bluuebunny/crossref_metadata_2025 huggingface dataset:
Prostaglandin D2 inhibits the production of interleukin‐12 in murine dendritic cells through multiple signaling pathways
Authors: Faveeuw Christelle , Gosset Philippe , Bureau Fabrice , Angeli Véronique , Hirai Hiroyuki , Maruyama Takayuki , Narumiya Shuh , Capron Monique , Trottein François
Published: March 2003

Prostaglandin (PG) D2, and its metabolites, are known to be important mediators during acute and chronic inflammation. However, their functions during the early phases of the immune response are poorly documented. In the present study, we show that PGD2 inhibits, in a dose‐dependent manner, the CD40‐ and LPS‐induced secretion of the Th1‐driving factor IL‐12 by murine splenic dendritic cells (DC), the most potent antigen‐presenting cells. The inhibition of IL‐12 production is mediated only in part by the cell surface Gαs protein‐coupled D prostanoid receptor (termed DP1) but not by the Gαi protein‐coupled DP receptor, DP2. We show that recruitment of DP1 in DC results in the activation of a cyclic AMP/protein kinase A pathway that is partially responsible for the inhibition of IL‐12 production. We also suggest that the DP1‐independent effects exerted by PGD2 on IL‐12 production may be due to the action of ist PGJ2, but not PGF2α, metabolites. Electrophoretic mobility shift assays demonstrated that PGD2 affects NF‐κB activation through (the) DP1‐independent pathway(s). Together these data suggest that PGD2, by interacting with DP1 and by binding to other target cellular proteins, may regulate immune responses by affecting IL‐12 production in DC.
Combinatorial immunoglobulin light chain variability creates sufficient B cell diversity to mount protective antibody responses against pathogen infections
Authors: Senn Beatrice M. , López‐Macías Constantino , Kalinke Ulrich , Lamarre Alain , Isibasi Armando , Zinkernagel Rolf M. , Hengartner Hans
Published: March 2003

To analyze how combinatorial light (L) chain diversity influences the B cell repertoire, we studied mice with a homozygous immunoglobulin‐heavy‐chain null mutation (μMT), in which the B cell developmental block was overridden by the expression of a transgenic immunoglobulin μ heavy (H) chain derived from a vesicular stomatitis virus Indiana serotype (VSV‐IND)‐neutralizing Ab (T11μMT mice). The randomly integrated transgene could not undergo secondary rearrangements and was expressed in combination with endogenous κ or λ chains. T11μMT mice had a skewed B cell repertoire as evidenced by 30–60% VSV‐IND‐specific peripheral B cells and spontaneous VSV‐IND‐neutralizing serum titers. Upon immunization, T11μMT mice mounted specific IgM antibody responses against VSV‐IND but, interestingly, they also responded against VSV New Jersey serotype (VSV‐NJ), lymphocytic choriomeningitis virus, poliovirus and Salmonella typhi porins. Variable‐region sequence analysis revealed that VSV‐NJ‐specific antibodies expressed numerous L chains in combination with the transgenic H chain, which was devoid of hypermutations. Thus, in T11μMT mice combinatorial L chain variability alone is able to build up a sufficiently complex B cell repertoire to mount protective immunoglobulin responses against a variety of pathogens.
Critical role for OX40 ligand in the development of pathogenic Th2 cells in a murine model of asthma
Authors: Hoshino Akihiko , Tanaka Yoshitaka , Akiba Hisaya , Asakura Yumiko , Mita Yasuo , Sakurai Takanobu , Takaoka Akiko , Nakaike Shiro , Ishii Naoto , Sugamura Kazuo , Yagita Hideo , Okumura Ko
Published: March 2003

Bronchial asthma is characterized by massive infiltration of eosinophils and airway hyperreactivity (AHR), which are caused by overproduction of Th2 cytokines (IL‐4, IL‐5, and IL‐13) by allergen‐specific T cells. We recently demonstrated a critical contribution of OX40 ligand (OX40L) to the development of Th2‐mediated experimental leishmaniasis. In this study, we have examined the role of OX40L in the development of Th2‐mediated pulmonary inflammation by utilizing OX40L‐deficient mice and a neutralizing anti‐OX40L mAb in a murine model of asthma. Sensitization and airway challenge with ovalbumin in wild‐type BALB/c mice induced a typical allergic asthma characterized by AHR, accumulation of eosinophils, increased mucus production, and high levels of Th2 cytokines in the lung.All these asthmatic responses were not induced in OX40L‐deficient BALB/c mice. Administration of neutralizing anti‐OX40L mAb in wild‐type BALB/c mice during the sensitization period
also abolished the induction of asthmatic responses. In contrast, administration of anti‐OX40L mAb during the challenge period did not inhibit the asthmatic responses. These results indicate a critical role for OX40L in the induction phase, which leads to the development of pathogenic Th2 cells, but not in the effector phase, which includes migration and activation of pathogenic Th2 cells in the lung.
CD40 can costimulate human memory T cells and favors IL‐10 secretion
Authors: Rogers Nicola Jane , Jackson Ian Michael , Jordan William James , Lombardi Giovanna , Delikouras Alexandros , Lechler Robert Ian
Published: March 2003

Optimal proliferation of T cells, although initiated via ligation of the CD3/TCR complex, requires additional costimulatory signals. While the most well‐defined in vitro pathway of costimulation is via the B7 family of molecules, a large body of data clearly demonstrates an in vivo role for the CD40/CD154 pathway in transplantation, autoimmunity and allergy. We have examined the role of CD40 as an independent costimulatory molecule by generating a panel of transfected human fibroblasts expressing DR1 with either CD80, CD86 or CD40. Functional assays using allogeneic CD4+ T cells as responders demonstrated that CD40 was capable of costimulating CD4+ T cell proliferation particularly in the CD45RO subset. Costimulation by CD40 induced much higher levels of IL‐10 than were induced by B7‐expressing cells. On day 3 the dominant costimulation was provided by CD40, while by day 5 this was overshadowed by CD80 and CD86. Nonetheless, the provision of costimulation by CD40 was enough to expand an alloreactive T cell line. These results were confirmed in experiments using primary cultures of CD40+CD80/CD86– renal tubular epithelial cells as the stimulator population. Thus, CD40 is capable of functioning independently (in the absence of B7) as a costimulatory molecule both in terms of proliferation and cytokine release. The data have interesting implications concerning the consequences of antigen presentation by tissue parenchymal cells.
Colonic lamina propria dendritic cells in mice with CD4+ T cell‐induced colitis
Authors: Krajina Tamara , Leithäuser Frank , Möller Peter , Trobonjaca Zlatko , Reimann Jörg
Published: March 2003

