bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in CD4
+
, CD8
+
, CD4
+
CD8
+
, and Immunoglobulin M-Positive Peripheral Blood Mononuclear Cells of Postweaning Multisystemic Wasting Syndrome-Affected Pigs and Age-Matched Uninfected Wasted and Healthy Pigs Correlate with Lesions and Porcine Circovirus Type 2 Load in Lymphoid Tissues
Authors: Darwich Laila , Segalés Joaquim , Domingo Mariano , Mateu Enric 
Published: July 2002

ABSTRACT

Forty-one 8- to 12-week-old wasted pigs were selected from several conventional farms with histories of postweaning multisystemic wasting syndrome (PMWS) and classified into two groups according to their porcine circovirus type 2 (PCV2) infection status, as determined by in situ hybridization (ISH). Twenty-four pigs tested positive for PCV2 (PCV2-positive group), while 17 pigs tested negative for PCV2 (PCV2-negative group). In addition, eight uninfected healthy pigs from an experimental farm were used as controls. Heparinized blood samples were taken to obtain peripheral blood mononuclear cells. The CD4
+
, CD8
+
, CD4
+
CD8
+
(double-positive [DP]), and immunoglobulin M-positive (IgM
+
) cell subsets were analyzed by flow cytometry with appropriate monoclonal antibodies. Histopathological studies were done to evaluate the apparent degrees of lymphocyte depletion in different lymphoid organs (superficial inguinal and mesenteric lymph nodes, Peyer's patches, tonsils, and spleen) and to determine the viral load of the PCV2 genome by using an ISH technique. Animals of the PCV2-positive group showed a significant downshift of the CD8
+
and DP cell subsets compared to the other groups (
P
< 0.05). Moreover, in PCV2-positive pigs, the amount of PCV2 genome in lymphoid tissues was related to the degree of cell depletion in those tissues (
P
< 0.05) as well as to the relative decrease in IgM
+
and CD8
+
cells in peripheral blood. These data support the notion that PCV2-positive pigs might have an impaired immune response.
Cell-Associated Interleukin-8 in Cord Blood of Term and Preterm Infants
Authors: Dembinski J. , Behrendt D. , Heep A. , Dorn C. , Reinsberg J. , Bartmann P. 
Published: July 2002

ABSTRACTTo assess the effect of gestational age and labor on the interleukin-8 (IL-8) concentration in whole cord blood and serum, IL-8 levels were determined simultaneously in cord blood serum and lysate in 134 infants. Following the elimination of some of the samples due to exclusion criteria, the data for 99 uninfected infants (71 term and 28 preterm) and 9 infants with neonatal bacterial infection delivered either vaginally or by elective or emergency cesarean section were analyzed. The effects of labor and gestational age were tested by analysis of variance. IL-8 was not detectable in the serum of 25 infants, whereas IL-8 levels in whole blood were measurable in all of the samples. The median IL-8 conncentrations in whole cord blood lysate were 106 pg/ml (range, 20 to 415 pg/ml) in preterm infants and 176 pg/ml (range, 34 to 1,667 pg/ml) in term infants. In contrast to the IL-8 levels in serum, IL-8 levels in whole blood were reduced after ECS. Gestational age had no independent effect on the IL-8 concentrations in either serum or whole blood; these concentrations increased in infected infants after labor. We conclude that the neonatal proinflammatory response to labor stress was more evident in the concentrations of IL-8 in whole blood than in serum. The levels of IL-8 in whole-blood lysate reflect proinflammatory stimulation in neonates and may be a useful diagnostic tool for the early diagnosis of neonatal infection.
Pathogenesis of Cerebral Malaria: Recent Experimental Data and Possible Applications for Humans
Authors: Lou Jinning , Lucas Ralf , Grau Georges E. 
Published: July 2002

