bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Chlamydial Genital Infection Resulting from Sexual Transmission from Male to Female Guinea Pigs and Determination of Infectious Dose
Authors: Rank Roger G. , Bowlin Anne K. , Reed Ronald L. , Darville Toni 
Published: October 2003

ABSTRACT

A major problem in the study of chlamydial genital infections in animal models has been the use of varied doses of chlamydiae for infection in different laboratories. It is clearly desirable to use a dose which approximates that of natural sexual infection, but that dose to date has not been determined because of the inability of researchers to quantify chlamydiae in semen. Fortunately, sexual transmission of chlamydiae has been described for the guinea pig model of infection with the chlamydial agent of guinea pig inclusion conjunctivitis (GPIC). In this study, we undertook to determine the approximate infection dose in actual sexual transmission by comparing the kinetics of infection in female guinea pigs acquired via sexual contact to those of genital infections induced artificially with known quantities of chlamydiae. Groups of guinea pigs were infected intravaginally with 10
4
, 10
3
, 10
2
, and 10
1
inclusion-forming units (IFU) of GPIC, and the kinetics of the infection were determined. Infection with 10
2
IFU produced infections with lower peak levels than those in animals receiving 10
4
or 10
3
IFU. Seventy percent of animals receiving 10
2
IFU became infected, while 100 and 79% of animals receiving 10
4
and 10
3
IFU, respectively, became infected. Animals receiving 10
2
IFU also had a longer incubation period. Of 19 animals that mated with infected males, 63.2% became infected, with an infection course which was not significantly different than that of the 10
2
-IFU-infected group. The data suggest that female guinea pigs received approximately 10
2
IFU by sexual transmission. Of interest was the observation that the guinea pigs infected by sexual transmission shed organisms for a significantly shorter time period than that of any group that was artificially infected. This result suggests that there may be factors associated with semen which passively transfer antimicrobial activity to the female or enhance the innate host response in the female. Immunization of females with an inactivated vaccine was also found to elicit a protective immune response against sexual challenge, demonstrating that the model can be used in the evaluation of possible vaccine candidates and/or methodologies. There is currently no other animal model available for any sexually transmitted disease in which the disease or the ability to prevent the disease may be studied in animals infected by the natural means.
Differential Expression of Genes in Uninfected and
Rickettsia
-Infected
Dermacentor variabilis
Ticks as Assessed by Differential-Display PCR
Authors: Macaluso Kevin R. , Mulenga Albert , Simser Jason A. , Azad Abdu F. 
Published: October 2003

ABSTRACT
Ticks serve as both the vector and the reservoir for members of the spotted fever group rickettsiae. The molecular interaction(s) that results from this close relationship is largely unknown. To identify genetic factors associated with the tick response to rickettsial infection, we utilized differential-display PCR. The majority of upregulation appeared in the infected tissue. We cloned and sequenced 54 differentially expressed transcripts and compared the sequences to those in the GenBank database. Nine of the 54 clones were assigned putative identities and included a clathrin-coated vesicle ATPase, peroxisomal farnesylated protein, Ena/vasodilator-stimulated phosphoprotein-like protein, α-catenin, tubulin α-chain, copper-transporting ATPase, salivary gland protein SGS-3 precursor, glycine-rich protein, and Dreg-2 protein. Confirmation of the rickettsial influence on the differential expression in the ovaries for a number of these clones was demonstrated by semiquantitative reverse transcription-PCR and Northern blot analyses, resulting in confirmation of six out of nine and three out of four assessed clones, respectively. Further characterization of the clones identified tissue-dependent expression in the midguts and salivary glands. The potential roles of these molecules in the maintenance and transmission of rickettsiae are discussed.
Genetic Basis for the Structural Difference between
Streptococcus pneumoniae
Serotype 15B and 15C Capsular Polysaccharides
Authors: van Selm Saskia , van Cann Lisette M. , Kolkman Marc A. B. , van der Zeijst Bernard A. M. , van Putten Jos P. M. 
Published: October 2003

