bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of Gene Expression in Human Macrophages Treated with the Anti-
Leishmania
Pentavalent Antimonial Drug Sodium Stibogluconate
Authors: El Fadili Karima , Imbeault Michaël , Messier Nadine , Roy Gaétan , Gourbal Benjamin , Bergeron Marc , Tremblay Michel J. , Légaré Danielle , Ouellette Marc 
Published: December 2007

ABSTRACT

Within the mammalian host,
Leishmania donovani
is an obligatory intracellular protozoan parasite that resides and multiplies exclusively in the phagolysosomes of macrophages.
Leishmania
control relies primarily on chemotherapy, with the mainstay being pentavalent antimony (SbV) complexed to carbohydrates in the form of sodium stibogluconate (Pentostam) or meglumine antimoniate (Glucantime). The mode of action of SbV is still not known precisely. To explore the effect of SbV on macrophage gene expression, a microarray analysis was performed using Affymetrix focus arrays to compare gene expression profiles in noninfected and
L. donovani
-infected THP-1 monocytic cells treated or not treated with sodium stibogluconate. Under our experimental conditions, SbV changed the expression of a few host genes, and this was independent of whether cells were infected or not infected with
Leishmania. Leishmania
infection had a greater effect on the modulation of host gene expression. Statistical analyses have indicated that the expression of eight genes was modified by at least twofold upon SbV treatment, with six genes upregulated and two genes downregulated. One gene whose expression was affected by SbV was the heme oxygenase gene
HMOX-1
, and this change was observed both in the monocytic cell line THP-1 and in primary human monocyte-derived macrophages. Another pathway that was affected was the glutathione biosynthesis pathway, where the expression of the glutamate-cysteine ligase modifier subunit was increased upon SbV treatment. Our analysis has suggested that, under our experimental conditions, the expression of a few genes is altered upon SbV treatment, and some of these encoded proteins may be implicated in the yet-to-be-defined mode of action of SbV.
Intracellular Efavirenz Levels in Peripheral Blood Mononuclear Cells from Human Immunodeficiency Virus-Infected Individuals
Authors: Tanaka Rie , Hanabusa Hideji , Kinai Ei , Hasegawa Naoki , Negishi Masayoshi , Kato Shingo 
Published: December 2007

ABSTRACT
We describe a novel method for isolating plasma-free peripheral blood mononuclear cells retaining intracellular efavirenz. Quantification of efavirenz in 13 human immunodeficiency virus-infected patients by liquid chromatography-tandem mass spectrometry showed a higher correlation of intracellular levels with unbound plasma levels (accumulation ratio, 1,190) than with total plasma levels.
Effective Production and Purification of the Glycosylated TSOL18 Antigen, Which Is Protective against Pig Cysticercosis
Authors: Cai Xuepeng , Yuan Gailing , Zheng Yadong , Luo Xuenong , Zhang Shaohua , Ding Juntao , Jing Zhizhong , Lu Chengping 
Published: December 2007

ABSTRACT

Cysticercosis caused by
Taenia solium
metacestodes is a worldwide public health problem. Important progress in the development of effective and practical vaccines against this disease has been made. In this study, the promising
T. solium
oncospheral vaccine candidate named TSOL18 antigen was produced in a 5-liter fermentor. During the process of fermentation, the pH of the culture was always kept below 5.0, and in order to prevent foaming, an antifoam agent was added. In addition, the oxygen content of the culture was constantly kept at >50% in our experiment. A high level of the glycosylated protein (2.5 g/liter) was obtained, and the protein was easily purified by gel chromatography. Vaccination trials showed that the recombinant TSOL18 antigen induced 94 and 100% reductions in metacestode burdens in vaccinated pigs, obviously higher than the 89% reduction in pigs immunized with cysticercus crude extracts in trial 1. These are very promising results in the development of an efficient tool to control cysticercosis in Asia.
Possible Role for Toll-Like Receptors in Interaction ofFasciola hepaticaExcretory/Secretory Products with Bovine Macrophages
Authors: Flynn Robin J. , Mulcahy Grace 
Published: December 2007