SUMMARYMalaria still is a major public health problem, partly because the pathogenesis of its major complication, cerebral malaria, remains incompletely understood. Experimental models represent useful tools to better understand the mechanisms of this syndrome. Here, data generated by several models are reviewed both in vivo and in vitro; we propose that some pathogenic mechanisms, drawn from data obtained from experiments in a mouse model, may be instrumental in humans. In particular, tumor necrosis factor (TNF) receptor 2 is involved in this syndrome, implying that the transmembrane form of TNF may be more important than the soluble form of the cytokine. It has also been shown that in addition to differences in immune responsiveness between genetically resistant and susceptible mice, there are marked differences at the level of the target cell of the lesion, namely, the brain endothelial cell. In murine cerebral malaria, a paradoxical role of platelets has been proposed. Indeed, platelets appear to be pathogenic rather than protective in inflammatory conditions because they can potentiate the deleterious effects of TNF. More recently, it has been shown that interactions among platelets, leukocytes, and endothelial cells have phenotypic and functional consequences for the endothelial cells. A better understanding of these complex interactions leading to vascular injury will help improve the outcome of cerebral malaria.
Toxins, Butyric Acid, and Other Short-Chain Fatty Acids Are Coordinately Expressed and Down-Regulated by Cysteine in
Clostridium difficile
Authors: Karlsson Sture , Lindberg Anette , Norin Elisabeth , Burman Lars G. , Åkerlund Thomas 
Published: July 2002

ABSTRACT

It was recently found that a mixture of nine amino acids down-regulate
Clostridium difficile
toxin production when added to peptone yeast extract (PY) cultures of strain VPI 10463 (S. Karlsson, L. G. Burman, and T. Åkerlund, Microbiology 145:1683–1693, 1999). In the present study, seven of these amino acids were found to exhibit a moderate suppression of toxin production, whereas proline and particularly cysteine had the greatest impact, on both reference strains (
n
= 6) and clinical isolates (
n
= 28) of
C. difficile
(>99% suppression by cysteine in the highest toxin-producing strain). Also, cysteine derivatives such as acetylcysteine, glutathione, and cystine effectively down-regulated toxin expression. An impact of both cysteine and cystine but not of thioglycolate on toxin yield indicated that toxin expression was not regulated by the oxidation-reduction potential. Several metabolic pathways, including butyric acid and butanol production, were coinduced with the toxins in PY and down-regulated by cysteine. The enzyme 3-hydroxybutyryl coenzyme A dehydrogenase, a key enzyme in solventogenesis in
Clostridium acetobutylicum
, was among the most up-regulated proteins during high toxin production. The addition of butyric acid to various growth media induced toxin production, whereas the addition of butanol had the opposite effect. The results indicate a coupling between specific metabolic processes and toxin expression in
C. difficile
and that certain amino acids can alter these pathways coordinately. We speculate that down-regulation of toxin production by the administration of such amino acids to the colon may become a novel approach to prophylaxis and therapy for
C. difficile
-associated diarrhea.
Modulation of Neutrophil Chemokine Receptors byStaphylococcus aureusSupernate
Authors: Veldkamp K. E. , Heezius H. C. J. M. , Verhoef J. , van Strijp J. A. G. , van Kessel K. P. M. 
Published: July 2002

ABSTRACTIn a previous study, we showed thatStaphylococcus aureussupernate (SaS) is a potent agonist for both neutrophils and mononuclear cells. To further investigate the immunomodulating effects of SaS, the effect on different neutrophil receptors was studied. Expression of various neutrophil receptors, before and after treatment with SaS, was quantified by flow cytometry. We found that SaS treatment of neutrophils resulted in a specific and total downregulation of the C5a and the fMLP receptor, both serpentine receptors, while other receptors were totally unaffected. Since these two receptors are both involved in chemotaxis, we tested the effect of SaS in calcium flux and chemotaxis assays. We showed that preincubation with SaS abrogated the rise in intracellular calcium concentration upon triggering with fMLP and C5a. We also showed that SaS is a potent inhibitor of neutrophil chemotaxis towards fMLP and C5a, but does not interfere with chemotaxis towards interleukin-8. These findings indicate thatS. aureusproduces a virulence factor extracellularly, which impairs chemotaxis towards the infected site.
Helicobacter pylori
Possesses Two CheY Response Regulators and a Histidine Kinase Sensor, CheA, Which Are Essential for Chemotaxis and Colonization of the Gastric Mucosa
Authors: Foynes Susan , Dorrell Nick , Ward Stephen J. , Stabler Richard A. , McColm Andy A. , Rycroft Andrew N. , Wren Brendan W. 
Published: July 2002

