bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macrophage Migration Inhibitory Factor Release by Macrophages after Ingestion ofPlasmodium chabaudi-Infected Erythrocytes: Possible Role in the Pathogenesis of Malarial Anemia
Authors: Martiney James A. , Sherry Barbara , Metz Christine N. , Espinoza Marisol , Ferrer Angel S. , Calandra Thierry , Broxmeyer Hal E. , Bucala Richard 
Published: July 2002

ABSTRACTHuman falciparum malaria, caused byPlasmodium falciparuminfection, results in 1 to 2 million deaths per year, mostly children under the age of 5 years. The two main causes of death are severe anemia and cerebral malaria. Malarial anemia is characterized by parasite red blood cell (RBC) destruction and suppression of erythropoiesis (the mechanism of which is unknown) in the presence of a robust host erythropoietin response. The production of a host-derived erythropoiesis inhibitor in response to parasite products has been implicated in the pathogenesis of malarial anemia. The identity of this putative host factor is unknown, but antibody neutralization studies have ruled out interleukin-1β, tumor necrosis factor alpha, and gamma interferon while injection of interleukin-12 protects susceptible mice against lethalP. chabaudiinfection. In this study, we report that ingestion ofP. chabaudi-infected erythrocytes or malarial pigment (hemozoin) induces the release of macrophage migration inhibitory factor (MIF) from macrophages. MIF, a proinflammatory mediator and counter-regulator of glucocorticoid action, inhibits erythroid (BFU-E), multipotential (CFU-GEMM), and granulocyte-macrophage (CFU-GM) progenitor-derived colony formation. MIF was detected in the sera ofP. chabaudi-infected BALB/c mice, and circulating levels correlated with disease severity. Liver MIF immunoreactivity increased concomitant with extensive pigment and parasitized RBC deposition. Finally, MIF was elevated three- to fourfold in the spleen and bone marrow ofP. chabaudi-infected mice with active disease, as compared to early disease, or of uninfected controls. In summary, the present results suggest that MIF may be a host-derived factor involved in the pathophysiology of malaria anemia.
Invasion of the Brain and Chronic Central Nervous System Infection after SystemicMycobacterium aviumComplex Infection in Mice
Authors: Wu Hsiu-Shan , Kolonoski Peter , Chang Yung Yee , Bermudez Luiz E. 
Published: July 2002

ABSTRACTCentral nervous system (CNS) infections caused by nontuberculous mycobacteria have been described previously, especially in patients with AIDS. To investigate specific aspects of the pathogenesis of this entity, C57BLbg+/bg−mice were infected intravenously withMycobacterium avium, and cultures of blood and brain as well as histopathology examination of brain tissue were carried out at several time points up to 6 months after infection. Low-grade inflammatory changes with small aggregates of lymphocytes and macrophages as well as perivascular cuffing were seen early in the infection. A small number of bacteria could be observed in the parenchyma of the choroid plexus. Six months after infection, numerous bacteria were present within the foamy macrophage of the granulomatous lesions along the ventricle and meninges. None of the mice developed clinical signs of meningitis or encephalitis or even died spontaneously during the period of observation. Use of CD18−/−knockout mice indicated that transport of the bacterium within neutrophils or monocytes into the brain is unlikely. Mild chronic CNS infection developed in the mice during sustained systemicM. aviuminfection, similar to what has been reported in most human cases.
Inhibition of Adhesion ofEscherichia coliK88ac Fimbria to Its Receptor, Intestinal Mucin-Type Glycoproteins, by a Monoclonal Antibody Directed against a Variable Domain of the Fimbria
Authors: Sun Ronggai , Anderson Timothy J. , Erickson Alan K. , Nelson Eric A. , Francis David H. 
Published: July 2002

