate than stainless steel tubing, since adsorption of proteins was less pronounced, and higher plate count can be obtained. Finally, after a careful system optimization, up to 40% increase of apparent column efficiency can be achieved compared to a regular UHPLC system, when using a 150×4.6mm UHPSEC columns packed with sub-3μm particles. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Advanced model-based control strategies for the intensification of upstream and downstream processing in mAb production.

    Science.gov (United States)

    Papathanasiou, Maria M; Quiroga-Campano, Ana L; Steinebach, Fabian; Elviro, Montaña; Mantalaris, Athanasios; Pistikopoulos, Efstratios N

    2017-07-01

    Current industrial trends encourage the development of sustainable, environmentally friendly processes with minimal energy and material consumption. In particular, the increasing market demand in biopharmaceutical industry and the tight regulations in product quality necessitate efficient operating procedures that guarantee products of high purity. In this direction, process intensification via continuous operation paves the way for the development of novel, eco-friendly processes, characterized by higher productivity and lower production costs. This work focuses on the development of advanced control strategies for (i) a cell culture system in a bioreactor and (ii) a semicontinuous purification process. More specifically, we consider a fed-batch culture of GS-NS0 cells and the semicontinuous Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) for the purification process. The controllers are designed following the PAROC framework/software platform and their capabilities are assessed in silico, against the process models. It is demonstrated that the proposed controllers efficiently manage to increase the system productivity, returning strategies that can lead to continuous, stable process operation. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:966-988, 2017. © 2017 American Institute of Chemical Engineers.

  7. Sequential Tc[sup 99m] mercaptoacetyl-triglycine (MAB3) renography as an evaluator of early renal transplant function

    Energy Technology Data Exchange (ETDEWEB)

    Carmody, E.; Greene, A.; Brennan, P.; Donohue, J.; Carmody, M.; Keeling, F. (Department of Radiology and Nephrology, Beaumont Hospital, Dublin, Ireland (United Kingdom))

    1993-01-01

    A prospective study was carried out to evaluate the role of sequential Tc[sup 99m] MAG3 renography in assessing transplant function in the early post-operative period. Twenty patients were included in the study. Studies were performed on all patients at intervals of 48-72 hours until discharge. There were 11 clinically diagnosed episodes of rejection, 9 of which were correctly diagnosed using MAG3 renography. Six episodes of rejection were diagnosed prior to the onset of clinical symptoms. Two patients with graft infarction were correctly diagnosed. Six patients had evidence of transient renographic abnormalities in the immediate post-operative phase which were not associated with clinical symptoms, all of these resolved spontaneously on subsequent examinations and were presumed to be related to resolving acute tubular necrosis (ATN). The perfusion index was of no discriminatory value in this study. Sequential Tc[sup 99m] MAG3 renography is highly sensitive but entirely nonspecific in the evaluation of pathology in the transplant kidney. Rejection in an uncomplicated transplant can be readily detected in many cases well in advance of clinical manifestations. This study demonstrates that Tc[sup 99m] MAG3 renography is certainly equal to Tc[sup 99m] DTPA renography or Iodine 131 renography in assessing early transplant function. However, TC[sup 99m] MAG3 exposes the patient to considerably less radiation and the images are of superior quality. (au) (15 refs.).

  8. Hydroxyurea-Induced Replication Stress

    Directory of Open Access Journals (Sweden)

    Kenza Lahkim Bennani-Belhaj

    2010-01-01

    Full Text Available Bloom's syndrome (BS displays one of the strongest known correlations between chromosomal instability and a high risk of cancer at an early age. BS cells combine a reduced average fork velocity with constitutive endogenous replication stress. However, the response of BS cells to replication stress induced by hydroxyurea (HU, which strongly slows the progression of replication forks, remains unclear due to publication of conflicting results. Using two different cellular models of BS, we showed that BLM deficiency is not associated with sensitivity to HU, in terms of clonogenic survival, DSB generation, and SCE induction. We suggest that surviving BLM-deficient cells are selected on the basis of their ability to deal with an endogenous replication stress induced by replication fork slowing, resulting in insensitivity to HU-induced replication stress.

  9. Uterine contraction induced by Ghanaian plants used to induce abortion

    DEFF Research Database (Denmark)

    Larsen, Birgitte HV; Soelberg, Jens; Kristiansen, Uffe

    2016-01-01

    Ethnomedicinal observations from the time of the Atlantic slave trade show women in Ghana historically used plants as emmenagogues (menstruation stimulants) and to induce abortion. This study investigates the effect of four of these plants on uterine contraction. The historically used plants were...

  10. Pump cavitation and inducer design

    International Nuclear Information System (INIS)

    Heslenfeld, M.W.; Hes, M. de

    2002-01-01

    Details of past work on sodium pump development and cavitation studies executed mainly for SNR 300 were reported earlier. Among the requirements for large sodium pumps are long life (200000 hours up to 300000 hours) and small size of impeller and pump, fully meeting the process and design criteria. These criteria are the required 'Q, H, r characteristics' in combination with a low NPSH value and the avoidance of cavitation damage to the pump. The pump designer has to develop a sound hydraulic combination consisting of suction arrangement, impeller design and diffuser. On the other hand the designer is free to choose an optimal pump speed. The pump speed in its turn influences the rotor dynamic pump design and the pump drive. The introduction of the inducer as an integral part of the pump design is based on following advantages: no tip cavitation; (possible) cavitation bubbles move to the open centre due to centrifugal forces on the fluid; the head of the inducer improves the inlet conditions of the impeller. The aim of an inducer is the increase in the suction specific speed (SA value) of a pump whereby the inducer functions as a pressure source improving the impeller inlet conditions. With inducer-impeller combinations values up to SA=15000 are realistic. With the use of an inducer the overall pump sizes can be reduced with Ca. 30%. Pumps commonly available have SA values up to a maximum of ca. 10000. A development programme was executed for SNR 300 in order to reach an increase of the suction specific speed of the impeller from SA 8200 to SA 11000. Further studies to optimize pumps design for the follow up line introduced the 'inducer acting as a pre-impeller' development. This programme was executed in the period 1979-1981. At the FDO premises a scale 1 2.8 inducer impeller combination with a suction specific speed SA=15000 was developed, constructed and tested at the water test rig. This water test rig is equipped with a perspex pipe allowing also visualisation

  11. Induced piezoelectricity in isotropic biomaterial.

    Science.gov (United States)

    Zimmerman, R L

    1976-01-01

    Isotropic material can be made to exhibit piezoelectric effects by the application of a constant electric field. For insulators, the piezoelectric strain constant is proportional to the applied electric field and for semiconductors, an additional out-of-phase component of piezoelectricity is proportional to the electric current density in the sample. The two induced coefficients are proportional to the strain-dependent dielectric constant (depsilon/dS + epsilon) and resistivity (drho/dS - rho), respectively. The latter is more important at frequencies such that rhoepsilonomega less than 1, often the case in biopolymers.Signals from induced piezoelectricity in nature may be larger than those from true piezoelectricity. PMID:990389

  12. Drug-induced hair loss.

    Science.gov (United States)

    2016-05-01

    Hair loss can have major psychological consequences. It can be due to a wide variety of causes, including hormonal disorders, dietary factors, infections, inflammation, trauma, emotional factors, and cancer. Drugs can also induce hair loss, by interacting with the hair growth cycle. Drug-induced hair loss may be immediate or delayed, sudden or gradual, and diffuse or localised. It is usually reversible after drug discontinuation. The drugs most often implicated in hair loss are anticancer agents, interferon, azole antifungals, lithium, immunosuppressants, and many other drugs belonging to a variety of pharmacological classes.

  13. Induced radioactivity in LDEF components

    Science.gov (United States)

    Harmon, B. A.; Fishman, G. J.; Parnell, T. A.; Laird, C. E.

    1992-01-01

    A systematic study of the induced radioactivity of the Long Duration Exposure Facility (LDEF) is being carried out in order to gather information about the low earth orbit radiation environment and its effects on materials. The large mass of the LDEF spacecraft, its stabilized configuration, and long mission duration have presented an opportunity to determine space radiation-induced radioactivities with a precision not possible before. Data presented include preliminary activities for steel and aluminum structural samples, and activation subexperiment foils. Effects seen in the data show a clear indication of the trapped proton anisotropy in the South Atlantic Anomaly and suggest contributions from different sources of external radiation fluxes.

  14. Cyclophosphamide-induced pulmonary toxicity

    International Nuclear Information System (INIS)

    Siemann, D.W.; Macler, L.; Penney, D.P.

    1986-01-01

    Unlike radiation effects, pulmonary toxicity following drug treatments may develop soon after exposure. The dose-response relationship between Cyclophosphamide and lung toxicity was investigated using increased breathing frequency assays used successfully for radiation induced injury. The data indicate that release of protein into the alveolus may play a significant role in Cy induced pulmonary toxicity. Although the mechanism responsible for the increased alveolar protein is as yet not identified, the present findings suggest that therapeutic intervention to inhibit protein release may be an approach to protect the lungs from toxic effects. (UK)

  15. Induced modules over group algebras

    CERN Document Server

    Karpilovsky, Gregory

    1990-01-01

    In 1898 Frobenius discovered a construction which, in present terminology, associates with every module of a subgroup the induced module of a group. This construction proved to be of fundamental importance and is one of the basic tools in the entire theory of group representations.This monograph is designed for research mathematicians and advanced graduate students and gives a picture of the general theory of induced modules as it exists at present. Much of the material has until now been available only in research articles. The approach is not intended to be encyclopedic, rather each topic is

  16. Exorcising ghosts in induced gravity

    Energy Technology Data Exchange (ETDEWEB)

    Narain, Gaurav [Chinese Academy of Sciences (CAS), Key Laboratory of Theoretical Physics, Kavli Institute for Theoretical Physics China (KITPC), Institute of Theoretical Physics, Beijing (China)

    2017-10-15

    Unitarity of the scale-invariant coupled theory of higher-derivative gravity and matter is investigated. A scalar field coupled with a Dirac fermion is taken as the matter sector. Following the idea of induced gravity the Einstein-Hilbert term is generated via dynamical symmetry breaking of scale invariance. The renormalisation group flows are computed and one-loop RG improved effective potential of scalar is calculated. The scalar field develops a new minimum via the Coleman-Weinberg procedure inducing the Newton constant and masses in the matter sector. The spin-2 problematic ghost and the spin-0 mode of the metric fluctuation get a mass in the broken phase of the theory. The energy dependence of the vacuum expectation value in the RG improved scenario implies a running for the induced parameters. This sets up platform to ask whether it is possible to evade the spin-2 ghost by keeping its mass always above the running energy scale? In broken phase this question is satisfactorily answered for a large domain of coupling parameter space where the ghost is evaded. The spin-0 mode can be made physically realisable or not depending upon the choice of the initial parameters. The induced Newton constant is seen to vanish in the ultraviolet case. By properly choosing parameters it is possible to make the matter fields physically unrealisable. (orig.)

  17. Eye changes induced by radium

    International Nuclear Information System (INIS)

    Taylor, G.N.; Lloyd, R.D.; Shabestari, Lorraine; Angus, Walter; Muggenburg, B.A.

    1989-01-01

    This report presents some features of the radium induced eye syndrome observed in beagles, including the prominence of intraocular pigmentary lesions and compares these with the results of rodent studies (Onychomys leucogaster) featuring a heavily pigmented uvea, and with the radiation syndrome reported in humans. (author)

  18. On condensation-induced waves

    NARCIS (Netherlands)

    Cheng, W.; Luo, X.; Dongen, van M.E.H.

    2010-01-01

    Complex wave patterns caused by unsteady heat release due to cloud formation in confined compressible flows are discussed. Two detailed numerical studies of condensation-induced waves are carried out. First, the response of a flow of nitrogen in a slender Laval nozzle to a sudden addition of water

  19. Hydralazine-induced constrictive pericarditis

    NARCIS (Netherlands)

    Franssen, CFC; ElGamal, MIH; Gans, ROB; Hoorntje, SJ

    A 59-year-old man was diagnosed as having constrictive pericarditis 17 months after a typical hydralazine-induced autoimmune syndrome, This late complication of hydralazine has been reported only once. Ten years later the patient was found to have anti-neutrophil cytoplasmic antibodies directed

  20. SPS Ion Induced Desorption Experiment

    CERN Multimedia

    Maximilien Brice

    2003-01-01

    This experiment will give a study about the induced desorption from heavy ion (Indium ion run from week 45 in SPS T4-H8 area) impacting LHC type graphite collimator. 4 different samples are located in the 4 chambers 90° one to each other: pure graphite, graphite with copper coating, graphite with NEG coating, 316LN stainless steal (reference).

  1. Food-Induced Acute Pancreatitis.

    Science.gov (United States)

    Manohar, Murli; Verma, Alok K; Upparahalli Venkateshaiah, Sathisha; Goyal, Hemant; Mishra, Anil

    2017-12-01

    Food allergy, a commonly increasing problem worldwide, defined as an adverse immune response to food. A variety of immune-related effector cells such as mast cells, eosinophils, neutrophils, and T cells are involved in food-related allergic responses categorized as IgE mediated, non-IgE mediated, and mixed (IgE and non-IgE) depending upon underlying immunological mechanisms. The dietary antigens mainly target the gastrointestinal tract including pancreas that gets inflamed due to food allergy and leads acute pancreatitis. Reports indicate several food proteins induce pancreatitis; however, detailed underlying mechanism of food-induced pancreatitis is unexplored. The aim of the review is to understand and update the current scenario of food-induced pancreatitis. A comprehensive literature search of relevant research articles has been performed through PubMed, and articles were chosen based on their relevance to food allergen-mediated pancreatitis. Several cases in the literature indicate that acute pancreatitis has been provoked after the consumption of mustard, milk, egg, banana, fish, and kiwi fruits. Food-induced pancreatitis is an ignored and unexplored area of research. The review highlights the significance of food in the development of pancreatitis and draws the attention of physicians and scientists to consider food allergies as a possible cause for initiation of pancreatitis pathogenesis.

  2. Local Anesthetic-Induced Neurotoxicity

    NARCIS (Netherlands)

    Verlinde, Mark; Hollmann, Markus W.; Stevens, Markus F.; Hermanns, Henning; Werdehausen, Robert; Lirk, Philipp

    2016-01-01

    This review summarizes current knowledge concerning incidence, risk factors, and mechanisms of perioperative nerve injury, with focus on local anesthetic-induced neurotoxicity. Perioperative nerve injury is a complex phenomenon and can be caused by a number of clinical factors. Anesthetic risk

  3. Ventilator and viral induced inflammation

    NARCIS (Netherlands)

    Hennus, M.P.

    2013-01-01

    This thesis expands current knowledge on ventilator induced lung injury and provides insights on the immunological effects of mechanical ventilation during viral respiratory infections. The experimental studies in the first part of this thesis improve our understanding of how mechanical ventilation

  4. UV-induced skin damage

    International Nuclear Information System (INIS)

    Ichihashi, M.; Ueda, M.; Budiyanto, A.; Bito, T.; Oka, M.; Fukunaga, M.; Tsuru, K.; Horikawa, T.

    2003-01-01

    Solar radiation induces acute and chronic reactions in human and animal skin. Chronic repeated exposures are the primary cause of benign and malignant skin tumors, including malignant melanoma. Among types of solar radiation, ultraviolet B (290-320 nm) radiation is highly mutagenic and carcinogenic in animal experiments compared to ultraviolet A (320-400 nm) radiation. Epidemiological studies suggest that solar UV radiation is responsible for skin tumor development via gene mutations and immunosuppression, and possibly for photoaging. In this review, recent understanding of DNA damage caused by direct UV radiation and by indirect stress via reactive oxygen species (ROS) and DNA repair mechanisms, particularly nucleotide excision repair of human cells, are discussed. In addition, mutations induced by solar UV radiation in p53, ras and patched genes of non-melanoma skin cancer cells, and the role of ROS as both a promoter in UV-carcinogenesis and an inducer of UV-apoptosis, are described based primarily on the findings reported during the last decade. Furthermore, the effect of UV on immunological reaction in the skin is discussed. Finally, possible prevention of UV-induced skin cancer by feeding or topical use of antioxidants, such as polyphenols, vitamin C, and vitamin E, is discussed

  5. Spaceflight-Induced Intracranial Hypertension.

    Science.gov (United States)

    Michael, Alex P; Marshall-Bowman, Karina

    2015-06-01

    Although once a widely speculated about and largely theoretical topic, spaceflight-induced intracranial hypertension has gained acceptance as a distinct clinical phenomenon, yet the underlying physiological mechanisms are still poorly understood. In the past, many terms were used to describe the symptoms of malaise, nausea, vomiting, and vertigo, though longer duration spaceflights have increased the prevalence of overlapping symptoms of headache and visual disturbance. Spaceflight-induced visual pathology is thought to be a manifestation of increased intracranial pressure (ICP) because of its similar presentation to cases of known intracranial hypertension on Earth as well as the documentation of increased ICP by lumbar puncture in symptomatic astronauts upon return to gravity. The most likely mechanisms of spaceflight-induced increased ICP include a cephalad shift of body fluids, venous outflow obstruction, blood-brain barrier breakdown, and disruption to CSF flow. The relative contribution of increased ICP to the symptoms experienced during spaceflight is currently unknown, though other factors recently posited to contribute include local effects on ocular structures, individual differences in metabolism, and the vasodilator effects of carbon dioxide. This review article attempts to consolidate the literature regarding spaceflight-induced intracranial hypertension and distinguish it from other pathologies with similar symptomatology. It discusses the proposed physiological causes and the pathological manifestations of increased ICP in the spaceflight environment and provides considerations for future long-term space travel. In the future, it will be critical to develop countermeasures so that astronauts can participate at their peak potential and return safely to Earth.

  6. Isolating highly connected induced subgraphs

    DEFF Research Database (Denmark)

    Penev, Irena; Thomasse, Stephan; Trotignon, Nicolas

    2016-01-01

    We prove that any graph G of minimum degree greater than 2k(2) - 1 has a (k + 1)-connected induced subgraph H such that the number of vertices of H that have neighbors outside of H is at most 2k(2) - 1. This generalizes a classical result of Mader, which states that a high minimum degree implies ...

  7. Ultrasound-induced radical polymerization

    NARCIS (Netherlands)

    Kuijpers, M.W.A.; Kemmere, M.F.; Keurentjes, J.T.F.

    2004-01-01

    Sonochemistry comprises all chemical effects that are induced by ultrasound. Most of these effects are caused by cavitations, ie, the collapse of microscopic bubbles in a liquid. The chemical effects of ultrasound include the formation of radicals and the enhancement of reaction rates at ambient

  8. Transdermal hyoscine induced unilateral mydriasis.

    LENUS (Irish Health Repository)

    Hannon, Breffni

    2012-03-20

    The authors present a case of unilateral mydriasis in a teenager prescribed transdermal hyoscine hydrobromide (scopolamine) for chemotherapy induced nausea and vomiting. The authors discuss the ocular side-effects associated with this particular drug and delivery system and the potential use of transdermal hyoscine as an antiemetic agent in this group.

  9. Late onset startle induced tics

    NARCIS (Netherlands)

    Tijssen, MAJ; Brown, P; Morris, HR; Lees, A

    1999-01-01

    Three cases of late onset Gilles de la Tourette's syndrome are presented. The motor ties were mainly induced by an unexpected startling stimulus, but the startle reflex was not exaggerated. The ties developed after physical trauma or a period of undue emotional stress. Reflex ties may occur in

  10. Late onset startle induced tics

    NARCIS (Netherlands)

    Tijssen, M. A.; Brown, P.; Morris, H. R.; Lees, A.

