bluuebunny/crossref_metadata_2025_split huggingface dataset:
A recombinant bispecific single‐chain antibody induces targeted, supra‐agonistic CD28‐stimulation and tumor cell killing
Authors: Grosse‐Hovest Ludger , Hartlapp Ingo , Marwan Wolfgang , Brem Gottfried , Rammensee Hans‐Georg , Jung Gundram 
Published: April 2003

AbstractEndowing tumor cells with costimulatory signals for T cell activation has emerged as a promising strategy for tumor immunotherapy. Costimulatory molecules were either transfected into tumor cells to generate vaccines or were fused, e.g. to antibodies against tumor‐associated antigens, to achieve targeted T cell costimulation in vivo. Here we report the production and purification of rM28, a recombinant bispecific single‐chain antibody directed to a melanoma‐associated proteoglycan and to the costimulatory CD28 molecule on human T cells. We found that a dimer of the recombinant molecule, bound to tumor target cells, induced pronounced T cell activation in peripheral blood mononuclear cell preparations without additional TCR/CD3 stimulation being required. Thelytic activity generated after 3 days of stimulation effectively prevented tumor cell growth. However, it was unspecific and predominantly mediated by non T cells. Our findings demonstrate that presentation of a CD28 antibody within a suitable recombinant, bispecific format may result in a "targeted supra‐agonistic stimulation" of the CD28 molecule, which leads to effective tumor cell killing after induction of unspecifically lytic cells.
Immunogenicity and protective efficacy of Plasmodium falciparum liver‐stage Ag‐3 in Aotus lemurinus griseimembra monkeys
Authors: Perlaza Blanca‐Liliana , Zapata Constanza , Valencia Anais Z. , Hurtado Silvia , Quintero Gustavo , Sauzet Jean‐Pierre , Brahimi Karima , Blanc Catherine , Arévalo‐Herrera Myriam , Druilhe Pierre , Herrera Sócrates 
Published: April 2003

AbstractThree recombinant proteins spanning the Plasmodium falciparum liver‐stage Ag‐3 (LSA‐3) were used to immunize Aotus monkeys. The proteins were delivered subcutaneously withoutadjuvant, adsorbed onto polystyrene 0.5 μm particles at a concentration of 2 μg per immunization. Control animals received glutathione‐S‐transferase formulated similarly. Animals were challenged as late as 5 months after the last immunization, by intravenous inoculation of 100,000 P. falciparum sporozoites of a strain heterologous to the one from which the immunogens were derived. Sterile protection was achieved in three of the five immunized monkeys but in none of four controls. Antibodies were at low titer, but reacted with the native parasite protein and were boostedby parasite challenge. Ag‐specific IFN‐γ secretion was detectable in all LSA‐3‐immunized animals in response to the LSA‐3‐derived Ag. The protection was apparently associated with high levels of IFN‐γ production in response to in vitro recall Ag. These results lend support to the vaccine potential of LSA‐3 indicated by previous results obtained in chimpanzees, as well as the value of yet another Ag‐delivery system. They also support the value of the Aotus model for the pre‐clinical development of pre‐erythrocytic‐stage vaccines.
Visualization of peptide presentation following oral application of antigen in normal and Peyer's patches‐deficient mice
Authors: Kunkel Désirée , Kirchhoff Dennis , Nishikawa Shin‐Ichi , Radbruch Andreas , Scheffold Alexander 
Published: April 2003

