bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammatory Mediators in Dengue Virus Infection in Children: Interleukin-8 and Its Relationship to Neutrophil Degranulation
Authors: Juffrie M. , van der Meer G. M. , Hack C. E. , Haasnoot K. , Sutaryo  , Veerman A. J. P. , Thijs L. G. 
Published: July 2002

ABSTRACTThe chemokine interleukin-8 (IL-8) has chemoattractant activity for neutrophils and is able to activate and degranulate these cells. We investigated whether IL-8 may exert these effects in children with dengue virus infection. Circulating levels of IL-8, neutrophilic elastase (a constituent of the azurophilic granula of neutrophils), and lactoferrin, released from specific granula, were measured in 186 children with dengue virus infection, 33 healthy children as negative controls and 11 children with bacterial infections as positive controls. Levels of IL-8 on admission were elevated in 71% of the dengue patients, while the elastase and lactoferrin levels were increased in 68 and 17% of patients, respectively. These levels were significantly higher than in healthy children (P< 0.05) for IL-8 and elastase but not for lactoferrin (by the Wilcoxon-Mann-Whitney [WMW] U test). Similar levels of IL-8 were found in patients with bacterial infections. Levels of IL-8 and elastase in patients with shock were significantly higher than in patients without shock (P= 0.02; WMW), but those of lactoferrin were not. IL-8 correlated with elastase and lactoferrin (r= 0.19 andP= 0.009 versusr= 0.24 andP= 0.001, respectively; two-tailed Spearman rank correlation). Thus, IL-8 levels are increased in most patients with dengue virus infection and correlate with degranulation of neutrophils as well as with some clinical and hemodynamic variables. These findings suggest a role for IL-8 in the pathogenesis of dengue virus infection.
EnterohemorrhagicEscherichia coliInduces Apoptosis Which Augments Bacterial Binding and Phosphatidylethanolamine Exposure on the Plasma Membrane Outer Leaflet
Authors: Barnett Foster Debora , Abul-Milh Maan , Huesca Mario , Lingwood Clifford A. 
Published: July 2002

ABSTRACTEnterohemorrhagicEscherichia coli(EHEC) is a gastrointestinal pathogen that causes watery diarrhea and hemorrhagic colitis and can lead to serious and even fatal complications such as hemolytic uremic syndrome. We investigated the ability of EHEC to kill host cells using three human epithelial cell lines. Analysis of phosphatidylserine expression, internucleosomal cleavage of host cell DNA and morphological changes detected by electron microscopy changes revealed evidence of apoptotic cell death. The rates and extents of cell death were similar for both verotoxin-producing and nonproducing strains of EHEC as well as for a related gastrointestinal pathogen, enteropathogenicE. coli(EPEC). The induction of apoptosis by bacterial attachment was independent of verotoxin production and greater than that produced by a similar treatment with verotoxin alone. Expression of phosphatidylethanolamine, previously reported to bind EHEC and EPEC, was also increased on apoptotic cells but with little correlation to phosphatidylserine expression. Phosphatidylethanolamine levels but not phosphatidylserine levels on dying cells correlated with EHEC binding. Cells treated with phosphatidylethanolamine-containing liposomes also showed increased EHEC binding. These results suggest that bacterial induction of apoptosis offers an advantage for bacterial attachment by augmenting outer leaflet levels of the phosphatidylethanolamine receptor.
Antibodies against Ribosomal Phosphoprotein P0 ofPlasmodium falciparumProtect Mice against Challenge withPlasmodium yoelii
Authors: Chatterjee Sanchita , Singh Subhash , Sohoni Rashmi , Singh Nevil J. , Vaidya Akhil , Long Carole , Sharma Shobhona 
Published: July 2002