CD11c+ (F4/80– CD68–) dendritic cells (DC) in the colonic lamina propria (cLP) of normal and immunodeficient (RAG1–/–) C57BL/6 (B6) mice show high surface expression of MHC class I/II molecules and CD1d, and low surface expression of CD40, CD80, CD86 costimulator molecules. CD4+ α β T cells from normal or MHC class II‐deficient B6 micetransferred into congenic RAG1–/– hosts induce a progressive, lethal colitis. Concomitant with colitis development, DC in the inflamed cLP increase in number and up‐regulate surface expression of CD1d, MHC class II molecules and CD40, CD80, CD86 costimulator molecules. cLP DC from non‐transplanted (healthy) and transplanted (diseased) mice produce similar amounts of IL‐12 p70 and IL‐10 in response to CD40 signaling, but the inducible IL‐12 p40 release is 5–15‐fold higher in mice with colitis than in non‐transplanted mice. Binding of IL‐12 p40 to p19 generates IL‐23. Freshly isolated cLP lymphocytes (cLPL) from transplanted, diseased mice express 3–10‐fold more p19 transcripts than cLPL from non‐transplanted, healthy mice. p19 expression by cLPL is further up‐regulated in response to CD40 ligation. Freshly isolated cLP DC from transplanted mice with colitis (but not from non‐transplanted controls) stimulate IFN‐γ (but not IL‐4 or IL‐13) release by co‐cultured NKT cells. Incolitis, DC accumulate in the cLP, show an activated surface phenotype, up‐regulate IL‐12 p40 and p19 expression, and ‘spontaneously’ stimulate NKT‐like cells. cLP DC may be interesting targets for novel therapeutic approaches to modulate mucosal T cell responses in situ.
Murine thymic plasmacytoid dendritic cells
Authors: Okada Tomoyuki , Lian Zhe‐Xiong , Naiki Mitsuru , Ansari Aftab A. , Ikehara Susumu , Gershwin M. Eric
Published: March 2003

We report herein heterogeneous murine thymic cell subsets expressing CD11c and B220 (CD45R). The CD11c+B220+ subset expresses Ly6Chigh and MHC class IIlow in contrast with previously described thymic DC (CD11c+B220– cells). Freshly isolated thymic CD11c+B220+ cells show typical plasmacytoid morphology which differentiates to mature DC, in vitro with CpG oligodeoxynucleotides (ODN) 2216; we term this subset thymic plasmacytoid DC (pDC). These thymic pDC are highly sensitive to spontaneous apoptosis in vitro and induce low T cell allo‐proliferation activity. Thymic pDC express low TLR2, TLR3 and TLR4 mRNA, normally found on human immature DC, and high TLR7 and TLR9 mRNA, normally found on human pDC. Thymic pDC also produce high amounts of IFN‐α following culture with CpG ODN 2216 (TLR9 ligands) as compared with the previously defined thymic DC lineage which expresses low TLR9 mRNA and produce high IL‐12 (p40) with CpG ODN 2216. These results indicate that thymic pDC are similar to IFN‐producing cells as well as human pDC. The TLR and cytokine production profiles are consistent with a nomenclature of pDC. The repertoire of this cell lineage to TLR9 ligands demonstrate that such responses are determined not only by the quantity of expression, but also cell lineage.
IFN‐γ‐mediated inhibition of antigen receptor‐induced B cell proliferation and CREB‐1 binding activity requires STAT‐1 transcription factor
Authors: Frissora Frank , Chen Hui‐Chen , Durbin Joan , Bondada Subbarao , Muthusamy Natarajan
Published: March 2003

We report here a role for cyclic AMP‐responsive element‐binding protein‐1 (CREB‐1) in B cell antigen receptor (BCR)‐induced growth inhibition by IFN‐γ. BCR‐induced proliferation is negatively regulated by IFN‐γ. Stimulation through BCR resulted in dose‐dependent induction of CREB‐1 binding to the consensus cyclic AMP‐responsive element. Recombinant IFN‐γ inhibited the BCR‐induced CREB‐1 DNA binding activity and cell proliferation in B cells from signal transducer and activator of transcription‐1 (STAT‐1)+/+, but not STAT‐1–/– mice. These studies provide the first evidence for cross‐talk between the STAT‐1 and CREB‐1 signaling pathways in IFN‐γ‐mediated negative regulation of B cell activation.
Plasmacytoid dendritic cells prime IFN‐γ‐secreting melanoma‐specific CD8 lymphocytes and are found in primary melanoma lesions
Authors: Salio Mariolina , Cella Marina , Vermi William , Facchetti Fabio , Palmowski Michael J. , Smith Caroline L. , Shepherd Dawn , Colonna Marco , Cerundolo Vincenzo
Published: March 2003

Plasmacytoid dendritic cells (PDC) are a small population of leukocytes specialized in the production of type I IFN. It has been shown that PDC have a potent T cell stimulatory capacity in allogeneic mixed lymphocyte reaction, However, their role in initiating primary immune responses remains elusive. We report that blood PDC efficiently prime naive CD8+ lymphocytes specific forthe melan‐A26–35 epitope to become IFN‐γ producing cells in vitro. In addition, we found that CD40L‐stimulated PDC induce expression on primed melan‐A‐specific T cells of cutaneous lymphocyte antigen and L‐selectin (CD62L), homing receptors that allow the migration of effector cells to the inflamed skin. Finally, we show that PDC can be found in the peri‐tumoralarea of most primary cutaneous melanomas in vivo and that type I IFN‐containing supernatants derived from PDC increase melanoma cell surface expression of CD95 and MHC class I and class II molecules in vitro. Our results suggest a new immunomodulatory role for tissue infiltrating PDC, which may prime tumor‐specific T cell responses and affect tumor growth via soluble factors.
Natural killer cell receptors in cattle: a bovine killer cell immunoglobulin‐like receptor multigene family contains members with divergent signaling motifs
Authors: Storset Anne K. , Slettedal Imer Ö. , Williams John L. , Law Andy , Dissen Erik
Published: March 2003

