Perfluorooctane Sulfonate (PFOS) and Related Perfluorinated Compounds in Human Maternal and Cord Blood Samples: Assessment of PFOS Exposure in a Susceptible Population during Pregnancy

Fluorinated organic compounds (FOCs), such as perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorooctane sulfonylamide (PFOSA), are widely used in the manufacture of plastic, electronics, textile, and construction material in the apparel, leather, and upholstery industries. FOCs have been detected in human blood samples. Studies have indicated that FOCs may be detrimental to rodent development possibly by affecting thyroid hormone levels. In the present study, we determined the concentrations of FOCs in maternal and cord blood samples. Pregnant women 17–37 years of age were enrolled as subjects. FOCs in 15 pairs of maternal and cord blood samples were analyzed by liquid chromatography–electrospray mass spectrometry coupled with online extraction. The limits of quantification of PFOS, PFOA, and PFOSA in human plasma or serum were 0.5, 0.5, and 1.0 ng/mL, respectively. The method enables the precise determination of FOCs and can be applied to the detection of FOCs in human blood samples for monitoring human exposure. PFOS concentrations in maternal samples ranged from 4.9 to 17.6 ng/mL, whereas those in fetal samples ranged from 1.6 to 5.3 ng/mL. In contrast, PFOSA was not detected in fetal or maternal samples, whereas PFOA was detected only in maternal samples (range, < 0.5 to 2.3 ng/mL, 4 of 15). Our results revealed a high correlation between PFOS concentrations in maternal and cord blood (r(2) = 0.876). However, we did not find any significant correlations between PFOS concentration in maternal and cord blood samples and age bracket, birth weight, or levels of thyroid-stimulating hormone or free thyroxine. Our study revealed that human fetuses in Japan may be exposed to relatively high levels of FOCs. Further investigation is required to determine the postnatal effects of fetal exposure to FOCs

Evidence of mature adipocyte proliferation regulated by proliferin

Despite much research, whether mature adipocytes proliferate remains controversial. Here, we examined 5-bromo-2&#x2032;-deoxyuridine (BrdU)-labelling of mature adipocytes. Although BrdU incorporation into subcutaneous adipocytes was less than that in visceral adipocytes, pioglitazone (Pio) treatment increased BrdU incorporation in subcutaneous, but not visceral, adipocytes in rats. Fully differentiated 3T3-L1 adipocytes exhibited an increase in cell number and BrdU incorporation with time, with this increase enhanced by Pio treatment. We therefore screened for genes that encode growth factors regulated by Pio, and selected proliferin (PLF). Both gene silencing of PLF by small interfering RNA and treatment with anti-PLF antibody suppressed proliferation in 3T3-L1 adipocytes. In adipocytes isolated from Pio-treated rats, the tissue-specific pattern of PLF expression was similar to that of BrdU incorporation. Administration of an anti-PLF antibody to mice reduced BrdU incorporation into adipocytes. Mature adipocytes thus have the ability to replicate, and this proliferation is positively regulated by PLF

Prediction of common hepatic artery catheter insertion based on celiac trunk morphology

PURPOSEThis study aimed to predict the ability to insert a 4–5 French (Fr) catheter insertion with a guidewire into the common hepatic artery (CHA) based on celiac trunk morphology.METHODSThis retrospective study included 64 patients who underwent balloon-occluded transcatheter arterial chemoembolization (n = 56), transcatheter arterial chemotherapy (n = 2), or were fitted with an implantable port system (n = 6) between June 2019 and December 2019 in our institution. The morphology of the celiac trunk was classified into three types (upward, horizontal, and downward) based on celiac angiography. The aortic–celiac trunk angle was measured on sagittal images of preprocedural contrast-enhanced computed tomography (CT). We reviewed whether a 4–5-Fr shepherd’s hook catheter could advance beyond the CHA using a 0.035-inch guidewire (Radifocus® Guidewire M; Terumo). Three patients were diagnosed with median arcuate ligament syndrome (MALS) based on the characteristic hook shape of the celiac artery on sagittal images of contrast-enhanced CT. The predictive ability of celiac angiography and preprocedural CT for CHA insertion success was evaluated. In unsuccessful cases, the balloon anchor technique (BAT) was attempted as follows: (1) a 2.7/2.8-Fr microballoon catheter (Attendant Delta; Terumo) was placed beyond the proper hepatic artery, and (2) the balloon was inflated as an anchor for parent catheter advancement.RESULTSUpward, horizontal, and downward celiac trunk types were noted in 42, 9, and 13 patients, respectively. The median CT angle was 122.83° (first quartile–third quartile, 102.88°–136.55°). Insertion in the CHA using the guidewire was successful in 56 of 64 patients (87.50%), and the success rate in the downward type was significantly lower than that in the upward type [42/42 (100%) vs. 7/13 (53.85%), P < 0.001]. The CT angle was significantly larger downward in the unsuccessful group than in the successful group (121.03° vs. 140.70°, P = 0.043). Celiac angiography had a significantly higher area under the curve (AUC) than preprocedural CT (AUC = 0.91 vs. AUC = 0.72, P = 0.040). All three cases of MALS showed unsuccessful CHA insertion. In all eight patients with unsuccessful insertion, the catheter could be advanced using the BAT [8/8 (100%)].CONCLUSIONCeliac angiography and preprocedural CT could predict CHA catheter insertion using a guidewire, and celiac angiography had high predictability. CT could detect MALS, a risk factor for unsuccessful CHA insertion

Three minute, but not one minute, ischemia and nicorandil have a preconditioning effect in patients with coronary artery disease

