bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevention of Gordonia and Nocardia Stabilized Foam Formation by Using Bacteriophage GTE7
Authors: Petrovski Steve , Seviour Robert J. , Tillett Daniel
Published: September 2011

Most activated sludge treatment plants suffer from the presence of foams on the surfaces of their aeration reactors. These are often stabilized by hydrophobic mycolic acid-synthesizing actinobacterial species. A polyvalent
Siphoviridae
phage, GTE7, which lysed several
Gordonia
and
Nocardia
species, is described here. Its genome has a modular structure similar to that described for
Rhodococcus
phage ReqiDocB7. In laboratory-scale experiments, we showed that GTE7 prevents stabilization of foams by these
Gordonia
and
Nocardia
species.
Characterization of Single-Nucleotide-Polymorphism Markers for Plasmopara viticola, the Causal Agent of Grapevine Downy Mildew
Authors: Delmotte F. , Machefer V. , Giresse X. , Richard-Cervera S. , Latorse M. P. , Beffa R.
Published: September 2011

We report 34 new nuclear single-nucleotide-polymorphism (SNP) markers that have been developed from an expressed sequence tag library of
Plasmopara viticola
, the causal agent of grapevine downy mildew. This newly developed battery of markers will provide useful additional genetic tools for population genetic studies of this important agronomic species.
Cross-Sectional and Longitudinal Comparisons of the Predominant Fecal Microbiota Compositions of a Group of Pediatric Patients with Cystic Fibrosis and Their Healthy Siblings
Authors: Duytschaever Gwen , Huys Geert , Bekaert Maarten , Boulanger Linda , De Boeck Kris , Vandamme Peter
Published: September 2011

Although only poorly documented, it can be assumed that intensive antibiotic treatments of chronic lung infections in patients with cystic fibrosis (CF) also affect the diversity and metabolic functioning of the gastrointestinal microbiota and potentially lead to a state of dysbiosis. A better knowledge of the differences in gut microbiota composition and stability between patients with CF and healthy subjects could lead to optimization of current antibiotic therapies and/or development of add-on therapies. Using conventional culturing and population fingerprinting by denaturing gradient gel electrophoresis (DGGE) of 16S rRNA amplicons, we compared the predominant fecal microbiota of 21 patients with CF and 24 healthy siblings in a cross-sectional study. General medium counts, as well as counts on media specific for lactic acid bacteria, clostridia,
Bifidobacterium
spp.,
Veillonella
spp., and
Bacteroides-Prevotella
spp., were consistently higher in sibling samples than in CF samples, whereas the reverse was found for enterobacterial counts. DGGE fingerprinting uncovered large intersubject variations in both study groups. On the other hand, the cross-sectional data indicated that the predominant fecal microbiota of patients and siblings had comparable species richness. In addition, a longitudinal study was performed on 7 or 8 consecutive samples collected over a 2-year period from two patients and their respective siblings. For these samples, DGGE profiling indicated an overall trend toward lower temporal stability and lower species richness in the predominant fecal CF microbiota. The observed compositional and dynamic perturbations provide the first evidence of a general dysbiosis in children with CF compared to their siblings.
Direct and Indirect Influence of Parental Bedrock on Streambed Microbial Community Structure in Forested Streams
Authors: Mosher Jennifer J. , Findlay Robert H.
Published: September 2011

A correlative study was performed to determine if variation in streambed microbial community structure in low-order forested streams can be directly or indirectly linked to the chemical nature of the parental bedrock of the environments through which the streams flow. Total microbial and photosynthetic biomass (phospholipid phosphate [PLP] and chlorophyll
a
), community structure (phospholipid fatty acid analysis), and physical and chemical parameters were measured in six streams, three located in sandstone and three in limestone regions of the Bankhead National Forest in northern Alabama. Although stream water flowing through the two different bedrock types differed significantly in chemical composition, there were no significant differences in total microbial and photosynthetic biomass in the sediments. In contrast, sedimentary microbial community structure differed between the bedrock types and was significantly correlated with stream water ion concentrations. A pattern of seasonal variation in microbial community structure was also observed. Further statistical analysis indicated dissolved organic matter (DOM) quality, which was previously shown to be influenced by geological variation, correlated with variation in bacterial community structure. These results indicate that the geology of underlying bedrock influences benthic microbial communities directly via changes in water chemistry and also indirectly via stream water DOM quality.
Two Large, Related, Cryptic Plasmids from Geographically Distinct Isolates of Sulfobacillus thermotolerans
Authors: Deane S. M. , Rawlings D. E.
Published: September 2011

Two large cryptic plasmids (59.2 and 65.9 kb) from isolates of
Sulfobacillus thermotolerans
from Yellowstone National Park (United States) and the Caribbean island of Montserrat were isolated and sequenced. This analysis revealed a common “backbone” region coding for a potential plasmid stability system plus a nonpheromone conjugation system containing homologues of both type IV and type II (tight adherence, or Tad-like) secretion systems.
Secreted Factors from Bifidobacterium animalis subsp.
lactis
Inhibit NF-κB-Mediated Interleukin-8 Gene Expression in Caco-2 Cells
Authors: Wang Zhonggui , Wang Jinfeng , Cheng Yi , Liu Xin , Huang Ying
Published: September 2011

The objective of the present study was to evaluate the anti-inflammatory effects of
Bifidobacterium animalis
subsp.
lactis
strain BB12 in stimulated Caco-2 cells and to characterize the factors responsible for these anti-inflammatory effects. Characterization and purification studies indicate that BB12's anti-inflammatory factors might include a 50-kDa proteinaceous compound that is stable under a variety of heat and pH conditions.
Rapid Screening Method for Compounds That Affect the Growth and Germination of Candida albicans, Using a Real-Time PCR Thermocycler
Authors: Jarosz Lucja M. , Krom Bastiaan P.
Published: September 2011

