bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Activated Protein C inHelicobacter pylori-Associated Gastritis
Authors: Oka Satoko , Gabazza Esteban Cesar , Taguchi Yukiko , Yamaguchi Michihiko , Nakashima Shigehito , Suzuki Koji , Adachi Yukihiko , Imoto Ichiro 
Published: July 2002

ABSTRACTThe protein C (PC) pathway has recently been suggested to play a role in the regulation of the inflammatory response. To further extend the anti-inflammatory effect of activated PC (APC) in vivo, particularly its biological relevance to human disease, the activity of APC in the mucosa of patients withHelicobacter pylori-associated gastritis and the effect of vacuolating cytotoxin (VacA), cytotoxin-associated antigen (CagA), andH. pylorilipopolysaccharide (LPS) on PC activation were evaluated. This study comprised 35 patients with chronic gastritis. There were 20 patients with and 15 withoutH. pyloriinfection. The levels of PC and APC-PC inhibitor (PCI) complex were measured by immunoassays. The level of PC was significantly decreased and the level of APC-PCI complex was significantly increased in biopsy specimens from gastric corpus and antrum in patients withH. pylori-associated gastritis as compared toH. pylori-negative subjects. The concentrations of VacA, CagA, and LPS were significantly correlated with those of the APC-PCI complex in biopsy mucosal specimens from the gastric corpus and antrum.H. pyloriLPS, VacA, and CagA induced a dose-dependent activation of PC on the surface of monocytic cells. APC inhibited the secretion of tumor necrosis factor alpha (TNF-α) induced byH. pyloriLPS. Overall, these results suggest thatH. pyloriinfection is associated with increased APC generation in the gastric mucosa. The inhibitory activity of APC on TNF-α secretion may serve to protectH. pylori-induced gastric mucosal damage.
Heterologous Expression of an Immunogenic Pneumococcal Type 3 Capsular Polysaccharide in
Lactococcus lactis
Authors: Gilbert Christophe , Robinson Karen , Le Page Richard W. F. , Wells Jeremy M. 
Published: July 2002

ABSTRACT

In order to develop a new system for the analysis of capsular biosynthetic pathways we have explored the possibility of expressing type 3 capsular polysaccharide (CPS) from the pathogen
Streptococcus pneumoniae
in
Lactococcus lactis
, an unencapsulated lactic acid bacterium being developed as a vaccine delivery vehicle for mucosal immunization. Only three of the four type 3 CPS biosynthesis genes were found to be necessary for the abundant formation (120 mg liter
−1
) of an extracellular type 3 CPS in
L. lactis
, implying a role for the type 3-specific synthase in the extracellular transport of the CPS or implying the existence of an alternative export system in
L. lactis
. The authenticity of the expressed heterologous polysaccharide was established by chemical and immunological analyses. Proton and carbon nuclear magnetic resonance spectroscopy of CPSs purified from
L. lactis
and
S. pneumoniae
showed that the two CPS structures were identical. When mice were immunized intraperitoneally with 3.5 × 10
6
CFU of live recombinant lactococci expressing a total of approximately 0.5 μg of type 3 CPS, the immune responses elicited appeared identical to those observed in mice inoculated with 0.5 μg of type 3 CPS purified from
S. pneumoniae
. These findings show that
L. lactis
is a useful host in which to study the role and function of genes involved in the production of bacterial capsules. Additionally,
L. lactis
shows potential as a host for the safe production of capsule antigens and as a vaccine delivery vehicle for polysaccharide antigens.
Host Resistance toListeria monocytogenesInfection Is Enhanced but Resistance toStaphylococcus aureusInfection Is Reduced in Acute Graft-versus-Host Disease in Mice
Authors: Miura Tomisato , Mizuki Daisuke , Sasaki Sanae , Hasegawa Suguru , Sashinami Hiroshi , Nakane Akio 
Published: July 2002

ABSTRACTAcute graft-versus-host disease (GVHD) is characterized by the production of high levels of T helper 1 (Th1)-type cytokines. Bone marrow transplantation from allogeneic C57BL/6 cells to CBF1mice produced acute GVHD. Host resistance to Th1-drivenListeria monocytogeneswas enhanced, whereas host resistance to Th2-drivenStaphylococcus aureuswas reduced during acute GVHD. These results suggest that opposite host responses are observed between Th1-driven and Th2-driven bacterial infections in acute GVHD.
Recombinant Antigen-Enterotoxin A2/B Chimeric Mucosal Immunogens Differentially Enhance Antibody Responses and B7-Dependent Costimulation of CD4+T Cells
Authors: Martin Michael , Hajishengallis George , Metzger Daniel J. , Michalek Suzanne M. , Connell Terry D. , Russell Michael W. 
Published: July 2002