ABSTRACT

In a search for the genetic basis for the structural difference between the related
Streptococcus pneumoniae
capsular serotypes 15B and 15C and for the reported reversible switching between these serotypes, the corresponding capsular polysaccharide synthesis (
cps
) loci were investigated by keeping in mind that at the structural level, the capsules differ only in O acetylation. The
cps
locus of a serotype 15B strain was identified, partially PCR amplified with primers based on the related serotype 14 sequence, and sequenced. Sequence analysis revealed, among other open reading frames, an intact open reading frame (designated
cps15bM
) whose product, at the protein level, exhibited characteristics of previously identified acetyltransferases. Genetic analysis of the corresponding region in a serotype15C strain indicated that the same gene was present but had a premature stop in translation. Closer analysis indicated that the serotype 15B gene contained a short tandem TA repeat consisting of eight TA units. In serotype 15C, this gene contained nine TA units that resulted in a frameshift and a truncated product. Genetic analysis of 17 serotype 15B and 15C clinical isolates revealed a perfect correlation between the serotype and the length of the short tandem repeat in the putative
O
-acetyltransferase gene. The number of TA repeating units varied between seven and nine in the various isolates. Together, the data strongly suggest that the structural difference between serotypes 15B and 15C is based on variation in the short tandem TA repeat in the
O
-acetyltransferase gene and that the transition between serotypes is due to slipped-strand mispairing with deletion or insertion of TA units in the
cps15bM
gene.
TheMIC3Gene ofToxoplasma gondiiIs a Novel Potent Vaccine Candidate against Toxoplasmosis
Authors: Ismael Alaa Bassuny , Sekkai Dalila , Collin Christine , Bout Daniel , Mévélec Marie-Noëlle 
Published: October 2003

ABSTRACTInfection with the intracellular protozoan parasiteToxoplasma gondiicauses serious public health problems and is of great economic importance worldwide. The micronemal protein MIC3, which is a potent adhesin ofT. gondii, could be a significant candidate vaccine against toxoplasmosis. In this study, all CBA/J mice intramuscularly vaccinated with a plasmid encoding the immature form of the MIC3 protein (pMIC3i) produced specific anti-MIC3 immunoglobulin G (IgG) antibodies, and their sera displayed high antibody titers. This response was increased by the coadministration of a plasmid encoding the granulocyte-macrophage colony-stimulating factor (pGM-CSF). Similarly, a specific and significant cellular immune response was obtained in mice immunized with pMIC3i, and this response was markedly enhanced by pGM-CSF coadministration. The cellular immune response was associated with the production of gamma interferon IFN-γ and interleukin-2 (IL-2), indicating that this was a Th1-type response. This was confirmed by the production of large amounts of IgG2a. Mice immunized with pMIC3i displayed significant protection against an oral challenge withT. gondii76K cysts, exhibiting fewer brain cysts than did the control mice. Coadministration of pGM-CSF enhanced this protection. In conclusion, this study describes the design of a potent DNA vaccine encoding the novelT. gondiitarget antigen, MIC3 protein, that elicits a strong specific immune response as well as providing effective protection againstT. gondiiinfection. In the attempt to achieve complete protection against toxoplasmosis, MIC3 is a good candidate vaccine which could be combined with other relevant and previously described candidates, such as SAG1 and GRA4.
DNA Immunization with the Gene Encoding P4 Nuclease ofLeishmania amazonensisProtects Mice against Cutaneous Leishmaniasis
Authors: Campbell Kimberly , Diao Hong , Ji Jiaxiang , Soong Lynn 
Published: October 2003

ABSTRACTInfection with the protozoan parasiteLeishmania amazonensiscan cause diverse clinical forms of leishmaniasis. Immunization with purified P4 nuclease protein has been shown to elicit a protective response in mice challenged withL. amazonensisandL. pifanoi.To explore the potential of a DNA-based vaccine, we tested theL. amazonensisgene encoding P4 nuclease as well as adjuvant constructs encoding murine interleukin-12 (IL-12) andL. amazonensisHSP70. Susceptible BALB/c mice were immunized with the DNA encoding P4 alone, P4/IL-12, or P4/HSP70 prior to challenge withL. amazonensispromastigotes. Mice given P4/IL-12 exhibited no lesion development and had a 3- to 4-log reduction in tissue parasite burdens compared to controls. This protection corresponded to significant increases in gamma interferon and tumor necrosis factor alpha production and a reduction in parasite-specific immunoglobulin G1, suggesting an enhancement in Th1 responses. Moreover, we immunized mice with theL. amazonensisvaccines to determine if this vaccine regimen could provide cross-protection against a genetically diverse species,L. major. While the P4/HSP70 vaccine led to self-healing lesions, the P4/IL-12 vaccine provided negligible protection againstL. majorinfection. This is the first report of successful use of a DNA vaccine to induce protection againstL. amazonensisinfection. Additionally, our results indicate that different vaccine combinations, including DNA encoding P4, HSP70, or IL-12, can provide significant protection against both Old World and New World cutaneous leishmaniasis.
Autodisplay
Authors: Rizos Konstantin , Lattemann Claus T. , Bumann Dirk , Meyer Thomas F. , Aebischer Toni 
Published: October 2003