ABSTRACTAntibodies against thePlasmodium falciparumP0 ribosomal phosphoprotein (PfP0) have been detected exclusively but extensively in malaria-immune persons. Polyclonal rabbit and mice sera were raised against two recombinant polypeptides ofP. falciparumP0 protein, PfP0N and PfP0C, covering amino acids 17 to 61 and the remaining amino acids 61 to 316, respectively. Sera against both these domains detected a 35-kDa protein fromPlasmodium yoeliisubsp.yoelii, a rodent malarial parasite, and stained the surface of merozoites in immunofluorescence assays. Total immunoglobulin G (IgG) purified from rabbit and mouse anti-PfP0 sera by ammonium sulfate and DEAE-cellulose chromatography was used for passive transfer experiments in mice. Mice passively immunized with both anti-PfP0N and anti-PfP0C showed distinctly lower levels of parasitemia than control mice. With immunizations on days −1, 0, 1, 3, and 5, about 50% of both sets of mice receiving anti-PfP0N and anti-PfP0C cleared the lethal 17XL strain ofP. yoeliiand revived by day 25. All the control mice died by day 10. By extending the immunization schedule, the survival period of the mice could be extended for every mouse that received anti-PfP0 IgG. These data demonstrate the cross-protection of the anti-PfP0 IgG and establish parasite P0 protein as a target for invasion-blocking antibodies.
Regulation of Cytokine Expression in Mice Immunized with Cryptococcal Polysaccharide, a Glucuronoxylomannan (GXM), Associated with Peritoneal Antigen-Presenting Cells (APC): Requirements for GXM, APC Activation, and Interleukin-12
Authors: Blackstock Rebecca , McElwee Norma , Neller Eric , Shaddix-White Jeremy 
Published: July 2002

ABSTRACTMice immunized with peritoneal exudate cells (PEC; used as antigen-presenting cells [APC]) that are pulsed ex vivo with cryptococcal capsular polysaccharide, a glucuronoxylomannan (GXM), exhibit increased survival times and delayed-type hypersensitivity reactions when they are infected withCryptococcus neoformans. These responses are GXM specific. The present study revealed that GXM-APC immunization enhanced development of anticryptococcal type-1 cytokine responses (interleukin-2 [IL-2] and gamma interferon) in mice infected withC. neoformans. The enhancement was not GXM specific, because immunization with GXM-APC and immunization with APC alone had similar effects. GXM-APC (or APC) immunization caused small increases in the expression of type-2 cytokines (IL-4 and IL-5), but the increases were not always statistically significant. IL-10 levels were not regulated by immunization with GXM-APC or APC. GXM-APC prepared with PEC harvested from mice injected with complete Freund's adjuvant (CFA) enhanced type-1 cytokine responses, while GXM-APC prepared with PEC induced with incomplete Freund's adjuvant were ineffective. The CFA-induced PEC had an activated phenotype characterized by increased numbers of F4/80+cells that expressed CD40, B7-1, and B7-2 on their membranes. The immunomodulatory activity of the CFA-induced APC population was not attributed to their production of IL-12 because GXM-APC prepared with peritoneal cells harvested from IL-12 knockout mice or their wild-type counterparts were equally effective in augmenting the type-1 response. Blocking of IL-12 in the recipients of GXM-APC early after APC infusion revealed that early induction of IL-12 secretion was not responsible for the immunomodulatory response elicited by GXM-APC. These data, considered together with previously reported data, reveal that the protective activity of GXM-APC immunization involves both antigen-specific and nonspecific activities of GXM-APC.
Presence of Phosphorylcholine on a Filarial Nematode Protein Influences Immunoglobulin G Subclass Response to the Molecule by an Interleukin-10-Dependent Mechanism
Authors: Houston Katrina M. , Wilson Emma H. , Eyres Linda , Brombacher Frank , Harnett Margaret M. , Alexander James , Harnett William 
Published: July 2002

