bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sigma Factor B and RsbU Are Required for Virulence in
Staphylococcus aureus
-Induced Arthritis and Sepsis
Authors: Jonsson Ing-Marie , Arvidson Staffan , Foster Simon , Tarkowski Andrzej 
Published: September 2004

ABSTRACT

The prototype
Staphylococcus aureus
strain 8325-4 produces high levels of hemolysins and proteases. Recently it has been shown that this property depends on a deficiency of sigma factor B (SigB) activity controlling the activation of regulatory genes such as
agr
and
sarA
. SigB deficiency is in turn due to a mutation in the
rsbU
gene, which is required for posttranslational activation of SigB. The
rsbU
defect of strain 8325-4 has recently been repaired, and we used this strain (SH1000), along with its isogenic
sigB
-negative mutant, to investigate the contributions of RsbU and SigB in a murine model of septic arthritis. Intravenous inoculation with the
rsbU
-repaired isogenic strain SH1000 resulted in significantly more severe arthritis, weight decrease, and mortality compared to those of the parental strain 8325-4 (
rsbU
-negative) or the isogenic
sigB
-negative mutant (MJH502). SH1000 also persisted more in kidneys and joints of infected mice. Our data strongly suggest that RsbU and SigB regulate important virulence factors, thereby contributing significantly to the outcome of staphylococcal infection.
Nucleic Acid Vaccination withSchistosoma mansoniAntioxidant Enzyme Cytosolic Superoxide Dismutase and the Structural Protein Filamin Confers Protection against the Adult Worm Stage
Authors: Cook Rosemary M. , Carvalho-Queiroz Claudia , Wilding Gregory , LoVerde Philip T. 
Published: September 2004

ABSTRACTSchistosomiasis remains a worldwide endemic cause of chronic and debilitating illness. There are two paradigms that exist in schistosome immunology. The first is that the schistosomule stages are the most susceptible to immune killing, and the second is that the adult stage, through evolution of defense mechanisms, can survive in the hostile host environment. One mechanism that seems to aid the adult worm in evading immune killing is the expression of antioxidant enzymes to neutralize the effects of reactive oxygen and nitrogen species. Here, we challenge one paradigm by targeting adultSchistosoma mansoniworms for immune elimination in an experimental mouse model using twoS. mansoniantioxidants, cytosolic superoxide dismutase (SmCT-SOD) and glutathione peroxidase (SmGPX), and a partial coding sequence for a structural protein, filamin, as DNA vaccine candidates. DNA vaccination with SmCT-SOD induced a mean of 39% protection, filamin induced a mean of 50% protection, and SmGPX induced no protection compared to controls following challenge with adult worms by surgical transfer. B- and T-cell responses were analyzed in an attempt to define the protective immune mechanism(s) involved in adult worm killing. SmCT-SOD-immunized mice presented with a T1 response, and filamin-immunized mice showed a mixed T1-T2 response. We provide evidence for natural boosting after vaccination. Our results demonstrate that adult worms can be targeted for immune elimination through vaccination. This represents an advance in schistosome vaccinology and allows for the development of a therapeutic as well as a prophylactic vaccine.
Host Cell Tropism Underlies Species Restriction of Human and Bovine
Cryptosporidium parvum
Genotypes
Authors: Hashim Amna , Clyne Marguerite , Mulcahy Grace , Akiyoshi Donna , Chalmers Rachel , Bourke Billy 
Published: September 2004

