141 research outputs found
小分子スクリーニングを用いたパーキンソン病関連因子DJ-1の機能解析
学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 津本 浩平, 東京大学教授 伊藤 耕一, 東京大学准教授 富田 野乃, 東京大学客員教授 本田 真也, 東京理科大学教授 和田 猛University of Tokyo(東京大学
Combined use of an epidural cooling catheter and systemic moderate hypothermia enhances spinal cord protection against ischemic injury in rabbits
BackgroundEpidural placement of a cooling catheter can protect against ischemic spinal cord injury. With the use of rabbits, we investigated whether this epidural cooling technique, when combined with systemic moderate hypothermia, can protect the spinal cord against ischemic metabolic stress.MethodsNew Zealand white rabbits (n = 28) were assigned to 1 of 4 different groups. Animals underwent abdominal aortic occlusion for 30 minutes using a 3F balloon catheter. Group 1 (n = 7) underwent epidural cooling by the catheter and systemic moderate hypothermia (35°C) induced with a cooling blanket. Group 2 (n = 7) underwent epidural cooling under systemic normothermia (38.5°C). Group 3 (n = 7) underwent systemic moderate hypothermia (35°C) without epidural cooling. Group 4 (n = 7) underwent neither epidural nor blanket cooling as a negative control. Neurologic status of their hind limbs was graded according to the modified Tarlov scale at 1, 2, and 7 days after surgery.ResultsDuring infrarenal aortic ischemia, epidural temperature was significantly lower in group 1 (18.5°C ± 0.8°C) than in group 2 (28.6°C ± 1.0°C; P = .0001), group 3 (34.2°C ± 0.06°C; P = .0001), or group 4 (38.5°C ± 0.2°C; P = .0001). Hind limb function recovery was greater in group 1 (mean Tarlov score, 4.9 ± 0.057) than in group 2 (2.6 ± 0.3; P = .0028), group 3 (2.1 ± 0.34; P = .0088), or group 4 (0.0 ± 0.0; P = .0003).ConclusionsEpidural cooling catheter combined with systemic moderate hypothermia produced additive cooling ability and protected the spinal cord against ischemia in rabbits more effectively than either intervention alone
A Catalytic Role of XoxF1 as La3+-Dependent Methanol Dehydrogenase in Methylobacterium extorquens Strain AM1
In the methylotrophic bacterium Methylobacterium extorquens strain AM1, MxaF, a Ca2+-dependent methanol dehydrogenase (MDH), is the main enzyme catalyzing methanol oxidation during growth on methanol. The genome of strain AM1 contains another MDH gene homologue, xoxF1, whose function in methanol metabolism has remained unclear. In this work, we show that XoxF1 also functions as an MDH and is La3+-dependent. Despite the absence of Ca2+ in the medium strain AM1 was able to grow on methanol in the presence of La3+. Addition of La3+ increased MDH activity but the addition had no effect on mxaF or xoxF1 expression level. We purified MDH from strain AM1 grown on methanol in the presence of La3+, and its N-terminal amino acid sequence corresponded to that of XoxF1. The enzyme contained La3+ as a cofactor. The ΔmxaF mutant strain could not grow on methanol in the presence of Ca2+, but was able to grow after supplementation with La3+. Taken together, these results show that XoxF1 participates in methanol metabolism as a La3+-dependent MDH in strain AM1
Keishibukuryogan Reduces Renal Injury in the Early Stage of Renal Failure in the Remnant Kidney Model
The effects of keishibukuryogan on the early stage of progressive renal failure were examined in rats subjected to 5/6 nephrectomy. Keishibukuryogan, one of the traditional herbal formulations, was given orally at a dose of 1% (w/w) and 3% (w/w) in chow. Administration of keishibukuryogan was started at 1 week after 5/6 nephrectomy and was continued for 4 weeks. At the end of the experiment, Azan staining did not reveal any severe histological changes in the kidneys of the nephrectomized rats. On the other hand, significant increases in mRNA expressions of transforming growth factor-β1 and fibronectin related to tissue fibrosis, as examined by Reverse Transcriptase-Polymerase Chain Reaction, were observed in nephrectomized rats, and they were significantly suppressed by 3% keishibukuryogan treatment. Against gene expressions related to macrophage infiltration, 3% keishibukuryogan treatment significantly suppressed osteopontin mRNA levels, and monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1 mRNA levels showed a tendency to decrease, but without statistical significance. It was also observed that 3% keishibukuryogan attenuated serum urea nitrogen and urinary protein excretion levels. From these results, it was suggested that keishibukuryogan exerts beneficial effects that result in slowing the progression of chronic renal failure
Spectral evolution of GRB 060904A observed with Swift and Suzaku -- Possibility of Inefficient Electron Acceleration
We observed an X-ray afterglow of GRB 060904A with the Swift and Suzaku
satellites. We found rapid spectral softening during both the prompt tail phase