ABSTRACT

Infection of the mucous layer of the human stomach by
Helicobacter pylori
requires the bacterium to be motile and presumably chemotactic. Previous studies have shown that fully functional flagella are essential for motility and colonization, but the role of chemotaxis remains unclear. The two-component regulatory system CheA/CheY has been shown to play a major role in chemotaxis in other enteric bacteria. Scrutiny of the 26695 genome sequence suggests that
H. pylori
has two CheY response regulators: one a separate protein (CheY1) and the other (CheY2) fused to the histidine kinase sensor CheA. Defined deletion mutations were introduced into
cheY1
,
cheY2
, and
cheA
in
H. pylori
strains N6 and SS1. Video tracking revealed that the wild-type
H. pylori
strain moves in short runs with frequent direction changes, in contrast to movement of
cheY2
,
cheAY2
, and
cheAY2 cheY1
mutants, whose motion was more linear. The
cheY1
mutant demonstrated a different motility phenotype of rapid tumbling. All mutants had impaired swarming and greatly reduced chemotactic responses to hog gastric mucin. Neither
cheY1
nor
cheAY2
mutants were able to colonize mice, but they generated a significant antibody response, suggesting that despite impaired chemotaxis, these mutants were able to survive in the stomach long enough to induce an immune response before being removed by gastric flow. Additionally, we demonstrated that
cheY1
failed to colonize gnotobiotic piglets. This study demonstrates the importance of the roles of
cheY1
,
cheY2
, and
cheA
in motility and virulence of
H. pylori
.
Characterization of Conserved T- and B-Cell Epitopes inPlasmodium falciparumMajor Merozoite Surface Protein 1
Authors: Parra Marcela , Hui George , Johnson Armead H. , Berzofsky Jay A. , Roberts Theodore , Quakyi Isabella A. , Taylor Diane W. 
Published: July 2002

ABSTRACTVaccines forP. falciparumwill need to contain both T- and B-cell epitopes. Conserved epitopes are the most desirable, but they are often poorly immunogenic. The major merozoite surface protein 1 (MSP-1) is currently a leading vaccine candidate antigen. In this study, six peptides from conserved or partly conserved regions of MSP-1 were evaluated for immunogenicity in B10 congenic mice. Following immunization with the peptides, murine T cells were tested for the ability to proliferate in vitro and antibody responses to MSP-1 were evaluated in vivo. The results showed that one highly conserved sequence (MSP-1#1, VTHESYQELVKKLEALEDAV; located at amino acid positions 20 to 39) and one partly conserved sequence (MSP-1#23, GLFHKEKMILNEEEITTKGA; located at positions 44 to 63) contained both T- and B-cell epitopes. Immunization of mice with these peptides resulted in T-cell proliferation and enhanced production of antibody to MSP-1 upon exposure to merozoites. MSP-1#1 stimulated T-cell responses in three of the six strains of mice evaluated, whereas MSP-1#23 was immunogenic in only one strain. Immunization with the other four peptides resulted in T-cell responses to the peptides, but none of the resulting peptide-specific T cells recognized native MSP-1. These results demonstrate that two sequences located in the N terminus of MSP-1 can induce T- and B-cell responses following immunization in a murine model. Clearly, these sequences merit further consideration for inclusion in a vaccine for malaria.
Role of EspB in Experimental Human Enteropathogenic
Escherichia coli
Infection
Authors: Tacket Carol O. , Sztein Marcelo B. , Losonsky Genevieve , Abe Akio , Finlay B. Brett , McNamara Barry P. , Fantry George T. , James Stephen P. , Nataro James P. , Levine Myron M. , Donnenberg Michael S. 
Published: July 2002

ABSTRACT

Enteropathogenic
Escherichia coli
(EPEC), a leading cause of diarrhea among infants in developing countries, induces dramatic alterations in host cell architecture that depend on a type III secretion system. EspB, one of the proteins secreted and translocated to the host cytoplasm via this system, is required for numerous alterations in host cell structure and function. To determine the role of EspB in virulence, we conducted a randomized, double-blind trial comparing the ability of wild-type EPEC and an isogenic Δ
espB
mutant strain to cause diarrhea in adult volunteers. Diarrhea developed in 9 of 10 volunteers who ingested the wild-type strain but in only 1 of 10 volunteers who ingested the Δ
espB
mutant strain. Marked destruction of the microvillous brush border adjacent to adherent organisms was observed in a jejunal biopsy from a volunteer who ingested the wild-type strain but not from two volunteers who ingested the Δ
espB
mutant strain. Humoral and cell-mediated immune responses to EPEC antigens were stronger among recipients of the wild-type strain. In addition, four of the volunteers who ingested the wild-type strain had lymphoproliferative responses to EspB. These results demonstrate that EspB is a critical virulence determinant of EPEC infections and suggest that EspB contributes to an immune response.
Salmonella enterica
Serovars Typhimurium and Dublin Can Lyse Macrophages by a Mechanism Distinct from Apoptosis
Authors: Watson Patricia R. , Gautier Anne V. , Paulin Sue M. , Bland A. Patricia , Jones Philip W. , Wallis Timothy S. 
Published: July 2002

