The saw-tooth sign as a clinical clue for intrathoracic central airway obstruction

BACKGROUND: The saw-tooth sign was first described by Sanders et al in patients with obstructive sleep apnea syndrome as one cause of extrathoracic central airway obstruction. The mechanism of the saw-tooth sign has not been conclusively clarified. The sign has also been described in various extrathoracic central airway diseases, such as in burn victims with thermal injury to the upper airways, Parkinson’s disease, tracheobronchomalacia, laryngeal dyskinesia, and pedunculated tumors of the upper airway. CASE PRESENTATION: A 61-year-old man was referred to our hospital with a two-month history of persistent dry cough and dyspnea. He was diagnosed with lung cancer located in an intrathoracic central airway, which was accompanied by the saw-tooth sign on flow-volume loops. This peculiar sign repeatedly improved and deteriorated, in accordance with the waxing and waning of central airway stenosis by anti-cancer treatments. CONCLUSION: This report suggests that the so-called saw-tooth sign may be found even in intrathoracic central airway obstruction due to lung cancer

Expression of leptin receptors in hepatic sinusoidal cells

Emerging evidence has suggested a critical role of leptin in hepatic inflammation and fibrogenesis, however, the precise mechanisms underlying the profibrogenic action of leptin in the liver has not been well elucidated. Therefore, the present study was designed to investigate the expression and functions of leptin receptors (Ob-R) in hepatic sinusoidal cells. Hepatic stellate cells (HSCs), Kupffer cells and sinusoidal endothelial cells (SECs) were isolated from rat livers by in situ collagenase perfusion followed by differential centrifugation technique, and expression of Ob-Ra and Ob-Rb, short and long Ob-R isoforms, respectively, were analyzed by RT-PCR. Ob-Ra mRNA was detected ubiquitously in HSCs and SECs. In contrast, Ob-Rb was detected clearly only in SECs and Kupffer cells, but not in 7-day cultured HSCs. Indeed, tyrosine-phosphorylation of STAT-3, a downstream event of Ob-Rb signaling, was observed in SECs, but not in HSCs, 1 hr after incubation with leptin. Further, leptin increased AP-1 DNA binding activity and TGF-beta 1 mRNA levels in Kupffer cells and SECs, whereas leptin failed to increase TGF-beta 1 mRNA in HSCs. These findings indicated that SECs and Kupffer cells, but not HSCs, express functional leptin receptors, through which leptin elicits production of TGF-beta 1. It is hypothesized therefore that leptin, produced systemically from adipocytes and locally from HSCs, up-regulates TGF-beta 1 thereby facilitate tissue repairing and fibrogenesis in the sinusoidal microenvironment

Rifaximin Exerts Beneficial Effects Independent of its Ability to Alter Microbiota Composition

Rifaximin has clinical benefits in minimal hepatic encephalopathy (MHE) but the mechanism of action is unclear. The antibiotic-dependent and -independent effects of rifaximin need to be elucidated in the setting of MHE-associated microbiota. To assess the action of rifaximin on intestinal barrier, inflammatory milieu and ammonia generation independent of microbiota using rifaximin

HER2 ヨウセイ ニュウガン ニ タイシテ Pertuzumab オ モチイタ ジュツゼン カガク リョウホウ オ セコウシタ 16レイ

Pertuzumab is a molecular-targeted drug that binds to the extracellular domain of human epidermal growth factor receptor 2 (HER2) and inhibits dimer formation. The combined use of pertuzumab and trastuzumab for HER2-positive breast cancer has been reported to significantly increase the rate of pathological complete response (pCR) compared to that with trastuzumab monotherapy. We reported the outcomes of HER2-positive breast cancer treated with neoadjuvant chemotherapy with pertuzumab. Sixteen patients with stages II–III HER2-positive breast cancer were treated with 4 cycles of docetaxel (75 mg/m2) with trastuzumab and pertuzumab, followed by 4 cycles of 5-fluorouracil (500 mg/m2), epirubicin (100 mg/m2), and cyclophosphamide (500 mg/m2). The participants were in the age range of 45–76 years; T1, T2 and T3 stages were reported in 2, 11, and 3 cases, respectively, and N0 and N1 stages were reported in 6 and 10 cases, respectively. Luminal HER2 and HER2-enriched subtypes were noted in 8 cases each. In all cases, scheduled chemotherapy was completely implemented. Grade 3, 2b, 1a and 1b histology were observed in 11, 3, 1, and 1 cases, respectively. The rate of pCR (ypT0/is + ypN0) was 69%, whereas the objective response rate was 94%. In 12 cases, breast-conserving surgery was undertaken, whereas 4 patients underwent total mastectomy. Pertuzumab did not cause any complications, including cardiac dysfunction.PertuzumabはHER2の細胞外ドメインに結合し、ダイマー形成を阻害するである。種々の試験において、trastuzumab単独よりもPertuzumabを併用した方が病理学的完全奏効率(pCR)を有意に上昇すると報告されている。今回、我々はHER2陽性乳癌に対してPertuzumabを用いた術前化学療法を行った。16名のStageII～IIIのHER2陽性乳患者に、Pertuzumab、Trastuzumab、Docetaxel（75 mg/m2）4コース、その後にFEC100療法4コースを施行した。年齢は45～76歳で、T1、T2、T3はそれぞれ2例、11例、3例、N0、N1はそれぞれ6例、10例であった。Luminal HER2 type、HER2 enrich typeともに8例であった。すべての症例で予定された化学療法が完全施行できた。組織学的効果はGrade3、2b、1a、1bがそれぞれ11例、3例、1例、1例であった。pCR（ypT0/is + ypN0）率は69％で、奏功率は94%であった。Pertuzumabによる心機能障害等の副作用は認められなかった