ABSTRACTThe ADP-ribosylating enterotoxins, cholera toxin (CT) and theEscherichia coliheat-labile toxin (LT-IIa), have been shown to enhance mucosal and systemic antibody (Ab) responses to coadministered antigens. The purpose of the present study was to compare the ability of the nontoxic A2/B subunits of these toxins, which have distinct targeting properties, to augment the immunogenicity of a genetically coupled protein antigen. Structurally similar chimeric proteins were generated by genetically replacing the toxic A1 subunit of CT or LT-IIa with the saliva-binding region (SBR) from the streptococcal adhesin AgI/II. Intranasal immunization of BALB/c mice with either chimeric protein induced significantly higher plasma and mucosal anti-SBR immunoglobulin A (IgA) and IgG Ab responses than SBR alone. Moreover, compared to SBR–LT-IIaA2/B, SBR-CTA2/B elicited significantly higher levels of plasma IgG1 and salivary IgA anti-SBR Ab responses. Ex vivo and in vitro experiments revealed that SBR-CTA2/B selectively up-regulated B7-2 expression on murine B cells isolated from both the nasal associated lymphoid tissue, cervical lymph nodes, and spleen. In contrast, SBR–LT-IIaA2/B had little effect on B7-1 or B7-2 expression on B220+, CD11b+, or CD11c+cells. Analysis of the functional costimulatory activity of SBR-CTA2/B-treated B cells revealed a significant enhancement in anti-CD3-stimulated CD4+T-cell proliferative responses, and this proliferation was significantly reduced by treatment with anti-B7-2 but not with anti-B7-1 or isotype control Abs. Thus, SBR-CTA2/B and SBR–LT-IIaA2/B exhibit distinct patterns of antibody responses associated with differential effects on B7-2 expression and subsequent costimulatory effects on CD4+T cells.
Development of a Recombinant Antigen Vaccine against Infection with the Filarial WormOnchocerca volvulus
Authors: Abraham David , Leon Ofra , Leon Shalom , Lustigman Sara 
Published: July 2002

ABSTRACTEfforts to controlOnchocerca volvulus, the etiologic agent of river blindness, have been limited to vector control and drug treatment to eliminate microfilariae, with no means available to prevent infection. The goal of this study was to develop a vaccine against this infection using recombinant antigens that are expressed in the early larval stages of the parasite. Five recombinant antigens, Ov7, Ov64, OvB8, Ov9M, and Ov73k, were identified by screening adult and larval cDNA libraries with antibodies from immune humans, chimpanzees, or rabbits. When mice were immunized with the five individual recombinant antigens, statistically significant reductions in parasite survival were induced in mice immunized with Ov7, OvB8, or Ov64, when administered in alum but not when injected in Freund's complete adjuvant (FCA). Live larvae recovered from control and immunized mice were analyzed to determine their developmental stages. A decrease in the percentage of larvae molting from the third stage to the fourth stage was observed with mice immunized with Ov7, Ov64, or OvB8 in alum but not with mice immunized with Ov9 and Ov73k or with mice immunized with any of the five antigens in FCA. Mice immunized with a cocktail of the three protective antigens developed protective immunity equal to that seen with mice immunized with individual antigens. This study has identified, for the first time, three recombinant antigens capable of inducing protective immunity toO. volvulus. Furthermore, since the antigens functioned with alum as the adjuvant, this vaccine could potentially be used clinically to prevent river blindness in humans.
Fish Monocytes as a Model for Mycobacterial Host-Pathogen Interactions
Authors: El-Etr Sahar H. , Yan Ling , Cirillo Jeffrey D. 
Published: July 2002

ABSTRACTMycobacterium marinum, a relatively rapid-growing fish and human pathogen, has become an important model for the investigation of mycobacterial pathogenesis.M. marinumis closely related to theMycobacterium tuberculosiscomplex and causes a disease in fish and amphibians with pathology similar to tuberculosis. We have developed an in vitro model for the study ofM. marinumvirulence mechanisms using the carp monocytic cell line CLC (carp leukocyte culture). We found that fish monocytes can differentiate between pathogenic and nonpathogenic mycobacterial species. Interestingly,M. marinumenters fish monocytes at a 40- to 60-fold-higher rate thanMycobacterium smegmatis. In addition,M. marinumsurvives and replicates in fish monocytes whileM. smegmatisis killed. We also found thatM. marinuminhibits lysosomal fusion in fish monocytes, indicating that these cells may be used to dissect the mechanisms of intracellular trafficking in mycobacteria. We conclude from these observations that monocytic cells from fish, a natural host forM. marinum, provide an extremely valuable model for the identification and characterization of mycobacterial virulence determinants in the laboratory.
Evidence that Mycobacterial PE_PGRS Proteins Are Cell Surface Constituents That Influence Interactions with Other Cells
Authors: Brennan Michael J. , Delogu Giovanni , Chen Yiping , Bardarov Stoyan , Kriakov Jordan , Alavi Mohammad , Jacobs William R. 
Published: July 2002

