bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disulfide bonds in merozoite surface protein 1 of the malaria parasite impede efficient antigen processing and affect the in vivo antibody response
Authors: Hensmann Meike , Li Ching , Moss Catherine , Lindo Viv , Greer Fiona , Watts Colin , Ogun Solabomi A. , Holder Anthony A. , Langhorne Jean 
Published: February 2004

AbstractThe 19 kDa C‐terminal fragment of the malaria parasite merozoite surface protein 1 (MSP119) is a leading malaria vaccine candidate. In rodents, high antibody levels to this protein confer protective immunity, and can be generated by immunization with the antigen in adjuvants. In natural human infections, however, MSP119‐specific antibody responses can be short‐lived andcomparatively low, despite repeated exposure to infection. The tightly folded structure of MSP119 is stabilized by five or six disulfide bonds. These bonds impede antigen processing and, thereby, may affect the generation of CD4+ T cells providing help for B cells. Asparagine endopeptidase could digest unfolded, but not native MSP119 in vitro. Immunization with unfolded MSP119 resulted in a faster antibody response, and a combination of unfolded and native MSP119 increased antibody responses to the native form. Immunization with either form of the antigen activated similar numbers of CD4+ T cells, but, unlike the antibody response, CD4+ T cells immunized with one form of MSP119 were able to respond in vitro to the other form of the protein. Although the reduced form of MSP119 does not induce protective antibodies, our data suggest that inclusion of unfolded protein may improve the efficacy of MSP119 as a vaccine.See correction http://dx.doi.org/10.1002/eji.200490004
Induction of FOXP3‐expressing regulatory CD4pos T cells by human mature autologous dendritic cells
Authors: Verhasselt Valérie , Vosters Olivier , Beuneu Claire , Nicaise Charles , Stordeur Patrick , Goldman Michel 
Published: February 2004

AbstractCurrent literature suggests that T cells recognizing antigen on mature dendritic cells (DC) differentiate into effector T cells whereas tolerance is induced when antigen is presented by immature DC. We investigated the consequences of the interactions between immature or lipopolysaccharide‐matured DC and CD4pos T lymphocytes in absence of foreign antigen. While immature DC did not induce significant CD4pos T cell activation, we observed that a significant fraction of CD4pos T cells cultured with mature autologous DC displayed phenotypic features of activation and produced IL‐2, IFN‐γ, IL‐10 and TGF‐β. Furthermore, CD4pos T lymphocytes primed by mature, but not immature, autologous DC acquired regulatory properties. Indeed, when added to an allogeneic mixed leukocyte reaction, they suppressed the response of alloreactive T lymphocytes to the priming DC while responses to third‐party stimulators were spared. The generation of CD4pos T cells with regulatory function by autologous stimulation did not require the presence of natural CD4posCD25pos regulatory T cells. In addition, the acquisition ofregulatory function by CD4posCD25neg T cells stimulated by autologous mature DC was accompanied by the induction of FOXP3 expression. Our data suggest that during inflammatory conditions, presentation of self antigens by mature DC to autologous T lymphocytes could contribute to the generation of regulatory mechanisms.
Viral infection and Toll‐like receptor agonists induce a differential expression of type I and λ interferons in human plasmacytoid and monocyte‐derived dendritic cells
Authors: Coccia Eliana M. , Severa Martina , Giacomini Elena , Monneron Danièle , Remoli Maria Elena , Julkunen Ilkka , Cella Marina , Lande Roberto , Uzé Gilles 
Published: February 2004

