bluuebunny/crossref_metadata_2025_split huggingface dataset:
An evaluation of an innovative audiotape method for keeping social care staff up to date with the latest research findings
Authors: Hagell Ann , Spencer Liz 
Published: March 2004

ABSTRACTA small scale exploratory evaluation of an innovative way (using audiotapes) of keeping social care staff informed about research findings is described. The research was mainly qualitative in style, and explored (i) the extent to which the audiotapes raised knowledge about issues at an individual level, and (ii) subsequent changes in agency practice in terms of discussing and sharing literature‐based information over a period of several months. The study was undertaken in four social services departments in England. A total of 29 social care staff answered an initial questionnaire before exposure to the tape itself. Following exposure, four focus groups involving a total of 25 social care staff were undertaken to reveal their attitudes to the content and style of presentation. Finally, three months later, 20 of the original 25 social care staff answered a further round of questions on subsequent use of the tapes as part of practice development. Results generally revealed that social care staff responded well to more informal, conversational styles of presentation on the tape but were critical where a more formal ‘lecture style’ was adopted. Their uptake of research messages was very driven by the specific demands of their own individual work role. Broader relevance for disseminating research results to social care staff is discussed.
Research Review: Teenage pregnancy and motherhood: the contribution of support
Authors: Bunting Lisa , McAuley Colette 
Published: March 2004

ABSTRACTThis paper aims to provide a critical analysis of the role of support in teenage motherhood. Family, partner and peer support are considered and literature emanating from both the USA and UK is reviewed. In summary the research literature indicates that family support is particularly important to teenage mothers and has been found to have a positive influence on parenting behaviours and practices. However, the mother–daughter relationship is not always a straightforward one and conflict between the two can diminish some of the positive impact. The research on partner support highlights how support from fathers and/or other male partners has been linked with improved financial and psychological outcomes for teenage mothers as well as having a positive influence on parenting behaviours. There is also evidence to suggest that support from partners may become increasingly important to teenage mothers over time and can be a valuable source of socializing participation and positive feedback. While the research available on peer support is much more limited it suggests that the emotional support of peers is perceived as being important by teenage mothers. Current research findings suggest that families, partners and peers tend to provide different, but complementary, forms of support for teenage mothers which, on the whole, appear to contribute to more positive outcomes for this group.
Highly Purified Vitamin B2 Presents a Promising Therapeutic Strategy for Sepsis and Septic Shock
Authors: Toyosawa Toshio , Suzuki Mamoru , Kodama Kohtarou , Araki Seiichi 
Published: March 2004

ABSTRACT
Highly purified vitamin B2 (riboflavin 5′-sodium phosphate; purity > 97%) treatment by intravenous infusion at doses above those used clinically to treat vitamin B2 deficiency showed therapeutic effects in mice not only in cases of endotoxin- and exotoxin-induced shock but also in cases of gram-negative and gram-positive bacterial infection even after the toxemia had already begun.
Mechanisms Involved in Apoptosis of Human Macrophages Induced by Lipopolysaccharide fromActinobacillus actinomycetemcomitansin the Presence of Cycloheximide
Authors: Suzuki Takao , Kobayashi Makoto , Isatsu Kyoko , Nishihara Tatsuji , Aiuchi Toshihiro , Nakaya Kazuyasu , Hasegawa Kohji 
Published: March 2004