ABSTRACTThe filarial nematode product ES-62 contains phosphorylcholine (PC) covalently attached to N-linked glycans. ES-62 induced high levels of immunoglobulin G1 (IgG1) antibodies, but no IgG2a, to non-PC epitopes of the molecule following subcutaneous injection into BALB/c mice. Conversely, mice given ES-62 lacking PC demonstrated significant production of both IgG subclasses. Thus, PC appears to block production of IgG2a antibodies to other epitopes on the parasite molecule. A role for interleukin-10 (IL-10) in this effect was shown by the ability of IL-10−/−mice to make an IgG2a antibody response to non-PC epitopes of ES-62.
Enhancement ofMycobacterium tuberculosis-Induced Tumor Necrosis Factor Alpha Production from Primary Human Monocytes by an Activated T-Cell Membrane-Mediated Mechanism
Authors: Warwick-Davies Jan , Watson Amanda J. , Griffin George E. , Krishna Sanjeev , Shattock Robin J. 
Published: July 2002

ABSTRACTMycobacterium tuberculosisalone induces small, donor-variable amounts of tumor necrosis factor alpha (TNF-α) from primary human monocytes in vitro. However, TNF-α release is increased 5- to 500-fold when fixed activated T cells (FAT) or their isolated, unfixed membranes are added to this system. This FAT-induced synergy was at least as potent as that induced by gamma interferon (IFN-γ) at 100 U/ml. FAT-enhanced TNF-α production is at least in part transcriptionally mediated, as reflected by quantitative changes in TNF-α mRNA between 2 and 6 h poststimulation. Unlike IFN-γ-cocultured cells, FAT-treated monocytes appeared not to have enhanced TNF-α message stability, suggesting that de novo transcription may be involved in this effect. Furthermore,M. tuberculosisalone induced only minimal DNA binding of monocyte NF-κB, but cells treated withM. tuberculosisand FAT potentiated NF-κB activity more effectively. It is therefore possible that one mechanism by which FAT synergize withM. tuberculosisto stimulate TNF-α production is via NF-κB-enhanced transcription. These data strongly suggest that in the interaction of cells involved in the immune response toM. tuberculosis, T-cell stimulation of monocyte TNF-α production involves a surface membrane interaction(s) as well as soluble mediators.
Identification and Characterization of a Novel Genomic Island Integrated at
selC
in Locus of Enterocyte Effacement-Negative, Shiga Toxin-Producing
Escherichia coli
Authors: Schmidt H. , Zhang W.-L. , Hemmrich U. , Jelacic S. , Brunder W. , Tarr P. I. , Dobrindt U. , Hacker J. , Karch H. 
Published: July 2002

ABSTRACT

The
selC
tRNA gene is a common site for the insertion of pathogenicity islands in a variety of bacterial enteric pathogens. We demonstrate here that
Escherichia coli
that produces Shiga toxin 2d and does not harbor the locus of enterocyte effacement (LEE) contains, instead, a novel genomic island. In one representative strain (
E
.
coli
O91:H
−
strain 4797/97), this island is 33,014 bp long and, like LEE in
E
.
coli
O157:H7, is integrated 15 bp downstream of
selC
. This
E
.
coli
O91:H
−
island contains genes encoding a novel serine protease, termed EspI; an adherence-associated locus, similar to
iha
of
E
.
coli
O157:H7; an
E
.
coli
vitamin B
12
receptor (BtuB); an AraC-type regulatory module; and four homologues of
E
.
coli
phosphotransferase proteins. The remaining sequence consists largely of complete and incomplete insertion sequences, prophage sequences, and an intact phage integrase gene that is located directly downstream of the chromosomal
selC
. Recombinant EspI demonstrates serine protease activity using pepsin A and human apolipoprotein A-I as substrates. We also detected Iha-reactive protein in outer membranes of a recombinant clone and 10 LEE-negative, Shiga toxin-producing
E
.
coli
(STEC) strains by immunoblot analysis. Using PCR analysis of various STEC, enteropathogenic
E
.
coli
, enterotoxigenic
E
.
coli
, enteroaggregative
E
.
coli
, uropathogenic
E
.
coli
, and enteroinvasive
E
.
coli
strains, we detected the
iha
homologue in 59 (62%) of 95 strains tested. In contrast,
espI
and
btuB
were present in only two (2%) and none of these strains, respectively. We conclude that the newly described island occurs exclusively in a subgroup of STEC strains that are
eae
negative and contain the variant
stx
2d
gene.
Evaluation of Cholera Vaccines Formulated with Toxin-Coregulated Pilin Peptide Plus Polymer Adjuvant in Mice
Authors: Wu Jia-Yan , Wade William F. , Taylor Ronald K. 
Published: July 2002