AbstractIn humans, the type I interferon (IFN) family consists of 13 IFN‐α subtypes, IFN‐β and IFN‐o the newly discovered IFN‐like family consists of IFN‐λ1, ‐λ2 and ‐λ3. We have investigated the expression of type I and λ IFN genes following virus infections or Toll‐like receptor (TLR) triggering in monocyte‐derived DC (MDDC) and plasmacytoid DC (pDC). We found thatall IFN‐α, ‐β, ‐o and ‐λ subtypes are expressed in influenza‐virus‐infected MDDC or pDC. Conversely, differential type I IFN gene transcription was induced in MDDC and pDC stimulated by specific TLR agonists. TLR‐9 stimulation by CpG DNA induced the expression of all IFN‐α, ‐β, ‐o and ‐λ subtypes in pDC, whereas TLR‐4 stimulation by LPS, or TLR‐3 stimulation bypoly I:C, induced only IFN‐β and IFN‐λ gene expression in MDDC. The expression pattern of IFN regulatory factor (IRF)‐5 and IRF‐7 in MDDC and pDC was also determined. IRF‐5 was constitutively expressed in the two DC subsets whereas IRF‐7 was constitutive in pDC but its expression was induced along MDDC maturation. Overall, our data indicate that the coordinated expression of IFN‐λ with IFN‐β would be of crucial importance for the maturation of DC.
Mycobacterium vaccae induces a population of pulmonary CD11c+ cells with regulatory potential in allergic mice
Authors: Adams Victoria C. , Hunt Jon R. F. , Martinelli Roberta , Palmer Rebecca , Rook Graham A. W. , Brunet Laura Rosa 
Published: February 2004

AbstractThe hygiene hypothesis proposes that common, harmless microorganisms, present throughout our evolutionary history, have helped to develop immunoregulatory mechanisms that prevent inappropriateimmune responses by the host. Using a mouse model of allergic pulmonary inflammation, we report that treatment with an ubiquitous saprophytic mycobacterium, Mycobacterium vaccae, significantly reduces allergic inflammation by decreasing type 2 responses such as eosinophilia and IL‐4 expression. Rather than observing an increase in type‐1 cytokine expression, we found elevated production of IL‐10 in the lungs suggesting a role for regulatory T cells. Since induction of these cells may be dependent on APC, we investigated the effects of M. vaccae treatment on pulmonary CD11c+ cells. Increased levels of IL‐10, TGF‐β and IFN‐α mRNA were detected in CD11c+ cells from M. vaccae‐treated allergic mice. We propose that M. vaccae‐induced CD11c+ cells have a potential regulatory role at the site of inflammation through their secretion of immunomodulatory cytokines.
Ectopic T cell receptor expression causes B cell immunodeficiency in transgenic mice
Authors: Lobito Adrian A. , Lopes Marcela F. , Lenardo Michael J. 
Published: February 2004

AbstractMice expressing transgenic T cell receptors (TCR) are used to explore important questions in immunity. However, transgene expression may have unexpected effects. We previously reported a B cell immunodeficiency, comprising decreased B cell numbers and diminished antibody responses, in mice that express a transgenic TCR specific for nicotinic acetylcholine receptor; the mice were generated using cassette vectors designed specifically for transgenic TCR expression [see Kouskoff et al. J. Immunol. Methods 1995. 180: 273–280]. We now show data suggesting that this defect is due to the expression and accumulation of TCR α and β chains inside B cells and induction of an endoplasmic reticulum stress response, causing apoptosis at the pre B‐I and later B cell stage. Thus, inappropriate transgene expression can profoundly affect B cells, leading to a previously undescribed mechanism of immunodeficiency.
Retinoids induce Fas(CD95) ligand cell surface expression via RARγ and nur77 in T cells
Authors: Tóth Beáta , Ludányi Katalin , Kiss Ildikó , Reichert Uwe , Michel Serge , Fésüs László , Szondy Zsuzsa 
Published: February 2004

