Less Invasive Quick Open Stenting using a J Graft Open Stent for Distal Arch Aneurysms.

A new device of aortic stent graft made in Japan has been available since July 2014. Here, we describe a novel, unique surgical technique named "less invasive quick open stenting" at a rectal temperature of 28°C without any cerebral perfusion for treating distal arch aneurysms. All 12 patients were discharged from the intensive care unit within 24 hours after surgery without any complications. This technique aids in the exclusion of atherosclerotic plaques on the aortic wall and shortens the duration of circulatory arrest; moreover, it represents a very attractive option to prevent recurrent nerve injury.

Incidence of drug interaction when using proton pump inhibitor and warfarin according to cytochrome P450 2C19 (CYP2C19) genotype in Japanese.

OBJECTIVES: The US Food and Drug Administration has suggested that proton pump inhibitors (PPIs) increase the international normalized ratio (INR) when used concomitantly with warfarin (WF) because of being metabolized by cytochrome P450 2C19 (CYP2C19). We assessed whether CYP2C19 genotypes and type of PPI accentuated the drug interaction. METHODS AND RESULTS: The study group was 82 patients who needed WF after surgery and had their CYP2C19 genotypes analyzed in advance. We randomly divided them into two groups: group I (n = 41) included patients who had lansoprazole 15 mg/day and group II (n = 41) included patients who had rabeprazole 10 mg/day. The dose of WF was controlled by the doctor in charge as a target INR of 1.6 to 2.6 during the 2 months after surgery. The maximum INR was significantly higher in group I (3.36 ± 0.98) than in group II (2.29 ± 0.55, p < 0.0001). The incidence of over-INR (> 3.5) was significantly higher in group I (15 cases) than in group II (2 cases, p = 0.0001). Several bleeding events complicated 10 patients in group I, but none in group II (p = 0.015). Logistic regression analysis revealed that over-INR (odds ratio [OR] 3.58, 95% confidence interval [CI]: 3.48-368.25, p < 0.0001), and pair of lansoprazole and CYP2C19 intermediate metabolizer (OR 2.39, 95% CI: 1.108-29.491, p = 0.0009) were independent predictors of bleeding events. CONCLUSION: If a patient has had the intermediate metabolizer CYP2C19 genotype and concomitant use of WF and a PPI after open heart surgery, lansoprazole intensifies the effects of WF and is associated with bleeding events.

RARGE II: an integrated phenotype database of Arabidopsis mutant traits using a controlled vocabulary.

Arabidopsis thaliana is one of the most popular experimental plants. However, only 40% of its genes have at least one experimental Gene Ontology (GO) annotation assigned. Systematic observation of mutant phenotypes is an important technique for elucidating gene functions. Indeed, several large-scale phenotypic analyses have been performed and have generated phenotypic data sets from many Arabidopsis mutant lines and overexpressing lines, which are freely available online. Since each Arabidopsis mutant line database uses individual phenotype expression, the differences in the structured term sets used by each database make it difficult to compare data sets and make it impossible to search across databases. Therefore, we obtained publicly available information for a total of 66,209 Arabidopsis mutant lines, including loss-of-function (RATM and TARAPPER) and gain-of-function (AtFOX and OsFOX) lines, and integrated the phenotype data by mapping the descriptions onto Plant Ontology (PO) and Phenotypic Quality Ontology (PATO) terms. This approach made it possible to manage the four different phenotype databases as one large data set. Here, we report a publicly accessible web-based database, the RIKEN Arabidopsis Genome Encyclopedia II (RARGE II; http://rarge-v2.psc.riken.jp/), in which all of the data described in this study are included. Using the database, we demonstrated consistency (in terms of protein function) with a previous study and identified the presumed function of an unknown gene. We provide examples of AT1G21600, which is a subunit in the plastid-encoded RNA polymerase complex, and AT5G56980, which is related to the jasmonic acid signaling pathway.

Screening and management for ischemic heart disease in patients undergoing emergency surgery for a type A acute aortic dissection.