ABSTRACTActinobacillus actinomycetemcomitansis a major periodontopathic bacterium with multiple virulence factors, including lipopolysaccharide (LPS). Previous reports have demonstrated that LPS induced apoptosis in a murine macrophage-like cell line, J744.1, as well as in peritoneal macrophages from C3H/HeN mice in the presence of cycloheximide (CHX). However, the detailed molecular mechanisms involved in the apoptosis of macrophages induced by LPS and CHX are not well known. To clarify the possible role of LPS in the induction of macrophage apoptosis, we investigated cell death induced by LPS fromA. actinomycetemcomitansand CHX in human macrophage-like U937 cells, which were differentiated by 12-O-tetradecanoylphorbol 13-acetate (TPA), and also assessed the molecular mechanisms involved in the process. We found that TPA-differentiated U937 cells usually showed resistance to LPS-induced apoptosis. However, in the presence of CHX, LPS induced release of cytochromecwithout modifying steady-state levels of Bcl-2, Bcl-xL, Bax, and Bak. Treatment with LPS in the presence of CHX also led to activation of caspase-3 and apoptosis via, in part, the CD14/toll-like receptor 4 (TLR4). The induction of cytochromecrelease may have been due to dephosphorylation of Akt and Bad, which were cooperatively induced by CHX and LPS. However, endogenous tumor necrosis factor alpha- and Fas-induced signals, extracellular signal-regulated kinase kinase/mitogen-activated protein kinases and I-κBα/nuclear factor-κB (NF-κB) were not required for caspase-3-dependent apoptosis. These results emphasize the possible important role of the mitochondrial apoptotic pathway leading to caspase-3 activation in LPS-induced apoptosis of human macrophages in the presence of CHX.
N-Linked Glycosylation Is Required for C1 Inhibitor-Mediated Protection from Endotoxin Shock in Mice
Authors: Liu Dongxu , Gu Xiaogang , Scafidi Jennifer , Davis Alvin E. 
Published: March 2004

ABSTRACTC1 inhibitor (C1INH) prevents endotoxin shock in mice via a direct interaction with lipopolysaccharide (LPS). This interaction requires the heavily glycosylated amino-terminal domain of C1INH. C1INH in which N-linked carbohydrate was removed by usingN-glycosidase F was markedly less effective in protecting mice from LPS-induced lethal septic shock. N-deglycosylated C1INH also failed to suppress fluorescein isothiocyanate (FITC)-LPS binding to and LPS-induced tumor necrosis factor alpha mRNA expression by the murine macrophage-like cell line, RAW 264.7, and cells in human whole blood. In an enzyme linked immunosorbent assay, the N-deglycosylated C1INH bound to LPS very poorly. In addition, C1INH was shown to bind to diphosphoryl lipid A (dLPA) but only weakly to monophosphoryl lipid A (mLPA). As with intact LPS, binding of N-deglycosylated C1INH to dLPA and mLPA was diminished in comparison with the native protein. Removal of O-linked carbohydrate had no effect on any of these activities. Neither detoxified LPS, dLPA, nor mLPA had any effect on the rate or extent of C1INH complex formation with C1s or on cleavage of the reactive center loop by trypsin. These data demonstrate that N-linked glycosylation of C1INH is essential to mediate its interaction with the LPA moiety of LPS and to protect mice from endotoxin shock.
Involvement ofSalmonellaPathogenicity Island 2 in the Up-Regulation of Interleukin-10 Expression in Macrophages: Role of Protein Kinase A Signal Pathway
Authors: Uchiya Kei-ichi , Groisman Eduardo A. , Nikai Toshiaki 
Published: March 2004