ABSTRACTAlternative activation of macrophages (Mφ) during helminth infection is a characteristic feature of the host immune response. Alternatively activated macrophages (AAMφ) are distinguished from others by high arginase 1 (Arg-1) activity, low nitric oxide (NO), and high interleukin 10 (IL-10) production. In murine models, these cells have been shown to possess anti-inflammatory properties. They have also been implicated in exacerbating a subsequent infection with a secondary pathogen. In this study we used cattle experimentally infected withFasciola hepaticato monitor the kinetics of IL-4 and IL-10 over the course of infection. Using naïve Mφ in vitro, we examined the effects of exposure toF.hepaticaexcretory/secretory products (FhepES) alone or in combination with IL-4. Our results suggest that FhepES may work in combination with IL-4 to produce AAMφ. The effects of FhepES on the subsequent responses to lipopolysaccharide (LPS) and purified protein derivative fromMycobacterium bovis(PPD-B), which are bovine Toll-like receptor 4 (TLR4) and TLR2 antagonists, respectively, were also examined. We found that Mφ stimulated with FhepES together with LPS or PPD-B have reduced NO or gamma interferon production, respectively. The ability of FhepES to produce AAMφ was found to be heat labile and partially dependent on glycan residues. A possible role for TLR recognition is discussed.
Enterobacter sakazakii
Invasion in Human Intestinal Caco-2 Cells Requires the Host Cell Cytoskeleton and Is Enhanced by Disruption of Tight Junction
Authors: Kim Kwang-Pyo , Loessner Martin J. 
Published: December 2007

ABSTRACT

Enterobacter sakazakii
is an opportunistic pathogen that causes systemic bacteremia and meningitis with high mortality, and powdered infant formula is a frequent source of this bacterium. However, the mechanisms that this organism uses to invade and translocate through the intestinal barrier are unknown. Using Caco-2 epithelial cells, we were able to demonstrate penetration of
E. sakazakii
and to determine invasion-associated properties. We found that
E. sakazakii
entry and invasion were dependent on the exposure time and multiplicity of infection and required bacterial de novo protein synthesis but was independent of cell polarity in the presence of tight junctions. Moreover, the presence of actin filaments and microtubule structures was required, and disruption of the tight junction significantly enhanced the initial association with Caco-2 cells and the efficiency of invasion, which provides a possible explanation for the preferential occurrence of this infection in babies and neonates. This is the first description of
E. sakazakii
invasion of host intestinal cells, and our findings suggest that this emerging pathogen employs a novel invasion mechanism for development of systemic infection.
Genetic Diversity among
Escherichia coli
O157:H7 Isolates and Identification of Genes Linked to Human Infections
Authors: Wu Guanghui , Carter Ben , Mafura Muriel , Liebana Ernesto , Woodward Martin J. , Anjum Muna F. 
Published: December 2007

ABSTRACT

An
Escherichia coli
oligonucleotide microarray based on three sequenced genomes was validated for comparative genomic microarray hybridization and used to study the diversity of
E. coli
O157 isolates from human infections and food and animal sources. Among 26 test strains, 24 (including both Shiga toxin [Stx]-positive and -negative strains) were found to be related to the two sequenced
E. coli
O157:H7 strains, EDL933 and Sakai. However, these strains showed much greater genetic diversity than those reported previously, and most of them could not be categorized as either lineage I or II. Some genes were found more often in isolates from human than from nonhuman sources; e.g., ECs1202 and ECs2976, associated with
stx2AB
and
stx1AB
, were in all isolates from human sources but in only 40% of those from nonhuman sources. Some (but not all) lineage I-specific or -dominant genes were also more frequently associated with isolates from human. The results suggested that it might be more effective to concentrate our efforts on finding markers that are directly related to infection rather than those specific to certain lineages. In addition, two Stx-negative O157 cattle isolates (one confirmed to be H7) were significantly different from other Stx-positive and -negative
E. coli
O157:H7 strains and were more similar to MG1655 in their gene content. This work demonstrates that not all
E. coli
O157:H7 strains belong to the same clonal group, and those that were similar to
E. coli
K-12 might be less virulent.
Activation of IκB Kinase β and NF-κB Is Essential for
Helicobacter pylori
-Induced Chronic Gastritis in Mongolian Gerbils
Authors: Yanai Ayako , Maeda Shin , Shibata Wataru , Hikiba Yohko , Sakamoto Kei , Nakagawa Hayato , Ohmae Tomoya , Hirata Yoshihiro , Ogura Keiji , Muto Susumu , Itai Akiko , Omata Masao 
Published: December 2007