    1999-01-01

    Three cases of late onset Gilles de la Tourette's syndrome are presented. The motor tics were mainly induced by an unexpected startling stimulus, but the startle reflex was not exaggerated. The tics developed after physical trauma or a period of undue emotional stress. Reflex tics may occur in

  11. Visualization of induced electric fields

    NARCIS (Netherlands)

    Deursen, van A.P.J.

    2005-01-01

    A cylindrical electrolytic tank between a set of Helmholtz coils provides a classroom demonstration of induced, nonconservative electric fields. The field strength is measured by a sensor consisting of a pair of tiny spheres immersed in the liquid. The sensor signal depends on position, frequency,

  12. Lithium-induced downbeat nystagmus.

    Science.gov (United States)

    Schein, Flora; Manoli, Pierre; Cathébras, Pascal

    2017-09-01

    We report the case of a 76-year old lady under lithium carbonate for a bipolar disorder who presented with a suspected optic neuritis. A typical lithium-induced downbeat nystagmus was observed. Discontinuation of lithium therapy resulted in frank improvement in visual acuity and disappearance of the nystagmus.

  13. Arthrogenicity of type II collagen monoclonal antibodies associated with complement activation and antigen affinity.

    Science.gov (United States)

    Koobkokkruad, Thongchai; Kadotani, Tatsuya; Hutamekalin, Pilaiwanwadee; Mizutani, Nobuaki; Yoshino, Shin

    2011-11-04

    The collagen antibody-induced arthritis (CAIA) model, which employs a cocktail of monoclonal antibodies (mAbs) to type II collagen (CII), has been widely used for studying the pathogenesis of autoimmune arthritis. In this model, not all mAbs to CII are capable of inducing arthritis because one of the initial events is the formation of collagen-antibody immune complexes on the cartilage surface or in the synovium, and subsequent activation of the complement by the complexes induces arthritis, suggesting that a combination of mAbs showing strong ability to bind mouse CII and activate the complement may effectively induce arthritis in mice. In the present study, we examined the relationship between the induction of arthritis by the combination of IgG2a (CII-6 and C2A-12), IgG2b (CII-3, C2B-14 and C2B-16) and IgM (CM-5) subclones of monoclonal antibodies (mAb) of anti-bovine or chicken CII and the ability of mAbs to activate complement and bind mouse CII. DBA/1J mice were injected with several combinations of mAbs followed by lipopolysaccharide. Furthermore, the ability of mAbs to activate the complement and bind mouse CII was examined by ELISA. First, DBA/1J mice were injected with the combined 4 mAbs (CII-3, CII-6, C2B-14, and CM-5) followed by lipopolysaccharide, resulting in moderate arthritis. Excluding one of the mAbs, i.e., using only CII-3, CII-6, and C2B-14, induced greater inflammation of the joints. Next, adding C2A-12 but not C2B-16 to these 3 mAbs produced more severe arthritis. A combination of five clones, consisting of all 5 mAbs, was less effective. Histologically, mice given the newly developed 4-clone cocktail had marked proliferation of synovial tissues, massive infiltration by inflammatory cells, and severe destruction of cartilage and bone. Furthermore, 4 of the 6 clones (CII-3, CII-6, C2B-14, and C2A-12) showed not only a strong cross-reaction with mouse CII but also marked activation of the complement in vitro. The combination of 4 mAbs showing

  14. Arthrogenicity of type II collagen monoclonal antibodies associated with complement activation and antigen affinity

    Directory of Open Access Journals (Sweden)

    Mizutani Nobuaki

    2011-11-01

    Full Text Available Abstract Background The collagen antibody-induced arthritis (CAIA model, which employs a cocktail of monoclonal antibodies (mAbs to type II collagen (CII, has been widely used for studying the pathogenesis of autoimmune arthritis. In this model, not all mAbs to CII are capable of inducing arthritis because one of the initial events is the formation of collagen-antibody immune complexes on the cartilage surface or in the synovium, and subsequent activation of the complement by the complexes induces arthritis, suggesting that a combination of mAbs showing strong ability to bind mouse CII and activate the complement may effectively induce arthritis in mice. In the present study, we examined the relationship between the induction of arthritis by the combination of IgG2a (CII-6 and C2A-12, IgG2b (CII-3, C2B-14 and C2B-16 and IgM (CM-5 subclones of monoclonal antibodies (mAb of anti-bovine or chicken CII and the ability of mAbs to activate complement and bind mouse CII. Methods DBA/1J mice were injected with several combinations of mAbs followed by lipopolysaccharide. Furthermore, the ability of mAbs to activate the complement and bind mouse CII was examined by ELISA. Results First, DBA/1J mice were injected with the combined 4 mAbs (CII-3, CII-6, C2B-14, and CM-5 followed by lipopolysaccharide, resulting in moderate arthritis. Excluding one of the mAbs, i.e., using only CII-3, CII-6, and C2B-14, induced greater inflammation of the joints. Next, adding C2A-12 but not C2B-16 to these 3 mAbs produced more severe arthritis. A combination of five clones, consisting of all 5 mAbs, was less effective. Histologically, mice given the newly developed 4-clone cocktail had marked proliferation of synovial tissues, massive infiltration by inflammatory cells, and severe destruction of cartilage and bone. Furthermore, 4 of the 6 clones (CII-3, CII-6, C2B-14, and C2A-12 showed not only a strong cross-reaction with mouse CII but also marked activation of the

  15. Characteristics of storms driving wave-induced seafloor mobility on the U.S. East Coast continental shelf

    Science.gov (United States)

    Dalyander, P. Soupy; Butman, Bradford

    2015-01-01

    This study investigates the relationship between spatial and temporal patterns of wave-driven sediment mobility events on the U.S. East Coast continental shelf and the characteristics of the storms responsible for them. Mobility events, defined as seafloor wave stress exceedance of the critical stress of 0.35 mm diameter sand (0.2160 Pa) for 12 or more hours, were identified from surface wave observations at National Data Buoy Center buoys in the Middle Atlantic Bight (MAB) and South Atlantic Bight (SAB) over the period of 1997-2007. In water depths ranging from 36-48 m, there were 4-9 mobility events/year of 1-2 days duration. Integrated wave stress during events (IWAVES) was used as a combined metric of wave-driven mobility intensity and duration. In the MAB, over 67% of IWAVES was caused by extratropical storms, while in the SAB, greater than 66% of IWAVES was caused by tropical storms. On average, mobility events were caused by waves generated by storms located 800+ km away. Far-field hurricanes generated swell 2-4 days before the waves caused mobility on the shelf. Throughout most of the SAB, mobility events were driven by storms to the south, east, and west. In the MAB and near Cape Hatteras, winds from more northerly storms and low-pressure extratropical systems in the mid-western U.S. also drove mobility events. Waves generated by storms off the SAB generated mobility events along the entire U.S. East Coast shelf north to Cape Cod, while Cape Hatteras shielded the SAB area from swell originating to the north offshore of the MAB.

  16. Antibody Response to Serpin B13 Induces Adaptive Changes in Mouse Pancreatic Islets and Slows Down the Decline in the Residual Beta Cell Function in Children with Recent Onset of Type 1 Diabetes Mellitus.

    Science.gov (United States)

    Kryvalap, Yury; Lo, Chi-Wen; Manuylova, Ekaterina; Baldzizhar, Raman; Jospe, Nicholas; Czyzyk, Jan

    2016-01-01

    Type 1 diabetes mellitus (T1D) is characterized by a heightened antibody (Ab) response to pancreatic islet self-antigens, which is a biomarker of progressive islet pathology. We recently identified a novel antibody to clade B serpin that reduces islet-associated T cell accumulation and is linked to the delayed onset of T1D. As natural immunity to clade B arises early in life, we hypothesized that it may influence islet development during that time. To test this possibility healthy young Balb/c male mice were injected with serpin B13 mAb or IgG control and examined for the number and cellularity of pancreatic islets by immunofluorescence and FACS. Beta cell proliferation was assessed by measuring nucleotide analog 5-ethynyl-2'-deoxyuridine (5-EdU) incorporation into the DNA and islet Reg gene expression was measured by real time PCR. Human studies involved measuring anti-serpin B13 autoantibodies by Luminex. We found that injecting anti-serpin B13 monoclonal Ab enhanced beta cell proliferation and Reg gene expression, induced the generation of ∼80 pancreatic islets per animal, and ultimately led to increase in the beta cell mass. These findings are relevant to human T1D because our analysis of subjects just diagnosed with T1D revealed an association between baseline anti-serpin activity and slower residual beta cell function decline in the first year after the onset of diabetes. Our findings reveal a new role for the anti-serpin immunological response in promoting adaptive changes in the endocrine pancreas and suggests that enhancement of this response could potentially help impede the progression of T1D in humans. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Fluid injection and induced seismicity

    Science.gov (United States)

    Kendall, Michael; Verdon, James

    2016-04-01

    The link between fluid injection, or extraction, and induced seismicity has been observed in reservoirs for many decades. In fact spatial mapping of low magnitude events is routinely used to estimate a stimulated reservoir volume. However, the link between subsurface fluid injection and larger felt seismicity is less clear and has attracted recent interest with a dramatic increase in earthquakes associated with the disposal of oilfield waste fluids. In a few cases, hydraulic fracturing has also been linked to induced seismicity. Much can be learned from past case-studies of induced seismicity so that we can better understand the risks posed. Here we examine 12 case examples and consider in particular controls on maximum event size, lateral event distributions, and event depths. Our results suggest that injection volume is a better control on maximum magnitude than past, natural seismicity in a region. This might, however, simply reflect the lack of baseline monitoring and/or long-term seismic records in certain regions. To address this in the UK, the British Geological Survey is leading the deployment of monitoring arrays in prospective shale gas areas in Lancashire and Yorkshire. In most cases, seismicity is generally located in close vicinity to the injection site. However, in some cases, the nearest events are up to 5km from the injection point. This gives an indication of the minimum radius of influence of such fluid injection projects. The most distant events are never more than 20km from the injection point, perhaps implying a maximum radius of influence. Some events are located in the target reservoir, but most occur below the injection depth. In fact, most events lie in the crystalline basement underlying the sedimentary rocks. This suggests that induced seismicity may not pose a leakage risk for fluid migration back to the surface, as it does not impact caprock integrity. A useful application for microseismic data is to try and forecast induced seismicity

  18. Radiation-induced thermoacoustic imaging

    International Nuclear Information System (INIS)

    Bowen, T.

    1984-01-01

    This invention provides a new technique for obtaining information non-invasively on the composition and structures of a material or body by detecting radiation-induced thermoacoustic image features. This is accomplished by utilizing the acoustic wave generated by sudden thermal stress. The sudden thermal stress is induced by a pulse of radiation which deposits energy causing a rapid, but very small, rise of temperature (typically, ΔT approximately 10sup(-6) - 10sup(-5) deg C). The radiation may be ionizing radiation, such as high energy electrons, photons (x-rays), neutrons, or other charged particles or it may be non-ionizing radiation, such as R.F. and microwave electromagnetic radiation and ultrasonic radiation. The choice of radiation depends on the nature of the body to be imaged and the type of information desired

  19. Esomeprazole-induced photoallergic dermatitis

    Directory of Open Access Journals (Sweden)

    Shukla A

    2010-01-01

    Full Text Available There are no published case reports of esomeprazole-induced photoallergic dermatitis. We report here a 58-year-old lady with prior history of propylthiouracil and carbimazole-induced photoallergy, who presented with heartburn and dysphagia. She was diagnosed to have erosive esophagitis and was treated with esomeprazole, following which she developed photoallergic dermatitis. It improved on cessation of the drug and did not recur on subsequent treatment with ranitidine. Naranjo score for this adverse drug event was 8, thereby making it a probable adverse drug reaction. This reaction may be due to sulphur moiety, which is common to all these drugs. Physicians must be aware of this possible side-effect, especially in patients with prior history of photoallergy to other drugs.

  20. Prediction of pilot induced oscillations

    Directory of Open Access Journals (Sweden)

    Valentin PANĂ

    2011-03-01

    Full Text Available An important problem in the design of flight-control systems for aircraft under pilotedcontrol is the determination of handling qualities and pilot-induced oscillations (PIO tendencieswhen significant nonlinearities exist in the vehicle description. The paper presents a method to detectpossible pilot-induced oscillations of Category II (with rate and position limiting, a phenomenonusually due to a misadaptation between the pilot and the aircraft response during some tasks in whichtight closed loop control of the aircraft is required from the pilot. For the analysis of Pilot in the LoopOscillations an approach, based on robust stability analysis of a system subject to uncertainparameters, is proposed. In this analysis the nonlinear elements are substituted by linear uncertainparameters. This approach assumes that PIO are characterized by a limit cycle behavior.

  1. Taxane-Induced Peripheral Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Roser Velasco

    2015-04-01

    Full Text Available Taxane-derived agents are chemotherapy drugs widely employed in cancer treatment. Among them, paclitaxel and docetaxel are most commonly administered, but newer formulations are being investigated. Taxane antineoplastic activity is mainly based on the ability of the drugs to promote microtubule assembly, leading to mitotic arrest and apoptosis in cancer cells. Peripheral neurotoxicity is the major non-hematological adverse effect of taxane, often manifested as painful neuropathy experienced during treatment, and it is sometimes irreversible. Unfortunately, taxane-induced neurotoxicity is an uncertainty prior to the initiation of treatment. The present review aims to dissect current knowledge on real incidence, underlying pathophysiology, clinical features and predisposing factors related with the development of taxane-induced neuropathy.

  2. Eye changes induced by radium

    International Nuclear Information System (INIS)

    Taylor, G.N.; Lloyd, R.D.; Shabestari, L.; Angus, W.; Muggenburg, B.A.

    1989-01-01

    Radium-induced intraocular neoplasia has not been reported in people, nor were the intraocular pigmentary changes observed in the beagles described in the dial painters or the radium 226 iatrogenic cases. However, Spiess (1969) has observed a 25% incidence of multiple pigmented naevi in the iris of the radium 224 German cases and Stefani, Spiess and Mays (1986) have noted an abnormal incidence of cataracts in this same group of patients. The reasons for the absence of the much less severe radium-induced eye changes in man as compared to the dog has not been determined. Reference is also made to the authors radium 226 rodent studies with mouse strain onychomys leucogaster. (author)

  3. Molecular mechanisms of induced pluripotency.

    Science.gov (United States)

    Kulcenty, Katarzyna; Wróblewska, Joanna; Mazurek, Sylwia; Liszewska, Ewa; Jaworski, Jacek

    2015-01-01

    Growing knowledge concerning transcriptional control of cellular pluripotency has led to the discovery that the fate of differentiated cells can be reversed, which has resulted in the generation, by means of genetic manipulation, of induced pluripotent stem cells. Overexpression of just four pluripotency-related transcription factors, namely Oct3/4, Sox2, Klf4, and c-Myc (Yamanaka factors, OKSM), in fibroblasts appears sufficient to produce this new cell type. Currently, we know that these factors induce several changes in genetic program of differentiated cells that can be divided in two general phases: the initial one is stochastic, and the subsequent one is highly hierarchical and organised. This review briefly discusses the molecular events leading to induction of pluripotency in response to forced presence of OKSM factors in somatic cells. We also discuss other reprogramming strategies used thus far as well as the advantages and disadvantages of laboratory approaches towards pluripotency induction in different cell types.

  4. CEREBRAL CORTEX DAMAGE INDUCED BY ACUTE ORAL ...

    African Journals Online (AJOL)

    2018-02-28

    Feb 28, 2018 ... This study examines alcohol-induced cerebral cortex damage and the association with oxidative ... alcohol has profound effects on the function ... Chronic use of ..... Alcohol induced brain damage and liver damage in young.

  5. Induced disease resistance signaling in plants

    NARCIS (Netherlands)

    Verhagen, B.W.M.; Loon, L.C. van; Pieterse, C.M.J.

    2006-01-01

    To protect themselves from disease, plants have evolved sophisticated inducible defense mechanisms in which the signal molecules salicylic acid, jasmonic acid and ethylene often play crucial roles. Elucidation of signaling pathways controlling induced disease resistance is a major objective in

  6. Inducing Lactation: Breastfeeding for Adoptive Moms

    Science.gov (United States)

    ... Dynamics > Adoption & Foster Care > Inducing Lactation: Breastfeeding for Adoptive Moms Family Life Listen Español Text Size Email Print Share Inducing Lactation: Breastfeeding for Adoptive Moms Page Content Article Body A growing number ...

  7. Induced Mutations in Thai Rice

    International Nuclear Information System (INIS)

    Klakhaeng, Kanchana

    2014-01-01

    Rice is the primary source of food for more than half of the world's population. It benefits greatly from technological inputs in the area of breeding such as induced mutation. Induced mutation can produce mutants with significant improvement in plant type, maturity, yields and protein ratio when compared to the parent. These improved traits enable the mutants to fit into farming systems with either shorter or longer growing seasons. Three induced mutant rice varieties, including RD6, RD10 and RD15, are well accepted by farmers and consumers in Thailand. RD6 and RD15 were aromatic, photosensitive varieties which were derived from KDML105 by acute irradiation of 20 and 15 kilorad gamma ray, respectively. After induced mutation, pedigree selection was applied. RD6 showed drought tolerance and also good grain quality including softness and good aroma with a higher average yield than the famous glutinous variety, San-Pah-Tong. Additionally, it was resistant to blast and brown spot diseases with an average yield of 4.19 tons/ha. RD15 showed drought tolerance and resistance to brown spot disease with the highest yield of 3.5 tons/ha. These two mutant varieties are currently the most famous aromatic rice varieties in Thailand. On the other hand, RD10 is a glutinous, photoperiod insensitive rice variety which was derived from RD1 by irradiation of 1 kilorad fast neutrons. RD10 showed good grain quality such as softness and stickiness with the yield of 4.25 tons/ha. As an on-going project, recommended rice varieties were irradiated with electron beam for anaerobic germination ability, submergence tolerance, stagnant-flood tolerance and also internode elongation.

  8. Abacavir-induced liver toxicity

    Directory of Open Access Journals (Sweden)

    Maria Diletta Pezzani

    2016-09-01

    Full Text Available Abacavir-induced liver toxicity is a rare event almost exclusively occurring in HLA B*5701-positive patients. Herein, we report one case of abnormal liver function tests occurring in a young HLA B*5701-negative woman on a stable nevirapine-based regimen with no history of liver problems or alcohol abuse after switching to abacavir from tenofovir. We also investigated the reasons for abacavir discontinuation in a cohort of patients treated with abacavir-lamivudine-nevirapine.

