bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promotion of Safety Helmets for Child Bicyclists: 2002 Update
Authors: Coffman Sherrilyn 
Published: April 2004

AbstractPurpose(1) Current research continues to show that bicycle helmets prevent serious injury and death in cyclists of all ages. Children are at special risk for head injury. The purpose of this review was to update information on the use and protective effect of bicycle helmets for child cyclists.Conclusions(2) Legislation, combined with community education and helmet promotion campaigns, remains the most cost‐effective approach for increasing helmet use. Nineteen states and the District of Columbia have passed helmet legislation. Modest gains in helmet‐wearing rates have been documented, with the greatest gains in young children, compared with adolescents.Implications(3) Nurses remain in strategic positions to encourage helmet use by educating children and parents. Nurses can participate in community‐based education and advocacy programs. Nurse researchers can carry out descriptive studies that increase community awareness of bicycle injuries and examine factors such as parental rules and adolescent risk‐taking.
Synthesis of Research Findings Regarding Alzheimer's Disease: Part III, Caregiver Burden and Care Settings
Authors: Bower Fay L. , McCullough Cyndi S. , Pille Barbara L. 
Published: April 2004

Abstract(1) While Alzheimer's disease (AD) is devastating for those who acquire it, AD can be equally devastating for the caregiver, whether that person is a professional or a family member. This article contains synthesized knowledge about the effects of AD on caregivers and the attempts that have been made to create special care units, residential living facilities, and group living arrangements to meet the unique needs of AD patients and their caregivers. While the research regarding caregivers of AD patients and the attempts to provide alternatives to institutionalization are not extensive, the findings presented here have proved to be very useful as a basis for clinical practice and future research.
Analysis of Haptoglobin and Hemoglobin-Haptoglobin Interactions with theNeisseria meningitidisTonB-Dependent Receptor HpuAB by Flow Cytometry
Authors: Rohde Kyle H. , Dyer David W. 
Published: April 2004

ABSTRACTNeisseria meningitidisexpresses a two-component TonB-dependent receptor, HpuAB, which mediates heme-iron (Hm-Fe) acquisition from hemoglobin and hemoglobin-haptoglobin complexes. Due to genetic polymorphisms in the human haptoglobin gene, haptoglobin (and hemoglobin-haptoglobin) exists as three structurally distinct phenotypes. In this study, we examined the influence of the haptoglobin phenotype on the interactions of HpuAB with apo-haptoglobin and hemoglobin-haptoglobin. Growth assays confirmed that HpuAB utilizes hemoglobin-haptoglobin more efficiently than hemoglobin as an Fe source and revealed a preference for human-specific, polymeric 2-2 or 2-1 hemoglobin-haptoglobin complexes. We developed a flow cytometry-based assay to measure the binding kinetics of fluorescein-labeled ligands to HpuAB on live, intact meningococci. The binding affinity of HpuAB for hemoglobin-haptoglobin phenotypes correlated well with the ability of each ligand to supportNeisseria meningitidisgrowth, with higher affinities exhibited for types 2-2 and 2-1 hemoglobin-haptoglobin. Saturable binding of Hb and apo-haptoglobin suggested that HpuAB-mediated utilization of hemoglobin-haptoglobin involves specific interactions with both components. In contrast to previous studies, we detected binding of HpuB expressed alone to hemoglobin, apo-haptoglobin, and hemoglobon-haptoglobin of all three phenotypes. However, in the absence of HpuA, the binding capacity and/or affinity of the receptor was reduced and the dissociation of hemoglobin was impaired. We did not detect binding of HpuA alone to hemoglobin, apo-haptoglobin, or hemoglobin-haptoglobin; however, the lipoprotein is crucial for optimal recognition and use of ligands by the receptor. Finally, this study confirmed the integral role of TonB and the proton motive force in the binding and dissociation of Hb and hemoglobin-haptoglobin from HpuAB.
Inhibition of Monocytic Interleukin-12 Production byCandida albicansvia Selective Activation of ERK Mitogen-Activated Protein Kinase
Authors: Tang Ningfeng , Liu Liming , Kang Kefei , Mukherjee Pranab K. , Takahara Masakazu , Chen Guofen , McCormick Thomas S. , Cooper Kevin D. , Ghannoum Mahmoud 
Published: April 2004