ABSTRACT

It has been recognized recently that human cryptosporidiosis is usually caused by
Cryptosporidium parvum
genotype I (“human”
C. parvum
), which is not found in animals. Compared to
C. parvum
genotype II, little is known of the biology of invasion of the human-restricted
C. parvum
genotype I. The aims of the present study were (i) to explore and compare with genotype II the pathogenesis of
C. parvum
genotype I infection by using an established in vitro model of infection and (ii) to examine the possibility that host-specific cell tropism determines species restriction among
C. parvum
genotypes by using a novel ex vivo small intestinal primary cell model of infection. Oocysts of
C. parvum
genotypes I and II were used to infect HCT-8 cells and primary intestinal epithelial cells in vitro. Primary cells were harvested from human endoscopic small-bowel biopsies and from bovine duodenum postmortem.
C. parvum
genotype I infected HCT-8 cells with lower efficiency than
C. parvum
genotype II. Actin colocalization at the host parasite interface and reduction in levels of invasion after treatment with microfilament inhibitors (cytochalasin B and cytochalasin D) were observed for both genotypes.
C. parvum
genotype II invaded primary intestinal epithelial cells, regardless of the species of origin. In contrast,
C. parvum
genotype I invaded only human small-bowel cells. The pathogenesis of
C. parvum
genotype I differs from
C. parvum
genotype II.
C parvum
genotype I does not enter primary bovine intestinal cells, suggesting that the species restriction of this genotype is due to host tissue tropism of the infecting isolate.
A Calcium-Calmodulin Antagonist Blocks Experimental
Vibrio vulnificus
Cytolysin-Induced Lethality in an Experimental Mouse Model
Authors: Lee Young-Rae , Park Kwang-Hyun , Lin Zhao-Zhen , Kho Young-Jong , Park Jin-Woo , Rho Hye-Won , Koo Bon-Sun , Kim Hyung-Rho , Song Eun-Kyung , Yu Hong-Nu , Han Myung-Kwan , Lee Seung-Ok , Jhee Eun-Chung , Kim Jong-Suk 
Published: September 2004

ABSTRACT

We demonstrated that trifluoperazine, a calcium-calmodulin antagonist, blocked the hyperpermeability induced by
Vibrio vulnificus
cytolysin in in vitro-modeled endothelium and prevented the deaths of mice. Furthermore, compared to tetracycline alone, tetracycline combined with trifluoperazine enhanced the survival rate of
V. vulnificus
-infected mice, indicating the role of the cytolysin as an important factor in pathogenesis.
The Extracellular Adherence Protein fromStaphylococcus aureusInhibits Neutrophil Binding to Endothelial Cells
Authors: Haggar Axana , Ehrnfelt Cecilia , Holgersson Jan , Flock Jan-Ingmar 
Published: September 2004

ABSTRACTExtracellular adherence protein (Eap) fromStaphylococcus aureusinhibits the adherence of neutrophils to nonstimulated and tumor necrosis factor alpha-stimulated endothelial cells in both static adhesion assays and flow adhesion assays. Consequently, Eap also impaired their transendothelial migration. During anS. aureusinfection, Eap may thus serve to reduce inflammation by inhibiting neutrophil adhesion and extravasation.
Limited Role for Interleukin-18 in the Host Protection Response to Pulmonary Infection with
Pseudomonas aeruginosa
in Mice
Authors: Nakasone Chikara , Kawakami Kazuyoshi , Hoshino Tomoaki , Kawase Yusuke , Yokota Koichi , Yoshino Kohichiro , Takeda Kiyoshi , Akira Shizuo , Saito Atsushi 
Published: September 2004

ABSTRACT

We report that clearance of
Pseudomonas aeruginosa
, accumulation of neutrophils, and synthesis of tumor necrosis factor alpha and macrophage inflammatory protein 2 in the infected lung were not largely different in interleukin-18 (IL-18) knockout or transgenic mice compared with control mice. Our results suggest a limited role for IL-18 in the host defense against
P. aeruginosa
.
The Fine Specificity, but Not the Invasion Inhibitory Activity, of 19-Kilodalton Merozoite Surface Protein 1-Specific Antibodies Is Associated with Resistance to Malarial Parasitemia in a Cross-Sectional Survey in The Gambia
Authors: Corran Patrick H. , O'Donnell Rebecca A. , Todd Jim , Uthaipibull Chairat , Holder Anthony A. , Crabb Brendan S. , Riley Eleanor M. 
Published: September 2004

ABSTRACTIn a cross-sectional survey of 187 Gambian children and adults, we have analyzed prevalence, fine specificity, and 19-kilodalton merozoite surface protein 1 (MSP-119)-specific erythrocyte invasion inhibitory activity of antibodies to MSP-119but find no significant association between any of these parameters and prevalence or density of malarial parasitemia, except that, after correcting for total anti-MSP-119antibody levels, individuals with anti-MSP-119antibodies that compete with an invasion inhibitory monoclonal antibody (12.10) were significantly less likely to have malaria infections with densities of ≥1,000 parasites/μl than were individuals without such antibodies. This association persisted after correction for age and ethnic origin.
Miniaturization and the Opening of The Mouth in a Greek Magical Text (Pgm Xii.270-350)
Authors: Moyer Ian , Dieleman Jacco 
Published: September 2004

