bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral Spore Vaccine Based on Live Attenuated Nontoxinogenic
Bacillus anthracis
Expressing Recombinant Mutant Protective Antigen
Authors: Aloni-Grinstein R. , Gat O. , Altboum Z. , Velan B. , Cohen S. , Shafferman A. 
Published: June 2005

ABSTRACT

An attenuated nontoxinogenic nonencapsulated
Bacillus anthracis
spore vaccine expressing high levels of recombinant mutant protective antigen (PA), which upon subcutaneous immunization provided protection against a lethal
B. anthracis
challenge, was found to have the potential to serve also as an oral vaccine. Guinea pigs immunized per os with the recombinant spore vaccine were primed to
B. anthracis
vegetative antigens as well as to PA, yet only a fraction of the animals (30% to 50%) mounted a humoral response to all of these antigens. Protective immunity provided by per os immunization correlated with a threshold level of PA neutralizing antibody titers and was long-lasting. Protection conferred by per os immunization was attained when the vaccine was administered in the sporogenic form, which, unlike the vegetative cells, survived passage through the gastrointestinal tract. A comparison of immunization of unirradiated spores with immunization of γ-irradiated spores demonstrated that germination and de novo synthesis of PA were prerequisites for mounting an immune protective response. Oral immunization of guinea pigs with attenuated
B. anthracis
spores resulted in a characteristic anti-PA immunoglobulin isotype profile (immunoglobulin [G1 IgG1] versus IgG2), as well as induction of specific anti-PA secretory IgA, indicating development of mucosal immunity.
Nontoxic Shiga Toxin Derivatives fromEscherichia coliPossess Adjuvant Activity for the Augmentation of Antigen-Specific Immune Responses via Dendritic Cell Activation
Authors: Ohmura Mari , Yamamoto Masafumi , Tomiyama-Miyaji Chikako , Yuki Yoshikazu , Takeda Yoshifumi , Kiyono Hiroshi 
Published: June 2005

ABSTRACTShiga toxin (Stx) derivatives, such as the Stx1 B subunit (StxB1), which mediates toxin binding to the membrane, and mutant Stx1 (mStx1), which is a nontoxic doubly mutated Stx1 harboring amino acid substitutions in the A subunit, possess adjuvant activity via the activation of dendritic cells (DCs). Our results showed that StxB1 and mStx1, but not native Stx1 (nStx1), resulted in enhanced expression of CD86, CD40, and major histocompatibility complex (MHC) class II molecules and, to some extent, also enhanced the expression of CD80 on bone marrow-derived DCs. StxB1-treated DCs exhibited an increase in tumor necrosis factor alpha and interleukin-12 (IL-12) production, a stimulation of DO11.10 T-cell proliferation, and the production of both Th1 and Th2 cytokines, including gamma interferon (IFN-γ), IL-4, IL-5, IL-6, and IL-10. When mice were given StxB1 subcutaneously, the levels of CD80, CD86, and CD40, as well as MHC class II expression by splenic DCs, were enhanced. The subcutaneous immunization of mice with ovalbumin (OVA) plus mStx1 or StxB1 induced high titers of OVA-specific immunoglobulin M (IgM), IgG1, and IgG2a in serum. OVA-specific CD4+T cells isolated from mice immunized with OVA plus mStx1 or StxB1 produced IFN-γ, IL-4, IL-5, IL-6, and IL-10, indicating that mStx1 and StxB1 elicit both Th1- and Th2-type responses. Importantly, mice immunized subcutaneously with tetanus toxoid plus mStx1 or StxB1 were protected from a lethal challenge with tetanus toxin. These results suggest that nontoxic Stx derivatives, including both StxB1 and mStx1, could be effective adjuvants for the induction of mixed Th-type CD4+T-cell-mediated antigen-specific antibody responses via the activation of DCs.
Saturation of Immunoglobulin E (IgE) Binding Sites by Polyclonal IgE Does Not Explain the Protective Effect of Helminth Infections against Atopy
Authors: Mitre Edward , Norwood Stephanie , Nutman Thomas B. 
Published: June 2005

