bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracisternal enzyme replacement therapy in lysosomal storage diseases: dispersal pathways, regional enzyme concentrations and the effect of posttreatment posture
Authors: Jolly R. D. , Marshall N. R. , Marshall J. , Hartman A. , Hemsley K. M. , Winner L. K. 
Published: December 2012

AimsTo investigate routes of dispersal of enzyme, its regional uptake and the effect of posture when replacement enzyme is administered directly into the cerebrospinal fluid (CSF).MethodsDispersal pathways of particles and solutes were investigated using intracisternal injections of india ink with visual assessment, and a contrast medium (Iohexol) with computer tomography (CT). Replacement enzyme was measured at 46 loci within the central nervous system (CNS) in four groups of dogs subjected to different post‐injection postural changes.ResultsIndia ink and CT studies showed dispersal pathways for CSF to be mainly via cisterns and sulci. Replacement enzyme reached all areas of the CNS tested, although mean concentrations varied 49‐fold over different areas of the brain. Posttreatment posture had only modest effects on enzyme uptake in limited anatomical sites.ConclusionsDispersal of solutes after injection is rapid and initially enhanced by the injection process. Preferential pathways for CSF flow in the subarachnoid spaces of the brain involve cisterns and sulci. The splenial and suprasplenial sulci in particular appear important conduits for dispersal to more dorsal and rostral areas of the brain. Expansion and contraction of these sulci during brain pulsation is considered important to the forward flow of solutes in CSF through these compartments. Following intracisternal enzyme replacement therapy, enzyme reached all areas of the brain, but there was considerable disparity of enzyme uptake with some areas recording much higher levels than others. Posttreatment posture made only modest differences to enzyme uptake.
Methylome of DNase I sensitive chromatin in Populus trichocarpa shoot apical meristematic cells: a simplified approach revealing characteristics of gene‐body DNA methylation in open chromatin state
Authors: Lafon‐Placette Clément , Faivre‐Rampant Patricia , Delaunay Alain , Street Nathaniel , Brignolas Franck , Maury Stéphane 
Published: December 2012

Summary

DNA methylation is involved in the control of plant development and adaptation to the environment through modifications of chromatin compaction and gene expression. In poplar (Populus trichocarpa), a perennial plant, variations in DNA methylation have been reported between genotypes and tissues or in response to drought. Nevertheless, the relationships between gene‐body DNA methylation, gene expression and chromatin compaction still need clarification.

Here, DNA methylation was mapped in the noncondensed chromatin fraction from P. trichocarpa shoot apical meristematic cells, the center of plant morphogenesis, where DNA methylation variations could influence the developmental trajectory. DNase I was used to isolate the noncondensed chromatin fraction. Methylated sequences were immunoprecipitated, sequenced using Illumina/Solexa technology and mapped on the v2.0 poplar genome. Bisulfite sequencing of candidate sequences was used to confirm mapping data and to assess cytosine contexts and methylation levels.

While the methylated DNase I hypersensitive site fraction covered 1.9% of the poplar genome, it contained sequences corresponding to 74% of poplar gene models, mostly exons. The level and cytosine context of gene‐body DNA methylation varied with the structural characteristics of the genes.

Taken together, our data show that DNA methylation is widespread and variable among genes in open chromatin of meristematic cells, in agreement with a role in their developmental trajectory.
Source–sink dynamics and proteomic reprogramming under elevated night temperature and their impact on rice yield and grain quality
Authors: Shi Wanju , Muthurajan Raveendran , Rahman Hifzur , Selvam Jagadeesh , Peng Shaobing , Zou Yinbin , Jagadish Krishna S. V. 
Published: December 2012

Summary

High night temperatures (HNTs) can reduce significantly the global rice (Oryza sativa) yield and quality. A systematic analysis of HNT response at the physiological and molecular levels was performed under field conditions.

Contrasting rice accessions, N22 (highly tolerant) and Gharib (susceptible), were evaluated at 22°C (control) and 28°C (HNT). Nitrogen (N) and nonstructural carbohydrate (NSC) translocation from different plant tissues into grains at key developmental stages, and their contribution to yield, grain‐filling dynamics and quality aspects, were evaluated. Proteomic profiling of flag leaf and spikelets at 100% flowering and 12 d after flowering was conducted, and their reprogramming patterns were explored.