AbstractOrally applied antigens generate systemic unresponsiveness by induction of anergy and deletion of specific T cells at high antigen doses, and induction of regulatory T cells at low doses of antigen. These different immune reactions have been attributed to different types of antigen‐presenting cells (APC) and/or different secondary lymphoid organs participating in the induction of the immune response. We used high‐sensitivity immunofluorescence to directly identify for the first time the cells presenting orally applied antigen in vivo. At low peptide doses (<1 mg) peptide presentation was exclusively detected on dendritic cells (DC) of the Peyer's patches (PP) and mesenteric lymph nodes (mLN). At high doses (>1 mg) peptides were presented systemically and by all types of APC but presentation was still maximal on DC of the PP (up to 65%). Nevertheless, at limiting antigen doses T cell activation in the gut‐associated lymphoid tissue occurs preferentially in the mLN but not in PP. PP‐deficient mice have the same frequencies of peptide‐presenting cells in mLN, peripheral lymph nodes and spleen and activation of naive T cells in vivo is not affected. Therefore, PP are not critical for antigen presentation as well as for T cell activation in response to orally applied soluble antigens.
Effective and selective immune surveillance of the brain by MHC class I‐restricted cytotoxic T lymphocytes
Authors: Cabarrocas Julie , Bauer Jan , Piaggio Eliane , Liblau Roland , Lassmann Hans 
Published: April 2003

AbstractCytotoxic CD8+ T cells are abundantly present in human virus‐induced or putative autoimmune diseases of the central nervous system (CNS). Their direct role in the induction of inflammatory brain damage is, however, poorly understood. We have studied CD8+ T cell‐mediated brain inflammation by transferring MHC class I‐restricted hemagglutinin (HA)‐reactive T cells from a TCR transgenic mouse line into transgenic mice, which express HA in astrocytes. We show that activated CD8+ T cells alone can induce monophasic brain inflammation in immunocompetent recipient animals. Similar to previous studies, involving transfer of CD4+ cells, brain inflammation peaks after 5–7 days and then declines. The pathology of brain inflammation, however, differs fundamentally from that induced by CD4+ cells. The inflammatory reaction is dominated by T cells and activated microglia in the virtual absence of hematogenous macrophages. This is associated with exquisitely specific destruction of antigen‐containing astrocytes in the absence of any bystander damage of myelin, oligodendrocytes or neurons. Furthermore, in contrast to CD4+ T cells, some CD8+ cells accumulate in the brain and activate microglia in recipient animals, even in the absence of the specific antigen in the CNS. These data indicate that CD8+ T cells areprime candidates for immune surveillance of the CNS.
Immunostimulatory effects of plasmid DNA and synthetic oligodeoxynucleotides
Authors: Zelenay Santiago , Elías Fernanda , Fló Juan 
Published: April 2003

AbstractNucleic acid immunization is a new vaccination technology. DNA vaccines do not only carry the genetic information for the antigen of interest but also deliver an adjuvant effect due to the presence of immunostimulatory sequences within the plasmid backbone. It is generally assumed that the adjuvant properties of plasmid DNA are equal to those described for oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs. To challenge this hypothesis we have carried out a series of experiments comparing the ability of single‐ and double‐stranded ODN containing CpG motifs to induce the activation of mouse spleen cells. Moreover, we compared the immunostimulatory properties of plasmids that were modified by the addition of two to four CpG motifs. Our results establish that plasmid DNA express their adjuvanticity as either double or single strands, and no differences were observed between modified and unmodified plasmids. On the other hand, the strongest stimulatory ODN sequences lost their adjuvant properties when administered as double‐strand DNA. Furthermore, the profile of cytokines induced on spleen cells by plasmid DNA and ODN is different. Strikingly, plasmid DNA induces a moderate synthesis of IL‐6 and a strong synthesis of IFN‐γ, whereas stimulation with ODN showed an inverse profile with a higher increase in the synthesis of IL‐6 but a moderate increase in IFN‐γ. Finally, in vivo studies were consistent with the results obtained in vitro. Mice immunized with modified or unmodified plasmids encoding the glycoprotein D of HSV showed similar levels of cellular and humoral immune responses.
Schistosome N‐glycans containing core α3‐fucose and core β2‐xylose epitopes are strong inducers of Th2 responses in mice
Authors: Faveeuw Christelle , Mallevaey Thierry , Paschinger Katharina , Wilson Iain B. H. , Fontaine Josette , Mollicone Rosella , Oriol Rafael , Altmann Friedrich , Lerouge Patrice , Capron Monique , Trottein François 
Published: April 2003