The ASTRO-H X-ray Observatory

The joint JAXA/NASA ASTRO-H mission is the sixth in a series of highly successful X-ray missions initiated by the Institute of Space and Astronautical Science (ISAS). ASTRO-H will investigate the physics of the high-energy universe via a suite of four instruments, covering a very wide energy range, from 0.3 keV to 600 keV. These instruments include a high-resolution, high-throughput spectrometer sensitive over 0.3-2 keV with high spectral resolution of Delta E < 7 eV, enabled by a micro-calorimeter array located in the focal plane of thin-foil X-ray optics; hard X-ray imaging spectrometers covering 5-80 keV, located in the focal plane of multilayer-coated, focusing hard X-ray mirrors; a wide-field imaging spectrometer sensitive over 0.4-12 keV, with an X-ray CCD camera in the focal plane of a soft X-ray telescope; and a non-focusing Compton-camera type soft gamma-ray detector, sensitive in the 40-600 keV band. The simultaneous broad bandpass, coupled with high spectral resolution, will enable the pursuit of a wide variety of important science themes.Comment: 22 pages, 17 figures, Proceedings of the SPIE Astronomical Instrumentation "Space Telescopes and Instrumentation 2012: Ultraviolet to Gamma Ray

The Quiescent Intracluster Medium in the Core of the Perseus Cluster

Clusters of galaxies are the most massive gravitationally-bound objects in the Universe and are still forming. They are thus important probes of cosmological parameters and a host of astrophysical processes. Knowledge of the dynamics of the pervasive hot gas, which dominates in mass over stars in a cluster, is a crucial missing ingredient. It can enable new insights into mechanical energy injection by the central supermassive black hole and the use of hydrostatic equilibrium for the determination of cluster masses. X-rays from the core of the Perseus cluster are emitted by the 50 million K diffuse hot plasma filling its gravitational potential well. The Active Galactic Nucleus of the central galaxy NGC1275 is pumping jetted energy into the surrounding intracluster medium, creating buoyant bubbles filled with relativistic plasma. These likely induce motions in the intracluster medium and heat the inner gas preventing runaway radiative cooling; a process known as Active Galactic Nucleus Feedback. Here we report on Hitomi X-ray observations of the Perseus cluster core, which reveal a remarkably quiescent atmosphere where the gas has a line-of-sight velocity dispersion of 164+/-10 km/s in a region 30-60 kpc from the central nucleus. A gradient in the line-of-sight velocity of 150+/-70 km/s is found across the 60 kpc image of the cluster core. Turbulent pressure support in the gas is 4% or less of the thermodynamic pressure, with large scale shear at most doubling that estimate. We infer that total cluster masses determined from hydrostatic equilibrium in the central regions need little correction for turbulent pressure.Comment: 31 pages, 11 Figs, published in Nature July

On the origin and evolution of the asteroid Ryugu: A comprehensive geochemical perspective

Presented here are the observations and interpretations from a comprehensive analysis of 16 representative particles returned from the C-type asteroid Ryugu by the Hayabusa2 mission. On average Ryugu particles consist of 50% phyllosilicate matrix, 41% porosity and 9% minor phases, including organic matter. The abundances of 70 elements from the particles are in close agreement with those of CI chondrites. Bulk Ryugu particles show higher δ18O, Δ17O, and ε54Cr values than CI chondrites. As such, Ryugu sampled the most primitive and least-thermally processed protosolar nebula reservoirs. Such a finding is consistent with multi-scale H-C-N isotopic compositions that are compatible with an origin for Ryugu organic matter within both the protosolar nebula and the interstellar medium. The analytical data obtained here, suggests that complex soluble organic matter formed during aqueous alteration on the Ryugu progenitor planetesimal (several 10’s of km), <2.6 Myr after CAI formation. Subsequently, the Ryugu progenitor planetesimal was fragmented and evolved into the current asteroid Ryugu through sublimation

Hitomi (ASTRO-H) X-ray Astronomy Satellite

The Hitomi (ASTRO-H) mission is the sixth Japanese x-ray astronomy satellite developed by a large international collaboration, including Japan, USA, Canada, and Europe. The mission aimed to provide the highest energy resolution ever achieved at E  >  2  keV, using a microcalorimeter instrument, and to cover a wide energy range spanning four decades in energy from soft x-rays to gamma rays. After a successful launch on February 17, 2016, the spacecraft lost its function on March 26, 2016, but the commissioning phase for about a month provided valuable information on the onboard instruments and the spacecraft system, including astrophysical results obtained from first light observations. The paper describes the Hitomi (ASTRO-H) mission, its capabilities, the initial operation, and the instruments/spacecraft performances confirmed during the commissioning operations for about a month

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