  9. Cough-induced rib fractures.

    Science.gov (United States)

    Hanak, Viktor; Hartman, Thomas E; Ryu, Jay H

    2005-07-01

    To define the demographic, clinical, and radiological features of patients with cough-induced rib fractures and to assess potential risk factors. For this retrospective, single-center study, we identified all cases of cough-induced rib fractures diagnosed at the Mayo Clinic in Rochester, Minn, over a 9-year period between January 1, 1996, and January 31, 2005. Bone densitometry data from patients' medical records were analyzed, and T scores were used to classify patients into bone density categories. The mean +/- SD age of the 54 study patients at presentation was 55+/-17 years, and 42 patients (78%) were female. Patients presented with chest wall pain after onset of cough. Rib fracture was associated with chronic cough (> or =3 weeks' duration) in 85% of patients. Rib fractures were documented by chest radiography, rib radiography, computed tomography, or bone scan. Chest radiography had been performed in 52 patients and revealed rib fracture in 30 (58%). There were 112 fractured ribs in 54 patients. One half of patients had more than one fractured rib. Right-sided rib fractures alone were present in 17 patients (26 fractured ribs), left-sided in 23 patients (35 fractured ribs), and bilateral in 14 patients (51 fractured ribs). The most commonly fractured rib on both sides was rib 6. The fractures were most common at the lateral aspect of the rib cage. Bone densitometry was done in 26 patients and revealed osteopenia or osteoporosis in 17 (65%). Cough-induced rib fractures occur primarily in women with chronic cough. Middle ribs along the lateral aspect of the rib cage are affected most commonly. Although reduced bone density is likely a risk factor, cough-induced rib fractures can occur in the presence of normal bone density.

  10. Radiation induced crosslinking of polytetrafluoroethylene

    International Nuclear Information System (INIS)

    Oshima, Akihiro; Tabata, Yoneho; Ikeda, Shigetoshi; Otsuhata, Kazushige; Kudoh, Hisaaki; Seguchi, Tadao.

    1995-01-01

    The Irradiation temperature effect on polytetrafluoroethylene (PTFE) from room temperature to 380degC was investigated by tensile test and thermal analysis. The behavior of tensile properties and changes of crystallinity on irradiation indicated the formation of a network structure in PTFE by radiation induced crosslinking in inert gas in the molten state just above the melting temperature of PTFE (327degC). The crosslinked PTFE showed a much improved radiation resistance in an atmospheric radiation field. (author)

  11. Peculiarities of radiation induced craniopharyngioma

    Energy Technology Data Exchange (ETDEWEB)

    Sataev, N.M. (Uzbekskij Nauchno-Issledovatel' skij Inst. Onkologii i Radiologii, Tashkent (USSR))

    1982-03-01

    Due to intracranial implantation of a radiosource in rabbit brain craniopharyngioma appeared. Its specific feature is grandular differentiation of embryonal epithelium of residuals of hypophysical (craniopharyngial) passage and the presence of focuses of blood vessel tumor degeneration of hemangioma type in its stroma. It is suggested that radiation craniopharyngioma is developed along the way of epigenetic changes of cellular elements of embryonal epithelium induced by radiation.

  12. Peculiarities of radiation induced craniopharyngioma

    International Nuclear Information System (INIS)

    Sataev, N.M.

    1982-01-01

    Due to intracranial implantation of a radiosource in rabbit brain craniopharyngioma appeared. Its specific feature is grandular differentiation of embryonal epithelium of residuals of hypophysical (craniopharyngial) passage and the presence of focuses of blood vessel tumor degeneration of hemangioma type in its stroma. It is suggested that radiation craniopharyngioma is developed along the way of epigenetic changes of cellular elements of embryonal epithelium induced by radiation

  13. MRI-induced retrocalcaneal bursitis

    International Nuclear Information System (INIS)

    Tol, J.L.; Dijk, C.N. van; Maas, M.

    1999-01-01

    This case report describes a patient with acute retrocalcaneal bursitis, which developed after MRI examination of the ankle. The sagittal T2*-weighted gradient echo sequence revealed an extensive susceptibility artifact in the area surrounding the Achilles tendon near its insertion at the os calcis. This artifact was caused by postsurgical metallic particles. We postulate that these particles were mechanically stimulated by the magnetic field and induced the inflammatory response. (orig.)

  14. MRI-induced retrocalcaneal bursitis

    Energy Technology Data Exchange (ETDEWEB)

    Tol, J.L.; Dijk, C.N. van [Dept. of Orthopaedic Surgery, University of Amsterdam (Netherlands); Maas, M. [Dept. of Radiology, University of Amsterdam (Netherlands)

    1999-10-01

    This case report describes a patient with acute retrocalcaneal bursitis, which developed after MRI examination of the ankle. The sagittal T2*-weighted gradient echo sequence revealed an extensive susceptibility artifact in the area surrounding the Achilles tendon near its insertion at the os calcis. This artifact was caused by postsurgical metallic particles. We postulate that these particles were mechanically stimulated by the magnetic field and induced the inflammatory response. (orig.)

  15. Teriparatide Induced Delayed Persistent Hypercalcemia

    Directory of Open Access Journals (Sweden)

    Nirosshan Thiruchelvam

    2014-01-01

    Full Text Available Teriparatide, a recombinant PTH, is an anabolic treatment for osteoporosis that increases bone density. Transient hypercalcemia is a reported side effect of teriparatide that is seen few hours following administration of teriparatide and resolves usually within 16 hours of drug administration. Persistent hypercalcemia, although not observed in clinical trials, is rarely reported. The current case describes a rare complication of teriparatide induced delayed persistent hypercalcemia.

  16. Laser-induced multiphoton transitions

    International Nuclear Information System (INIS)

    Stenholm, S.

    1978-06-01

    Laser induced multiphoton processes are reviewed. The effects of strong fields on atoms are discussed. The perturbation treatment is presented and also its generalization to treat intermediate resonances. The influence of atomic coherence is discussed heuristically and the relation between quantal and classical descriptions of the field is elucidated by reference to the dressed atom description. Atomic ionization experiments are reviewed and the present understanding of multiphoton dissociation of molecules is explained. Finally some prospects for the future are discussed. (author)

  17. Drug-induced liver injury

    DEFF Research Database (Denmark)

    Nielsen, Mille Bækdal; Ytting, Henriette; Skalshøi Kjær, Mette

    2017-01-01

    OBJECTIVE: The idiosyncratic subtype of drug-induced liver injury (DILI) is a rare reaction to medical treatment that in severe cases can lead to acute liver failure and death. The aim of this study was to describe the presentation and outcome of DILI and to identify potential predictive factors...... that DILI may be severe and run a fatal course, and that bilirubin and INR levels may predict poor outcome....

  18. Risperidone-induced reversible neutropenia.

    Science.gov (United States)

    Kattalai Kailasam, Vasanth; Chima, Victoria; Nnamdi, Uchechukwu; Sharma, Kavita; Shah, Kairav

    2017-01-01

    This case report presents a 44-year-old man with a history of schizophrenia who developed neutropenia on risperidone therapy. The patient's laboratory reports showed a gradual decline of leukocytes and neutrophils after resolution and rechallenging. This was reversed with the discontinuation of risperidone and by switching to olanzapine. In this case report, we also discuss the updated evidence base for management of risperidone-induced neutropenia.

  19. Induced draught circular cooling tower

    International Nuclear Information System (INIS)

    Blanquet, J.C.

    1980-01-01

    Induced draught atmospheric cooling towers are described, to wit those in which the circulation is by power fans. This technique with fans grouped together in the centre enables a single tower to be used and provides an excellent integration of the steam wreath into the atmosphere. This type of cooling tower has been chosen for fitting out two 900 MW units of the Chinon power station in France [fr

  20. Secondary pseudomyopia induced by amisulpride.

    Science.gov (United States)

    Stratos, Aimilianos A; Peponis, Vasileios G; Portaliou, Dimitra M; Stroubini, Theodora E; Skouriotis, Sotirios; Kymionis, George D

    2011-11-01

    To report a case of pseudomyopia induced by antipsychotic drug administration. A 30-year-old woman was referred to our ophthalmology department complaining of blurred vision, especially at distance, in both eyes. The patient had been prescribed antipsychotic drugs (haloperidol and biperiden) as treatment for her schizophrenic symptoms and had recently undergone a change of treatment to amisulpride. She had a manifest refraction of -4.00/-1.00 × 180 in the OD and -3.75/-1.25 × 175 in the OS whereas her cycloplegic refraction was -1.75/-1.00 × 180 in the OD and -1.00/-1.25 × 175 in the OS, respectively. A diagnosis of likely drug-induced pseudomyopia was made. Therefore, the patient was advised to visit her psychiatrist, who added an extra 2 mg of biperiden, an anticholinergic agent, to the pre-existing amisulpride treatment, achieving a cessation of the visual symptoms a few days later. Pseudomyopia can be induced by the antipsychotic drug amisulpride. Additional treatment with anticholinergic agents can be used to eliminate this side effect.

  1. Radiation-induced chromosomal instability

    International Nuclear Information System (INIS)

    Ritter, S.

    1999-01-01

    Recent studies on radiation-induced chromosomal instability in the progeny of exposed mammalian cells were briefly described as well as other related studies. For the analysis of chromosomal damage in clones, cells were seeded directly after exposure in cell well-dish to form single cell clones and post-irradiation chromosome aberrations were scored. Both exposure to isoeffective doses of X-ray or 270 MeV/u C-ions (13 keV/μm) increased the number of clones with abnormal karyotype and the increase was similar for X-ray and for C-ions. Meanwhile, in the progeny of cells for mass cultures, there was no indication of a delayed expression of chromosomal damage up to 40 population doublings after the exposure. A high number of aberrant cells were only observed directly after exposure to 10.7 MeV/u O-ions, i.e. in the first cycle cells and decreased with subsequent cell divisions. The reason for these differences in the radiation-induced chromosomal instability between clonal isolates and mass culture has not been clarified. Recent studies indicated that genomic instability occurs at a high frequency in the progeny of cells irradiated with both sparsely and densely ionizing radiation. Such genomic instability is thought likely to increase the risk of carcinogenesis, but more data are required for a well understanding of the health risks resulting from radiation-induced delayed instability. (M.N.)

  2. Induced mutation of Dendrobium orchid

    International Nuclear Information System (INIS)

    Sakinah Ariffin; Mohd Nazir Basiran

    2000-01-01

    Dendrobiiim orchids serve as the main orchid cut flower export of Malaysia. The wide range of colour and forms presently available in the market are obtained through hybridisation. Induced mutation breeding program was initiated on a commercial variety Dendrobium 'Sonia Kai' to explore the possibilities of obtaining new colour and forms. Matured seeds from self pollination were cultured and irradiated at 35 Gy at the protocorm-like bodies (PLBS) stage. Selection of induced mutations was done after the first flowering of the plants regenerated from the irradiated protocorms. Results showed changes in flower colour, shape and size. Most of these chances are expressed in different combinations in the petals, sepals and lip of the flowers. Thus, resulting. in a very wide spectrum of mutations. Some of these chances are not stable. To date, mutants that showed stable characteristics changes are grouped into 11 categories based on flower colour and form. These results show that the combination of its vitro technique and induced mutation can be applied in orchid breeding to produce new interesting and attractive variety for the market

  3. [Secondary osteoporosis induced by anticoagulants?].

    Science.gov (United States)

    Riess, H; Loew, A; Himmelreich, G

    2001-07-01

    Generalized osteoporosis is a result of different causes and pathogenic mechanisms, which often combine forces to become clinically relevant. Among the different exogenic factors, drugs play an important role, frequently in connection with other factors such as immobilization or pregnancy. It has been suggested that anticoagulation therapy with heparins or coumarins may induce osteoporotic changes or enhance the development of osteoporosis for other reasons. According to in vitro experiments, preclinical trials, and clinical investigations, it seems reasonable to assume that heparins induce increased bone loss in a time- and dose-related manner. Low-molecular-weight heparins most likely have less effect on bone turnover when compared to unfractionated heparin. Oral anticoagulation therapy with vitamin K-antagonists is believed to have a weak effect on induction of osteoporosis, but clinical studies are contradictory. In spite of the fact that a relevant effect of these drugs on the induction of osteoporosis is questionable, it must be taken into consideration that anticoagulant drugs may enhance the negative effects on bone density of other risk factors capable of inducing osteoporosis such as immobilization, pregnancy, or endocrinological disorders.

  4. Radiation-induced heart injury

    International Nuclear Information System (INIS)

    Suzuki, Yoshihiko; Niibe, Hideo

    1975-01-01

    In order to identify radiation-induced heart injury and to differentiate it from heart disease, an attempt was made to clarify post-irradiation heart injury by investigating the histological changes which occur during the internal between the irradiation and the time of demonstrable histological changes. A study was made of 83 autopsies in which most of the primary neoplasms were breast cancers, lung cancers and mediastinal tumors. In 43 of these autopsies the heart had been irradiated. Sixty eight dd-strain mice were also used for microautoradiographic study. Histological changes in the heart were observed in 27 of the 43 cases receiving irradiation. The limit of the tolerance dose to the heart for indicating histological changes was 1220 ret in humans. The latent period without histological changes was 2.7 months after initiation of radiation therapy. Greater heart injury was observed after re-irradiation or after the combined therapy of radiation and chemotherapy especially mitomycin (MMC). The histological findings after treatment with MMC were similar to those of radiation-induced heart injury. Results of the study indicate that the damage is secondary to radiation-induced changes of the vascula connective tissue. (Evans, G.)

  5. Could visual neglect induce amblyopia?

    Science.gov (United States)

    Bier, J C; Vokaer, M; Fery, P; Garbusinski, J; Van Campenhoudt, G; Blecic, S A; Bartholomé, E J

    2004-12-01

    Oculomotor nerve disease is a common cause of diplopia. When strabismus is present, absence of diplopia has to induce the research of either uncovering of visual fields or monocular suppression, amblyopia or blindness. We describe the case of a 41-year-old woman presenting with right oculomotor paresis and left object-centred visual neglect due to a right fronto-parietal haemorrhage expanding to the right peri-mesencephalic cisterna caused by the rupture of a right middle cerebral artery aneurysm. She never complained of diplopia despite binocular vision and progressive recovery of strabismus, excluding uncovering of visual fields. Since all other causes were excluded in this case, we hypothesise that the absence of diplopia was due to the object-centred visual neglect. Partial internal right oculomotor paresis causes an ocular deviation in abduction; the image being perceived deviated contralaterally to the left. Thus, in our case, the neglect of the left image is equivalent to a right monocular functional blindness. However, bell cancellation test clearly worsened when assessed in left monocular vision confirming that eye patching can worsen attentional visual neglect. In conclusion, our case argues for the possibility of a functional monocular blindness induced by visual neglect. We think that in presence of strabismus, absence of diplopia should induce the search for hemispatial visual neglect when supratentorial lesions are suspected.

  6. [Drug-induced oral ulcerations].

    Science.gov (United States)

    Madinier, I; Berry, N; Chichmanian, R M

    2000-06-01

    Different side effects of drugs have been described in the oral cavity, including oral ulcerations. Direct contact between drugs and oral mucosa may induce chemical burn or local hypersensitivity. Less frequently, these drug-induced oral ulcerations are part of a complex reaction with cutaneous or systemic manifestations. Sometimes, one or more oral ulcerations appear as the main side-effect of a drug, or exceptionally as solitary lesions. Solitary oral ulcerations usually appear after few weeks of treatment. In most of cases, these lesions resist to conventional treatments, with a rapid healing following the suppression of the responsible drug. This diagnosis is usually difficult, particularly with patients receiving multiple drug therapy. Besides, special attention must be paid to new drugs. Oral ulcerations following symptoms of burning mouth, metallic taste, dysgueusia or agueusia are strongly suggestive of a pharmacological origin. Most of the molecules able to induce solitary oral ulcerations are commonly prescribed in a) rheumatology: NSAI (diclofenac, flurbiprofen, indomethacin, naproxen), long-term rheumatoid arthritis therapy (azathioprine, methotrexate, penicillamine, gold compounds, tiopronin); b) cardiology: angiotensin-converting-enzyme inhibitors (captopril, enalapril), angiotensin 2-receptor antagonist (losartan), anti-angorous (nicorandil), c) psychiatry: antidepressants (fluoxetine, lithium), d) AIDS therapy (foscarnet, zalcitabine).

  7. Second-order nonlinearity induced transparency.

    Science.gov (United States)

    Zhou, Y H; Zhang, S S; Shen, H Z; Yi, X X

    2017-04-01

    In analogy to electromagnetically induced transparency, optomechanically induced transparency was proposed recently in [Science330, 1520 (2010)SCIEAS0036-807510.1126/science.1195596]. In this Letter, we demonstrate another form of induced transparency enabled by second-order nonlinearity. A practical application of the second-order nonlinearity induced transparency is to measure the second-order nonlinear coefficient. Our scheme might find applications in quantum optics and quantum information processing.

  8. Characterizing wave- and current- induced bottom shear stress: U.S. middle Atlantic continental shelf

    Science.gov (United States)

    Dalyander, P. Soupy; Butman, Bradford; Sherwood, Christopher R.; Signell, Richard P.; Wilkin, John L.

    2013-01-01

    Waves and currents create bottom shear stress, a force at the seabed that influences sediment texture distribution, micro-topography, habitat, and anthropogenic use. This paper presents a methodology for assessing the magnitude, variability, and driving mechanisms of bottom stress and resultant sediment mobility on regional scales using numerical model output. The analysis was applied to the Middle Atlantic Bight (MAB), off the U.S. East Coast, and identified a tidally-dominated shallow region with relatively high stress southeast of Massachusetts over Nantucket Shoals, where sediment mobility thresholds are exceeded over 50% of the time; a coastal band extending offshore to about 30 m water depth dominated by waves, where mobility occurs more than 20% of the time; and a quiescent low stress region southeast of Long Island, approximately coincident with an area of fine-grained sediments called the “Mud Patch”. The regional high in stress and mobility over Nantucket Shoals supports the hypothesis that fine grain sediment winnowed away in this region maintains the Mud Patch to the southwest. The analysis identified waves as the driving mechanism for stress throughout most of the MAB, excluding Nantucket Shoals and sheltered coastal bays where tides dominate; however, the relative dominance of low-frequency events varied regionally, and increased southward toward Cape Hatteras. The correlation between wave stress and local wind stress was lowest in the central MAB, indicating a relatively high contribution of swell to bottom stress in this area, rather than locally generated waves. Accurate prediction of the wave energy spectrum was critical to produce good estimates of bottom shear stress, which was sensitive to energy in the long period waves.

  9. Diffuse Transcranial Electrical Stimulation (DTES)-induced ...

    African Journals Online (AJOL)

    Higher voltages were needed to induce convulsion in pretreated animals than in normal animals. It is therefore suggestive that DTES-induced hypermotility can be used as an animal model for testing drugs that can be of advantage in the management of non convulsive (petit mal) status epilepticus (SE), and DTES induced ...

  10. In vivo antibody-mediated modulation of aminopeptidase A in mouse proximal tubular epithelial cells.

    Science.gov (United States)

    Mentzel, S; Dijkman, H B; van Son, J P; Wetzels, J F; Assmann, K J

    1999-07-01

    Aminopeptidase A (APA) is one of the many renal hydrolases. In mouse kidney, APA is predominantly expressed on the brush borders and sparsely on the basolateral membranes of proximal tubular epithelial cells. However, when large amounts of monoclonal antibodies (MAbs) against APA were injected into mice, we observed strong binding of the MAbs to the basolateral membranes, whereas the MAbs bound only transiently to the brush borders of the proximal tubular epithelial cells. In parallel, APA itself disappeared from the brush borders by both endocytosis and shedding, whereas it was increasingly expressed on the basolateral sides. Using ultrastructural immunohistology, we found no evidence for transcellular transport of endocytosed APA to the basolateral side of the proximal tubular epithelial cells. The absence of transcellular transport was confirmed by experiments in which we used a low dose of the MAbs. Such a low dose did not result in binding of the MAbs to the brush borders and had no effect on the presence of APA in the brush borders of the proximal tubular epithelial cells. In these experiments we still could observe binding of the MAbs to the basolateral membranes in parallel with the local appearance of APA. In addition, treatment of mice with chlorpromazine, a calmodulin antagonist that interferes with cytoskeletal function, largely inhibited the MAb-induced modulation of APA. Our studies suggest that injection of MAbs to APA specifically interrupts the normal intracellular traffic of this enzyme in proximal tubular epithelial cells. This intracellular transport is dependent on the action of cytoskeletal proteins.