ABSTRACTStrains of enterotoxigenicEscherichia colithat express K88 fimbriae are among the most common causes of diarrhea in young pigs. Adhesion of bacteria to receptors on intestinal epithelial cells, mediated by K88 fimbriae, is the initial step in the establishment of infection. Three antigenic variants of K88 fimbriae exist in nature: K88ab, K88ac, and K88ad. K88ac is the most prevalent and may be the only variant of significance in swine disease. Each K88 fimbrial variant is composed of multiple antigenic determinants. Some of these determinants are shared among the three variants and may be referred to as conserved epitopes, whereas others are unique to a specific variant and may be referred to as variable epitopes. In this study, monoclonal antibodies (MAbs) specific to either variable or conserved epitopes of K88ac fimbriae were produced. The specificity of each MAb was tested by enzyme-linked immunosorbent and immunoblot assays. Fab fragments were prepared from these MAbs and were tested for their ability to block the binding of K88-positive bacteria and purified fimbriae to porcine enterocyte brush border vesicles and purified K88 receptors, respectively. The purified receptors were intestinal mucin-type sialoglycoproteins (IMTGP) isolated from porcine enterocytes (A. K. Erickson, D. R. Baker, B. T. Bosworth, T. A. Casey, D. A. Benfield, and D. H. Francis, Infect. Immun. 62:5404–5410, 1994). Fab fragments prepared from MAbs specific for variable epitopes blocked the binding of bacteria to brush borders and of fimbriae to IMTGP. However, those from MAbs specific for a conserved epitope did not. These observations indicate that the receptor-binding domain of a K88ac fimbria is contained, at least in part, within the antigenically variable epitopes of that fimbria. Epitope mapping for one of the MAbs, which recognizes a linear epitope on K88ac fimbriae, indicated that this MAb binds to the region from amino acid no. 64 to no. 107 on the major subunit of K88ac fimbriae.
Monitoring BioluminescentStaphylococcus aureusInfections in Living Mice Using a NovelluxABCDEConstruct
Authors: Francis Kevin P. , Joh Danny , Bellinger-Kawahara Carolyn , Hawkinson Matthew J. , Purchio Tony F. , Contag Pamela R. 
Published: July 2002

ABSTRACTStrains ofStaphylococcus aureuswere transformed with plasmid DNA containing aPhotorhabdus luminescens luxoperon (luxABCDE) that was genetically modified to be functional in both gram-positive and gram-negative bacteria.S. aureuscells containing this novelluxconstruct, downstream of an appropriate promoter sequence, are highly bioluminescent, allowing the detection of fewer than 100 CFU in vitro (direct detection of exponentially dividing cells in liquid culture). Furthermore, these bacteria produce light stably at 37°C and do not require exogenous aldehyde substrate, thus allowingS. aureusinfections in living animals to be monitored by bioluminescence. Two strains ofS. aureus8325-4 that produce high levels of constitutive bioluminescence were injected into the thigh muscles of mice, and the animals were then either treated with the antibiotic amoxicillin or left untreated. Bioluminescence from bacteria present in the thighs of the mice was monitored in vivo over a period of 24 h. The effectiveness of the antibiotic in the treated animals could be measured by a decrease in the light signal. At 8 h, the infection in both groups of treated animals had begun to clear, as judged by a decrease in bioluminescence, and by 24 h no light signal could be detected. In contrast, both groups of untreated mice had strong bioluminescent signals at 24 h. Quantification of CFU from bacteria extracted from the thigh muscles of the mice correlated well with the bioluminescence data. This paper shows for the first time that bioluminescence offers a method for monitoringS. aureusinfections in vivo that is sensitive and noninvasive and requires fewer animals than conventional methodologies.
Adjuvant Activity of a Nontoxic Mutant ofEscherichia coliHeat-Labile Enterotoxin on Systemic and Mucosal Immune Responses Elicited against a Heterologous Antigen Carried by a LiveSalmonella entericaSerovar Typhimurium Vaccine Strain
Authors: Guillobel Heloisa C. R. , Carinhanha Joana I. , Cárdenas Lucia , Clements John D. , de Almeida Darcy F. , Ferreira Luís C. S. 
Published: July 2002