ABSTRACTCholera is an acute diarrheal disease that is caused by the gram-negative bacteriumVibrio cholerae. The low efficacy of currently available killed-whole-cell vaccines and the reactinogenicity coupled with potential reversion of live vaccines have thus far precluded widespread vaccination for the control of cholera. Recent studies on the molecular nature of the virulence components that contribute toV. choleraepathogenesis have provided insights into possible approaches for the development of a defined subunit cholera vaccine. Genetic analysis has demonstrated that the toxin-coregulated pilus (TCP) is the major factor that contributes to colonization of the human intestine byV. cholerae. In addition, polyclonal and several monoclonal antibodies directed against TCP have been shown to provide passive immunity to disease in the infant mouse cholera model. In the present study, synthetic peptides corresponding to portions of the C-terminal disulfide region of TcpA pilin were formulated with polymer adjuvants currently in clinical trials and used to actively immunize adult female CD-1 mice. The experimental vaccine formulations elicited high levels of antigen-specific immunoglobulin G (IgG), including a broad spectrum of subclasses (IgG1, IgG2a, IgG2b, and IgG3), and lower levels of IgA. Infant mice born to the immunized mothers showed 100% protection against a 50% lethal dose (1 LD50) challenge and 50% protection against a 10-LD50challenge with virulent strain O395. These results indicate that specific regions of TcpA, including those delineated by the peptides used in this study, have the potential to be incorporated into an effective defined subunit vaccine for cholera.
Multiple Overlapping Epitopes in the Repetitive Unit of the Shed Acute-Phase Antigen from
Trypanosoma cruzi
Enhance Its Immunogenic Properties
Authors: Alvarez Paula , Leguizamón M. Susana , Buscaglia Carlos A. , Pitcovsky Tamara A. , Campetella Oscar 
Published: July 2002

ABSTRACT

The repetitive shed acute-phase antigen (SAPA) from
Trypanosoma cruzi
was thoroughly mapped by SPOT peptides and phage display strategies, showing that a single SAPA repeat is composed of multiple overlapping B-cell epitopes. We propose that this intricate antigenic structure constitutes an alternative device to repetitiveness in order to improve its immunogenicity.
Initial Characterization of the Hemolysin Stachylysin fromStachybotrys chartarum
Authors: Vesper Stephen J. , Magnuson Matthew L. , Dearborn Dorr G. , Yike Iwona , Haugland Richard A. 
Published: July 2002

ABSTRACTStachybotrys chartarumis a toxigenic fungus that has been associated with human health concerns, including pulmonary hemorrhage and hemosiderosis. This fungus produces a hemolysin, stachylysin, which in its apparent monomeric form has a molecular mass of 11,920 Da as determined by matrix-assisted laser desorption ionization–time of flight mass spectrometry. However, it appears to form polydispersed aggregates, which confounds understanding of the actual hemolytically active form. Exhaustive dialysis or heat treatment at 60°C for 30 min inactivated stachylysin. Stachylysin is composed of about 40% nonpolar amino acids and contains two cysteine residues. Purified stachylysin required more than 6 h to begin lysing sheep erythrocytes, but by 48 h, lysis was complete. Stachylysin also formed pores in sheep erythrocyte membranes.
Antibody Responses to Infections with Strains ofPlasmodium falciparumExpressing Diverse Forms of Merozoite Surface Protein 2
Authors: Weisman Simon , Wang Lina , Billman-Jacobe Helen , Nhan Doan Hanh , Richie Thomas L. , Coppel Ross L. 
Published: July 2002

