137 research outputs found
Incisional atrial reentrant tachycardia: experimental study on the conduction property through the isthmus
AbstractBackgroundIncisional atrial reentrant tachycardia is a life-threatening tachyarrhythmia after surgery for congenital heart disease. Slow conduction through an isthmus between anatomical barriers, such as a right atriotomy or the sites for cannulation, has been shown to be a prerequisite for perpetuation of the incisional atrial reentrant tachycardia. However, the conduction property through the isthmus has not been examined in detail.MethodsTo examine the conduction property, 2 tandem incisions were made on the lateral right atrium with various distances (3 to 20 mm) between the incisions in 16 canines. Four weeks after the surgery, the lateral right atrium was mapped epicardially during pacing to examine the conduction property through the isthmus. The conduction property was characterized by approximated curves of the conduction velocity through the isthmus in accordance with the pacing cycle lengths. The atrial tissue at the isthmus was examined microscopically.ResultsThe approximated curves of the conduction velocity were classified into 3 different types. Decremental conduction was observed only in the isthmi between 5 and 15 mm in width. A small amount of surviving myocardium between the scars formed the critical isthmus microscopically (decremental type). In the isthmi wider than 15 mm in width, slow conduction was not seen at any paced cycle length (nondecremental type). In the extremely narrow isthmi less than 5 mm in width, all of the atrial myocardium at the isthmus was replaced by fibrous tissue. Conduction was blocked at the isthmus and the activation detoured around the incisions (block type). There was a statistically significant difference in the approximated curves between the 3 different types of conduction properties (P < .01).ConclusionThe width of the isthmus determines the conduction property through the isthmus that contributes to the development of the incisional atrial reentrant tachycardia. Thus, the incisional atrial reentrant tachycardia may be preventable by leaving a sufficient amount of surviving myocardium between the incisions or by connecting the incisions by an ablative procedure
A quantitatively-modeled homozygosity mapping algorithm, qHomozygosityMapping, utilizing whole genome single nucleotide polymorphism genotyping data
Homozygosity mapping is a powerful procedure that is capable of detecting recessive disease-causing genes in a few patients from families with a history of inbreeding. We report here a homozygosity mapping algorithm for high-density single nucleotide polymorphism arrays that is able to (i) correct genotyping errors, (ii) search for autozygous segments genome-wide through regions with runs of homozygous SNPs, (iii) check the validity of the inbreeding history, and (iv) calculate the probability of the disease-causing gene being located in the regions identified. The genotyping error correction restored an average of 94.2% of the total length of all regions with run of homozygous SNPs, and 99.9% of the total length of them that were longer than 2 cM. At the end of the analysis, we would know the probability that regions identified contain a disease-causing gene, and we would be able to determine how much effort should be devoted to scrutinizing the regions. We confirmed the power of this algorithm using 6 patients with Siiyama-type α1-antitrypsin deficiency, a rare autosomal recessive disease in Japan. Our procedure will accelerate the identification of disease-causing genes using high-density SNP array data
The effect of 5-aminolevulinic acid on cytochrome c oxidase activity in mouse liver
<p>Abstract</p> <p>Background</p> <p>5-Aminolevulinic acid (ALA) is a precursor of heme that is fundamentally important in aerobic energy metabolism. Among the enzymes involved in aerobic energy metabolism, cytochrome <it>c </it>oxidase (COX) is crucial. In this study, the effect of ALA on cytochrome <it>c </it>oxidase activity was measured.</p> <p>Findings</p> <p>c57BL/6N species of mice were administered ALA orally for 15 weeks. After ALA administration, mice were sacrificed and livers were obtained. COX activity in mitochondria from ALA-administered mouse livers was 1.5-fold higher than that in mitochondria from PBS-administered mouse livers (P < 0.05). Furthermore, ATP levels in ALA-administered mouse livers were much higher than those in PBS-administered mouse livers. These data suggest that oral administration of ALA promotes aerobic energy metabolism, especially COX activity.</p> <p>Conclusions</p> <p>This is the first report of a drug that functions in aerobic energy metabolism directly. Since COX activity is decreased in various diseases and aging, the pharmacological effects of ALA will be expanding.</p
Crystal Growth of Thiol-Stabilized Gold Nanoparticles by Heat-Induced Coalescence
A monolayer of dodecanethiol-stabilized gold nanoparticles changed into two-dimensional and three-dimensional self-organized structures by annealing at 323 K. Subsequent crystal growth of gold nanoparticles occurred. Thiol molecules, although chemisorbed, form relatively unstable bonds with the gold surface; a few thiols desorbed from the surface and oxidized to disulfides at 323 K, because the interaction energy between thiol macromolecules is larger than that between a thiol and a nanoparticle. The gold nanoparticles approached each other and grew into large single or twinned crystals because of the van der Waals attraction and the heat generated by the exothermic formation of disulfides
CVIT expert consensus document on primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) in 2018