AbstractCells from the CD4+ murine T hybridoma line IP‐12‐7 enter the apoptotic suicide program via the Fas ligand (FasL)/Fas‐mediated pathway upon TCR stimulation. This stimulus regulates the sensitization of the Fas death pathway and the cell surface appearance of preformed FasL. The apoptosis is dependent on new mRNA and protein synthesis and involves up‐regulation of nur77.Two groups of nuclear receptors for retinoic acids (RA) have been identified: retinoic acid receptors (RAR) and retinoid X receptors. IP‐12‐7 cells express RARα and RARγ. Here we show that,in the IP‐12‐7 T cells, RA also induced the expression and DNA binding of nur77, and the cell surface appearance of FasL. The induction was mediated via RARγ. Despite the induced expression of cell surface FasL, only two structurally related RARγ‐selective compounds, CD437 and CD2325, initiated apoptosis in these cells. The lack of apoptosis induction by natural RA was related to the inability of RARγ to sensitize the Fas death‐pathway. Cell surface FasL, however, was able to induce cell death in Fas‐bearing target cells. Natural RA also induced the expression of FasL in phytohemagglutinin‐activated peripheral murine T cells. It is proposed that therapeutically administered RA might induce apoptosis in Fas‐sensitive cells via induction of FasL expression in activated Tcells.
Ex vivo detection of myelin basic protein‐reactive T cells in multiple sclerosis and controls using specific TCR oligonucleotide probes
Authors: Hong Jian , Zang Ying C. Q. , Li Sufang , Rivera Victor M. , Zhang Jingwu Z. 
Published: February 2004

AbstractT cell reactivity to candidate myelin autoantigens, such as myelin basic protein (MBP), may play an important role in the pathogenesis of multiple sclerosis (MS). Although MBP‐reactive T cellshave been found to undergo in vivo activation in patients with MS, their true precursor frequency in MS is unknown as current frequency analysis is commonly based on the T cell functional responses to MBP. In this study, we developed a TCR sequence‐based ex vivo detection system using colony hybridization with oligonucleotide probes specific for CDR3 of selected T cell clones for the analysis of true T cell precursor frequency in PBMC. The results revealed that the precursor frequency of five independent T cell clones recognizing the immunodominant MBP83–99 region was found to be in the range of 1.6×10–4 in total T cells in three HLA‐DR2 patients with MS compared to that of 0.25×10–4 in HLA‐DR2 healthy individuals. The observed frequency of MBP83–99–reactive T cells in MS patients was considerably higher than those measured in parallel by cell culture‐based analysis (2.3×10–6) or by enzyme‐linked immunospot assay (3.9×10–5) in the same peripheral blood mononuclear cell specimens. Furthermore, the study showed that MBP83–99–reactive T cells detected ex vivo belonged to CD45RA+, CD25+ and CD95– T cell subsets as evidenced by preferential expression of specific TCR transcripts in these cell fractions.
Disulfide bonds in merozoite surface protein 1 of the malaria parasite impede efficient antigen processing and affect the in vivo antibody response
Authors: Hensmann M. , Li C. , Moss C. , Lindo V. , Greer F. , Watts C. , Ogun S. A. , Holder A. A. , Langhorne J. 
Published: February 2004

AbstractVol. 34(3) 2004, DOI 10.1002/eji.200324514Due to a technical error, the wrong affiliations were given for C. Moss and V. Lindo. These are correct as given above.See original article http://dx.doi.org/10.1002/eji.200324514
The Synthesis of Arylalkyne‐Substituted Tetrapyrazinoporphyrazines and an Evaluation of Their Potential as Photosensitisers for Photodynamic Therapy
Authors: Mitzel Frieder , FitzGerald Simon , Beeby Andrew , Faust Rüdiger 
Published: February 2004

