bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomics and proteomics of allergic disease
Authors: Toda Masako , Ono Santa Jeremy 
Published: March 2003

SummaryThe world‐wide effort to identify susceptibility genes for allergic diseases is motivated by the conviction that the identification of disease genes may permit the design of new classes of anti‐inflammatory compounds. Molecules concerned with the allergic reaction, such as cytokines, chemokines, their receptors, major histocompatibility complex molecules, and transcription factors, could provide the candidate genes of the allergic diseases. On the basis of genetic studies, multiple research groups have attempted to identify a susceptibility gene for allergy using the candidate gene approach and/or genome‐wide screening. Both of these approaches suggest genetic heterogeneity of allergic diseases. Many variants of candidate genes are or are not associated with particular diseases in different ethnic groups and the function of variants is now being investigated. Based on the information accumulated thus far and the information on the human genome sequence, future advances in research on genetic factors for allergic diseases will be likely lead to the establishment of more effective prophylaxis and therapy for these diseases.
Type I interferon gene therapy protects against cytomegalovirus‐induced myocarditis
Authors: Cull Vanessa S. , Bartlett Emmalene J. , James Cassandra M. 
Published: March 2003

SummaryType I interferons (IFNs) are produced early in response to viral infection and modulate adaptive immunity. Previously we demonstrated localized protection against murine cytomegalovirus (MCMV) infection in IFN DNA‐inoculated mice. Here we examine the effect of seven IFN subtypes (IFNA1, A2, A4, A5, A6, A9 and B), administered by DNA inoculation, on systemic MCMV infection and myocarditis. IFN transgene expression altered the pathogenesis of MCMV infection with regard to virus titre and myocarditis. IFNA6 treatment reduced MCMV replication whilst IFNA5 and A2 enhanced virus replication. IFNA6, A9, and B treatment inhibited acute myocarditis. A T helper type 1‐like, antibody and cytokine, response correlated with decreased virus titre and myocarditis. In addition, IFNA6 was able to reduce chronic cardiac inflammation. This research into the effectiveness of seven type I IFNs, using DNA gene therapy, highlights the need for correct subtype usage in the treatment of disease. We demonstrate effective subtypes for treatment in both the acute and chronic phases of MCMV infection and the resultant development of myocarditis.
Effect of cell density on in vitro mouse immunoglobulin E production
Authors: Rabah Dania , Conrad Daniel H. 
Published: March 2003

Summary In vitro immunoglobulin E (IgE) production was found to be sensitive to increasing cell concentration in culture wells. While class switching to IgE is intact as suggested by surface IgE staining, ELISPOT analysis provided evidence that the differentiation of IgE committed B cells to the plasma cell stage was arrested at high cell doses. In fact, splitting the cells at higher concentrations after culture initiation increased IgE production. Cells plated at higher doses were found to be more prone to apoptosis as assessed by Annexin staining. Interestingly, inhibiting apoptosis by the use of the caspase inhibitor DEVD significantly increased IgE levels implicating apoptosis in the preferential deletion of IgE expressing cells. These data not only highlight the caveat against using a single B‐cell dose for IgE production in vitro but also suggest for the first time a possible IgE regulatory mechanism mediated by cell density.
Heritability estimates for the constitutional levels of the collectins mannan‐binding lectin and lung surfactant protein D. A study of unselected like‐sexed mono‐ and dizygotic twins at the age of 6–9 years
Authors: Husby Steffen , Herskind Anne Maria , Jensenius Jens Christian , Holmskov Uffe 
Published: March 2003

SummaryThe collectins mannan‐binding lectin (MBL) and lung surfactant protein D (SP‐D) play a significant role in innate immunity. Structural as wells as promoter variants are known for MBL and different alleles correlate with low MBL concentrations in serum and predispose to infectious diseases. Structural variants are also known for SP‐D but these have not been linked to disease states. The aim of the present study was to provide heritability estimates for the constitutional levels of MBL and SP‐D in children. A population of 26 monozygotic (MZ) and 36 dizygotic (DZ) like‐sexed twin pairs aged 6–9 years was studied. Intraclass correlations were significantly higher in MZ than in DZ twins, indicating substantial genetic influence on both MBL and SP‐D levels. Biometric model fitting showed that the estimated heritability was 0·96 (95% CI 0·92–0·97) for MBL with the presence of non‐additive genetic factors and non‐shared environmental factors and 0·91 (95% CI 0·83–0·95) for SP‐D with additive genetic and non‐shared environmental factors. The data indicate quantitatively very strong genetic dependence for the serum levels of both MBL and SP‐D.
Insight into the potential for DNA idiotypic fusion vaccines designed for patients by analysing xenogeneic anti‐idiotypic antibody responses
Authors: Forconi Francesco , King Catherine A. , Sahota Surinder S. , Kennaway Christopher K. , Russell Nigel H. , Stevenson Freda K. 
Published: March 2003

