In-air microparticle induced X-ray emission analysis of particles in interstitial pneumonia lung tissue obtained by transbronchial biopsy

Interstitial pneumonia develops in association with inhaled particles. In-air microparticle induced X-ray emission (in-air micro) analysis was previously employed to assess the spatial distribution and content of particles in surgical lung biopsy specimens. The aim of this study was to assess the efficacy of in-air micro-analysis for transbronchial lung biopsy specimens in patients with or without occupational exposure. The elements composing lung particles and their locations could be identified by in-air micro-analysis. Silicon was the major component of particles. Quantitative analysis revealed that the elements composing lung particles varied between patients. In a patient with suspected nickel exposure, aluminium, vanadium, and calcium were detected, but was not detected. In a patient without a work history (housewife), various elements were detected. In-air micro-analysis was useful for assessing the spatial distribution and content of particles in specimens from patients. Occupational exposure was not necessarily associated with deposition of particles in the lungs. Therefore, in the diagnosis of, elemental analysis of specimens by in-air micro-analysis could be useful for assessing exposure to particles objectively

Sodium Channelopathy Underlying Familial Sick Sinus Syndrome With Early Onset and Predominantly Male Characteristics

Background-Sick sinus syndrome (SSS) is a common arrhythmia often associated with aging or organic heart diseases but may also occur in a familial form with a variable mode of inheritance. Despite the identifcation of causative genes, including cardiac Na channel (SCN5A), the pathogenesis and molecular epidemiology of familial SSS remain undetermined primarily because of its rarity. Methods and Results-We genetically screened 48 members of 15 SSS families for mutations in several candidate genes and determined the functional properties of mutant Na channels using whole-cell patch clamping. We identifed 6 SCN5A mutations including a compound heterozygous mutation. Heterologously expressed mutant Na channels showed loss-of-function properties of reduced or no Na current density in conjunction with gating modulations. Among 19 family members with SCN5A mutations, QT prolongation and Brugada syndrome were associated in 4 and 2 individuals, respectively. Age of onset in probands carrying SCN5A mutations was signifcantly less (mean±SE, 12.4±4.6 years; n=5) than in SCN5A-negative probands (47.0±4.6 years; n=10; P<0.001) or nonfamilial SSS (74.3±0.4 years; n=538; P<0.001). Meta-analysis of SSS probands carrying SCN5A mutations (n=29) indicated profound male predominance (79.3%) resembling Brugada syndrome but with a considerably earlier age of onset (20.9±3.4 years). Conclusions-The notable pathophysiological overlap between familial SSS and Na channelopathy indicates that familial SSS with SCN5A mutations may represent a subset of cardiac Na channelopathy with strong male predominance and early clinical manifestations

Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls.

PURPOSE: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate. METHODS: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants. RESULTS: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 × 10-18) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 × 10-13). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency. CONCLUSION: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing

Development and Application of an Elemental Mapping System using an Ion MicrobeamDevelopment and Application of an Elemental Mapping System using an Ion Microbeam

直径1～数μmの3MeVのH+マイクロビームを試料に照射することで励起するX線を測定する微量元素マッピングシステム（マイクロPIXE分析システム) の利用を推進している。高崎量子応用研究所で開発したこのシステムでは、マイクロビームを、有機膜を通して大気中に取り出すことで、生体試料等の含水試料への照射を可能とした。さらに、真空中の照射では、トモグラフィ技術を取り入れることで、非破壊で三次元マッピングができる技術を開発し、直径数10μmの吸着材の中に残存する金属元素の分布から溶離率の改善につながる知見を得た。加えて、本システムと併用できるイオンビーム誘起発光分析システムの開発を行い、前者のみでは困難であった化合物の推定も可能になりつつある。これらの技術により、マイクロPIXE分析システムのさらなる応用の拡大が期待できる。IUMRS-ICAM 201

Infectious prion protein in the filtrate even after 15 nm filtration.

The evaluation of the removal efficacy during manufacturing is important for the risk assessment of plasma products with respect to possible contamination by infectious prions, as recently reported in several papers on the potential for prion transmission through plasma products. Here, we evaluated a virus removal filter which has 15 nm pores. An antithrombin sample immediately prior to nano-filtration was spiked with prion material prepared in two different ways. The removal (log reduction factor) of prion infectivity using animal bioassays was >or=4.72 and 4.00 in two independent filtrations. However, infectivity was detected in both the pellet and supernatant following ultracentrifugation of the 15 nm filtered samples, indicating difficulty in complete removal. The data supports the conclusion that a certain amount of infectious prion protein is present as a smaller and/or soluble form (less than approximately 15 nm in diameter)

Status of ion sources at the national institutes for quantum and radiological science and technolog

QSTにおける各種イオン源開発の紹介のうちの一つとして、核融合プラズマ加熱装置に使用される負イオン源の開発について報告する