PURPOSE: We assessed the incidence of coronary artery disease (CAD) during hospitalization after emergency surgery for a type A acute aortic dissection. METHODS: A total of 123 patients underwent multi-slice computed tomography (MSCT) scans during an early stage after surgery. The patients were divided into two groups: group I consisted of 14 patients (11.4%) who had coronary artery stenosis of more than 75% on MSCT, and group II consisted of 109 patients (88.6%) who had no coronary lesions. RESULTS: The prevalence of diabetes, dyslipidemia and a smoking history was significantly higher in group I. Although the serum low-density lipoprotein cholesterol levels were similar, the high-density lipoprotein cholesterol (HDL) level was significantly lower in group I (36.4 ± 7.9 mg/dl) than in group II (49.6 ± 13.5 mg/dl, P = 0.0005). The maximum carotid intima-media thickness (IMT) was significantly thicker in group I (1.17 ± 0.37 mm) compared to group II (0.96 ± 0.33 mm, P = 0.0297). The logistic regression analysis detected that a carotid IMT over 1.1 mm (odds ratio 4.35, P = 0.0371) and HDL less than 40 mg/dl (odds ratio 3.90, P = 0.0482) were predictors for CAD. CONCLUSIONS: CAD screening should be recommended for patients with aortic dissection who have several atherosclerosis risk factors, even after emergency surgery.

UniVIO: a multiple omics database with hormonome and transcriptome data from rice.

Plant hormones play important roles as signaling molecules in the regulation of growth and development by controlling the expression of downstream genes. Since the hormone signaling system represents a complex network involving functional cross-talk through the mutual regulation of signaling and metabolism, a comprehensive and integrative analysis of plant hormone concentrations and gene expression is important for a deeper understanding of hormone actions. We have developed a database named Uniformed Viewer for Integrated Omics (UniVIO: http://univio.psc.riken.jp/), which displays hormone-metabolome (hormonome) and transcriptome data in a single formatted (uniformed) heat map. At the present time, hormonome and transcriptome data obtained from 14 organ parts of rice plants at the reproductive stage and seedling shoots of three gibberellin signaling mutants are included in the database. The hormone concentration and gene expression data can be searched by substance name, probe ID, gene locus ID or gene description. A correlation search function has been implemented to enable users to obtain information of correlated substance accumulation and gene expression. In the correlation search, calculation method, range of correlation coefficient and plant samples can be selected freely.

PRIMe Update: innovative content for plant metabolomics and integration of gene expression and metabolite accumulation.

PRIMe (http://prime.psc.riken.jp/), the Platform for RIKEN Metabolomics, is a website that was designed and implemented to support research and analyses ranging from metabolomics to transcriptomics. To achieve functional genomics and annotation of unknown metabolites, we established the following PRIMe contents: MS2T, a library comprising >1 million entries of untargeted tandem mass spectrometry (MS/MS) data of plant metabolites; AtMetExpress LC-MS, a database of transcriptomics and metabolomics approaches in Arabidopsis developmental stages (AtMetExpress Development LC-MS) and a data set of the composition of secondary metabolites among 20 Arabidopsis ecotypes (AtMetExpress 20 ecotypes LC-MS); and ReSpect, hybrid reference MS/MS data resources (acquisitions and literature). PRIMeLink is a new web application that allows access to the innovative data resources of PRIMe. The MS2T library was generated from a set of MS/MS spectra acquired using the automatic data acquisition function of mass spectrometry. To increase the understanding of mechanisms driving variations in metabolic profiles among plant tissues, we further provided the AtMetExpress Development LC-MS database in PRIMe, facilitating the investigation of relationships between gene expression and metabolite accumulation. This information platform therefore provides an integrative analysis resource by linking Arabidopsis transcriptome and metabolome data. Moreover, we developed the ReSpect database, a plant-specific MS/MS data resource, which allows users to identify candidate structures from the suite of complex phytochemical structures. Finally, we integrated the three databases into PRIMeLink and established a walk-through link between transcriptome and metabolome information. PRIMeLink offers a bi-directional searchable function, from the gene and the metabolite perspective, to search for targets seamlessly and effectively.

The Chloroplast Function Database II: a comprehensive collection of homozygous mutants and their phenotypic/genotypic traits for nuclear-encoded chloroplast proteins.