ABSTRACTOne hypothesis for the decreased rates of atopy observed among helminth-infected individuals is that parasite-induced polyclonal immunoglobulin E (IgE) outcompetes allergen-specific IgE for FcεRI binding on basophils and mast cells. In experiments with fresh blood drawn from filaria-infected patients, we found no association between ratios of polyclonal toBrugia malayiantigen (BmAg)-specific IgE (range, 14:1 to 388:1) and basophil responses to BmAg as measured by histamine release. Using serum samples from a filaria-infected patient who also had dust mite (Dermatophagoides pteronyssinus)-specific IgE antibodies from time points with various ratios of polyclonal toD. pteronyssinus-specific IgE (16:1 to 86:1), we demonstrated that increased ratios of polyclonal toD. pteronyssinus-specific IgE did not attenuate basophil sensitization as measured byD. pteronyssinus-specific histamine release. Suppression of histamine release was likely not observed in either of these sets of experiments because polyclonal to antigen-specific IgE ratios were not sufficiently high, as concurrent passive sensitization of basophil experiments required ratios of polyclonal to antigen-specific IgE of greater than 500:1 to suppress basophil histamine release. Further, the intensity of IgE staining in basophil populations from 20 patients with active filaria infections correlated strongly with total serum IgE levels (rho = 0.698;P= 0.0024) with no plateau in intensity of IgE staining, even though some patients had total IgE levels of greater than 10,000 ng/ml. Our data therefore suggest that in helminth infections (and in filarial infections in particular), the ratios of polyclonal to allergen-specific IgE rarely reach those levels necessary to inhibit allergen-specific IgE-FcεRI binding and to suppress allergen-induced degranulation of mast cells and basophils.
Trichomonas vaginalis-Induced Epithelial Monolayer Disruption and Human Immunodeficiency Virus Type 1 (HIV-1) Replication: Implications for the Sexual Transmission of HIV-1
Authors: Guenthner Patricia C. , Secor W. Evan , Dezzutti Charlene S. 
Published: June 2005

ABSTRACTThe objective of this study was to evaluate potential mechanisms ofTrichomonas vaginalisinvolvement in human immunodeficiency virus type 1 (HIV-1) transmission. Polarized monolayer integrity of primary cervical and prostate epithelial cells or cell lines cultured withT. vaginaliswas measured by monitoring transepithelium resistance. The effect ofT. vaginalisisolates on HIV-1 passage through polarized epithelial cell monolayers was evaluated for HIV-1 p24gagin the basolateral supernatants. Coincubation withT. vaginalisisolates induced disruption of monolayer integrity and resulted in passage of virus to the basolateral side of the monolayer. Furthermore, there was isolate variability in which two isolates induced greater monolayer damage and increased HIV-1 passage than did the other two isolates. Coincubation ofT. vaginalisisolates with acutely HIV-1-infected peripheral blood mononuclear cells enhanced HIV-1 replication. This enhancement was associated with cellular proliferation and activation, as well as with tumor necrosis factor alpha production. In contrast to the monolayer disruption, the effect ofT. vaginalison HIV-1 replication was not isolate dependent. Thus, two mechanisms have been identified that could contribute to the epidemiologic association of trichomoniasis with the sexual transmission of HIV-1. (i)T. vaginalisdisruption of urogenital epithelial monolayers could facilitate passage of HIV-1 to underlying layers. (ii) Activation of local immune cells byT. vaginalisin the presence of infectious HIV-1 might lead to increased viral replication. Collectively, these data suggest the need for more vigilant efforts in the diagnosis and treatment ofT. vaginalisin women and men, especially in countries with a high prevalence of HIV-1.
Differential Regulation of β-Chemokines in Children with
Plasmodium falciparum
Malaria
Authors: Ochiel Daniel O. , Awandare Gordon A. , Keller Christopher C. , Hittner James B. , Kremsner Peter G. , Weinberg J. Brice , Perkins Douglas J. 
Published: June 2005

