bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping of Murine Th1 Helper T-Cell Epitopes of Mycolyl Transferases Ag85A, Ag85B, and Ag85C fromMycobacterium tuberculosis
Authors: D'Souza S. , Rosseels V. , Romano M. , Tanghe A. , Denis O. , Jurion F. , Castiglione N. , Vanonckelen A. , Palfliet K. , Huygen Kris 
Published: December 2002

ABSTRACTBALB/c (H-2d) and C57BL/6 (H-2b) mice were infected intravenously withMycobacterium tuberculosisH37Rv or vaccinated intramuscularly with plasmid DNA encoding each of the three mycolyl transferases Ag85A, Ag85B, and Ag85C fromM. tuberculosis. Th1-type spleen cell cytokine secretion of interleukin-2 (IL-2) and gamma interferon (IFN-γ) was analyzed in response to purified Ag85 components and synthetic overlapping peptides covering the three mature sequences. Tuberculosis-infected C57BL/6 mice reacted strongly to some peptides from Ag85A and Ag85B but not from Ag85C, whereas tuberculosis-infected BALB/c mice reacted only to peptides from Ag85A. In contrast, spleen cells from both mouse strains produced elevated levels of IL-2 and IFN-γ following vaccination with Ag85A, Ag85B, and Ag85C DNA in response to peptides of the three Ag85 proteins, and the epitope repertoire was broader than in infected mice. Despite pronounced sequence homology, a number of immunodominant regions contained component specific epitopes. Thus, BALB/c mice vaccinated with all three Ag85 genes reacted against the same amino acid region, 101 to 120, that was also immunodominant for Ag85A inM. bovisBCG-vaccinated and tuberculosis-infectedH-2dhaplotype mice, but responses were completely component specific. In C57BL/6 mice, a cross-reactive T-cell response was detected against two carboxy-terminal peptides spanning amino acids 241 to 260 and 261 to 280 of Ag85A and Ag85B. These regions were not recognized at all in C57BL/6 mice vaccinated with Ag85C DNA. Our results underline the need for comparative analysis of all three Ag85 components in future vaccination studies.
Cholera Toxin Induces Migration of Dendritic Cells from the Subepithelial Dome Region to T- and B-Cell Areas of Peyer's Patches
Authors: Shreedhar Vijay K. , Kelsall Brian L. , Neutra Marian R. 
Published: December 2002

ABSTRACTIntestinal M cells deliver macromolecules, particles, and pathogens into the subepithelial dome (SED) region of Peyer's patch mucosa, an area rich in dendritic cells (DCs). We tested whether uptake of the mucosal adjuvant cholera toxin (CT) or liveSalmonellabacteria can induce DC migration within Peyer's patches. Virus-sized, fluorescent polystyrene microparticles were efficiently transported by M cells and ingested by CD11c+, CD11b−, and CD8a−DCs in the SED region. DCs loaded with microparticles remained in the SED for up to 14 days. CT (but not the CT B subunit) and live attenuatedSalmonella entericaserovar Typhimurium bacteria induced migration of the microparticle-loaded DCs from the SED region into underlying B-cell follicles and adjacent parafollicular T-cell zones. Our data provide the first demonstration that DCs move in response to enterotoxin adjuvants and live bacteria that enter the mucosa via M cells.
Role of
sarA
in the Pathogenesis of
Staphylococcus aureus
Musculoskeletal Infection
Authors: Blevins Jon S. , Elasri Mohamed O. , Allmendinger Scott D. , Beenken Karen E. , Skinner Robert A. , Thomas J. Roby , Smeltzer Mark S. 
Published: December 2002

ABSTRACT

We recently demonstrated that mutation of
sarA
in clinical isolates of
Staphylococcus aureus
results in a phenotype that is distinct by comparison to
sarA
mutants generated in the laboratory strain RN6390 (J. S. Blevins, K. E. Beenken, M. O. Elasri, B. K. Hurlburt, and M. S. Smeltzer, Infect. Immun. 70:470-480, 2002). This raises the possibility that studies demonstrating that RN6390
sarA
mutants are attenuated do not accurately reflect the role of
sarA
in the pathogenesis of staphylococcal disease. To test this hypothesis, we used a murine model of musculoskeletal infection to assess the virulence of
sarA
and
agr
mutants generated in a clinical isolate of
S. aureus
(UAMS-1). By using this model, we confirmed that mutation of
sarA
and/or
agr
results in a reduced capacity to cause both septic arthritis and osteomyelitis.
Production of Macrophage Inflammatory Protein 3α (MIP-3α) (CCL20) and MIP-3β (CCL19) by Human Peripheral Blood Neutrophils in Response to Microbial Pathogens
Authors: Akahoshi Tohru , Sasahara Takeshi , Namai Rie , Matsui Toshimichi , Watabe Hiroyuki , Kitasato Hidero , Inoue Matsuhisa , Kondo Hirobumi 
Published: December 2002