ABSTRACTSystemic and mucosal antibody responses against both the major subunit of colonization factor antigen I (CFA/I) of enterotoxigenicEscherichia coli(ETEC) and the somatic lipopolysaccharide expressed by recombinant bivalentSalmonellavaccine strains were significantly enhanced by coadministration of a detoxified derivative with preserved adjuvant effects of the ETEC heat-labile toxin, LT(R192G). The results further support the adjuvant effects of LT(R192G)and represent a simple alternative to improve responses against passenger antigens expressed by orally deliveredSalmonellavaccine strains.
Cloning of Genes of Nontypeable
Haemophilus influenzae
Involved in Penetration between Human Lung Epithelial Cells
Authors: van Schilfgaarde Muriel , van Ulsen Peter , van der Steeg Wim , Winter Victor , Eijk Paul , Everts Vincent , Dankert Jacob , van Alphen Loek 
Published: July 2002

ABSTRACT

Haemophilus influenzae
penetrates between epithelial cells via an unknown mechanism. A chromosomal library of nonencapsulated
H. influenzae
strain A960053 DNA was constructed in
Escherichia coli
DH5α to identify bacterial genes contributing to this paracytosis. Two
E. coli
clones that contained open reading frames (ORFs) homologous to HI0636 to HI0641 of
H. influenzae
strain Rd and that showed an increased penetration in epithelial cell layers of the human bronchial epithelial cell line NCI-H292 were identified. ORFs HI0636 and HI0638, encoding two small proteins of unknown functions, were further investigated. The clone containing ORFs HI0636 and HI0637 as well as the clone containing ORF HI0638 showed a significant increase in penetration. Disruption of HI0638 by kanamycin box insertion in
H. influenzae
strain A960053 resulted in loss of penetration into the epithelial cell layers. Disruption of HI0636 had no effect on penetration in this model system. Since a role for HI0637 in the paracytosis of
H. influenzae
is very unlikely because it encodes TrpS, we conclude that the protein encoded by ORF HI0638 may function as a paracytin, while that encoded by HI0636 may have an auxiliary function.
Regulation of Human β-Defensins by Gastric Epithelial Cells in Response to Infection withHelicobacter pylorior Stimulation with Interleukin-1
Authors: O'Neil Deborah A. , Cole Sheri P. , Martin-Porter Edith , Housley Michael P. , Liu Lide , Ganz Tomas , Kagnoff Martin F. 
Published: July 2002

ABSTRACTGastric epithelial cells in vitro and in vivo are shown to constitutively express the peptide antibiotic human β-defensin type 1 (hBD-1). In contrast, hBD-2 expression is regulated in gastric epithelial cells and increases in response to infection withHelicobacter pylorior stimulation with the proinflammatory cytokine interleukin-1. These data suggest that hBD-2 is a component of the regulated host gastric epithelial cell response toH. pyloriinfection and proinflammatory mediators.
Cyclophosphamide Decreases Nitrotyrosine Formation and Inhibits Nitric Oxide Production by Alveolar Macrophages in Mycoplasmosis
Authors: Hickman-Davis Judy M. , Lindsey J. Russell , Matalon Sadis 
Published: July 2002