AbstractNew aryl‐terminated octaalkynyl tetrapyrazinoporphyrazines were prepared in three steps starting from functionalised bisarylalkynyl 1,2‐diones. While the tert‐butylphenyl substituents were shown to aid solubility in organic solvents and to reduce chromophore aggregation efficiently, more hydrophilic tetrapyrazinoporphyrazines were obtained through the use of polyethylene glycol‐substituted (PEG‐substituted) phenyl groups. The absorption profiles and the singlet oxygen quantum yields of the acetylenic tetrapyrazinoporphyrazines were determined with a view to assess their suitability for PDT applications. In all cases the presence of the terminal aryl moieties resulted in noticeable bathochromic and hyperchromic shifts of the lowest‐energy absorption maxima to 680 nm and of the extinction coefficients to beyond 320000. If magnesium is coordinated in the centre of the acetylenic tetrapyrazinoporphyrazines the compounds have singlet oxygen quantum yields of 0.40 in THF. With zinc as the central metal ion, the singlet oxygen quantum yields in the same solvent increase to 0.70. The absorption characteristics of the newly prepared chromophores, as well as their ability to generate singlet oxygen, suggest that these phthalocyanine analogues are interesting candidates as PDT‐sensitisers. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Cycloaddition Reactions of 1,4‐Dihydronaphthalene‐1,4‐epoxide with Cyclohexadiene and 7‐(Methoxycarbonyl)cycloheptatriene: Selectivity in Additions
Authors: Menzek Abdullah , Altundaş Aliye , Çoruh Ufuk , Akbulut Nihat , López Ezequiel M. Vázquez , Hökelek Tuncer , Erdönmez Ahmet 
Published: February 2004

AbstractCycloaddition reactions of naphthalene‐1,4‐epoxide (1) with both 7‐(methoxycarbonyl)cycloheptatriene (2) and cyclohexadiene (4) give adducts of type 3 and 5 exclusively. Selectivity was observed for the cycloaddition and bromination reactions, but neighboring group participation also occurrs in the latter. The formation of the products is discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Drastic Increase in the Flexibility of Open Host Frameworks of a Steroidal Host Compound upon Shortening Its Spacer
Authors: Kato Kazuaki , Sugahara Michihiro , Tohnai Norimitsu , Sada Kazuki , Miyata Mikiji 
Published: February 2004

AbstractNordeoxycholic acid (NDCA), which has a shorter side chain than the steroidal host compound, deoxycholic acid (DCA), forms inclusion crystals with various organic substances at 1:1 or 2:1 host−guest ratios. X‐ray crystallographic studies reveal that four types of host frameworks (bilayer, monolayer, tape, and hexagonal) are generated by NDCA, in stark contrast to the robust and dominant bilayer frameworks formed from DCA, although they have the same functional groups capable of hydrogen bonding. The first three host frameworks are further divided into three, two, and four sub‐types by arrangements of the hydrogen‐bonded host columns, tapes, or layers, respectively. A total of nine types of open host frameworks are observed depending on the nature of the guest compounds. The sizes of the guest compounds induce isomerization of these host frameworks having molecular cavities, which is rationalized by the range of values of PCcavity, which are ratios of the volumes between the guest compound and the host cavities. Such a drastic increase of flexibility of the open host framework by the slight chemical modification from DCA to NDCA deserves attention with respect to crystal engineering. Unique 21 helical assemblies of DCA are linked by the carboxyl group at the side chain to form a robust sheet‐like structural motif. In NDCA, on the other hand, the linkage between the helices becomes impossible because of the shortening of the side chain’s length, which results in destruction of the sheet‐like motif to yield renewed molecular voids among the unique 21 helical assemblies. These remarkable differences in the flexibility of the open host frameworks provide us with a possible strategy for designing of new host compounds. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Lycoperdinoside A and B, New Glycosides from the Slime Mold Enteridium lycoperdon
Authors: Řezanka Tomáš , Dvořáková Radmila , Hanuš Lumír O. , Dembitsky Valery M. 
Published: February 2004