AbstractOBJECTIVESThis study focused on 1) the determination of the optimal preconditioning (PC) duration, and 2) the protective effect of nicorandil (NC), a hybrid nitrate with a Katpchannel opening effect, during a percutaneous transluminal coronary angioplasty (PTCA) model in humans.BACKGROUNDThe ischemic PC effect is induced in 180 s ischemia, but not in 120 s ischemia in rabbit hearts. However, the duration of ischemia that induces PC effect and the role of the Katpchannel in the PC effect in humans are still unclear.METHODSForty-six patients with stable angina were randomly allocated to four groups: the duration of the first inflation as PC ischemia was 60 s in the PC60 group (n = 12), and 180 s in the PC180 group (n = 12). In the other groups, NC (80 μg/kg) was intravenously given for 1 min in the NC group (n = 12), and isosorbide dinitrate (ISDN) (40 μg/kg) was given in the ISDN group (n = 10). Five minutes after first inflation or drug administration, a second inflation was conducted for 120 s in each group. In the ECG, the lead with the largest shift in ST segment (deltaST max), and the sum of elevated ST levels in all leads (sigmaST) were determined.RESULTSIn the PC60 group, no significant difference was observed in either deltaST max or sigmaST between the first and second inflation. However, the second inflation in the PC180 group showed significantly lower levels of deltaST max and sigmaST compared with those of the first inflation. In the NC group, both deltaST max and sigmaST measured at 30 s and 60 s after balloon inflation were significantly lower than those of the first inflation in the PC60 and PC180 control groups. In the ISDN group, no significant difference was observed in deltaST max or sigmaST.CONCLUSIONIn human PTCA models, a PC effect is observed in 180 s ischemia, but not in 60 s ischemia. A pharmacological PC effect is induced by NC, a Katpchannel opener with a nitrate-like effect but not ISDN. This suggests that the opening of Katpchannels plays an important role in the protecting effect of NC

The Nature of Ultra-Luminous Compact X-Ray Sources in Nearby Spiral Galaxies

Studies were made of ASCA spectra of seven ultra-luminous compact X-ray sources (ULXs) in nearby spiral galaxies; M33 X-8 (Takano et al. 1994), M81 X-6 (Fabbiano 1988b; Kohmura et al. 1994; Uno 1997), IC 342 Source 1 (Okada et al. 1998), Dwingeloo 1 X-1 (Reynolds et al. 1997), NGC 1313 Source B (Fabbiano & Trinchieri 1987; Petre et al. 1994), and two sources in NGC 4565 (Mizuno et al. 1999). With the 0.5--10 keV luminosities in the range 10^{39-40} ergs/s, they are thought to represent a class of enigmatic X-ray sources often found in spiral galaxies. For some of them, the ASCA data are newly processed, or the published spectra are reanalyzed. For others, the published results are quoted. The ASCA spectra of all these seven sources have been described successfully with so called multi-color disk blackbody (MCD) emission arising from optically-thick standard accretion disks around black holes. Except the case of M33 X-8, the spectra do not exhibit hard tails. For the source luminosities not to exceed the Eddington limits, the black holes are inferred to have rather high masses, up to ~100 solar masses. However, the observed innermost disk temperatures of these objects, Tin = 1.1--1.8 keV, are too high to be compatible with the required high black-hole masses, as long as the standard accretion disks around Schwarzschild black holes are assumed. Similarly high disk temperatures are also observed from two Galactic transients with superluminal motions, GRO 1655-40 and GRS 1915+105. The issue of unusually high disk temperature may be explained by the black hole rotation, which makes the disk get closer to the black hole, and hence hotter.Comment: submitted to ApJ, December 199

CLICK:One-step generation of conditional knockout mice

Abstract Background CRISPR/Cas9 enables the targeting of genes in zygotes; however, efficient approaches to create loxP-flanked (floxed) alleles remain elusive. Results Here, we show that the electroporation of Cas9, two gRNAs, and long single-stranded DNA (lssDNA) into zygotes, termed CLICK (CRISPR with lssDNA inducing conditional knockout alleles), enables the quick generation of floxed alleles in mice and rats. Conclusions The high efficiency of CLICK provides homozygous knock-ins in oocytes carrying tissue-specific Cre, which allows the one-step generation of conditional knockouts in founder (F0) mice

免疫組織化学法を用いた一側内耳破壊ラットの前庭代償の新しい評価法の開発

Background: Unilateral labyrinthectomy (UL) causes the disappearance of ipsilateral medial vestibular nuclear (ipsi-MVe) activity and induces spontaneous nystagmus (SN), which disappears during the initial process of vestibular compensation (VC). Ipsi-MVe-activity restores in the late process of VC. Objective: We evaluated the late process of VC after UL in rats and examined the effects of thioperamide (H3 antagonist) on VC. Materials and methods: MK801 (NMDA antagonist)-induced Fos-like immunoreactive (-LIR) neurons in contra-MVe, which had been suppressed by NMDA-mediated cerebellar inhibition in UL-rats was used as an index. Results: The number of MK801-induced Fos-LIR neurons in contra-MVe gradually decreased to the same level as that of sham-operated rats 14 days after UL. Thioperamide moved the disappearance of the MK801-induced Fos-LIR neurons 2 days earlier. The number of MK801-induced Fos-LIR neurons in thioperamide-treated rats was significantly decreased, compared with that of vehicle-rats on days 7 and 12 after UL. But, thioperamide did not influence the decline of SN frequency in UL-rats. Conclusion: There findings suggested that the number of MK801-induced Fos-LIR neurons in contra-MVe was decreased in concordance with the restoration of ipsi-MVe-activity during the late process of VC after UL and that thioperamide accelerated the late, but not the initial process of VC

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