We propose a screening method for compounds affecting growth and germination in
Candida albicans
using a real-time PCR thermocycler to quantify green fluorescent protein (GFP) fluorescence. Using P

ACT1
-GFP

and P

HWP1
-GFP

reporter strains, the effects of a wide range of compounds on growth and hyphal formation were quantitatively assessed within 3 h after inoculation.
The Level of AdpA Directly Affects Expression of Developmental Genes in Streptomyces coelicolor
Authors: Wolański Marcin , Donczew Rafał , Kois-Ostrowska Agnieszka , Masiewicz Paweł , Jakimowicz Dagmara , Zakrzewska-Czerwińska Jolanta
Published: September 2011

AdpA is a key regulator of morphological differentiation in
Streptomyces
. In contrast to
Streptomyces griseus
, relatively little is known about AdpA protein functions in
Streptomyces coelicolor
. Here, we report for the first time the translation accumulation profile of the
S. coelicolor
adpA
(

adpA
Sc

) gene; the level of
S. coelicolor
AdpA (AdpA

Sc

) increased, reaching a maximum in the early stage of aerial mycelium formation (after 36 h), and remained relatively stable for the next several hours (48 to 60 h), and then the signal intensity decreased considerably. AdpA

Sc

specifically binds the

adpA
Sc

promoter region
in vitro
and
in vivo
, suggesting that its expression is autoregulated; surprisingly, in contrast to
S. griseus
, the protein presumably acts as a transcriptional activator. We also demonstrate a direct influence of AdpA

Sc

on the expression of several genes whose products play key roles in the differentiation of
S. coelicolor
: STI, a protease inhibitor; RamR, an atypical response regulator that itself activates expression of the genes for a small modified peptide that is required for aerial growth; and ClpP1, an ATP-dependent protease. The diverse influence of AdpA

Sc

protein on the expression of the analyzed genes presumably results mainly from different affinities of AdpA

Sc

protein to individual promoters.
CodY-Mediated Regulation of Guanosine Uptake in Bacillus subtilis
Authors: Belitsky Boris R. , Sonenshein Abraham L.
Published: September 2011

CodY is a global transcriptional regulator known to control expression of more than 100 genes and operons in
Bacillus subtilis
. Some of the most strongly repressed targets of CodY, the
nupNOPQ
(formerly,
yufNOPQ
) genes, were found to encode a guanosine transporter. Using DNase I footprinting experiments, we identified two high-affinity CodY-binding sites in the regulatory region of the
nupN
gene. The two sites are located 50 bp upstream and 163 bp downstream of the transcription start site. The downstream site was responsible for 6- to 8-fold
nupN
repression in the absence of the upstream site. When the upstream site was intact, however, only a minor contribution of the downstream site to
nupN
regulation could be detected under the conditions tested. Both sites contained 15-bp CodY-binding motifs with two mismatches each with respect to the consensus sequence, AATTTTCWGTTTTAA. However, the experimentally determined binding sites included additional sequences flanking the 15-bp CodY-binding motifs. An additional version of the 15-bp CodY-binding motif, with 5 mismatches with respect to the consensus but essential for efficient regulation by CodY, was found within the upstream site. The presence of multiple 15-bp motifs may be a common feature of CodY-binding sites.
Expression Level of a Chimeric Kinase Governs Entry into Sporulation in Bacillus subtilis
Authors: Eswaramoorthy Prahathees , Dravis Ashlee , Devi Seram Nganbiton , Vishnoi Monika , Dao Hoang-Anh , Fujita Masaya
Published: September 2011

Upon starvation,Bacillus subtiliscells switch from growth to sporulation. It is believed that the N-terminal sensor domain of the cytoplasmic histidine kinase KinA is responsible for detection of the sporulation-specific signal(s) that appears to be produced only under starvation conditions. Following the sensing of the signal, KinA triggers autophosphorylation of the catalytic histidine residue in the C-terminal domain to transmit the phosphate moiety, via phosphorelay, to the master regulator for sporulation, Spo0A. However, there is no direct evidence to support the function of the sensor domain, because the specific signal(s) has never been found. To investigate the role of the N-terminal sensor domain, we replaced the endogenous three-PAS repeat in the N-terminal domain of KinA with a two-PAS repeat derived fromEscherichia coliand examined the function of the resulting chimeric protein. Despite the introduction of a foreign domain, we found that the resulting chimeric protein, in a concentration-dependent manner, triggered sporulation by activating Spo0A through phosphorelay, irrespective of nutrient availability. Further, by using chemical cross-linking, we showed that the chimeric protein exists predominantly as a tetramer, mediated by the N-terminal domain, as was found for KinA. These results suggest that tetramer formation mediated by the N-terminal domain, regardless of the origin of the protein, is important and sufficient for the kinase activity catalyzed by the C-terminal domain. Taken together with our previous observations, we propose that the primary role of the N-terminal domain of KinA is to form a functional tetramer, but not for sensing an unknown signal.
How event reporting by US hospitals has changed from 2005 to 2009
Authors: Farley Donna O , Haviland Amelia , Haas Ann , Pham Chau , Munier William B , Battles James B
Published: September 2011

Context

Information is needed on the performance of hospitals' adverse-event reporting systems and the effects of national patient-safety initiatives, including the Patient Safety and Quality Improvement Act (PSQIA) of 2005. Results are presented of a 2009 survey of a sample of non-federal US hospitals and changes between 2005 and 2009 are examined.