ABSTRACTThe elucidation of the genomic sequence ofMycobacterium tuberculosisrevealed the presence of a novel multigene family designated PE/PE_PGRS that encodes numerous, highly related proteins of unknown function. In this study, we demonstrate that a transposon insertion in a PE_PGRS gene (1818PE_PGRS) found inMycobacterium bovisBCG Pasteur, which is the BCG homologue of theM.tuberculosisH37Rv geneRv1818c, introduces new phenotypic properties to this BCG strain. These properties include dispersed growth in liquid medium and reduced infection of macrophages. Complementation of the 1818PE_PGRS::Tn5367mutant with the wild-type gene restores both aggregative growth (clumping) in liquid medium and reestablishes infectivity of macrophages to levels equivalent to those for the parent BCG strain. Western blot analysis using antisera raised against the 1818PE_PGRSprotein shows that PE_PGRS proteins are found in cell lysates of BCG andM.tuberculosisH37Ra and in the cell wall fraction ofM.tuberculosisH37Rv. Moreover, immunofluorescent labeling of mycobacteria indicates that certain PE_PGRS proteins are localized at the cell surface of BCG andM.tuberculosis. Together these results suggest that certain PE_PGRS proteins may be found at the surface of mycobacteria and influence both cell surface interactions among mycobacteria as well as the interactions of mycobacteria with macrophages.
Nippocystatin, a Cysteine Protease Inhibitor fromNippostrongylus brasiliensis, Inhibits Antigen Processing and Modulates Antigen-Specific Immune Response
Authors: Dainichi Teruki , Maekawa Yoichi , Ishii Kazunari , Zhang Tianqian , Nashed Baher Fawzy , Sakai Tohru , Takashima Miwa , Himeno Kunisuke 
Published: July 2002

ABSTRACTDuring infection, parasites evade the host immune system by modulating or exploiting the immune system; e.g., they suppress expression of major histocompatibility complex class II molecules or secrete cytokine-like molecules. However, it is not clear whether helminths disturb the immune responses of their hosts by controlling the antigen-processing pathways of the hosts. In this study, we identified a new cysteine protease inhibitor, nippocystatin, derived from excretory-secretory (ES) products of an intestinal nematode,Nippostrongylus brasiliensis. Nippocystatin, which belongs to cystatin family 2, consists of 144 amino acids and is secreted as a 14-kDa mature form. In vivo treatment of ovalbumin (OVA)-immunized mice with recombinant nippocystatin (rNbCys) profoundly suppressed OVA-specific proliferation of splenocytes but not non-antigen-specific proliferation of splenocytes. OVA-specific cytokine production was also greatly suppressed in rNbCys-treated mice. Although the serum levels of both OVA-specific immunoglobulin G1 (IgG1) and IgG2a were not affected by rNbCys treatment, OVA-specific IgE was preferentially downregulated in rNbCys-treated mice. In vitro rNbCys inhibited processing of OVA by lysosomal cysteine proteases from the spleens of mice. Mice with anti-nippocystatin antibodies became partially resistant to infection withN. brasiliensis. Based on these findings,N. brasiliensisappears to skillfully evade host immune systems by secreting nippocystatin, which modulates antigen processing in antigen-presenting cells of hosts.
BrkA Protein ofBordetella pertussisInhibits the Classical Pathway of Complement after C1 Deposition
Authors: Barnes Michael G. , Weiss Alison A. 
Published: July 2002

