bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outer Membrane Protein A of
Escherichia coli
O157:H7 Stimulates Dendritic Cell Activation
Authors: Torres Alfredo G. , Li Yongguo , Tutt Christopher B. , Xin Lijun , Eaves-Pyles Tonyia , Soong Lynn 
Published: April 2006

ABSTRACT

Outer membrane protein A (OmpA) is located in the membrane of
Escherichia coli
and other gram-negative bacteria and plays a multifunctional role in bacterial physiology and pathogenesis. In enterohemorrhagic
E. coli
(EHEC), especially serotype O157:H7, OmpA interacts with cultured human intestinal cells and likely acts as an important component to stimulate the immune response during infection. To test this hypothesis, we analyzed the effect of EHEC OmpA on cytokine production by dendritic cells (DCs) and on DC migration across polarized intestinal epithelial cells. OmpA induced murine DCs to secrete interleukin-1 (IL-1), IL-10, and IL-12 in a dose-dependent manner, and this effect was independent of Toll-like receptor 4. Although DCs displayed differential responses to EHEC OmpA and OmpA-specific antibodies enhanced DC cytokine secretion, we cannot discard that other EHEC surface elements were likely to be involved. While OmpA was required for bacterial binding to polarized Caco-2 cells, it was not needed for the induction of cytokine production by Caco-2 cells or for human DC migration across polarized cells.
Characterization of the Opsonic and Protective Activity against
Staphylococcus aureus
of Fully Human Monoclonal Antibodies Specific for the Bacterial Surface Polysaccharide Poly-
N
-Acetylglucosamine
Authors: Kelly-Quintos Casie , Cavacini Lisa A. , Posner Marshall R. , Goldmann Donald , Pier Gerald B. 
Published: April 2006

ABSTRACT

Carbohydrate antigens are important targets of the immune system in clearing bacterial pathogens. Although the immune system almost exclusively uses antibodies in response to foreign carbohydrates, there is still much to learn about the role of different epitopes on the carbohydrate as targets of protective immunity. We examined the role of acetyl group-dependent and -independent epitopes on the staphylococcal surface of polysaccharide poly-
N
-acetylated glucosamine (PNAG) by use of human monoclonal antibodies (MAbs) specific for such epitopes. We utilized hybridoma technology to produce fully human immunoglobulin G2 (IgG2) MAbs from B cells of an individual post-
Staphylococcus aureus
infection and cloned the antibody variable regions to produce an IgG1 form of each original MAb. Specificity and functionality of the purified MAbs were tested in vitro using enzyme-linked immunosorbent assays, complement deposition, and opsonophagocytic assays. We found that a MAb (MAb F598) that bound the best to nonacetylated or backbone epitopes on PNAG had superior complement deposition and opsonophagocytic activity compared to two MAbs that bound optimally to PNAG that was expressed with a native level (>90%) of
N
-acetyl groups (MAbs F628 and F630). Protection of mice against lethality due to
S. aureus
strains Mn8 and Reynolds further showed that the backbone-specific MAb had optimal protective efficacy compared with the acetate-specific MAbs. These results provide evidence for the importance of epitope specificity in inducing the optimal protective antibody response to PNAG and indicate that MAbs to the deacetylated form of PNAG could be immunotherapeutic agents for preventing or treating staphylococcal infections.
In Vivo Activation of Naive CD4+T Cells in Nasal Mucosa-Associated Lymphoid Tissue following Intranasal Immunization with RecombinantStreptococcus gordonii
Authors: Medaglini Donata , Ciabattini Annalisa , Cuppone Anna Maria , Costa Caterina , Ricci Susanna , Costalonga Massimo , Pozzi Gianni 
Published: April 2006