ABSTRACT

Chemokines regulate the host immune response to a variety of infectious pathogens. Since the role of chemokines in regulating host immunity in children with
Plasmodium falciparum
malaria has not previously been reported, circulating levels of β-chemokines (MIP-1α, MIP-1β, and RANTES) and their respective transcriptional profiles in ex vivo peripheral blood mononuclear cells (PBMCs) were investigated. Peripheral blood MIP-1α and MIP-1β levels were significantly elevated in mild and severe malaria, while RANTES levels decreased with increasing disease severity. β-Chemokine gene expression profiles in blood mononuclear cells closely matched those of circulating β-chemokines, illustrating that PBMCs are a primary source for the observed pattern of β-chemokine production during acute malaria. Statistical modeling revealed that none of the chemokines was significantly associated with either parasitemia or anemia. Additional investigations in healthy children with a known history of malaria showed that children with prior severe malaria had significantly lower baseline RANTES production than children with a history of mild malaria, suggesting inherent differences in the ability to produce RANTES in these two groups. Baseline MIP-1α and MIP-1β did not significantly differ between children with prior severe malaria and those with mild malaria. Additional in vitro experiments in PBMCs from healthy, malaria-naïve donors revealed that
P. falciparum
-derived hemozoin (Hz; malarial pigment) and synthetic Hz (β-hematin) promote a similar pattern of β-chemokine gene expression. Taken together, the results presented here demonstrate that children with severe malaria have a distinct profile of β-chemokines characterized by increased circulating levels of MIP-1α and MIP-1β and decreased RANTES. Altered patterns of circulating β-chemokines result, at least in part, from Hz-induced changes in β-chemokine gene expression in blood mononuclear cells.
Roles of 3-Deoxy-
d
-
manno
-2-Octulosonic Acid Transferase from
Moraxella catarrhalis
in Lipooligosaccharide Biosynthesis and Virulence
Authors: Peng Daxin , Choudhury Biswa P. , Petralia Ronald S. , Carlson Russell W. , Gu Xin-Xing 
Published: June 2005

ABSTRACT

Lipooligosaccharide (LOS), a major outer membrane component of
Moraxella catarrhalis
, is a possible virulence factor in the pathogenesis of human infections caused by the organism. However, information about the roles of the oligosaccharide chain from LOS in bacterial infection remains limited. Here, a
kdtA
gene encoding 3-deoxy-
d
-
manno
-2-octulosonic acid (Kdo) transferase, which is responsible for adding Kdo residues to the lipid A portion of the LOS, was identified by transposon mutagenesis and construction of an isogenic
kdtA
mutant in strain O35E. The resulting O35EkdtA mutant produced only lipid A without any core oligosaccharide, and it was viable. Physicochemical and biological analysis revealed that the mutant was susceptible to hydrophobic reagents and a hydrophilic glycopeptide and was sensitive to bactericidal activity of normal human serum. Importantly, the mutant showed decreased toxicity by the
Limulus
amebocyte lysate assay, reduced adherence to human epithelial cells, and enhanced clearance in lungs and nasopharynx in a mouse aerosol challenge model. These data suggest that the oligosaccharide moiety of the LOS is important for the biological activity of the LOS and the virulence capability of the bacteria in vitro and in vivo. This study may bring new insights into novel vaccines or therapeutic interventions against
M. catarrhalis
infections.
SepZ/EspZ Is Secreted and Translocated into HeLa Cells by the Enteropathogenic
Escherichia coli
Type III Secretion System
Authors: Kanack Kristen J. , Crawford J. Adam , Tatsuno Ichiro , Karmali Mohamed A. , Kaper James B. 
Published: June 2005

ABSTRACT

Enteropathogenic
Escherichia coli
(EPEC) is a major bacterial cause of infantile diarrhea in developing countries and is the prototype for a group of gastrointestinal pathogens causing characteristic attaching and effacing (A/E) histopathology on intestinal epithelia. A/E pathogens utilize a type III secretion system (TTSS), encoded by the locus of enterocyte effacement (LEE) pathogenicity island, to deliver effector proteins into host cells. Here, we investigate sequence divergence of the LEE-encoded SepZ protein and identify it as a TTSS-secreted and -translocated molecule. SepZ is hypervariable among A/E pathogens, with sequences sharing between 60 to 81% amino acid identity with SepZ of EPEC. A SepZ-CyaA fusion was secreted and translocated into HeLa cells in a TTSS-dependent manner. Additionally, we determined that the first 20 amino acids of SepZ were sufficient to direct its translocation. In contrast to previous studies suggesting a role in invasion and the structure and/or regulation of the TTSS, we found that SepZ does not mediate uptake of EPEC into host cells or affect translocation and tyrosine phosphorylation of the translocated intimin receptor. Immunohistochemistry reveals that, after an extended HeLa cell infection, accumulated SepZ can be detected beneath the site of bacterial attachment in a subset of pedestal regions. To indicate its newly identified status as a translocated effector protein, we propose to rename SepZ as EspZ.
Involvement ofListeria monocytogenesPhosphatidylinositol-Specific Phospholipase C and Host Protein Kinase C in Permeabilization of the Macrophage Phagosome
Authors: Poussin Mathilde A. , Goldfine Howard 
Published: June 2005