ABSTRACTSalmonellae are facultative intracellular bacteria capable of surviving within macrophages.Salmonellapathogenicity island 2 (SPI-2) is required for growth within macrophages and for virulence in mice. In this study, we show the involvement of SPI-2 in a signal transduction pathway that induces cytokine expression inSalmonella-infected macrophages. High levels of interleukin-10 (IL-10) mRNA were induced in macrophages by infection with wild-type salmonellae compared to a strain carrying a mutation in thespiCgene, which is encoded within SPI-2. The two strains had the same effect on the expression of proinflammatory cytokines such as IL-1α, IL-6, and tumor necrosis factor alpha. IL-10 expression was dose dependently blocked by treatment of infected macrophages with the protein kinase A (PKA) inhibitor H-89, while IL-10 expression was increased by the PKA activator dibutyryl cyclic AMP. Cyclic AMP-dependent PKA activity was higher in macrophages infected with wild-type salmonellae compared to thespiCmutant, and Ser132phosphorylation of cyclic AMP response element-binding protein (CREB), which is an important mediator of PKA activation, correlated with the levels of PKA activity. Taken together, these results indicate that salmonellae cause an SPI-2-dependent increase in PKA activity that leads to CREB phosphorylation, resulting in up-regulation of IL-10 expression inSalmonella-infected macrophages. Suppression of IL-10 expression by an antisense oligonucleotide did not affect the growth of wild-type salmonellae within macrophages, whereas growth was dose dependently inhibited by H-89, suggesting that the PKA signaling pathway plays a significant role in intramacrophageSalmonellasurvival.
Effects of Gamma Interferon, Interleukin-10, and Transforming Growth Factor β on the Survival ofMycobacterium aviumsubsp.paratuberculosisin Monocyte-Derived Macrophages from Naturally Infected Cattle
Authors: Khalifeh M. S. , Stabel J. R. 
Published: March 2004

ABSTRACTGamma interferon (IFN-γ) plays a significant role in the control of mycobacterial infections, includingMycobacterium aviumsubsp.paratuberculosis. However, the contribution of other immunoregulatory cytokines, such as interleukin-10 (IL-10) and transforming growth factor β (TGF-β), in Johne's disease has not been investigated as yet. In this study, we examined the effects of in vivo and in vitro infection withM. aviumsubsp.paratuberculosison the production of IFN-γ, IL-10, and TGF-β by peripheral blood mononuclear cells (PBMC). We also examined the effects of exogenous IFN-γ, IL-10, and TGF-β onM. aviumsubsp.paratuberculosissurvival in the cell cultures. PBMC obtained from naturally infected cows, regardless of their disease status, specifically upregulated IL-10 and TGF-β in culture supernatants in response to stimulation with liveM. aviumsubsp.paratuberculosis. Nonstimulated PBMC recovered from subclinically infected animals secreted the lowest levels of TGF-β, but after stimulation with liveM. aviumsubsp.paratuberculosis, TGF-β levels in the culture supernatants increased to levels similar to that produced by PBMC from healthy animals. The numbers of viableM. aviumsubsp.paratuberculosisrecovered from cultures from naturally infected animals were higher than those from healthy cows after in vitro infection withM. aviumsubsp.paratuberculosis. The addition of exogenous IL-10 and TGF-β to PBMC isolated from healthy cows inhibited the bactericidal activity of these cells as evidenced by the increased number of viableM. aviumsubsp.paratuberculosisrecovered from these cultures compared to cell cultures containing medium alone. These data suggest important immune regulatory roles for IL-10 and TGF-β during infection withM. aviumsubsp.paratuberculosisthat may be directly related to their effects on macrophage activation and killing ofM. aviumsubsp.paratuberculosis.
Dendritic Cell Populations inLeishmania major-Infected Skin and Draining Lymph Nodes
Authors: Baldwin Tracey , Henri Sandrine , Curtis Joan , O'Keeffe Meredith , Vremec David , Shortman Ken , Handman Emanuela 
Published: March 2004