While primary percutaneous coronary intervention (PCI) has significantly contributed to improve the mortality in patients with ST segment elevation myocardial infarction even in cardiogenic shock, primary PCI is a standard of care in most of Japanese institutions. Whereas there are high numbers of available facilities providing primary PCI in Japan, there are no clear guidelines focusing on procedural aspect of the standardized care. Whilst updated guidelines for the management of acute myocardial infarction were recently published by European Society of Cardiology, the following major changes are indicated; (1) radial access and drug-eluting stent over bare metal stent were recommended as Class I indication, and (2) complete revascularization before hospital discharge (either immediate or staged) is now considered as Class IIa recommendation. Although the primary PCI is consistently recommended in recent and previous guidelines, the device lag from Europe, the frequent usage of coronary imaging modalities in Japan, and the difference in available medical therapy or mechanical support may prevent direct application of European guidelines to Japanese population. The Task Force on Primary Percutaneous Coronary Intervention of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) has now proposed the expert consensus document for the management of acute myocardial infarction focusing on procedural aspect of primary PCI
Let-7 MicroRNA Family Is Selectively Secreted into the Extracellular Environment via Exosomes in a Metastatic Gastric Cancer Cell Line
Background: Exosomes play a major role in cell-to-cell communication, targeting cells to transfer exosomal molecules including proteins, mRNAs, and microRNAs (miRNAs) by an endocytosis-like pathway. miRNAs are small noncoding RNA molecules on average 22 nucleotides in length that regulate numerous biological processes including cancer pathogenesis and mediate gene downregulation by targeting mRNAs to induce RNA degradation and/or interfering with translation. Recent reports imply that miRNAs can be stably detected in circulating plasma and serum since miRNAs are packaged by exosomes to be protected from RNA degradation. Thus, profiling exosomal miRNAs are in need to clarify intercellular signaling and discover a novel disease marker as well. Methodology/Principal Findings: Exosomes were isolated from cultured cancer cell lines and their quality was validated by analyses of transmission electron microscopy and western blotting. One of the cell lines tested, a metastatic gastric cancer cell line, AZ-P7a, showed the highest RNA yield in the released exosomes and distinctive shape in morphology. In addition, RNAs were isolated from cells and culture media, and profiles of these three miRNA fractions were obtained using microarray analysis. By comparing signal intensities of microarray data and the following validation using RT-PCR analysis, we found that let-7 miRNA family was abundant in both the intracellular and extracellular fractions from AZ-P7a cells, while low metastatic AZ-521, the parental cell line of AZ-P7a, as well as other cancer cell lines showed no such propensity. Conclusions/Significance: The enrichment of let-7 miRNA family in the extracellular fractions, particularly, in the exosome
CVIT expert consensus document on primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) in 2018
While primary percutaneous coronary intervention (PCI) has significantly contributed to improve the mortality in patients with ST segment elevation myocardial infarction even in cardiogenic shock, primary PCI is a standard of care in most of Japanese institutions. Whereas there are high numbers of available facilities providing primary PCI in Japan, there are no clear guidelines focusing on procedural aspect of the standardized care. Whilst updated guidelines for the management of acute myocardial infarction were recently published by European Society of Cardiology, the following major changes are indicated; (1) radial access and drug-eluting stent over bare metal stent were recommended as Class I indication, and (2) complete revascularization before hospital discharge (either immediate or staged) is now considered as Class IIa recommendation. Although the primary PCI is consistently recommended in recent and previous guidelines, the device lag from Europe, the frequent usage of coronary imaging modalities in Japan, and the difference in available medical therapy or mechanical support may prevent direct application of European guidelines to Japanese population. The Task Force on Primary Percutaneous Coronary Intervention of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) has now proposed the expert consensus document for the management of acute myocardial infarction focusing on procedural aspect of primary PCI
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Oxygen isotope evidence from Ryugu samples for early water delivery to Earth by CI chondrites
The delivery of water to the inner Solar System, including Earth, is still a debated topic. A preferential role for hydrated asteroids in this process is supported by isotopic measurements. Carbonaceous chondrite (CC) meteorites represent our main source of information about these volatile-rich asteroids. However, the destruction of weaker materials during atmospheric entry creates a bias in our CC data. The return of surface materials from the C-type asteroid 162173 Ryugu by the Hayabusa2 spacecraft provides a unique opportunity to study high-porosity, low-density, primitive materials, unrepresented in the meteorite record. We measured the bulk oxygen isotope composition from four Ryugu particles and show that they most closely resemble the rare CI (CC Ivuna-type) chondrites, but with some differences that we attribute to the terrestrial contamination of the CI meteorites. We suggest that CI-related material is widespread among carbonaceous asteroids and a more important source of Earth’s water and other volatiles than its limited presence in our meteoritic collection indicates
The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection
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