bluuebunny/crossref_metadata_2025_split huggingface dataset:
ZapA, a Virulence Factor in a Rat Model of
Proteus mirabilis
-Induced Acute and Chronic Prostatitis
Authors: Phan Van , Belas Robert , Gilmore Brendan F. , Ceri Howard 
Published: August 2008

ABSTRACT

Our knowledge of pathogenesis has benefited from a better understanding of the roles of specific virulence factors in disease. To determine the role of the virulence factor ZapA, a 54-kDa metalloproteinase of
Proteus mirabilis
, in prostatitis, rats were infected with either wild-type (WT)
P. mirabilis
or its isogenic ZapA
−
mutant KW360. The WT produced both acute and chronic prostatitis showing the typical histological progressions that are the hallmarks of these diseases. Infection with the ZapA
−
mutant, however, resulted in reduced levels of acute prostatitis, as determined from lower levels of tissue damage, bacterial colonization, and inflammation. Further, the ZapA
−
mutant failed to establish a chronic infection, in that bacteria were cleared from the prostate, inflammation was resolved, and tissue was seen to be healing. Clearance from the prostate was not the result of a reduced capacity of the ZapA
−
mutant to form biofilms in vitro. These finding clearly define ZapA as an important virulence factor in both acute and chronic bacterial prostatitis.
The Interaction of
Streptococcus pneumoniae
with Plasmin Mediates Transmigration across Endothelial and Epithelial Monolayers by Intercellular Junction Cleavage
Authors: Attali Cécile , Durmort Claire , Vernet Thierry , Di Guilmi Anne Marie 
Published: August 2008

ABSTRACT

The precise mechanisms by which
Streptococcus pneumoniae
overcomes epithelial and endothelial barriers to access underlying human tissues remain to be determined. The plasminogen system is highly important for the tissue barrier degradation which allows cell migration. Plasminogen is known to interact with pneumococci via enolase, glyceraldehyde-3-phosphate dehydrogenase, and choline-binding protein E. These observations prompted us to evaluate the role of this proteolytic system in the pneumococcal invasion process. We observed that coating of
S. pneumoniae
R6 strain with plasminogen or inactivated plasmin increased adherence to pulmonary epithelial A549 and vascular endothelial EaHy cells in vitro. This indicates that plasminogen-mediated adherence is independent of the protease activity and involves plasminogen binding to receptors on eukaryotic cell surfaces. Conversely, decreased adherence of bacterial cells coated with active plasmin was observed, indicating that the protease activity limits bacterial attachment on the cell surface. We were then interested in investigating the role of the proteolytic plasmin activity in the traversal of tissue barriers. We observed that adherence of plasmin-coated D39 (encapsulated) or R6 (unencapsulated) pneumococci induced sporadic disruptions of EaHy and A549 monolayer cell junctions. This was not observed when plasmin was inhibited by aprotinin. Endothelial junction disorganization may proceed by proteolysis of the cell junction components. This is supported by our observation of the in vitro cleavage by plasmin bound to pneumococci of recombinant vascular endothelial cadherin, the main component of endothelial adherens junctions. Finally, junction damage induced by plasmin may be related to tissue barrier traversal, as we measured an increase of
S. pneumoniae
transmigration across epithelial A549 and endothelial EaHy layers when active plasmin was present on the bacterial surface. Our results highlight a novel function for the plasminogen recruitment at the bacterial surface in facilitating adherence of pneumococci to endothelial and epithelial cells, while active plasmin degrades intercellular junctions. This process promotes migration of pneumococci through cell barriers by a pericellular route, a prerequisite for dissemination of
S. pneumoniae
in the host organism.
Temporal Delay of Peak T-Cell Immunity DeterminesChlamydia pneumoniaePulmonary Disease in Mice
Authors: Wang Chengming , van Ginkel Frederik W. , Kim Teayoun , Li Dan , Li Yihang , Dennis John C. , Kaltenboeck Bernhard 
Published: August 2008