SummaryDNA vaccines induce immune responses against encoded proteins, and have clear potential for cancer vaccines. For B‐cell tumours, idiotypic (Id) immunoglobulin encoded by the variable region genes provides a target antigen. When assembled as single chain Fv (scFv), and fused to an immunoenhancing sequence from tetanus toxin (TT), DNA fusion vaccines induce anti‐Id antibodies. In lymphoma models, these antibodies have a critical role in mediating protection. For application to patients with lymphoma, two questions arise: first, whether pre‐existing antibody against TT affects induction of anti‐scFv antibodies; second, whether individual human scFv fusion sequences are able to fold consistently to generate antibodies able to recognize private conformational Id determinants expressed by tumour cells. Using xenogeneic vaccination with scFv sequences from four patients, we have shown that pre‐existing anti‐TT immunity slows, but does not prevent, anti‐Id antibody responses. To determine folding, we have monitored the ability of nine DNAscFv–FrC patients' vaccines to induce xenogeneic anti‐Id antibodies. Antibodies were induced in all cases, and were strikingly specific for each patient's immunoglobulin with little cross‐reactivity between patients, even when similar VH or VL genes were involved. Blocking experiments with human serum confirmed reactivity against private determinants in 26–97% of total antibody. Both immunoglobulin G1 (IgG1) and IgG2a subclasses were present at 1·3 : 1–15 : 1 consistent with a T helper 2‐dominated response. Xenogeneic vaccination provides a simple route for testing individual patients' DNAscFv–FrC fusion vaccines, and offers a strategy for production of anti‐Id antibodies. The findings underpin the approach of DNA idiotypic fusion vaccination for patients with B‐cell tumours.
krox‐20/egr‐2 is up‐regulated following non‐specific and homophilic adhesion in rat macrophages
Authors: Hirano Seishiro , Anuradha Cunigaipur D. , Kanno Sanae 
Published: March 2003

SummaryMacrophages are known to adhere to a plastic dish via β2 integrin (CR3) and scavenger receptors. Although their functions such as phagocytosis, endocytosis, and nitric oxide production have been investigated on adherent macrophages in vitro, very little is known about intracellular signals triggered by adhesion to a plastic dish. Recently we reported that the mRNA level of krox‐20/egr‐2 was significantly increased in rat alveolar macrophages following exposure to fibrous titanium dioxide particles. In the present study we report that up‐regulation of krox‐20/egr‐2 gene expression following adhesion to a plastic dish and homophilic adhesion in rat alveolar macrophages and rat macrophage cell line, NR8383. The mRNA level of krox‐20/egr‐2 increased with a peak 1 hr after adhesion to a plastic dish in both cell types. Piceatannol inhibited tyrosine‐phosphorylation of Syk and decreased both adhesion and krox‐20/egr‐2 mRNA level. In contrast staurosporine, a serine/threonine kinase inhibitor, increased adherence of macrophages and yet prohibited the adhesion‐dependent increase in krox‐20/egr‐2 gene expression. When NR8383 cells are cultured in suspension, the cells aggregated naturally and produced cell clumps. The mRNA level of krox‐20/egr‐2 also increased in response to the homophilic intercellular adhesion. The increased mRNA level of krox‐20/egr‐2 was not caused by inflammatory stimuli, because lipopolysaccharide did not affect the aggregation‐dependent up‐regulation of krox‐20/egr‐2 gene. The up‐regulation of krox‐20/egr‐2 gene due to the homophilic cell aggregation was also inhibited either by piceatannol or staurosporine. Those results suggest that krox‐20/egr‐2 gene expression is triggered by sensing non‐specific and homophilic cellular adhesion and the following phosphorylation of signal transducing proteins including Syk and staurosporine‐inhibitable kinases.
Both exogenous and endogenous interleukin‐10 affects the maturation of bone‐marrow‐derived dendritic cells in vitro and strongly influences T‐cell priming in vivo
Authors: Haase Claus , Jørgensen Trine N. , Michelsen Birgitte K. 
Published: March 2003

