bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carrier‐induced epitope‐specific regulation and its bypass in a protein‐protein conjugate
Authors: Kaliyaperumal Arunan , Chauhan Virender S. , Talwar Gursaran Prasad , Raghupathy Raj 
Published: March 2007

AbstractIn the course of clinical trials on a birth control vaccine, it was found that some of the immunized women responded poorly to booster immunizations. This vaccine consists of a dimer of the β chain of human chorionic gonadotropin (βhCG) and the α chain of ovine luteinizing hormone (αoLH), linked to tetanus toxoid (TT) as a carrier. Changing this carrier to diphtheria toxoid resulted in reversion to high anti‐hCG antibody titers, indicating the extent to which the carrier influences anti‐ligand responses in this system. The suppression of anti‐hCG responses after booster immunizations was reminiscent of the phenomenon of carrier‐induced, epitope‐specific regulation. In a mouse model designed to test the effects of preimmunization with TT on anti‐hCG responses, we found that a single preimmunization with TT causes reduced anti‐hCG antibody responses in two out of four mouse strains, while anti‐αoLH antibody responses were not affected by the preimmunization with TT. This is particularly interesting considering that βhCG and αoLH were not presented when linked separately to TT. In an effort to devise a strategy to circumvent this carrier‐induced, ligand‐specific hyporesponsiveness, we investigated the effectiveness of a synthetic T helper epitope from TT as carrier. We show that preimmunization with TT causes a less profound reduction in anti‐hCG titers if the preimmunized mice are subsequently injected with αoLH‐βhCG conjugated to a synthetic tetanus toxin peptide recognized by TT‐induced and peptide‐induced T cells.
Two signaling pathways can lead to Fas ligand expression in CD8+ cytotoxic T lymphocyte clones
Authors: Anel Alberto , Simon Anna Katharina , Auphan Nathalie , Buferne Michel , Boyer Claude , Golstein Pierre , Schmitt‐Verhulst Anne Marie 
Published: March 2007

AbstractAs shown previously, a given cytotoxic T lymphocyte (CTL) clone (KB5.C20) could be induced to express the Fas ligand (FasL) by either T cell receptor (TCR) engagement or phorbol 12‐myristate 13‐acetate (PMA)/ionomycin stimulation. In contrast, another CTL clone (BM3.3) has now been found to exert Fas‐based cytotoxicity only after TCR engagement, but not after PMA/ionomycin stimulation. This suggested the existence of a PMA‐insensitive, antigeninduced pathway leading to FasL expression. The inability of PMA to promote Fas‐based cytotoxicity in BM3.3 cells was correlated with a defect in expression of the classical protein kinase C (PKC) isoforms α and βI. In KB5.C20 cells depleted of PMA‐sensitive PKC isoforms and thus no longer responsive to PMA, Fas‐based cytotoxicity could still be induced via the TCR/CD3 pathway. On the other hand, a requirement for phosphatidylinositol‐3 kinase (PI3K) selectively in this TCR/CD3‐induced pathway was demonstrated by specific inhibition with wortmannin. These results suggest that FasL expression when induced via the TCR/CD3 involves PI3K, and when induced by PMA/ionomycin requires the expression of PMA‐sensitive PKC isoforms absent in clone BM3.3. Additional data suggest that in neither case was NF‐χB activation implicated in FasL expression.
CD14lowCD16high: A cytokine‐producing monocyte subset which expands during human immunodeficiency virus infection
Authors: Thieblemont Nathalie , Weiss Laurence , Sadeghi Hoss M. , Estcourt Claudia , Haeffner‐Cavaillon Nicole 
Published: March 2007