Natural killer (NK) cells recognize and kill certain tumor cells, virally infected cells and MHC class I‐disparate normal hematopoietic cells. NK cell cytotoxicity is regulated by a multitude of receptors with either activating or inhibitory signaling function. We here report the molecular cloning of bovine CD94 [killer cell lectin‐like receptor (KLR)‐D1] and NKp46 orthologues, four members of a bovine CD158 [killer cell immunoglobulin‐like receptor (KIR)] family, and a novel KLR. This novel receptor was termed KLRJ1 and is most similar to Ly‐49 (KLRA). The KLRD1 and KLRJ1 loci were mapped to a bovine NK gene complex on chromosome 5 by radiation hybrid mapping, whereas KIR2DL1 and NKP46 were localized to chromosome 18. Two of the bovine KIR(KIR2DL1 and KIR3DL1) contain immunoreceptor tyrosine‐based inhibition motifs (ITIM), suggesting an inhibitory function. Bovine KIR2DS1 and KIR3DS1 lack ITIM but have an arginine‐containing motif in their transmembrane domain, similar to primate KIR2DL4. Thus, KIR multigene families with divergent signaling motifs do not only exist in primates. Based on sequence comparison, it appears that the primate and bovine KIR multigene families may have evolved independently.
The IL‐1 receptor 1 is critical for Th2 cell type airway immune responses in a mild but not in a more severe asthma model
Authors: Schmitz Nicole , Kurrer Michael , Kopf Manfred
Published: March 2003

IL‐1α and IL‐1β are potent pro‐inflammatory cytokines that regulate many physiological systems by binding and signaling to the same receptor termed IL‐1 receptor type 1 (IL‐1R1). We have investigated the role of IL‐1 for pulmonary immune responses in models of allergic asthma using IL‐1R1‐deficient (IL‐1R1–/–) mice. In a model of mild asthma, based on repeated sensitization of mice with low doses of ovalbumin in the absence of any adjuvant and multiple intranasal challenges, the pulmonary eosinophilic inflammation and goblet cell hyperplasia were strongly reduced in IL‐1R1–/– as compared to control BALB/c mice. Moreover, priming of CD4+ T cells in bronchial lymph nodes and their recruitment to the lung was affected in IL‐1R1–/– miceassociated with impaired antibody responses including IgG, IgE, and IgA. In contrast, sensitization of mice in the presence of alum adjuvant, a more severe asthma model, rendered the IL‐1 pathway dispensable for the development of pulmonary allergic Th2 responses, as eosinophilic inflammation, antibody responses, and CD4+ T cell priming in lymph nodes were comparable between IL‐1R1–/– and wild‐type mice. These results suggest a critical role of IL‐1/IL‐1R1 for development of allergic Th2 responses, but its requirement can be overcome by using alum as adjuvant for sensitization.
Cooperation between toll‐like receptor 2 and 4 in the brain of mice challenged with cell wall components derived from gram‐negative and gram‐positive bacteria
Authors: Laflamme Nathalie , Echchannaoui Hakim , Landmann Régine , Rivest Serge
Published: March 2003

In this study we investigated whether induction of toll‐like receptor 2 (TLR2) amplifies the effect of a cell wall component derived from gram‐positive bacteria, namely peptidoglycan (PGN). Mice received a first systemic lipopolysaccharide (LPS) injection to pre‐induce TLR2 in various regions of the brain, and 6 h later, a second administration of either LPS or PGN. The data show a robust transcriptional activation of TLR2, TNF‐α and monocyte chemotactic protein‐1 (MCP‐1) in microglial cells of mice challenged twice with LPS, whereas PGN essentially abolished this response. TLR4 plays a critical role in this process, because C3H/HeJ mice no longer responded to LPS but exhibited a normal reaction to PGN. Conversely, a robust signal for genes encoding innate immune proteinswas found in the brain of TLR2‐deficient mice challenged with LPS. However, the second LPS bolus failed to trigger TNF‐α and IL‐12 in TLR2‐deficient mice, while the same treatment caused a strong induction of these genes in the cerebral tissue of wild‐type littermates. The present data provide evidence that cooperation exists between TLR4 and TLR2. While TLR4 is absolutely necessary to engage the innate immune response in the brain, TLR2 participates in the regulation of genes encoding TNF‐α and IL‐12 during severe endotoxemia. Such collaboration between TLR4 and TLR2 may be determinant for the transfer from the innate to the adaptive immunity within the CNS of infected animals.
Toll‐like receptor 2 (TLR2) and TLR4 differentially activate human mast cells
Authors: Varadaradjalou Sonia , Féger Frédéric , Thieblemont Nathalie , Hamouda Nadine Ben , Pleau Jean‐Marie , Dy Michel , Arock Michel
Published: March 2003

In the present report we have analyzed whether human normal cord blood‐derived mast cells (CBMC) could interact with bacterial products, especially lipopolysaccharide (LPS) from Escherichia coli and peptidoglycan (PGN) from Staphylococcus aureus, known as Toll‐like receptor (TLR) 4 and TLR2 agonists, respectively. We found that both LPS and PGN induced significant release of not only tumor necrosis factor‐α (TNF‐α), but also IL‐5, IL‐10 and IL‐13 by human mast cells (MC). We also established that the stimulation of CBMC with LPS or with PGN is mediated through interactions with TLR4 or with TLR2, respectively. Thus, our data indicate that activation of either TLR2 or TLR4 pathway may lead to a pro‐Th2 immune response. However, the release of TNF‐α induced by LPS, conversely to PGN, required the priming of CBMC by IL‐4 and the presence of serum components, in particular soluble CD14. Of interest, stimulation by PGN, but not by LPS, induced release of histamine by human MC. Altogether, these findings provide the first evidence that human MC differentially respond towards bacterial components, and that their responses depend on TLR pathways and reveal human specificities in the pattern of cytokine production.
Kinetics and STAT4‐ or STAT6‐mediated regulation of genes involved in lymphocyte polarization to Th1 and Th2 cells
Authors: Lund Riikka J. , Ylikoski Emmi K. , Aittokallio Tero , Nevalainen Olli , Lahesmaa Riitta
Published: March 2003