Methods

The Adverse Event Reporting System survey was fielded in 2005 and 2009 using a mixed-mode design with stratified random samples of non-federal US hospitals; risk managers were respondents. Response rates were 81% in 2005 and 79% in 2009.

Results

Virtually all hospitals reported they had centralised adverse-event-reporting systems. However, scores on four performance indexes suggested that hospitals have not effectively implemented key components of reporting systems. Average index scores improved somewhat between 2005 and 2009 for supportive environment (0.7 increase; p<0.05) and types of staff reporting (0.08 increase; p<0.001). Average scores did not change for timely distribution of event reports or discussion with key departments and committees. Some within-hospital inconsistencies in responses between 2005 and 2009 were found. These self-reported responses may be optimistic assessments of hospital performance.

Conclusions

The 2009 survey confirmed improvement needs identified by the 2005 survey for hospitals' event reporting processes, while finding signs of progress. Optimising the use of surveys to assess the effects of national patient-safety initiatives such as PSQIA will require decreasing within-hospital variations in reporting rates.
A novel fluorinated stilbene exerts hepatoprotective properties in CCl4-induced acute liver damage
Authors: Rivera Horacio , Morales-Ríos Martha S. , Bautista Wendy , Shibayama Mineko , Tsutsumi Víctor , Muriel Pablo , Pérez-Álvarez Víctor
Published: September 2011

There has been a recently increase in the development of novel stilbene-based compounds with in vitro anti-inflamatory properties. For this study, we synthesized and evaluated the anti-inflammatory properties of 2 fluorinated stilbenes on carbon tetrachloride (CCl4)-induced acute liver damage. To achieve this, CCl4 (4 g·kg–1, per os) was administered to male Wistar rats, followed by either 2-fluoro-4′-methoxystilbene (FME) or 2,3-difluoro-4′-methoxystilbene (DFME) (10 mg·kg–1, per os). We found that although both of the latter compounds prevented cholestatic damage (γ-glutamyl transpeptidase activity), only DFME showed partial but consistent results in the prevention of necrosis, as assessed by both alanine aminotransferase activity and histological analysis. Since inflammatory responses are mediated by cytokines, mainly tumour necrosis factor α (TNF-α), we used the Western blot technique to determine the action of FME and DFME on the expression level of this cytokine. The observed increase in the level of TNF-α caused by CCl4 administration was only prevented by treatment with DFME, in agreement with our biochemical findings. This result was confirmed by measuring interleukin-6 (IL-6) levels, since the expression of this protein depends on the level of TNF-α. In this case, DFME completely blocked the CCl4-induced increase of IL-6. Our results suggest that DFME possesses greater anti-inflammatory properties in vivo than FME. DFME constitutes a possible therapeutic agent for liver disease and could serve as a template for structure optimization.
File-system litter
Authors: Neville-Neil George V.
Published: September 2011

Cleaning up your storage space quickly and efficiently.
Don't turn social media into another 'Literary Digest' poll
Authors: Gayo-Avello Daniel
Published: September 2011

The power to predict outcomes based on Twitter data is greatly exaggerated, especially for political elections.
Roles for redox mechanisms controlling protein kinase G in pulmonary and coronary artery responses to hypoxia
Authors: Neo Boon Hwa , Kandhi Sharath , Wolin Michael S.
Published: September 2011

We previously reported that isolated endothelium-removed bovine pulmonary arteries (BPAs) contract to hypoxia associated with removal of peroxide- and cGMP-mediated relaxation. In contrast, bovine coronary arteries (BCAs) relax to hypoxia associated with cytosolic NADPH oxidation coordinating multiple relaxing mechanisms. Since we recently found that H2O2 relaxes BPAs through PKG activation by both soluble guanylate cyclase (sGC)/cGMP-dependent and cGMP-independent thiol oxidation/subunit dimerization mechanisms, we investigated if these mechanisms participate in BPA contraction and BCA relaxation to hypoxia. The contraction of BPA (precontracted with 20 mM KCl) to hypoxia was associated with decreased PKG dimerization and PKG-mediated vasodilator-stimulated phosphoprotein (VASP) phosphorylation. In contrast, exposure of 20 mM KCl-precontracted endothelium-removed BCAs to hypoxia caused relaxation and increased dimerization and VASP phosphorylation. Depletion of sGC by organoid culture of BPAs with an oxidant of the sGC heme (10 μM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) increased aerobic force generation, decreased VASP phosphorylation, and inhibited further contraction to hypoxia and changes in VASP phosphorylation. Thiol reduction with dithiothreitol increased aerobic force in BPAs and decreased PKG dimerization, VASP phosphorylation, and the contraction to hypoxia. Furthermore, PKG-1α and sGC β1-subunit small interfering RNA-transfected BPAs demonstrated increased aerobic K+ force and inhibition of further contraction to hypoxia, associated with an attenuation of H2O2-elicited relaxation and VASP phosphorylation. Thus, decreases in both a sGC/cGMP-dependent and a dimerization-dependent activation of PKG by H2O2 appear to contribute to the contraction of BPAs elicited by hypoxia. In addition, stimulation of PKG activation by dimerization may be important in the relaxation of coronary arteries to hypoxia.
Thromboxane-induced actin polymerization in hypoxic pulmonary artery is independent of Rho
Authors: Fediuk Jena , Gutsol Alexey , Nolette Nora , Dakshinamurti Shyamala
Published: September 2011