The Chloroplast Function Database has so far offered phenotype information on mutants of the nuclear-encoded chloroplast proteins in Arabidopsis that pertains to >200 phenotypic data sets that were obtained from 1,722 transposon- or T-DNA-tagged lines. Here, we present the development of the second version of the database, which is named the Chloroplast Function Database II and was redesigned to increase the number of mutant characters and new user-friendly tools for data mining and integration. The upgraded database offers information on genome-wide mutant screens for any visible phenotype against 2,495 tagged lines to create a comprehensive homozygous mutant collection. The collection consists of 147 lines with seedling phenotypes and 185 lines for which we could not obtain homozygotes, as well as 1,740 homozygotes with wild-type phenotypes. Besides providing basic information about primer lists that were used for the PCR genotyping of T-DNA-tagged lines and explanations about the preparation of homozygous mutants and phenotype screening, the database includes access to a link between the gene locus and existing publicly available databases. This gives users access to a combined pool of data, enabling them to gain valuable insights into biological processes. In addition, high-resolution images of plastid morphologies of mutants with seedling-specific chloroplast defects as observed with transmission electron microscopy (TEM) are available in the current database. This database is used to compare the phenotypes of visually identifiable mutants with their plastid ultrastructures and to evaluate their potential significance from characteristic patterns of plastid morphology in vivo. Thus, the Chloroplast Function Database II is a useful and comprehensive information resource that can help researchers to connect individual Arabidopsis genes to plastid functions on the basis of phenotype analysis of our tagged mutant collection. It can be freely accessed at http://rarge.psc.riken.jp/chloroplast/.

Rapid aortic enlargement requiring surgery in patients with chronic type B aortic dissection.

We report the relationship between rapid aortic enlargement of chronic type B aortic dissection and sleep disorder due to anxiety after Tohoku disaster. Five patients underwent surgical procedures due to rapid aortic enlargement after the earthquake disaster. They reported that their morning blood pressure increased to approximately 190 mm Hg after the disaster. They were troubled with severe insomnia due to anxiety about the continuing aftershocks. In primary care for patients with mental stress after a big disaster, it is important to keep a careful monitoring of blood pressure besides assessment of anxiety and sleep.

Concomitant aortic valve and ascending aorta replacement with moderate hypothermic circulatory arrest to treat an aortic bicuspid valve with post-stenotic dilatation.

We recommend concomitant surgery for aortic valve replacement (AVR) and ascending aortic replacement using moderate hypothermic circulatory arrest (CA) for post-stenotic dilatation complicated by an aortic bicuspid valve. Cardiopulmonary bypass (CPB) was established from the right atrium to the dilated ascending aorta. As soon as the rectal temperature decreased to 28 °C, CA was commenced and the open distal anastomosis of a polyester prosthesis, without any cerebral perfusion, was completed. AVR was then carried out during rapid re-warming with CPB using a side arm of the prosthesis. This procedure exhibited safe and satisfactory results. There are many benefits of carrying out the procedure in this way; it avoids the requirement for cannulation to a calcified aortic arch, provides a good operative field, for an easier distal anastomosis and suturing at the valve site, and reduces the risk of further dilatation or dissection of the residual ascending aorta in the later phase.

The Chloroplast Function Database: a large-scale collection of Arabidopsis Ds/Spm- or T-DNA-tagged homozygous lines for nuclear-encoded chloroplast proteins, and their systematic phenotype analysis.

A majority of the proteins of the chloroplast are encoded by the nuclear genome, and are post-translationally targeted to the chloroplast. From databases of tagged insertion lines at international seed stock centers and our own stock, we selected 3246 Ds/Spm (dissociator/suppressor-mutator) transposon- or T-DNA-tagged Arabidopsis lines for genes encoding 1369 chloroplast proteins (about 66% of the 2090 predicted chloroplast proteins) in which insertions disrupt the protein-coding regions. We systematically observed 3-week-old seedlings grown on agar plates, identified mutants with abnormal phenotypes and collected homozygous lines with wild-type phenotypes. We also identified insertion lines for which no homozygous plants were obtained. To date, we have identified 111 lines with reproducible seedling phenotypes, 122 lines for which we could not obtain homozygotes and 1290 homozygous lines without a visible phenotype. The Chloroplast Function Database presents the molecular and phenotypic information obtained from this resource. The database provides tools for searching for mutant lines using Arabidopsis Genome Initiative (AGI) locus numbers, tagged line numbers and phenotypes, and provides rapid access to detailed information on the tagged line resources. Moreover, our collection of insertion homozygotes provides a powerful tool to accelerate the functional analysis of nuclear-encoded chloroplast proteins in Arabidopsis. The Chloroplast Function Database is freely available at http://rarge.psc.riken.jp/chloroplast/. The homozygous lines generated in this project are also available from the various Arabidopsis stock centers. We have donated the insertion homozygotes to their originating seed stock centers.