ABSTRACT

We previously reported that congenic C57BL/6 inducible nitric oxide synthase
−/−
(iNOS
−/−
) mice infected with
Mycoplasma pulmonis
developed higher bacterial numbers and lung lesion scores than C57BL/6 iNOS
+/+
controls but had similar lung nitrotyrosine levels. The present studies investigated the role of inflammatory cells in nitrotyrosine formation during mycoplasmal infection. iNOS
+/+
and iNOS
−/−
mice were injected with cyclophosphamide (CYP) and inoculated with 10
7
CFU of
M. pulmonis
. CYP pretreatment of
M. pulmonis
-infected iNOS
+/+
and iNOS
−/−
mice reduced polymorphonuclear cells (PMNs) within bronchoalveolar lavages (BALs) by 88 and 72%, respectively, and whole-lung myeloperoxidase levels by 80 and 78%, respectively, at 72 h postinfection but did not alter the number of alveolar macrophages (AMs) in BALs. CYP treatment also significantly decreased nitrate and nitrite (NOx) levels in BALs and plasma of infected iNOS
+/+
mice, whereas neither CYP nor mycoplasmal infection altered NOx in iNOS
−/−
mice. CYP reduced lung nitrotyrosine levels in both iNOS
+/+
and iNOS
−/−
mice to uninfected-control levels as shown by immunohistochemical staining and enzyme-linked immunosorbent assay and inhibited mycoplasmal killing by iNOS
+/+
mice in vivo. CYP inhibited the production of gamma interferon-inducible NOx by iNOS
+/+
AMs in vitro but did not alter the number of iNOS-positive AMs, as detected by immunocytochemistry. In addition, AMs from CYP-treated iNOS
+/+
mice had significantly decreased ability to kill mycoplasmas in vitro. These results demonstrate that reactive species generated by inflammatory cells as well as PMN myeloperoxidase are important contributors to nitrotyrosine formation during mycoplasmal infection and that treatment with CYP decreases NO
⋅
production by AMs and inhibits mycoplasmal killing.
Characterization of FasG Segments Required for 987P Fimbria-Mediated Binding to Piglet Glycoprotein Receptors
Authors: Choi Byung-Kwon , Schifferli Dieter M. 
Published: July 2002

ABSTRACT

The 987P fimbriae of enterotoxigenic strains of
Escherichia coli
bind to both glycoprotein and glycolipid receptors on the brush borders of piglet enterocytes. A mutation in lysine residue 117 of the adhesive subunit FasG [
fasG
(K117A)] previously shown to abrogate 987P binding to the lipid receptor sulfatide did not affect the interaction with the glycoprotein receptors. Both the fimbriae and the FasG subunits of the wild type and the
fasG
(K117A) mutant bound to the glycoprotein receptors, confirming that lysine 117 was not required for binding to the glycoprotein receptors. Truncated FasG molecules were used to identify domains required for glycoprotein receptor recognition. At least two segments which did not include lysine117, namely, residues 211 (glutamine) to 220 (serine) and 20 (aspartic acid) to 41 (serine), were shown to be involved in the FasG-glycoprotein receptor interactions by ligand-blotting assays. Changing isoleucine 217 or leucine 215 of FasG to alanine abolished the property of a truncated FasG fusion protein to inhibit 987P recognition of its glycoprotein receptors. Thus, the K117 residue of FasG is required only for binding to the glycolipid receptor, whereas the newly identified hydrophobic residues of the FasG subunit are required specifically for the recognition of the glycoprotein receptor. Taken together, our data indicate that different residues of the FasG adhesin are important in 987P fimbrial binding to sulfatide and glycoprotein receptors, suggesting different mechanisms of interaction.
Dual-Function Vaccine for
Pseudomonas aeruginosa
: Characterization of Chimeric Exotoxin A-Pilin Protein
Authors: Hertle Ralf , Mrsny Randall , Fitzgerald David J. 
Published: July 2002

ABSTRACT

Pseudomonas aeruginosa
is the major infectious agent of concern for cystic fibrosis patients. Strategies to prevent colonization by this bacterium and/or neutralize its virulence factors are clearly needed. Here we characterize a dual-function vaccine designed to generate antibodies to reduce bacterial adherence and to neutralize the cytotoxic activity of exotoxin A. To construct the vaccine, key sequences from type IV pilin were inserted into a vector encoding a nontoxic (active-site deletion) version of exotoxin A. The chimeric protein, termed PE64Δ553pil, was expressed in
Escherichia coli
, refolded to a near-native conformation, and then characterized by various biochemical and immunological assays. PE64Δ553pil bound specifically to asialo-GM1, and, when injected into rabbits, produced antibodies that reduced bacterial adherence and neutralized the cell-killing activity of exotoxin A. Results support further evaluation of this chimeric protein as a vaccine to prevent
Pseudomonas
colonization in susceptible individuals.
How Giardia Swim and Divide
Authors: Ghosh Sudip , Frisardi Marta , Rogers Rick , Samuelson John 
Published: July 2002