  11. Mutations induced by ultraviolet light

    International Nuclear Information System (INIS)

    Pfeifer, Gerd P.; You, Young-Hyun; Besaratinia, Ahmad

    2005-01-01

    The different ultraviolet (UV) wavelength components, UVA (320-400 nm), UVB (280-320 nm), and UVC (200-280 nm), have distinct mutagenic properties. A hallmark of UVC and UVB mutagenesis is the high frequency of transition mutations at dipyrimidine sequences containing cytosine. In human skin cancers, about 35% of all mutations in the p53 gene are transitions at dipyrimidines within the sequence 5'-TCG and 5'-CCG, and these are localized at several mutational hotspots. Since 5'-CG sequences are methylated along the p53 coding sequence in human cells, these mutations may be derived from sunlight-induced pyrimidine dimers forming at sequences that contain 5-methylcytosine. Cyclobutane pyrimidine dimers (CPDs) form preferentially at dipyrimidines containing 5-methylcytosine when cells are irradiated with UVB or sunlight. In order to define the contribution of 5-methylcytosine to sunlight-induced mutations, the lacI and cII transgenes in mouse fibroblasts were used as mutational targets. After 254 nm UVC irradiation, only 6-9% of the base substitutions were at dipyrimidines containing 5-methylcytosine. However, 24-32% of the solar light-induced mutations were at dipyrimidines that contain 5-methylcytosine and most of these mutations were transitions. Thus, CPDs forming preferentially at dipyrimidines with 5-methylcytosine are responsible for a considerable fraction of the mutations induced by sunlight in mammalian cells. Using mouse cell lines harboring photoproduct-specific photolyases and mutational reporter genes, we showed that CPDs (rather than 6-4 photoproducts or other lesions) are responsible for the great majority of UVB-induced mutations. An important component of UVB mutagenesis is the deamination of cytosine and 5-methylcytosine within CPDs. The mutational specificity of long-wave UVA (340-400 nm) is distinct from that of the shorter wavelength UV and is characterized mainly by G to T transversions presumably arising through mechanisms involving oxidized DNA

  12. Statistical Seismology and Induced Seismicity

    Science.gov (United States)

    Tiampo, K. F.; González, P. J.; Kazemian, J.

    2014-12-01

    While seismicity triggered or induced by natural resources production such as mining or water impoundment in large dams has long been recognized, the recent increase in the unconventional production of oil and gas has been linked to rapid rise in seismicity in many places, including central North America (Ellsworth et al., 2012; Ellsworth, 2013). Worldwide, induced events of M~5 have occurred and, although rare, have resulted in both damage and public concern (Horton, 2012; Keranen et al., 2013). In addition, over the past twenty years, the increase in both number and coverage of seismic stations has resulted in an unprecedented ability to precisely record the magnitude and location of large numbers of small magnitude events. The increase in the number and type of seismic sequences available for detailed study has revealed differences in their statistics that previously difficult to quantify. For example, seismic swarms that produce significant numbers of foreshocks as well as aftershocks have been observed in different tectonic settings, including California, Iceland, and the East Pacific Rise (McGuire et al., 2005; Shearer, 2012; Kazemian et al., 2014). Similarly, smaller events have been observed prior to larger induced events in several occurrences from energy production. The field of statistical seismology has long focused on the question of triggering and the mechanisms responsible (Stein et al., 1992; Hill et al., 1993; Steacy et al., 2005; Parsons, 2005; Main et al., 2006). For example, in most cases the associated stress perturbations are much smaller than the earthquake stress drop, suggesting an inherent sensitivity to relatively small stress changes (Nalbant et al., 2005). Induced seismicity provides the opportunity to investigate triggering and, in particular, the differences between long- and short-range triggering. Here we investigate the statistics of induced seismicity sequences from around the world, including central North America and Spain, and

  13. Ion beam induced luminescence: Relevance to radiation induced bystander effects

    Science.gov (United States)

    Ahmad, S. B.; McNeill, F. E.; Byun, S. H.; Prestwich, W. V.; Seymour, C.; Mothersill, C. E.

    2012-10-01

    The aim of this work is quantify the light emitted as a result of charged particle interaction in materials which may be of relevance to radiation induced "bystander effects" studies. We have developed a system which employs single photon counting to measure the light emitted from samples irradiated under vacuum by a charged particle beam. The system uses a fast photomultiplier tube with a peak cathode response at 420 nm. It has been tested in a proof-of-principle experiment using polystyrene targets. Light output, as a result of irradiation, was measured. The luminescence yield appears to have a non-linear behavior with the incident ion fluence: it rises exponentially to an asymptotic value. The target was irradiated with beam energies varying from 1 to 2 MeV and showed saturation at or before an incident fluence rate of 3 × 1013 H+/cm2 s. The average saturation value for the photon output was found to be 40 × 106 cps. Some measurements were performed using filters to study the emission at specific wavelengths. In the case of filtered light measurements, the photon output was found to saturate at 28 × 103, 10 × 106, and 35 × 106 cps for wavelengths of 280 ± 5 nm, 320 ± 5 nm and 340 ± 5 nm respectively. The light output reaches a maximum value because of damage induced in the polymer. Our measurements indicate a "damage cross section" of the order of 10-14 cm2. The average radiant intensity was found to increase at wavelengths of 280 and 320 nm when the proton energy was increased. This was not found to occur at 340 nm. In conclusion, the light emission at specific wavelengths was found to depend upon the incident proton fluence and the proton energy. The wavelengths of the emitted light measured in this study have significance for the understanding of radiation induced bystander effects.

  14. Sad music induces pleasant emotion.

    Science.gov (United States)

    Kawakami, Ai; Furukawa, Kiyoshi; Katahira, Kentaro; Okanoya, Kazuo

    2013-01-01

    In general, sad music is thought to cause us to experience sadness, which is considered an unpleasant emotion. As a result, the question arises as to why we listen to sad music if it evokes sadness. One possible answer to this question is that we may actually feel positive emotions when we listen to sad music. This suggestion may appear to be counterintuitive; however, in this study, by dividing musical emotion into perceived emotion and felt emotion, we investigated this potential emotional response to music. We hypothesized that felt and perceived emotion may not actually coincide in this respect: sad music would be perceived as sad, but the experience of listening to sad music would evoke positive emotions. A total of 44 participants listened to musical excerpts and provided data on perceived and felt emotions by rating 62 descriptive words or phrases related to emotions on a scale that ranged from 0 (not at all) to 4 (very much). The results revealed that the sad music was perceived to be more tragic, whereas the actual experiences of the participants listening to the sad music induced them to feel more romantic, more blithe, and less tragic emotions than they actually perceived with respect to the same music. Thus, the participants experienced ambivalent emotions when they listened to the sad music. After considering the possible reasons that listeners were induced to experience emotional ambivalence by the sad music, we concluded that the formulation of a new model would be essential for examining the emotions induced by music and that this new model must entertain the possibility that what we experience when listening to music is vicarious emotion.

  15. Sad music induces pleasant emotion

    Science.gov (United States)

    Kawakami, Ai; Furukawa, Kiyoshi; Katahira, Kentaro; Okanoya, Kazuo

    2013-01-01

    In general, sad music is thought to cause us to experience sadness, which is considered an unpleasant emotion. As a result, the question arises as to why we listen to sad music if it evokes sadness. One possible answer to this question is that we may actually feel positive emotions when we listen to sad music. This suggestion may appear to be counterintuitive; however, in this study, by dividing musical emotion into perceived emotion and felt emotion, we investigated this potential emotional response to music. We hypothesized that felt and perceived emotion may not actually coincide in this respect: sad music would be perceived as sad, but the experience of listening to sad music would evoke positive emotions. A total of 44 participants listened to musical excerpts and provided data on perceived and felt emotions by rating 62 descriptive words or phrases related to emotions on a scale that ranged from 0 (not at all) to 4 (very much). The results revealed that the sad music was perceived to be more tragic, whereas the actual experiences of the participants listening to the sad music induced them to feel more romantic, more blithe, and less tragic emotions than they actually perceived with respect to the same music. Thus, the participants experienced ambivalent emotions when they listened to the sad music. After considering the possible reasons that listeners were induced to experience emotional ambivalence by the sad music, we concluded that the formulation of a new model would be essential for examining the emotions induced by music and that this new model must entertain the possibility that what we experience when listening to music is vicarious emotion. PMID:23785342

  16. Arthrogenicity of type II collagen monoclonal antibodies associated with complement activation and antigen affinity

    OpenAIRE

    Koobkokkruad, Thongchai; Kadotani, Tatsuya; Hutamekalin, Pilaiwanwadee; Mizutani, Nobuaki; Yoshino, Shin

    2011-01-01

    Abstract Background The collagen antibody-induced arthritis (CAIA) model, which employs a cocktail of monoclonal antibodies (mAbs) to type II collagen (CII), has been widely used for studying the pathogenesis of autoimmune arthritis. In this model, not all mAbs to CII are capable of inducing arthritis because one of the initial events is the formation of collagen-antibody immune complexes on the cartilage surface or in the synovium, and subsequent activation of the complement by the complexes...

  17. Cetirizine-Induced atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Altuğ Osken

    2016-01-01

    Full Text Available Atrial fibrillation (AF is the most common observed arrhythmia in clinical practice. In the literature, AF events associated with drug induction are available. Cetirizine is a second-generation histamine antagonist used in the treatment of allergies, angioedema, and urticaria. We wish to present an atypical case who took cetirizine medication for relieving symptoms of upper tract respiratory system infection, experienced rapid ventricular response AF and treated successfully. To best of our knowledge, this is the first case of cetirizine-induced AF.

  18. Current-Induced Membrane Discharge

    DEFF Research Database (Denmark)

    Andersen, Mathias Bækbo; van Soestbergen, M.; Mani, A.

    2012-01-01

    . Salt depletion leads to a large electric field resulting in a local pH shift within the membrane with the effect that the membrane discharges and loses its ion selectivity. Since salt co-ions, H+ ions, and OH- ions contribute to OLC, CIMD interferes with electrodialysis (salt counterion removal...... neglects chemical effects and remains to be quantitatively tested. Here, we show that charge regulation and water self-ionization can lead to OLC by "current-induced membrane discharge'' (CIMD), even in the absence of fluid flow, in ion-exchange membranes much thicker than the local Debye screening length...

  19. Adsorption-induced step formation

    DEFF Research Database (Denmark)

    Thostrup, P.; Christoffersen, Ebbe; Lorensen, Henrik Qvist

    2001-01-01

    Through an interplay between density functional calculations, Monte Carlo simulations and scanning tunneling microscopy experiments, we show that an intermediate coverage of CO on the Pt(110) surface gives rise to a new rough equilibrium structure with more than 50% step atoms. CO is shown to bind...... so strongly to low-coordinated Pt atoms that it can break Pt-Pt bonds and spontaneously form steps on the surface. It is argued that adsorption-induced step formation may be a general effect, in particular at high gas pressures and temperatures....

  20. Psychological sequelae of induced abortion.

    Science.gov (United States)

    Romans-Clarkson, S E

    1989-12-01

    This article reviews the scientific literature on the psychological sequelae of induced abortion. The methodology and results of studies carried out over the last twenty-two years are examined critically. The unanimous consensus is that abortion does not cause deleterious psychological effects. Women most likely to show subsequent problems are those who were pressured into the operation against their own wishes, either by relatives or because their pregnancy had medical or foetal contraindications. Legislation which restricts abortion causes problems for women with unwanted pregnancies and their doctors. It is also unjust, as it adversely most affects lower socio-economic class women.

  1. Plasma generation induced by triboelectrification

    DEFF Research Database (Denmark)

    Kusano, Yukihiro; Singh, Shailendra Vikram; Michelsen, Poul

    2009-01-01

    A gas discharge plasma can be induced by triboelectrification around a sliding contact. The detailed physical mechanism of triboelectrification is unknown, but an empirical classification scheme can be referred to in practice. It is reported that intense ultra-violet emission from a plasma...... is observed adjacent to the sliding contact, of which the location has a gap ranging from approximately 1 μm to 11 μm. When the gap is short enough, a theory predicts that the breakdown voltage can monotonically decrease with a decrease in the gap. However, when the gap is comparable to electron’s mean free...

  2. Clozapine-induced late leukopenia.

    LENUS (Irish Health Repository)

    Latif, Z

    2012-03-01

    A patient with a 28-year history of schizophrenia was treated with a wide range of antipsychotic medications since diagnosis. She had experienced no clinically significant symptomatic relief until she commenced treatment on clozapine. Her psychotic symptoms, self care, and general sense of well-being improved significantly. After 6 years of successful treatment, she developed leukopenia and clozapine was discontinued. The following issues will be discussed in the article: rechallenge with clozapine following leukopenia during previous therapy and the choice of and haematological monitoring needs with other antipsychotic medications after clozapine-induced blood dyscrasia.

  3. CRBRP flow induced vibration program

    Energy Technology Data Exchange (ETDEWEB)

    Novendstern, E H [Westinghouse Advanced Reactor Division, Madison, PA (United States); Grochowski, F A; Yang, T M [General Electric Co., Fast Breeder Reactor Department, Sunnyvale, CA (United States); Ryan, J A; Mulcahy, T M

    1977-12-01

    The program to assure the structural adequacy of Clinch River Breeder Reactor (CRBRP) components during its planned 30 years of operation is described. The program includes (1) an assessment of reactor components relative to their susceptibility to FIV, (2) designing to minimize component excitation due to Fluid induced vibrations (FIV), (3) scale model tests to measure structural response during simulated operating conditions and (4) preoperational tests. An overview of the CRBRP test program is described. Additionally, details of scale model testing of reactor internals and the steam generator is described in more detail. (author)

  4. Drug-induced peripheral neuropathy

    DEFF Research Database (Denmark)

    Vilholm, Ole Jakob; Christensen, Alex Alban; Zedan, Ahmed

    2014-01-01

    Peripheral neuropathy can be caused by medication, and various descriptions have been applied for this condition. In this MiniReview, the term 'drug-induced peripheral neuropathy' (DIPN) is used with the suggested definition: Damage to nerves of the peripheral nervous system caused by a chemical...... substance used in the treatment, cure, prevention or diagnosis of a disease. Optic neuropathy is included in this definition. A distinction between DIPN and other aetiologies of peripheral neuropathy is often quite difficult and thus, the aim of this MiniReview is to discuss the major agents associated...

  5. Basic reactions induced by radiation

    International Nuclear Information System (INIS)

    Charlesby, A.

    1980-01-01

    This paper summarises some of the basic reactions resulting from exposure to high energy radiation. In the initial stages energy is absorbed, but not necessarily at random, giving radical and ion species which may then react to promote the final chemical change. However, it is possible to intervene at intermediate stages to modify or reduce the radiation effect. Under certain conditions enhanced reactions are also possible. Several expressions are given to calculate radiation yield in terms of energy absorbed. Some analogies between radiation-induced reactions in polymers, and those studied in radiobiology are outlined. (author)

  6. Diseases induced by ionising radiation

    International Nuclear Information System (INIS)

    1984-11-01

    An interim report is presented by the Industrial Injuries Advisory Council in accordance with Section 141 of the Social Security Act 1975 on the question whether the terms of prescription for occupational diseases induced by ionising radiation should be amended to cover a wider range of conditions. A lack of persuasive statistical data has prevented reliable estimates of health risks of radiation workers in the UK to be made. However the report gives details of the progress made so far and the difficulties encountered. (U.K.)

  7. Radiation Induced Polymerization of Pyrrole

    International Nuclear Information System (INIS)

    Sarada Idris; Ratnam, C.T.; Ahmad Ashrif Abu Bakar

    2016-01-01

    We demonstrate the polymerization of pyrrole by gamma irradiation. The pyrrole films were exposed to gamma ray from cobalt 60 source at doses ranging from 0 to 150 kGy. The films were subjected to structural and morphological analyses by using FTIR, SEM and AFM techniques. Similar studies were also made on pristine pyrrole film which serve as control. Results revealed that pyrrole has been successfully polymerized through irradiation induced reactions. The SEM images depicted the formation of cauliflower shape upon gamma irradiation. The structural changes of pyrrole also evidenced by FTIR spectra. Surface topography and roughness of pyrrole before and after gamma irradiation found to show significant differences. (author)

  8. [Pregnancy-induced haemolytic anaemia].

    Science.gov (United States)

    Karagiozova, J; Masseva, A; Ivanov, St; Marinov, B; Kulinska, R; Boiadjiev, D; Jordanova, D

    2014-01-01

    This is the clinical case of a primiparous eight month pregnant female, presenting with symptoms of pregnancy-induced acute haemolytic anaemia (haemolytic aneamia provoked by an immune mechanism, intra- and extra-erythrocyte defects, and HELLP syndrome were excluded). The anaemia progressed to become life-threatening for both the pregnant women and the foetus, which brought the following questions into consideration: diagnosis of anaemia during pregnancy; dosing of corticosteroid therapy; possibility of giving birth to a viable foetus and prognosis for next pregnancies. Owing to the inter-disciplinary efforts, the life and health of this pregnant woman were preserved, but the foetus was lost.

  9. Ion beam induced luminescence: Relevance to radiation induced bystander effects

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, S.B., E-mail: ahmad.rabilal@gmail.com [Medical Physics and Applied Radiation Sciences, University of McMaster, Hamilton, Ontario (Canada); McNeill, F.E., E-mail: fmcneill@mcmaster.ca [Medical Physics and Applied Radiation Sciences, University of McMaster, Hamilton, Ontario (Canada); Byun, S.H., E-mail: soohyun@mcmaster.ca [Medical Physics and Applied Radiation Sciences, University of McMaster, Hamilton, Ontario (Canada); Prestwich, W.V., E-mail: prestwic@mcmaster.ca [Medical Physics and Applied Radiation Sciences, University of McMaster, Hamilton, Ontario (Canada); Seymour, C., E-mail: seymouc@mcmaster.ca [Medical Physics and Applied Radiation Sciences, University of McMaster, Hamilton, Ontario (Canada); Mothersill, C.E., E-mail: mothers@mcmaster.ca [Medical Physics and Applied Radiation Sciences, University of McMaster, Hamilton, Ontario (Canada)

    2012-10-01

    The aim of this work is quantify the light emitted as a result of charged particle interaction in materials which may be of relevance to radiation induced 'bystander effects' studies. We have developed a system which employs single photon counting to measure the light emitted from samples irradiated under vacuum by a charged particle beam. The system uses a fast photomultiplier tube with a peak cathode response at 420 nm. It has been tested in a proof-of-principle experiment using polystyrene targets. Light output, as a result of irradiation, was measured. The luminescence yield appears to have a non-linear behavior with the incident ion fluence: it rises exponentially to an asymptotic value. The target was irradiated with beam energies varying from 1 to 2 MeV and showed saturation at or before an incident fluence rate of 3 Multiplication-Sign 10{sup 13} H{sup +}/cm{sup 2} s. The average saturation value for the photon output was found to be 40 Multiplication-Sign 10{sup 6} cps. Some measurements were performed using filters to study the emission at specific wavelengths. In the case of filtered light measurements, the photon output was found to saturate at 28 Multiplication-Sign 10{sup 3}, 10 Multiplication-Sign 10{sup 6}, and 35 Multiplication-Sign 10{sup 6} cps for wavelengths of 280 {+-} 5 nm, 320 {+-} 5 nm and 340 {+-} 5 nm respectively. The light output reaches a maximum value because of damage induced in the polymer. Our measurements indicate a 'damage cross section' of the order of 10{sup -14} cm{sup 2}. The average radiant intensity was found to increase at wavelengths of 280 and 320 nm when the proton energy was increased. This was not found to occur at 340 nm. In conclusion, the light emission at specific wavelengths was found to depend upon the incident proton fluence and the proton energy. The wavelengths of the emitted light measured in this study have significance for the understanding of radiation induced bystander effects.