AbstractTwo, novel, six‐membered lactone glycosides (lycoperdinoside A and B) were isolated from the slime mold Enteridium lycoperdon. Their structures, including the absolute configurations of the hydroxy and methyl groups, were determined by means of extensive spectroscopic data such as MS, IR, UV, and 1D and 2D NMR spectra and chemical degradation. The compounds have structures containing a β‐L‐amicetosyl‐(1⇄4)‐α‐L‐amicetosyl unit and a β‐L‐amicetosyl‐(1⇄4)‐α‐L‐amicetosyl‐(1⇄4)‐β‐L‐rhodinosyl unit, respectively. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis of the Trisaccharide and Tetrasaccharide Moieties of the Potent Immunoadjuvant QS‐21
Authors: Zhu Xiangming , Yu Biao , Hui Yongzheng , Schmidt Richard R. 
Published: February 2004

AbstractThe title trisaccharide and tetrasaccharide moieties have been synthesized as part of our research programme to construct the complex triterpenoid saponin QS‐21, a potent immunoadjuvant, which has been used in a series of clinical immunization trials. In view of the unwillingness of glucuronic acid as glycosyl acceptor, the branched glucuronic acid‐containing trisaccharide20was synthesized fromD‐glucose, which was in turn glycosylated at positions 2 and 3, followed by oxidation at position 6, in a linear sequence of 15 steps and in good overall yield. The apiose‐containing tetrasaccharide36was constructed by a linear glycosylation strategy from the non‐reducing terminal sugar,D‐apiose, which was prepared fromD‐xylose by a known procedure, also in a linear sequence of 15 steps. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
SASAPOS Cascades of Perfluorinated Aromatic Carboxylic Acids: Low‐Temperature Decarboxylation Triggered by Electrostatic Effects of Polycationic Ligand Sets
Authors: Pühlhofer Frank G. , Weiss Robert 
Published: February 2004

AbstractPolycationically substituted derivatives of benzoic and phthalic acids were synthesized for the first time via SASAPOS cascades of the corresponding perfluoro(di)carboxylic acids or acyl chlorides (SASAPOS: self‐activated silyl‐assisted poly‐onio substitution). The carboxylic acids decarboxylate with extreme ease (e.g. at room temperature or below) via the corresponding carboxylates. Electrostatically highly stabilized phenylanion derivatives figure as potent electrofuges in these reactions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Solvent‐Free Microwave‐Assisted Preparation of Chiral Ionic Liquids from (−)‐N‐Methylephedrine
Authors: Thanh Giang Vo , Pegot Bruce , Loupy André 
Published: February 2004

AbstractAn efficient method for the preparation of chiral ionic liquids based on (1R,2S)‐(−)‐ephedrinium salts under solvent‐free conditions and microwave activation is described. The influence of non‐specifically thermal microwave effects − consistent with mechanistic considerations − is discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Regioflexibility in the Functionalization of Multiply Halogenated Quinolines
Authors: Marull Marc , Schlosser Manfred 
Published: February 2004

Abstract4‐Bromo‐6‐fluoro‐2‐(trifluoromethyl)quinoline (1) and 4‐bromo‐7‐fluoro‐2‐(trifluoromethyl)quinoline (13) were selected as model substrates to explore under what conditions regiochemically exhaustive functionalization reactions can be carried out. This goal was achieved by using trimethylsilyl entities and iodine atoms as the sole auxiliary substituents. The organolithium intermediates could be generated and the protective groups removed without impairing the bromine atom present at the 4‐position. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis of 2‐(Arylamino)‐2‐(arylimino)acetamides
Authors: Langer Peter , Schroeder Rita 
Published: February 2004

AbstractThe reaction of 2‐(arylamino)‐2‐oxoacetates with PCl5 afforded 2‐(arylamino)‐2,2‐dichloroacetates. The reaction of these compounds with aniline derivatives allowed a convenient synthesis of a great variety of 2‐(arylamino)‐2‐(arylimino)acetamides. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Selective Host Amplification from a Dynamic Combinatorial Library of Oligoimines for the Syntheses of Different Optically Active Polyazamacrocycles
Authors: González‐Álvarez Almudena , Alfonso Ignacio , López‐Ortiz Fernando , Aguirre Ángel , García‐Granda Santiago , Gotor Vicente 
Published: February 2004