ABSTRACTEffects of bacterial pathogens on the production of macrophage inflammatory protein 3α (MIP-3α) and MIP-3β from human peripheral blood neutrophils were investigated. Neutrophils produced both chemokines by coincubation with either gram-positive or gram-negative bacteria. Neutrophils may initiate antigen-specific immune responses through the release of these chemokines that are capable of promoting selective recruitment of dendritic cells and T-cell subsets.
Role of Virulence Factors in Resistance of Avian Pathogenic
Escherichia coli
to Serum and in Pathogenicity
Authors: Mellata Melha , Dho-Moulin Maryvonne , Dozois Charles M. , Curtiss Roy , Brown Peter K. , Arné Pascal , Brée Annie , Desautels Clarisse , Fairbrother John M. 
Published: December 2002

ABSTRACT

In chickens, colibacillosis is caused by avian pathogenic
Escherichia coli
(APEC) via respiratory tract infection. Many virulence factors, including type 1 (F1A) and P (F11) fimbriae, curli, aerobactin, K1 capsule, and temperature-sensitive hemagglutinin (Tsh) and plasmid DNA regions have been associated with APEC. A strong correlation between serum resistance and virulence has been demonstrated, but roles of virulence factors in serum resistance have not been well elucidated. By using mutants of APEC strains TK3, MT78, and χ7122, which belong to serogroups O1, O2, and O78, respectively, we investigated the role of virulence factors in resistance to serum and pathogenicity in chickens. Our results showed that serum resistance is one of the pathogenicity mechanisms of APEC strains. Virulence factors that increased bacterial resistance to serum and colonization of internal organs of infected chickens were O78 lipopolysaccharide of
E. coli
χ7122 and the K1 capsule of
E. coli
MT78. In contrast, curli, type 1, and P fimbriae did not appear to contribute to serum resistance. We also showed that the
iss
gene, which was previously demonstrated to increase resistance to serum in certain
E. coli
strains, is located on plasmid pAPEC-1 of
E. coli
χ7122 but does not play a major role in resistance to serum for strain χ7122.
MprF-Mediated Lysinylation of Phospholipids in
Staphylococcus aureus
Leads to Protection against Oxygen-Independent Neutrophil Killing
Authors: Kristian Sascha A. , Dürr Manuela , Van Strijp Jos A. G. , Neumeister Birgid , Peschel Andreas 
Published: December 2002

ABSTRACT

Staphylococcus aureus
achieves resistance to defensins and similar cationic antimicrobial peptides (CAMPs) by modifying anionic membrane lipids via MprF with
l
-lysine, which leads to repulsion of these host defense molecules.
S. aureus
Δ
mprF
, which lacks the modification, was very efficiently killed by neutrophil defensins and CAMP-producing leukocytes, even when oxygen-dependent killing was disrupted, but was as susceptible as wild-type bacteria to inactivation by myeloperoxidase or human monocytes lacking defensins. These results demonstrate the impact and specificity of MprF-mediated CAMP resistance and underscore the role of defensin-like peptides in innate host defense.
Involvement of
Trypanosoma cruzi
Metacyclic Trypomastigote Surface Molecule gp82 in Adhesion to Gastric Mucin and Invasion of Epithelial Cells
Authors: Neira Ivan , Silva Fernando A. , Cortez Mauro , Yoshida Nobuko 
Published: December 2002