ABSTRACT

Live attenuated
Salmonella
strains expressing antigens of pathogens are promising oral vaccine candidates. There is growing evidence that the topology of expression of the foreign antigens can have a dramatic impact on the immunogenicity. We examined the potential of the AIDA-I (
Escherichia coli
adhesin involved in diffuse adherence) autotransporter domain to display antigenic fragments of the urease A subunit of
Helicobacter pylori
for the induction of a protective immune response. In the murine
H. pylori
model, protection is mainly mediated by CD4
+
T cells, and we therefore used the AIDA-I expression system to successfully express both nearly full-length UreA and defined T-helper-cell epitopes on the surface of an attenuated
Salmonella enterica
serovar Typhimurium vaccine strain. Surface exposure of the large UreA fragment or of one UreA T-cell epitope mediated a significant reduction in the level of
H. pylori
in immunized mice after challenge infection, whereas conventional cytoplasmic expression of UreA in
Salmonella
had no effect. These results support the concept that surface display increases the immunogenicity of recombinant antigens expressed on oral live vaccine carriers and further demonstrate the feasibility of immunizing against
H. pylori
with
Salmonella
vaccine strains expressing CD4
+
T-cell epitopes.
Human Neutrophil Chemotaxis Is Modulated by Capsule and O Antigen from an Extraintestinal PathogenicEscherichia coliStrain
Authors: Russo Thomas A. , Davidson Bruce A. , Topolnycky Diana M. , Olson Ruth , Morrill Stacy A. , Knight Paul R. , Murphy Philip M. 
Published: October 2003

ABSTRACTGram-negative enteric bacilli, such asEscherichia coli, are common causes of nosocomial pneumonia. The interaction between pulmonary neutrophils and the infecting pathogen is a critical step in determining the outcome. Previous studies from our laboratory, for which a rat model of pneumonia was used, established that pulmonary neutrophil recruitment was modulated by theE. colivirulence factors capsule and O-specific antigen. To begin to understand the mechanism by which this recruitment occurs, we conducted in vitro and ex vivo chemotaxis assays, for which we used a clinically relevantE. coliisolate (CP9) and isogenic derivatives that were deficient in only the O antigen (CP921) or capsule (CP9.137) as chemoattractants with or without the high-affinity N-formylmethionyl-leucyl-phenylalanine receptor antagonistN-tert-butoxycarbonyl-methionine-leucine-phenylalanine (N-t-BOC). Given that only liveE. coliwas used for the initial in vitro chemotaxis assays, it was predicted that onlyN-t-BOC-sensitive chemotaxis would occur. However, bothN-t-BOC-sensitive and -insensitive chemotaxis was observed.N-t-BOC-insensitive chemotaxis was mediated in part by interleukin 8, which was produced by neutrophils that had migrated towardE. coli.N-t-BOC-insensitive chemotaxis was only observed when liveE. colibacteria, not cell-freeE. coliculture supernatants, were used as chemoattractants, suggesting that a directE. coli-neutrophil interaction was necessary. The presence of both capsule and O antigen diminished total,N-t-BOC-sensitive, andN-t-BOC-insensitive neutrophil chemotaxis in vitro. The presence of capsule significantly decreased total,N-t-BOC-sensitive, andN-t-BOC-insensitive neutrophil chemotaxis ex vivo when cell-free bronchoalveolar lavage fluid from infected rats was used as the source of chemotactic factors. These effects ofE. colicapsule and O antigen on neutrophil chemotaxis are novel, and they expand our understanding of the mechanisms by which these virulence traits contribute to the pathogenesis of gram-negative pneumonia and other extraintestinal infections.
Enhanced Expression of Interleukin-1α and Tumor Necrosis Factor Receptor-Associated Protein 1 in Ileal Tissues of Cattle Infected withMycobacterium aviumsubsp.paratuberculosis
Authors: Aho Abraham D. , McNulty Amanda M. , Coussens Paul M. 
Published: October 2003