RiceFOX: a database of Arabidopsis mutant lines overexpressing rice full-length cDNA that contains a wide range of trait information to facilitate analysis of gene function.

Identification of gene function is important not only for basic research but also for applied science, especially with regard to improvements in crop production. For rapid and efficient elucidation of useful traits, we developed a system named FOX hunting (Full-length cDNA Over-eXpressor gene hunting) using full-length cDNAs (fl-cDNAs). A heterologous expression approach provides a solution for the high-throughput characterization of gene functions in agricultural plant species. Since fl-cDNAs contain all the information of functional mRNAs and proteins, we introduced rice fl-cDNAs into Arabidopsis plants for systematic gain-of-function mutation. We generated >30,000 independent Arabidopsis transgenic lines expressing rice fl-cDNAs (rice FOX Arabidopsis mutant lines). These rice FOX Arabidopsis lines were screened systematically for various criteria such as morphology, photosynthesis, UV resistance, element composition, plant hormone profile, metabolite profile/fingerprinting, bacterial resistance, and heat and salt tolerance. The information obtained from these screenings was compiled into a database named 'RiceFOX'. This database contains around 18,000 records of rice FOX Arabidopsis lines and allows users to search against all the observed results, ranging from morphological to invisible traits. The number of searchable items is approximately 100; moreover, the rice FOX Arabidopsis lines can be searched by rice and Arabidopsis gene/protein identifiers, sequence similarity to the introduced rice fl-cDNA and traits. The RiceFOX database is available at http://ricefox.psc.riken.jp/.

sORF finder: a program package to identify small open reading frames with high coding potential.

SUMMARY: sORF finder is a program package for identifying small open reading frames (sORFs) with high-coding potential. This application allows the identification of coding sORFs according to the nucleotide composition bias among coding sequences and the potential functional constraint at the amino acid level through evaluation of synonymous and non-synonymous substitution rates. AVAILABILITY: Online tools and source codes are freely available at http://evolver.psc.riken.jp/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

AtMetExpress development: a phytochemical atlas of Arabidopsis development.

Plants possess many metabolic genes for the production of a wide variety of phytochemicals in a tissue-specific manner. However, the metabolic systems behind the diversity and tissue-dependent regulation still remain unknown due to incomplete characterization of phytochemicals produced in a single plant species. Thus, having a metabolome dataset in addition to the genome and transcriptome information resources would enrich our knowledge of plant secondary metabolism. Here we analyzed phytochemical accumulation during development of the model plant Arabidopsis (Arabidopsis thaliana) using liquid chromatography-mass spectrometry in samples covering many growth stages and organs. We also obtained tandem mass spectrometry spectral tags of many metabolites as a resource for elucidation of metabolite structure. These are part of the AtMetExpress metabolite accumulation atlas. Based on the dataset, we detected 1,589 metabolite signals from which the structures of 167 metabolites were elucidated. The integrated analyses with transcriptome data demonstrated that Arabidopsis produces various phytochemicals in a highly tissue-specific manner, which often accompanies the expression of key biosynthesis-related genes. We also found that a set of biosynthesis-related genes is coordinately expressed among the tissues. These data suggested that the simple mode of regulation, transcript to metabolite, is an origin of the dynamics and diversity of plant secondary metabolism.

Myocardial protective effect of human atrial natriuretic Peptide in cardiac surgery. -hANP Shot" in clinical safety trial-.