and the decline phase of an X-ray flare in the BAT and XRT data. The observed
spectra were fit by power-law photon indices which rapidly changed from to within a few hundred
seconds in the prompt tail. This is one of the steepest X-ray spectra ever
observed, making it quite difficult to explain by simple electron acceleration
and synchrotron radiation. Then, we applied an alternative spectral fitting
using a broken power-law with exponential cutoff (BPEC) model. It is valid to
consider the situation that the cutoff energy is equivalent to the synchrotron
frequency of the maximum energy electrons in their energy distribution. Since
the spectral cutoff appears in the soft X-ray band, we conclude the electron
acceleration has been inefficient in the internal shocks of GRB 060904A. These
cutoff spectra suddenly disappeared at the transition time from the prompt tail
phase to the shallow decay one. After that, typical afterglow spectra with the
photon indices of 2.0 are continuously and preciously monitored by both XRT and
Suzaku/XIS up to 1 day since the burst trigger time. We could successfully
trace the temporal history of two characteristic break energies (peak energy
and cutoff energy) and they show the time dependence of while the following afterglow spectra are quite stable. This fact
indicates that the emitting material of prompt tail is due to completely
different dynamics from the shallow decay component. Therefore we conclude the
emission sites of two distinct phenomena obviously differ from each other.Comment: 19 pages, 9 figures, accepted for publication in PASJ (Suzaku 2nd
Special Issue
Prevention of lethal hepatic injury in Long-Evans Cinnamon (LEC) rats by D-galactosamine hydrochloride
Repeated injections of D-galactosamine hydrochloride (GalN) increase the survival rate of Long-Evans Cinnamon (LEC) rats, an animal model of Wilson’s disease. The aim of the present study was to investigate the mechanism of GalN for prevention of spontaneous lethal hepatic injury in LEC rats. MaleLEC rats were given a single subcutaneous injection of 300mg/kg of GalN or vehicle (0.9%NaCl) at 14weeks, and killed at 28 weeks of age. Next, 6-week-old male LEC rats were given weekly subcutaneous injections of 300 mg/kg of GalN or vehicle for 3 or 12 weeks, and their hepatic 8-hydroxydeoxy-2’-guanosine (8-OHdG), glutathione peroxidase (GPX), and catalase activities were measured. None of GalN-treated rats died of hepatic injury (0/12), whereas the mortality rate of control rats given 0.9% NaCl was 17% (2/12). GalN administration for 12 weeks decreased the hepatic 8-OHdG, and GalN administration for either 3 or 12weeks increased the glutathione peroxidase activity. GalN administration increased the serum level of alanine aminotransferase, and accelerated megalocytic degeneration of the hepatocytes. GalN treatment is effective in preventing lethal hepatitis in LEC rats and decrease of oxidative DNA damage by GalN plays an important role in increase of the survival rate
The antitumor activity of xanthohumol
Xanthohumol (XN), a simple prenylated chalcone, can be isolated from hops and has the potential to be a cancer chemopreventive agent against several human tumor cell lines. We previously identified valosin-containing protein (VCP) as a target of XN; VCP can also play crucial roles in cancer progression and prognosis. Therefore, we investigated the molecular mechanisms governing the contribution of VCP to the antitumor activity of XN. Several human tumor cell lines were treated with XN to investigate which human tumor cell lines are sensitive to XN. Several cell lines exhibited high sensitivity to XN both in vitro and in vivo. shRNA screening and bioinformatics analysis identified that the inhibition of the adenylate cyclase (AC) pathway synergistically facilitated apoptosis induced by VCP inhibition. These results suggest that there is crosstalk between the AC pathway and VCP function, and targeting both VCP and the AC pathway is a potential chemotherapeutic strategy for a subset of tumor cells
Cerebral air embolism as a complication of peptic ulcer in the gastric tube: case report
<p>Abstract</p> <p>Background</p> <p>The reported incidence of ulcer formation in the gastric tube in esophageal replacement is rare.</p> <p>Case Presentation</p> <p>This is the first report of a case of cerebral air embolism as a result of spontaneous perforation of an ulcer in the constructed gastric tube into the pulmonary vein during post-operative follow-up in a patient with esophageal cancer.</p> <p>Conclusions</p> <p>Cerebral air embolism is a rare complication of penetrating gastric ulcer, but should be considered in patients with a history of esophagectomy with gastric conduit that present with acute neurologic findings.</p
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
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