AbstractDuring murine schistosomiasis, egg‐derived glycoconjugates play a key role in skewing the immune response towards a Th2 phenotype. Among the candidates responsible for this effect, complex‐type N‐glycans containing the core α3‐fucose and core β2‐xylose determinants, two glycan epitopes found in some invertebrate‐ and plant‐derived allergens, may be important. Here, we show that core α3‐fucose and core β2‐xylose determinants are expressed in the different developmental stages of Schistosoma mansoni, particularly in the excretory‐secretory systems of schistosomula and adult worms and in eggs deposited in the liver. Glycosyltransferase assays confirmed the presence of core α3‐fucosyltransferase and core β2‐xylosyltransferase activities in egg extracts. Using a model of immunization with pulsed dendritic cells, we show that egg‐derived glycoproteins containing the core α3‐fucose and core β2‐xylose determinants generate a strong Th2‐biased cellular response in mice and that the glycan moieties of this extract are important in this effect. During murine infection, these complex‐type N‐glycans induce a glycan‐specific Th2 cellular response and elicit T‐dependent anti‐core α3‐fucose and anti‐core β2‐xylose IgG1 (a Th2‐associated isotype), but not IgG2b (a Th1‐associated isotype) Ab. Taken together, our results point out theimportance of core fucosylated/xylosylated N‐glycans in the Th2 immune response during murine schistosomiasis.
Major histocompatibility complex class II‐restricted presentation of a cytosolic antigen by autophagy
Authors: Nimmerjahn Falk , Milosevic Slavoljub , Behrends Uta , Jaffee Elizabeth M. , Pardoll Drew M. , Bornkamm Georg W. , Mautner Josef 
Published: April 2003

AbstractBiochemical and functional studies have demonstrated major histocompatibility complex (MHC) class II‐restricted presentation of peptides derived from cytosolic proteins, but the underlying processing and presentation pathways have remained elusive. Here we show that endogenous presentation of an epitope derived from the cytosolic protein neomycin phosphotransferase II (NeoR) on MHC classII is mediated by autophagy. This presentation pathway involves the sequestration of NeoR into autophagosomes, and subsequent delivery into the lytic compartment. These results identify endosomes/lysosomes as the processing compartment for cytosolic antigens and furthermore link endogenous antigen presentation on MHC class II with the process of cellular protein turnover by autophagy.
TGF‐β1 modulates Fas (APO‐1/CD95)‐mediated apoptosis of human pre‐B cell lines
Authors: Lanvin Olivia , Guglielmi Paul , Fuentes Vincent , Gouilleux‐Gruart Valérie , Mazière Cécile , Bissac Eliane , R´egnier Aline , Benlagha Kamel , Gouilleux Fabrice , Lassoued Kaiss 
Published: April 2003