BACKGROUND: We studied low-dose human atrial natriuretic peptide (hANP) infusion therapy during cardiac surgery and reported the cardiac and renal protective effects. The efficacy of a bolus injection of hANP (the "hANP shot") simultaneously with induction of cardioplegia has been proven in animal experiments. In the present study the clinical effects of this "hANP shot" were examined. METHODS AND RESULTS: The subjects were 67 patients undergoing Coronary artery bypass grafting. At the time of inducing cardioplegia, 1 group received a simultaneous bolus injection of 100 µg of hANP (hANP group) and the other group received an injection of physiological saline (placebo group). The primary endpoints were (1) operative mortality and complications, and (2) the creatine kinase isoenzyme MB (CPK-MB), troponin-I, and human heart fatty acid binding protein (H-FABP) levels. The secondary endpoints were (1) the incidence of arrhythmia, and levels of (2) atrial and B-type natriuretic peptides, and cyclic guanosine monophosphate (cGMP), and (3) renin, angiotensin II, and aldosterone. Postoperative CPK-MB, troponin-I, and H-FABP levels were significantly lower in the hANP group than in the placebo group. Postoperative arrhythmia was significantly less frequent in the hANP group than in the placebo group. CONCLUSIONS: It is possible to achieve cardioprotective effects based on the safety of the "hANP shot", as well as from biomarkers of ischemia and results related to arrhythmia. The "hANP shot" should also be evaluated as a safer and new cardioprotective method for cardiac surgery.

Total arch replacement and open stent graft implantation using a newly developed stent graft: report of a case.

We experienced a case in which a total arch replacement and an open stent implantation were performed for a distal aortic arch aneurysm using a newly developed stent graft (Ube CL-0201; Ube Medical, Tokyo, Japan). This novel stent graft is composed of a woven polyester graft and a nickel-titanium alloy stent, and has been under evaluation in clinical trials at four institutions in Japan, including our hospital, since 2008. The patient was weaned from the respirator on the day after surgery, and 9 months have passed since the surgery with no complications. A follow-up computed tomography scan showed that the stent part was sufficiently open, and no complications, such as an endoleak, have been observed.

Systematic approaches to using the FOX hunting system to identify useful rice genes.

Ectopic gene expression, or the gain-of-function approach, has the advantage that once the function of a gene is known the gene can be transferred to many different plants by transformation. We previously reported a method, called FOX hunting, that involves ectopic expression of Arabidopsis full-length cDNAs in Arabidopsis to systematically generate gain-of-function mutants. This technology is most beneficial for generating a heterologous gene resource for analysis of useful plant gene functions. As an initial model we generated more than 23,000 independent Arabidopsis transgenic lines that expressed rice fl-cDNAs (Rice FOX Arabidopsis lines). The short generation time and rapid and efficient transformation frequency of Arabidopsis enabled the functions of the rice genes to be analyzed rapidly. We screened rice FOX Arabidopsis lines for alterations in morphology, photosynthesis, element accumulation, pigment accumulation, hormone profiles, secondary metabolites, pathogen resistance, salt tolerance, UV signaling, high light tolerance, and heat stress tolerance. Some of the mutant phenotypes displayed by rice FOX Arabidopsis lines resulted from the expression of rice genes that had no homologs in Arabidopsis. This result demonstrated that rice fl-cDNAs could be used to introduce new gene functions in Arabidopsis. Furthermore, these findings showed that rice gene function could be analyzed by employing Arabidopsis as a heterologous host. This technology provides a framework for the analysis of plant gene function in a heterologous host and of plant improvement by using heterologous gene resources.

Statistical indices for simultaneous large-scale metabolite detections for a single NMR spectrum.

NMR-based metabolomics has become a practical and analytical methodology for discovering novel genes, biomarkers, metabolic phenotypes, and dynamic cell behaviors in organisms. Recent developments in NMR-based metabolomics, however, have not concentrated on improvements of comprehensiveness in terms of simultaneous large-scale metabolite detections. To resolve this, we have devised and implemented a statistical index, the SpinAssign p-value, in NMR-based metabolomics for large-scale metabolite annotation and publicized this information. It enables simultaneous annotation of more than 200 candidate metabolites from the single (13)C-HSQC (heteronuclear single quantum coherence) NMR spectrum of a single sample of cell extract.

Toward genome-wide metabolotyping and elucidation of metabolic system: metabolic profiling of large-scale bioresources.