ABSTRACT

Salmonella enterica
serovars Typhimurium and Dublin lysed primary bovine alveolar macrophages and immortalized J774.2 macrophage-like cells in the absence of either the morphological changes or DNA fragmentation characteristic of apoptosis. Macrophage lysis was dependent on a subset of caspases and an intact
sipB
gene.
Identification of Three Essential Regulatory Gene Loci Governing Expression of
Staphylococcus epidermidis
Polysaccharide Intercellular Adhesin and Biofilm Formation
Authors: Mack Dietrich , Rohde Holger , Dobinsky Sabine , Riedewald Joachim , Nedelmann Max , Knobloch Johannes K.-M. , Elsner Holger-A. , Feucht Hubert H. 
Published: July 2002

ABSTRACT

The formation of adherent multilayered biofilms embedded into a glycocalyx represents an essential factor in the pathogenesis of
Staphylococcus epidermidis
biomaterial-related infections. Using biofilm-producing
S. epidermidis
1457 and transposon Tn
917
carried on plasmid pTV1ts, we isolated nine isogenic biofilm-negative transposon mutants. Transduction by
S. epidermidis
phage 71 was used to prove the genetic linkage of transposon insertions and altered phenotypes. Mapping of the different transposon insertions by Southern hybridization and pulsed-field gel electrophoresis indicated that these were inserted in four unlinked genetic loci. According to their phenotypes, including quantitative differences in biofilm production in different growth media, in the amount of the polysaccharide intercellular adhesin (PIA) produced, in the hemagglutination titers, and in the altered colony morphology, the mutants could be separated into four phenotypic classes corresponding with the genetic classes. Synthesis of PIA was not detectable with class I and II mutants, whereas the amount of PIA produced reflected the residual degree of biofilm production of class III and IV mutants in different growth media. Chromosomal DNA flanking the transposon insertions of five class I mutants was cloned and sequenced, and the insertions were mapped to different locations of
icaADBC
, representing the synthetic genes for PIA. Expression of
icaADBC
from a xylose-dependent promoter in the different isogenic mutant classes reconstituted biofilm production in all mutants. In a Northern blot analysis no
icaADBC
-specific transcripts were observed in RNA isolated from mutants of classes II, III, and IV. Apparently, in addition to
icaADBC
, three other gene loci have a direct or indirect regulatory influence on expression of the synthetic genes for PIA on the level of transcription.
A Novel Factor Isolated fromActinobacillus actinomycetemcomitansStimulates Mouse B Cells and Human Peripheral Blood Mononuclear Cells
Authors: Jeong Soo-Jin , Yee Sung-Tae , Jo Wol-Soon , Yu Seong-Ho , Lee Sang-Hwa , Lim Young-Jin , Yoo Young-Hyun , Kim Jung-Man , Lee Jae-Dong , Jeong Min-Ho 
Published: July 2002

ABSTRACTA novel immunostimulating factor (ISTF) ofActinobacillus actinomycetemcomitansATCC 29522 was isolated and characterized as inducing proliferation of mouse B cells and human peripheral blood mononuclear cells. This factor was isolated from the bacterial culture medium and purified by size exclusion chromatography, dye-ligand affinity chromatography, immunoaffinity chromatography using monoclonal antibodies, and preparative electrophoresis. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the purified ISTF migrated as a single band corresponding to a molecular mass of 13 kDa. ISTF was a proteinaceous material distinct from lipopolysaccharide; it directly induced the proliferation of B lymphocytes but had no effect on the proliferation of T lymphocytes, even in the presence of antigen-presenting cells. A B-lymphocyte-mitogenic activity of ISTF was also shown by flow cytometric analysis of responding cell subpopulations. Immunoblot analysis revealed that ISTF was a component of the outer membranes of bacteria, could exist as a soluble form, and was released by growing and/or lysed bacteria. These results suggest that ISTF produced byA. actinomycetemcomitansmay play an important role in immunopathologic changes associated withA. actinomycetemcomitansinfections.
Single-Copy
IMH3
Allele Is Sufficient To Confer Resistance to Mycophenolic Acid in
Candida albicans
and To Mediate Transformation of Clinical
Candida
Species
Authors: Beckerman Janna , Chibana Hiroji , Turner Joshua , Magee P. T. 
Published: July 2002