AbstractTwo different macrocyclic hosts are amplified and expressed by metal guests from the same dynamic combinatorial library (DCL) of oligoimines. We studied the thermodynamic template effect and the structure of the final compounds by a combination of ESI‐MS, UV and NMR spectroscopy, and X‐ray crystallography techniques. The use of BaIIor CdIImetal salts allows the selective synthesis of dimeric [2+2] or trimeric [3+3] cyclic structures, respectively. We observed a cooperative molding effect for the Cd ion‐templated process. A study of the DCL behavior in situ demonstrated a second level of molecular diversity, based on the imine/α‐methoxyamine equilibrium. This process is probably promoted by metal ion coordination and shows an interesting diastereoselectivity in the formation of the new chiral centers. Semiempirical (PM3) theoretical calculations also support these experimental observations. Reduction of the imine bonds allows the selective preparation and isolation of each macrocyclic polyamine on a synthetic scale and in a one‐pot procedure. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
The Superbase‐Mediated Pairwise Substitution of the 2,2′‐ and 6,6′‐Positions in a Biphenyl Derivative
Authors: Schlosser Manfred , Mangano Guiseppe , Leroux Frédéric 
Published: February 2004

AbstractThe superbasic mixture of butyllithium and potassium tert‐butoxide is powerful enough to enable the double proton abstraction from one ortho and one ortho′ position of 4,4′‐di‐tert‐butylbiphenyl. In this way, a series of functionalized derivatives becomes readily accessible, among them 4,4′‐di‐tert‐butylbiphenyldiyl‐2,2′‐dicarboxylic acid (2a) and 4,4′‐di‐tert‐butylbiphenyl‐2,2′‐diol (2d). The latter compound can be subjected again to a superbase‐promoted double metalation, thus giving rise to 2,2′,6,6′‐tetrasubstituted biphenyl derivatives. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Acylation of Alkyl Halides and Amino Aldehydes with a Phosphane Oxide‐Based d1‐Synthon
Authors: Brünjes Marco , Kujat Christof , Monenschein Holger , Kirschning Andreas 
Published: February 2004

AbstractAlkyl iodides and α‐amino aldehydes can be homologated to the corresponding methyl esters and β‐amino methyl esters, including β‐amino‐α‐hydroxy methyl esters, using lithiated (dimethoxymethyl)diphenylphosphane oxide. The primary α,α‐(dimethoxy)diphenylphosphane oxides obtained by this Horner−Wittig type process collapse to give the target esters under proton‐catalyzed conditions in the presence of water. Detailed and carefully conducted mechanistic studies revealed that the diphenylphosphane oxide group is activated by protonation, and acts as the initial leaving group in this process. In the cases of adducts derived from the reaction of the phosphane oxide‐stabilized anion with α‐amino aldehydes, homologation to the β‐amino‐ and β‐amino‐α‐hydroxy methyl esters can be achieved by KOtBu‐mediated elimination to the intermediate O,O‐ketene acetals. These may either be allowed to react with water under acidic conditions to yield the β‐amino methyl esters, or may be treated under the Sharpless asymmetric dihydroxylation conditions to directly furnish the β‐amino‐α‐hydroxy methyl esters. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis of (4R,9Z)‐9‐Octadecen‐4‐olide, the Female Sex Pheromone ofJanus integer, and Its Enantiomer
Authors: Shibata Chié , Mori Kenji 
Published: February 2004

AbstractEnantiomer separation of (±)‐8‐tert‐butyldiphenylsilyloxy‐1‐octyn‐3‐ol was achieved by lipase‐mediated asymmetric acetylation. The resolved (R)‐alkynol was converted into (4R,9Z)‐9‐octadecen‐4‐olide, which was identical with the female sex pheromone of the currant stem girdler (Janus integer). The absolute configuration of the natural pheromone was thus established asR. (4S,9Z)‐9‐Octadecen‐4‐olide was also synthesized, and found to be pheromonally inhibitory. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)