Many genes implicated in Th1 and Th2 differentiation have been identified in both human and mouse. However, the functional roles and hierarchy of these factors in the signaling pathways leading to either Th1 or Th2 responses are less clear. To explore at which stage of polarization the differences between Th1 and Th2 cells occur, we have studied the expression of 23 key genes implicated in the process during the first week of polarization from human precursor T helper cells using quantitative real‐time reverse transcription‐PCR. According to our results, 14 of the genes were clearly regulated differentially in Th1 and Th2 conditions in distinct time‐dependent patterns, either during the first 2 days or after 1 week of polarization. Furthermore, 6 of these genes were identified to be targets of STAT4/6 regulation. Thus, for the first time we demonstrate expression kinetics of a number of key genes involved in Th1 and Th2 differentiation during the first week of polarization in both human and mouse. In addition, our study shows for the first time that the genes BCL‐6 and TRADD are differentially regulated during the polarization of human Th1 and Th2 cells.
Enantioselective Recognition of Aliphatic Amino Acids by β‐Cyclodextrin Derivatives Bearing Aromatic Organoselenium Moieties on the Primary or Secondary Side
Authors: Liu Yu , You Chang‐Cheng , Zhang Heng‐Yi , Zhao Yan‐Li
Published: March 2003

Spectrophotometric titrations have been performed in order to determine the stability constants of inclusion complexation of some aliphatic amino acids with four structurally related organoselenium‐modified β‐cyclodextrins: mono(6‐phenylseleno‐6‐deoxy)‐β‐cyclodextrin (1a), mono[6‐(p‐methoxyphenylseleno)‐6‐deoxy]‐β‐cyclodextrin (1b), mono(2‐phenylseleno‐2‐deoxy)‐β‐cyclodextrin (2a), and mono[2‐(p‐methoxyphenylseleno)‐2‐deoxy]‐β‐cyclodextrin (2b). Conformation analysis by circular dichroism and 2D NMR spectroscopic studies revealed that the aryl‐substituted β‐cyclodextrins gave self‐inclusion intramolecular complexes in aqueous solution, while the extent of penetration depended both on the positions and on the structures of substituents. Quantitative investigation on the binding ability of the hosts with amino acids showed that they were able to recognize the size and the shape of guests, affording supramolecular complexes with quite small stability constants ranging from 24 to 355 M−1. The molecular recognition abilities are discussed from the viewpoints of induced‐fitting mechanisms, geometric complementary, and cooperative binding processes. Furthermore, these β‐cyclodextrin derivatives displayed considerable enantioselectivity towards L/D‐amino acid isomers, giving the highest L‐enantioselectivity (up to 8.4) for inclusion complexation between leucine and 2a. The binding modes of L/D‐leucine with 1b were elucidated from NOESY studies and the chiral recognition phenomena were interpreted accordingly. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Access to Isolable Azomethine Ylides by Photochemical Transformation of 2,3‐Dihydroisoxazoles
Authors: Lopez‐Calle Eloisa , Keller Manfred , Eberbach Wolfgang
Published: March 2003

Photochemical excitation of the 2,3‐dihydroisoxazoles 19−21 resulted in the formation of the stable azomethine ylides 22, 25, and 28, representing the first isolable examples of such species bearing stabilizing groups only at one end of the 1,3‐dipole. The UV and NMR spectroscopic data of the photoproducts clearly indicate that the iminium and the anionic parts of the azomethine ylide systems are not planar. This conclusion is unambiguously confirmed by crystal structure analysis of 25b, in which a twist angle of 73° was determined between the two polar moieties. In the case of 25d the rotation barrier around the central CN bond amounts to 16 kcal/mol at 333 K. In line with the unusual stability of the ylides is their low reactivity against dipolarophiles. Only the highly reactive N‐methyltriazolidinedione gives formation of the products 33a, 35a−c, and 41, but these are the result not of an initial 1,3‐dipolar cycloaddition but rather of a formal [4+2] addition with involvement of 34a, 36a−c, and 41 as unstable primary products. On heating in refluxing toluene the azomethine ylides are transformed into annulated pyrrole systems (42/43, 46/47, 48/49). In contrast to other examples, the direct thermal transformation of the annulated 2,3‐dihydroisoxazoles into pyrroles is not successful, but the reaction can be achieved by simultaneous thermal and photochemical activation, as shown for the conversion of 19 into the pyrroles 42/43. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Substituent Effects in the Vinylcyclopropane Radical Cation Rearrangement: A Computational Road to a New Synthetic Tool
Authors: Oxgaard Jonas , Wiest Olaf
Published: March 2003

The effect of substituents on the rearrangement of vinylcyclopropane radical cation to cyclopentene was explored by density functional theory. Correlations have been established between the activation energy of the system and the nature, as well as the position, of the substituents. It was found that radical‐ or cation‐stabilizing substituents in select positions reduce the activation energy for the rearrangement substantially, while activation energies for competing hydrogen shifts were largely left unchanged. We have identified positions in the vinylcyclopropane where substitution is necessary, and others that can be substituted less discriminately. The mechanism of the rearrangement changes from stepwise to concerted when a strongly cation‐stabilizing substituent is used, because the first step in the stepwise reaction becomes a barrierless ring opening of a strained cyclopropane. Steric effects were also explored and have been found to be of crucial importance for the success of a rearrangement. Finally, a simple set of rules has been devised to predict the outcome of oxidation of a vinylcyclopropane without requiring detailed mechanistic investigations. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Quinoline‐Containing Calixarene Fluoroionophores: A Combined NMR, Photophysical and Modeling Study
Authors: Casnati Alessandro , Sansone Francesco , Sartori Andrea , Prodi Luca , Montalti Marco , Zaccheroni Nelsi , Ugozzoli Franco , Ungaro Rocco
Published: March 2003