ABSTRACT

Upon oral infection,
Trypanosoma cruzi
metacyclic trypomastigotes invade and replicate in the gastric mucosal epithelium, being apparently uniquely specialized for adhesion to mucin and mucosal invasion. Here we investigated the involvement of gp82, the metacyclic-stage-specific surface glycoprotein implicated in host cell entry, in both adhesion to gastric mucin and invasion of the mucosal epithelium upon oral challenge. Metacyclic forms, preincubated with a control monoclonal antibody (MAb) or with MAb 3F6 directed to gp82, were administered orally to BALB/c mice, and parasitemia was monitored. Mice that received parasites treated with MAb 3F6 had greatly reduced parasitemia, displaying at the peak a mean number of blood parasites more than 100-fold lower than that of the control group. MAbs directed to other
T. cruzi
surface glycoproteins had no such effect. gp82, as either a native or a recombinant molecule, but not the metacyclic trypomastigote surface molecule gp90 or gp35/50, bound to gastric mucin in enzyme-linked immunosorbent assays. MAb 3F6 significantly inhibited the penetration of cultured epithelial HeLa cells by metacyclic forms in the absence or in the presence of gastric mucin. Mucin alone did not affect parasite internalization. Parasite infectivity was not altered by treatment of metacyclic forms with pepsin, to which gp82 was resistant, or with proteinase K, which removed the N-terminal portion of gp82 but preserved its host cell binding site. Taken together, these findings suggest that gp82 mediates the interaction of metacyclic trypomastigotes with gastric mucin and the subsequent penetration of underlying epithelial cells.
Enhanced Immunogenicity to
Mycobacterium tuberculosis
by Vaccination with an Alphavirus Plasmid Replicon Expressing Antigen 85A
Authors: Kirman Joanna R. , Turon Tara , Su Hua , Li Amy , Kraus Carl , Polo John M. , Belisle John , Morris Sheldon , Seder Robert A. 
Published: December 2002

ABSTRACT

The immunogenicity of a plasmid DNA vaccine incorporating Sindbis virus RNA replicase functions (pSINCP) and expressing antigen 85A (Ag85A) from
Mycobacterium tuberculosis
was compared with a conventional plasmid DNA vector encoding Ag85A. pSINCP-85A was highly immunogenic in mice and gave enhanced long-term protection against
M. tuberculosis
compared with the conventional vector.
Association of
Helicobacter pylori
Antioxidant Activities with Host Colonization Proficiency
Authors: Olczak Adriana A. , Seyler, Richard W. , Olson Jonathan W. , Maier Robert J. 
Published: December 2002

ABSTRACT

To assess the importance of two separate antioxidant activities in
Helicobacter pylori
, we tested the abilities of strains with mutations in either
tpx
(encoding thiolperoxidase) or
ahpC
(encoding alkyl hydroperoxide reductase [AhpC]) to colonize the stomachs of mice. The
tpx
strain was clearly more sensitive than the parent strain to both oxygen and cumene hydroperoxide. The strain colonized only 5% of the inoculated mice. Two different classes of oxygen-sensitive
ahpC
mutants in the type strain (ATCC 43504) were recently described (A. A. Olczak, J. W. Olson, and R. J. Maier, J. Bacteriol. 184:3186-3193, 2002). The same two classes of mutants were recovered upon
ahpC
mutagenesis of the mouse-adapted strain, SS1. Neither of these mutants was able to colonize mouse stomachs, whereas 78% of the mice inoculated with the parent strain became
H. pylori
positive.
Biodefense-Driven Murine Model of Pneumonic Melioidosis
Authors: Jeddeloh J. A. , Fritz D. L. , Waag D. M. , Hartings J. M. , Andrews G. P. 
Published: December 2002

ABSTRACT

A whole-body mouse model of pneumonic melioidosis was established for future evaluation of biodefense vaccine candidates. The aerosol 50% lethal doses of
Burkholderia pseudomallei
strain 1026b for BALB/c and C57BL/6 mice and the times to death, dissemination in organs, and tissue loads after exposure of the mice to low- and high-dose aerosols are reported. In addition,
rpsL
mutant backgrounds were attenuated in this acute model of disease.
Interaction of Pulmonary Surfactant Protein C with CD14 and Lipopolysaccharide
Authors: Augusto Luis A. , Synguelakis Monique , Johansson Jan , Pedron Thierry , Girard Robert , Chaby Richard 
Published: December 2002

ABSTRACTIn addition to their effects on alveolar surface tension, some components of lung surfactant also have immunological functions. We found recently that the hydrophobic lung surfactant protein SP-C specifically binds to the lipid A region of lipopolysaccharide (LPS). In this study, we show that SP-C also interacts with CD14. Four observations showed cross talk between the three molecules SP-C, LPS, and CD14. (i) Like LBP, SP-C allows the binding of a fluorescent LPS to cells expressing CD14 (the other surfactant components were ineffective). (ii) Recombinant radiolabeled CD14 and SP-C (or a synthetic analog of SP-C) interact in a dose-dependent manner. (iii) LPS blocks the binding of radiolabeled CD14 to SP-C-coated wells. (iv) SP-C enhances the binding of radiolabeled CD14 to LPS-coated wells. These results, obtained with native murine SP-C and with three synthetic analogs, suggest that LPS and CD14 interact with the same region of SP-C and that binding of SP-C modifies the conformation of CD14 or the accessibility of its LPS-binding site, allowing it to bind LPS. This ability of SP-C to interact with the pattern recognition molecule CD14 extends the possible immunological targets of SP-C to a large panel of microorganisms that can enter the airways.
Effects of Tumor Necrosis Factor Alpha on Dendritic Cell Accumulation in Lymph Nodes Draining the Immunization Site and the Impact on the Anticryptococcal Cell-Mediated Immune Response
Authors: Bauman Sean K. , Huffnagle Gary B. , Murphy Juneann W. 
Published: December 2002