ABSTRACT

The Mongolian gerbil model of
Helicobacter pylori
infection resembles human gastritis. In this study, we investigated the role of NF-κB activation in
H. pylori
-infected gerbils. Activated macrophages were significantly increased in
H. pylori
-infected gastric mucosa and were identified as being important cells with potent activation of NF-κB, which plays an important part in producing proinflammatory cytokines. Macrophage depletion by the administration of clodronate resulted in milder inflammation in gerbils infected with
H. pylori
. In macrophages, the inhibition of IκB kinase β (IKKβ), which is a critical kinase for NF-κB activation, resulted in lower proinflammatory cytokine expression caused by heat-killed
H. pylori
cells. Furthermore, treatment with IKKβ inhibitor resulted in milder inflammation in gerbils with
H. pylori
gastritis. Collectively, our data suggest that
H. pylori
-mediated gastric inflammation critically depends on the efficient recruitment and activation of macrophages, with sufficient NF-κB activation.
Interferons Increase Cell Resistance to Staphylococcal Alpha-Toxin
Authors: Yarovinsky Timur O. , Monick Martha M. , Husmann Matthias , Hunninghake Gary W. 
Published: December 2007

ABSTRACTMany bacterial pathogens, includingStaphylococcus aureus, use a variety of pore-forming toxins as important virulence factors. Staphylococcal alpha-toxin, a prototype β-barrel pore-forming toxin, triggers the release of proinflammatory mediators and induces primarily necrotic death in susceptible cells. However, whether host factors released in response to staphylococcal infections may increase cell resistance to alpha-toxin is not known. Here we show that prior exposure to interferons (IFNs) prevents alpha-toxin-induced membrane permeabilization, the depletion of ATP, and cell death. Moreover, pretreatment with IFN-α decreases alpha-toxin-induced secretion of interleukin 1β (IL-1β). IFN-α, IFN-β, and IFN-γ specifically protect cells from alpha-toxin, whereas tumor necrosis factor alpha (TNF-α), IL-6, and IL-4 have no effects. Furthermore, we show that IFN-α-induced protection from alpha-toxin is not dependent on caspase-1 or mitogen-activated protein kinases, but requires protein synthesis and fatty acid synthase activity. Our results demonstrate that IFNs may increase cell resistance to staphylococcal alpha-toxin via the regulation of lipid metabolism and suggest that interferons play a protective role during staphylococcal infections.
Humoral Responses toPlasmodium falciparumBlood-Stage Antigens and Association with Incidence of Clinical Malaria in Children Living in an Area of Seasonal Malaria Transmission in Burkina Faso, West Africa
Authors: Nebie Issa , Diarra Amidou , Ouedraogo Alphonse , Soulama Issiaka , Bougouma Edith C. , Tiono Alfred B. , Konate Amadou T. , Chilengi Roma , Theisen Michael , Dodoo Daniel , Remarque Ed , Bosomprah Samuel , Milligan Paul , Sirima Sodiomon B. 
Published: December 2007

ABSTRACTThere is longstanding evidence that immunoglobulin G (IgG) has a role in protection against clinical malaria, and human antibodies of the cytophilic subclasses are thought to be particularly critical in this respect. In this cohort study, 286 Burkinabè children 6 months to 15 years old were kept under malaria surveillance in order to assess the protective role of antibody responses against four antigens which are currently being evaluated as vaccine candidates: apical membrane antigen 1 (AMA1), merozoite surface protein 1-19 (MSP1-19), MSP3, and glutamate-rich protein (GLURP). Total IgG, IgM, and IgG subclass responses were measured just before the malaria transmission season. The incidence of malaria was 2.4 episodes per child year of risk. After adjusting for the confounding effects of age, the level of total IgG to GLURP was strongly associated with reduced malaria incidence (incidence rate ratio associated with a doubling of total IgG, 0.79; 95% confidence interval, 0.66 to 0.94;P= 0.009.); there was a borderline statistically significant association between the level of total IgG to MSP3 and malaria incidence and no evidence of an association for total IgG to AMA1 and to MSP1-19. Of the IgG subclass responses studied, only IgG3 and IgG4 against GLURP and IgG1 against AMA1 were associated with reduced risk of clinical malaria. There was no evidence of an interaction between responses to AMA1 and baseline parasitemia in their effects on malaria incidence. Currently included in malaria vaccine formulations for clinical trials in humans, these blood-stage antigens, AMA1 and GLURP, offer good prospects for malaria vaccine development.
Evasion of Innate Immune Responses: Evidence for Mannose Binding Lectin Inhibition of Tumor Necrosis Factor Alpha Production by Macrophages in Response toBlastomyces dermatitidis
Authors: Koneti Adi , Linke Michael J. , Brummer Elmer , Stevens David A. 
Published: December 2007