The 8‐alkoxy‐5‐chloroquinoline fluorophore was appended at the lower rim of a calix[4]arene triamide with two different orientations. In ligand1the quinoline part is linked to the calixarene skeleton through the pyridine C2atom, while in2it is linked through the phenolic oxygen atom of the chromophore. The binding properties of both ligands, investigated in chloroform and methanol solutions, indicate that they are efficient fluoroionophores, with selectivity for sodium and strontium ions among alkali and alkaline earth metal ions. Combined NMR, photophysical, and modeling studies disclosed the peculiar conformational and coordination features of monovalent and divalent metal ion complexes. Lanthanide metal ion complexes were prepared and studied in acetonitrile solution showing good luminescence in the case of Nd3+, Yb3+, and Er3+ions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis of Methyl N‐Acetyl‐4‐amino‐2,4,6‐trideoxy‐3‐C‐methyl‐α‐L‐rhamnohexopyranoside − Towards Elucidation of the Relative Configuration of Saccharocarcin E Sugar
Authors: Langner Martin , Laschat Sabine , Grunenberg Jörg
Published: March 2003

L‐Olivomycal 8, obtained from L‐rhamnose (10) in six steps, was used as a precursor for the preparation of methyl N‐acetyl‐4‐amino‐2,4,6‐trideoxy‐3‐C‐methyl‐α‐L‐rhamnohexopyranoside (5b). The amino group at C‐4 of 5b was introduced by intramolecular nucleophilic displacement of a (trichloromethyl)imidate derived from 8, yielding the 3,4‐trans‐(trichloromethyl)oxazoline 13 with retention of configuration. Compound 13 was further converted into the N‐acetamide 14 by basic hydrolysis and subsequent acetylation. N‐Iodosuccinimide‐promoted glycosylation and reductive dehalogenation yielded the target molecule 5b, together with its β epimer 5c (α/β = 85:15). Comparison of the NMR spectroscopic data of 5b with those of saccharocarcin E sugar and several other 4‐amino‐2‐deoxyhexoses revealed similarities between saccharocarcin E sugar and kijanimicin derivative 23, which suggest the proposed β‐L‐xylo‐hexopyranose configuration 4d for saccharocarcin E sugar. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
D‐Glucose as a Pentavalent Chiral Scaffold
Authors: Opatz Till , Kallus Christopher , Wunberg Tobias , Schmidt Wolfgang , Henke Stefan , Kunz Horst
Published: March 2003

A novel carbohydrate‐based scaffold for combinatorial chemistry has been developed. This scaffold allows the selective attachment of five different side chains, giving rise to products of enormous structural diversity. As a demonstration of its usefulness, a series of model compounds has been prepared in high purity and yield by multistep parallel synthesis on a solid phase. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis of Novel Amino Acids and Dehydroamino Acids Containing the Benzo[b]thiophene Moiety
Authors: Abreu Ana S. , Silva Natália O. , Ferreira Paula M. T. , Queiroz Maria‐João R. P.
Published: March 2003

Several novel amino acids and dehydroamino acids containing the benzo[b]thiophene moiety were prepared by Michael addition or sequential Michael addition and palladium‐catalyzed C−C or C−N cross couplings. The substrates for Michael addition were the methyl esters of N,N‐bis(tert‐butyloxycarbonyl)dehydroalanine [Boc2−ΔAla−OMe] and N‐(4‐toluenesulfonyl)‐N‐(tert‐butyloxycarbonyl)dehydroalanine [Tos−ΔAla(N‐Boc)−OMe], and the nucleophiles were aromatic thiols and 3‐iodobenzylamine. The addition of mercaptobenzo[b]thiophenes directly to Tos−ΔAla(N‐Boc)−OMe gave stereoselectively, in good yields, the E‐isomer of the corresponding dehydrocysteine. When thiophenols and 3‐iodobenzylamine were used as nucleophiles the presence of an additional function (halogen or amine) allowed a subsequent palladium‐catalyzed cross‐coupling reaction with functionalized benzo[b]thiophenes (boronic acids, a halogen or an amine). Using this strategy, several racemic amino acid and dehydroamino acid derivatives, which are linked to the benzo[b]thiophene moiety by an aromatic spacer, were obtained in good yields. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Recommendable Routes to Trifluoromethyl‐Substituted Pyridine‐ and Quinolinecarboxylic Acids
Authors: Cottet Fabrice , Marull Marc , Lefebvre Olivier , Schlosser Manfred
Published: March 2003

As part of a case study, rational strategies for the preparation of all ten 2‐, 3‐, or 4‐pyridinecarboxylic acids and all nine 2‐, 3‐, 4‐, or 8‐quinolinecarboxylic acids bearing trifluoromethyl substituents at the 2‐, 3‐, or 4‐position were elaborated. The trifluoromethyl group, if not already present in the precursor, was introduced either by the deoxygenative fluorination of suitable carboxylic acids with sulfur tetrafluoride or by the displacement of ring‐bound bromine or iodine by trifluoromethylcopper generated in situ. The carboxy function was produced by treatment of organolithium or organomagnesium intermediates, products of halogen/metal or hydrogen/metal permutation, with carbon dioxide. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Selective and Efficient Structural Elaboration of 2‐(Trifluoromethyl)quinolinones
Authors: Marull Marc , Schlosser Manfred
Published: March 2003

The acid‐catalyzed cyclization‐condensation between anilines and ethyl 4,4,4‐trifluoroacetoacetate affords 1,4‐dihydro‐2‐trifluoromethyl‐4H‐4‐quinolinones (1), which can easily be converted into 4‐bromo‐2‐(trifluoromethyl)quinolines. These undergo halogen/metal exchange, generating 2‐trifluoromethyl‐4‐quinolyllithiums, when treated with butyllithium, and hydrogen/metal exchange, generating 4‐bromo‐2‐trifluoromethyl‐3‐quinolyllithiums, when treated with lithium diisopropylamide. Trapping of the latter intermediates provides 3‐functionalized products that may be further elaborated by electrophilic substitution of the bromine atom. A few unexpected findings resulted from these investigations, the most noteworthy being an unprecedented buttressing effect and a counterintuitive halogen reactivity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Process‐Integrated Microbial Mercury Removal from Wastewater of Chlor‐Alkali Electrolysis Plants
Authors: Wagner‐Döbler I. , von Canstein H. , Li Y. , Leonhäuser J. , Deckwer W.‐D.
Published: March 2003