ABSTRACT

Parasexual genetic analysis of
Candida albicans
utilized the dominant selectable marker that conferred resistance to mycophenolic acid. We cloned and sequenced the
IMH3
r
gene from
C. albicans
strain 1006, which was previously identified as resistant to mycophenolic acid (MPA) (A. K. Goshorn and S. Scherer, Genetics 123:213–218, 1989). MPA is an inhibitor of IMP dehydrogenase, an enzyme necessary for the de novo biosynthesis of GMP. G. A. Kohler et al. (J. Bacteriol. 179:2331–2338, 1997) have shown that the wild-type
IMH3
gene, when expressed in high copy number, will confer resistance to this antibiotic. We demonstrate that the
IMH3
r
gene from strain 1006 has three amino acid changes, two of which are nonconservative, and demonstrate that at least two of the three mutations are required to confer resistance to MPA. We used this gene as a dominant selectable marker in clinical isolates of
C. albicans
and
Candida tropicalis
. We also identified the presence of autonously replicating sequence elements that permit autonomous replication in the promoter region of this gene. Finally, we found the excision of a φ-type long terminal repeat element outside the
IMH3
open reading frame of the gene in some strains. We used the
IMH3
r
allele to disrupt one allele of
ARG4
in two clinical isolates, WO-1 and FC18, thus demonstrating that a single ectopic integration of this dominant selectable marker is sufficient to confer resistance to MPA.
Release of Toll-Like Receptor-2-Activating Bacterial Lipoproteins inShigella flexneriCulture Supernatants
Authors: Aliprantis Antonios O. , Weiss David S. , Radolf Justin D. , Zychlinsky Arturo 
Published: July 2002

ABSTRACTShigellaspp. cause dysentery, a severe form of bloody diarrhea. Apoptosis, or programmed cell death, is induced duringShigellainfections and has been proposed to be a key event in the pathogenesis of dysentery. Here, we describe a novel cytotoxic activity in the sterile-culture supernatants ofShigella flexneri. An identical activity was identified in purifiedS. flexneriendotoxin, defined here as a mixture of lipopolysaccharide (LPS) and endotoxin-associated proteins (EP). Separation of endotoxin into EP and LPS revealed the activity to partition exclusively to the EP fraction. Biochemical characterization ofS. flexneriEP and culture supernatants, including enzymatic deactivation, reverse-phase high-pressure liquid chromatography analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and a Toll-like receptor-2 (TLR2) activation assay, indicates that the cytotoxic component is a mixture of bacterial lipoproteins (BLP). We show that biologically active BLP are liberated into culture supernatants of actively growingS. flexneri. In addition, our data indicate that BLP, and not LPS, are the component of endotoxin of gram-negative organisms responsible for activating TLR2. The activation of apoptosis by BLP shed fromS. flexneriis discussed as a novel aspect of the interaction of bacteria with the host.
Plasmodium falciparumGenotypes, Low Complexity of Infection, and Resistance to Subsequent Malaria in Participants in the Asembo Bay Cohort Project
Authors: Branch Oralee H. , Takala Shannon , Kariuki Simon , Nahlen Bernard L. , Kolczak Margaret , Hawley William , Lal Altaf A. 
Published: July 2002

ABSTRACTTo assess the relationship between the within-host diversity of malaria infections and the susceptibility of the host to subsequent infection, we genotyped 60 children's successive infections from birth through 3 years of life. MSP-1 Block2 genotypes were used to estimate the complexity of infection (COI). Malaria transmission and age were positively associated with the number of K1 and Mad20 alleles detected (COIKM) (P< 0.003). Controlling for previous parasitemia, transmission, drug treatment, parasite density, sickle cell, and age, COIKMwas negatively correlated with resistance to parasitemia of >500/μl (P< 0.0001). Parasitemias with the RO-genotype were more resistant than those without this genotype (P< 0.0000). The resistance in low COIKMinfections was not genotype specific. We discuss the impact of genotype-transcending immunity to conserved antigenic determinants. We also propose a diversity-driven immunomodulation hypothesis that may explain the delayed development of natural immunity in the first few years of life and suggest that interventions that decrease the COIKMcould facilitate the development of protective immunity.