Grain yield reduction in susceptible Gharib was traced back to the significant reduction in N and NSC translocation after flowering, resulting in reduced maximum and mean grain‐filling rate, grain weight and grain quality. A combined increase in heat shock proteins (HSPs), Ca signaling proteins and efficient protein modification and repair mechanisms (particularly at the early grain‐filling stage) enhanced N22 tolerance for HNT.

The increased rate of grain filling and efficient proteomic protection, fueled by better assimilate translocation, overcome HNT tolerance in rice. Temporal and spatial proteome programming alters dynamically between key developmental stages and guides future transgenic and molecular analysis targeted towards crop improvement.
Prevalence of Stroke among Patients with Paroxysmal Supraventricular Tachycardia
Authors: BREMBILLA‐PERROT BÉATRICE , DELOBELLE JULIEN 
Published: December 2012

BackgroundTo assess the prevalence of unexplained stroke in patients with paroxysmal supraventricular tachycardia (SVT). The risk of atrial fibrillation (AF) is well known and risk of stroke can be expected.MethodsA total of 1,362 patients were referred for SVT, confirmed by electrophysiological study. Patients with anterograde conduction over accessory pathway (AP) were excluded. Clinical and electrophysiological data were collected.ResultsStroke was noted in 38 patients with a prevalence of 2.8%. Patients with stroke were older (62 ± 12 years vs 49 ± 19 years; P < 0.0001). Heart disease (34% vs 10%; P < 0.0001) and AF history (10.5% vs 2%; P < 0.001) were more frequent. Male gender was as frequent in patients with and without stroke (45% vs 39.5%; NS). SVT mechanism was similar: AV reentrant tachycardia over concealed AP was 10.5% in patients with stroke and 18.5% in other patients (NS). Atrioventricular node reentrant tachycardias represent other mechanisms. After 2.6 ± 2.5 years, SVT ablation was performed less frequently in patients with stroke (37% vs 63%; P < 0.001); three patients without previous stroke presented a stroke. AF and cardiovascular death were more frequent in patients with stroke (21% vs 4.6%; P < 0.000), (8% vs 2%; P < 0.008). Note that 7.6% of patients treated with ablation and 6% of patients without ablation had an event (stroke, AF, death; NS).ConclusionsUnexplained stroke was rare in patients with SVT, noted in 2.8% of this population. Old age and AF history were the predictors of stroke. These patients had a risk of adverse events as AF or death. SVT ablation did not seem to reduce the risk of new stroke, AF or death.
Characteristics of and weaning strategies in tube‐dependent children
Authors: Ishizaki Akiko , Hironaka Shouji , Tatsuno Masaru , Mukai Yoshiharu 
Published: December 2012

AbstractBackgroundDespite resolution of the symptoms of eating and/or swallowing disorders, prolonged tube feeding is maintained in some children. This study summarized the characteristics of children with tube dependence and investigated the causes of tube dependence.MethodsClinical and growth data were evaluated using medical records and referral forms for 35 tube‐dependent children.ResultsThe children in this study had a median age of 30 months (range, 17–37 months) on the first visit and 35.5 months (range, 21.3–44.8 months) at tube removal. Seven children were not weaned from the feeding tube within the study period. Twenty‐two (63%) of the children were girls, 20 (57%) were able to walk, 24 (69%) had mild mental retardation, and 33 (94%) had underlying disease. Tube‐dependent children tended to weigh less than age‐matched normal children. Sixteen children (45.7%) were underweight. Children who had their feeding tubes removed before age 3 were significantly younger at the initial visit than those who had their tubes removed after 3 years of age. Increased finger feeding was observed during the period before tube removal.ConclusionTube‐dependent children tend to be close to normal in body growth and intellectual development. When weaning from tube feeding, interventions at earlier ages are more efficient. Reduction in or discontinuation of tube feeding and encouragement of self‐feeding were effective to wean off tube feeding.
Neuroendocrinological responses to alcohol intoxication in healthy males: Relationship with impulsivity, drinking behavior, and subjective effects
Authors: Magrys S. A. , Olmstead M. C. , Wynne‐Edwards K. E. , Balodis I. M. 
Published: December 2012

