bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Importance of the Phagocytes' Innate Response in Resolution of the Infection Induced by a Low Virulent Candida albicans Mutant
Authors: Molero G. , Guillén M. V. , Martínez‐Solano L. , Gil C. , Pla J. , Nombela C. , Sánchez‐Pérez M. , Diez‐Orejas R. 
Published: September 2005

AbstractWe have reported that a Candida albicans mkc1Δ/mkc1Δ mutant, deleted in the Mkc1p mitogen‐activated protein kinase, an essential element of the cell integrity signalling pathway, has reduced virulence in a murine model of systemic infection. We analyse here the immunological basis for this feature in view of its failure to vaccinate. Firstly, the influence of the Th response was analysed by infecting different knockout mice, revealing the importance of interferon‐γ in the resolution of mkc1 systemic infection. Secondly, the role of innate immunity was studied. The infection of neutropenic mice revealed that the candidacidal activity of neutrophils is crucial during the first 3 days of infection for the mutant strain. Macrophages played a critical role in the clearance of infection. Although a similar anti‐Candida activity was found for both fungal strains with naïve macrophages, activated macrophages discriminated between both strains. In vitro experiments revealed that the mutant strain displayed a greater susceptibility to nitric oxide (NO), a reduced inhibitory effect on macrophage NO production and an increased capacity of macrophage stimulation by cell wall extracts. The importance of NO in systemic infection with the mutant strain was confirmed by the strong increase in the susceptibility of aminoguanidine (an iNOs inhibitor)‐treated mice.
24‐h Monitoring of Calcineurin Phosphatase Activity in Healthy Subjects
Authors: Koefoed‐Nielsen P. B. , Karamperis N. , Jørgensen K. A. 
Published: September 2005

AbstractThe calcineurin inhibitors cyclosporine and tacrolimus are the cornerstone immunosuppressants used in solid organ transplantation. Studies investigating calcineurin (CaN) activity in renal transplanted patients have been published, but basic properties of the enzyme activity in healthy subjects remain to be described. The aim of this study was to investigate whether CaN displays circadian variation or sex difference is present in healthy subjects. Twenty subjects had blood samples drawn every 4 h for a 24‐h period. CaN activity was determined in whole blood as the release of 32P from a phosphorylated peptide. Activity of the 32P was quantitated by liquid scintillation and results converted to units CaN utilizing a calibration curve. We found no circadian variation in CaN activity and no difference between the two sexes. The clinical importance of these findings is that blood samples for calcineurin activity can be drawn without taking the exact time of day into consideration, but only considering the time of drug intake.
Direct Allorecognition Promotes Activation of Bystander Dendritic Cells and Licenses Them for Th1 Priming: A Functional Link Between Direct and Indirect Allosensitization
Authors: Wallgren A. C. , Andersson B. , Bäcker A. , Karlsson‐Parra A. 
Published: September 2005

AbstractT‐cell sensitization to indirectly presented alloantigens (indirect pathway of allorecognition) plays a critical role in chronic rejection. The usual very efficient priming of such self‐restricted, T helper type 1 (Th1)‐deviated CD4+ T cells obviously conflicts with the fact that allogeneic MHC molecules are poorly immunogenic per se. The aim of the present study is to elucidate whether direct allosensitization induces production of inflammatory mediators that may affect recruitment and activation of immature bystander (host) dendritic cells (DC). These potential mechanisms were studied in vitro by conducting primary allogeneic mixed leucocyte reactions (MLR), mimicking the priming phase in secondary lymphoid organs, and secondary MLR, mimicking the effector phase within the graft. Primary, and particularly secondary, MLR supernatants were found to contain high levels of monocyte/immature DC‐recruiting CC chemokines and pro‐inflammatory cytokines. Exposure of immature DC to primary or secondary MLR supernatants was found to upregulate CD40 expression and further enhanced lipopolysaccharide‐induced interleukin‐12 (IL‐12) p70 production. Secondary MLR supernatants additionally induced upregulation of CD86 and deviated allogeneic T‐cell responses towards Th1 (enhanced interferon‐γ production without concomitant induction of detectable IL‐4 or IL‐10 production). These findings indicate that direct allorecognition may act as a Th1‐deviating adjuvant for indirect allosensitization.
Distribution of Productive Antigen‐Processing Activity for MHC class II Presentation in Macrophages
Authors: Von Delwig A. , Musson J. A. , Shim H.‐K. , Lee J. J. , Walker N. , Harding C. V. , Williamson E. D. , Robinson J. H. 
Published: September 2005