ABSTRACTIndividuals living in areas wherePlasmodium falciparumis endemic experience numerous episodes of infection. These episodes may or may not be symptomatic, with the outcome depending on a combination of parasite and host factors, several of which are poorly understood. One factor is believed to be the particular alleles of several parasite proteins to which the host is capable of mounting protective immune responses. We report a study examining antibody responses to MSP2 in 15 semi-immune teenagers and adults living in the Khanh-Hoa area of southern-central Vietnam, whereP. falciparumis highly endemic; subjects were serially infected with multiple strains ofP. falciparum. The MSP2 alleles infecting these subjects were determined by nucleotide sequencing. A total of 62 MSP2 genes belonging to both dimorphic families were identified, of which 33 contained distinct alleles, with 61% of the alleles being detected once. Clear changes in the repertoire occurred between infections. Most infections contained a mixture of parasites expressing MSP2 alleles from both dimorphic families. Two examples of reinfection with a strain expressing a previously encountered allele were detected. Significant changes in antibody levels to various regions of MSP2 were detected over the course of the experiment. There was no clear relation between the infecting form of MSP2 and the ensuing antibody response. This study highlights the complexity of host-parasite relationship for this important human pathogen.
Serological Basis for Use of Meningococcal Serogroup C Conjugate Vaccines in the United Kingdom: Reevaluation of Correlates of Protection
Authors: Borrow Ray , Andrews Nick , Goldblatt David , Miller Elizabeth 
Published: July 2002

ABSTRACTThe antibody data supporting the use of meningococcal serogroup C conjugate (MCC) vaccines in the United Kingdom were generated by serum bactericidal assay (SBA) using rabbit complement (rSBA). This may give higher titers than those obtained with human complement (hSBA), for which the “gold standard” correlate of protection for meningococcal C disease is a titer of ≥4. Comparison of rSBA and hSBA titers in sera from unvaccinated adults with an rSBA titer of ≥8 showed that for 93% (27 of 29) the titer was ≥4 by hSBA, confirming natural protection. Furthermore, sera from MCC vaccinees showed that an rSBA titer of <8 or ≥128 discriminated susceptibility and protection well (85% with rSBA titers of <8 had hSBA titers of <4, and 99% with rSBA titers of ≥128 had hSBA titers of ≥4). However, discrimination was poor in the rSBA titer range 8 to 64, with only 60% having hSBA titers of ≥4. In such cases we propose that protection can be assumed if there is a fourfold rise in titer between pre- and postvaccination sera or if there is a characteristic booster response to a polysaccharide challenge dose with, if available, evidence of antibody avidity maturation or an hSBA titer of result ≥4. Applying these criteria to toddlers, 10 to 40% of whom had titers in the range 8 to 64 after a single dose of MCC vaccine, showed that 94% had a fourfold rise in titer, including 98% of those in the titer range 8 to 64. In addition, of those with titers of <128 post-MCC vaccination, 90% had titers of ≥128 after a 10-μg polysaccharide booster dose, compared with only 7% of unprimed age-matched toddlers given a full 50-μg dose. Furthermore, the increase in geometric mean avidity index pre- and postbooster was independent of post-primary MCC titer. These results indicated that the majority of toddlers with an rSBA titer between 8 and 64, and some of those with an hSBA result of <4, have mounted a protective immune response with the induction of immunological memory.
Expression of Cytokine and Chemokine Genes by Human Middle Ear Epithelial Cells Induced by Formalin-KilledHaemophilus influenzaeor Its LipooligosaccharidehtrBandrfaDMutants
Authors: Tong H. H. , Chen Y. , James M. , Van Deusen J. , Welling D. B. , DeMaria T. F. 
Published: July 2002