AbstractInfection with the human immunodeficiency virus HIV‐1 is associated with the expansion of a CD14lowCD16high monocyte subset in peripheral blood. This subset, which represents a minor subpopulation of monocytes in healthy individuals, increases during HIV infection and, in patients with AIDS, may represent up to 40% of the total circulating monocyte cell population. The CD14lowCD16high circulating monocytes co‐express MAX.1, p150,95 and HLADR which are typical of tissue macrophage markers. These cells also express higher levels of intracellular interleukin (IL)‐1α and tumor necrosis factor (TNF)‐α than the CD14highCD16low monocyte population from the same patients. The CD14lowCD16high cells also express low levels of CD35, CD11a and CD4 in common with normal monocytes. When cultured in vitro, monocytes from HIV‐seropositive individuals differentiated within a few hours into an elongated fibroblastoid shape characteristic of migratory cells. Our results suggest that the expansion of the CD14lowCD16high monocyte subset, which produce high amounts of TNF‐α and IL‐1α, may participate in the immune dysfunction observed during HIV infection.
Definition of sites on HLA‐DR1 involved in the T cell response to staphylococcal enterotoxins E and C2
Authors: Hargreaves Roseanna E. G. , Brehm Rossalyn D. , Tranter Howard , Warrens Anthony N. , Lombardi Giovanna , Lechler Robert I. 
Published: March 2007

AbstractWe have exploited the relative inefficiency of interaction between staphylococcal enterotoxins, SEE or SEC2, and H‐2Ek compared to HLA‐DR1 molecules to deduce which regions of the major histocompatibility complex (MHC) class II molecule are involved in the T cell response to these superantigens. Transfectants expressing hybrid DR/H‐2E MHC class II molecules were used to present SEE to the T cell receptor Vβ8.1‐expressing Jurkat cell line, and SEC2 to human peripheral blood T cells. For SEE, the critical region of the class II molecule for T cell reactivity and for binding was the β1 domain α‐helix. The functional data were corroborated by measurements of direct binding. Sequence comparison between DR and H‐2E raised the possibility that the glutamic acid at position 84 in the β chain of H‐2Ek, in place of glycine was responsible for the observed functional effects. This suggestion was supported by the finding that DQw2 (glutamine at 84) transfectants supported the SEE response much more efficiently than DQw6 that has glutamic acid at this position. In addition, amino acid substitutions at either position 36 or 39 in the DRα1 domain abolished T cell reactivity without any obvious alteration in binding. For SEC2, use of transfectants expressing exon‐shuffled α and β chain genes showed that replacement of the α1, α2 and β1 domains with H‐2E sequence inhibited the presentation of SEC2. Similarly, the substitutions at positions 36 and 39 in the α1 domain abolished the Tcell response to SEC2. Taken together, these data may be best explained by a model in which these two toxins have primary binding sites on the β1 domain (SEE) and the α1 and α2 domains (SEC2), but by virtue of a secondary binding site on the opposite surface of the class II molecule, cross‐link two adjacent DR molecules. Such cross‐linking may be important in the induction of T cell reactivity.
Supportive cellular elements for hepatic T cell differentiation: T cells expressing intermediate levels of the T cell receptor are cytotoxic against syngeneic hepatoma, and are lost after hepatocyte damage
Authors: Kawachi Yasuyuki , Arai Katsumitsu , Moroda Tetsuya , Kawamura Toshihiko , Umezu Hajime , Naito Makoto , Ohtsuka Kazuo , Hasegawa Katsuhiko , Takahashi‐Iwanaga Hiromi , Iwanaga Toshihiko , Shultz Leonard D. , Watanabe Hisami , Abo Toru 
Published: March 2007