ABSTRACTThe antigen-specific primary activation of CD4+T cells was studied in vivo by adoptive transfer of ovalbumin-specific transgenic T cells (KJ1-26+CD4+) following intranasal immunization with recombinantStreptococcus gordonii. A strain ofS. gordoniiexpressing on its surface a model vaccine antigen fused to the ovalbumin (OVA) peptide from position 323 to 339 was constructed and used to study the OVA-specific T-cell activation in nasal mucosa-associated lymphoid tissue (NALT), lymph nodes, and spleens of mice immunized by the intranasal route. The recombinant strain, but not the wild type, activated the OVA-specific CD4+T-cell population in the NALT (89% of KJ1-26+CD4+T cells) just 3 days following immunization. In the cervical lymph nodes and in the spleen, the percentage of proliferating cells was initially low, but it reached the peak of activation at day 5 (90%). This antigen-specific clonal expansion of KJ1-26+CD4+T cells after intranasal immunization was obtained with live and inactivated recombinant bacteria, and it indicates that the NALT is the site of antigen-specific T-cell priming.
Modulation of the Triggering Receptor Expressed on the Myeloid Cell Type 1 Pathway in Murine Septic Shock
Authors: Gibot Sébastien , Buonsanti Cecilia , Massin Frédéric , Romano Michele , Kolopp-Sarda Marie-Nathalie , Benigni Fabio , Faure Gilbert C. , Béné Marie-Christine , Panina-Bordignon Paola , Passini Nadia , Lévy Bruno 
Published: April 2006

ABSTRACTThe triggering receptor expressed on myeloid cell type 1 (TREM-1) is a cell surface molecule that has been identified on both human and murine polymorphonuclear neutrophils and mature monocytes. The activation of TREM-1 in the presence of microbial components amplifies the inflammatory response and may be responsible for the hyperresponsiveness observed during the initial stage of sepsis. To investigate the effect of the modulation of the TREM-1 pathway during experimental murine sepsis, we used analogue synthetic peptides derived from the extracellular moiety of TREM-1. The TREM-1 ligand was expressed on both peritoneal and peripheral neutrophils during experimental peritonitis in mice. The TREM-1 peptides inhibited the recognition by TREM-1 of its ligand and protected endotoxinic mice from death. In septic rats, the TREM-1 peptides improved the hemodynamic status, attenuated the development of lactic acidosis, modulated the production of such proinflammatory cytokines as tumor necrosis factor alpha and interleukin-1β, and improved survival. The protective effect of these peptides on arterial pressure could partly be explained by a decreased production of nitric oxide. These data suggest that in vivo modulation of TREM-1 might be a suitable therapeutic tool for the treatment of sepsis.
Bordetella pertussisInhibition of Interleukin-12 (IL-12) p70 in Human Monocyte-Derived Dendritic Cells Blocks IL-12 p35 through Adenylate Cyclase Toxin-Dependent Cyclic AMP Induction
Authors: Spensieri Fabiana , Fedele Giorgio , Fazio Cecilia , Nasso Maria , Stefanelli Paola , Mastrantonio Paola , Ausiello Clara Maria 
Published: April 2006

ABSTRACTBordetella pertussis, the causative agent of whooping cough, possesses an array of virulence factors, including adenylate cyclase toxin (ACT), relevant in the establishment of infection. Here we better define the impact of cyclic AMP (cAMP) intoxication due to the action of ACT on dendritic cell (DC)-driven immune response, by infecting monocyte-derived DC (MDDC) with an ACT-deficientB. pertussismutant (ACT−18HS19) or its parental strain (WT18323). Both strains induced MDDC maturation and antigen-presenting cell functions; however, only ACT−18HS19 infected MDDC-induced production of interleukin-12 (IL-12) p70. Gene expression analysis of the IL-12 cytokine family subunits revealed that both strains induced high levels of p40 (protein chain communal to IL-12 p70 and IL-23) as well as p19, a subunit of IL-23. Conversely only ACT−18HS19 infection induced consistent transcription of IL-12 p35, a subunit of IL-12 p70. Addition of the cAMP analogousd-butyril-cAMP (d-cAMP) abolished IL-12 p70 production and IL-12 p35 expression in ACT−18HS19-infected MDDC. ACT−18HS19 infection induced the expression of the transcription factors interferon regulatory factor 1 (IRF-1) and IRF-8 and of beta interferon, involved in IL-12 p35 regulation, and the expression of these genes was inhibited byd-cAMP addition and in WT18323-infected MDDC. The concomitant expression of IL-12 p70 and IL-23 allowed ACT−18HS19 to trigger a more pronounced T helper 1 polarization compared to WT18323. The present study suggests that ACT-dependent cAMP induction leads to the inhibition of pathways ultimately leading to IL-12 p35 production, thus representing a mechanism forB. pertussisto escape the host immune response.
Mucosal Adjuvant Properties of theShigellaInvasin Complex
Authors: Kaminski Robert W. , Turbyfill K. Ross , Oaks Edwin V. 
Published: April 2006