  10. On the Induced Gravitational Collapse

    Directory of Open Access Journals (Sweden)

    M. Becerra Laura

    2018-01-01

    Full Text Available The induced gravitational collapse (IGC paradigm has been applied to explain the long gamma ray burst (GRB associated with type Ic supernova, and recently the Xray flashes (XRFs. The progenitor is a binary systems of a carbon-oxygen core (CO and a neutron star (NS. The CO core collapses and undergoes a supernova explosion which triggers the hypercritical accretion onto the NS companion (up to 10-2 M⊙s-1. For the binary driven hypernova (BdHNe, the binary system is enough bound, the NS reach its critical mass, and collapse to a black hole (BH with a GRB emission characterized by an isotropic energy Eiso > 1052 erg. Otherwise, for binary systems with larger binary separations, the hypercritical accretion onto the NS is not sufficient to induced its gravitational collapse, a X-ray flash is produced with Eiso < 1052 erg. We’re going to focus in identify the binary parameters that limits the BdHNe systems with the XRFs systems.

  11. Cough-induced rib fractures.

    Science.gov (United States)

    Sano, Atsushi; Tashiro, Ken; Fukuda, Tsutomu

    2015-10-01

    Occasionally, patients who complain of chest pain after the onset of coughing are diagnosed with rib fractures. We investigated the characteristics of cough-induced rib fractures. Between April 2008 and December 2013, 17 patients were referred to our hospital with chest pain after the onset of coughing. Rib radiography was performed, focusing on the location of the chest pain. When the patient had other signs and symptoms such as fever or persistent cough, computed tomography of the chest was carried out. We analyzed the data retrospectively. Rib fractures were found in 14 of the 17 patients. The age of the patients ranged from 14 to 86 years (median 39.5 years). Ten patients were female and 4 were male. Three patients had chronic lung disease. There was a single rib fracture in 9 patients, and 5 had two or more fractures. The middle and lower ribs were the most commonly involved; the 10th rib was fractured most frequently. Cough-induced rib fractures occur in every age group regardless of the presence or absence of underlying disease. Since rib fractures often occur in the lower and middle ribs, rib radiography is useful for diagnosis. © The Author(s) 2015.

  12. Induced gravity II: grand unification

    Energy Technology Data Exchange (ETDEWEB)

    Einhorn, Martin B. [Kavli Institute for Theoretical Physics, Kohn Hall,University of California,Santa Barbara, CA 93106-4030 (United States); Jones, D.R. Timothy [Kavli Institute for Theoretical Physics, Kohn Hall,University of California,Santa Barbara, CA 93106-4030 (United States); Dept. of Mathematical Sciences, University of Liverpool,Peach Street, Liverpool L69 3BX (United Kingdom)

    2016-05-31

    As an illustration of a renormalizable, asymptotically-free model of induced gravity, we consider an SO(10) gauge theory interacting with a real scalar multiplet in the adjoint representation. We show that dimensional transmutation can occur, spontaneously breaking SO(10) to SU(5)⊗U(1), while inducing the Planck mass and a positive cosmological constant, all proportional to the same scale v. All mass ratios are functions of the values of coupling constants at that scale. Below this scale (at which the Big Bang may occur), the model takes the usual form of Einstein-Hilbert gravity in de Sitter space plus calculable corrections. We show that there exist regions of parameter space in which the breaking results in a local minimum of the effective action giving a positive dilaton (mass){sup 2} from two-loop corrections associated with the conformal anomaly. Furthermore, unlike the singlet case we considered previously, some minima lie within the basin of attraction of the ultraviolet fixed point. Moreover, the asymptotic behavior of the coupling constants also lie within the range of convergence of the Euclidean path integral, so there is hope that there will be candidates for sensible vacua. Although open questions remain concerning unitarity of all such renormalizable models of gravity, it is not obvious that, in curved backgrounds such as those considered here, unitarity is violated. In any case, any violation that may remain will be suppressed by inverse powers of the reduced Planck mass.

  13. Inducer Hydrodynamic Load Measurement Devices

    Science.gov (United States)

    Skelley, Stephen E.; Zoladz, Thomas F.

    2002-01-01

    Marshall Space Flight Center (MSFC) has demonstrated two measurement devices for sensing and resolving the hydrodynamic loads on fluid machinery. The first - a derivative of the six component wind tunnel balance - senses the forces and moments on the rotating device through a weakened shaft section instrumented with a series of strain gauges. This "rotating balance" was designed to directly measure the steady and unsteady hydrodynamic loads on an inducer, thereby defining both the amplitude and frequency content associated with operating in various cavitation modes. The second device - a high frequency response pressure transducer surface mounted on a rotating component - was merely an extension of existing technology for application in water. MSFC has recently completed experimental evaluations of both the rotating balance and surface-mount transducers in a water test loop. The measurement bandwidth of the rotating balance was severely limited by the relative flexibility of the device itself, resulting in an unexpectedly low structural bending mode and invalidating the higher frequency response data. Despite these limitations, measurements confirmed that the integrated loads on the four-bladed inducer respond to both cavitation intensity and cavitation phenomena. Likewise, the surface-mount pressure transducers were subjected to a range of temperatures and flow conditions in a non-rotating environment to record bias shifts and transfer functions between the transducers and a reference device. The pressure transducer static performance was within manufacturer's specifications and dynamic response accurately followed that of the reference.

  14. Chaos for induced hyperspace maps

    International Nuclear Information System (INIS)

    Banks, John

    2005-01-01

    For (X,d) be a metric space, f:X->X a continuous map and (K(X),H) the space of non-empty compact subsets of X with the Hausdorff metric, one may study the dynamical properties of the induced map (*)f-bar :K(X)->K(X):A-bar f(A).H. Roman-Flores [A note on in set-valued discrete systems. Chaos, Solitons and Fractals 2003;17:99-104] has shown that if f-bar is topologically transitive then so is f, but that the reverse implication does not hold. This paper shows that the topological transitivity of f-bar is in fact equivalent to weak topological mixing on the part of f. This is proved in the more general context of an induced map on some suitable hyperspace H of X with the Vietoris topology (which agrees with the topology of the Hausdorff metric in the case discussed by Roman-Flores

  15. Condensation induced water hammer safety

    International Nuclear Information System (INIS)

    Gintner, M.A.

    1997-01-01

    Condensation induced water hammer events in piping systems can cause catastrophic steam system failures which can result in equipment damage, personal injury, and even death. As an industry, we have learned to become accustomed to the ''banging'' that we often hear in our steam piping systems, and complacent in our actions to prevent it. It is unfortunate that lives are lost needlessly, as this type of water hammer event is preventable if one only applies some basic principles when operating and maintaining their steam systems. At the U. S. Department of Energy's Hanford Site where I work, there was one such accident that occurred in 1993 which took the life of a former co-worker and friend of mine. Hanford was established as part of the Manhattan Project during World War II. it is a 560 square mile complex located along the banks of the Columbia River in Southeastern Washington State. For almost 45 years, hanford's mission was to produce weapons grade plutonium for our nations defense programs. Today, Hanford no longer produces plutonium, but is focused on site clean-up and economic diversification. Hanford still uses steam for heating and processing activities, utilizing over 20 miles of piping distribution systems similar to those found in industry. Although these aging systems are still sound, they cannot stand up to the extreme pressure pulses developed by a condensation induced water hammer

  16. Psychosocial aspects of induced abortion.

    Science.gov (United States)

    Stotland, N L

    1997-09-01

    US anti-abortion groups have used misinformation on the long-term psychological impact of induced abortion to advance their position. This article reviews the available research evidence on the definition, history, cultural context, and emotional and psychiatric sequelae of induced abortion. Notable has been a confusion of normative, transient reactions to unintended pregnancy and abortion (e.g., guilt, depression, anxiety) with serious mental disorders. Studies of the psychiatric aspects of abortion have been limited by methodological problems such as the impossibility of randomly assigning women to study and control groups, resistance to follow-up, and confounding variables. Among the factors that may impact on an unintended pregnancy and the decision to abort are ongoing or past psychiatric illness, poverty, social chaos, youth and immaturity, abandonment issues, ongoing domestic responsibilities, rape and incest, domestic violence, religion, and contraceptive failure. Among the risk factors for postabortion psychosocial difficulties are previous or concurrent psychiatric illness, coercion to abort, genetic or medical indications, lack of social supports, ambivalence, and increasing length of gestation. Overall, the literature indicates that serious psychiatric illness is at least 8 times more common among postpartum than among postabortion women. Abortion center staff should acknowledge that the termination of a pregnancy may be experienced as a loss even when it is a voluntary choice. Referrals should be offered to women who show great emotional distress, have had several previous abortions, or request psychiatric consultation.

  17. Drug-induced hepatic injury

    DEFF Research Database (Denmark)

    Friis, Henrik; Andreasen, P B

    1992-01-01

    The Danish Committee on Adverse Drug Reactions received 1100 reports of suspected drug-induced hepatic injury during the decade 1978-1987. The causal relationship between drug and hepatic injury was classified as definite in 57 (5.2%) reports, probable in 989 (89.9%) reports, possible in 50 (4.......5%) reports and unclassifiable in four (0.4%) reports. Hepatic injuries accounted for 5.9% of all adverse drug reactions reported, and 14.7% of the lethal adverse drug reactions. A total of 47.2% were classified as acute cytotoxic, 16.2% as acute cholestatic and 26.9% as abnormal hepatic function. In 52 (4.......7%) cases the hepatic injury was lethal; only 14 (1.3%) cases were chronic. Halothane accounted for 25% of the cases. The incidence of halothane-induced hepatic injury is decreasing, and only one lethal case has been reported since 1981. Next to halothane, sulfasalazine was the drug most often suspected...

  18. Condensation induced water hammer safety

    Energy Technology Data Exchange (ETDEWEB)

    Gintner, M.A.

    1997-03-10

    Condensation induced water hammer events in piping systems can cause catastrophic steam system failures which can result in equipment damage, personal injury, and even death. As an industry, we have learned to become accustomed to the ''banging'' that we often hear in our steam piping systems, and complacent in our actions to prevent it. It is unfortunate that lives are lost needlessly, as this type of water hammer event is preventable if one only applies some basic principles when operating and maintaining their steam systems. At the U. S. Department of Energy's Hanford Site where I work, there was one such accident that occurred in 1993 which took the life of a former co-worker and friend of mine. Hanford was established as part of the Manhattan Project during World War II. it is a 560 square mile complex located along the banks of the Columbia River in Southeastern Washington State. For almost 45 years, hanford's mission was to produce weapons grade plutonium for our nations defense programs. Today, Hanford no longer produces plutonium, but is focused on site clean-up and economic diversification. Hanford still uses steam for heating and processing activities, utilizing over 20 miles of piping distribution systems similar to those found in industry. Although these aging systems are still sound, they cannot stand up to the extreme pressure pulses developed by a condensation induced water hammer.

  19. Shear induced phase transitions induced in edible fats

    Science.gov (United States)

    Mazzanti, Gianfranco; Welch, Sarah E.; Marangoni, Alejandro G.; Sirota, Eric B.; Idziak, Stefan H. J.

    2003-03-01

    The food industry crystallizes fats under different conditions of temperature and shear to obtain products with desired crystalline phases. Milk fat, palm oil, cocoa butter and chocolate were crystallized from the melt in a temperature controlled Couette cell. Synchrotron x-ray diffraction studies were conducted to examine the role of shear on the phase transitions seen in edible fats. The shear forces on the crystals induced acceleration of the alpha to beta-prime phase transition with increasing shear rate in milk fat and palm oil. The increase was slow at low shear rates and became very strong above 360 s-1. In cocoa butter the acceleration between beta-prime-III and beta-V phase transition increased until a maximum of at 360 s-1, and then decreased, showing competition between enhanced heat transfer and viscous heat generation.

  20. Amoxicillin-induced aseptic meningoencephalitis

    Directory of Open Access Journals (Sweden)

    Radi Shahien

    2010-06-01

    Full Text Available Radi Shahien1, Vetaly Vieksler1, Abdalla Bowirrat11Department of Neurology and Neurophysiology, Ziv Medical Center, Safed, IsraelAbstract: Meningitis is usually produced by an infectious agent, but there are multiple noninfectious causes. Drug-induced aseptic meningitis (DIAM is an important entity and has been reported as an uncommon adverse reaction with numerous agents. Thus, DIAM constitutes a diagnostic and patient management challenge. We present a patient with three episodes of aseptic meningitis due to amoxicillin, and then review the literature on this rare idiosyncratic event which may occur after local or systemic drug administration. A 77-year-old man was admitted to our hospital with fever, headache, and neck stiffness. Seven days before admission he had a dental and gingival inflammation. He was treated with two oral doses of 500 mg daily of amoxicillin for one week. The seventh day he awoke with the complaints that prompted hospital admittance. Amoxicillin was stopped 1 day before his admission. From his history we knew of two similar episodes: The first episode was after a dental procedure 3 months before this incident. He had received a 1-week course of postprocedure amoxicillin of 500 mg daily and had similar headache, fever, and chills during the entire course of treatment. He wasn’t admitted to the hospital, because he stopped taking amoxicillin and he felt spontaneous pain relief after taking symptomatic pain treatment. The second episodes was 6 months after his first admission, he had been admitted to our hospital with the same symptoms. Amoxicillin was stopped and changed with intravenous (IV ceftriaxone (CTRX for 10 days due to suspected partial untreated meningitis. The patient improved rapidly within 2 days and was discharged from the hospital. On the basis of these three confirmed episodes of meningitis after recurrent exposure to amoxicillin, with repetitive negative testing for viral, bacterial, and mycobacterial

  1. Hemolysis induced by PMIVSD occluder

    Directory of Open Access Journals (Sweden)

    D. Sheshagiri Rao

    2016-09-01

    Full Text Available Hemolysis related to occluder, prosthetic valve, and prosthetic ring used for mitral valve annuloplasty are not very unusual. However, hemolysis related to transcathetor closure of post-myocardial infarction ventricular septal defect (PMIVSD is infrequent. A close follow-up for spontaneous resolution with or without blood transfusion has been reported in a few cases. Occasionally, surgical retrieval is unavoidable or lifelong blood transfusion is required if surgery cannot be done because of higher risk. In this illustration, we have showed a close follow-up of a case of hemolysis induced by atrial septal occluder used for VSD closure after myocardial infarction. Despite successful device closure of PMIVSD which is difficult, a close watch is needed for complications like residual leak, device embolization, and hemolysis.

  2. Hemolysis induced by PMIVSD occluder.

    Science.gov (United States)

    Rao, D Sheshagiri; Barik, Ramachandra; Siva Prasad, Akula

    2016-09-01

    Hemolysis related to occluder, prosthetic valve, and prosthetic ring used for mitral valve annuloplasty are not very unusual. However, hemolysis related to transcathetor closure of post-myocardial infarction ventricular septal defect (PMIVSD) is infrequent. A close follow-up for spontaneous resolution with or without blood transfusion has been reported in a few cases. Occasionally, surgical retrieval is unavoidable or lifelong blood transfusion is required if surgery cannot be done because of higher risk. In this illustration, we have showed a close follow-up of a case of hemolysis induced by atrial septal occluder used for VSD closure after myocardial infarction. Despite successful device closure of PMIVSD which is difficult, a close watch is needed for complications like residual leak, device embolization, and hemolysis. Copyright © 2016 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  3. Rice breeding with induced mutations

    Energy Technology Data Exchange (ETDEWEB)

    1968-06-01

    The Joint FAO/IAEA Division of Atomic Energy in Food and Agriculture decided in 1964 to organize a co-ordinated research programme on the use of induced mutations in rice breeding. The programme was organized within the framework of activities of the International Rice Commission. This is a report of the Third Co-ordination Meeting of the participants, which was held in Taipei, 5-9 June 1967. As the projects, which together make up the co-ordinated programme, are at different stages of progress, the report contains a variety of papers including completed studies, field and progress reports, and highlights of the discussions with some additional recommendations prepared by the participants. Refs, figs and tabs.

  4. Uncommon vancomycin: induced side effects

    Directory of Open Access Journals (Sweden)

    Rocha Jaime Luís Lopes

    2002-01-01

    Full Text Available Vancomycin has been used with increased frequency during the past 15 years and the most common toxicity with this drug is the "red man syndrome". Other adverse effects include neutropenia, fever, phlebitis, nephrotoxicity, ototoxicity, thrombocytopenia, interstitial nephritis, lacrimation, linear IgA bullous dermatosis, necrotizing cutaneous vasculitis and toxic epidermal necrolysis. Only two cases of vancomycin-induced Stevens-Johnson syndrome and one case of pancytopenia have been reported in the medical literature. The treatment for both situations is based on cessation of the vancomycin therapy; in cases of Stevens-Johnson syndrome, antihistamine and/or steroid agents can be used. This article reports a case of pancytopenia and a case of erythema major associated with neutropenia.

  5. Typhoon-Induced Ground Deformation

    Science.gov (United States)

    Mouyen, M.; Canitano, A.; Chao, B. F.; Hsu, Y.-J.; Steer, P.; Longuevergne, L.; Boy, J.-P.

    2017-11-01

    Geodetic instruments now offer compelling sensitivity, allowing to investigate how solid Earth and surface processes interact. By combining surface air pressure data, nontidal sea level variations model, and rainfall data, we systematically analyze the volumetric deformation of the shallow crust at seven borehole strainmeters in Taiwan induced by 31 tropical cyclones (typhoons) that made landfall to the island from 2004 to 2013. The typhoon's signature consists in a ground dilatation due to air pressure drop, generally followed by a larger ground compression. We show that this compression phase can be mostly explained by the mass loading of rainwater that falls on the ground and concentrates in the valleys towards the strainmeter sensitivity zone. Further, our analysis shows that borehole strainmeters can help quantifying the amount of rainwater accumulating and flowing over a watershed during heavy rainfalls, which is a useful constraint for building hydrological models.