The enzymatic reduction of Hg(II) to water‐insoluble Hg(0) by mercury‐resistant bacteria has been used for the removal of mercury from wastewater of a chlor‐alkali electrolysis plant. The demercurization process essentially consists of a pretreatment step for pH adjustment, a fixed‐bed bioreactor with pumice granules as carrier for the immobilized mercury‐resistant bacteria followed by an activated carbon filter.
Product Recovery and Reduction of Wastewater Disposal Costs in a Detergent Production Facility
Authors: Forstmeier M. , Goers B. , Wozny G.
Published: March 2003

In an applied research project in cooperation with industrial partners investigations have been made on the application of ultrafiltration and nanofiltration membrane processes for the separation of surfactants from cleaning‐in‐place rinsing waters in a liquid detergent production plant. A membrane screening as well as pilot plant experiments have been performed. Chemical oxygen demand reductions in the wastewater of up to 96 % have been achieved resulting in less environmental impact and lower wastewater disposal costs.
Continuous Xylitol Production from Synthetic Xylose Solutions by Candida guilliermondii: Influence of pH and Temperature
Authors: Converti A. , Torre P. , De Luca E. , Perego P. , Del Borghi M. , da Silva S.S.
Published: March 2003

The effects of pH and temperature on continuous xylitol production by Candida guilliermondii have been studied under semiaerobic conditions. The specific productivites obtained at different pH have been used in the model proposed by Villadsen et al. with the aim to get information on the enzyme likely limiting xylitol production (xylose reductase). The kinetic results obtained at different temperatures have been utilized to estimate the thermodynamic parameters either of the reduction of xylose to xylitol (ΔH# = 62 kJ mol–1; ΔS# = –0.12 kJ mol–1 K–1) or of the biocatalyst thermal inactivation (ΔHD° = 90 kJ mol–1; ΔSD° = 0.30 kJ mol–1 K–1). Finally, the well‐known empirical procedure of Sizer has been compared with the so‐called “thermodynamic approach” from the viewpoint of their ability to explain the physical meaning of the related thermodynamic parameters.
Studies on organoleptic properties of food products from fresh egg and egg powder through principal component analysis
Authors: Chauhan Valentina Singh , Sharma Alka
Published: March 2003

The population which is below the poverty line is devoid of nutritious diet. Egg and milk are categorized as complete foods. The defensive organizations are situated in such remote places where fresh food material is not available. Keeping in view these problems, the study of organoleptic variables, viz., color, appearance, aroma, texture and taste in the food products of cake, omelet doughnut, coconut macaroon and mayonnaise from fresh egg and egg powder, was conducted. Principal component analysis was carried out. Organoleptic properties of doughnut prepared from egg powder were superior compared to fresh egg which had better sensory traits for coconut macaroon. The sensory traits like taste, texture and aroma were the most influential traits studied to pronouncing as a panel decision. It is proposed that fresh egg and egg powder should be preferred in the process of preparation of coconut macaroon and doughnut, respectively.
Use of starch/xanthan gum combinations as thickeners of cocoa syrups
Authors: Sikora Marek , Juszczak Lesław , Sady Marek , Krawontka Jan
Published: March 2003

The influence of starch‐xanthan thickening systems on the sensory, textural and rheological properties of cocoa syrups was studied. The results of whole and partial sensory analyses of syrups obtained under laboratory conditions were presented and compared to those of commercially available syrups. In the evaluation of texture such parameters as hardness, adhesiveness, cohesiveness, gumminess and stringiness were considered. The results of rheological measurements were presented in the form of flow curves as well as viscosity/time and viscosity/temperature relationships. Flow curves were fitted to the models of Ostwald‐de Waele and Casson, which allowed characterising the syrups under study to non‐Newtonian, pseudoplastic, and thixotropic fluids. It was concluded that the quantity of thickeners used influenced not only rheological, but also textural and sensory properties of the syrups. The decrease of pseudoplasticity and hardness with an increase of xanthan addition was a result of high sugars level in the syrups. This phenomenon was a result of competition between sugars (mono‐, di‐, and oligosaccharides) and hydrocolloids for water molecules in the systems under study.
Nutritional value of broad bean seeds. Part 1: Starch and fibre
Authors: Giczewska Anna , Borowska Julitta
Published: March 2003

This paper characterizes starch and dietary fibre in the seeds of fine‐size and large‐size seed varieties of broad bean and in edible varieties of pea for comparison. The experimental material included seeds at full physiological maturity. The fine‐size seed varieties of broad bean, Gobik and Goral, contained slightly less total starch (62.32% and 62.19% of dry matter) than the large‐size seed varieties, Windsor Bialy and Bartom (65.32% and 65.26% of dry matter). It was shown that fine‐size seed varieties of broad bean are a good source of resistant starch, which is comparable to large‐size seed varieties. As far as the content of total starch is concerned, the share of this form of starch in broad bean seeds amounted to 1/3. Digestible starch in broad beans was in the range of 39–42% of dry matter, pea contained approximately one half less starch of this type. Moreover, it was found that the relation of rapidly digestible starch to slowly digestible starch amounted to 1 : 1 irrespective of broad bean variety. Dietary fibre in broad beans was in the range of 20.36%–26.79% of dry matter while half of it was found to be concentrated in the seed coat. The soluble fraction of the total content of fibre amounted to 11.81% in the Bartom variety and up to 15.89% in the Gobik variety.
Nutritional value of broad bean seeds. Part 2: Selected biologically active components
Authors: Borowska Julitta , Giczewska Anna , Zadernowski Ryszard
Published: March 2003