ABSTRACTUsing a metacyclic promastigote ear infection model of cutaneous leishmaniasis, we examined the phenotype, parasite load, and cytokine production of dendritic cells in the skin and draining lymph nodes of resistant C57BL/6J and susceptible BALB/c mice. Five dendritic cell populations were isolated from the skin and lymph nodes, and the main difference between the groups of mice was an increased number of plasmacytoid dendritic cells in the lymph nodes of the susceptible mice. Although similar cell types were present in the skin emigrants of both strains, there was a 10-fold larger number of cells in BALB/c mouse skin early in infection than in C57BL/6J mouse skin. None of the dendritic cells in the lymph nodes harbored parasites until 3 weeks after infection, with the Langerhans cells having the largest load and the plasmacytoid dendritic cells having the smallest load but the longest lasting infection. Although parasites could be detected in the lymph nodes a few hours after infection, none of the skin emigrants harbored parasites, indicating that they are not the vehicle that ferries the parasites from the skin to the lymph nodes. The presence of larger numbers of plasmacytoid cells in infected BALB/c mice, the more protracted infection of these cells, and their production of alpha interferon point to a complex and important role for the plasmacytoid cells in leishmaniasis.
Induction of Protective Cellular Immunity againstMycobacterium tuberculosisby Recombinant Attenuated Self-DestructingListeria monocytogenesStrains Harboring Eukaryotic Expression Plasmids for Antigen 85 Complex and MPB/MPT51
Authors: Miki Keita , Nagata Toshi , Tanaka Takao , Kim Yeung-Hyen , Uchijima Masato , Ohara Naoya , Nakamura Satoshi , Okada Masaji , Koide Yukio 
Published: March 2004

ABSTRACTWe report here the induction of specific protective cellular immunity againstMycobacterium tuberculosisby the employment of vaccination with recombinant attenuatedListeria monocytogenesstrains. We constructed self-destructing attenuatedL. monocytogenesΔ2 strains carrying eukaryotic expression plasmids for the antigen 85 complex (Ag85A and Ag85B) and for MPB/MPT51 (mycobacterial protein secreted byM. bovisBCG/mycobacterial protein secreted byM. tuberculosis) molecules. Infection of these recombinant bacteria allowed expression of the genes in the J774A.1 murine macrophage cell line. Intraperitoneal vaccination of C57BL/6 mice with these recombinant bacteria was capable of inducing purified protein derivative-specific cellular immune responses, such as foot pad reactions, proliferative responses of splenocytes, and gamma interferon production from splenocytes, suggesting the efficacy of vaccination against mycobacterial infection by use of these recombinantL. monocytogenesstrains. Furthermore, intravenous vaccination with recombinant bacteria carrying expression plasmids for Ag85A, Ag85B, or MPB/MPT51 in BALB/c mice elicited significant protective responses, comparable to those evoked by a liveMycobacterium bovisBCG vaccine. Notably, this is the first report to show that MPB/MPT51 is a major protective antigen in addition to Ag85A and Ag85B, which have been reported to be major mycobacterial protective antigens.
The Nature of Extracellular Iron Influences Iron Acquisition byMycobacterium tuberculosisResiding within Human Macrophages
Authors: Olakanmi Oyebode , Schlesinger Larry S. , Ahmed Ambar , Britigan Bradley E. 
Published: March 2004

ABSTRACTWe have reported thatMycobacterium tuberculosisresiding within the phagosomes of human monocyte-derived macrophages (MDM) can acquire Fe from extracellular transferrin (TF) and sources within the MDM. In the lung, Fe is also bound to lactoferrin (LF) and low-molecular-weight chelates. We therefore investigated the ability of intraphagosomalM. tuberculosisto acquire Fe from these sources.M. tuberculosisacquired 30-fold and 3-fold more Fe from LF and citrate, respectively, compared to TF, in spite of similar MDM-associated Fe.M. tuberculosisinfection decreased MDM-associated Fe relative to uninfected MDM as follows: TF (38.7%), citrate (21.1%), and LF (15.3%).M. tuberculosisFe acquisition from extracellular chelates (exogenous source) and from endogenous MDM Fe initially acquired from the three chelates (endogenous source) was compared.M. tuberculosisFe acquisition was similar from exogenous and endogenous sources supplied as Fe-TF. In contrast, there was much greater intracellularM. tuberculosisFe uptake from LF and citrate from the exogenous than endogenous source. Gamma interferon (IFN-γ) reduced MDM Fe uptake from each chelate by ∼50% and augmented theM. tuberculosis-induced decrease in MDM Fe uptake from exogenous TF, but not from LF or citrate. IFN-γ minimally decreased intracellularM. tuberculosisFe acquisition from exogenous Fe-TF but significantly increased Fe uptake from LF and citrate. IntraphagosomalM. tuberculosisFe acquisition from both exogenous and endogenous MDM sources, and the effect of IFN-γ on this process, is influenced by the nature of the extracellular Fe chelate.M. tuberculosishas developed efficient mechanisms of acquiring Fe from a variety of Fe chelates that it likely encounters within the human lung.
Degenerate Peptide Recognition by
Candida albicans
Adhesins Als5p and Als1p
Authors: Klotz Stephen A. , Gaur Nand K. , Lake Douglas F. , Chan Vincent , Rauceo Jason , Lipke Peter N. 
Published: March 2004