  6. Mental disorders induced by carbamazepine.

    Science.gov (United States)

    Mizukami, K; Naito, Y; Yoshida, M; Nakanishi, T; Koizumi, J

    1990-03-01

    We present here a case with various physical and neuropsychiatric symptoms caused by the administration of carbamazepine. The patient suffering from right ophthalmic neuralgia showed fever, eczema, erythema, lymphoadenopathy, eosinophilia, vomiting, headache, dizziness, nystagmus, and various mental disorders which consisted of emotional instability, personality change, delusions of reference and persecution, depressive state, and hyperventilation syndrome during the administration of carbamazepine. The physical symptoms in the present case were conformable to the side effect of carbamazepine. The mental disorders appeared in a few days from the start of carbamazepine administration and disappeared after the discontinuation of the administration of this drug without antipsychotic therapy and have never relapsed until now. The mental disorders and the physical symptoms were in parallel with their clinical course. This kind of mental disorders induced by carbamazepine has not yet been reported.

  7. Antiphospholipid Antibody Induced by Nivolumab

    Directory of Open Access Journals (Sweden)

    Ahmed Aburahma

    2018-01-01

    Full Text Available Nivolumab is a monoclonal antibody against the programmed death protein 1 and is used for patients with advanced melanoma. It is associated with potentially immune-related adverse events, including disorders of the skin, GI tract, and the thyroid; these disorders were successfully treated with prednisone and infliximab. Other immunotherapeutic agents were observed to induce the formation of antiphospholipid antibody (APA including α-interferon and interleukin-2. We present a case of APA development after the third dose of nivolumab in a 71-year-old male with advanced melanoma. The APA was detected after finding a prolonged aPTT; the lupus anticoagulant assay tested positive. The patient was treated with prednisone but, unfortunately, he expired a few days later.

  8. Human-induced Arctic moistening.

    Science.gov (United States)

    Min, Seung-Ki; Zhang, Xuebin; Zwiers, Francis

    2008-04-25

    The Arctic and northern subpolar regions are critical for climate change. Ice-albedo feedback amplifies warming in the Arctic, and fluctuations of regional fresh water inflow to the Arctic Ocean modulate the deep ocean circulation and thus exert a strong global influence. By comparing observations to simulations from 22 coupled climate models, we find influence from anthropogenic greenhouse gases and sulfate aerosols in the space-time pattern of precipitation change over high-latitude land areas north of 55 degrees N during the second half of the 20th century. The human-induced Arctic moistening is consistent with observed increases in Arctic river discharge and freshening of Arctic water masses. This result provides new evidence that human activity has contributed to Arctic hydrological change.

  9. Valproic Acid-induced Agranulocytosis

    Directory of Open Access Journals (Sweden)

    Hui-Chuan Hsu

    2009-06-01

    Full Text Available Valproic acid is considered to be the most well-tolerated antiepileptic drug. However, few cases of neutropenia or leukopenia caused by valproic acid have been reported. We present a patient who took valproic acid to treat a complication of brain surgery and in whom severe agranulocytosis occurred after 2.5 months. Valproic acid was stopped immediately, and granulocyte colony-stimulating factor was administered for 2 days. The patient's white blood cell count returned to normal within 2 weeks. The result of bone marrow aspiration was compatible with drug-induced agranulocytosis. This case illustrates that patients who take valproic acid may need regular checking of complete blood cell count.

  10. Magnetic field induced dynamical chaos.

    Science.gov (United States)

    Ray, Somrita; Baura, Alendu; Bag, Bidhan Chandra

    2013-12-01

    In this article, we have studied the dynamics of a particle having charge in the presence of a magnetic field. The motion of the particle is confined in the x-y plane under a two dimensional nonlinear potential. We have shown that constant magnetic field induced dynamical chaos is possible even for a force which is derived from a simple potential. For a given strength of the magnetic field, initial position, and velocity of the particle, the dynamics may be regular, but it may become chaotic when the field is time dependent. Chaotic dynamics is very often if the field is time dependent. Origin of chaos has been explored using the Hamiltonian function of the dynamics in terms of action and angle variables. Applicability of the present study has been discussed with a few examples.

  11. Gravity induced wave function collapse

    Science.gov (United States)

    Gasbarri, G.; Toroš, M.; Donadi, S.; Bassi, A.

    2017-11-01

    Starting from an idea of S. L. Adler [in Quantum Nonlocality and Reality: 50 Years of Bell's Theorem, edited by M. Bell and S. Gao (Cambridge University Press, Cambridge, England 2016)], we develop a novel model of gravity induced spontaneous wave function collapse. The collapse is driven by complex stochastic fluctuations of the spacetime metric. After deriving the fundamental equations, we prove the collapse and amplification mechanism, the two most important features of a consistent collapse model. Under reasonable simplifying assumptions, we constrain the strength ξ of the complex metric fluctuations with available experimental data. We show that ξ ≥10-26 in order for the model to guarantee classicality of macro-objects, and at the same time ξ ≤10-20 in order not to contradict experimental evidence. As a comparison, in the recent discovery of gravitational waves in the frequency range 35 to 250 Hz, the (real) metric fluctuations reach a peak of ξ ˜10-21.

  12. Molecular Mechanisms of Induced Pluripotency

    Science.gov (United States)

    Muchkaeva, I.A.; Dashinimaev, E.B.; Terskikh, V.V.; Sukhanov, Y.V.; Vasiliev, A.V.

    2012-01-01

    In this review the distinct aspects of somatic cell reprogramming are discussed. The molecular mechanisms of generation of induced pluripotent stem (iPS) cells from somatic cells via the introduction of transcription factors into adult somatic cells are considered. Particular attention is focused on the generation of iPS cells without genome modifications via the introduction of the mRNA of transcription factors or the use of small molecules. Furthermore, the strategy of direct reprogramming of somatic cells omitting the generation of iPS cells is considered. The data concerning the differences between ES and iPS cells and the problem of epigenetic memory are also discussed. In conclusion, the possibility of using iPS cells in regenerative medicine is considered. PMID:22708059

  13. Drug-induced status epilepticus.

    Science.gov (United States)

    Cock, Hannah R

    2015-08-01

    Drug-induced status epilepticus (SE) is a relatively uncommon phenomenon, probably accounting for less than 5% of all SE cases, although limitations in case ascertainment and establishing causation substantially weaken epidemiological estimates. Some antiepileptic drugs, particularly those with sodium channel or GABA(γ-aminobutyric acid)-ergic properties, frequently exacerbate seizures and may lead to SE if used inadvertently in generalized epilepsies or less frequently in other epilepsies. Tiagabine seems to have a particular propensity for triggering nonconvulsive SE sometimes in patients with no prior history of seizures. In therapeutic practice, SE is most commonly seen in association with antibiotics (cephalosporins, quinolones, and some others) and immunotherapies/chemotherapies, the latter often in the context of a reversible encephalopathy syndrome. Status epilepticus following accidental or intentional overdoses, particularly of antidepressants or other psychotropic medications, has also featured prominently in the literature: whilst there are sometimes fatal consequences, this is more commonly because of cardiorespiratory or metabolic complications than as a result of seizure activity. A high index of suspicion is required in identifying those at risk and in recognizing potential clues from the presentation, but even with a careful analysis of patient and drug factors, establishing causation can be difficult. In addition to eliminating the potential trigger, management should be as for SE in any other circumstances, with the exception that phenobarbitone is recommended as a second-line treatment for suspected toxicity-related SE where the risk of cardiovascular complications is higher anyways and may be exacerbated by phenytoin. There are also specific recommendations/antidotes in some situations. The outcome of drug-induced status epilepticus is mostly good when promptly identified and treated, though less so in the context of overdoses. This article is

  14. Induced gravity and gauge interactions revisited

    International Nuclear Information System (INIS)

    Broda, Boguslaw; Szanecki, Michal

    2009-01-01

    It has been shown that the primary, old-fashioned idea of Sakharov's induced gravity and gauge interactions, in the 'one-loop dominance' version, works astonishingly well yielding phenomenologically reasonable results. As a byproduct, the issue of the role of the UV cutoff in the context of the induced gravity has been reexamined (an idea of self-cutoff induced gravity). As an additional check, the black hole entropy has been used in the place of the action. Finally, it has been explicitly shown that the induced coupling constants of gauge interactions of the standard model assume qualitatively realistic values.

  15. Radiation-induced instability of human genome

    International Nuclear Information System (INIS)

    Ryabchenko, N.N.; Demina, Eh.A.

    2014-01-01

    A brief review is dedicated to the phenomenon of radiation-induced genomic instability where the increased level of genomic changes in the offspring of irradiated cells is characteristic. Particular attention is paid to the problems of genomic instability induced by the low-dose radiation, role of the bystander effect in formation of radiation-induced instability, and its relationship with individual radiosensitivity. We believe that in accordance with the paradigm of modern radiobiology the increased human individual radiosensitivity can be formed due to the genome instability onset and is a significant risk factor for radiation-induced cancer

  16. Quinine-induced tinnitus in rats.

    Science.gov (United States)

    Jastreboff, P J; Brennan, J F; Sasaki, C T

    1991-10-01

    Quinine ingestion reportedly induces tinnitus in humans. To expand our salicylate-based animal model of tinnitus, a series of conditioned suppression experiments was performed on 54 male-pigmented rats using quinine injections to induce tinnitus. Quinine induced changes in both the extent of suppression and recovery of licking, which followed a pattern that paralleled those produced after salicylate injections, and which may be interpreted as the result of tinnitus perception in animals. These changes depended on the dose and time schedule of quinine administration. Additionally, the calcium channel blocker, nimodipine, abolished the quinine-induced effect in a dose-dependent manner.

  17. An evaluation of a hubless inducer and a full flow hydraulic turbine driven inducer boost pump

    Science.gov (United States)

    Lindley, B. K.; Martinson, A. R.

    1971-01-01

    The purpose of the study was to compare the performance of several configurations of hubless inducers with a hydrodynamically similar conventional inducer and to demonstrate the performance of a full flow hydraulic turbine driven inducer boost pump using these inducers. A boost pump of this type consists of an inducer connected to a hydraulic turbine with a high speed rotor located in between. All the flow passes through the inducer, rotor, and hydraulic turbine, then into the main pump. The rotor, which is attached to the main pump shaft, provides the input power to drive the hydraulic turbine which, in turn, drives the inducer. The inducer, rotating at a lower speed, develops the necessary head to prevent rotor cavitation. The rotor speed is consistent with present main engine liquid hydrogen pump designs and the overall boost pump head rise is sufficient to provide adequate main pump suction head. This system would have the potential for operating at lower liquid hydrogen tank pressures.

  18. The transition time induced narrow linewidth of the electromagnetically induced transparency in caesium vapour

    International Nuclear Information System (INIS)

    Li Luming; Peng Xiang; Liu Cheng; Guo Hong; Chen Xuzong

    2004-01-01

    We observed a narrow linewidth (∼60 kHz) in a Doppler-broadened system showing electromagnetically induced transparency in caesium atomic vapour. The transition time induced reduction of the linewidth is illustrated both theoretically and experimentally

  19. Monoclonal Antibodies Follow Distinct Aggregation Pathways During Production-Relevant Acidic Incubation and Neutralization

    DEFF Research Database (Denmark)

    Pedersen, Thomas Skamris; Tian, Xinsheng; Thorolfsson, Matthias

    2016-01-01

    and orthogonal analytical methods, including small-angle X-ray scattering and dynamic light scattering and supplemented the experimental data with crystal structure-based spatial aggregation propensity (SAP) calculations. RESULTS: We revealed distinct solution behaviors between the three mAb models: At acidic p......PURPOSE: Aggregation aspects of therapeutic monoclonal antibodies (mAbs) are of common concern to the pharmaceutical industry. Low pH treatment is applied during affinity purification and to inactivate endogenous retroviruses, directing interest to the mechanisms of acid-induced antibody...... distinguish between reversible and irreversible mAb aggregation pathways at early stages of acidic treatment....

  20. Towards inducing superconductivity into graphene

    Science.gov (United States)

    Efetov, Dmitri K.

    Graphenes transport properties have been extensively studied in the 10 years since its discovery in 2004, with ground-breaking experimental observations such as Klein tunneling, fractional quantum Hall effect and Hofstadters butterfly. Though, so far, it turned out to be rather poor on complex correlated electronic ground states and phase transitions, despite various theoretical predictions. The purpose of this thesis is to help understanding the underlying theoretical and experimental reasons for the lack of strong electronic interactions in graphene, and, employing graphenes high tunability and versatility, to identify and alter experimental parameters that could help to induce stronger correlations. In particular graphene holds one last, not yet experimentally discovered prediction, namely exhibiting intrinsic superconductivity. With its vanishingly small Fermi surface at the Dirac point, graphene is a semi-metal with very weak electronic interactions. Though, if it is doped into the metallic regime, where the size of the Fermi surface becomes comparable to the size of the Brillouin zone, the density of states becomes sizeable and electronic interactions are predicted to be dramatically enhanced, resulting in competing correlated ground states such as superconductivity, magnetism and charge density wave formation. Following these predictions, this thesis first describes the creation of metallic graphene at high carrier doping via electrostatic doping techniques based on electrolytic gates. Due to graphenes surface only properties, we are able to induce carrier densities above n>1014 cm-2 (epsilonF>1eV) into the chemically inert graphene. While at these record high carrier densities we yet do not observe superconductivity, we do observe fundamentally altered transport properties as compared to semi-metallic graphene. Here, detailed measurements of the low temperature resistivity reveal that the electron-phonon interactions are governed by a reduced, density

  1. Intracellular S1P generation is essential for S1P-induced motility of human lung endothelial cells: role of sphingosine kinase 1 and S1P lyase.

    Directory of Open Access Journals (Sweden)

    Evgeny V Berdyshev

    Full Text Available BACKGROUND: Earlier we have shown that extracellular sphingosine-1-phosphate (S1P induces migration of human pulmonary artery endothelial cells (HPAECs through the activation of S1P(1 receptor, PKCε, and PLD2-PKCζ-Rac1 signaling cascade. As endothelial cells generate intracellular S1P, here we have investigated the role of sphingosine kinases (SphKs and S1P lyase (S1PL, that regulate intracellular S1P accumulation, in HPAEC motility. METHODOLOGY/PRINCIPAL FINDINGS: Inhibition of SphK activity with a SphK inhibitor 2-(p-Hydroxyanilino-4-(p-Chlorophenyl Thiazole or down-regulation of Sphk1, but not SphK2, with siRNA decreased S1P(int, and attenuated S1P(ext or serum-induced motility of HPAECs. On the contrary, inhibition of S1PL with 4-deoxypyridoxine or knockdown of S1PL with siRNA increased S1P(int and potentiated motility of HPAECs to S1P(ext or serum. S1P(ext mediates cell motility through activation of Rac1 and IQGAP1 signal transduction in HPAECs. Silencing of SphK1 by siRNA attenuated Rac1 and IQGAP1 translocation to the cell periphery; however, knockdown of S1PL with siRNA or 4-deoxypyridoxine augmented activated Rac1 and stimulated Rac1 and IQGAP1 translocation to cell periphery. The increased cell motility mediated by down-regulation was S1PL was pertussis toxin sensitive suggesting "inside-out" signaling of intracellularly generated S1P. Although S1P did not accumulate significantly in media under basal or S1PL knockdown conditions, addition of sodium vanadate increased S1P levels in the medium and inside the cells most likely by blocking phosphatases including lipid phosphate phosphatases (LPPs. Furthermore, addition of anti-S1P mAb to the incubation medium blocked S1P(ext or 4-deoxypyridoxine-dependent endothelial cell motility. CONCLUSIONS/SIGNIFICANCE: These results suggest S1P(ext mediated endothelial cell motility is dependent on intracellular S1P production, which is regulated, in part, by SphK1 and S1PL.

  2. Intracellular S1P Generation Is Essential for S1P-Induced Motility of Human Lung Endothelial Cells: Role of Sphingosine Kinase 1 and S1P Lyase

    Science.gov (United States)

    Berdyshev, Evgeny V.; Gorshkova, Irina; Usatyuk, Peter; Kalari, Satish; Zhao, Yutong; Pyne, Nigel J.; Pyne, Susan; Sabbadini, Roger A.; Garcia, Joe G. N.; Natarajan, Viswanathan

    2011-01-01

    Background Earlier we have shown that extracellular sphingosine-1-phosphate (S1P) induces migration of human pulmonary artery endothelial cells (HPAECs) through the activation of S1P1 receptor, PKCε, and PLD2-PKCζ-Rac1 signaling cascade. As endothelial cells generate intracellular S1P, here we have investigated the role of sphingosine kinases (SphKs) and S1P lyase (S1PL), that regulate intracellular S1P accumulation, in HPAEC motility. Methodology/Principal Findings Inhibition of SphK activity with a SphK inhibitor 2-(p-Hydroxyanilino)-4-(p-Chlorophenyl) Thiazole or down-regulation of Sphk1, but not SphK2, with siRNA decreased S1Pint, and attenuated S1Pext or serum-induced motility of HPAECs. On the contrary, inhibition of S1PL with 4-deoxypyridoxine or knockdown of S1PL with siRNA increased S1Pint and potentiated motility of HPAECs to S1Pext or serum. S1Pext mediates cell motility through activation of Rac1 and IQGAP1 signal transduction in HPAECs. Silencing of SphK1 by siRNA attenuated Rac1 and IQGAP1 translocation to the cell periphery; however, knockdown of S1PL with siRNA or 4-deoxypyridoxine augmented activated Rac1 and stimulated Rac1 and IQGAP1 translocation to cell periphery. The increased cell motility mediated by down-regulation was S1PL was pertussis toxin sensitive suggesting “inside-out” signaling of intracellularly generated S1P. Although S1P did not accumulate significantly in media under basal or S1PL knockdown conditions, addition of sodium vanadate increased S1P levels in the medium and inside the cells most likely by blocking phosphatases including lipid phosphate phosphatases (LPPs). Furthermore, addition of anti-S1P mAb to the incubation medium blocked S1Pext or 4-deoxypyridoxine-dependent endothelial cell motility. Conclusions/Significance These results suggest S1Pext mediated endothelial cell motility is dependent on intracellular S1P production, which is regulated, in part, by SphK1 and S1PL. PMID:21304987

  3. Vaccination with IL-6 analogues induces autoantibodies to IL-6 and influences experimentally induced inflammation

    DEFF Research Database (Denmark)

    Galle, Pia; Jensen, Lene; Andersson, Christina

    2007-01-01

    ; yet they appear healthy and do not exhibit overt clinical or laboratory abnormalities. We induced comparable levels of aAb-IL-6 in different mouse strains by vaccination with immunogenic IL-6 analogues. We observed that the induced aAb-IL-6 protected against collagen-induced arthritis and experimental...