Selected biologically active non‐nutrient components (BANS) were determined in broad bean seeds of fine‐size and large‐size seed varieties and in pea seeds for comparison. Among the analysed biologically active substances the broad bean seeds of fine‐size and large‐size seed varieties were differentiated mainly by phenolic compounds (including flavanols and proantocyanidines) which appear in twice as large quantities in large‐size seed varieties. It was shown that in comparison to pea, broad bean seeds are characterised by a higher content of phenolic compounds, phytates as well as a higher activity of inhibitors of trypsin and amylases. Moreover, it was found that phenolic compounds accumulate mainly in the dark‐colored seed coats of large‐size broad bean and this fact is related to higher activity inhibiting α‐amylases of methanol extracts from this fraction of seeds.
Unexpected condensation reaction of two units of 1,2‐dihydrophosphinine 1‐oxides in the presence of tetracyanoethylene
Authors: Keglevich György , Kovács János , Szöllősy Áron , Kovács Attila , Szabó Andrea , Ludányi Krisztina , Kádas István , Tőke László
Published: March 2003

In the presence of tetracyanoethylene, the reaction of two molecules of dihydrophosphinine oxide 2B followed an unexpected route to afford diphosphatricyclododecatrienes 4 instead of the corresponding Diels–Alder cycloadducts (3). Structures of the products (4) have been elucidated by a joint application of spectroscopy and quantum chemical calculations. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:29–35, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10062
One‐step transformation of ammonium dialkyl phosphoroselenoates into dialkyl phosphoramidates
Authors: Mielniczak Grażyna , Łopusiński Andrzej
Published: March 2003

Ammonium dialkyl phosphoroselenoates are directly converted into the dialkyl phosphoramidates by iodosobenzene and iodoxybenzene. The inversion of configuration at the phosphorus atom, using model diastereoisomeric ammonium cis‐ and trans‐2‐oxo‐2‐seleno‐4‐methyl‐1,3,2‐dioxaphosphinan system, was observed. The mechanistic scheme of this transformation is discussed. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:121–127, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10110
Photochromic Properties of New Benzoindene‐Fused 2H‐Chromenes
Authors: Martins Cristina I. , Coelho Paulo J. , Carvalho Luis M. , Oliveira‐Campos Ana M. F. , Samat André , Guglielmetti Robert
Published: March 2003

The synthesis and the photochromic properties of new photochromic 6,7‐ and 7,8‐benzoindene annellated benzopyrans are described. When compared to parent indeno‐fused 2H‐chromenes (2H‐[1]benzopyrans), compounds 10 and 12 exhibit a significant bathochromic shift of maximum‐absorption wavelength, an increase in the colorability, and similar fading rates.
Designing Novel Contrast Agents for Magnetic Resonance Imaging. Synthesis and Relaxometric Characterization of three Gadolinium(III) Complexes Based on Functionalized Pyridine‐Containing Macrocyclic Ligands
Authors: Aime Silvio , Gianolio Eliana , Corpillo Davide , Cavallotti Camilla , Palmisano Giovanni , Sisti Massimo , Giovenzana Giovanni B. , Pagliarin Roberto
Published: March 2003

The three novel pyridine‐containing 12‐membered macrocyclic ligands 1–3 were synthesized. The coordinating arms are represented by three acetate moieties in 1 and 3 and by one acetate and two phosphonate moieties in 2. In all three ligands, the acetate arm in the distal position is substituted, with a benzyl group in 1 and 2 and with an arylmethyl moiety in 3. The relaxivities r1p (20 MHz, 25°) of GdIII complexes are: GD⋅1, r1p=8.3 mM−1 s−1; GD⋅2, r1p8.1 mM−1 s−1; Gd⋅3, r1p10.5 mM−1 s−1. 1H‐NMRD and 17O‐NMR T2 data show that Gd⋅1 and Gd⋅3 contain two H2O molecules in the inner sphere, whereas the presence of two phosphonate arms allows the coordination of only one H2O molecule in Gd⋅2. Interestingly, the exchange lifetime of coordinated H2O in the three complexes is similar in spite of the difference in the coordination number of the GdIII ion (i.e., 9 in Gd⋅1 and Gd⋅3, and 8 in Gd⋅2). 1H‐Relaxometric measurements at different pH and in the presence of lactate and oxalate were carried out to get some insight into the formation of ternary complexes from Gd⋅1 and Gd⋅3. Finally, it was found that binding to human‐serum albumin (HSA) of Gd⋅1 and Gd⋅2, though weak, yields limited relaxivity enhancements, likely as a consequence of effects on the hydration sphere caused by donor atoms on the surface of the protein.
Studies on the Stereoselective Synthesis of Deuterated D‐Ribose Derivatives
Authors: Kundu Mrinal K. , Földesi Andras , Chattopadhyaya Jyoti
Published: March 2003

In view of the importance of the site‐specific substitution of the H‐atom by its stable isotope 2H in a stereoselective/stereospecific manner at the pentose sugar residue, decreasing the spectral overcrowding in various regions of 1D and 2D homo‐ and heteronuclear correlation spectra of oligo‐DNA and ‐RNA, there is always a need for the development of new methods for the incorporation of 2H at different sites of a ribose. High‐yielding multistep syntheses of C(2)‐, and (5R)‐ and (5S)‐3,5‐deuterated ribose derivatives have been envisaged for the application of site‐specific incorporation of multilabeled nucleosides into oligomers to facilitate their structure elucidation by NMR spectroscopy. All syntheses started from D‐glucose after proper derivatization. In the case of C(2), >97 atom‐% isotope was incorporated, employing an inversion of the configuration at C(2) as the key reaction. For C(5), two different routes were envisaged: on the one hand, deuterated achiral reagent was treated with a conformationally locked sugar moiety 15, while, on the other, chiral protonated sources were used to transfer the H‐atom to a C(5)‐deuterated aldehyde 18. In all cases, enantiomeric and isotopic purities were found to be as high as >97% as determined by NMR spectroscopy.
An Efficient Synthesis of 3′‐Amino‐3′‐deoxyguanosine from Guanosine
Authors: Zhang Lei , Cui Zhiyong , Zhang Biliang
Published: March 2003