ABSTRACTInfection withMycobacterium aviumsubsp. paratuberculosisis associated with high levels of morbidity, decreased production, and early culling in dairy cattle. Clinical symptoms of Johne's disease include persistent diarrhea, inappetence, and resultant weight loss due to chronic inflammation of the small intestine. Although the presence or absence of intestinal lesions cannot be used as a definitive indicator ofM. aviumsubsp.paratuberculosisinfection, most infected cattle exhibit significant changes to intestinal mucosa, with the focus of pathology surrounding the ileal cecal junction. Typical pathology ofM. aviumsubsp.paratuberculosisinfection includes inflammation, thickening of the lumenal wall, and hyperplasia in draining lymph nodes. To further understand the pathology of Johne's disease, we compared the gene expression profiles of ileal tissues from Johne's disease-positive (n= 6), and Johne's disease-negative (n= 5) Holstein cattle. Gene expression profiles were compared with a bovine total leukocyte (BOTL-3) cDNA microarray. Genes that were expressed at significantly higher levels (>1.5-fold;P< 0.05) in tissues from Johne's disease-infected animals relative to noninfected animals included those encoding tumor necrosis factor receptor-associated protein 1 (TRAF1), interleukin-1α (IL-1α), MCP-2, N-cadherin, and β1 integrin (CD29). Dramatic upregulation of IL-1α (21.5-fold) and TRAF1 (27.5-fold) gene expression in tissues of Johne's disease-positive cows relative to tissues from control cows was confirmed by quantitative real-time PCR. Western blot analysis confirmed that IL-1α and TRAF1 mRNA levels resulted in increased protein expression in tissues of Johne's disease-positive cattle relative to tissues from control cattle. High levels of IL-1α can produce symptoms similar to those found in clinical Johne's disease. Taken together, the data presented in this report suggest that many outward symptoms of Johne's disease may be due to IL-1α toxicity. In addition, enhanced levels of TRAF1 could result in cells within the lesions of Johne's disease-positive cattle that are highly resistant to TNF-α-induced signaling.
Correlation betweencagPathogenicity Island Composition andHelicobacter pylori-Associated Gastroduodenal Disease
Authors: Nilsson Christina , Sillén Anna , Eriksson Lena , Strand Mona-Lisa , Enroth Helena , Normark Staffan , Falk Per , Engstrand Lars 
Published: October 2003

ABSTRACTHelicobacter pyloriinfection is associated with a variety of outcomes ranging from seemingly asymptomatic coexistence to peptic ulcer disease and gastric cancer. Thecagpathogenicity island (PAI) contains genes associated with a more aggressive phenotype and has been suggested to be a determinant of severe disease outcome. ThecagAgene has served as a marker for thecagPAI. However, the presence of this single gene does not necessarily indicate the presence of a complete set ofcagPAI genes. We have analyzed the composition of thecagPAI in 66 clinical isolates obtained from patients with duodenal ulcer, gastric cancer, and nonulcer dyspepsia. Hybridization of DNA to microarrays containing all the genes of thecagPAI showed that 76 and 9% of the strains contained all or none of thecagPAI genes, respectively. Partial deletions of thecagPAI were found in 10 isolates (15%), of which 3 werecagAnegative. The ability to induce interleukin-8 (IL-8) production in AGS cells was correlated to the presence of a completecagPAI. Strains carrying only parts of the island induced IL-8 at levels significantly lower than those induced bycagPAI-positive isolates. The presence of an intactcagPAI correlates with development of more severe pathology, and such strains were found more frequently in patients with severe gastroduodenal disease (odds ratio, 5.13; 95% confidence interval, 1.5 to 17.4). Partial deletions of thecagPAI appear to be sufficient to render the organism less pathogenic.
Mice Deficient in Nuclear Factor of Activated T-Cell Transcription Factor c2 Mount Increased Th2 Responses after Infection withNippostrongylus brasiliensisand Decreased Th1 Responses after Mycobacterial Infection
Authors: Erb Klaus J. , Twardzik Thomas , Palmetshofer Alois , Wohlleben Gisela , Tatsch Ursula , Serfling Edgar 
Published: October 2003

ABSTRACTInfection of nuclear factor of activated T-cell transcription factor c2 (NFATc2)-deficient mice with the helminthNippostrongylus brasiliensisled to a distinct increase in interleukin-4 (IL-4) and IL-5 protein synthesis by lymph node and spleen cells and to elevated serum immunoglobulin E (IgE) levels in comparison to those seen with infected control mice. While IL-4, IL-5, and IL-13 mRNA expression was also enhanced in lymph node cells from the lungs of infected NFATc2−/−mice, the number of T cells secreting Th2-type lymphokines remained the same in mice infected withN. brasiliensis. In contrast, lymphocytes from NFATc2-deficient mice infected withMycobacterium bovisBCG secreted less gamma interferon than lymphocytes from infected control mice. These findings indicate that NFATc2 is an activator of Th1 responses and a suppressor of Th2 responses in vivo.
Helicobacter pylori cagPathogenicity Island Is Associated with Reduced Expression of Interleukin-4 (IL-4) mRNA and Modulation of the IL-4δ2 mRNA Isoform in Human Gastric Mucosa
Authors: Orsini Barbara , Ottanelli Barbara , Amedei Amedeo , Surrenti Elisabetta , Capanni Marco , Del Prete Gianfranco , Amorosi Andrea , Milani Stefano , D'Elios Mario Milco , Surrenti Calogero 
Published: October 2003