Actin polymerization (APM), regulated by Rho GTPases, promotes myocyte force generation. Hypoxia is known to impede postnatal disassembly of the actin cytoskeleton in pulmonary arterial (PA) myocytes. We compared basal and agonist-induced APM in myocytes from PA and descending aorta (Ao), under hypoxic and normoxic conditions. We also examined effects of thromboxane challenge on force generation and cytoskeletal assembly in resistance PA and renal arteries from neonatal swine with persistent pulmonary hypertension (PPHN) induced by 72-h normobaric hypoxia, compared with age-matched controls. Synthetic and contractile phenotype myocytes from neonatal porcine PA or Ao were grown in hypoxia (10% O2) or normoxia (21% O2) for 7 days, then challenged with 10−6 M thromboxane mimetic U46619. F/G actin ratio was quantified by laser-scanning cytometry and by cytoskeletal fractionation. Thromboxane receptor (TP) G protein coupling was measured by immunoprecipitation and probing for Gαq, G12, or G13, RhoA activation by Rhotekin-RBD affinity precipitation, and LIM kinase (LIMK) and cofilin phosphorylation by Western blot. Isometric force to serial concentrations of U46619 was measured in muscular pulmonary and renal arteries from PPHN and control swine; APM was quantified in fixed contracted vessels. Contractile PA myocytes exhibit marked Rho-dependent APM in hypoxia, with increased active RhoA and LIMK phosphorylation. Their additional APM response to U46619 challenge is independent of RhoA, reflecting decreased TP association with G12/13 in favor of Gαq. In contrast, hypoxic contractile Ao myocytes polymerize actin modestly and depolymerize to U46619. Both basal APM and the APM response to U46619 are increased in PPHN PA. APM corresponds with increased force generation to U46619 challenge in PPHN PA but not renal arteries.
Intra-airway administration of small interfering RNA targeting plasminogen activator inhibitor-1 attenuates allergic asthma in mice
Authors: Miyamoto Shintaro , Hattori Noboru , Senoo Tadashi , Onari Yojiro , Iwamoto Hiroshi , Kanehara Masashi , Ishikawa Nobuhisa , Fujitaka Kazunori , Haruta Yoshinori , Murai Hiroshi , Yokoyama Akihito , Kohno Nobuoki
Published: September 2011

Recent studies suggest that plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of the fibrinolytic system, may promote the development of asthma. To further investigate the significance of PAI-1 in the pathogenesis of asthma and determine the possibility that PAI-1 could be a therapeutic target for asthma, this study was conducted. First, PAI-1 levels in induced sputum (IS) from asthmatic subjects and healthy controls were measured. In asthmatic subjects, IS PAI-1 levels were elevated, compared with that of healthy controls, and were significantly higher in patients with long-duration asthma compared with short-duration asthma. PAI-1 levels were also found to correlate with IS transforming growth factor-β levels. Then, acute and chronic asthma models induced by ovalbumin were established in PAI-1-deficient mice and wild-type mice that received intra-airway administrations of small interfering RNA against PAI-1 (PAI-1-siRNA). We could demonstrate that eosinophilic airway inflammation and airway hyperresponsiveness were reduced in an acute asthma model, and airway remodeling was suppressed in a chronic asthma model in both PAI-1-deficient mice and wild-type mice that received intra-airway administration of PAI-1-siRNA. These results indicate that PAI-1 is strongly involved in the pathogenesis of asthma, and intra-airway administration of PAI-1-siRNA may be able to become a new therapeutic approach for asthma.
Relation between trunk fat volume and reduction of total lung capacity in obese men
Authors: Watson R. A. , Pride N. B. , Thomas E. Louise , Ind P. W. , Bell J. D.
Published: September 2011

Reduction in total lung capacity (TLC) in obese men is associated with restricted expansion of the thoracic cavity at full inflation. We hypothesized that thoracic expansion was reduced by the load imposed by increased total trunk fat volume or its distribution. Using MRI, we measured internal and subcutaneous trunk fat and total abdominal and thoracic volumes at full inflation in 14 obese men [mean age: 52.4 yr, body mass index (BMI): 38.8 (range: 36–44) kg/m2] and 7 control men [mean age: 50.1 yr, BMI: 25.0 (range: 22–27.5) kg/m2]. TLC was measured by multibreath helium dilution and was restricted (<80% of the predicted value) in six obese men (the OR subgroup). All measurements were made with subjects in the supine position. Mean total trunk fat volume was 16.65 (range: 12.6–21.8) liters in obese men and 6.98 (range: 3.0–10.8) liters in control men. Anthropometry and mean total trunk fat volumes were similar in OR men and obese men without restriction (the ON subgroup). Mean total intraabdominal volume was 9.41 liters in OR men and 11.15 liters in ON men. In obese men, reduced thoracic expansion at full inflation and restriction of TLC were not inversely related to a large volume of 1) intra-abdominal or total abdominal fat, 2) subcutaneous fat volume around the thorax, or 3) total trunk fat volume. In addition, trunk fat volumes in obese men were not inversely related to gas volume or estimated intrathoracic volume at supine functional residual capacity. In conclusion, this study failed to support the hypotheses that restriction of TLC or impaired expansion of the thorax at full inflation in middle-aged obese men was simply a consequence of a large abdominal volume or total trunk fat volume or its distribution.
Cabozantinib (XL184), a Novel MET and VEGFR2 Inhibitor, Simultaneously Suppresses Metastasis, Angiogenesis, and Tumor Growth
Authors: Yakes F. Michael , Chen Jason , Tan Jenny , Yamaguchi Kyoko , Shi Yongchang , Yu Peiwen , Qian Fawn , Chu Felix , Bentzien Frauke , Cancilla Belinda , Orf Jessica , You Andrew , Laird A. Douglas , Engst Stefan , Lee Lillian , Lesch Justin , Chou Yu-Chien , Joly Alison H.
Published: September 2011