ABSTRACTSevere chlamydial disease typically occurs after previous infections and results from a hypersensitivity response that is also required for chlamydial elimination. Here, we quantitatively dissected the immune and disease responses to repeatedChlamydia pneumoniaelung infection by multivariate modeling with four dichotomous effects: mouse strain (A/J or C57BL/6), dietary protein content (14% protein and 0.3%l-cysteine-0.9%l-arginine, or 24% protein and 0.5%l-cysteine-2.0%l-arginine), dietary antioxidant content (90 IU α-tocopherol/kg body weight versus 450 IU α-tocopherol/kg and 0.1% gl-ascorbate), and time course (3 or 10 days postinfection). Following intranasalC. pneumoniaechallenge, C57BL/6 mice on a low-protein/low-antioxidant diet, but not C57BL/6 mice on other diets or A/J mice, exhibited profoundly suppressed early lung inflammatory and pan-T-cell (CD3δ+) and helper T-cell (CD45) responses on day 3 but later strongly exacerbated disease on day 10. Contrast analyses characterized severeC. pneumoniaedisease as being a delayed-type hypersensitivity (DTH) response with increased lung macrophage and Th1 cell marker transcripts, increased Th1:Th2 ratios, and Th1 cytokine-driven inflammation. Results from functional analyses by DTH, enzyme-linked immunospot, and immunohistofluorescence assays were consistent with the results obtained by transcript analysis. Thus, chlamydial disease after secondary infection is a temporal dysregulation of the T-cell response characterized by a profoundly delayed T-helper cell response that results in a failure to eliminate the pathogen and provokes later pathological Th1 inflammation. This delayed T-cell response is under host genetic control and nutritional influence. The mechanism that temporally and quantitatively regulates the host T-cell population is the critical determinant in chlamydial pathogenesis.
Pulmonary fibrosis in l-NAME-treated mice is dependent on an activated endothelin systemThis article is one of a selection of papers published in the special issue (part 2 of 2) on Forefronts in Endothelin.
Authors: Kalk Philipp , Mach Alexander , Thone-Reineke Christa , Godes Michael , Heiden Susi , Sharkovska Yuliya , von Websky Karoline , Relle Katharina , Hocher Berthold 
Published: August 2008

Activation of the endothelin (ET) system promotes vasoconstriction, inflammation, and fibrosis in various tissues, including the lung. Therefore, ET-1 transgenic mice overexpressing ET-1 develop pulmonary fibrosis in a slow, age-dependent manner. In vivo, NO is the most important counterregulatory mediator of the ET system and decreases ET-1 promoter activity. The aim of our study was to elucidate the impact on pulmonary inflammation and fibrosis of the interaction between NO and the ET system in young ET-1 transgenic mice before the onset of pulmonary fibrosis. Male ET-1 transgenic mice and wild-type littermates at the age of 8 weeks were randomly allocated to the following 6 groups: WT (n = 11), wild-type animals without treatment; WT + l-NAME (n = 14), wild-type animals receiving l-NAME, an inhibitor of NO synthase; WT + l-NAME + LU (n = 13), wild-type animals receiving l-NAME and LU 302872, a dual ETA/ETB-receptor antagonist; ET1tg (n = 10), ET-1 transgenic mice; ET1tg + l-NAME (n = 13); and ET1tg + l-NAME + LU (n = 13). After 6 weeks, animals were euthanized, and hearts and lungs were harvested for histology and immunohistochemistry. No differences in pulmonary inflammation, as indicated by macrophage infiltration, or in interstitial fibrosis were observed between WT and ET1tg mice at baseline; however, inflammation and interstitial fibrosis were significantly enhanced in ET1tg mice, but not in WT groups, after l-NAME treatment. The combined ETA/ETB-receptor antagonist LU 302872 abolished inflammation and interstitial fibrosis in l-NAME-treated ET1tg mice. Perivascular fibrosis and media/lumen ratio of pulmonary bronchi and arteries did not differ between all study groups. In our study l-NAME induced pulmonary fibrosis and inflammation only in young ET1tg mice. Additional treatment with LU 302872 abolished these effects. We thus conclude that an imbalance between an activated ET system and a suppressed NO system contributes to pulmonary inflammation and fibrosis.
Malignant Pleural Mesothelioma–Targeted CREBBP/EP300 Inhibitory Protein 1 Promoter System for Gene Therapy and Virotherapy
Authors: Fukazawa Takuya , Matsuoka Junji , Naomoto Yoshio , Maeda Yutaka , Durbin Mary L. , Tanaka Noriaki 
Published: August 2008