ABSTRACTTheShigellainvasin complex (Invaplex) is an effective mucosal vaccine capable of protecting againstShigellachallenge in animal models. The major antigenic constituents of Invaplex are the Ipa proteins and lipopolysaccharide. The cell-binding capacity of the Ipa proteins prompted the investigation into the adjuvanticity of Invaplex. Using ovalbumin (OVA) as a model antigen, intranasal immunization with OVA combined with Invaplex was found to enhance anti-OVA serum immunoglobulin G (IgG) and IgA responses and induce OVA-specific mucosal antibody responses at sites located both proximal and distal to the immunization site. The immune responses induced with OVA and Invaplex were comparable in both magnitude and duration to the immune responses induced after immunization with OVA and cholera toxin. The OVA-specific immune response was characterized by high levels of serum IgG1 and increased production of interleukin-4 (IL-4), IL-5, or IL-10 from lymphoid cells of immunized animals, suggesting a Th2 response. In addition to enhancing the immunogenicity of OVA, Invaplex-specific immune responses were also induced, indicating the potential for the development of a combination vaccine consisting of Invaplex and other immunogens. Preexisting Invaplex-specific immunity did not interfere with the capacity to enhance the immunogenicity of a second, unrelated vaccine antigen, suggesting that Invaplex could be used as a mucosal adjuvant in multiple vaccine regimens.
Cytokine mRNA Expression inMycobacteriam ulcerans-Infected Human Skin and Correlation with Local Inflammatory Response
Authors: Phillips R. , Horsfield C. , Mangan J. , Laing K. , Etuaful S. , Awuah P. , Nyarko K. , Osei-Sarpong F. , Butcher P. , Lucas S. , Wansbrough-Jones M. 
Published: April 2006

ABSTRACTCytokine mRNA expression in biopsies ofMycobacterium ulcerans-infected human tissue was investigated using real-time PCR, and the findings were correlated with the clinical stages of disease and histopathologies. A broad range of cytokine mRNAs were detected in 16 early nodules and 28 late-stage ulcers, including those for the Th1 cytokines tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) and the Th2 cytokine interleukin 10 (IL-10). IFN-γ was strongly expressed in both nodules and ulcers, suggesting that a Th1 response begins early in the disease. There was a significantly higher expression of IL-8 and other proinflammatory cytokines in results from 32 biopsies with neutrophilia than in those from 12 biopsies without acute inflammation. Ten tissue samples containing granulomas showed high mRNA expression for IFN-γ, IL-1β, IL-12p35, IL-12p40, IL-15, and TNF-α relative to 34 tissue samples without granulomas. These results suggest that the human immune response toM. ulceransis similar to that seen with some other mycobacteria despite the presence of the toxin mycolactone in the tissues.
The Anti-
Candida
Vaccine Based on the Recombinant N-Terminal Domain of Als1p Is Broadly Active against Disseminated Candidiasis
Authors: Ibrahim Ashraf S. , Spellberg Brad J. , Avanesian Valentina , Fu Yue , Edwards John E. 
Published: April 2006

ABSTRACT

We have previously shown that vaccination with a vaccine based on the recombinant N-terminal domain of Als1p (rAls1p-N) protected BALB/c mice against disseminated infection caused by a single strain of
Candida albicans
(A. S. Ibrahim, B. J. Spellberg, V. Avenissian, Y. Fu, S. G. Filler, and J. E. Edwards, Jr., Infect. Immun.
73:
999-1005, 2005, and B. J. Spellberg, A. S. Ibrahim, V. Avenissian, S. G. Filler, C. Myers, Y. Fu, and J. E. Edwards, Jr., Infect. Immun.
73:
6191-6193, 2005). Here we show that the rAls1p-N vaccine also improves survival of outbred mice from disseminated candidiasis and that it is active against multiple virulent strains of
C. albicans
and non-
C. albicans
spp.
Requirement of Histidine Kinases HP0165 and HP1364 for Acid Resistance in
Helicobacter pylori
Authors: Loh John T. , Cover Timothy L. 
Published: April 2006