3′‐Amino‐3′‐deoxyguanosine was synthesized from guanosine in eight steps and 58% overall yield. The 2′,3′‐diol of 5′‐O‐[(tert‐butyl)diphenylsilyl]‐2‐N‐[(dimethylamino)methylidene]guanosine was reacted with α‐acetoxyisobutyryl bromide and treated with 0.5n NH3 in MeOH to yield 9‐{2′‐O‐acetyl‐3′‐bromo‐5′‐O‐[(tert‐butyl)diphenylsilyl]‐3′‐deoxy‐β‐D‐xylofuranosyl]‐2‐N‐[(dimethylamino)methylidene]guanine, which was reacted with benzyl isocyanate, NaH, and then 3.0n NaOH, and finally with Pd/C (10%) and HCO2NH4 in EtOH/AcOH to afford 3′‐amino‐3′‐deoxyguanosine.
Structural Diversity in Thallium Chemistry. Part V
Authors: Linden Anthony , Petridis Alexander , James Bruce D.
Published: March 2003

From thallium(III) bromide solution, the unsubstituted pyridinium cation yields a complex (1) with the [Tl2Br9]3− anionic stoichiometry. The Raman spectrum and single‐crystal X‐ray crystallographic analysis showed that the salt contains independent [TlBr4]− and bromide anions. A variety of mono‐ and disubstituted pyridinium cations were also employed in similar syntheses. The 2‐bromopyridinium cation gave a salt 2 with [TlBr5]2− stoichiometry, but the crystal structure revealed very weakly interacting [TlBr4]− and bromide anions with a Tl ⋅⋅⋅Br− distance of 4.1545(6) Å. The 2‐(ammoniomethyl)pyridinium and 2‐amino‐4‐methylpyridinium cations yielded complexes containing [TlBr5]2− (3) and [TlBr4]− (4) species, respectively, which were confirmed by Raman spectroscopy and X‐ray crystallographic analyses. For 3, the [TlBr5]2− anion has a highly distorted trigonal bipyramidal conformation with one long axial Tl ⋅⋅⋅Br bond of 3.400(2) Å. Microanalytical results in conjunction with Raman spectra from a further five salts confirmed that they all contain the simple [TlBr4]− anion. NH ⋅⋅⋅Br Hydrogen bonds clearly influence the nature of the anionic species obtained in these systems.
‘Oligomere' Kondensationsprodukte von (1E,3E,5E)‐1,6‐Di(2‐furyl)hexa‐1,3,5‐trien mit Acetaldehyd: Tetrahydro‐tetramethyl‐octaepoxy[60]annulen(6.1.6.1.6.1.6.1)
Authors: Märkl Gottfried , Ehrl Robert , Kreitmeier Peter
Published: March 2003

Oligomeric Condensation Products of (1E,3E,5E)‐1,6‐Di(2‐furyl)hexa‐1,3,5‐triene with Acetaldehyde: Tetrahydro‐tetramethyl‐octaepoxy[60]annulene(6.1.6.1.6.1.6.1)

The Ca(NO3)2‐induced condensation of (1E,3E,5E)‐1,6‐di(2‐furyl)hexa‐1,3,5‐triene (6) with acetaldehyde yields the linear ‘oligomers' 7–11 with 2–6 1,6‐di(2‐furyl)hexa‐1,3,5‐triene units and 1–4 acetaldehyde units, besides a cyclic condensation product 12 obtained from 4 equiv. of 6 with 4 equiv. of acetaldehyde. According to spectroscopic studies, 12 is the tetrahydro‐tetramethyl‐octaepoxy[60]annulene(6.1.6.1.6.1.6.1) as the most expanded annulene system known so far. While the dehydrogenation of 12 to give the tetramethyl‐octaepoxy[60]annulene(6.1.6.1.6.1.6.1) cannot be achieved, the oxidation of 12 with Br2 yields a black, in all organic solvents nearly insoluble solid 14, which possibly is the tetramethyl‐octaepoxy[58]annulene(6.1.6.1.6.1.6.1) dication. Because of the insolubility of 14, unfortunately most of its spectroscopic data are not available. However, the λmax values in the UV/VIS/NIR spectrum of 14 (Soret and Q bands) are in line with the values of the tetraepoxy[26]annulene(4.2.4.2) dication, the tetraepoxy[30]annulene(4.4.4.4) dication, and the tetraepoxy[34]annulene(6.4.6.4) dication.
Two Novel ent‐Kaurene Diterpenoids from Isodon rubescens
Authors: Han Quan‐Bin , Jiang Bei , Zhang Ji‐Xia , Niu Xue‐Mei , Sun Han‐Dong
Published: March 2003

A novel 20‐nor‐ent‐kaurene diterpenoid, rubescensin N (1), and a new 7,20‐epoxy‐ent‐kaurene diterpenoid, rubescensin O (2), along with the seven known diterpenoids rabdoternins A–F and xerophilusin N, were isolated from Isodon rubescens collected in Jiyuan prefecture, Henan Province, China. Their structures were established by extensive spectroscopic analysis. Compound 1 is the first example of a naturally occurring 20‐nor‐ent‐kaurene diterpenoid from the Isodon genus plants.
Pseudolarolides O and P, Two Novel Triterpene Dilactones from Pseudolarix kaempferi
Authors: Chen Guo‐Fu , Tan Chang‐Heng , Li Zhu‐Lian , Jiang Shan‐Hao , Zhu Da‐Yuan
Published: March 2003

Pseudolarolides O (1) and P (2), two novel triterpenoids with a cycloartane‐type framework, were isolated from the seeds of Pseudolarix kaempferi Gord. (Pinaceae). Their structures were elucidated as (16R,23S,25R)‐16,23‐epoxy‐3,4 : 9,10‐disecocycloartan‐1(10),9(11)‐diene‐3(4),26(23)‐diolide (1), and (9S,16R,23S,25R)‐1,9 : 16,23‐diepoxy‐8,9 : 9,10‐disecocycloartan‐1(29),5(6),10(19)‐triene‐3(4),26(23)‐diolide (2), respectively, on the basis of spectroscopic techniques and X‐ray‐diffraction studies.