AbstractWe have previously shown that Fas‐induced apoptosis is markedly enhanced by IL‐7 in human pre‐B but not pro‐B cell lines. In addition, pre‐B cell receptor (pre‐BCR) ligation significantly potentiates the IL‐7 effects on Fas‐triggered pre‐B cell death. We show herein that transforming growth factor (TGF)‐β1 sharply reduces Fas‐induced death rate of pre‐B but not pro‐B cells. TGF‐β1 causes inhibition of Fas‐mediated disruption of mitochondrial transmembrane potential and cleavage of caspase 8, Bid and caspase 3. Bcl2 expression is markedly increased in TGF‐β1‐treated pre‐B cells, whereas cellular FLICE‐like inhibitory protein long (c‐FLIPL), Bcl‐XL, Bax, and Bad expression remains unchanged. TGF‐β1 causes a selective growth arrest of pre‐B cells in G0/G1 phase of the cell cycle and induces a partial down‐modulation of both Fas and pre‐BCR expression. All TGF‐β1‐mediated effects, but Bcl2 up‐regulation, can be reproduced by the LY294002 phosphatidylinositol 3‐kinase (PI3K)/Akt inhibitor but not by inhibitors of the MAPK/ERK (MEK) and Janus kinase (Jak)/STAT pathways, which promote cell death. Akt phosphorylation is strongly inhibited by TGF‐β1 in pre‐B but not pro‐B cells and is not modified by Fas engagement. Altogether, our findings suggest that TGF‐β1 prevents Fas‐induced apoptosis of pre‐B lines by inhibiting PI3K pathway and by enhancing expression of Bcl2. They also suggest that the PI3K/Akt pathway is involved in the control of Fas and pre‐BCR expression, a checkpoint in B cell development.
Schistosoma mansoni antigens modulate the activity of the innate immune response and prevent onset of type 1 diabetes
Authors: Zaccone Paola , Fehérvári Zoltán , Jones Frances M. , Sidobre Stéphane , Kronenberg Mitchell , Dunne David W. , Cooke Anne 
Published: April 2003

AbstractInfection with Schistosoma mansoni (S. mansoni) or exposure to eggs from this helminth inhibits the development of type 1 diabetes in NOD mice. In this study we show that soluble extracts of S. mansoni worm or egg completely prevent onset of type 1 diabetes in these mice but only if injection is started at 4 weeks of age. T cells from diabetes‐protected mice make IL‐10 in recall responses to parasite antigens. These cells are furthermore impaired in their ability to transfer diabetes to NOD‐SCID recipients. Bone marrow dendritic cells derived from NOD mice are found to make more IL‐10 and less IL‐12 following culture with S. mansoni soluble egg antigens in conjunction with lipopolysaccharides. NOD mice are deficient in NKT cells. Soluble worm and egg antigens increase the numbers of Vα14i NKT cells in NOD mice. These effects of schistosome antigens on the innate immune system provide a mechanism for their ability to prevent type 1 diabetes in NOD mice.
Exchange Coupling in Metal Complexes of the Second Transition Series: A Theoretical Exploration
Authors: Desplanches Cédric , Ruiz Eliseo , Alvarez Santiago 
Published: April 2003

AbstractTheoretical methods based on density functional theory using hybrid functionals provide good estimates of the exchange coupling constants for complexes with metals of the second transition series, with accuracy similar to that previously obtained for complexes with lighter transition metals. The influence of the basis set and effective core potentials has been analyzed. The more diffuse nature of the 4d orbitals, in comparison with the 3d ones, considerably modifies the electronic structure and, consequently, the magnetic properties enhancing the antiferromagnetic contributions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Organotin‐Drug Interactions. Organotin Adducts of Lornoxicam, Synthesis and Characterisation of the First Complexes of Lornoxicam
Authors: Galani Angeliki , Demertzis Mavroudis A. , Kubicki Maciej , Kovala‐Demertzi Dimitra 
Published: April 2003

AbstractThe synthesis and spectral characterisation of novel organotin complexes [SnMe2(lorn)] (1) and [SnBu2(lorn)] (2) of the potent and widely used anti‐inflammatory drug lornoxicam, H2lorn, are reported. Crystal structure determinations of complexes1 and 2 showed that the ligand is doubly deprotonated at the oxygen and amide nitrogen atoms and is coordinated to the SnR2 fragment via four‐ and six‐membered chelate rings. The monomers of 1 are linked through intermolecular hydrogen bonds of C−H‐‐O type and through C−H−π intermolecular interactions. There are two similar molecules in the asymmetric unit of 2. The dimers of 2 are arranged in polymers with a stacking of alternate parallel chains and are linked through intermolecular hydrogen bonds of C−H‐‐O type, and through C−H−π intermolecular interactions. An extended network of Sn−O−Sn, C−H‐‐O and C−H‐‐π contacts lead to aggregation and a supramolecular assembly. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Self‐Assembly of Five Cadmium(II) Coordination Polymers from 4,4′‐Diaminodiphenylmethane
Authors: Luo Junhua , Hong Maochun , Wang Ruihu , Cao Rong , Shi Qian , Weng Jiabao 
Published: April 2003