ABSTRACTOur previous data demonstrated that liveCandida albicansinhibits interleukin-12 (IL-12) production by human monocytes. Here we explored whetherC. albicansinhibits IL-12 via a released factor and whether the inhibition is mediated via mitogen-activated protein kinase (MAPK) regulation. Supernatant fluids were obtained from culturedC. albicans(SC5314) as well as culturedSaccharomyces cerevisiaeafter 20 h of incubation. At 2 h postincubation of monocytes with heat-killedC. albicans(HKCA) (2:1) to stimulate IL-12, concentrated fungal supernatant fluids were added and incubated for an additional 20 h. The present data show that, unlike supernatant fluids obtained fromS. cerevisiae, theC. albicanssupernatant fluids significantly suppressed IL-12 production induced by HKCA. This suggested that the inhibition isCandidaspecific. A preliminary biochemical analysis revealed that this secretory IL-12 inhibitory factor is glycoprotein in nature. The inhibitory activity had no effect on the phagocytosis of yeasts. Supernatant fluids fromC. albicansmarkedly induced the phosphorylation of ERK44/42 MAPK, but not p38 and SAPK, 1 min after they were added to monocytes. To test if the induction of ERK44/42 MAPK was central to the IL-12 inhibition, we used gamma interferon (IFN-γ) (1 ng/ml) plus lipopolysaccharide (LPS) (100 ng/ml) to stimulate IL-12 production by monocytes. The inhibition of ERK MAPK by the specific inhibitor PD 98059 significantly reduced phospho-ERK44/42 MAPK levels induced byC. albicanssupernatant fluids in the IFN-γ-plus-LPS-driven monocytes. Concomitantly, PD 98059 reversed the IL-12 inhibitory activity of theC. albicanssupernatant (P< 0.01). These data indicate thatC. albicanscan inhibit IL-12 production by secreting an ERK44/42 MAPK-stimulating factor and thus can attenuate effective immune responses.
Regulation of Proinflammatory Cytokine Expression by Shiga Toxin 1 and/or Lipopolysaccharides in the Human Monocytic Cell Line THP-1
Authors: Harrison Lisa M. , van Haaften Wilhelmina C. E. , Tesh Vernon L. 
Published: April 2004

ABSTRACTInfection with Shiga toxin (Stx)-producing bacteria and the subsequent release of Stxs and endotoxins into the bloodstream may damage blood vessels in the colon, kidneys, and central nervous system, leading to bloody diarrhea, acute renal failure, and neurological complications. The proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) may contribute to the pathogenesis of Stx-induced vascular lesions by up-regulating toxin receptor expression on endothelial cells. We previously showed that macrophages treated with purified Shiga toxin 1 (Stx1) or lipopolysaccharides (LPS) secrete TNF-α and IL-1β. Northern blot analysis revealed that treatment of the human monocytic cell line THP-1 with LPS induced a rapid and transient increase in steady-state TNF-α and IL-1β transcripts. In contrast, Stx1 induced slower but prolonged elevations in cytokine transcripts. The presence of both stimulants resulted in optimal cytokine mRNA induction in terms of kinetics and prolonged expression. Compared to LPS, Stx1 was a poor inducer of IL-1β protein expression, although levels of soluble IL-1β induced by all treatments continually increased over 72 h. IL-1β transcripts were not induced by Stx1 B-subunits. Using the transcriptional inhibitor actinomycin D, we determined that treatment with Stx1 or Stx1 plus LPS induced cytokine transcripts with increased stability compared to transcripts induced by LPS alone. For all treatments, IL-1β mRNA decay was slower than TNF-α. Collectively, our data suggest that Stxs affect cytokine expression, in part, at the posttranscriptional level by stabilizing mRNAs. Optimal TNF-α expression occurs when both Stxs and LPS are present.
Human Leukocyte Antigen Class II Alleles Influence Levels of Antibodies to thePlasmodium falciparumAsexual-Stage Apical Membrane Antigen 1 but Not to Merozoite Surface Antigen 2 and Merozoite Surface Protein 1
Authors: Johnson Armead H. , Leke Rose G. F. , Mendell Nancy R. , Shon Dewon , Suh Young Ju , Bomba-Nkolo Dennis , Tchinda Viviane , Kouontchou Samuel , Thuita Lucy W. , van der Wel Anne Marie , Thomas Alan , Stowers Anthony , Saul Allan , Zhou Ainong , Taylor Diane W. , Quakyi Isabella A. 
Published: April 2004