  4. Protective immunity to UV radiation-induced skin tumours induced by skin grafts and epidermal cells

    International Nuclear Information System (INIS)

    Ronald Sluyter; Kylie S Yuen; Gary M Halliday

    2001-01-01

    There is little evidence that cutaneous dendritic cells (DC), including epidermal Langerhans cells (LC), can induce immunity to UV radiation (UVR)-induced skin tumours. Here, it is shown that cells within skin can induce protective antitumour immunity against a UVR-induced fibrosarcoma. Transplantation of the skin overlying subcutaneous tumours onto naive recipients could induce protective antitumour immunity, probably because the grafting stimulated the tumour Ag-loaded DC to migrate to local lymph nodes. This suggests that cutaneous APC can present tumour Ag to induce protective antitumour immunity. Previously, it has been shown that immunization of mice with MHC class II+ epidermal cells (EC) pulsed with tumour extracts could induce delayed-type hypersensitivity against tumour cells. Here, this same immunization protocol could induce protective immunity against a minimum tumorigenic dose of UVR-induced fibrosarcoma cells, but not higher doses. Epidermal cells obtained from semiallogeneic donors and pulsed with tumour extract could also induce protective immunity. However, presentation of BSA Ag from the culture medium was found to contribute to this result using semiallogeneic EC. The results suggest that LC overlying skin tumours may be able to induce protective immunity to UVR-induced tumours if stimulated to migrate from the skin. Copyright (2001) Australasian Society of Immunology Inc

  5. Psychiatric sequelae of induced abortion.

    Science.gov (United States)

    Gibbons, M

    1984-03-01

    An attempt is made to identify and document the problems of comparative evaluation of the more recent studies of psychiatric morbidity after abortion and to determine the current consensus so that when the results of the joint RCGP/RCOG study of the sequelae of induced abortion become available they can be viewed in a more informed context. The legalization of abortion has provided more opportunities for studies of subsequent morbidity. New laws have contributed to the changing attitudes of society, and the increasing acceptability of the operation has probably influenced the occurrence of psychiatric sequelae. The complexity of measuring psychiatric sequelae is evident from the many terms used to describe symptomatology and behavioral patterns and from the number of assessment techniques involved. Numerous techniques have been used to quantify psychiatric sequelae. Several authors conclude that few psychiatric problems follow an induced abortion, but many studies were deficient in methodology, material, or length of follow-up. A British study in 1975 reported a favorable outcome for a "representative sample" of 50 National Health Service patients: 68% of these patients had an absence of or only mild feelings of guilt, loss, or self reproach and considered abortion as the best solution to their problem. The 32% who had an adverse outcome reported moderate to severe feelings of guilt, regret, loss, and self reproach, and there was evidence of mental illness. In most of these cases the adverse outcome was related to the patient's environment since the abortion. A follow-up study of 126 women, which compared the overall reaction to therapeutic abortion between women with a history of previous mild psychiatric illness and those without reported that a significantly different emotional reaction could not be demonstrated between the 2 groups. In a survey among women seeking an abortion 271 who were referred for a psychiatric opinion regarding terminations of pregnancy

  6. Mechanistic review of drug-induced steatohepatitis

    International Nuclear Information System (INIS)

    Schumacher, Justin D.; Guo, Grace L.

    2015-01-01

    Drug-induced steatohepatitis is a rare form of liver injury known to be caused by only a handful of compounds. These compounds stimulate the development of steatohepatitis through their toxicity to hepatocyte mitochondria; inhibition of beta-oxidation, mitochondrial respiration, and/or oxidative phosphorylation. Other mechanisms discussed include the disruption of phospholipid metabolism in lysosomes, prevention of lipid egress from hepatocytes, targeting mitochondrial DNA and topoisomerase, decreasing intestinal barrier function, activation of the adenosine pathway, increasing fatty acid synthesis, and sequestration of coenzyme A. It has been found that the majority of compounds that induce steatohepatitis have cationic amphiphilic structures; a lipophilic ring structure with a side chain containing a cationic secondary or tertiary amine. Within the last decade, the ability of many chemotherapeutics to cause steatohepatitis has become more evident coining the term chemotherapy-associated steatohepatitis (CASH). The mechanisms behind drug-induced steatohepatitis are discussed with a focus on cationic amphiphilic drugs and chemotherapeutic agents. - Highlights: • Reviewed the mechanisms underlying drug-induced steatohepatitis for many compounds • Mitochondrial dysfunction is critical in the development of drug-induced steatohepatitis. • Majority of drugs that induce steatohepatitis are cationic amphiphilic drugs. • Chemotherapeutics that induce CASH are cationic amphiphilic drugs. • Majority of drugs that induce steatohepatitis are carnitine palmitoyltransferase-I inhibitors.

  7. Distribution of induced activity in tungsten targets

    International Nuclear Information System (INIS)

    Donahue, R.J.; Nelson, W.R.

    1988-09-01

    Estimates are made of the induced activity created during high-energy electron showers in tungsten, using the EGS4 code. Photon track lengths, neutron yields and spatial profiles of the induced activity are presented. 8 refs., 9 figs., 1 tab

  8. On helicon wave induced radial plasma transport

    International Nuclear Information System (INIS)

    Petrzilka, V.

    1993-04-01

    Estimates of helicon wave induced radial plasma transport are presented. The wave induced transport grows or decreases in dependence on the sign of the azimuthal wave number; these changes in transport may play an important role in helicon wave plasma sources. (author) 5 figs., 18 refs

  9. Induced topological pressure for topological dynamical systems

    International Nuclear Information System (INIS)

    Xing, Zhitao; Chen, Ercai

    2015-01-01

    In this paper, inspired by the article [J. Jaerisch et al., Stochastics Dyn. 14, 1350016, pp. 1-30 (2014)], we introduce the induced topological pressure for a topological dynamical system. In particular, we prove a variational principle for the induced topological pressure

  10. Linking aboveground and belowground inducible plant resistance

    NARCIS (Netherlands)

    Bezemer, T.M.

    2009-01-01

    Induced resistance of plants against pests and diseases via plant defense responses is well documented and can occur aboveground, in the leaves, and belowground in the roots. A number of recent studies have shown that soil-borne pests can also induce plant resistance aboveground and vice versa.

  11. Studies of positron induced luminescence from polymers

    International Nuclear Information System (INIS)

    Xu, J.; Hulett, L.D. Jr.; Lewis, T.A.; Tolk, N.H.

    1994-01-01

    Light emission from polymers (anthracene dissolved in polystryrene) induced by low-energy positrons and electrons has been studied. Results indicate a clear difference between optical emissions under positron and electron bombardment. The positron-induced luminescence spectrum is believed to be generated by both collisional and annihilation processes

  12. Gravitational Zero Point Energy induces Physical Observables

    OpenAIRE

    Garattini, Remo

    2010-01-01

    We consider the contribution of Zero Point Energy on the induced Cosmological Constant and on the induced Electric/Magnetic charge in absence of matter fields. The method is applicable to every spherically symmetric background. Extensions to a generic $f(R) $ theory are also allowed. Only the graviton appears to be fundamental to the determination of Zero Point Energy.

  13. Laughter-induced left bundle branch block.

    Science.gov (United States)

    Chow, Grant V; Desai, Dipan; Spragg, David D; Zakaria, Sammy

    2012-10-01

    We present the case of a patient with ischemic heart disease and intermittent left bundle branch block, reproducibly induced by laughter. Following treatment of ischemia with successful deployment of a drug-eluting stent, no further episodes of inducible LBBB were seen. Transient ischemia, exacerbated by elevated intrathoracic pressure during laughter, may have contributed to onset of this phenomenon. © 2012 Wiley Periodicals, Inc.

  14. Inducible limb-shaking transitory ischemic attacks

    DEFF Research Database (Denmark)

    Rosenbaum, Sverre; Ovesen, Christian; Futrell, Nancy

    2016-01-01

    with exercise-induced weakness associated with tremor in his right arm. His left internal carotid artery was occluded at the bifurcation. Administration of statin and antiplatelet did not relieve his symptoms, and his stereotypic, exercise-induced "limb-shaking" episodes persisted. He underwent successful...

  15. Mechanistic review of drug-induced steatohepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Schumacher, Justin D., E-mail: Justin.d.schumacher@rutgers.edu; Guo, Grace L.

    2015-11-15

    Drug-induced steatohepatitis is a rare form of liver injury known to be caused by only a handful of compounds. These compounds stimulate the development of steatohepatitis through their toxicity to hepatocyte mitochondria; inhibition of beta-oxidation, mitochondrial respiration, and/or oxidative phosphorylation. Other mechanisms discussed include the disruption of phospholipid metabolism in lysosomes, prevention of lipid egress from hepatocytes, targeting mitochondrial DNA and topoisomerase, decreasing intestinal barrier function, activation of the adenosine pathway, increasing fatty acid synthesis, and sequestration of coenzyme A. It has been found that the majority of compounds that induce steatohepatitis have cationic amphiphilic structures; a lipophilic ring structure with a side chain containing a cationic secondary or tertiary amine. Within the last decade, the ability of many chemotherapeutics to cause steatohepatitis has become more evident coining the term chemotherapy-associated steatohepatitis (CASH). The mechanisms behind drug-induced steatohepatitis are discussed with a focus on cationic amphiphilic drugs and chemotherapeutic agents. - Highlights: • Reviewed the mechanisms underlying drug-induced steatohepatitis for many compounds • Mitochondrial dysfunction is critical in the development of drug-induced steatohepatitis. • Majority of drugs that induce steatohepatitis are cationic amphiphilic drugs. • Chemotherapeutics that induce CASH are cationic amphiphilic drugs. • Majority of drugs that induce steatohepatitis are carnitine palmitoyltransferase-I inhibitors.

  16. Proton induced X-ray emission analysis

    International Nuclear Information System (INIS)

    Khan, Rashiduzzman

    1976-09-01

    The developments in proton induced X-ray emission analysis are reviewed. Techniques for analyzing thick and thin samples of different origin are described. Discussions on the application of proton induced X-ray emission analysis in different fields, comparison of the sensitivity of this method with other analytical techniques, its limitations and possible improvements are presented

  17. Treatment of lithium induced tremor with atenolol.

    Science.gov (United States)

    Davé, M

    1989-03-01

    This is the first report on the successful treatment of one patient with lithium induced tremor with hydrophilic atenolol, which is a relatively selective beta 1 adrenergic receptor blocker. Atenolol's advantages over lipophilic beta blockers in the treatment of lithium induced tremor are discussed.

  18. Collagen-induced arthritis in mice

    NARCIS (Netherlands)

    Bevaart, Lisette; Vervoordeldonk, Margriet J.; Tak, Paul P.

    2010-01-01

    Collagen-induced arthritis (CIA) in mice is an animal model for rheumatoid arthritis (RA) and can be induced in DBA/1 and C57BL/6 mice using different protocols. The CIA model can be used to unravel mechanisms involved in the development of arthritis and is frequently used to study the effect of new

  19. Uridine prevents fenofibrate-induced fatty liver.

    Directory of Open Access Journals (Sweden)

    Thuc T Le

    Full Text Available Uridine, a pyrimidine nucleoside, can modulate liver lipid metabolism although its specific acting targets have not been identified. Using mice with fenofibrate-induced fatty liver as a model system, the effects of uridine on liver lipid metabolism are examined. At a daily dosage of 400 mg/kg, fenofibrate treatment causes reduction of liver NAD(+/NADH ratio, induces hyper-acetylation of peroxisomal bifunctional enzyme (ECHD and acyl-CoA oxidase 1 (ACOX1, and induces excessive accumulation of long chain fatty acids (LCFA and very long chain fatty acids (VLCFA. Uridine co-administration at a daily dosage of 400 mg/kg raises NAD(+/NADH ratio, inhibits fenofibrate-induced hyper-acetylation of ECHD, ACOX1, and reduces accumulation of LCFA and VLCFA. Our data indicates a therapeutic potential for uridine co-administration to prevent fenofibrate-induced fatty liver.

  20. The origin of electromagnetically induced absorption

    International Nuclear Information System (INIS)

    Park, Jong Dae; Hwang, Sung Tae; Lee, Ho Seong; Park, Sung Jong; Cho, Hyuck; Choi, Won Sik

    2000-01-01

    Recently, there have been a lot of interests in the coherence superposition of atomic states which are formed by laser fields. Coherent population trapping(CTP), electromagnetically induced transparency(EIT), enhancement of the refractive index without absorption, lasing without inversion(LWI), and electromagnetically induced absorption(EIA) are the examples where coherence effects are important. Previously, the spontaneous transfer of the light-induced coherence from the excited level to the ground one was emphasized for the essential ingredient for electromagnetically induced absorption. In this paper, we have considered a case where linearly polarized coupling laser and probe laser are applied to the same degenerated ground and excited levels. We have solved the master equations for density matrix using time varying Hamiltonian and studied the absorption spectra at various conditions. We demonstrate that EIA can be observed without spontaneous transfer of the light-induced coherence in F g = 1 -> F e = 2 D2 transitions of Hydrogen atoms

  1. Charge-mediated Fab-Fc interactions in an IgG1 antibody induce reversible self-association, cluster formation, and elevated viscosity.

    Science.gov (United States)

    Arora, Jayant; Hu, Yue; Esfandiary, Reza; Sathish, Hasige A; Bishop, Steven M; Joshi, Sangeeta B; Middaugh, C Russell; Volkin, David B; Weis, David D

    Concentration-dependent reversible self-association (RSA) of monoclonal antibodies (mAbs) poses a challenge to their pharmaceutical development as viable candidates for subcutaneous delivery. While the role of the antigen-binding fragment (Fab) in initiating RSA is well-established, little evidence supports the involvement of the crystallizable fragment (Fc). In this report, a variety of biophysical tools, including hydrogen exchange mass spectrometry, are used to elucidate the protein interface of such non-covalent protein-protein interactions. Using dynamic and static light scattering combined with viscosity measurements, we find that an IgG1 mAb (mAb-J) undergoes RSA primarily through electrostatic interactions and forms a monomer-dimer-tetramer equilibrium. We provide the first direct experimental mapping of the interface formed between the Fab and Fc domains of an antibody at high protein concentrations. Charge distribution heterogeneity between the positively charged interface spanning complementarity-determining regions CDR3H and CDR2L in the Fab and a negatively charged region in C H 3/Fc domain mediates the RSA of mAb-J. When arginine and NaCl are added, they disrupt RSA of mAb-J and decrease the solution viscosity. Fab-Fc domain interactions between mAb monomers may promote the formation of large transient antibody complexes that ultimately cause increases in solution viscosity. Our findings illustrate how limited specific arrangements of amino-acid residues can cause mAbs to undergo RSA at high protein concentrations and how conserved regions in the Fc portion of the antibody can also play an important role in initiating weak and transient protein-protein interactions.

  2. Thalidomide induces apoptosis in undifferentiated human induced pluripotent stem cells.

    Science.gov (United States)

    Tachikawa, Saoko; Nishimura, Toshinobu; Nakauchi, Hiromitsu; Ohnuma, Kiyoshi

    2017-10-01

    Thalidomide, which was formerly available commercially to control the symptoms of morning sickness, is a strong teratogen that causes fetal abnormalities. However, the mechanism of thalidomide teratogenicity is not fully understood; thalidomide toxicity is not apparent in rodents, and the use of human embryos is ethically and technically untenable. In this study, we designed an experimental system featuring human-induced pluripotent stem cells (hiPSCs) to investigate the effects of thalidomide. These cells exhibit the same characteristics as those of epiblasts originating from implanted fertilized ova, which give rise to the fetus. Therefore, theoretically, thalidomide exposure during hiPSC differentiation is equivalent to that in the human fetus. We examined the effects of thalidomide on undifferentiated hiPSCs and early-differentiated hiPSCs cultured in media containing bone morphogenetic protein-4, which correspond, respectively, to epiblast (future fetus) and trophoblast (future extra-embryonic tissue). We found that only the number of undifferentiated cells was reduced. In undifferentiated cells, application of thalidomide increased the number of apoptotic and dead cells at day 2 but not day 4. Application of thalidomide did not affect the cell cycle. Furthermore, immunostaining and flow cytometric analysis revealed that thalidomide exposure had no effect on the expression of specific markers of undifferentiated and early trophectodermal differentiated cells. These results suggest that the effect of thalidomide was successfully detected in our experimental system and that thalidomide eliminated a subpopulation of undifferentiated hiPSCs. This study may help to elucidate the mechanisms underlying thalidomide teratogenicity and reveal potential strategies for safely prescribing this drug to pregnant women.

  3. Diet-induced obesity attenuates endotoxin-induced cognitive deficits.

    Science.gov (United States)

    Setti, Sharay E; Littlefield, Alyssa M; Johnson, Samantha W; Kohman, Rachel A

    2015-03-15

    Activation of the immune system can impair cognitive function, particularly on hippocampus dependent tasks. Several factors such as normal aging and prenatal experiences can modify the severity of these cognitive deficits. One additional factor that may modulate the behavioral response to immune activation is obesity. Prior work has shown that obesity alters the activity of the immune system. Whether diet-induced obesity (DIO) influences the cognitive deficits associated with inflammation is currently unknown. The present study explored whether DIO alters the behavioral response to the bacterial endotoxin, lipopolysaccharide (LPS). Female C57BL/6J mice were fed a high-fat (60% fat) or control diet (10% fat) for a total of five months. After consuming their respective diets for four months, mice received an LPS or saline injection and were assessed for alterations in spatial learning. One month later, mice received a second injection of LPS or saline and tissue samples were collected to assess the inflammatory response within the periphery and central nervous system. Results showed that LPS administration impaired spatial learning in the control diet mice, but had no effect in DIO mice. This lack of a cognitive deficit in the DIO female mice is likely due to a blunted inflammatory response within the brain. While cytokine production within the periphery (i.e., plasma, adipose, and spleen) was similar between the DIO and control mice, the DIO mice failed to show an increase in IL-6 and CD74 in the brain following LPS administration. Collectively, these data indicate that DIO can reduce aspects of the neuroinflammatory response as well as blunt the behavioral reaction to an immune challenge. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Saw palmetto-induced pancreatitis.

    Science.gov (United States)

    Jibrin, Ismaila; Erinle, Ayodele; Saidi, Abdulfattah; Aliyu, Zakari Y

    2006-06-01

    Saw palmetto is a frequently used botanical agent in benign prostatic enlargement (BPH). Although it has been reported to cause cholestatic hepatitis and many medical conditions, Saw palmetto has not been implicated in acute pancreatitis. We report a case of a probable Saw palmetto induced acute hepatitis and pancreatitis. A 55-year-old reformed alcoholic, sober for greater than 15 years, presented with severe non-radiating epigastric pain associated with nausea and vomiting. His only significant comorbidity is BPH for which he intermittently took Saw palmetto for about four years. Physical examination revealed normal vital signs, tender epigastrium without guarding or rebound tenderness. Cullen and Gray Turner signs were negative. Complete blood count and basic metabolic profile were normal. Additional laboratory values include a serum amylase: 2,152 mmol/L, lipase: 39,346 mmol/L, serum triglyceride: 38 mmol/L, AST: 1265, ALT: 1232 and alkaline phosphatase was 185. Abdominal ultrasound and magnetic resonance cholangiography revealed sludge without stones. A hepatic indole diacetic acid scan was negative. Patient responded clinically and biochemically to withdrawal of Saw palmetto. Two similar episodes of improvements followed by recurrence were noted with discontinuations and reinstitution of Saw Palmetto. Simultaneous and sustained response of hepatitis and pancreatitis to Saw palmetto abstinence with reoccurrence on reinstitution strongly favors drug effect. "Natural" medicinal preparations are therefore not necessarily safe and the importance of detailed medication history (including "supplements") cannot be over emphasized.

  5. Dipole-induced exchange bias.

    Science.gov (United States)

    Torres, Felipe; Morales, Rafael; Schuller, Ivan K; Kiwi, Miguel

    2017-11-09

    The discovery of dipole-induced exchange bias (EB), switching from negative to positive sign, is reported in systems where the antiferromagnet and the ferromagnet are separated by a paramagnetic spacer (AFM-PM-FM). The magnitude and sign of the EB is determined by the cooling field strength and the PM thickness. The same cooling field yields negative EB for thin spacers, and positive EB for thicker ones. The EB decay profile as a function of the spacer thickness, and the change of sign, are attributed to long-ranged dipole coupling. Our model, which accounts quantitatively for the experimental results, ignores the short range interfacial exchange interactions of the usual EB theories. Instead, it retains solely the long range dipole field that allows for the coupling of the FM and AFM across the PM spacer. The experiments allow for novel switching capabilities of long range EB systems, while the theory allows description of the structures where the FM and AFM are not in atomic contact. The results provide a new approach to design novel interacting heterostructures.