The signaling pathway of the receptor tyrosine kinase MET and its ligand hepatocyte growth factor (HGF) is important for cell growth, survival, and motility and is functionally linked to the signaling pathway of VEGF, which is widely recognized as a key effector in angiogenesis and cancer progression. Dysregulation of the MET/VEGF axis is found in a number of human malignancies and has been associated with tumorigenesis. Cabozantinib (XL184) is a small-molecule kinase inhibitor with potent activity toward MET and VEGF receptor 2 (VEGFR2), as well as a number of other receptor tyrosine kinases that have also been implicated in tumor pathobiology, including RET, KIT, AXL, and FLT3. Treatment with cabozantinib inhibited MET and VEGFR2 phosphorylation in vitro and in tumor models in vivo and led to significant reductions in cell invasion in vitro. In mouse models, cabozantinib dramatically altered tumor pathology, resulting in decreased tumor and endothelial cell proliferation coupled with increased apoptosis and dose-dependent inhibition of tumor growth in breast, lung, and glioma tumor models. Importantly, treatment with cabozantinib did not increase lung tumor burden in an experimental model of metastasis, which has been observed with inhibitors of VEGF signaling that do not target MET. Collectively, these data suggest that cabozantinib is a promising agent for inhibiting tumor angiogenesis and metastasis in cancers with dysregulated MET and VEGFR signaling. Mol Cancer Ther; 10(12); 2298–308. ©2011 AACR.
Plasma C-Terminal Pro-Endothelin-1 and the Natriuretic Pro-Peptides NT-proBNP and MR-proANP in Very Preterm Infants with Patent Ductus Arteriosus
Authors: Letzner Julia , Berger Florian , Schwabe Sarah , Benzing Jörg , Morgenthaler Nils G. , Bucher Hans Ulrich , Bührer Christoph , Arlettaz Romaine , Wellmann Sven
Published: September 2011

Background: In very preterm infants, clinical decision-making, such as closing a patent ductus arteriosus (PDA), may be aided by measuring circulating natriuretic and endothelial pro-peptides. Objectives: To investigate the association between perinatal characteristics, PDA echocardiography and plasma concentrations of stable pro-peptides of B-type natriuretic peptide (NT-proBNP), atrial natriuretic peptide (MR-proANP) and endothelin-1 (CT-proET-1). Methods: A prospective, cross-sectional, single-center study was performed in 66 infants who were less than 32 weeks of gestational age. Pro-peptide concentrations were determined at birth and at day 2–3 of life. Results: Plasma concentrations of all 3 pro-peptides increased on average 2- to 5-fold from birth to day 2–3 of life. NT-proBNP and MR-proANP were closely related at birth and at day 2–3 (Rs 0.902 and 0.897, respectively, p < 0.001), whereas CT-proET-1 was related to NT-proBNP and MR-proANP at birth (Rs 0.478 and 0.460, respectively, p < 0.001) but not at day 2–3. Birth weight was negatively related to all 3 pro-peptides at birth (p < 0.01); however, preeclampsia and compromised placental perfusion were associated with elevated NT-proBNP and MR-proANP concentrations at birth. At day 2–3, MR-proANP and NT-proBNP correlated significantly with the ductal diameter (Rs 0.416 and 0.415, respectively, both p = 0.011), whereas CT-proET-1 correlated with the left atrium/aorta ratio (Rs 0.506, p = 0.027). CT-proET-1 was elevated in infants with treated compared to untreated PDA [median (5–95% range) 388 (272–723) vs. 303 (152–422) pmol/l, p = 0.011], but not NT-proBNP or MR-proANP. Conclusion: CT-proET-1 is a promising predictor in determining the need for PDA intervention.
Cortical and Hippocampal Atrophy in Patients with Autosomal Dominant Familial Alzheimer’s Disease
Authors: Apostolova Liana G. , Hwang Kristy S. , Medina Luis D. , Green Amity E. , Braskie Meredith N. , Dutton Rebecca A. , Lai Jeffrey , Geschwind Daniel H. , Cummings Jeffrey L. , Thompson Paul M. , Ringman John M.
Published: September 2011

Background: Both familial and sporadic Alzheimer’s disease (AD) result in progressive cortical and subcortical atrophy. Familial autosomal dominant AD (FAD) allows us to study AD brain changes presymptomatically. Methods: 33 subjects at risk for FAD (25 for PSEN1 and 8 for APP mutations; 22 mutation carriers and 11 controls) and 3 demented PSEN1 mutation carriers underwent T1-weighted MPRAGE 1.5T MRI. Using the hippocampal radial distance and cortical pattern matching techniques, we investigated the effects of carrier status and dementia diagnosis on cortical and hippocampal atrophy. All analyses were corrected for age and relative age (years to median age of disease onset in the family). Results: The dementia cases had pronounced cortical atrophy in the lateral and medial parietal, posterior cingulate and frontal cortices and hippocampal atrophy bilaterally relative to both nondemented carriers and controls. Nondemented carriers did not show significant cortical thinning or hippocampal atrophy relative to controls. Conclusions: FAD is associated with thinning of the posterior association and frontal cortices and hippocampal atrophy. Larger sample sizes may be necessary to reliably identify cortical atrophy in presymptomatic carriers.
Bacterial Contamination and the Transport Vial Material Affect Cerebrospinal Fluid Concentrations of β-Amyloid and Tau Protein as Determined by Enzyme Immunoassay
Authors: Fronek Kathrin , Lange Peter , Spreer Annette , Eiffert Helmut , Nau Roland
Published: September 2011