ABSTRACTTo define the role of nontypeableHaemophilus influenzae(NTHI) lipooligosaccharide (LOS) in the induction of proinflammatory cytokine gene expression during otitis media, we compared the abilities of formalin-killed NTHI strain 2019 and its LOShtrBandrfaDmutants to stimulate human middle ear epithelial (HMEE) cell cytokine and chemokine gene expression and production in vitro. Strain DK-1, anrfaDgene mutant, expresses a truncated LOS consisting of only three deoxy-d-manno-octulosonic acid residues, a single heptose, and lipid A. Strain B29, an isogenichtrBmutant, possesses an altered oligosaccharide core and an altered lipid A. HMEE cells were incubated with formalin-killed NTHI 2019, B29, or DK-1. The supernatants and the cells were collected at 2, 4, 8, and 24 h after stimulation. Expression of genes for the cytokines tumor necrosis factor alpha (TNF-α), interleukin lβ (IL-1β), and IL-6 and for the chemokines macrophage inflammatory protein 1β (MIP-1β), monocyte chemotactic peptide 1 (MCP-1), and IL-8 was quantitated by real-time PCR. NTHI B29 did not significantly stimulate any cytokine or chemokine mRNA expression in HMEE cells. In striking contrast, NTHI 2019 induced up to 105-, 139-, and 187-fold increases in HMEE cell expression of IL-1β, TNF-α, and MIP-1β, respectively (P< 0.01 [2019 versus B29]). NTHI 2019 also induced upregulation of IL-8, IL-6, and MCP-1 mRNA expression (by 26-, 44-, and 14-fold, respectively [P< 0.05 {2019 versus B29}]). The significant induction of cytokine genes was confirmed by quantitating the secretion of cytokines in culture supernatants with an enzyme-linked immunosorbent assay. There were no significant differences in mRNA expression of IL-8, IL-6, and MCP-1 between the 2019- and DK-1-treated groups. The low levels of gene transcripts observed after incubation of HMEE cells with B29 indicate that products of the disrupted NTHIhtrBLOS gene may play a major role in induction of these particular inflammatory mediators.
Vaccination withBordetella pertussis-Pulsed Autologous or Heterologous Dendritic Cells Induces a Mucosal Antibody Response In Vivo and Protects against Infection
Authors: George-Chandy Annie , Mielcarek Nathalie , Nordström Inger , Holmgren Jan , Eriksson Kristina 
Published: July 2002

ABSTRACTThis study demonstrates for the first time that vaccination with either autologous or heterologous dendritic cells (DC) pulsed with specific antigen induces protective immune responses against noninvasive bacteria, namelyBordetella pertussis. The DC-mediated protection is associated with strongB. pertussis-specific immunoglobulin G (IgG) and IgA responses in the lung.
Establishment of a Persistent
Escherichia coli
Reservoir during the Acute Phase of a Bladder Infection
Authors: Mulvey Matthew A. , Schilling Joel D. , Hultgren Scott J. 
Published: July 2002

ABSTRACT

The vast majority of urinary tract infections are caused by strains of uropathogenic
Escherichia coli
that encode filamentous adhesive organelles called type 1 pili. These structures mediate both bacterial attachment to and invasion of bladder epithelial cells. However, the mechanism by which type 1 pilus-mediated bacterial invasion contributes to the pathogenesis of a urinary tract infection is unknown. Here we show that type 1-piliated uropathogens can invade the superficial epithelial cells that line the lumenal surface of the bladder and subsequently replicate, forming massive foci of intracellular
E. coli
termed bacterial factories. In response to infection, superficial bladder cells exfoliate and are removed with the flow of urine. To avoid clearance by exfoliation, intracellular uropathogens can reemerge and eventually establish a persistent, quiescent bacterial reservoir within the bladder mucosa that may serve as a source for recurrent acute infections. These observations suggest that urinary tract infections are more chronic and invasive than generally assumed.