AbstractExtrathymic T cells exist in the liver and are often seen in close contact with Kupffer cells in the hepatic sinusoids. Since selective depletion of Kupffer cells has become possible by using liposome‐encapsulated clodronate, it was investigated whether elimination of Kupffer cells influences the level of extrathymic T cells in the liver. Extrathymic T cells were identified as interleukin‐2 receptor β‐chain (IL‐2Rβ) intermediate TCR (TCRint) cells by two‐color staining for CD3 or T cell receptor (TCR) and IL‐2Rβ. The elimination of Kupffer cells did not significantly affect levels of TCRint cells up to 7 days after treatment. We then examined monocyte colony stimulating factor (M‐CSF)‐deficient op/op mice (low levels of Kupffer cells). Extrathymic T cells both in the liver and spleen of these mice were detected at a level comparable to that of control mice. Since extrathymic T cells in the liver are sometimes located in the parenchymal space, the relationship between extrathymic T cells and hepatocytes was then examined. Electron microscopy revealed that some hepatic T cells adhered directly to hepatocytes. When hepatocytes were damaged by a single injection of CCl4, hepatocyte death and subsequent hepatic fibrosis were induced. Beginning 3 days after injection, CD3int cells, but not other type of cells, decreased prominently. Purified CD3int cells, as well as whole lymphocytes in the liver, were cytotoxic against syngeneic hepatoma. In parallel with the above‐mentioned hepatic damage, the cytotoxic activity of lymphocytes against such targets was impaired in the liver. These results suggest that extrathymic generation of TCRint cells and their acquisition of cytotoxic function are relatively independent of Kupffer cells, but are dependent on hepatocytes.
Expression of the complement alternative pathway by human myoblasts in vitro: Biosynthesis of C3, factor B, factor H and factor I
Authors: Legoedec Jocelyne , Gasque Philippe , Jeanne Jean‐François , Fontaine Marc 
Published: March 2007

AbstractIn this study, we demonstrate expression in vitro of complement alternative pathway components C3, factor B, factor H and factor I by normal human myoblasts and human rhabdomyosarcoma cell lines CRL1558 and HTB153. Proteins in culture supernatants were detected by Western (protein) blot analysis and biosynthetic labeling followed by immunoprecipitation experiments, and quantified by ELISA. Newly secreted proteins were structurally and functionally similar to their serum counterparts. An additional polypeptide of 43 kDa with factor H immunoreactivity was detected, which could correspond to the N‐terminal truncated form found in plasma. Protein expression was correlated with mRNA expression by reverse transcriptase‐polymerase chain reaction analysis. The major proteins of complement alternative pathway C3, factor B and factor H were produced constitutively by skeletal muscle cells at a rate of 50 to 150 ng/106 cells/ml and factor I was expressed 20 ng/106 cells/ml. These syntheses in vitro were regulated by inflammatory cytokines. Interferon‐γ significantly upregulated C3, factor B and factor H expression, but had no effect on factor I production. Interleukin‐1β strongly enhanced C3 and factor B production and had a weak enhancing or no effect on factor I and factor H secretion. Human myoblast cell lines constitute an interesting model to analyze complement biosynthesis by human skeletal muscle cells. Local complement expression by skeletal muscle in vivo may be implicated in some muscular inflammatory or pathological processes.
Interleukin‐6 signal transducer gp130 has specific binding sites for different cytokines as determined by antagonistic and agonistic anti‐gp130 monoclonal antibodies
Authors: Wijdenes John , Heinrich Peter C. , Müller‐Newen Gerhard , Roche Catherine , Gu Zong‐Jiang , Clément Claude , Klein Bernard 
Published: March 2007