ABSTRACTThe apical membrane antigen 1 (AMA1), merozoite surface antigen 2 (MSA2), and merozoite surface protein 1 (MSP1) are asexual-stage proteins currently being evaluated for inclusion in a vaccine forPlasmodium falciparum. Accordingly, it is important to understand factors that control antibody responses to these antigens. Antibody levels in plasma from residents of Etoa, Cameroon, between the ages of 5 and 70 years, were determined using recombinant AMA1, MSA2, and the N-terminal region of MSP1 (MSP1-190L). In addition, antibody responses to four variants of the C-terminal region of MSP1 (MSP119) were assessed. Results showed that all individuals produced antibodies to AMA1, MSA2, and MSP1-190L; however, a proportion of individuals never produced antibodies to the MSP119variants, although the percentage of nonresponders decreased with age. The influence of age and human leukocyte antigen (HLA)-DRB1/DQB1 alleles on antibody levels was evaluated using two-way analysis of variance. Age was correlated with levels of antibodies to AMA1 and MSP119but not with levels of antibodies to MSA2 and MSP1-190L. No association was found between a single HLA allele and levels of antibodies to MSA2, MSP1-190L, or any of the MSP119variants. However, individuals positive for DRB1*1201 had higher levels of antibodies to the variant of recombinant AMA1 tested than did individuals of all other HLA types. Since the effect was seen across all age groups, HLA influenced the level but not the rate of antibody acquisition. This association for AMA1, combined with the previously reported association between HLA class II alleles and levels of antibodies to rhoptry-associated protein 1 (RAP1) and RAP2, indicates that HLA influences the levels of antibodies to three of the five vaccine candidate antigens that we have evaluated.
Clostridium difficileToxin A Carboxyl-Terminus Peptide Lacking ADP-Ribosyltransferase Activity Acts as a Mucosal Adjuvant
Authors: Castagliuolo Ignazio , Sardina Marina , Brun Paola , DeRos Chiara , Mastrotto Cristina , Lovato Laura , Palù Giorgio 
Published: April 2004