Abstract
Gene therapy and virotherapy are one of the approaches used to treat malignant pleural mesothelioma. To improve the efficiency of targeting malignant mesothelioma cells, we designed a novel system using the promoter of the CREBBP/EP300 inhibitory protein 1 (CRI1), a gene specifically expressed in malignant pleural mesothelioma. Four tandem repeats of the CRI1 promoter (CRI1−138 4x) caused significantly high promoter activity in malignant pleural mesothelioma cells but little promoter activity in normal mesothelial cells and normal fibroblasts. The recombinant adenoviral vector expressing proapoptotic BH3-interacting death agonist or early region 1A driven by the CRI1−138 4x promoter induced cell death in malignant mesothelioma cells but not in normal cells. Moreover, these viruses showed antitumor effects in a mesothelioma xenograft mouse model. Here, we describe a novel strategy to target malignant mesothelioma using the CRI1−138 4x promoter system. [Cancer Res 2008;68(17):7120–9]
Isoaspartate-Glycine-Arginine: A New Tumor Vasculature–Targeting Motif
Authors: Curnis Flavio , Sacchi Angelina , Gasparri Anna , Longhi Renato , Bachi Angela , Doglioni Claudio , Bordignon Claudio , Traversari Catia , Rizzardi Gian-Paolo , Corti Angelo 
Published: August 2008

AbstractAsparagine deamidation in peptides or in fibronectin fragments containing the asparagine-glycine-arginine sequence generates isoaspartate-glycine-arginine (isoDGR), a new αvβ3 integrin-binding motif. Because αvβ3 is expressed in angiogenic vessels, we hypothesized that isoDGR-containing peptides could be exploited as ligands for targeted delivery of drugs to tumor neovasculature. We found that a cyclic CisoDGRC peptide coupled to fluorescent nanoparticles (quantum dots) could bind αvβ3 integrin and colocalize with anti-CD31, anti-αvβ3, and anti-α5β1 antibodies in human renal cell carcinoma tissue sections, indicating that this peptide could efficiently recognize endothelial cells of angiogenic vessels. Using CisoDGRC fused to tumor necrosis factor α (TNF) we observed that ultralow doses (1–10 pg) of this product (called isoDGR-TNF), but not of TNF or CDGRC-TNF fusion protein, were sufficient to induce antitumor effects when administered alone or in combination with chemotherapy to tumor-bearing mice. The antitumor activity of isoDGR-TNF was efficiently inhibited by coadministration with an excess of free CisoDGRC, as expected for ligand-directed targeting mechanisms. These results suggest that isoDGR is a novel tumor vasculature–targeting motif. Peptides containing isoDGR could be exploited as ligands for targeted delivery of drugs, imaging agents, or other compounds to tumor vasculature. [Cancer Res 2008;68(17):7073–82]
Validity and responsiveness of the Rehabilitation Activities Profile (RAP) in patients with rheumatoid arthritis
Authors: Verhoef J. , Toussaint PJ , Putter H. , Zwetsloot-Schonk JHM , Vliet Vlieland TPM 
Published: August 2008

Objective: To investigate the internal consistency, validity and responsiveness of the Rehabilitation Activities Profile (RAP; a rehabilitation tool structuring the multidisciplinary team care process) in patients with rheumatoid arthritis. Methods: In 85 rheumatoid arthritis patients admitted to a rheumatology clinic the RAP was applied at admission, at discharge, and six weeks thereafter. Additional assessments included measures of physical and psychological functioning, disease activity and quality of life. The internal consistency of the RAP was determined with Cronbach's alpha. Associations between the RAP and other outcome measures were determined by Spearman rank correlation coefficients. Responsiveness measures included the standardized response mean (SRM), effect size (ES) and responsiveness ratio (RR). Results: Cronbach's alpha of the RAP total score was 0.78. The RAP total score correlated significantly with all other outcome measures. The mean RAP total score improved from 15.2 to 13.2 at discharge (change -2.0; 95% confidence interval (CI) -3.4 to -0.7) and to 11.5 (change -3.7; 95% CI -3.9 to -1.5) six weeks thereafter. The responsiveness of the RAP total score was low (standardized response mean -0.34, effect size -0.30) to high (responsiveness ratio -0.87) at discharge and moderate (standardized response mean -0.54, effect size -0.55) to high (responsiveness ratio -1.56) six weeks thereafter. Conclusions: The RAP appeared to be an internally consistent, valid and responsive measure to reflect limitations on the level of activities and participation in patients with rheumatoid arthritis admitted for multidisciplinary team care.
Neuropsychological predictors of powered wheelchair use: a prospective follow-up study
Authors: Cullen Breda , O'Neill Brian , Evans Jonathan J 
Published: August 2008