ABSTRACTCell-mediated immune (CMI) responses and tumor necrosis factor alpha (TNF-α) have been shown to be essential in acquired protection againstCryptococcus neoformans. Induction of a protective anticryptococcal CMI response includes increases in dendritic cells (DC) and activated CD4+T cells in draining lymph nodes (DLN). During the expression phase, activated CD4+T cells accumulate at a peripheral site where cryptococcal antigen is injected, resulting in a classical delayed-type hypersensitivity (DTH) reaction. Induction of a nonprotective anticryptococcal CMI response results in no significant increases in the numbers of DC or activated CD4+T cells in DLN. This study focuses on examining the role of TNF-α in induction of protective and nonprotective anticryptococcal CMI responses. We found that neutralization of TNF-α at the time of immunization with the protective immunogen (i) reduces the numbers of Langerhans cells, myeloid and lymphoid DC, and activated CD4+T cells in DLN and (ii) diminishes the total numbers of cells, the numbers of activated CD4+T cells, and amount of gamma interferon at the DTH reaction site. Although TNF-α neutralization during induction of the nonprotective CMI response had little effect on cellular and cytokine parameters measured, it did cause a reduction in footpad swelling when mice received challenge in the footpad. Our findings show that TNF-α functions during induction of the protective CMI response by influencing the accumulation of all three DC subsets into DLN. Without antigen stimulated DC in DLN, activated CD4+T cells are not induced and thus not available for the expression phase of the CMI response.
Both Family 1 and Family 2 PspA Proteins Can Inhibit Complement Deposition and Confer Virulence to a Capsular Serotype 3 Strain of
Streptococcus pneumoniae
Authors: Ren Bing , Szalai Alexander J. , Thomas Orlanda , Hollingshead Susan K. , Briles David E. 
Published: December 2002

ABSTRACT

Pneumococcal surface protein A (PspA), a virulence factor of
Streptococcus pneumoniae
, is exceptionally diverse, being classified into two major families which are over 50% divergent by sequence analysis. A family 1 PspA from strain WU2 was previously shown to impede the clearance of pneumococci from mouse blood and to interfere with complement deposition on the bacterial surface. To determine whether a family 2 PspA can perform the same role as family 1 PspA, the family 1 PspA (from strain WU2) was replaced with a family 2 PspA (from strain TIGR4) by molecular genetic methods to make an isogenic pair of strains expressing different PspA proteins. Surface binding of lactoferrin and interference with C3 deposition by the two types of PspA proteins were determined by flow cytometry, and virulence was assessed in a mouse bacteremia model. Although the family 2 PspA appeared to bind less human lactoferrin than did the family 1 PspA, both PspA proteins could interfere with complement deposition on the pneumococcal surface and could provide full virulence in the mouse infection model. A mutant form of the family 2 PspA with a deletion within the choline-binding region was also produced. Pneumococci with this mutant PspA failed to bind human lactoferrin even though the PspA was present on the pneumococcal surface. The mutant PspA only partially interfered with complement deposition and moderately attenuated virulence. These results suggest that family 1 and family 2 PspA proteins play similar roles in virulence and that surface accessibility of PspA is important for their function.
Role ofBordetellaO Antigen in Respiratory Tract Infection
Authors: Burns Valorie C. , Pishko Elizabeth J. , Preston Andrew , Maskell Duncan J. , Harvill Eric T. 
Published: December 2002