Background/Aims: Determination of marker proteins of neuronal degeneration in cerebrospinal fluid (CSF) is of increasing importance. However, preanalytical problems may compromise the results. Methods: We studied the influence of the transport tube material and shaking at room temperature on the CSF concentrations of β-amyloid and tau protein determined by enzyme immunoassays. Results: The materials of the transport tube moderately influenced the CSF concentrations of β-amyloid and tau protein. Polyethylene and polypropylene tubes were well suited, but glass, polycarbonate and polystyrene tubes caused a decrease in the CSF β-amyloid and tau protein concentrations. The strongest impact, however, was caused by bacterial contamination of samples. Contamination with high concentrations of Pseudomonas aeruginosa and related species rendered β-amyloid undetectable and strongly diminished tau protein concentrations. The effects of several Gram-positive bacteria were less pronounced. Addition of 0.1% sodium azide prior to bacterial contamination increased the interval at which CSF could be kept at room temperature without a substantial reduction of the β-amyloid or tau protein concentration. Conclusion: Polyethylene or polypropylene tubes are suitable transport vessels for CSF samples. Bacterial contamination during sampling and portioning must be avoided. Addition of sodium azide may be an option when transport of the sample is delayed.
Remote-Conditioning Ischemia Provides a Potential Approach to Mitigate Contrast Medium-Induced Reduction in Kidney Function: A Retrospective Observational Cohort Study
Authors: Whittaker Peter , Przyklenk Karin
Published: September 2011

Contrast medium administration during imaging and therapeutic procedures can cause renal injury, partly due to ischemia. Therefore, we hypothesized that brief ischemia and reperfusion episodes applied at a distant site – multiple balloon inflations and deflations during angioplasty – may serve as a remote-conditioning (RC) stimulus and thereby protect against contrast-induced kidney injury. To test this hypothesis, we (1) utilized cases from a prior study in which patients undergoing emergent angioplasty for ST segment elevation myocardial infarction received either 1–3 balloon inflations (controls) or were ‘conditioned’ with multiple (≧4) inflations, and (2) assessed renal function for 3 days in patients with an estimated glomerular filtration rate (eGFR) of <90 ml/min/1.73 m2 prior to revascularization (mild kidney disease). Both groups displayed increased eGFR at day 1 after angioplasty versus baseline; attributed to in-hospital hydration (control: 77 ± 14 vs. 68 ± 12 ml/min/1.73 m2; p < 0.01; RC: 81 ± 21 vs. 69 ± 12 ml/min/1.73 m2; p < 0.01). In controls, this improvement was transient: eGFR subsequently decreased to 70 ± 14 ml/min/1.73 m2 at day 3 (p < 0.05). In contrast, the RC group (despite receiving 25% more contrast volume) showed no functional decline at day 3 (80 ± 14 ml/min/1.73 m2). These results are consistent with remote ischemic conditioning providing a novel potential approach to attenuate contrast-associated renal injury.
Silent Cardiac Ischemia after an Ischemic Stroke of the Right Hemisphere
Authors: Kasius Kristel M. , Lamfers Evert J.P. , Venderink Dick J. , Verhagen Wim I.M.
Published: September 2011

A patient is described who previously had daily complaints of angina pectoris, yet no longer experienced chest pain after an ischemic stroke of the right hemisphere, despite several recorded episodes of electrocardiographic changes and an elevation of cardiac enzymes compatible with myocardial ischemia. The cingulate gyrus is involved in spatial attention and neglect, and is, according to positron emission tomography studies, less activated in silent myocardial ischemia. We suggest that this patient was not aware of the angina because of putamen ischemia and secondary disturbed projection to the cingulate gyrus and no longer felt or experienced this referred pain.
Fetal Growth and Preterm Birth Influence Cardiovascular Risk Factors and Arterial Health in Young Adults
Authors: Skilton Michael R. , Viikari Jorma S.A. , Juonala Markus , Laitinen Tomi , Lehtimäki Terho , Taittonen Leena , Kähönen Mika , Celermajer David S. , Raitakari Olli T.
Published: September 2011

Objective—

Impaired fetal growth is associated with cardiovascular disease in adulthood. The mechanisms of this association remain poorly described. We aimed to determine the associations of impaired fetal growth and preterm birth with cardiovascular risk factors and arterial health in a large cohort of young adults.

Methods and Results—

Carotid intima-media thickness, brachial flow-mediated dilatation and cardiovascular risk factors were compared between young adults (24–45 years) born at term with impaired fetal growth (birth weight <10th percentile; n=207), born preterm (<37 weeks' gestation; n=253), and a control group born at term with normal fetal growth (birth weight 50–90th percentile; n=835), in the Cardiovascular Risk in Young Finns study. Compared with controls, those with impaired fetal growth had elevated triglycerides (
P
=0.006), C-reactive protein (
P
=0.004), low-density lipoprotein cholesterol, systolic blood pressure (both
P
=0.06), and intima-media thickness and impaired flow-mediated dilatation (both
P
=0.02), the latter partially mediated by systolic blood pressure, C-reactive protein, and triglycerides. Those born preterm had higher intima-media thickness (
P
=0.005) and lower flow-mediated dilatation (
P
=0.03) compared with controls, although this was restricted to those with concurrent fetal growth restriction.