ABSTRACTSerum factors, including mannose binding lectins (MBL), influence innate responses to microbes. Little is known about the effects of serum factors or MBL on the interaction ofBlastomyces dermatitidis, a pulmonary fungal pathogen, with macrophages or on tumor necrosis factor alpha (TNF-α) production. Since macrophage production of TNF-α is an important innate immune response, we examined a mouse peritoneal macrophage (PM) cell line (RAW) and resident PM from CD-1 mice to study TNF-α production by PM stimulated with heat-killed (HK) or liveB. dermatitidisyeast cells. Mouse serum and heat-inactivated mouse serum inhibited TNF-α production 94% when macrophages were stimulated byB. dermatitidis, whereas mouse immunoglobulin G (IgG) did not have this effect. HKB. dermatitidisincubated with serum and then washed also failed to stimulate significant TNF-α production by PM. By the sandwich immunofluorescent antibody (IFA) method with anti-mouse MBL (MBL-A or -C), we showed that serum MBL bound toB. dermatitidis. When serum was absorbed with HKB. dermatitidisor liveB. dermatitidis, absorbed serum failed to significantly inhibit TNF-α production by RAW cells plusB. dermatitidis, and immunoblotting showed that absorbed serum was depleted of MBL-C. If serum was absorbed with liveB. dermatitidis, unbound serum was eluted, and bound serum factor(s) (BS) was released with guanidine buffer, BS inhibited TNF-α production by PM plusB. dermatitidisin a concentration-dependent manner. BS contained MBL-C, which boundB. dermatitidis, as shown by IFA assay. 1,3-β-Glucan stimulated TNF-α production by PM, and this was inhibited by mouse serum. Treatment ofB. dermatitidiswith anti-1,3-β-glucan antibody inhibited TNF-α production by PM. With anti-1,3-β-glucan antibody, we showed by IFA assay thatB. dermatitidiscontained 1,3-β-glucan. In an IFA study withB. dermatitidis, serum with an anti-mouse IgG conjugate did not result in fluorescence, yet serum blocked IFA staining ofB. dermatitidisby anti-1,3-β-glucan IgG antibody. This indicated that non-IgG serum factors binding toB. dermatitidisprevented access to 1,3-β-glucan by anti-1,3-β-glucan antibody. These results suggest that the mechanism of inhibition of the innate proinflammatory immune response of PM toB. dermatitidisis mediated by serum MBL binding toB. dermatitidisat 1,3-β-glucan sites or sterically masking 1,3-β-glucan sites, thus preventing 1,3-β-glucan stimulation of PM for TNF-α production.
Chlamydia pneumoniaeInfection Increases Adherence of Mouse Macrophages to Mouse Endothelial Cells In Vitro and to Aortas Ex Vivo
Authors: Takaoka Naohisa , Campbell Lee Ann , Lee Amy , Rosenfeld Michael E. , Kuo Cho-Chou 
Published: December 2007

ABSTRACTInteractions between monocytes/macrophages and endothelial cells play an important role in the pathogenesis of atherosclerosis, and the adherence of monocytes to the arterial endothelium is one of the early events in atherogenesis. In the present study, peritoneal macrophages harvested from green fluorescent protein (GFP) transgenic mice were used to analyze howChlamydia pneumoniaeinfection affects the adherence of GFP-macrophages to mouse endothelial cells in vitro and to the aorta from normolipidemic and hyperlipidemic mice ex vivo. In vitro studies showed thatC.pneumoniae-infected GFP-macrophages adhered better than uninfected macrophages to endothelial cells and GFP-macrophages adhered better to infected than uninfected endothelial cells. The ex vivo studies showed thatC.pneumoniae-infected macrophages adhered better than uninfected macrophages to aortas from both normolipidemic and hyperlipidemic C57BL/6J mice and apolipoprotein E (ApoE)-deficient mice. In contrast, adherence ofC.pneumoniae-infected macrophages to the aortas of intercellular adhesion molecule 1 (ICAM-1) knockout mice was not enhanced, suggesting that ICAM-1 is crucial for activation of the adherence ofC.pneumoniae-infected macrophages to the endothelium. In conclusion, the present study defined a homing mechanism by whichC.pneumoniaepromotes the adherence of mononuclear phagocytes to the endothelium at the site of atherosclerotic lesion formation to promote the progression of atherosclerosis.
Immunogenic and Plasminogen-Binding Surface-Associated α-Enolase of
Trichomonas vaginalis
Authors: Mundodi V. , Kucknoor A. S. , Alderete J. F. 
Published: December 2007