AbstractAmbiguous biochemical and subjective responses to alcohol may relate to preexisting individual differences in alcohol expectations, experience, or impulsivity. This study examined cortisol and alpha‐amylase responses to alcohol and their association with trait impulsivity, alcohol expectancy, and subjective reports of alcohol's effects. Eighty‐seven males assigned to an alcohol, sober, or placebo group provided biochemical and self‐report measures. Both cortisol and alpha‐amylase increased following alcohol administration. Impulsivity correlated with cortisol changes, and the greatest rise in cortisol correlated with high stimulating effects in the alcohol group. These findings emphasize the importance of individual differences in alcohol responses and support a relationship between hormonal responses and alcohol use.
Development of anELISAto detect circulating anti‐asparaginase antibodies in dogs with lymphoid neoplasia treated withEscherichia colil‐asparaginase
Authors: Kidd J. A. , Ross P. , Buntzman A. S. , Hess P. R. 
Published: December 2012

AbstractResistance toEscherichia colil‐asparaginase in canine lymphoma occurs frequently with repeated administration, a phenomenon often attributed, without substantiation, to the induction of neutralizing antibodies. To test the hypothesis that treated dogs develop antibodies against the drug, we created an enzyme‐linked immunosorbent assay (ELISA) to measure plasma anti‐asparaginase immunoglobulin G responses. Using samples from dogs that had received multiple doses, specific reactivity againstl‐asparaginase was demonstrated, while naïve patients' samples were negative. The optimizedELISAappeared sensitive, with endpoint titers >1 600 000 in positive control dogs. Intra‐ and inter‐assay coefficients of variation were 3.6 and 14.5%. The assay was supported by the observation thatELISA‐positive plasma could immunoprecipitate asparaginase activity. When clinical patients were evaluated, 3/10 dogs developed titers after a single injection; with repeated administration, 4/7 dogs were positive.l‐asparaginase antibodies showed reduced binding to thePEGylateddrug formulation. TheELISAshould prove useful in investigating the potential correlation of antibody responses with resistance.
Imaging and characterization of stretch‐induced ATP release from alveolar A549 cells
Authors: Grygorczyk Ryszard , Furuya Kishio , Sokabe Masahiro 
Published: December 2012

Key point
Translation of mechanical forces into biological effects often involves ATP release and activation of the purinergic signalling cascade.
In the lungs, stretch is an important physical stimulus but its impact on ATP release and intercellular signalling is poorly understood.
Here, we report that in the A549 alveolar cell model, a single stretch of more than 10% induces ATP release sufficient to stimulate purinergic receptors on neighbouring cells up to 150 μm away from the source cell.
Stretch‐induced ATP release is significantly enhanced during healing in scratch‐wound areas.
These results demonstrate that mechano‐purinergic signalling may play an important role in modulating alveolar processes, including electrolyte transport, surfactant secretion and wound healing.
Abstract  Mechano‐transduction at cellular and tissue levels often involves ATP release and activation of the purinergic signalling cascade. In the lungs, stretch is an important physical stimulus but its impact on ATP release, the underlying release mechanisms and transduction pathways are poorly understood. Here, we investigated the effect of unidirectional stretch on ATP release from human alveolar A549 cells by real‐time luciferin–luciferase bioluminescence imaging coupled with simultaneous infrared imaging, to monitor the extent of cell stretch and to identify ATP releasing cells. In subconfluent (<90%) cell cultures, single 1 s stretch (10–40%)‐induced transient ATP release from a small fraction (≤1.5%) of cells that grew in number dose‐dependently with increasing extent of stretch. ATP concentration in the proximity (≤150 μm) of releasing cells often exceeded 10 μm, sufficient for autocrine/paracrine purinoreceptor stimulation of neighbouring cells. ATP release responses were insensitive to the putative ATP channel blockers carbenoxolone and 5‐nitro‐2‐(3‐phenylpropyl‐amino) benzoic acid, but were inhibited by N‐ethylmaleimide and bafilomycin. In confluent cell cultures, the maximal fraction of responding cells dropped to <0.2%, but was enhanced several‐fold in the wound/scratch area after it was repopulated by new cells during the healing process. Fluo8 fluorescence experiments revealed two types of stretch‐induced intracellular Ca2+ responses, rapid sustained Ca2+ elevations in a limited number of cells and delayed secondary responses in neighbouring cells, seen as Ca2+ waves whose propagation was consistent with extracellular diffusion of released ATP. Our experiments revealed that a single >10% stretch was sufficient to initiate intercellular purinergic signalling in alveolar cells, which may contribute to the regulation of surfactant secretion and wound healing.
Impact of the fixed gantry angle approximation on dosimetric accuracy for helical tomotherapy plans
Authors: Tudor G. Samuel J. , Thomas Simon J. 
Published: December 2012