ABSTRACTThe receptor binding domains of the most potent mucosal adjuvants, bacterial toxins and plant lectins, are organized in repeat units to recognize specific sugar residues. The lectin-like structure of the C-terminal region ofClostridium difficiletoxin A prompted us to investigate the mucosal adjuvant properties of a nontoxigenic peptide corresponding to amino acids 2394 to 2706 (TxAC314). We compared TxAC314adjuvant activity to those of cholera toxin (CT) andEscherichia coliheat-labile enterotoxin subunit B (EtxB) coadministered orally or nasotracheally with poor peptide antigens (keyhole limpet hemocyanin [KLH] and hen egg lysozyme [HEL]). Levels of anti-KLH-specific serum immunoglobulin G (IgG) and IgA as well as that of mucosal IgA were significantly higher in animals immunized orally with TxAC314plus KLH than with KLH alone, CT plus KLH, or EtxB plus KLH. Following intranasal immunization with TxAC314plus HEL, levels of serum- and mucosa-specific antibodies were comparable to those induced by coadministering HEL with CT or EtxB. The TxAC314adjuvant effect following oral, but not intranasal, immunization was dose dependent. The analysis of the subclasses of anti-KLH-specific IgG isotypes and the cytokines released from splenocytes of immunized mice challenged in vitro with KLH indicates the induction of a mixed Th1/Th2-type immune response, with prevalence of the Th1 branch. We conclude that TxAC314enhances immune responses against mucosa-coadministered foreign antigens and represents a promising mucosal adjuvant, especially because its ability to stimulate mixed Th1/Th2 responses with a strong a Th1 component is extremely worthwhile against intracellular pathogens.
Bacterial and Host Factors Involved in the Major Histocompatibility Complex Class Ib-Restricted Presentation ofSalmonellaHsp 60: Novel Pathway
Authors: Lo Wei-Feng , Dunn Cory D. , Ong Helena , Metcalf Eleanor S. , Soloski Mark J. 
Published: April 2004

ABSTRACTPreviously, a peptide epitope derived from the Hsp 60 molecule ofSalmonellathat is presented by the major histocompatibility complex (MHC) class Ib molecule Qa-1 to CD8+cytotoxic T cells (CTLs) was described. In the present study we investigated theSalmonella-induced processing and presentation pathway for generating this Qa-1-restricted epitope. Live bacteria and, to a lesser extent, opsonized heat-killed bacteria are able to sensitize target cells for lysis bySalmonella-specific CTL. In contrast, heat-killed bacteria cannot sensitize target cells. Presentation of the Hsp 60 epitope appears independent of bacterial internalization, because cytochalasin D does not affect presentation. Moreover,Salmonellastrains defective in the InvA or InvE operon, two critical components of the type III secretion pathway, are as efficient as wild-typeSalmonella entericaserovar Typhimurium in sensitizing infected targets to lysis. Collectively, these results suggest the existence of a novel antigen-processing pathway in which exogenous antigens gain access to the cytosolic MHC class I processing machinery. Considering the abundant nature of bacterial Hsp 60 and the upregulation of this protein afterSalmonellainfection of eukaryotic cells, this mode of antigen presentation may be particularly relevant to understanding the host defense mechanisms against gram-negative bacteria.
Mycobacteria Inhibit Nitric Oxide Synthase Recruitment to Phagosomes during Macrophage Infection
Authors: Miller Barbara H. , Fratti Rutilio A. , Poschet Jens F. , Timmins Graham S. , Master Sharon S. , Burgos Marcos , Marletta Michael A. , Deretic Vojo 
Published: April 2004

ABSTRACTInducible nitric oxide synthase (iNOS) is a cytoplasmic protein responsible for the generation of nitric oxide (NO · ) in macrophages. In this work, we hypothesized that the intracellular localization of iNOS is significant for effective delivery of NO ·  to phagosomes containing ingested microorganisms. Using immunofluorescence microscopy and Western blot analysis, iNOS was shown to localize in the vicinity of phagosomes containing latex beads in stimulated macrophages. iNOS also localized to phagosomes containingEscherichia coli. The colocalization of iNOS with ingested latex beads was an actin-dependent process, since treatment with the actin microfilament disrupter cytochalasin D prevented iNOS recruitment to latex bead phagosomes. In contrast toE. coliand inert particle phagosomes, mycobacterial phagosomes did not colocalize with iNOS. This study demonstrates that (i) iNOS can be recruited to phagosomes; (ii) this recruitment is dependent on a functional actin cytoskeleton; (iii) certain microorganisms have the ability to prevent or reduce colocalization with iNOS; and (iv) spatial exclusion of iNOS may play a role inMycobacterium tuberculosispathogenesis.
Erythrocyte Invasion by
Babesia bovis
Merozoites Is Inhibited by Polyclonal Antisera Directed against Peptides Derived from a Homologue of
Plasmodium falciparum
Apical Membrane Antigen 1
Authors: Gaffar Fasila R. , Yatsuda Ana P. , Franssen Frits F. J. , de Vries Erik 
Published: April 2004