ABSTRACTBordetella pertussisproduces a 73-kDa protein,BrkA (Bordetellaresistance to killing), which inhibits the bactericidal activity of complement. In this study we characterized the step in the complement cascade where BrkA acts, using three strains: a wild-type strain, a strain containing an insertional disruption ofbrkA, and a strain containing two copies of thebrkAlocus. Following incubation with 10% human serum, killing was greatest for the BrkA mutant, followed by that for the wild-type strain, while the strain with two copies ofbrkAwas the most resistant. Complement activation was monitored by enzyme-linked immunosorbent assay (ELISA) or Western blotting. ELISAs for SC5b-9, the soluble membrane attack complex, showed that production of SC5b-9 was greatest with thebrkAmutant, less with the wild type, and least with the strain containing two copies ofbrkA. Deposition of complement proteins on the bacteria was monitored by Western blotting. A decrease in deposition on the bacteria of C4, C3, and C9 corresponded with decreased complement sensitivity. Deposition of C1, however, was not affected by the presence of BrkA. These studies show that BrkA inhibits the classical pathway of complement activation and prevents accumulation of deposited C4.
Meningococcal Outer Membrane Vesicle Vaccine Given Intranasally Can Induce Immunological Memory and Booster Responses without Evidence of Tolerance
Authors: Bakke Hilde , Lie Kristian , Haugen Inger Lise , Korsvold Gro Ellen , Høiby E. Arne , Næss Lisbeth Meyer , Holst Johan , Aaberge Ingeborg S. , Oftung Fredrik , Haneberg Bjørn 
Published: July 2002

ABSTRACTWe have studied the ability of outer membrane vesicle (OMV) vaccines fromNeisseria meningitidisserogroup B to induce vaccine-specific antibody and spleen cell proliferative responses in mice after being administered intranasally (i.n.) and/or subcutaneously (s.c.). A series of four weekly i.n. doses (25 μg) without adjuvant or a single s.c. dose (2.5 μg) with aluminum hydroxide was followed 2 months later by secondary i.n. or s.c. immunizations. After i.n. priming, both immunoglobulin G (IgG) antibody responses in serum, measured by enzyme-linked immunosorbent assay, and IgA antibodies in saliva and extracts of feces were significantly boosted by later i.n. immunizations. The IgG antibody responses in serum were also significantly augmented by secondary s.c. immunization after i.n. as well as s.c. priming. Sera from mice immunized i.n. reached the same level of bactericidal activity as after s.c. immunizations. The s.c. immunizations alone, however, had no effect on mucosal IgA antibody responses, but could prime for booster antibody responses in secretions to later i.n. immunizations. The i.n. immunizations also led to marked OMV-specific spleen cell proliferation in vitro. Both serum antibody responses and spleen cell proliferation were higher after i.n. priming and later s.c. immunizations than after s.c. immunizations alone. There was thus no evidence that i.n. priming had induced immunological tolerance within the B- or T-cell system. Our results indicate that a nonproliferating meningococcal OMV vaccine given i.n. can induce immunological memory and that it may be favorably combined with similar vaccines for injections.
Recognition of Lewis x Derivatives Present on Mucins by Flagellar Components of
Pseudomonas aeruginosa
Authors: Scharfman Andree , Arora Shiwani K. , Delmotte Philippe , Van Brussel Edwige , Mazurier Joel , Ramphal Reuben , Roussel Philippe 
Published: July 2002

ABSTRACT

Pseudomonas aeruginosa
binds to human respiratory mucins by mechanisms involving flagellar component-receptor interactions. The adhesion of
P. aeruginosa
strain PAK is mediated by the flagellar cap protein, FliD, without the involvement of flagellin. Two distinct types of FliD proteins have been identified in
P. aeruginosa
: A type, found in strain PAK, and B type, found in strain PAO1. In the present work, studies performed with the
P. aeruginosa
B-type strain PAO1 indicate that both the FliD protein and the flagellin of this strain are involved in the binding to respiratory mucins. Using polyacrylamide-based fluorescent glycoconjugates in a flow cytometry assay, it was previously demonstrated that
P. aeruginosa
recognizes Le
x
(or Lewis x) derivatives found at the periphery of human respiratory mucins. The aim of the present work was therefore to determine whether these carbohydrate epitopes (or glycotopes) are receptors for FliD proteins and flagellin. The results obtained by both flow cytometry and a microplate adhesion assay indicate that the FliD protein of strain PAO1 is involved in the binding of glycoconjugates bearing Le
x
or sialyl-Le
x
determinants, while the binding of flagellin is restricted to the glycoconjugate bearing Le
x
glycotope. In contrast, the type A cap protein of
P. aeruginosa
strain PAK is not involved in the binding to glycoconjugates bearing Le
x
, sialyl-Le
x
, or sulfosialyl-Le
x
glycotopes. This study demonstrates a clear association between a specific
Pseudomonas
adhesin and a specific mucin glycotope and demonstrates that fine specificities exist in mucin recognition by
P. aeruginosa
.
Accumulation of Human Heat Shock Protein 60-Reactive T Cells in the Gingival Tissues of Periodontitis Patients
Authors: Yamazaki Kazuhisa , Ohsawa Yutaka , Tabeta Koichi , Ito Harue , Ueki Kaoru , Oda Taro , Yoshie Hiromasa , Seymour Gregory J. 
Published: July 2002