AbstractWe demonstrated that an epitope from the recombinant protective antigen (rPA) of Bacillus anthracis was presented by mature major histocompatibility complex class II (MHC‐II) molecules, whereas an epitope from the recombinant virulent (rV) antigen of Yersinia pestis was presented by newly synthesized MHC‐II. We addressed which endosomal compartments were involved in the antigen processing of each epitope. Bone‐marrow‐derived macrophages were subjected to subcellular fractionation; fractions were analysed for the expression of endosomal markers and used as a source of enzyme activity for the processing of rPA and rV antigens. The rPA epitope was productively processed by dense lysosomal fractions and light membrane fractions expressing early endosomal markers Rab5 and early endosomal antigen‐1 as well as markers of antigen‐presenting compartments (MHC‐II, DM, DO and Ii chain). In contrast, the rV epitope was productively processed only by dense fractions with lysosomal activity. No productive antigen‐processing activity was associated with fractions of intermediate density expressing Rab7 and Rab9, characteristic of late endosomes. The data suggest that endosomal compartments expressing Rab5 guanosine triphosphatase can productively process protein antigens for presentation by mature MHC class II molecules.
Immunoglobulin G Antibodies Against Environmental Moulds in a Norwegian Healthy Population Shows a Bimodal Distribution for Aspergillus versicolor
Authors: Rydjord B. , Hetland G. , Wiker H. G. 
Published: September 2005

AbstractImmunoglobulin G (IgG) antibodies against moulds related to indoor dampness problems are used as biomarkers to indicate exposure. In the present study, we evaluated the frequency of mould exposure in an adult healthy population by examining levels of mould‐specific IgG antibodies in Norwegian blood donors. Using enzyme‐linked immunosorbent assay, 106 blood donor sera were analyzed for IgG antibodies to Aspergillus versicolor, Penicillium chrysogenum, Cladosporium herbarum, Stachybotrys chartarum and Fusarium oxysporum. The levels of specific IgG antibodies to P. chrysogenum, C. herbarum and S. chartarum correlated (r = 0.46–0.62). Responses to A. versicolor were considerably stronger than to the other moulds, and another 996 blood donor sera were analyzed for IgG antibodies to this mould. Women had significantly higher levels of specific IgG antibodies to A. versicolor than men. The concentration of A. versicolor‐specific IgG antibodies showed a non‐Gaussian, bimodal distribution profile, in which 12.5% were defined as positive to exposure. This suggests that significant mould exposure in a healthy population can be calculated from mean + 1SD. Western blotting analyses showed that antibody responses to A. versicolor were largely directed against carbohydrate antigens of unknown saccharides.
Collie eye anomaly in a mixed‐breed dog
Authors: Rampazzo Antonella , D’Angelo Antonio , Capucchio Maria Teresa , Sereno Sandra , Peruccio Claudio 
Published: September 2005

AbstractA 5‐year‐old, mixed‐breed dog was presented for tetraparesis. Neurologic alterations included a decreased menace response in both eyes. Therefore, an ophthalmic examination was requested. The dog was visual, but menace response, dazzle and pupillary light reflexes were reduced bilaterally. Indirect ophthalmoscopy revealed bilateral optic nerve coloboma and severe choroidal hypoplasia. These lesions closely resembled the ophthalmoscopic features of Collie eye anomaly (CEA). In spite of treatment, the dog's condition worsened and the animal was therefore euthanized. Histology of the globes confirmed severe choroidal hypoplasia and optic disc coloboma in both eyes. The dog was diagnosed to have a lymphoma involving the spinal cord. The two entities were considered not related. As only moderate sight impairment was caused by the posterior segment anomalies, it is by chance that these lesions resembling CEA were found in this mixed‐breed dog.
Anti‐inflammatory effect of germanium‐concentrated yeast against paw oedema is related to the inhibition of arachidonic acid release and prostaglandin E2 production in RBL 2H3 cells
Authors: Lee J. H. , Kim K. W. , Yoon M. Y. , Lee J. Y. , Kim C. J. , Sim S. S. 
Published: September 2005