Purpose:The purpose of the work was to determine the accuracy of the dose calculation of off‐axis, small target helical tomotherapy treatments using 51 calculation angles, and to determine the increase in calculation angles required to improve the accuracy to acceptable standards.Methods:A previously described dose calculation program [S. J. Thomas, K. R. Eyre, G. S. J. Tudor, and J. Fairfoul, “Dose calculation software for helical tomotherapy, utilizing patient CT data to calculate an independent three‐dimensional dose cube,” Med. Phys. 39, – (2012) 10.1118/1.3668061] was modified to permit decomposition of each projection into several subprojections, allowing more accurate modeling of the temporal distribution of fluence within each beamlet. Four plans of small off‐axis spherical targets were recalculated several times with different numbers of subprojections, with the minimum dose to 95% of the PTV (D95%) and the minimum dose to 2% of the PTV (D2%) calculated for each, in order to determine the minimum number of subprojections required for accurate dose statistics. A further nine plans were used to determine the effect on conventional calculation accuracy of varying target size, target position, modulation factor, and pitch. For this analysis, the mean dose and equivalent uniform dose were considered in addition to D95% and D2%.Results:The differences between calculations made using the 51 angle approximation and using the closest approximation to real treatment delivery were notable, with up to 11.0% overestimate of D95% for the cases studied. A previously unreported underestimate of dose to parts of the PTV was observed due to this effect, with D2% being underestimated by up to 3.3%. The effect is dependent on target size, position, modulation factor, and the angular distribution of fluence within the sinogram but not pitch. Decomposing each projection into three subprojections left differences in dose statistics that were of reduced magnitude but still appreciable. The effect of increasing the number of subprojections beyond five had little effect.Conclusions:When applied to small, off‐axis targets, the limitations of the 51 calculation angle model can substantially affect the veracity of PTV dose statistics, including both underestimation and overestimation of dose depending on position within the PTV. Increasing the number of calculation angles by a factor of 5 reduces the effect to insignificant levels. While the latest release of TomoTherapy planning software will ameliorate the problem, the studied effect is best avoided by positioning small targets near to the bore center. Where this is not possible, it is recommended to ensure a high actual modulation factor and to use an unscaled delivery for patient‐specific quality assurance.
High precision semiautomated computed tomography measurement of lumbar disk and vertebral heights
Authors: Tan Sovira , Yao Jianhua , Yao Lawrence , Ward Michael M. 
Published: December 2012