ABSTRACT

Candida albicans
and
Saccharomyces cerevisiae
expressing the adhesins Als5p or Als1p adhere to immobilized peptides and proteins that possess appropriate sequences of amino acids in addition to a sterically accessible peptide backbone. In an attempt to further define the nature of these targets, we surveyed the ability of yeast cells to adhere to 90-μm-diameter polyethylene glycol beads coated with a 7-mer peptide from a library of 19
7
unique peptide-beads.
C. albicans
bound to ca. 10% of beads from the library, whereas
S. cerevisiae
expressing Als5p or Als1p bound to ca. 0.1 to 1% of randomly selected peptide-beads.
S. cerevisiae
expressing Als1p had a distinctly different adherence phenotype than did cells expressing Als5p. The former adhered in groups or clumps of cells, whereas the latter adhered initially as single cells, an event which was followed by the build up of cell-cell aggregates. Beads with adherent cells were removed, and the peptide attached to the bead was determined by amino acid sequencing. All adhesive beads carried a three-amino-acid sequence motif (τφ+) that possessed a vast combinatorial potential. Adherence was sequence specific and was inhibited when soluble peptide identical to the immobilized peptide was added. The Als5p adhesin recognized some peptides that went unrecognized by Als1p. The sequence motif of adhesive peptides identified by this method is common in proteins and offers so many possible sequence combinations that target recognition by the Als proteins is clearly degenerate. A degenerate recognition system provides the fungi with the potential of adhering to a multitude of proteins and peptides, an advantage for any microorganism attempting to establish a commensal or pathogenic relationship with a host.
Whole-Genome DNA Array Analysis of the Response of
Borrelia burgdorferi
to a Bactericidal Monoclonal Antibody
Authors: Anderton Julie M. , Tokarz Rafal , Thill Charles D. , Kuhlow Christopher J. , Brooks Chad S. , Akins Darrin R. , Katona Laura I. , Benach Jorge L. 
Published: March 2004

ABSTRACT

Identification and characterization of genes that contribute to infection with
Borrelia burgdorferi
and, of those, genes that are targets of host responses is important for understanding the pathogenesis of Lyme disease. The complement-independent bactericidal monoclonal antibody (MAb) CB2 recognizes a carboxy-terminal, hydrophilic epitope of the outer surface protein B (OspB). CB2 kills
B. burgdorferi
by an unknown bactericidal mechanism. Upon binding of CB2 to OspB, differentially expressed gene products may be responsible for, or associated with, the death of the organism. A time course of the response of
B. burgdorferi
to CB2 was completed to analyze the differential gene expression in the bacteria over a period of visual morphological changes. Bacteria were treated with a sublethal concentration in which spirochetes were visibly distressed by the antibody but not lysed. Preliminary whole-genome DNA arrays at various time points within 1 h of incubation of
B. burgdorferi
with the antibody showed that most significant changes occurred at 25 min. Circular plasmid 32 (cp32)-encoded genes were active in this period of time, including the
blyA
homologs, phage holin system genes. DNA array data show that three
blyA
homologs were upregulated significantly, ≥2 standard deviations from the mean of the log ratios, and a
P
value of ≤0.01. Quantitative real-time PCR analysis verified
blyA
and
blyB
upregulation over an 18- to 35-min time course. The hypothesis to test is whether the killing mechanism of CB2 is through uncontrolled expression of the
blyA
and
blyB
phage holin system.
Intraspleen Delivery of a DNA Vaccine Coding for Superoxide Dismutase (SOD) ofBrucella abortusInduces SOD-Specific CD4+and CD8+T Cells
Authors: Muñoz-Montesino Carola , Andrews Edilia , Rivers Rodolfo , González-Smith Andrés , Moraga-Cid Gustavo , Folch Hugo , Céspedes Sandra , Oñate Angel A. 
Published: March 2004