Conclusion—

Impaired fetal growth is associated with impaired endothelial function and elevated preclinical atherosclerosis in young adults, partly mediated by inflammation, blood pressure, and triglycerides. This association is most marked for those also born preterm.
Proteomic Analysis of Polymorphonuclear Neutrophils Identifies Catalase as a Novel Biomarker of Abdominal Aortic Aneurysm: Potential Implication of Oxidative Stress in Abdominal Aortic Aneurysm Progression
Authors: Ramos-Mozo Priscila , Madrigal-Matute Julio , Martinez-Pinna Roxana , Blanco-Colio Luis Miguel , Lopez Juan Antonio , Camafeita Emilio , Meilhac Olivier , Michel Jean-Baptiste , Aparicio Cesar , de Ceniga Melina Vega , Egido Jesus , Martín-Ventura José Luis
Published: September 2011

Objective—

Polymorphonuclear neutrophils (PMNs) play a main role in abdominal aortic aneurysm (AAA) progression. We have analyzed circulating PMNs isolated from AAA patients and controls by a proteomic approach to identify proteins potentially involved in AAA pathogenesis.

Methods and Results—

PMNs from 8 AAA patients (4 large AAA >5 cm and 4 small AAA 3–5 cm) and 4 controls were analyzed by 2D differential in-gel electrophoresis. Among differentially expressed spots, several proteins involved in redox balance were identified by mass spectrometry (eg, cyclophilin, thioredoxin reductase, catalase). Diminished catalase expression and activity were observed in PMNs from AAA patients compared with controls. In contrast, PMNs from AAA patients displayed higher H
2
O
2
and myeloperoxidase levels than PMNs from controls. Moreover, a significant decrease in catalase mRNA levels was observed in PMNs after phorbol 12-myristate 13-acetate incubation. Catalase plasma levels were also decreased in large (n=47) and small (n=56) AAA patients compared with controls (n=34). We observed catalase expression in AAA thrombus and thrombus-conditioned medium, associated with PMN infiltration. Furthermore, increased H
2
O
2
levels were observed in AAA thrombus-conditioned medium compared with the media layer.

Conclusion—

Diminished catalase levels in circulating PMNs and plasma are observed in AAA patients, supporting an important role of oxidative stress in AAA evolution.
Notch3 Arg170Cys Knock-In Mice Display Pathologic and Clinical Features of the Neurovascular Disorder Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy
Authors: Wallays Goedele , Nuyens Dieter , Silasi-Mansat Robert , Souffreau Joris , Callaerts-Vegh Zsuzsanna , Van Nuffelen An , Moons Lieve , D'Hooge Rudi , Lupu Florea , Carmeliet Peter , Collen Désiré , Dewerchin Mieke
Published: September 2011

Objective—

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult-onset neurovascular disorder caused by stereotyped mutations in the NOTCH3 receptor. Elucidation of its pathobiology is still incomplete and remains a challenge, in part because the available preclinical mouse models to date do not reproduce the full spectrum of CADASIL pathology and clinical disease.

Methods and Results—

Here, we report a novel knock-in mouse with Arg170Cys substitution in murine Notch3, corresponding to the prevalent Arg169Cys substitution in CADASIL. The Notch3
Arg170Cys
mice displayed late-onset, dominant CADASIL arteriopathy with typical granular osmiophilic material deposition and developed brain histopathology including thrombosis, microbleeds, gliosis, and microinfarction. Furthermore, Notch3
Arg170Cys
mice experienced neurological symptoms with motor defects such as staggering gait and limb paresis.

Conclusion—

This model, for the first time, phenocopies the arteriopathy and the histopathologic as well as clinical features of CADASIL and may offer novel opportunities to investigate disease pathogenesis.
Clinical Value of Absolute Quantification of Myocardial Perfusion With
15
O-Water in Coronary Artery Disease
Authors: Kajander Sami A. , Joutsiniemi Esa , Saraste Markku , Pietilä Mikko , Ukkonen Heikki , Saraste Antti , Sipilä Hannu T. , Teräs Mika , Mäki Maija , Airaksinen Juhani , Hartiala Jaakko , Knuuti Juhani
Published: September 2011

Background—

The standard interpretation of perfusion imaging is based on the assessment of relative perfusion distribution. The limitations of that approach have been recognized in patients with multivessel disease and endothelial dysfunction. To date, however, no large clinical studies have investigated the value of measuring quantitative blood flow and compared that with relative uptake.

Methods and Results—

One hundred four patients with moderate (30%–70%) pretest likelihood of coronary artery disease (CAD) underwent PET imaging during adenosine stress using
15
O-water and dynamic imaging. Absolute myocardial blood flow was calculated from which both standard relative myocardial perfusion images and images scaled to a known absolute scale were produced. The patients and the regions then were classified as normal or abnormal and compared against the reference of conventional angiography with fractional flow reserve. In patient-based analysis, the positive predictive value, negative predictive value, and accuracy of absolute perfusion in the detection of any obstructive CAD were 86%, 97%, and 92%, respectively, with absolute quantification. The corresponding values with relative analysis were 61%, 83%, and 73%, respectively. In region-based analysis, the receiver operating characteristic curves confirmed that the absolute quantification was superior to relative assessment. In particular, the specificity and positive predictive value were low using just relative differences in flow. Only 9 of 24 patients with 3-vessel disease were correctly assessed using relative analysis.