AbstractPGM XII.270-350, a text prescribing rituals for the creation and use of a magical ring, provides a particularly useful example through which to explore the phenomenon of miniaturized ritual in the magical papyri of late Graeco-Roman Egypt (as elucidated by Smith 1995). The ritual for creating and consecrating the ring's gemstone makes it clear that the stone is considered a miniature cult statue. The subsequent "Ouphor" invocation to be performed whenever the ring is used corresponds in name and function to the Egyptian wp. t-r or Opening the Mouth ritual as used in daily temple liturgy. The nature of these ritual miniatures reveals the sophisticated discursive and conceptual level at which the traditional forms of temple ritual were adapted and redeployed for use in other contexts by members of the Egyptian priestly class in late antiquity.
Combination therapy for adult T-cell leukemia–xenografted mice: flavopiridol and anti-CD25 monoclonal antibody
Authors: Zhang Meili , Zhang Zhuo , Goldman Carolyn K. , Janik John , Waldmann Thomas A. 
Published: September 2004

AbstractAdult T-cell leukemia (ATL) develops in a small proportion of individuals infected with human T-cell lymphotrophic virus-1. The leukemia consists of an overabundance of activated T cells, which express CD25 on their cell surfaces. Presently, there is no accepted curative therapy for ATL. Flavopiridol, an inhibitor of cyclin-dependent kinases, has potent antiproliferative effects and antitumor activity. We investigated the therapeutic efficacy of flavopiridol alone and in combination with humanized anti-Tac antibody (HAT), which recognizes CD25, in a murine model of human ATL. The ATL model was established by intraperitoneal injection of MET-1 leukemic cells into nonobese diabetic/severe combined immunodeficient mice. Either flavopiridol, given 2.5 mg/kg body weight daily for 5 days, or HAT, given 100 μg weekly for 4 weeks, inhibited tumor growth as monitored by serum levels of human β-2-microglobulin (β2μ; P &lt; .01), and prolonged survival of the leukemia-bearing mice (P &lt; .05) as compared with the control group. Combination of the 2 agents dramatically enhanced the antitumor effect, as shown by both β2μ levels and survival of the mice, when compared with those in the flavopiridol or HAT alone group (P &lt; .01). The significantly improved therapeutic efficacy by combining flavopiridol with HAT provides support for a clinical trial in the treatment of ATL.
Selective Rac1 inhibition in dendritic cells diminishes apoptotic cell uptake and cross-presentation in vivo
Authors: Kerksiek Kristen M. , Niedergang Florence , Chavrier Philippe , Busch Dirk H. , Brocker Thomas 
Published: September 2004

AbstractTo better understand the influence of cytoskeletal regulation on dendritic cell (DC) function in vivo, the Rho guanosine triphosphatase (GTPase) Rac1 was selectively inhibited in DCs in transgenic (Tg) mice. Although transgene expression did not interfere with the migratory capacities of DC in vivo, a decreased uptake of fluorescent probes was observed. Interestingly, the absence of full Rac1 function most strongly affected the development and function of CD8+ DCs. Apoptotic cell uptake was severely reduced in Tg mice, impairing subsequent DC-mediated cross-presentation and priming of bacteria-specific T-cell responses. These findings highlight a special role for Rac1 in the capacity of CD8+ DCs to endocytose apoptotic cells and prime T cells via cross-presentation.
FbsA, a fibrinogen-binding protein from Streptococcus agalactiae, mediates platelet aggregation
Authors: Pietrocola Giampiero , Schubert Axel , Visai Livia , Torti Mauro , Fitzgerald J. Ross , Foster Timothy J. , Reinscheid Dieter J. , Speziale Pietro 
Published: September 2004