An improvement in plant production is increasingly important for a sustainable human society. For this purpose, understanding the mechanism of plant production, that is, the plant metabolic system, is an immediate necessity. After the sequencing of the Arabidopsis genome, it has become possible to obtain a bird's eye view of its metabolism by means of omics such as transcriptomics and proteomics. Availability of thousands of transcriptome data points in the public domain has resulted in great advances in the methodology of functional genomics. Metabolome data can be a "gold mine" of biological findings. However, as the total throughput of metabolomics is far lower than that of transcriptomics due to technical difficulties, there is currently no publicly available large-scale metabolome dataset that is comparable in size to the transcriptome dataset. Recently, we established a novel methodology, termed widely targeted metabolomics, which can generate thousands of metabolome data points in a high-throughput manner. We previously conducted a targeted metabolite analysis of large-scale Arabidopsis bioresources, namely transposon-tagged mutants and accessions, to make a smaller dataset of metabolite accumulation. In this paper, we release approximately 3,000 metabolic profiles obtained by targeted analysis for 36 metabolites and discuss the possible regulation of amino acid accumulation.

The AtGenExpress hormone and chemical treatment data set: experimental design, data evaluation, model data analysis and data access.

We analyzed global gene expression in Arabidopsis in response to various hormones and in related experiments as part of the AtGenExpress project. The experimental agents included seven basic phytohormones (auxin, cytokinin, gibberellin, brassinosteroid, abscisic acid, jasmonate and ethylene) and their inhibitors. In addition, gene expression was investigated in hormone-related mutants and during seed germination and sulfate starvation. Hormone-inducible genes were identified from the hormone response data. The effects of each hormone and the relevance of the gene lists were verified by comparing expression profiles for the hormone treatments and related experiments using Pearson's correlation coefficient. This approach was also used to analyze the relationships among expression profiles for hormone responses and those included in the AtGenExpress stress-response data set. The expected correlations were observed, indicating that this approach is useful to monitor the hormonal status in the stress-related samples. Global interactions among hormones-inducible genes were analyzed in a pairwise fashion, and several known and novel hormone interactions were detected. Genome-wide transcriptional gene-to-gene correlations, analyzed by hierarchical cluster analysis (HCA), indicated that our data set is useful for identification of clusters of co-expressed genes, and to predict the functions of unknown genes, even if a gene's function is not directly related to the experiments included in AtGenExpress. Our data are available online from AtGenExpressJapan; the results of genome-wide HCA are available from PRIMe. The data set presented here will be a versatile resource for future hormone studies, and constitutes a reference for genome-wide gene expression in Arabidopsis.

Widely targeted metabolomics based on large-scale MS/MS data for elucidating metabolite accumulation patterns in plants.

Metabolomics is an 'omics' approach that aims to analyze all metabolites in a biological sample comprehensively. The detailed metabolite profiling of thousands of plant samples has great potential for directly elucidating plant metabolic processes. However, both a comprehensive analysis and a high throughput are difficult to achieve at the same time due to the wide diversity of metabolites in plants. Here, we have established a novel and practical metabolomics methodology for quantifying hundreds of targeted metabolites in a high-throughput manner. Multiple reaction monitoring (MRM) using tandem quadrupole mass spectrometry (TQMS), which monitors both the specific precursor ions and product ions of each metabolite, is a standard technique in targeted metabolomics, as it enables high sensitivity, reproducibility and a broad dynamic range. In this study, we optimized the MRM conditions for specific compounds by performing automated flow injection analyses with TQMS. Based on a total of 61,920 spectra for 860 authentic compounds, the MRM conditions of 497 compounds were successfully optimized. These were applied to high-throughput automated analysis of biological samples using TQMS coupled with ultra performance liquid chromatography (UPLC). By this analysis, approximately 100 metabolites were quantified in each of 14 plant accessions from Brassicaceae, Gramineae and Fabaceae. A hierarchical cluster analysis based on the metabolite accumulation patterns clearly showed differences among the plant families, and family-specific metabolites could be predicted using a batch-learning self-organizing map analysis. Thus, the automated widely targeted metabolomics approach established here should pave the way for large-scale metabolite profiling and comparative metabolomics.