ABSTRACTWe have previously shown that phosphatidylinositol-specific phospholipase C (PI-PLC) produced byListeria monocytogenesactivates a host protein kinase C (PKC) cascade which promotes escape of the bacterium from a macrophage-like cell phagosome. Here, we provide evidence linking bacterial PI-PLC and host PKC β to phagosome permeabilization, which precedes escape.
Cross-Recognition ofN-Formylmethionine Peptides Is a General Characteristic of H2-M3-Restricted CD8+T Cells
Authors: Ploss Alexander , Tran An , Menet Ewa , Leiner Ingrid , Pamer Eric G. 
Published: June 2005

ABSTRACTH2-M3-restricted CD8+T cells can exhibit cross-reactivity to different bacterially derivedN-formylmethionine peptides. The extent of this promiscuity is unclear. We deleted the nonredundant fMIVTLF epitope and found thatListeria monocytogenesstill primed fMIVTLF-specific T cells. Thus, cross-reactivity appears to be a more general characteristic of H2-M3-restricted T cells.
Campylobacter jejuni
Induces Secretion of Proinflammatory Chemokines from Human Intestinal Epithelial Cells
Authors: Hu Lan , Hickey Thomas E. 
Published: June 2005

ABSTRACT

Campylobacter jejuni
is a common cause of diarrhea in humans. While the pathogenic mechanisms of
C. jejuni
are not completely understood, host inflammatory responses are thought to be contributing factors. In this report,
C. jejuni
81-176 is shown to up-regulate chemokines essential to inflammatory responses. Growth-related oncogene α (GROα), GROγ, macrophage inflammatory protein 1, monocyte chemoattractant protein 1 (MCP-1), and gamma interferon-inducible protein 10 (γIP-10) mRNA transcription in INT-407 cells was enhanced within 4 h of bacterial exposure. Infection with viable campylobacters was necessary for sustained chemokine transcription and was NF-κB dependent. GROα, γIP-10, and MCP-1 chemokine secretions were confirmed by immunological assays.
Genome Scale Identification ofTreponema pallidumAntigens
Authors: McKevitt Matthew , Brinkman Mary Beth , McLoughlin Melanie , Perez Carla , Howell Jerrilyn K. , Weinstock George M. , Norris Steven J. , Palzkill Timothy 
Published: June 2005

ABSTRACTAntibody responses for 882 of the 1,039 proteins in the proteome ofTreponema pallidumwere examined. Sera collected from infected rabbits were used to systematically identify 106 antigenic proteins, including 22 previously identified antigens and 84 novel antigens. Additionally, sera collected from rabbits throughout the course of infection demonstrated a progression in the breadth and intensity of humoral immunoreactivity against a representative panel ofT. pallidumantigens.
INTERPRETING GROUPS AND FIELDS IN SOME NONELEMENTARY CLASSES
Authors: HYTTINEN TAPANI , LESSMANN OLIVIER , SHELAH SAHARON 
Published: June 2005

This paper is concerned with extensions of geometric stability theory to some nonelementary classes. We prove the following theorem:Theorem. Let [Formula: see text] be a large homogeneous model of a stable diagram D. Let p, q ∈ SD(A), where p is quasiminimal and q unbounded. Let [Formula: see text] and [Formula: see text]. Suppose that there exists an integer n < ω such that [Formula: see text] for any independent a1, …, an∈ P and finite subset C ⊆ Q, but [Formula: see text] for some independent a1, …, an, an+1∈ P and some finite subset C ⊆ Q.Then [Formula: see text] interprets a group G which acts on the geometry P′ obtained from P. Furthermore, either [Formula: see text] interprets a non-classical group, or n = 1,2,3 and•If n = 1 then G is abelian and acts regularly on P′.•If n = 2 the action of G on P′ is isomorphic to the affine action of K ⋊ K* on the algebraically closed field K.•If n = 3 the action of G on P′ is isomorphic to the action of PGL2(K) on the projective line ℙ1(K) of the algebraically closed field K.We prove a similar result for excellent classes.
BOLD indirect vs. ASL direct measurement of muscle perfusion
Authors: Leroy-Willig A. 
Published: June 2005