Summary 1 To investigate anti‐inflammatory activity of organic germanium, we measured the effect of germanium‐concentrated yeast on arachidonic acid release, prostaglandin E2 (PGE2) production, histamine release, and intracellular H2O2 or hydroperoxide generation in RBL 2H3 cells, and carrageenan‐induced paw oedema in rats. 2 Germanium‐concentrated yeast dose‐dependently inhibited carrageenan‐induced paw oedema, suggesting that germanium‐concentrated yeast has anti‐inflammatory activity in acute inflammation. 3 Germanium‐concentrated yeast significantly inhibited melittin‐induced arachidonic acid release and PGE2 production in RBL 2H3 cells. 4 Germanium‐concentrated yeast did not affect melittin‐induced histamine release and silica‐induced intracellular H2O2 or hydroperoxide generation in RBL 2H3 cells. 5 These results suggest that anti‐inflammatory activity of germanium‐concentrated yeast appears partly to be related to the inhibition of arachidonic acid release and PGE2 production in RBL 2H3 cells.
Chloroethylclonidine reveals that α1A‐adrenoceptors mediate contraction in aorta of α1D‐adrenoceptor knockout mice
Authors: Lázaro‐Suárez M. L. , Gómez‐Zamudio J. H. , Gallardo‐Ortíz I. A. , Tanoue A. , Tsujimoto G. , Farias‐Rodríguez V. M. , Villalobos‐Molina R. 
Published: September 2005

Summary 1 We have characterized the α1‐adrenoceptor subtypes present in isolated aorta of the α1D‐adrenoceptor knockout (KO) mice, by chloroethylclonidine (CEC)‐induced alkylation and their protection by selective α1‐adrenoceptor antagonists. 2 The α1D‐adrenoceptor is involved in the contractile response to noradrenaline in wild type (WT) mouse aorta. 3 In WT mice 5‐methylurapidil (5‐MU, an α1A‐adrenoceptor antagonist) or BMY 7378 (8‐[2‐[4‐(2‐methoxyphenyl)‐1‐piperazinyl] ethyl]‐8‐azaspiro[4.5] decane‐7,9 dione, a selective α1D‐adrenoceptor antagonist), protected the receptors from CEC‐induced (α1B/D‐adrenoceptor) alkylation, the combination of both antagonists resulted in complete protection, while AH11110A (1‐[biphenyl‐2‐yloxy]‐4‐imino‐4‐piperidin‐1‐yl‐butan‐2‐ol, an α1B‐adrenoceptor antagonist) did not protect. 4 In aorta of KO mice there was a 19‐fold rightward shift in noradrenaline effective concentration (EC50) compared with WT; while 5‐MU alone or in combination with AH11110A protected α1‐adrenoceptors to the same extent. 5 The data indicate that α1A‐adrenoceptors mediate contraction and suggest their role in maintaining homeostasis in the α1D‐adrenoceptors KO mice.
Neuroscience and the Detection of Deception
Authors: Happel Mark D. 
Published: September 2005

AbstractThe detection of deception is among the most important and pressing requirements faced by federal agencies with national security responsibilities. The polygraph is insufficient in its present state of development for meeting the needs of national security. While some neuroscience‐based alternatives to the polygraph have been proposed (e.g., EEG and fMRI), there are significant problems with these techniques and consideration of their operational use is premature. The development of a more effective means for detecting deception will require substantial conceptual advances in the science of deception, in particular the establishment of a sound theoretical basis on which to design such a system. Neuroscience and related fields can make significant contributions toward the development of a theory of deception, given sufficient government support and commitment to such an effort. However, even a sound theory of deception cannot guarantee success; it is vital that the associated policy, legal, and ethical implications of such a system be taken into account.
SseJ Deacylase Activity by
Salmonella enterica
Serovar Typhimurium Promotes Virulence in Mice
Authors: Ohlson Maikke B. , Fluhr Kerry , Birmingham Cheryl L. , Brumell John H. , Miller Samuel I. 
Published: September 2005