AbstractFive cadmium(II) coordination polymers formed from dadpm (dadpm = 4,4′‐diaminodiphenylmethane), namely, [Cd(dadpm)(I)2]n (1), [{Cd(dadpm)2(Cl)}(dca)]n (2) [dca = dicyanamide anion, N(CN)2−], [{Cd(dadpm)2(Br)}(dca)]n (3), [Cd(dadpm)(SCN)2]n (4) and [Cd(dadpm)(dca)2]n (5) have been synthesized and characterized by NMR, IR, and fluorescence spectroscopy as well as TG analysis. The ligand dadpm in 1 bridges the metal centers to form a zigzag chain where the halide anion I− acts as a terminal ligand. Weak Cd···I interactions between adjacent chains extend the zig‐zag chains into a wave‐like layer. Complexes 2 and 3 are isomorphous, the metal centers are bridged by dadpm to generate a double‐stranded chain containing the metallacycles of [Cd2(dadpm)2], and the halide anions (Cl− in 2 and Br− in 3) link adjacent chains into 2D layer structures in a trans mode. Dicyanamide anions in the two complexes lie between the layers as supported anions and link the adjacent layers into 3D structures through hydrogen bonds. In complex 4, the metal centers are bonded by the thiocyanate anions to form double‐stranded chains, which are linked by dadpm in different orientations resulting in a cross‐linked 3D structure. In 5, dicyanamide anions connect the cadmium(II) centers to form a [Cd(dca)2]n 2D layer, which contains 24‐membered ring units [Cd4(μ1,1‐dca‐N,N)4]. The dadpm ligand links the adjacent layers into an α‐Po‐like 3D network structure. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Cyanide‐Bridged Oligonuclear Complexes Containing Ni‐CN‐Cu and Pt‐CN‐Cu Linkages
Authors: Flay Marie‐Louise , Vahrenkamp Heinrich 
Published: April 2003

AbstractThe central building blocks Ni(CN)42− and Pt(CN)42− can be combined with one, two or four CuIIL units (L = tren, Me6tren, tpa) to form di‐, tri‐ and pentanuclear complexes with Ni‐CN‐Cu and Pt‐CN‐Cu linkages. Structure determinations of these and the side product [(tren)Cu−CN−Cu(tren)] (ClO4)2 reveal mostly linear M‐C‐N‐Cu arrays and cis‐, trans‐ and star‐like arrangements of the CN‐Cu units around the central Ni or Pt ions. The $\tilde {\nu}$
(CN) IR data for the bridging cyanides show a characteristic hypsochromic effect compared to the data for the free M(CN)42− complexes. The absorption bands in the visible spectra of the oligonuclear complexes are shifted to shorter wavelengths than those of the free LCuII‐X complexes. The CuII/CuI redox steps in the cyclic voltammograms allow the conclusion that there is electronic communication between the external CuL units when they are arranged in a trans‐orientation at PtII, but not NiII, centers. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Electroanalytical Flow Measurements–Recent Advances
Authors: Trojanowicz Marek , Szewczynska Malgorzata , Wcislo Marzena 
Published: April 2003