ABSTRACT

Trichomonas vaginalis
is a protist that causes the most common human sexually transmitted infection. A
T
.
vaginalis
cDNA expression library was screened with pooled sera from patients with trichomoniasis. A highly reactive cDNA clone of 1,428 bp encoded a trichomonad protein of 472 amino acids with sequence identity to α-enolase (tv-
eno1
). The sequence alignment confirmed the highly conserved nature of the enzyme with 65% to 84% identity among organisms. The expression of tv-
eno1
was up-regulated by contact of parasites with vaginal epithelial cells, and this is the first report demonstrating up-regulation by cytoadherence of a plasminogen-binding α-enolase in
T
.
vaginalis
. Immunofluorescence with monoclonal antibody of nonpermeabilized trichomonads showed tv-ENO1 on the surface. The recombinant tv-ENO1 was expressed in
Escherichia coli
as a glutathione
S
-transferase (GST)::tv-ENO1 fusion protein, which was cleaved using thrombin to obtain affinity-purified recombinant tv-ENO1 protein (tv-rENO1) detectable in immunoblots by sera of patients. Immobilized tv-rENO1 bound human plasminogen in a dose-dependent manner, and plasminogen binding by tv-rENO1 was confirmed in a ligand blot assay. The plasminogen-specific inhibitor ε-aminocaproic acid blocked the tv-rENO1-plasminogen association, indicating that lysines play a role in binding to tv-rENO1. Further, both parasites and tv-rENO1 activate plasminogen to plasmin that is mediated by tissue plasminogen activator. These data indicate that as with other bacterial pathogens, tv-ENO1 is an anchorless, surface-associated glycolytic enzyme of
T
.
vaginalis
.
Dose-Response Model for
Listeria monocytogenes
-Induced Stillbirths in Nonhuman Primates
Authors: Smith Mary Alice , Takeuchi Kazue , Anderson Gary , Ware Glenn O. , McClure Harold M. , Raybourne Richard B. , Mytle Nutan , Doyle Michael P. 
Published: December 2007

ABSTRACT

A dose-response model using rhesus monkeys as a surrogate for pregnant women indicates that oral exposure to 10
7
CFU of
Listeria monocytogenes
results in about 50% stillbirths. Ten of 33 pregnant rhesus monkeys exposed orally to a single dose of 10
2
to 10
10
CFU of
L
.
monocytogenes
had stillbirths. A log-logistic model predicts a dose affecting 50% of animals at 10
7
CFU, comparable to an estimated 10
6
CFU based on an outbreak among pregnant women but much less than the extrapolated estimate (10
13
CFU) from the FDA-U.S. Department of Agriculture-CDC risk assessment using an exponential curve based on mouse data. Exposure and etiology of the disease are the same in humans and primates but not in mice. This information will aid in risk assessment, assist policy makers, and provide a model for mechanistic studies of
L
.
monocytogenes
-induced stillbirths.
Characteristics at haematoxylin and eosin staining of ruptures of the long head of the biceps tendon
Authors: Longo U G , Franceschi F , Ruzzini L , Rabitti C , Morini S , Maffulli N , Denaro V 
Published: December 2007

Objective:To examine the relative prevalence of histological changes that have been found to be associated with the process of tendinopathy in lesions of the tendon of the long head of the biceps brachii and to evaluate the reliability of histopathological evaluation of tendon tissue in lesions of the tendon of the long head of the biceps.Design:Tendon samples were taken from 51 patients (31 men, 20 women; mean age 63.2 years) who underwent arthroscopic release of the long head of the biceps tendon because of refractory biceps tendinopathy and from 5 male patients who died of cardiovascular events (mean age 69.6 years). Histological examination was performed using haematoxylin and eosin staining of sections, which were interpreted using a semiquantitative grading scale assessing fibre structure and arrangement, rounding of the nuclei, regional variations in cellularity, increased vascularity, decreased collagen staining and hyalinisation.Results:The mean (SD) pathological sum score of ruptured tendons was greater than that of control tendons (15.76 (3.11) vs 3.4 (1.9), p<0.001). Within each specific category of tendon abnormalities, the χ2test showed significant differences between the control and ruptured tendons; all the variables were significantly different (Mann–Whitney U test 0.05, p<0.001). Using the κ statistic, the agreement between the two readings ranged from 0.53 to 0.85.Conclusions:Unruptured tendons of the long head of the biceps, even at an advanced age and ruptured tendons of the long head of the biceps are clearly part of two distinct populations.