Objectives: To investigate (1) rates of powered wheelchair use and level of user-rated functional performance at one-month follow-up, and (2) whether psychological variables were prospectively predictive of outcome. Design: Prospective follow-up study. Setting: UK hospital-based regional rehabilitation and mobility centre. Participants: Volunteer adults with impaired mobility. Of 155 approached, 103 had baseline assessments. Of these, 81 (79%) provided outcome data. Mean age was 65.6 years (SD = 13.5); 55% were male. Main outcome measures: Rate of day-to-day powerchair use, and users' perceptions of how well the powerchair allowed them to perform functional tasks. Results: Among those with indoor-only chairs, 48% were 'less frequent' users; this rose to 72% among those with indoor/outdoor chairs. Excluding environmental reasons, rate of indoor use was predicted by baseline measures of verbal recall (P<0.001), figure copying (P=0.003) and global cognition (P=0.021). Among those with indoor/outdoor chairs, total rate of use was predicted by verbal recall (P= 0.001). Participants reported that the powerchair was effective in meeting their functional needs. Conclusions: Powered wheelchair use was predicted by cognitive measures. Rates of use were relatively low, despite users' reports that the powerchair facilitated their everyday functioning well.
Recurrent leukoencephalopathy with microhemorrhages: gradient-echo MRI study diagnostic value in CNS primary angiitis
Authors: Arias M , Osorio XR , Dapena D , Arias-Rivas S , Vázquez F 
Published: August 2008

Diagnosis of primary angiitis of the central nervous system (PACNS) is difficult in relation to variability in its clinical manifestations and absence of specific signs in neuroimaging. A young patient presented with a recurrent encephalopathic clinical course. T2 and fluid-attenuated inversion recovery-magnetic resonance imaging (FLAIR-MRI) showed hyperintense lesions in the cerebral white matter suggesting demyelination. Those lesions decreased or even disappeared after treatment with steroids and immunoglobulins. In echo gradient MRI (T2*-MRI), there were permanent cortical-subcortical petechial hypointense lesions (microhemorrhages). Definite diagnosis was established after cerebral biopsy. Intravenous cyclophosphamide was administrated with no new relapses in more than 18 months of follow-up. In a compatible clinical course, the finding of petechial hemorrhages in T2*-WI could play an important role in early diagnosis of PACNS.
Detection of genome-wide polymorphisms in the AT-rich Plasmodium falciparum genome using a high-density microarray
Authors: Jiang Hongying , Yi Ming , Mu Jianbing , Zhang Louie , Ivens Al , Klimczak Leszek J , Huyen Yentram , Stephens Robert M , Su Xin-zhuan 
Published: August 2008

Abstract

Background
Genetic mapping is a powerful method to identify mutations that cause drug resistance and other phenotypic changes in the human malaria parasite Plasmodium falciparum. For efficient mapping of a target gene, it is often necessary to genotype a large number of polymorphic markers. Currently, a community effort is underway to collect single nucleotide polymorphisms (SNP) from the parasite genome. Here we evaluate polymorphism detection accuracy of a high-density 'tiling' microarray with 2.56 million probes by comparing single feature polymorphisms (SFP) calls from the microarray with known SNP among parasite isolates.

Results
We found that probe GC content, SNP position in a probe, probe coverage, and signal ratio cutoff values were important factors for accurate detection of SFP in the parasite genome. We established a set of SFP calling parameters that could predict mSFP (SFP called by multiple overlapping probes) with high accuracy (≥ 94%) and identified 121,087 mSFP genome-wide from five parasite isolates including 40,354 unique mSFP (excluding those from multi-gene families) and ~18,000 new mSFP, producing a genetic map with an average of one unique mSFP per 570 bp. Genomic copy number variation (CNV) among the parasites was also cataloged and compared.