AbstractAs general trends in current development of chemical analysis, including electroanalysis, one can indicate a search for methods fast and multianalyte, for miniaturized measuring devices, mechanization and automation of analytical processes. In all these trends a significant role is played by measurements in flow conditions. The major advantage of flow electroanalysis is a possibility of utilizing a kinetic discrimination in potentiometric measurements and enhancement of mass transport in voltammetric techniques. Flow injection techniques provide shortening of time of a single analytical determination due to reproducible use of transient signal from the detector without need of obtaining a steady‐state equilibrium signal. Electrochemical detection in HPLC gives often improved selectivity and detection limit for electroactive solutes, whereas in capillary electrophoresis it allows a convenient design of portable, integrated chips for field application. This review presents state‐of‐the ‐art of flow electroanalysis based on 226 cited literature references
Electrochemical Detection of Copper(II) at an Electrode Modified by a Carnosine–Silica Hybrid Material
Authors: Sayen Stéphanie , Gérardin Christine , Rodehüser Ludwig , Walcarius Alain 
Published: April 2003

AbstractA new solid‐phase extractant based on carnosine moieties covalently attached to a silica backbone (S‐Car) was introduced into a carbon paste electrode (CPE), and the resulting modified electrode (S‐Car‐MCPE) was applied to the preconcentration and subsequent voltammetric quantification of copper(II). The electrode modifier was a solid organic‐inorganic hybrid prepared by co‐condensation of tetraethoxysilane with an organotri‐ethoxysilane containing a carnosine dipeptide (β‐alanyl‐l‐histidine) derivative. This hybrid material has propensity for binding CuII species from aqueous solutions. The basic voltammetric characterization of S‐Car‐MCPE, previously loaded with CuII, indicates clearly that its electrochemical activity requires desorption of the analyte out of the solid material prior to undergoing charge transfer. A two‐step analytical procedure was then applied, involving the sequence “accumulation at open‐circuit – voltammetric detection by anodic stripping differential pulse voltammetry”. Both these steps have been optimized with respect to various experimental parameters (electrode composition, pH and composition of both detection and accumulation media, preconcentration time, detection mode, presence of interference). Linear response to copper(II) was found in the 5×10−8 M to 10−6 M concentration range, with a detection limit estimated at 4×10−9 M (0.06 ppb). This new immobilization approach for peptide‐based materials on electrode surfaces is promising for further developments of organic‐inorganic hybrids in electroanalysis.
Two‐Surface Strategy in Electrochemical DNA Hybridization Assays: Detection of Osmium‐Labeled Target DNA at Carbon Electrodes
Authors: Fojta Miroslav , Havran Ludek , Billova Sabina , Kostecka Pavel , Masarik Michal , Kizek Rene 
Published: April 2003

AbstractTarget DNAs, including a 71‐mer oligonucleotide, a PCR product and a plasmid DNA, all containing oligo(A) stretches, were hybridized at magnetic Dynabeads oligo(dT)25 (DBT). The hybridization events were detected using a technique based on chemical modification of the target DNA with a complex of osmium tetroxide with 2,2′‐bipyridine (Os, bipy) and voltammetric detection at carbon electrodes. DNA was modified with Os, bipy prior to capture at DBT, at the beads, or after release from the beads. In the latter case, DNA‐Os, bipy was detected in the reaction mixture using adsorptive transfer stripping voltammetry involving extraction of unreacted Os, bipy from the electrode by organic solvents. Pre‐labeling of the target plasmid DNA and the PCR product with Os, bipy significantly increased the yield of DNA captured at the beads. Tens of femtomoles of both short (the 71‐mer oligonucleotide) and long (the 3‐kilobase plasmid) target DNAs in a 20‐microliter hybridization sample can be easily detected by means of these techniques. Various carbon electrode materials, including pyrolytic graphite (PGE), highly oriented pyrolytic graphite (HOPGE), carbon paste (CPE), glassy carbon and pencil graphite, were tested regarding their suitability for the detection of osmium‐labeled DNA. Among them, PGE and HOPGE appeared usable in the measurements of both purified DNA‐Os, bipy and its mixtures with unreacted Os, bipy while CPE was suitable for the detection purified osmium‐labeled DNA.