ABSTRACT

To determine how binuclear giardia swim, we used video microscopy to observe trophozoites of
Giardia intestinalis
, which were labeled with an amino-specific Alexa Fluor dye that highlighted the flagella and adherence disc. Giardia swam forward by means of the synchronous beating of anterior, posterolateral, and ventral flagella in the plane of the ventral disc, while caudal flagella swam in a plane perpendicular to the disc. Giardia turned in the plane of the disc by means of a rudder-like motion of its tail, which was constant rather than beating. To determine how giardia divide, we used three-dimensional confocal microscopy, the same surface label, nuclear stains, and antitubulin antibodies. Giardia divided with mirror-image symmetry in the plane of the adherence disc, so that the right nucleus of the mother became the left nucleus of the daughter. Pairs of nuclei were tethered together by microtubules which surrounded nuclei and prevented mother or daughter giardia from receiving two copies of the same nucleus. New adherence discs formed upon a spiral backbone of microtubules, which had a clockwise rotation when viewed from the ventral surface. These dynamic observations of the parasite begin to reveal how giardia swim and divide.
Infection of Synovial Fibroblasts in Culture by
Yersinia enterocolitica
and
Salmonella enterica
Serovar Enteritidis: Ultrastructural Investigation with Respect to the Pathogenesis of Reactive Arthritis
Authors: Meyer-Bahlburg Almut , Brinkhoff Jörg , Krenn Veit , Trebesius Karlheinz , Heesemann Jürgen , Huppertz Hans-Iko 
Published: July 2002

ABSTRACT

Synovial fibroblasts were infected with
Yersinia enterocolitica
or
Salmonella enterica
serovar Enteritidis and analyzed by electron microscopy and fluorescence in situ hybridization. Intracellular bacterial replication was followed by degradation leading to “ghosts” possessing lipopolysaccharides but not DNA. However, single bacteria survived for more than 2 weeks. Therefore, transient intra-articular infection might be the missing link between initial intestinal infection and late synovial inflammation in the pathogenesis of reactive arthritis.
Human Infection withAscaris lumbricoidesIs Associated with Suppression of the Interleukin-2 Response to Recombinant Cholera Toxin B Subunit following Vaccination with the Live Oral Cholera Vaccine CVD 103-HgR
Authors: Cooper Philip J. , Chico Martha , Sandoval Carlos , Espinel Ivan , Guevara Angel , Levine Myron M. , Griffin George E. , Nutman Thomas B. 
Published: July 2002

ABSTRACTTo investigate the potential immunomodulatory effects of concurrent ascariasis on the cytokine response to a live oral vaccine, we measured cytokine responses to cholera toxin B subunit (CT-B) following vaccination with the live oral cholera vaccine CVD 103-HgR inAscaris lumbricoides-infected subjects randomized in a double-blind study to receive two doses of either albendazole or placebo prior to vaccination and in a group of healthy U.S. controls. Postvaccination cytokine responses to CT-B were characterized by transient increases in the production of interleukin-2 (IL-2;P= 0.02) and gamma interferon (IFN-γ;P= 0.001) in the three study groups combined; however, postvaccination increases in IFN-γ were significant only in the albendazole-treatedA. lumbricoidesinfection group (P= 0.008). Postvaccination levels of IL-2 were significantly greater in the albendazole-treated group compared with the placebo group (P= 0.03). No changes in levels of Th1 and Th2 cytokines in response to control ascaris antigens were observed over the same period. These findings indicate that vaccination with CVD 103-HgR is associated with a Th1 cytokine response (IL-2 and IFN-γ) to CT-B, that infection withA. lumbricoidesdiminishes the magnitude of this response, and that albendazole treatment prior to vaccination was able to partially reverse the deficit in IL-2. The potential modulation of the immune response to oral vaccines by geohelminth parasites has important implications for the design of vaccination campaigns in geohelminth-endemic areas.
Rat Mannose-Binding Protein A Binds CD14
Authors: Chiba Hirofumi , Sano Hitomi , Iwaki Daisuke , Murakami Seiji , Mitsuzawa Hiroaki , Takahashi Toru , Konishi Masanori , Takahashi Hiroki , Kuroki Yoshio 
Published: July 2002