AbstractThe cytokines interleukin (IL)‐6, IL‐11, ciliary neurotrophic factor (CNTF), leukemia inhibitor factor (LIF), oncostatin M (OSM) and probably the recently cloned cytokine cardiotrophin‐1, signal, in combination with their specific receptors, through the common signal transducer gp130. Here, we report that the signaling activities of IL‐6, IL‐11, CNTF and OSM/LIF can be specifically blocked by different anti‐gp130 monoclonal antibodies (mAb). Furthermore, we found two mAb, B‐P8 and B‐S12, which directly activate gp130 independently of the presence of cytokines or their receptors. This agonistic activity includes induction of cytokine‐dependent cell proliferation and stimulation of acute‐phase protein synthesis in liver cells. Compared to B‐P8 mAb, the B‐S12 mAb exhibited the strongest agonistic activity, while both mAb are synergistic in their action. This activity could not be blocked by inhibiting mAb against IL‐6 and the IL‐6 receptor. In contrast to F(ab′)2 of B‐S12 which still could activate gp130, Fab fragments completely lost their agonistic activity. Activation by tyrosine phosphorylation of the transcription factors Stat1 and APRF/Stat3 was also induced by B‐S12 and B‐P8, suggesting that both mAb induce homodimerization of gp130. Since hematopoietic stem cells express gp130 on their plasma membrane, it was anticipated that the agonistic anti‐gp130 mAb could stimulate the proliferation of these stem cells. Indeed, B‐S12 and B‐P8 were able to stimulate CD34+ cells. In summary, our data show for the first time that mAb against gp130 can specifically block the action of distinct IL‐6‐type cytokines that signal through gp130. Such mAb might be of great value for therapeutic applications in diseases where a single cytokine action needs to be inhibited. In addition, the agonistic gp130 mAb may be used as growth factors for maintenance and expansion of stem cells prior to grafting.
Perforin dependence of natural killer cell‐mediated tumor control in vivo
Authors: van den Broek Maries F. , Kägi David , Zinkernagel Rolf M. , Hengartner Hans 
Published: March 2007

AbstractAdaptive immune surveillance by T cells against infections and tumors depends on the presence of antigenic peptides presented by major histocompatibility complex (MHC) molecules. If antigenic tumor‐specific peptides or MHC class I molecules are absent, the adaptive T cell immune response fails. Natural killer (NK) cells seem to complement the specific T cells by recognizing target cells lacking MHC class I (e.g. RMA‐S). The role of perforin, which is crucially involved in T cell and NK cell‐mediated target cell lysis, was evaluated in mice lacking perforin with respect to their capacity to eliminate a syngeneic lymphoid tumor. Here, we show that growth of MHC class I− RMA‐S tumor cells in unprimed mice was controlled by NK cells through perforin‐dependent cytotoxicity.
A role for CD44 in T cell development and function during direct competition between CD44+ and CD44– cells
Authors: Graham Victoria A. , Marzo Amanda L. , Tough David F. 
Published: March 2007

AbstractThe role of CD44 in T cell biology remains incompletely understood. Although studies using anti‐CD44 antibodies have implicated this cell adhesion molecule in a variety of important T cell processes, few T cell defects have been reported in CD44‐deficient mice. We have assessed the requirement for CD44 in T cell development and mature T cell function by analyzing mice in which CD44–/– and WT cells were produced simultaneously. In mixed (CD44–/– + CD44+/+) bone marrow chimeras, production of CD44–/– T cells was shown to be reduced compared to WT cells due to inefficient intrathymic development. In addition, mature CD44–/– CD8+ T cells generated a substantially lower response than WT T cells after infection of mice with lymphocytic choriomeningitis virus, with the reduction in response apparent in both lymphoid and non‐lymphoid tissues. Overall, these results demonstrate a poor capacity of CD44–/– T lineage cells to compete with WT cells at multiple levels, implicating CD44 in normal T cell function.
The tyrosine phosphatase SHP‐2 regulates differentiation and apoptosis of individual primary T lymphocytes
Authors: Hoff Holger , Brunner‐Weinzierl Monika C. 
Published: March 2007

AbstractAlthough phosphatases are key players of intracellular processes, not much is known about the phosphatase SHP‐2 during T cell differentiation. Here we show that ectopic over‐expression of SHP‐2 in primary T helper cells directly reduced the frequency of individual lymphocytes expressing pro‐inflammatory cytokines after antigen‐specific stimulation by a mechanism impairing activation of protein kinase C. In addition we demonstrate that SHP‐2 mediates enhanced migration upon CXCR4 signaling in a G‐protein‐dependent manner. Most strikingly, SHP‐2 mediated a dramatic increase in apoptosis by highly enhanced activation of caspases. Co‐immunoprecipitations of SHP‐2 and c‐Cbl from primary T helper cells demonstrated that SHP‐2 strongly interacts with the ubiquitin ligase c‐Cbl, indicating that c‐Cbl could mediate the negative signals of SHP‐2. Our results show that SHP‐2 signal transduction regulates central checkpoints of T cell differentiation by the activation of distinct signaling cascades.
Bacterial clearance of Pseudomonas aeruginosa is enhanced by the inhibition of COX‐2
Authors: Sadikot Ruxana T. , Zeng Heng , Azim Anser C. , Joo Myungsoo , Dey Sudhansu K. , Breyer Richard M. , Peebles R. Stokes , Blackwell Timothy S. , Christman John W. 
Published: March 2007