SummaryIn order to avoid autoimmunity and excessive tissue destruction, the action of certain immunoinhibitory substances are very important for negative regulation of the immune system. Interleukin‐10 (IL‐10) is an important immunoregulatory cytokine which is thought to negatively affect both T cells and antigen‐presenting cells in vivo. Adoptive transfer of IL‐10‐treated bone‐marrow‐derived dendritic cells (BMDCs) may be one therapeutic avenue to inhibit autoimmunity. In this study we present a comprehensive analysis of the effects of IL‐10 on murine BMDC. We demonstrate that IL‐10 can prevent BMDC maturation, as measured by both cytokine production and T‐cell priming capacity in vitro. Furthermore, we show that IL‐10 can inhibit DC maturation induced by strong stimulatory signals such as lipopolysaccharide or a mixture of cytokines (interferon‐γ, tumour necrosis factor‐α, IL‐4). Interestingly, maturation of both T helper 1‐ and T helper 2‐inducing DCs, characterized by the induction of high levels of interferon‐γ and IL‐4‐production by responding T cells, respectively, was inhibited by IL‐10 in vitro. Finally, our data suggest that both endogenous and exogenous IL‐10 affect the T‐cell stimulatory capacity of BMDCs after injection of in vitro‐treated BMDCs into naïve mice. These data both support existing data as well as point towards a new understanding of the many aspects of IL‐10‐mediated immunosuppression.
Three T‐cell determinants of Cry j 1 and Cry j 2, the major Japanese cedar pollen antigens, retain their immunogenicity and tolerogenicity in a linked peptide
Authors: Yoshitomi Tomomi , Hirahara Kazuki , Kawaguchi Junko , Serizawa Nobufusa , Taniguchi Yoshifumi , Saito Saburo , Sakaguchi Masahiro , Inouye Sakae , Shiraishi Akio 
Published: March 2003

SummaryIt has been demonstrated in detail that administration of a dominant T‐cell determinant to animals induces activation or immunological tolerance of T cells. However, it has not been determined whether multiple T‐cell determinants, when integrated into a single peptide, retain their potential to induce T‐cell activation and tolerance. We prepared a synthetic peptide comprising three T‐cell determinants of Cry j 1 and Cry j 2, the major Japanese cedar pollen antigens, and investigated the immunogenicity and tolerogenicity of each T‐cell determinant in the linked peptide by means of lymph node cell proliferation assays using mice. Lymph node cells from mice immunized with each of the three T‐cell determinants proliferated against the linked peptide in a dose‐dependent manner, similar to that of the immunized peptide. Lymph node cells from mice immunized with the linked peptide proliferated against all of the three T‐cell determinants. In addition, the degree of proliferation against the three T‐cell determinants occurred according to their original immunogenicity, as observed in the native protein antigens. Oral administration of the linked peptide to mice before they were immunized with Cry j 1 and Cry j 2 inhibited lymph node cell proliferation against the three T‐cell determinants, depending on the dose of the linked peptide administered. In conclusion, it was demonstrated that three T‐cell determinants retain their original immunogenicity and tolerogenicity in a linked peptide comprising them.
Induction of 4‐1BB (CD137) expression by DNA damaging agents in human T lymphocytes
Authors: Kim Kwang‐Mi , Kim Ho Won , Kim Jae‐Ouk , Baek Kyoung‐Min , Kim Joong Gon , Kang Chang‐Yuil 
Published: March 2003

Summary4‐1BB(CD137) is a member of the tumour necrosis factor receptor superfamily and is expressed on activated T cells, monocytes and natural killer (NK) cells. The interaction of 4‐1BB and 4‐1BB ligand provides a costimulatory signal leading to T‐cell activation. The expression of 4‐1BB has been known to be activation dependent. Interestingly, we found that expression of 4‐1BB increased in human peripheral blood mononuclear cells after exposure to mitomycin C. Thus, we tested whether the treatment with other DNA‐damaging agents, such as doxorubicin, bleomycin, and γ‐irradiation, could induce 4‐1BB expression. The data indicated that 4‐1BB expression increased dose‐dependently by these agents reaching maximum at 2–3 days after the exposure. We found that the major 4‐1BB‐expressing population was CD3+T cells, although a moderate number of CD14+cells and a few NKB1+cells also expressed 4‐1BB. The levels of 4‐1BB expression induced by anticancer drugs, were relatively lower than that induced by CD3 ligation. Interestingly, at subcytotoxic concentrations, doxorubicin and bleomycin considerably enhanced 4‐1BB expression induced by CD3 ligation in CEM cells. The ligation of the damage‐induced 4‐1BB by monoclonal antibody enhanced the viability and proliferating capacity of the cells. In conclusion, the expression of 4‐1BB might be one of the cellular responses of the immune cells against various genotoxic stresses.
Human CD8 T cells of the peripheral blood contain a low CD8 expressing cytotoxic/effector subpopulation
Authors: Trautmann Axel , Rückert Beate , Schmid‐Grendelmeier Peter , Niederer Eva , Bröcker Eva‐B. , Blaser Kurt , Akdis Cezmi A. 
Published: March 2003