ABSTRACTLipopolysaccharide (LPS) has been known to induce inflammation by interacting with CD14, which serves as a receptor for LPS. Mannose-binding protein (MBP) belongs to the collectin subgroup of the C-type lectin superfamily, along with surfactant proteins SP-A and SP-D. We have recently demonstrated that SP-A modulates LPS-induced cellular responses by interaction with CD14 (H. Sano, H. Sohma, T. Muta, S. Nomura, D. R. Voelker, and Y. Kuroki, J. Immunol. 163:387–395, 2000) and that SP-D also interacts with CD14 (H. Sano, H. Chiba, D. Iwaki, H. Sohma, D. R. Voelker, and Y. Kuroki, J. Biol. Chem. 275:22442–22451, 2000). In this study, we examined whether MBP, a collectin highly homologous to SP-A and SP-D, could bind CD14. Recombinant rat MBP-A bound recombinant human soluble CD14 in a concentration-dependent manner. Its binding was not inhibited in the presence of excess mannose or EDTA. MBP-A bound deglycosylated CD14 treated withN-glycosidase F, neuraminidase, andO-glycosidase, indicating that MBP-A interacts with the peptide portion of CD14. Since LPS was also a ligand for the collectins, we compared the characteristics of binding of MBP-A to LPS with those of binding to CD14. MBP-A bound to lipid A fromSalmonella entericaserovar Minnesota and rough LPS (S. entericaserovar Minnesota Re595 andEscherichia coliJ5, Rc), but not to smooth LPS (E. coliO26:B6 and O111:B4). Unlike CD14 binding, EDTA and excess mannose attenuated the binding of MBP-A to rough LPS. From these results, we conclude that CD14 is a novel ligand for MBP-A and that MBP-A utilizes a different mechanism for CD14 recognition from that for LPS.
Acid-Induced Gene Expression in
Helicobacter pylori
: Study in Genomic Scale by Microarray
Authors: Ang Sunny , Lee Cha-Ze , Peck Konan , Sindici Michelle , Matrubutham Udayakumar , Gleeson Martin A. , Wang Jin-Town 
Published: July 2002

ABSTRACT

To understand the RNA expression in response to acid stress of
Helicobacter pylori
in genomic scale, a microarray membrane containing 1,534 open reading frames (ORFs) from strain 26695 was used. Total RNAs of
H. pylori
under growth conditions of pH 7.2 and 5.5 were extracted, reverse transcribed into cDNA, and labeled with biotin. Each microarray membrane was hybridized with cDNA probe from the same strain under two different pH conditions and developed by a catalyzed reporter deposition method. Gene expression of all ORFs was measured by densitometry. Among the 1,534 ORFs, 53 ORFs were highly expressed (≧30% of rRNA control in densitometry ratios). There were 445 ORFs which were stably expressed (<30% of rRNA in densitometry) under both pH conditions without significant variation. A total of 80 ORFs had significantly increased expression levels at low pH, while expressions of 4 ORFs were suppressed under acidic condition. The remaining 952 ORFs were not detectable under either pH condition. These data were highly reproducible and comparable to those obtained by the RNA slot blot method. Our results suggest that microarray can be used in monitoring prokaryotic gene expression in genomic scale.