AbstractProstanoids generated by COX‐2 are involved in the regulation of inflammation but their exact role in the innate immune response has not been defined. We investigated whether COX‐2 is involved in host defense against Pseudomonas aeruginosa pneumonia. In vitro studies, in a macrophage cell line, showed that cytotoxic strain of P aeruginosa (PA103) induced significant COX‐2 protein expression and enzymatic function. In vivo data showed that infection with PA103 increased COX‐2 protein production in whole lung tissue compared to mice that were infected with mutant bacteria that lack ExoU (ΔU) or ExoU and ExoT (ΔUT). COX‐2–/– mice had accentuated clearance of cytotoxic P. aeruginosa from the lungs. We further tested the effects of COX‐2 products such as prostaglandin E2 on the function of phagocytic cells. Our studies indicate that prostaglandin E2 may be involved through interacting with the EP2 receptors in modulating the host response because treatment of macrophages with prostaglandin E2 suppressed production of reactive oxygen species. Furthermore there was enhanced bacterial clearance in EP2 receptor–/– mice compared to the wild‐type controls. Thus it is possible that inhibition of COX‐2 or EP2 receptors could be an effective adjunctive treatment for severe or resistant P. aeruginosa pneumonia.
New Anions of Pentacoordinate Phosphorus Containing Fluorine and Trifluoromethyl Groups
Authors: Pavlenko Natalya V. , Babadzhanova Lesya A. , Gerus Igor I. , Yagupolskii Yurii L. , Tyrra Wieland , Naumann Dieter 
Published: March 2007

AbstractThe unique pseudo‐trigonal‐bipyramidal CF3PF3O– and (CF3)2PF2O– anions were obtained and characterised for the first time. They were formed by the reactions of (PhO)3P(O), Me3SiCF3 and the fluoride ion sources [Me4N]F and CsF, respectively, in glyme. These anions represent the stable transition states postulated for nucleophilic substitution at a tetrahedral phosphorus atom. The salt Cs[(CF3)2PF2O] (7) is stable at room temperature for a month, while [Me4N][CF3PF3O] (1) dismutates into [Me4N][CF3PF(O)O] (2) and [Me4N][CF3PF5] (3) above 0 °C. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Synthesis, Characterization, and Catalytic Activity of Some Neodymium(III), Ytterbium(II), and Europium(II) Complexes with Pyrrolidinyl‐ and Piperidinyl‐Functionalized Indenyl Ligands
Authors: Zhou Shuangliu , Wang Shaowu , Sheng Enhong , Zhang Lijun , Yu Zeyan , Xi Xiaobing , Chen Guodong , Luo Wei , Li Yan 
Published: March 2007