AbstractThe bacterium Streptococcus agalactiae is an etiologic agent in the pathogenesis of endocarditis in humans. FbsA, a fibrinogen-binding protein produced by this pathogen, is considered an important virulence factor. In the present study we provide evidence that S agalactiae clinical isolates bearing FbsA attach to fibrinogen and elicit a fibrinogen-dependent aggregation of platelets. Mutants of S agalactiae lacking the fbsA gene lost the ability to attach to fibrinogen and to aggregate platelets. Plasmid-mediated expression of fbsA restored the capability for fibrinogen binding and platelet aggregation in S agalactiae fbsA mutants, and allowed Lactococcus lactis to interact with fibrinogen and to aggregate human platelets. Moreover, a monoclonal anti-FbsA antibody inhibited bacterial adherence to fibrinogen and S agalactiae–induced platelet aggregation. Platelet aggregation was inhibited by aspirin, prostaglandin E1, the peptide RGDS, and the antibody abciximab, demonstrating the specificity of platelet aggregation by S agalactiae and indicating an involvement of integrin glycoprotein IIb/IIIa in the induction of platelet aggregation. Aggregation was also dependent on anti-FbsA IgG and could be inhibited by an antibody against the platelet FcγRIIA receptor. These findings indicate that FbsA is a crucial factor in S agalactiae–induced platelet aggregation and may therefore play an important role in S agalactiae–induced endocarditis.
Relevance of sexual dimorphism to regulatory T cells: estradiol promotes IFN-γ production by invariant natural killer T cells
Authors: Gourdy Pierre , Araujo Luiza M. , Zhu Ren , Garmy-Susini Barbara , Diem Séverine , Laurell Henrik , Leite-de-Moraes Maria , Dy Michel , Arnal Jean François , Bayard Francis , Herbelin André 
Published: September 2004

AbstractMechanisms accounting for gender dimorphism during immune responses are still poorly understood. Since invariant natural killer T (iNKT) cells exert important regulatory functions through their capacity to produce both T helper 1 (Th1) and Th2 cytokines, we addressed the question of whether these activities could be modulated by sexual hormones. We found that in vivo challenge with the specific ligand of iNKT cells, α-galactosylceramide (α-GalCer), induced significantly higher concentrations of interferon γ (IFN-γ) in the serum of female than in that of male mice, while interleukin 4 (IL-4) production was not modified. In support of a crucial role of ovarian hormones in this phenomenon, a significant decrease of serum IFN-γ concentrations occurred in ovariectomized females, in response to treatment with α-GalCer, while orchidectomy affected neither IFN-γ nor IL-4 serum concentrations in males. The implication of estrogens in this selective enhancement of IFN-γ production by iNKT cells was demonstrated by (1) the increased α-GalCer–induced IFN-γ synthesis by iNKT cells upon both in vitro and in vivo exposure to estradiol and (2) the abolition of the sex-linked difference in α-GalCer–induced IFN-γ release in estrogen receptor α-deficient mice. These results provide the first evidence that estrogens influence iNKT cells leading to this gender dimorphism in their cytokine production profile.
PEDRo: A database for storing, searching and disseminating experimental proteomics data
Authors: Garwood Kevin , McLaughlin Thomas , Garwood Chris , Joens Scott , Morrison Norman , Taylor Christopher F , Carroll Kathleen , Evans Caroline , Whetton Anthony D , Hart Sarah , Stead David , Yin Zhikang , Brown Alistair JP , Hesketh Andrew , Chater Keith , Hansson Lena , Mewissen Muriel , Ghazal Peter , Howard Julie , Lilley Kathryn S , Gaskell Simon J , Brass Andy , Hubbard Simon J , Oliver Stephen G , Paton Norman W 
Published: September 2004

Abstract
Background
Proteomics is rapidly evolving into a high-throughput technology, in which substantial and systematic studies are conducted on samples from a wide range of physiological, developmental, or pathological conditions. Reference maps from 2D gels are widely circulated. However, there is, as yet, no formally accepted standard representation to support the sharing of proteomics data, and little systematic dissemination of comprehensive proteomic data sets.

Results
This paper describes the design, implementation and use of a P roteome E xperimental D ata R epo sitory (PEDRo), which makes comprehensive proteomics data sets available for browsing, searching and downloading. It is also serves to extend the debate on the level of detail at which proteomics data should be captured, the sorts of facilities that should be provided by proteome data management systems, and the techniques by which such facilities can be made available.

Conclusions
The PEDRo database provides access to a collection of comprehensive descriptions of experimental data sets in proteomics. Not only are these data sets interesting in and of themselves, they also provide a useful early validation of the PEDRo data model, which has served as a starting point for the ongoing standardisation activity through the Proteome Standards Initiative of the Human Proteome Organisation.
Activation of Erk and JNK MAPK pathways by acute swim stress in rat brain regions
Authors: Shen Chang-peng , Tsimberg Yelena , Salvadore Christopher , Meller Emanuel 
Published: September 2004