ABSTRACT

In this study, we investigated a potential requirement of two-component signal transduction systems for acid resistance in
Helicobacter pylori
. In comparison to a wild-type strain, isogenic strains with null mutations in either HP0165 or HP1364 histidine kinases were impaired in their ability to grow at pH 5.0. The growth of complemented mutant strains was similar to that of the wild-type strain.
H. pylori
DNA array analyses and transcriptional reporter assays indicated that acid-responsive gene transcription was altered in the HP0165 and HP1364 null mutant strains compared to the parental wild-type strain. These results indicate that intact HP0165 and HP1364 histidine kinases are required for acid resistance in
H. pylori
.
Role of the Histone-Like Nucleoid Structuring Protein in Colonization, Motility, and Bile-Dependent Repression of Virulence Gene Expression in
Vibrio cholerae
Authors: Ghosh Amalendu , Paul Kalidas , Chowdhury Rukhsana 
Published: April 2006

ABSTRACT

Bile-mediated repression of virulence gene expression is relieved in a
Vibrio cholerae hns
mutant. The mutant also exhibited reduced motility due to lower
flrA
expression, higher in vivo production of the virulence factors, and lower colonization efficiency. The colonization defect of the mutant was due to low FlrA production.
Methanocaldococcus jannaschii
Uses a Modified Mevalonate Pathway for Biosynthesis of Isopentenyl Diphosphate
Authors: Grochowski Laura L. , Xu Huimin , White Robert H. 
Published: April 2006

ABSTRACT

Archaea have been shown to produce isoprenoids from mevalonate; however, genome analysis has failed to identify several genes in the mevalonate pathway on the basis of sequence similarity. A predicted archaeal kinase, coded for by the MJ0044 gene, was associated with other mevalonate pathway genes in the archaea and was predicted to be the “missing” phosphomevalonate kinase. The MJ0044-derived protein was tested for phosphomevalonate kinase activity and was found not to catalyze this reaction. The MJ0044 gene product was found to phosphorylate isopentenyl phosphate, generating isopentenyl diphosphate. Unlike other known kinases associated with isoprene biosynthesis,
Methanocaldococcus jannaschii
isopentenyl phosphate kinase is predicted to be a member of the aspartokinase superfamily.
Selenium Is Involved in Regulation of Periplasmic Hydrogenase Gene Expression in
Desulfovibrio vulgaris
Hildenborough
Authors: Valente Filipa M. A. , Almeida Cláudia C. , Pacheco Isabel , Carita João , Saraiva Lígia M. , Pereira Inês A. C. 
Published: April 2006

ABSTRACT

Desulfovibrio vulgaris
Hildenborough is a good model organism to study hydrogen metabolism in sulfate-reducing bacteria. Hydrogen is a key compound for these organisms, since it is one of their major energy sources in natural habitats and also an intermediate in the energy metabolism. The
D. vulgaris
Hildenborough genome codes for six different hydrogenases, but only three of them, the periplasmic-facing [FeFe], [FeNi]
1
, and [FeNiSe] hydrogenases, are usually detected. In this work, we studied the synthesis of each of these enzymes in response to different electron donors and acceptors for growth as well as in response to the availability of Ni and Se. The formation of the three hydrogenases was not very strongly affected by the electron donors or acceptors used, but the highest levels were observed after growth with hydrogen as electron donor and lowest with thiosulfate as electron acceptor. The major effect observed was with inclusion of Se in the growth medium, which led to a strong repression of the [FeFe] and [NiFe]
1
hydrogenases and a strong increase in the [NiFeSe] hydrogenase that is not detected in the absence of Se. Ni also led to increased formation of the [NiFe]
1
hydrogenase, except for growth with H
2
, where its synthesis is very high even without Ni added to the medium. Growth with H
2
results in a strong increase in the soluble forms of the [NiFe]
1
and [NiFeSe] hydrogenases. This study is an important contribution to understanding why
D. vulgaris
Hildenborough has three periplasmic hydrogenases. It supports their similar physiological role in H
2
oxidation and reveals that element availability has a strong influence in their relative expression.
Identification and Functional Characterization of theLactococcus lactisCodY-Regulated Branched-Chain Amino Acid Permease BcaP (CtrA)
Authors: den Hengst Chris D. , Groeneveld Maarten , Kuipers Oscar P. , Kok Jan 
Published: April 2006