Conclusion
A large number of mSFP were discovered from the P. falciparum genome using a high-density microarray, most of which were in clusters of highly polymorphic genes at chromosome ends. Our method for accurate mSFP detection and the mSFP identified will greatly facilitate large-scale studies of genome variation in the P. falciparum parasite and provide useful resources for mapping important parasite traits.
Recombination and selectional forces in cyanopeptolin NRPS operons from highly similar, but geographically remote Planktothrix strains
Authors: Rounge Trine B , Rohrlack Thomas , Kristensen Tom , Jakobsen Kjetill S 
Published: August 2008

Abstract

Background
Cyanopeptolins are nonribosomally produced heptapetides showing a highly variable composition. The cyanopeptolin synthetase operon has previously been investigated in three strains from the genera Microcystis, Planktothrix and Anabaena. Cyanopeptolins are displaying protease inhibitor activity, but the biological function(s) is (are) unknown. Cyanopeptolin gene cluster variability and biological functions of the peptide variants are likely to be interconnected.

Results
We have investigated two cyanopeptolin gene clusters from highly similar, but geographically remote strains of the same genus. Sequencing of a nonribosomal peptide synthetase (NRPS) cyanopeptolin gene cluster from the Japanese strain Planktothrix NIES 205 (205-oci), showed the 30 kb gene cluster to be highly similar to the oci gene cluster previously described in Planktothrix NIVA CYA 116, isolated in Norway. Both operons contained seven NRPS modules, a sulfotransferase (S) and a glyceric acid loading (GA)-domain. Sequence analyses showed a high degree of conservation, except for the presence of an epimerase domain in NIES 205 and the regions around the epimerase, showing high substitution rates and Ka/Ks values above 1. The two strains produce almost identical cyanopeptolins, cyanopeptolin-1138 and oscillapeptin E respectively, but with slight differences regarding the production of minor cyanopeptolin variants. These variants may be the result of relaxed adenylation (A)-domain specificity in the nonribosomal enzyme complex. Other genetic markers (16S rRNA, ntcA and the phycocyanin cpcBA spacer) were identical, supporting that these geographically separated Planktothrix strains are closely related.

Conclusion
A horizontal gene transfer event resulting in exchange of a whole module-encoding region was observed. Nucleotide statistics indicate that both purifying selection and positive selection forces are operating on the gene cluster. The positive selection forces are acting within and around the epimerase insertion while purifying selection conserves the remaining (major) part of the gene cluster. The presence of an epimerase in the gene cluster is in line with the D-configuration of Htyr, determined experimentally in oscillapeptin E in a previous study.
Mutant polycystin-2 induces proliferation in primary rat tubular epithelial cells in a STAT-1/p21-independent fashion accompanied instead by alterations in expression of p57KIP2and Cdk2
Authors: Felekkis Kyriacos N , Koupepidou Panayiota , Kastanos Evdokia , Witzgall Ralph , Bai Chang-Xi , Li Li , Tsiokas Leonidas , Gretz Norbert , Deltas Constantinos 
Published: August 2008

AbstractBackgroundAutosomal Dominant Polycystic Kidney Disease (ADPKD) is characterized by the formation of multiple fluid-filled cysts that destroy the kidney architecture resulting in end-stage renal failure. Mutations in genesPKD1andPKD2account for nearly all cases of ADPKD. Increased cell proliferation is one of the key features of the disease. Several studies indicated that polycystin-1 regulates cellular proliferation through various signaling pathways, but little is known about the role played by polycystin-2, the product ofPKD2. Recently, it was reported that as with polycystin-1, polycystin-2 can act as a negative regulator of cell growth by modulating the levels of the cyclin-dependent kinase inhibitor, p21 and the activity of the cyclin-dependent kinase 2, Cdk2.MethodsHere we utilized different kidney cell-lines expressing wild-type and mutantPKD2as well as primary tubular epithelial cells isolated from a PKD transgenic rat to further explore the contribution of the p21/Cdk2 pathway in ADPKD proliferation.ResultsSurprisingly, over-expression of wild-typePKD2in renal cell lines failed to inactivate Cdk2 and consequently had no effect on cell proliferation. On the other hand, expression of mutatedPKD2augmented proliferation only in the primary tubular epithelial cells of a rat model but this was independent of the STAT-1/p21 pathway. On the contrary, multiple approaches revealed unequivocally that expression of the cyclin-dependent kinase inhibitor, p57KIP2, is downregulated, while p21 remains unchanged. This p57 reduction is accompanied by an increase in Cdk2 levels.ConclusionOur results indicate the probable involvement of p57KIP2on epithelial cell proliferation in ADPKD implicating a new mechanism for mutant polycystin-2 induced proliferation. Most importantly, contrary to previous studies, abnormal proliferation in cells expressing mutant polycystin-2 appears to be independent of STAT-1/p21.