Abstract
Background
The mitogen-activated protein kinases (MAPKs) have been shown to participate in a wide array of cellular functions. A role for some MAPKs (e.g., extracellular signal-regulated kinase, Erk1/2) has been documented in response to certain physiological stimuli, such as ischemia, visceral pain and electroconvulsive shock. We recently demonstrated that restraint stress activates the Erk MAPK pathway, but not c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK) or p38MAPK, in several rat brain regions. In the present study, we investigated the effects of a different stressor, acute forced swim stress, on the phosphorylation (P) state of these MAPKs in the hippocampus, neocortex, prefrontal cortex, amygdala and striatum. In addition, effects on the phosphorylation state of the upstream activators of the MAPKs, their respective MAPK kinases (MAPKKs; P-MEK1/2, P-MKK4 and P-MKK3/6), were determined. Finally, because the Erk pathway can activate c-AMP response element (CRE) binding (CREB) protein, and swim stress has recently been reported to enhance CREB phosphorylation, changes in P-CREB were also examined.

Results
A single 15 min session of forced swimming increased P-Erk2 levels 2–3-fold in the neocortex, prefrontal cortex and striatum, but not in the hippocampus or amygdala. P-JNK levels (P-JNK1 and/or P-JNK2/3) were increased in all brain regions about 2–5-fold, whereas P-p38MAPK levels remained essentially unchanged. Surprisingly, levels of the phosphorylated MAPKKs, P-MEK1/2 and P-MKK4 (activators of the Erk and JNK pathways, respectively) were increased in all five brain regions, and much more dramatically (P-MEK1/2, 4.5 to > 100-fold; P-MKK4, 12 to ~300-fold). Consistent with the lack of forced swim on phosphorylation of p38MAPK, there appeared to be no change in levels of its activator, P-MKK3/6. P-CREB was increased in all but cortical (prefrontal, neocortex) areas.

Conclusions
Swim stress specifically and markedly enhanced the phosphorylation of the MAPKKs P-MEK1/2 and P-MKK4 in all brain regions tested without apparent alteration in the phosphorylation of P-MKK3/6. Curiously, phosphorylation of their cognate substrates (Erk and JNK) was increased to a much more modest extent, and in some brain regions was not altered. Similarly, there was a region-specific discrepancy between Erk and CREB phosphorylation. Possible explanations for these findings and comparison with the effects of restraint stress will be discussed.
Suboptimal clinical response to ciprofloxacin in patients with enteric fever due to Salmonella spp. with reduced fluoroquinolone susceptibility: a case series
Authors: Slinger Robert , Desjardins Marc , McCarthy Anne E , Ramotar Karam , Jessamine Peter , Guibord Christiane , Toye Baldwin 
Published: September 2004

Abstract
Background
Salmonella spp. with reduced susceptibility to fluoroquinolones have higher than usual MICs to these agents but are still considered "susceptible" by NCCLS criteria. Delayed treatment response to fluoroquinolones has been noted, especially in cases of enteric fever due to such strains. We reviewed the ciprofloxacin susceptibility and clinical outcome of our recent enteric fever cases.

Methods
Salmonella enterica Serotype Typhi (S. Typhi) and Serotype Paratyphi (S. Paratyphi) blood culture isolates (1998–2002) were tested against nalidixic acid by disk diffusion (DD) and agar dilution (AD) and to ciprofloxacin by AD using NCCLS methods and interpretive criteria. Reduced fluoroquinolone susceptibility was defined as a ciprofloxacin MIC of 0.125–1.0 mg/L. The clinical records of patients treated with ciprofloxacin for isolates with reduced fluoroquinolone susceptibility were reviewed.

Results
Seven of 21 (33%) S. Typhi and S. Paratyphi isolates had reduced susceptibility to fluoroquinolones (MIC range 0.125–0.5 mg/L). All 7 were nalidixic acid resistant by DD (no zone) and by AD (MIC 128- >512 mg/L). The other 14 isolates were nalidixic acid susceptible and fully susceptible to ciprofloxacin (MIC range 0.015–0.03 mg/L).
Five of the 7 cases were treated initially with oral ciprofloxacin. One patient remained febrile on IV ciprofloxacin until cefotaxime was added, with fever recurrence when cefotaxime was discontinued. Two continued on oral or IV ciprofloxacin alone but had prolonged fevers of 9–10 days duration, one was switched to IV beta-lactam therapy after remaining febrile for 3 days on oral/IV ciprofloxacin and one was treated successfully with oral ciprofloxacin. Four of the 5 required hospitalization.

Conclusions
Our cases provide further evidence that reduced fluoroquinolone susceptibility of S. Typhi and S. Paratyphi is clinically significant. Laboratories should test extra-intestinal Salmonella spp. for reduced fluoroquinolone susceptibility.