SummaryHeterogeneity of lymphocyte populations demonstrates the diversity of cellular immune responses and provide a better understanding of the immune system. CD3+ CD8+ T cells exhibit a low CD8 expressing (CD8low) population in flow cytometric analysis of peripheral blood T cells. In healthy donors, this population consists of 0·2–7·0% of all CD8 T cells. The majority of the CD8low T cell population showed an elevated expression of CD25, CD45RA, and CD95L, and low levels of CD28, CD62L and CD45RO. Circulating CD8low T cells resemble cytotoxic effector cells because they express cytolytic mediators and are able to execute cytotoxicity. A restricted T cell receptor profile with increased Vβ9, Vβ14 and Vβ23 expression was observed and the CD8low T cell population contain Epstein–Barr virus‐specific T cells. Therefore, the CD8low population represent a subset of activated CD8 effector T cells, resulting most probably from a continous and/or balanced immune response to intracellular pathogens.
DEC: a new miniature inverted‐repeat transposable element from the genome of the beetle Tenebrio molitor
Authors: Braquart C. , Royer V. , Bouhin H. 
Published: March 2003

AbstractIn this paper we describe a novel family of miniature inverted‐repeat transposable elements (MITEs), named DEC, isolated from the genome of the beetle Tenebrio molitor. These elements are highly reiterated and their number is estimated to be around 3500 per haploid genome. Two of them have been isolated and the two sequences are 84% identical. Like other MITEs, they are characterized by their small size, their A + T richness, the presence of terminal inverted repeats and the absence of open reading frames. These data suggest that MITEs are probably widely distributed in arthropods.
Phylogenetic status of a fecundity‐enhancing Wolbachia that does not induce thelytoky in Trichogramma
Authors: Vavre F. , Girin C. , Boulétreau M. 
Published: March 2003

Abstract Wolbachia are widespread bacteria which infect a number of species of insects and other arthropods. They manipulate the reproduction of their hosts at their own advantage. In Trichogramma species all Wolbachia known so far induce thelytoky and form a monophyletic group in the B subdivision of Wolbachia. Here we show that some strains of the arrhenotokous species Trichogramma bourarachae harbour Wolbachia symbionts that locate in the A subdivision, and which do not induce thelytoky. Although the symbiont of T. bourarachae is closely related to Wolbachia that induce cytoplasmic incompatibility in other insects, no cytoplasmic incompatibilities were found in crosses involving infected and uninfected strains. In T. bourarachae the presence of this Wolbachia is associated with a higher fecundity of strains. Our results strongly suggest that Wolbachia are involved in this increased fecundity. Theoretical models on the evolution of host‐Wolbachia interaction predict that a reduced effect on reproduction can be selected for if cost of infection is reduced. The effect in T. bourarachae should illustrate this prediction.
Microsatellite frequency and size variation in the parthenogenetic parasitic waspVenturia canescens(Gravenhorst) (Hymenoptera: Ichneumonidae)
Authors: Butcher R. D. J. , Hubbard S. F. , Whitfield W. G. F. 
Published: March 2003

AbstractNine genomic libraries of the parthenogenetic waspVenturia canescenswere screened for microsatellite loci. In contrast to other Hymenoptera (GT)nand not (CT)n, was the predominant repeat category found with 14 kb and 28 kb genomic DNA between loci, respectively. Mono‐ and trinucleotide microsatellites were rarer, occurring at frequencies between 231 kb and 589 kb of genome, whilst tetranucleotide repeats are scarce, with (ATTC)nand (CCGG)nloci occurring every 692 kb and 983 kb, respectively, and only one small imperfect (GATA)nlocus and no (GACA)nloci were revealed. Over 70% of the dinucleotide, and all the trinucleotide microsatellites were small (less than eleven repeats), whilst 60% to 80% of loci were imperfect. Moreover, very few compound microsatellites and only a single association between different microsatellites were observed.
The kdr mutation occurs in the Mopti form of Anopheles gambiaes.s. through introgression
Authors: Weill M. , Chandre F. , Brengues C. , Manguin S. , Akogbeto M. , Pasteur N. , Guillet P. , Raymond M. 
Published: March 2003