AbstractA series of organolanthanide complexes with pyrrolidinyl‐ and piperidinyl‐ functionalized indenyl ligands were synthesized by reaction of [(Me3Si)2N]3LnIII(μ‐Cl)Li(THF)3 (Ln = Yb, Eu, Nd) with the corresponding indene compounds. Treatment of [(Me3Si)2N]3YbIII(μ‐Cl)Li(THF)3 with 2 equiv. of C9H6‐1‐R‐3‐CH2SiMe2NC4H8 (R = H, CH3) in refluxing toluene produced the corresponding organoytterbium(II) complexes with formula [ηm:η1‐C9H5‐1‐R‐3‐CH2SiMe2NC4H8]2YbII [m = 5, R = H (2); m = 3, R = CH3 (3)] in 49 and 58 % yield, respectively. Treatment of [(Me3Si)2N]3LnIII(μ‐Cl)Li(THF)3 (Ln = Yb, Eu, Nd) with 2 equiv. of C9H7CH2SiMe2NC5H10 (1) in toluene at moderately high temperatures afforded, after workup, the corresponding organolanthanide complexes with formula [η5:η1‐C9H6CH2SiMe2NC5H10]2YbII (4), [η5:η1‐C9H6CH2SiMe2NC5H10]2EuII (5), and [C9H6CH2SiMe2NC5H10]3NdIII·THF (6) in 37, 71, and 29 % yield, respectively. All the compounds were fully characterized by spectroscopic methods and elemental analyses. The structures of complexes 2, 3, 5, and 6 were additionally determined by single‐crystal X‐ray analyses. The catalytic properties of all the organolanthanide complexes on the ring‐opening polymerization of ϵ‐caprolactone have been studied. The effects of temperature, solvent, and coordination on the catalytic activities of the complexes were examined. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Recent Advances in Asymmetric Organocatalytic 1,4‐Conjugate Additions
Authors: Tsogoeva Svetlana B. 
Published: March 2007

AbstractRecent progress in the field of asymmetric organocatalytic 1,4‐conjugate addition reactions, regarded as belonging among the more synthetically important carbon–carbon bond‐forming reactions, is described. The focus is on some recent advances in the following selected reactions: additions of various nucleophiles to α,β‐unsaturated cyclic and acyclic enals, enones, vinyl sulfones and nitro olefins, addition of malonates and/or ketones to acyclic enones, or of aldehydes and ketones to vinyl ketones and nitro olefins, together with some multicomponent domino reactions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Synthesis of Bridged and Nonbridged N‐Heterocycles by Cyclocondensation of Bis(silyl enol ethers) with Iminium Salts
Authors: Langer Peter 
Published: March 2007

AbstractCyclization reactions of iminium salts with bis(silyl enol ethers) – such as 1,3‐bis(silyloxy)‐1,3‐butadienes and 1,1‐bis(silyloxy)ketene acetals – allow a convenient synthesis of various bridged and nonbridged N‐heterocycles. The iminium salts were generated in situ from pyridines, quinolines, isoquinolines, quinoxalines, pyrazines, quinazolines, and 2,5‐dimethoxypyrrolidines. The products include 4‐oxa‐9‐aza‐7,8‐benzobicyclo[3.3.1]nonan‐3‐ones, 7‐oxa‐1,4‐diaza‐2,3‐benzobicyclo[4.3.0]non‐2‐en‐6‐ones, 7‐oxa‐1,4‐diazabicyclo[4.3.0]non‐2‐en‐6‐ones, 3‐hydroxy‐9‐aza‐7,8‐benzobicyclo[3.3.1]non‐3‐enes, 4‐hydroxy‐1,9‐diaza‐7,8‐benzobicyclo[3.3.1]non‐4‐enes, alkylidene‐7‐oxa‐1,4‐diaza‐2,3‐benzobicyclo[4.3.0]non‐2‐enes, and tropinones.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Fluorous “Racemic” Mixture Synthesis: Simultaneous Strategy for Demixing and Enantioseparation of Racemic Fluorous‐Tagged Products
Authors: Tonoi Takayuki , Mikami Koichi 
Published: March 2007

AbstractReported herein is the concept of fluorous “racemic” mixture synthesis (FRMS), which is applied to two types of proof‐of‐concept experiments. Mixtures of racemic O‐benzoylmandelate derivatives and prochiral crotonamide derivatives, respectively, bearing different lengths of fluorous‐cleavable tags are taken through a segmented reaction sequence to provide their enantiomers, as well as their individual derivatives, by virtue of chiral β‐cyclodextrin columns. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)