ABSTRACTInterleukin-4 (IL-4) and IL-4δ2 mRNA gastric expression was evaluated in healthy subjects and patients who did not have ulcers but were infected withHelicobacter pyloriwith or without thecagpathogenicity island (cagPAI). IL-4 mRNA was physiologically expressed by gastric epithelium and negatively influenced byH.pylori. Also, nonepithelial cells in the lamina propria ofH.pylori-infected patients expressed IL-4 mRNA, whereas IL-4δ2 mRNA was found only incagPAI-negative patients. Thus, gastric IL-4 takes part in the local immune response toH.pylori.
Increased Density of Human Immunodeficiency Virus Type 1 Coreceptors CCR5 and CXCR4 on the Surfaces of CD4
+
T Cells and Monocytes of Patients with
Schistosoma mansoni
Infection
Authors: Secor W. Evan , Shah Amil , Mwinzi Pauline M. N. , Ndenga Bryson A. , Watta Caroline O. , Karanja Diana M. S. 
Published: October 2003

ABSTRACT

Distribution of chemokine receptors CCR5 and CXCR4, which are also coreceptors for human immunodeficiency virus type 1 invasion of cells, was measured on the surfaces of CD4
+
T cells and monocytes in peripheral blood samples from a group of Kenyan car washers. Patients with active schistosomiasis displayed higher cell surface densities of these receptors than did cured schistosomiasis patients.
Dissimilarity between Seasonal Changes in Airway Responsiveness to Adenosine-5’-Monophosphate and Methacholine in Patients with Grass Pollen Allergic Rhinitis: Relation to Induced Sputum
Authors: Beier Jutta , Beeh Kai Michael , Kornmann Oliver , Morankic Emila , Ritter Nicole , Buhl Roland 
Published: October 2003

<i>Background:</i> In patients with allergic rhinitis, bronchial hyperresponsiveness (BHR) and airway inflammation may increase during pollen exposure. BHR can be assessed by adenosine-5′-monophosphate (AMP) or methacholine challenge. It has been suggested that BHR to AMP is more closely related to airway inflammation than BHR to methacholine. Seasonal allergic rhinitis offers a dynamic model to study changes in BHR and airway inflammation during natural allergen exposure. <i>Methods:</i> We measured BHR [provocative concentration causing a 20% fall (PC<sub>20</sub>) in forced expiratory volume in 1 s (FEV<sub>1</sub>)] to AMP and methacholine, and induced sputum cells in 16 rhinitis patients before and during the 2001 grass pollen season. <i>Results:</i> There was a decrease in PC<sub>20</sub> methacholine during pollen exposure (geometric mean PC<sub>20</sub> from 3.22 to 1.73 mg/ml, p = 0.0023), whereas no reduction was observed for PC<sub>20</sub> AMP (p = 0.11). There was no increase in sputum eosinophils [pre: 0.69% (95% confidence interval 0.22–2.07); during: 1.85 (0.55– 5.6), p = 0.31]. Although the correlation of log PC<sub>20</sub> methacholine and log PC<sub>20</sub> AMP at baseline was good (r = 0.76, p = 0.001), individual seasonal changes (doubling concentrations) in PC<sub>20</sub> methacholine were not correlated with changes in PC<sub>20</sub> AMP (ρ = 0.21, p = 0.44). There was no correlation between baseline log PC<sub>20</sub> methacholine or seasonal changes in PC<sub>20</sub> methacholine and sputum eosinophils (p > 0.12, all correlations). In contrast, there was a significant correlation between seasonal changes in PC<sub>20</sub> AMP and changes in sputum eosinophils (ρ = –0.59, p = 0.025). <i>Conclusions:</i> These data show dissimilarity between seasonal changes in PC<sub>20</sub> AMP and methacholine in patients with seasonal allergic rhinitis. Moreover, PC<sub>20</sub> AMP seems to be more closely related to sputum eosinophils than PC<sub>20</sub> methacholine. The clinical significance of this discrepancy is unclear.