ABSTRACT

Apical membrane antigen 1 (AMA-1) is a micronemal protein secreted to the surface of merozoites of
Plasmodium
species and
Toxoplasma gondii
tachyzoites in order to fulfill an essential but noncharacterized function in host cell invasion. Here we describe cloning and characterization of a
Babesia bovis
AMA-1 homologue designated BbAMA-1. The overall level of similarity of BbAMA-1 to
P. falciparum
AMA-1 was low (18%), but characteristic features like a transmembrane domain near the C terminus, a predicted short cytoplasmic C-terminal sequence with conserved sequence properties, and an extracellular domain containing 14 conserved cysteine residues putatively involved in disulfide bridge formation are typical of AMA-1. Rabbit polyclonal antisera were raised against three synthetic peptides derived from the N-terminal region and domains II and III of the putative extracellular domain and were shown to recognize specifically recombinant BbAMA-1 expressed in
Escherichia coli
. Immunofluorescence microscopy showed that there was labeling of the apical half of merozoites with these antisera. Preincubation of free merozoites with all three antisera reduced the efficiency of invasion of erythrocytes by a maximum of 65%. Antisera raised against the N-terminal peptide detected a 82-kDa protein on Western blots and a 69-kDa protein in the supernatant that was harvested after in vitro invasion, suggesting that proteolytic processing and secretion take place during or shortly after invasion. A combination of two-dimensional Western blotting and metabolic labeling allowing direct identification of spots reacting with the BbAMA-1 peptide antisera together with the very low silver staining intensity of these spots indicated that very low levels of BbAMA-1 are present in
Babesia
merozoites.
Role of Macrophages in Host Resistance to Group A Streptococci
Authors: Goldmann Oliver , Rohde Manfred , Chhatwal Gursharan Singh , Medina Eva 
Published: April 2004

ABSTRACTMacrophages provide the first line of defense against invading pathogens. The aim of this study was to determine the role of macrophages during infection with group A streptococci (Streptococcus pyogenes) in mice. Here, we report that resident macrophages can efficiently take up and killS. pyogenesduring in vivo infection, as demonstrated by immunofluorescence and electron microscopy, as well as colony counts. To evaluate the contribution of macrophages to the resolution of experimental infection withS. pyogenes, we compared the susceptibility of BALB/c mice rendered macrophage deficient by treatment with carrageenan with that of intact mice. The results show that depletion of macrophages enhanced the susceptibility of BALB/c mice toS. pyogenesinfection, as evidenced by 100% mortality of macrophage-depleted mice compared to 90% survival of nondepleted control animals. The in vivo depletion of macrophages strongly enhanced bacterial loads in the blood and systemic organs. Resistance toS. pyogenescan be restored in macrophage-depleted mice by adoptive transfer of purified macrophages. The in vivo blocking of the macrophage phagocytic function by treatment with gadolinium III chloride also resulted in enhanced susceptibility toS. pyogenes.Interestingly, depletion of macrophages prior to or during the first 24 h of infection decreased survival dramatically; in contrast, no mortality was observed in infected nondepleted animals or mice depleted after 48 h of infection. These results emphasize the important contribution of macrophages to the early control ofS. pyogenesinfection.
Tick Saliva Reduces Adherence and Area of Human Neutrophils
Authors: Montgomery Ruth R. , Lusitani Denise , de Boisfleury Chevance Anne , Malawista Stephen E. 
Published: April 2004