Purpose:Evaluation of treatments of many spine disorders requires precise measurement of the heights of vertebral bodies and disk spaces. The authors present a semiautomated computer algorithm measuring those heights from spine computed tomography (CT) scans and evaluate its precision.Methods:Eight patients underwent two spine CT scans in the same day. In each scan, five thoracolumbar vertebral heights and four disk heights were estimated using the algorithm. To assess precision, the authors computed the differences between the height measurements in the two scans, coefficients of variation (CV), and 95% limits of agreement. Intraoperator and interoperator precisions were evaluated. For local vertebral and disk height measurement (anterior, middle, posterior) the algorithm was compared to a manual mid‐sagittal plane method.Results:The mean (standard deviation) interscan difference was as low as 0.043 (0.031) mm for disk heights and 0.044 (0.043) mm for vertebral heights. The corresponding 95% limits of agreement were [−0.085, 0.11] and [−0.10, 0.12] mm, respectively. Intraoperator and interoperator precision was high, with a maximal CV of 0.30%. For local vertebral and disk heights, the algorithm improved upon the precision of the manual mid‐sagittal plane measurement by as much as a factor of 6 and 4, respectively.Conclusions:The authors evaluated the precision of a novel computer algorithm for measuring vertebral body heights and disk heights using short term repeat CT scans of patients. The 95% limits of agreement indicate that the algorithm can detect small height changes of the order of 0.1 mm.
Treatment Duration for Uncomplicated Staphylococcus aureus Bacteremia To Prevent Relapse: Analysis of a Prospective Observational Cohort Study
Authors: Chong Yong Pil , Moon Song Mi , Bang Kyung-Mi , Park Hyun Jung , Park So-Youn , Kim Mi-Na , Park Ki-Ho , Kim Sung-Han , Lee Sang-Oh , Choi Sang-Ho , Jeong Jin-Yong , Woo Jun Hee , Kim Yang Soo 
Published: December 2012

ABSTRACT

Practice guidelines recommend at least 14 days of antibiotic therapy for uncomplicated
Staphylococcus aureus
bacteremia (SAB). However, these recommendations have not been formally evaluated in clinical studies. To evaluate the duration of therapy for uncomplicated SAB, we analyzed data from our prospective cohort of patients with SAB. A prospective observational cohort study was performed in patients with SAB at a tertiary-care hospital in Korea between August 2008 and September 2010. All adult patients with SAB were prospectively enrolled and observed over a 12-week period. Uncomplicated SAB was defined as follows: negative results of follow-up blood cultures at 2 to 4 days, defervescence within 72 h of therapy, no evidence of metastatic infection, and catheter-related bloodstream infection or primary bacteremia without evidence of endocarditis on echocardiography. Of 483 patients with SAB, 111 met the study criteria for uncomplicated SAB. Fifty-three (47.7%) had methicillin-resistant SAB. When short-course therapy (<14 days) and intermediate-course therapy (≥14 days) were compared, the treatment failure rates (10/38 [26.3%] versus 16/73 [21.9%]) and crude mortality (7/38 [18.4%] versus 16/73 [21.9%]) did not differ significantly between the two groups. However, short-course therapy was significantly associated with relapse (3/38 [7.9%] versus 0/73;
P
= 0.036). In multivariate analysis, primary bacteremia was associated with a trend toward increased treatment failure (
P
= 0.06). Therefore, in the treatment of uncomplicated SAB, it seems reasonable to consider at least 14 days of antibiotic therapy to prevent relapse, as practice guidelines recommend. Because of its poor prognosis, primary bacteremia, even with a low risk of complication, should not be treated with short-course therapy.
Accessory Gene Regulator (
agr
) Dysfunction in Staphylococcus aureus Bloodstream Isolates from South Korean Patients
Authors: Chong Yong Pil , Kim Eun Sil , Park Su-Jin , Park Ki-Ho , Kim Tark , Kim Mi-Na , Kim Sung-Han , Lee Sang-Oh , Choi Sang-Ho , Woo Jun Hee , Jeong Jin-Yong , Kim Yang Soo 
Published: December 2012

ABSTRACT

We describe the genetic and microbiological characteristics of methicillin-resistant
Staphylococcus aureus
(MRSA) bloodstream isolates with
agr
dysfunction from a tertiary-care hospital in Korea. Of these, ST5-SCC
mec
type II-
agr
group II MRSA isolates, which are known to be prevalent in hospital-acquired infections in Korea, were the most abundant, because of the clonal spread of a specific
agr
-defective lineage. This finding suggests that the loss of
agr
function may confer a potential advantage in a hospital setting. Clonal spread of a specific defective-
agr
strain was not observed among community-associated MRSA or methicillin-susceptible
S. aureus
clones, regardless of community or hospital acquisition of infection.
agr
-defective clones, including ST5 and ST239 MRSA, were enriched for heteroresistant vancomycin-intermediate
S. aureus
.