ABSTRACTTranscriptome analyses have previously revealed that a gene encoding the putative amino acid transporter CtrA (YhdG) is one of the major targets of the pleiotropic regulator CodY inLactococcus lactisandBacillus subtilis. The role ofctrAinL. lactiswas further investigated with respect to both transport activity as well as CodY-mediated regulation. CtrA is required for optimal growth in media containing free amino acids as the only amino acid source. Amino acid transport studies showed thatctrAencodes a secondary amino acid transport system that is specific for branched-chain amino acids (BCAAs) (isoleucine, leucine, and valine) and methionine, which is in disagreement with its previously proposed function (a cationic amino acid transporter), which was assigned based on homology. We propose to rename CtrA BcaP, for branched-chain amino acid permease. BcaP is a member of a group of conserved transport systems, as homologs are widely distributed among gram-positive bacteria. Deletion ofbcaPresulted in the loss of most of the BCAA uptake activity ofL. lactis, indicating that BcaP is the major BCAA carrier of this organism. Deletion ofbcaPtogether with a second (putative) BCAA permease, encoded bybrnQ, further reduced the viability of the strain. DNA microarray analysis showed that deletion ofbcaPpredominantly affects genes belonging to the regulons of the transcriptional regulator CodY, which is involved in global nitrogen metabolism and needs BCAAs for its activation, and of CmbR, which is involved in sulfur amino acid metabolism.
Educating Undergraduate Medical Students About Oncology: A Literature Review
Authors: Gaffan Judith , Dacre Jane , Jones Alison 
Published: April 2006

Purpose This article is a review of the literature regarding teaching oncology to undergraduate medical students. Methods MEDLINE, Psychinfo, ERIC, TIMELIT, EMBASE, CINAHL and the Cochrane CENTRAL Register of Controlled Trials (CENTRAL) were searched, using the search terms cancer, oncology, education, undergraduate, and teaching. Results The main findings can be summarized as follows: the involvement of patients in teaching is popular with students and portfolio learning is a successful way of involving patients; the use of standardized patients to teach breast examination improves students' performance in clinical assessment; the use of silicone models to teach breast examination improves students' sensitivity for detecting breast lumps; computer aided learning modules have a role, but are not superior to other types of learning; learning about cancer screening and prevention increases students' knowledge, improves their self rated skills, and changes their behavior; and cancer patients have an important role to play in teaching undergraduate communication skills. Conclusion We have found 48 articles on undergraduate teaching in oncology. Oncology teachers should consider adopting the evidence based approaches outlined in this review, and there should be more emphasis on educational research within the field of oncology.
Assessment of Tumor Necrosis Factor Alpha Blockade As an Intervention to Improve Tolerability of Dose-Intensive Chemotherapy in Cancer Patients
Authors: Monk J. Paul , Phillips Gary , Waite Ross , Kuhn John , Schaaf Larry J. , Otterson Gregory A. , Guttridge Denis , Rhoades Chris , Shah Manisha , Criswell Tamara , Caligiuri Michael A. , Villalona-Calero Miguel A. 
Published: April 2006

PurposeMaintaining dose-intensity with chemotherapeutic agents is hindered by a number of adverse effects including asthenia/fatigue. Tumor necrosis factor (TNF) is one of the cytokines responsible for the fatigue and cachexia associated with malignancies. We used etanercept (TNF-decoy receptor) to maintain dose-intensity of weekly docetaxel.Patients and MethodsInitially, 12 patients with advanced malignancies were randomly assigned to either docetaxel 43 mg/m2weekly alone (cohort A) or the same docetaxel dose plus etanercept 25 mg subcutaneously twice weekly (cohort B). Subsequently, higher doses of docetaxel in combination with etanercept were evaluated. Pharmacokinetics (PKs), nuclear factor-kappa B (NF-κB) activation, and intracellular cytokines levels were measured. Patients completed weekly questionnaires quantifying asthenia/fatigue.ResultsTwenty-nine of 36 intended docetaxel doses during the first cycle were delivered in cohort A, and 35 of 36 doses were delivered in cohort B (P = .055). Three cohort B patients received additional cycles in the absence of disease progression or severe toxicity, whereas no patients from cohort A received additional cycles. Escalation to docetaxel 52 mg/m2weekly with etanercept resulted in neutropenia, not fatigue, as the limiting adverse effect, and the addition of filgrastim permitted the maintenance of dose-intensity in additional patients. Patients randomly selected to receive etanercept/docetaxel self-reported less fatigue (P < .001), and docetaxel PKs show no relevant influence of etanercept. NF-κB activation and increased expression of TNF-α were associated with increments in docetaxel dose. Antitumor activity was noticed exclusively in patients receiving etanercept.ConclusionThe addition of etanercept is safe and had no impact on docetaxel concentrations. The significant improvement in tolerability and the trend toward preservation of dose-intensity suggests further exploration of TNF blockade as an adjunct to cancer therapies.