ABSTRACTDuring natural infection with the agent of Lyme disease,Borrelia burgdorferi, spirochetes are delivered with vector saliva, which contains anti-inflammatory and antihemostatic activities. We show here that the saliva of ixodid ticks reduces polymorphonuclear leukocyte (PMN) adhesion via downregulation of β2-integrins and decreases the efficiency of PMN in the uptake and killing of spirochetes. Inhibition of integrin adhesion and signaling reduces anti-inflammatory functions of PMN. These effects may favor the initial survival of spirochetes in vivo.
Vaccination with anOstertagia ostertagiPolyprotein Allergen Protects Calves against Homologous Challenge Infection
Authors: Vercauteren Isabel , Geldhof Peter , Vercruysse Jozef , Peelaers Iris , Van Den Broeck Wim , Gevaert Kris , Claerebout Edwin 
Published: April 2004

ABSTRACTAs an alternative to antihelminthic drugs, we are exploiting vaccination to control infections with the abomasal nematodeOstertagia ostertagiin cattle. Our focus for vaccine targets is excretory-secretory (ES) products of this parasite. One of the most abundant antigens in larval and adultOstertagiaES products is a protein homologous to nematode polyprotein allergens. We found that theOstertagiapolyprotein allergen (OPA) is encoded by a single-copy gene. OPA comprises three or more repeated units, and only the 15-kDa subunits are found in ES products. The native antigen is localized in the intestinal cells of third-stage larvae and in the hypodermis and cuticle of fourth-stage larvae and adult parasites. Vaccination of cattle with native OPA (nOPA) in combination with QuilA resulted in protection againstOstertagiachallenge infections. The geometric mean cumulative fecal egg counts in the nOPA-vaccinated animals were reduced by 60% compared to the counts in the control group during the 2-month course of the experiment. Both male and female adult worms in nOPA-vaccinated animals were significantly shorter than the worms in the control animals. In the abomasal mucus of vaccinated animals the nOPA-specific immunoglobulin G1 (IgG1) and IgG2 levels were significantly elevated compared to the levels in the control animals. Reductions in theOstertagiaegg output and the length of the adult parasites were significantly correlated with IgG1 levels. IgG2 titers were only negatively associated with adult worm length. Protected animals showed no accumulation of effector cells (mast cells, globular leukocytes, and eosinophils) in the mucosa. In contrast to the native antigen, recombinant OPA expressed inEscherichia colidid not stimulate any protection.
The Extra Cytoplasmic Function Sigma Factor σ
E
Is Essential for
Mycobacterium tuberculosis
Virulence in Mice
Authors: Manganelli Riccardo , Fattorini Lanfranco , Tan Dejiang , Iona Elisabetta , Orefici Graziella , Altavilla Giuseppe , Cusatelli Paola , Smith Issar 
Published: April 2004

ABSTRACT

The virulence of a
Mycobacterium tuberculosis
H37Rv
sigE
mutant was studied in immunodeficient and immunocompetent mice. The mutant was strongly attenuated in both animal models and induced formation of granulomas with different characteristics than those induced by the wild-type strain.
Presence of Pili on the Surface of
Francisella tularensis
Authors: Gil Horacio , Benach Jorge L. , Thanassi David G. 
Published: April 2004

ABSTRACT

Francisella tularensis
is a highly infectious gram-negative bacterium with potential for use as a bioweapon. Analysis of the
F. tularensis
live vaccine strain (LVS) ultrastructure by electron microscopy revealed the presence of long, thin fibers, similar in appearance to type 4 pili. The highly virulent
F. tularensis
Schu S4 strain was found to contain type 4 pilus genes, and we confirmed that these genes are present and expressed in the LVS.
Legionella pneumophila
Replication Vacuole Formation Involves Rapid Recruitment of Proteins of the Early Secretory System
Authors: Derré Isabelle , Isberg Ralph R. 
Published: April 2004

ABSTRACT

Legionella pneumophila
vacuole biogenesis was analyzed by using a cell-free system. We show that calnexin, Sec22b, and Rab1 are recruited to the vacuole very shortly after bacterial uptake, and we have identified Rab1 as a potential host factor involved in the endoplasmic reticulum recruitment process.