ABSTRACTLipopolysaccharide (LPS), as the major surface molecule of gram-negative bacteria, interacts with the host in complex ways, both inducing and protecting against aspects of inflammatory and adaptive immunity. The membrane-distal repeated carbohydrate structure of LPS, the O antigen, can prevent antibody functions and may vary as a mechanism of immune evasion. Genes of thewbmlocus are required for the assembly of O antigen on the animal pathogenBordetella bronchisepticaand the human pathogenB. parapertussis. However, the important human pathogenB. pertussislacks these genes and a number of in vitro and in vivo characteristics associated with O antigen in other organisms. To determine the specific functions of O antigen in these closely relatedBordetellasubspecies, we comparedwbmdeletion (Δwbm) mutants ofB. bronchisepticaandB. parapertussisin a variety of assays relevant to natural respiratory tract infection. Complement was not activated or depleted by wild-type bordetellae expressing O antigen, but both Δwbmmutants activated complement and were highly sensitive to complement-mediated killing in vitro. Although the O-antigen structures appear to be substantially similar, the two mutants differed strikingly in their defects within the respiratory tract. TheB. parapertussisΔwbmmutant was severely defective in colonization of the tracheas and lungs of mice, while theB. bronchisepticaΔwbmmutant showed almost no defect. While in vitro characteristics such as serum resistance may be attributable to O antigen directly, the role of O antigen during infection appears to be more complex, possibly involving factors differing among the closely related bordetellae or different interactions between each one and its host.
Magnesium in stroke treatment
Authors: Muir K W 
Published: December 2002

Abstract
Magnesium is involved in multiple physiological processes that may be relevant to cerebral ischaemia, including antagonism of glutamate release, NMDA receptor blockade, calcium channel antagonism, and maintenance of cerebral blood flow. Systemically administered magnesium at doses that double physiological serum concentration significantly reduces infarct volume in animal models of stroke, with a window of up to six hours after onset and favourable dose-response characteristics when compared with previously tested neuroprotective agents. Small clinical trials have reported benefit, but results are not statistically significant in systematic review. A large ongoing trial (IMAGES) will report in 2003–4 and further trials are planned.
Managing liver failure
Authors: Kelly D A 
Published: December 2002

Abstract
Liver disease is rare in childhood, but important new developments have altered the natural history and outcome. It is important that clinicians are aware of these diseases and their management. Acute liver failure is most often due to viral hepatitis, paracetamol overdose, or inherited metabolic liver disease. The clinical presentation includes jaundice, coagulopathy, and encephalopathy. Early diagnosis is necessary to prevent complications such as cerebral oedema, gastrointestinal bleeding, and renal failure. Early supportive management, in particular intravenous N-acetylcysteine, may be effective but liver transplantation is usually the definitive treatment and thus early referral to a specialist unit for liver transplantation is mandatory. Chronic liver failure may be due to unresolved neonatal liver disease, either inherited biliary hypoplasia or extrahepatic biliary atresia, while in older children, autoimmune liver disease or cystic fibrosis are the commonest causes. Treatment includes specific medication, nutritional support, and liver transplantation, which now has a 90% survival with good quality life.
Costs of waiting for gall bladder surgery
Authors: Somasekar K , Shankar P J , Foster M E , Lewis M H 
Published: December 2002

Abstract
Laparoscopic cholecystectomy is one of the most commonly awaited general surgical procedures in the UK. However, many patients awaiting a cholecystectomy are admitted with recurrent gallstone related symptoms while on the waiting list, resulting in significant morbidity. The aim of this study was to quantify this problem, and also to analyse the cost implications of these admissions for the NHS. A retrospective study was performed of all patients who underwent an elective cholecystectomy by three consultants in a district general hospital between January 1999 and January 2000. The demographic details, indications for surgery, details of the emergency admissions while on the waiting list, and the treatment given during these episodes were recorded. One hundred and fifty six patients were included in the study, of which 122 (78%) were females. The mean (SD) age of the patients was 54 (5) years. The mean waiting time for surgery in these patients was 12 (3) months. Thirty seven patients (23.7%) were admitted as an emergency due to gallstone related symptoms and complications while awaiting surgery. There were 47 episodes of admissions in total, of which 32 were for biliary colic, 13 were for acute cholecystitis, and two were for acute pancreatitis. In addition to routine blood tests, 20 abdominal radiographs, 10 chest radiographs, three endoscopic retrograde cholangiopancreatography tests, five ultrasonograms, and one computed tomogram were carried out in these patients. The mean duration of each episode of admission was three days. The cost of treatment per episode was £946 and the total cost of treating the 37 patients was calculated to be £44 462. Performing early laparoscopic cholecystectomy for acute cholecystitis may help to reduce costs by preventing recurrent emergency admissions in these patients. Further studies to identify risk factors associated with recurrent symptoms and complications in patients with gallstone disease may help to prioritise them for early surgery.