ABSTRACTHeat shock protein 60s (hsp60) are remarkably immunogenic, and both T-cell and antibody responses to hsp60 have been reported in various inflammatory conditions. To clarify the role of hsp60 in T-cell responses in periodontitis, we examined the proliferative response of peripheral blood mononuclear cells (PBMC), as well as the cytokine profile and T-cell clonality, for periodontitis patients and controls following stimulation with recombinant human hsp60 andPorphyromonas gingivalisGroEL. To confirm the infiltration of hsp60-reactive T-cell clones into periodontitis lesions, nucleotide sequences within complementarity-determining region 3 of the T-cell receptor (TCR) β-chain were compared between hsp60-reactive peripheral blood T cells and periodontitis lesion-infiltrating T cells. Periodontitis patients demonstrated significantly higher proliferative responses of PBMC to human hsp60, but not toP. gingivalisGroEL, than control subjects. The response was inhibited by anti-major histocompatibility complex class II antibodies. Analysis of the nucleotide sequences of the TCR demonstrated that human hsp60-reactive T-cell clones and periodontitis lesion-infiltrating T cells have the same receptors, suggesting that hsp60-reactive T cells accumulate in periodontitis lesions. Analysis of the cytokine profile demonstrated that hsp60-reactive PBMC produced significant levels of gamma interferon (IFN-γ) in periodontitis patients, whereasP. gingivalisGroEL did not induce any skewing toward a type1 or type2 cytokine profile. In control subjects no significant expression of IFN-γ or interleukin 4 was induced. These results suggest that periodontitis patients have human hsp60-reactive T cells with a type 1 cytokine profile in their peripheral blood T-cell pools.
Protection of Mice againstCoccidioides immitisIntranasal Infection by Vaccination with Recombinant Antigen 2/PRA
Authors: Shubitz Lisa , Peng Tao , Perrill Robert , Simons Julie , Orsborn Kris , Galgiani John N 
Published: July 2002

ABSTRACTSubcutaneous vaccination with recombinant antigen 2/PRA (rAg2/PRA) protected BALB/c mice against intranasal infection withCoccidioides immitis. Subcutaneously vaccinated C57BL/6 mice and intranasally vaccinated BALB/c mice were protected against larger numbers of infecting spores. Weight loss correlated with lethality, but histologic appearance did not. These studies support rAg2/PRA vaccination to prevent coccidioidomycosis.
Control of Initiation of Sporulation by Replication Initiation Genes in
Bacillus subtilis
Authors: Lemon Katherine P. , Kurtser Iren , Wu Judy , Grossman Alan D. 
Published: July 2002

ABSTRACT

Initiation of spore formation in
Bacillus subtilis
appears to depend on initiation of DNA replication. This regulation was first identified using a temperature-sensitive mutation in
dnaB
. We found that mutations in the replication initiation genes
dnaA
and
dnaD
also inhibit sporulation, indicating that inhibition of sporulation is triggered by general defects in the function of replication initiation proteins.
Analysis of Guanine Nucleotide Binding and Exchange Kinetics of the
Escherichia coli
GTPase Era
Authors: Sullivan S. M. , Mishra R. , Neubig R. R. , Maddock J. R. 
Published: July 2002

ABSTRACT

Era is an essential
Escherichia coli
guanine nucleotide binding protein that appears to play a number of cellular roles. Although the kinetics of Era guanine nucleotide binding and hydrolysis have been described, guanine nucleotide exchange rates have never been reported. Here we describe a kinetic analysis of guanine nucleotide binding, exchange, and hydrolysis by Era using the fluorescent mant (
N
-methyl-3′-
O
-anthraniloyl) guanine nucleotide analogs. The equilibrium binding constants (

K
D

) for mGDP and mGTP (0.61 ± 0.12 μM and 3.6 ± 0.80 μM, respectively) are similar to those of the unmodified nucleotides. The single turnover rates for mGTP hydrolysis by Era were 3.1 ± 0.2 mmol of mGTP hydrolyzed/min/mol in the presence of 5 mM MgCl
2
and 5.6 ± 0.3 mmol of mGTP hydrolyzed/min/mol in the presence of 0.2 mM MgCl
2
. Moreover, Era associates with and exchanges guanine nucleotide rapidly (on the order of seconds) in both the presence and absence of Mg
2+
. We suggest that models of Era function should reflect the rapid exchange of nucleotides in addition to the GTPase activity inherent to Era.