Abstract Anopheles gambiae
s.s. is a complex of sibling taxa characterized by various paracentric inversions. In west and central Africa, where several taxa are sympatric, a kdr mutation responsible for pyrethroid resistance has been described in only one (the S taxon), suggesting an absence of gene flow between them. Following a thorough sampling, we have found a kdr mutation in another taxon (M). To establish whether this mutation is the same event or not, the large intron upstream of the kdr mutation was sequenced to find polymorphic sites in susceptible/resistant and M/S mosquitoes. The low genetic diversity found in this DNA region indicates that a local genetic sweep has recently occurred. However, some polymorphic sites were found, and it is therefore concluded that the kdr mutation in the M taxon is not an independent mutation event, and is best explained by an introgression from the S taxon. These results are discussed within the context of possible gene flow between members of An. gambiae s.s. taxa, and with the possible spread of the kdr mutation in other closely related malaria vectors of the An. gambiae complex.
Psyllid endosymbionts exhibit patterns of co‐speciation with hosts and destabilizing substitutions in ribosomal RNA
Authors: Spaulding Allen W. , von Dohlen Carol D. 
Published: March 2003

AbstractEubacterial 16S rDNAs were sequenced from endosymbionts of seven psyllids (Psylloidea) and one whitefly (Aleyrodoidea), to investigate the evolution of endosymbionts and their hosts. Primary endosymbionts from all psyllids formed a highly supported clade, tentatively placed as the sister to whitefly primary endosymbionts, and showing several points of congruence with the host morphological phylogeny. Almost all host taxa yielded an additional eubacterial sequence, related either to known psyllid secondary endosymbionts or to other insect endosymbionts or parasites. The relationships of some secondary endosymbionts also suggested cospeciation with psyllid hosts, or ancient horizontal transfers. All primary endosymbionts, and some secondary endosymbionts, exhibited molecular genetic effects of a long‐term, intracellular existence in their biased nucleotide content and decreased stability of rRNA secondary structure.
Molecular evidence of incipient speciation within Anopheles gambiae s.s. in West Africa
Authors: Torre A. della , Fanello C. , Akogbeto M. , Dossou‐yovo J. , Favia G. , Petrarca V. , Coluzzi M. 
Published: March 2003

AbstractWe karyotyped and identified by polymerase chain reaction restriction fragment length polymorphism (PCR‐RFLP) analysis Anopheles gambiae s.s. samples collected in several African countries. The data show the existence of two non‐panmictic molecular forms, named S and M, whose distribution extended from forest to savannahs. Mosquitoes of the S and M forms are homosequential standard for chromosome‐2 inversions in forest areas. In dry savannahs, S is characterized mainly by inversion polymorphisms typical of Savanna and Bamako chromosomal forms, while M shows chromosome‐2 arrangements typical of Mopti and/or Savanna and/or Bissau, depending on its geographical origin. Chromosome‐2 inversions therefore seem to be involved in ecotypic adaptation rather than in mate‐recognition systems. Strong support for the reproductive isolation of S and M in Ivory Coast comes from the observation that the kdr allele is found at high frequencies in S specimens and not at all in chromosomal identical M specimens. However, the kdr allele does not segregate with molecular forms in Benin.
Phylogeny of raspberry beetles and other Byturidae (Coleoptera)
Authors: Malloch G. , Fenton B. , Goodrich M. A. 
Published: March 2003

AbstractNuclear ribosomal ITS2 and mitochondrial cytochrome oxidase DNA sequences were analysed from the Byturidae (Coleoptera), which includes the raspberry beetles. The secondary structure of ITS2 was plotted and interspecific changes analysed. Evidence for selection on simple sequence repeats within the ITS2 was found. Phylogenetic trees based on the mitochondrial and ribosomal sequences were compared. They were in parity, indicating they reflect the true evolutionary histories of these insects. There was no evidence for hybridization in the populations surveyed, but there was evidence that the American raspberry beetle, Byturus unicolor, is divided into at least three distinct groupings. Despite sharing a related host, the raspberry pests from America were not the most related to the European raspberry beetle. Instead, links between Byturus affinis from Japan and the American raspberry beetle suggest that this lineage originated in Asia and colonized the Western USA.