ABSTRACTIn the development of vaccines capable of providing immunity against brucellosis, Cu-Zn superoxide dismutase (SOD) has been demonstrated to be one of the protective immunogens ofBrucella abortus. In an earlier study, we provided strong evidence that intramuscular injection with a plasmid DNA carrying the SOD gene (pcDNA-SOD) was able to induce a protective immune response. The present study was designed to characterize T-cell immune responses after an intraspleen (i.s.) vaccination of BALB/c mice with pcDNA-SOD. Animals vaccinated with pcDNA-SOD did not develop SOD-specific antibodies, at least until week 4 after immunization (the end of the experiment), and in vitro stimulation of their splenocytes with either recombinant Cu-Zn SOD or crudeBrucellaprotein induced the secretion of gamma interferon (IFN-γ), but not interleukin-4, and elicited the induction of cytotoxic-T-lymphocyte activity. Upon analyzing the SOD-specific T-cell responses, the pcDNA-SOD vaccination was found to be stimulating both CD4+- and CD8+-T-cell populations. However, only the CD4+population was able to produce IFN-γ and only the CD8+population was able to induce cytotoxic activity. Nevertheless, although i.s. route vaccination induces a significant level of protection in BALB/c mice against challenge with the virulentB. abortusstrain 2308, vaccination by the intramuscular route with a similar amount of plasmid DNA does not protect. Based on these results, we conclude that i.s. immunization with pcDNA-SOD vaccine efficiently induced a Th1 type of immune response and a protective response that could be related to IFN-γ production and cytotoxic activity against infected cells by SOD-specific CD4+and CD8+T cells, respectively.
Inhibition of Major Histocompatibility Complex II Expression and Antigen Processing in Murine Alveolar Macrophages byMycobacterium bovisBCG and the 19-Kilodalton Mycobacterial Lipoprotein
Authors: Fulton Scott A. , Reba Scott M. , Pai Rish K. , Pennini Meghan , Torres Martha , Harding Clifford V. , Boom W. Henry 
Published: March 2004

ABSTRACTAlveolar macrophages constitute a primary defense againstMycobacterium tuberculosis, but they are unable to controlM. tuberculosiswithout acquired T-cell immunity. This study determined the antigen-presenting cell function of murine alveolar macrophages and the ability of the model mycobacterium,Mycobacterium bovisBCG, to modulate it. The majority (80 to 85%) of alveolar macrophages expressed both CD80 (B7.1) and CD11c, and 20 to 30% coexpressed major histocompatibility complex II (MHC-II). Gamma interferon (IFN-γ) enhanced MHC-II but not B7.1 expression. Naive or IFN-γ-treated alveolar macrophages did not express CD86 (B7.2), CD11b, Mac-3, CD40, or F4/80.M. bovisBCG and the 19-kDa mycobacterial lipoprotein inhibited IFN-γ-regulated MHC-II expression on alveolar macrophages, and inhibition was dependent on Toll-like receptor 2. The inhibition of MHC-II expression by the 19-kDa lipoprotein was associated with decreased presentation of soluble antigen to T cells. Thus, susceptibility to tuberculosis may result from the ability of mycobacteria to interfere with MHC-II expression and antigen presentation by alveolar macrophages.