  6. Flow induced vibrations of piping

    International Nuclear Information System (INIS)

    Gibert, R.J.; Axisa, F.

    1977-01-01

    In order to design the supports of piping systems, estimations of the vibrations induced by the fluid conveyed through the pipes are generally needed. For that purpose it is necessary to calculate the model parameters of liquid containing pipes. In most computer codes, fluid effects are accounted for just by adding the fuid mass to the structure. This may lead to serious errors.- Inertial effects from the fluid are not correctly evaluated especially in the case of bended or of non-uniform section pipes. Fluid boundary conditions are simply ignored. - In many practical problems fluid compressibility cannot be negelcted, even in the low frequencies domain which corresponds to efficient excitation by turbulent sources of the flow. This paper presents a method to take into account these efects, by solving a coupled mechanical acoustical problem: the computer code TEDEL of the C.E.A./D.E.M.T. System, based on the finite-elements method, has been extended to calculate simultaneously the pressure fluctuations in the fluid and the vibrations of the pipe. (Auth.)

  7. Pairing induced superconductivity in holography

    Science.gov (United States)

    Bagrov, Andrey; Meszena, Balazs; Schalm, Koenraad

    2014-09-01

    We study pairing induced superconductivity in large N strongly coupled systems at finite density using holography. In the weakly coupled dual gravitational theory the mechanism is conventional BCS theory. An IR hard wall cut-off is included to ensure that we can controllably address the dynamics of a single confined Fermi surface. We address in detail the interplay between the scalar order parameter field and fermion pairing. Adding an explicitly dynamical scalar operator with the same quantum numbers as the fermion-pair, the theory experiences a BCS/BEC crossover controlled by the relative scaling dimensions. We find the novel result that this BCS/BEC crossover exposes resonances in the canonical expectation value of the scalar operator. This occurs not only when the scaling dimension is degenerate with the Cooper pair, but also with that of higher derivative paired operators. We speculate that a proper definition of the order parameter which takes mixing with these operators into account stays finite nevertheless.

  8. Mantle superplumes induce geomagnetic superchrons

    Directory of Open Access Journals (Sweden)

    Peter eOlson

    2015-07-01

    Full Text Available We use polarity reversal systematics from numerical dynamos to quantify the hypothesis that the modulation of geomagnetic reversal frequency, including geomagnetic superchrons, results from changes in core heat flux related to growth and collapse of lower mantle superplumes. We parameterize the reversal frequency sensitivity from numerical dynamos in terms of average core heat flux normalized by the difference between the present-day core heat flux and the core heat flux at geomagnetic superchron onset. A low-order polynomial fit to the 0-300 Ma Geomagnetic Polarity Time Scale (GPTS reveals that a decrease in core heat flux relative to present-day of approximately 30% can account for the Cretaceous Normal Polarity and Kiaman Reverse Polarity Superchrons, whereas the hyper-reversing periods in the Jurassic require a core heat flux equal to or higher than present-day. Possible links between GPTS transitions, large igneous provinces (LIPs, and the two lower mantle superplumes are explored. Lower mantle superplume growth and collapse induce GPTS transitions by increasing and decreasing core heat flux, respectively. Age clusters of major LIPs postdate transitions from hyper-reversing to superchron geodynamo states by 30-60 Myr, suggesting that superchron onset may be contemporaneous with LIP-forming instabilities produced during collapses of lower mantle superplumes.

  9. Chemotherapy-induced sclerosing cholangitis

    Energy Technology Data Exchange (ETDEWEB)

    Sandrasegaran, K.; Alazmi, W.M.; Tann, M.; Fogel, E.L.; McHenry, L.; Lehman, G.A

    2006-08-15

    Aim: To review the computed tomography (CT), magnetic resonance imaging (MRI) and cholangiographic findings of chemotherapy-induced sclerosing cholangitis (CISC). Methods: Between January 1995 and December 2004, 11 patients in the endoscopic retrograde cholangiography database were identified with CISC. Twelve CT, four MRI, 69 endoscopic and nine antegrade cholangiographic studies in these patients were reviewed. Serial change in appearance and response to endoscopic treatment were recorded. Results: CISC showed segmental irregular biliary dilatation with strictures of proximal extrahepatic bile ducts. The distal 5 cm of common bile duct was not affected in any patient. CT and MRI findings included altered vascular perfusion of one or more liver segments, liver metastases or peritoneal carcinomatosis. Biliary strictures needed repeated stenting in 10 patients (mean: every 4.7 months). Cirrhosis (n = 1) or confluent fibrosis (n = 0) were uncommon findings. Conclusion: CISC shares similar cholangiographic appearances to primary sclerosing cholangitis (PSC). Unlike PSC, biliary disease primarily involved ducts at the hepatic porta rather than intrahepatic ducts. Multiphasic contrast-enhanced CT or MRI may show evidence of perfusion abnormalities, cavitary liver lesions, or metastatic disease.

  10. Radiation induced sulfur dioxide removal

    International Nuclear Information System (INIS)

    Chmielewski, A.G.

    2000-01-01

    The biggest source of air pollution is the combustion of fossil fuels, were pollutants such as particulate, sulfur dioxide (SO 2 ), nitrogen oxides (NO x ), and volatile organic compounds (VOC) are emitted. Among these pollutants, sulfur dioxide plays the main role in acidification of the environment. The mechanism of sulfur dioxide transformation in the environment is partly photochemical. This is not direct photooxidation, however, but oxidation through formed radicals. Heterogenic reactions play an important role in this transformation as well; therefore, observations from environmental chemistry can be used in air pollution control engineering. One of the most promising technologies for desulfurization of the flue gases (and simultaneous denitrification) is radiation technology with an electron accelerator application. Contrary to the nitrogen oxides (NO x ) removal processes, which is based on pure radiation induced reactions, sulfur dioxide removal depends on two pathways: a thermochemical reaction in the presence of ammonia/water vapor and a radiation set of radiochemical reactions. The mechanism of these reactions and the consequent technological parameters of the process are discussed in this paper. The industrial application of this radiation technology is being implemented in an industrial pilot plant operated by INCT at EPS Kaweczyn. A full-scale industrial plant is currently in operation in China, and two others are under development in Japan and Poland. (author)

  11. Valproic Acid Induced Hyperammonaemic Encephalopathy

    International Nuclear Information System (INIS)

    Amanat, S.; Shahbaz, N.; Hassan, Y.

    2013-01-01

    Objective: To observe clinical and laboratory features of valproic acid-induced hyperammonaemic encephalopathy in patients taking valproic acid. Methods: Observational study was conducted at the Neurology Department, Dow University of Health Sciences, Civil Hospital, Karachi, from February 26, 2010 to March 20, 2011. Ten patients on valproic acid therapy of any age group with idiopathic or secondary epilepsy, who presented with encephalopathic symptoms, were registered and followed up during the study. Serum ammonia level, serum valproic acid level, liver function test, cerebrospinal fluid examination, electroencephalogram and brain imaging of all the patients were done. Other causes of encephalopathy were excluded after clinical and appropriate laboratory investigations. Microsoft Excel 2007 was used for statistical analysis. Results: Hyperammonaemia was found in all patients with encephalopathic symptoms. Rise in serum ammonia was independent of dose and serum level of valproic acid. Liver function was also found to be normal in 80% (n=8) of the patients. Valproic acid was withdrawn in all patients. Three (30%) patients improved only after the withdrawal of valproic acid. Six (60%) patients improved after L-Carnitine replacement, one (10%) after sodium benzoate. On followup, serum ammonia had reduced to normal in five (50%) patients and to more than half of the baseline level in two (20%) patients. Three (30%) patients were lost to followup after complete clinical improvement. Conclusion: Within therapeutic dose and serum levels, valproic acid can cause symptomatic hyperammonaemia resulting in encephalopathy. All patients taking valproic acid presenting with encephalopathic symptoms must be monitored for the condition. (author)

  12. Radiation induced estane polymer crosslinking

    International Nuclear Information System (INIS)

    Fletcher, M.; Foster, P.

    1997-01-01

    The exposure of polymeric materials to radiation has been known to induce the effects of crosslinking and degradation. The crosslinking phenomena comes about when two long chain polymers become linked together by a primary bond that extends the chain and increases the viscosity, molecular weight and the elastic modules of the polymer. This process has been observed in relatively short periods of time with fairly high doses of radiation, on the order of several megarads/hour. This paper address low dose exposure over long periods of time to determine what the radiation effects are on the polymeric binder material in PBX 9501. An experimental sample of binder material without explosives will be placed into a thermal and radiation field produced from a W-48 put mod 0. Another sample will be placed in a thermal environment without the radiation. The following is the test plan that was submitted to the Pantex process. The data presented here will be from the first few weeks of exposure and this test will be continued over the next few years. Subsequent data will hopefully be presented in the next compatibility and aging conference

  13. Recurrent laughter-induced syncope.

    Science.gov (United States)

    Gaitatzis, Athanasios; Petzold, Axel

    2012-07-01

    Syncope is a common presenting complaint in Neurology clinics or Emergency departments, but its causes are sometimes difficult to diagnose. Apart from vasovagal attacks, other benign, neurally mediated syncopes include "situational" syncopes, which occur after urination, coughing, swallowing, or defecation. A healthy 42-year-old male patient presented to the neurology clinic with a long history of faints triggered by spontaneous laughter, especially after funny jokes. Physical and neurological examination, and electroencephalography and magnetic resonance imaging were unremarkable. There was no evidence to suggest cardiogenic causes, epilepsy, or cataplexy and a diagnosis of laughing syncope was made. Laughter-induced syncope is usually a single event in the majority of cases, but may present as recurrent attacks as in our case. Some cases occur in association with underlying neurological conditions. Prognosis is good in the case of neurally mediated attacks. Laughter may not be recognized by physicians as a cause of syncope, which may lead to unnecessary investigations or misdiagnosis, and affect patients' quality of life.

  14. Anatomopathological Changes Induced by Mycotoxins

    Directory of Open Access Journals (Sweden)

    Emil Tirziu

    2011-10-01

    Full Text Available Fungi or mycetes represents the biggest group of microorganisms from the entire biologic system (nearly 250.000 species, very widespread in nature. They are inferior vegetal organisms, heterotrophic, lacking chlorophyll or other trophic pigments, which grow up on live organic substrates or on decaying substrates. The intensive researches from the last two decades had proved that only 30 – 40% from the total number of fungi species is capable to synthesize some toxic metabolites, and, among this species, only 60 species had proved to be dangerous for human or animals. Researches about mycotoxins action upon factors that interfere with the natural or acquired immunity are relatively recent and most of them refer to aflatoxins. The immune-suppression phenomena rely on morphological and histological modifications of lymphoid organs, changes of blood parameters, changes of functional capacity of humoral and some cellular factors. The presence of mycotoxins in feed causes major economic losses, either by their direct action (defined by disease state or indirectly, by affecting the specific and nonspecific resistance of the organism. In the present study we studied the effect of aflatoxins upon the main organs involved in immune response, pathological changes induced by mycotoxins. To determine the influence of mycotoxins on food conversion, weighings were made at the beginning and the end of the experimental period.

  15. Cisplatin-induced hypokalemic paralysis.

    Science.gov (United States)

    Mohammadianpanah, Mohammad; Omidvari, Shapour; Mosalaei, Ahmad; Ahmadloo, Niloofar

    2004-08-01

    Profound hypokalemic conditions resulting from cisplatin therapy have been known to produce hypokalemic paralysis in rare cases. We describe such a case of cisplatin-induced hypokalemic paralysis. A 15-year-old Persian girl with ovarian dysgerminoma presented with severe generalized weakness and paraplegia 1 week after the fourth course of cisplatin-based chemotherapy. On physical examination, there was symmetric flaccid paralysis and areflexia in all of the extremities and particularly in the lower limbs. Her serum potassium concentration was 1.7 mmol/L. Metastatic disease was excluded by a comprehensive systemic evaluation. Complete clinical and paraclinical recovery was achieved after short-term administration of potassium supplement. Adverse drug reactions are common with cisplatin, but the drug is only rarely associated with hypokalemic paralysis. Based on the Naranjo causality algorithm, an objective assessment revealed cisplatin to be a probable cause of hypokalemic paralysis in this case. This adverse drug event--whether isolated or secondary to hypomagnesemia--may be deceptive, leading to a fatal mistake in the oncology setting, and should therefore be precisely differentiated from cancer-related complications. This case suggests that cisplatin should be added to the list of agents causing hypokalemic paralysis. Regular serum electrolyte measurement, the early detection of cation deficiency, and appropriate replacement of cations are all recommended.

  16. Coronary spasm induced by dipyridamole

    International Nuclear Information System (INIS)

    Wartski, M.; Caussin, C.; Lancelin, B.

    2001-01-01

    A 59 years old man was admitted at hospital for recurrent instable angina 1 month after coronary artery bypass surgery. Coronary artery disease started with a transmural antero-septo-apical myocardial infarction without thrombolysis and a percutaneous angioplasty with endo-prothesis on proximal left anterior descendant artery (LAD) is performed Because of recurrent rest angina and subacute stent thrombosis, a coronary artery bypass surgery (CABG) is performed with anastomosis of the left internal thoracic artery on LAD. The patient is admitted for recurrent rest angina one month after CABG. On ECG performed during chest pain, a ST-T segment elevation occurred on inferior leads. Coronary angiography showed no significant stenosis on endo-prothesis and no bypass graft dysfunction. Dipyridamole scintigraphy was realized. 2 minutes after the beginning of Dipyridamole infusion, a ST-T elevation occurred on inferior leads and two marked antero-septal and inferior defects were noticed on myocardial scintigraphy. Images at rest showed a clear improvement in the anterior wall and the inferior wall became normally perfused Patient was treated with anti-spastic drugs and a new coronarography with methyl-ergotamine test was performed inducing chest pain, ST-T elevation on inferior leads and tri-truncular coronary spasm. Patient's treatment was then modified with introduction of Nifedipine. The patient did not experienced new recurrent chest pain and remained totally asymptomatic few months later. (authors)

  17. Hypermagnesemia-induced paralytic ileus.

    Science.gov (United States)

    Golzarian, J; Scott, H W; Richards, W O

    1994-05-01

    Hypermagnesemia is a well-known cause of hypotension and cardiac dysfunction but not well recognized is the induction of paralytic ileus. This report details the second and third adult patients reported with hypermagnesemia-induced paralytic ileus. The first patient was a 65-year-old white woman with normal renal function, who had consumed large amounts of magnesium citrate and milk of magnesia. As magnesium blood level fell from 5.1 mg/dl on admission to 2.4 mg/dl on day 3, the vomiting, obstipation, and abdominal distension resolved. The second patient was a 67-year-old woman with mild renal insufficiency, who consumed a large amount of Epsom salts containing magnesium sulfate to treat her constipation. Magnesium levels of 8.1 mg/dl on admission fell to below 3.1 mg/dl on the third hospital day and the paralytic ileus resolved. Mechanical obstruction was ruled out by colonoscopy, gastrographin enema, and barium small bowel series in both patients. Although the clinical findings of muscle weakness, flaccid paralysis, respiratory muscle paralysis or cardiac arrest due to hypermagnesemia are well described in the literature, intestinal smooth muscle dysfunction leading to paralytic ileus has only been reported in one other adult patient. The laboratory and clinical course of these two patients strongly suggest a causal relationship between hypermagnesemia and paralytic ileus.

  18. Laser induced fusion - theoretical aspects

    International Nuclear Information System (INIS)

    Lawande, S.V.; Gunye, M.R.

    1979-01-01

    The theoretical aspects of thermonuclear fusion induced by laser are discussed. After outlining the basic features and the energetics of laser fusion in the chapter 1, various non-linear mechanisms responsible for an enhanced absorption of laser energy into the plasma and the stimulated scattering processes which hinder the absorption are discussed in the second chapter on laser plasma interactions. The third chapter on gas dynamics and the shock phenomena presents the mathematical formulation of the compression to high densities of the core of the pellet for its implosion. A hydrodynamic model developed to stimulate the evolution of laser heated symmetric plasma is outlined in the chapter four on numerichigly relativistic noninteracting particles, regular bouncing states may occur at high densities, or at high temperatures. The latter case is considered in details for the collapse phase of a hot universe; lepton pair creation may completely decelerate the collapse of a hot hadronic plasma, provided the observational parameters, the Hubble constant Hsub(deg), the matter parameter Ωsub(deg) and the deceleration parameter qsub(deg) satisfy certain constraint conditions

  19. Hydrogen-induced cracking: 2

    International Nuclear Information System (INIS)

    Puls, M.P.

    1984-12-01

    There is a strong motivation for understanding the factors controlling zirconium hydride reorientation under stress because of the important role this plays in hydrogen-induced crack growth and/or crack initiation in zirconium and its alloys, particularly under thermal cycling conditions. Following an approach developed by Sauthoff, an analysis of the orienting effect of external stress on the nucleation, growth and coarsening of γ- and delta-zirconium hydride precipitates in zirconium and its alloys is presented. The analysis is based on a previous theoretical study of some of the factors affecting hydride solubility in stressed and unstressed solids. Expressions are derived for the effect of stress on nucleation, growth and coarsening. We conclude, on the basis of these that the preferential orientation of hydride precipitates under stress is most efficient during the nucleation stage. The reason for this is that the overall driving force for nucleation, for the chosen parameters and the usual experimental conditions, is fairly small. Therefore, the driving force for orientating under stress can be a substantial fraction of the overall driving force. The analysis shows that hydride growth is unlikely to play a role in preferential orientation, but coarsening could be important under carefully chosen experimental conditions, which may be relevant to the hydride-cracking process

  20. Antithyroid Drug-induced Agranulocytosis

    Directory of Open Access Journals (Sweden)

    Ming-Tsung Sun

    2009-08-01

    Full Text Available Antithyroid drugs are widely used to treat hyperthyroidism, especially Graves' disease, but they tend to cause agranulocytosis, which increases the mortality rate. Granulocyte colony-stimulating factor decreases the duration of recovery from agranulocytosis. We retrospectively studied cases of antithyroid drug-induced agranulocytosis over the past 10 years in a northern Taiwan medical center. A clinical evaluation was conducted, including a review of complete blood cell counts and differential counts. Four cases were included in this analysis. Agranulocytosis persisted in 2 cases despite a change in therapy from propylthiouracil to methimazole. Fever, sore throat, and diarrhea were common symptoms of agranulocytosis. Initial white blood cell counts ranged from 450 to 1,710/μL. Only 1 case had a positive result from a throat swab culture (Staphylococcus aureus. Three of 4 cases received granulocyte colony-stimulating factor therapy, and the recovery time ranged from 3 to 13 days. All of the patients recovered from agranulocytosis. We concluded that: (1 conducting a routine complete blood cell count is beneficial in alerting caregivers to the possibility of agranulocytosis; (2 educating patients about the common symptoms of agranulocytosis may contribute to an early diagnosis; (3 providing granulocyte colony-stimulating factor therapy to patients results in good prognosis; and (4 monitoring for cross-reactions between drugs should be performed to prevent further episodes of agranulocytosis.