Conclusions—

The measurement of myocardial blood flow in absolute terms has a significant impact on the interpretation of myocardial perfusion. As expected, multivessel disease is more accurately detected.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00627172.
Left Atrial Remodeling and Response to Valsartan in the Prevention of Recurrent Atrial Fibrillation
Authors: Staszewsky Lidia , Wong Maylene , Masson Serge , Raimondi Elena , Gramenzi Silvana , Proietti Gianni , Bicego Dario , Emanuelli Carlo , Pulitanò Giancarlo , Taddei Filippo , Nicolis Enrico B. , Correale Ernesto , Fabbri Gianna , Bertocchi Federico , Franzosi Maria Grazia , Maggioni Aldo P. , Tognoni Gianni , Disertori Marcello , Latini Roberto
Published: September 2011

Background—

Left atrial (LA) dilation precedes or appears early after the onset of atrial fibrillation (AF) and factors in perpetuating the arrhythmia. Angiotensin receptor blockers were proposed for reversing LA remodeling. We evaluated the effect of valsartan on LA remodeling in patients with a recent episode of AF and the effect of LA size on AF recurrence (AFr).

Methods and Results—

LA and left ventricular (LV) echocardiographic variables were measured at baseline and 6 and 12 months in 340 patients from GISSI-AF, a trial testing valsartan prevention of AFr. Reversal of remodeling was considered as a decrease in LA size over 12 months. Changes in patients with and without recurrence and the relationship to duration of AFr were analyzed. Patients were 68.4±8.8 years old, with history of hypertension (85.3%) and cardioversion in the previous 2 weeks (87.4%) or ≥2 AFr in the previous 6 months (40.4%). Baseline LA maximal volume (LAVmax) was severely increased (>40 mL/m
2
); LV dimensions and function were relatively normal. Over 12 months, 54.4% of patients had AFr. LAVmax was unchanged by rhythm, time, or randomized treatment. Higher baseline LAVmax and lower LA emptying fraction were linearly related to increasing AFr duration during follow-up.

Conclusions—

GISSI-AF patients in sinus rhythm and history of AF showed severely increased LAVmax with mostly normal LV volume, mass, and systolic and diastolic function. Valsartan for 1 year did not reverse LA remodeling or prevent AFr. Half of the patients without AFr had severe LA dilation; therefore, mechanisms other than structural remodeling triggered recurrence.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00376272.
Siblings With Ischemic Stroke Study
Authors: Meschia James F. , Nalls Michael , Matarin Mar , Brott Thomas G. , Brown Robert D. , Hardy John , Kissela Brett , Rich Stephen S. , Singleton Andrew , Hernandez Dena , Ferrucci Luigi , Pearce Kerra , Keller Margaret , Worrall Bradford B. ,   for the Siblings With Ischemic Stroke Study Investigators*
Published: September 2011

Background and Purpose—

Ischemic stroke has a strong familial component to risk. The Siblings With Ischemic Stroke Study (SWISS) is a genome-wide, family-based analysis that included use of imputed genotypes. The Siblings With Ischemic Stroke Study was conducted to examine the associations between single-nucleotide polymorphisms (SNPs) and risk of stroke and stroke subtypes within pairs.

Methods—

The Siblings With Ischemic Stroke Study enrolled 312 probands with ischemic stroke from 70 US and Canadian centers. Affected siblings were ascertained by centers and confirmed by central record review; unaffected siblings were ascertained by telephone contact. Ischemic stroke was subtyped according to Trial of Org 10172 in Acute Stroke Treatment criteria. Genotyping was performed with an Illumina 610 quad array (probands) and an Illumina linkage V array (affected siblings). SNPs were imputed by using 1000 Genomes Project data and MACH software. Family-based association analyses were conducted by using the sibling transmission-disequilibrium test.

Results—

For all pairs, the correlation of age at stroke within pairs of affected siblings was
r
=0.83 (95% CI, 0.78–0.86;
P
<2.2×10
−16
). The correlation did not differ substantially by subtype. The concordance of stroke subtypes among affected pairs was 33.8% (kappa=0.13;
P
=5.06×10
−4
) and did not differ by age at stroke in the proband. Although no SNP achieved genome-wide significance for risk of ischemic stroke, there was clustering of the most associated SNPs on chromosomes 3p and 6p.

Conclusions—

Stroke subtype and age at stroke in affected sibling pairs exhibit significant clustering. No individual SNP reached genome-wide significance. However, 2 promising candidate loci were, although these risk loci warrant further examination in larger sample collections.
Systemic Hematologic Status Following Intraventricular Recombinant Tissue-Type Plasminogen Activator for Intraventricular Hemorrhage
Authors: Herrick Daniel B. , Ziai Wendy C. , Thompson Carol B. , Lane Karen , McBee Nichol A. , Hanley Daniel F.
Published: September 2011

Background and Purpose—

This is the first prospective evaluation of changes in systemic hematologic status following administration of intraventricular recombinant tissue-type plasminogen activator in patients with intraventricular hemorrhage (IVH).

Methods—

Laboratory data from subjects enrolled onto the Clot Lysis: Evaluating Accelerated Resolution of IVH (CLEAR IVH) Trials were analyzed. We analyzed pre- and post- recombinant tissue-type plasminogen activator dosing coagulation parameters. Longer-term changes in hematologic status were studied in subjects who received the study agent after blood clot in the third/fourth ventricles had resolved radiologically.

Results—

Plasma fibrinogen increased significantly in both treatment groups. Dosing did not have a significant impact on any systemic coagulation parameters in either treatment group.

Conclusions—

Intraventricular recombinant tissue-type plasminogen activator is unlikely to impact systemic coagulation or to compound the effects of systemic anticoagulation for deep venous thrombosis prophylaxis.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT00650858.