ABSTRACT

Salmonella enterica
serovar Typhimurium utilizes a type III secretion system (TTSS) encoded on
Salmonella
pathogenicity island-2 (SPI2) to promote intracellular replication during infection, but little is known about the molecular function of SPI2-translocated effectors and how they contribute to this process. SseJ is a SPI2 TTSS effector protein that is homologous to enzymes called glycerophospholipid-cholesterol acyltransferases and, following translocation, localizes to the
Salmonella
-containing vacuole and
Salmonella-
induced filaments. Full virulence requires SseJ, as
sseJ
null mutants exhibit decreased replication in cultured cells and host tissues. This work demonstrates that SseJ is an enzyme with deacylase activity in vitro and identifies three active-site residues. Catalytic SseJ mutants display wild-type translocation and subcellular localization but fail to complement the virulence defect of an
sseJ
null mutant. In contrast to the wild type, SseJ catalytic mutants fail to down regulate
Salmonella
-induced filament formation and fail to restore the
sifA
null mutant phenotype of loss of phagosomal membrane to
sifA sseJ
null double mutants, suggesting that wild-type SseJ modifies the vacuolar membrane. This is the first demonstration of an enzymatic activity for a SPI2 effector protein and provides support for the hypothesis that the deacylation of lipids on the
Salmonella
-containing vacuole membrane is important to bacterial pathogenesis.
Identification of New Secreted Effectors in
Salmonella enterica
Serovar Typhimurium
Authors: Geddes Kaoru , Worley Micah , Niemann George , Heffron Fred 
Published: September 2005

ABSTRACT

A common theme in bacterial pathogenesis is the secretion of bacterial products that modify cellular functions to overcome host defenses. Gram-negative bacterial pathogens use type III secretion systems (TTSSs) to inject effector proteins into host cells. The genes encoding the structural components of the type III secretion apparatus are conserved among bacterial species and can be identified by sequence homology. In contrast, the sequences of secreted effector proteins are less conserved and are therefore difficult to identify. A strategy was developed to identify virulence factors secreted by
Salmonella enterica
serovar Typhimurium into the host cell cytoplasm. We constructed a transposon, which we refer to as mini-Tn
5
-cycler, to generate translational fusions between
Salmonella
chromosomal genes and a fragment of the calmodulin-dependent adenylate cyclase gene derived from
Bordetella pertussis
(
cyaA
′). In-frame fusions to bacterial proteins that are secreted into the eukaryotic cell cytoplasm were identified by high levels of cyclic AMP in infected cells. The assay was sufficiently sensitive that a single secreted fusion could be identified among several hundred that were not secreted. This approach identified three new effectors as well as seven that have been previously characterized. A deletion of one of the new effectors,
steA
(
Salmonella
translocated effector A), attenuated virulence. In addition, SteA localizes to the
trans
-Golgi network in both transfected and infected cells. This approach has identified new secreted effector proteins in
Salmonella
and will likely be useful for other organisms, even those in which genetic manipulation is more difficult.
Live Nonpathogenic Parasitic Vector as a Candidate Vaccine against Visceral Leishmaniasis
Authors: Breton Marie , Tremblay Michel J , Ouellette Marc , Papadopoulou Barbara 
Published: September 2005

ABSTRACTTo date, there are no proven vaccines against any form of leishmaniasis. The development of live attenuated vectors shows promise in the field ofLeishmaniavaccination because these organisms mimic more effectively the course of real infections and can elicit potent activation of the immune system. In the present study, we investigated the potential of a parasitic protozoan that is nonpathogenic to humans,Leishmania tarentolae, as a live candidate vaccine that efficiently targets dendritic cells and lymphoid organs, thus enhancing antigen presentation and consequently influencing the magnitude and quality of T-cell immune responses. We demonstrated thatL. tarentolaeactivates the dendritic cell maturation process and induces T-cell proliferation and the production of gamma interferon, thus skewing CD4+T cells toward a Th1 cell phenotype. More importantly, we found that a single intraperitoneal injection ofL. tarentolaecould elicit a protective immune response against infectious challenge withLeishmania donovaniin susceptible BALB/c mice. These results suggest that the use ofL. tarentolaeas a live vaccine vector may represent a promising approach for improving the effectiveness and safety of candidate live vaccines againstLeishmaniainfections and possibly other intracellular pathogens for which T-cell mediated responses are critical for the development of protective immunity.
Anti-Idiotypic Antibody as a Potential Candidate Vaccine forNeisseria meningitidisSerogroup B
Authors: Park In Ho , Youn Ju Ho , Choi In-Hong , Nahm Moon H. , Kim Se Jong , Shin Jeon-Soo 
Published: September 2005