The following is the abstract of the article discussed in the subsequent letter: Although skeletal muscle perfusion is fundamental to proper muscle function, in vivo measurements are typically limited to those of limb or arterial blood flow, rather than flow within the muscle bed itself. We present a noninvasive functional MRI (fMRI) technique for measuring perfusion-related signal intensity (SI) changes in human skeletal muscle during and after contractions and demonstrate its application to the question of occlusion during a range of contraction intensities. Eight healthy men (aged 20–31 yr) performed a series of isometric ankle dorsiflexor contractions from 10 to 100% maximal voluntary contraction. Axial gradient-echo echo-planar images (repetition time = 500 ms, echo time = 18.6 ms) were acquired continuously before, during, and following each 10-s contraction, with 4.5-min rest between contractions. Average SI in the dorsiflexor muscles was calculated for all 240 images in each contraction series. Postcontraction hyperemia for each force level was determined as peak change in SI after contraction, which was then scaled to that obtained following a 5-min cuff occlusion of the thigh (i.e., maximal hyperemia). A subset of subjects ( n = 4) performed parallel studies using venous occlusion plethysmography to measure limb blood flow. Hyperemia measured by fMRI and plethysmography demonstrated good agreement. Postcontraction hyperemia measured by fMRI scaled with contraction intensity up to 60% maximal voluntary contraction. fMRI provides a noninvasive means of quantifying perfusion-related changes during and following skeletal muscle contractions in humans. Temporal changes in perfusion can be observed, as can the heterogeneity of perfusion across the muscle bed.
Commitment to Science
Authors: Box Steven , Ford Julienne 
Published: June 2005

In this paper it is suggested that a sociological explanation of the process of differential professional socialization among working class chemistry students can be derived from an application of the theory of marginality. The working class university student is in a structural situation of marginality, but his unique experience of this situation and subsequent response to it will be mediated by three sets of variables. Factors pertaining to his past experience, present environment, and expectations about the future are all relevant to an understanding of the nature of his marginality. Where the experience of marginality takes the form of an acute identity crisis a solution may be found in the total embracement of one role. We suggest that of the roles available to the science student that of the dedicated scientist offers one of the most attractive identities. Data is presented which provides some support for the suggestion that embracement of this role, in the form of commitment to science, may be viewed as a solution to a marginality crisis for some upwardly mobile students.
CXCL13 is an arrest chemokine for B cells in high endothelial venules
Authors: Kanemitsu Naotoshi , Ebisuno Yukihiko , Tanaka Toshiyuki , Otani Kazuhiro , Hayasaka Haruko , Kaisho Tsuneyasu , Akira Shizuo , Katagiri Koko , Kinashi Tatsuo , Fujita Naoya , Tsuruo Takashi , Miyasaka Masayuki 
Published: June 2005

Abstract
Chemokine receptor signaling is critical for lymphocyte trafficking across high endothelial venules (HEVs), but the exact mode of action of individual chemokines expressed in the HEVs is unclear. Here we report that CXCL13, expressed in a substantial proportion of HEVs in both lymph nodes (LNs) and Peyer patches (PPs), serves as an arrest chemokine for B cells. Whole-mount analysis of mesenteric LNs (MLNs) showed that, unlike T cells, B cellsa dhere poorly to the HEVs of CXCL13–/– mice and that B-cell adhesion is substantially restored in CXCL13–/– HEVs when CXCL13 is added to the MLNs by superfusion, as we have previously observed in PP HEVs by intravital microscopy. In vitro, CXCL13 activated the small guanosine triphosphatase (GTPase) Rap1 in B cells, and corroborating this observation, a deficiency of RAPL, the Rap1 effector molecule, caused a significant reduction in shear-resistant B-cell adhesion to intercellular adhesion molecule 1 (ICAM-1). In addition, CXCL13 induced B-cell adhesion to mucosal addressin cell adhesion molecule 1 (MAdCAM-1) by activating α4 integrin. These data identify CXCL13 as an arrest chemokine for B cells in HEVs and show that CXCL13 plays an important role in B-cell entry into not only PPs but also MLNs.