ABSTRACTSepsis and meningitis caused byNeisseria meningitidisserogroup B (NMGB) are serious diseases in infants and young adults, but no effective vaccine is available. The capsular polysaccharide (PS) of NMGB has poor immunogenicity and a structural similarity to polysialic acid (PSA) on neuronal tissue that may elicit autoantibodies. Using HmenB3, a protective and nonautoreactive monoclonal antibody (MAb) to NMGB capsular PS, we produced an anti-idiotypic MAb, Naid60, which mimics the capsular PS of NMGB. We produced an anti-anti-idiotypic MAb, MoB34, by using the immunogenic site on Naid60 responsible for inducing the anti-NMGB PS antibody response. MoB34 elicited the complement-mediated killing of representative strains of serogroup B meningococci. MoB34 did not bind to CHP-134, a neuroblastoma cell line expressing α(2-8) PSA, or to mouse brain cryosections at a high concentration. Naid60-keyhole limpet hemocyanin immunization inhibited the growth of live NMGB in intraperitoneally challenged mice; in contrast, three of five control mice developed bacteremia. Thus, Naid60 has an immunogenic site that elicits antibodies with bactericidal activity against NMGB and no autoimmunity to PSA. We suggest that the immunogenic region of Naid60 is a candidate for the development of a new vaccine against NMGB.
Comparative Genomic Analysis ofChlamydia trachomatisOculotropic and Genitotropic Strains
Authors: Carlson John H. , Porcella Stephen F. , McClarty Grant , Caldwell Harlan D. 
Published: September 2005

ABSTRACTChlamydia trachomatisinfection is an important cause of preventable blindness and sexually transmitted disease (STD) in humans.C. trachomatisexists as multiple serovariants that exhibit distinct organotropism for the eye or urogenital tract. We previously reported tissue-tropic correlations with the presence or absence of a functional tryptophan synthase and a putative GTPase-inactivating domain of the chlamydial toxin gene. This suggested that these genes may be the primary factors responsible for chlamydial disease organotropism. To test this hypothesis, the genome of an oculotropic trachoma isolate (A/HAR-13) was sequenced and compared to the genome of a genitotropic (D/UW-3) isolate. Remarkably, the genomes share 99.6% identity, supporting the conclusion that a functional tryptophan synthase enzyme and toxin might be the principal virulence factors underlying disease organotropism. Tarp (translocated actin-recruiting phosphoprotein) was identified to have variable numbers of repeat units within the N and C portions of the protein. A correlation exists between lymphogranuloma venereum serovars and the number of N-terminal repeats. Single-nucleotide polymorphism (SNP) analysis between the two genomes highlighted the minimal genetic variation. A disproportionate number of SNPs were observed within some members of the polymorphic membrane protein (pmp) autotransporter gene family that corresponded to predicted T-cell epitopes that bind HLA class I and II alleles. These results implicate Pmps as novel immune targets, which could advance future chlamydial vaccine strategies. Lastly, a novel target for PCR diagnostics was discovered that can discriminate between ocular and genital strains. This discovery will enhance epidemiological investigations in nations where both trachoma and chlamydial STD are endemic.
Role of an Alginate Lyase for Alginate Transport in Mucoid
Pseudomonas aeruginosa
Authors: Jain Sumita , Ohman Dennis E. 
Published: September 2005

ABSTRACT

The opportunistic pathogen
Pseudomonas aeruginosa
secretes a capsule-like polysaccharide called alginate that is important for evasion of host defenses, especially during chronic pulmonary disease of patients with cystic fibrosis (CF). Most proteins for alginate biosynthesis are encoded by the 12-gene
algD
operon. Interestingly, this operon also encodes AlgL, a lyase that degrades alginate. Mutants lacking AlgG, AlgK, or AlgX, also encoded by the operon, synthesize alginate polymers that are digested by the coregulated protein AlgL. We examined the phenotype of an Δ
algL
mutation in the highly mucoid CF isolate FRD1. Generating a true Δ
algL
mutant was possible only when the
algD
operon was under the control of a LacI
q
-repressed
trc
promoter. Upon induction of alginate production with isopropyl-β-
d
-thiogalactopyranoside, the Δ
algL
mutant cells were lysed within a few hours. Electron micrographs of the Δ
algL
mutant showed that alginate polymers accumulated in the periplasm, which ultimately burst the bacterial cell wall. The requirement of AlgL in an alginate-overproducing strain led to a new model for alginate secretion in which a multiprotein secretion complex (or scaffold, that includes AlgG, AlgK, AlgX, and AlgL) guides new polymers through the periplasm for secretion across the outer membrane. In this model, AlgL is bifunctional with a structural role in the scaffold and a role in degrading free alginate polymers in the periplasm.