21 research outputs found
ニュウボウ オンゾン リョウホウゴ ニ ハッショウ シタ bronchiolitis obliterans organizing pneumoniaヨウ ハイエン ノ 1レイ
Multiple Translocation of the AVR-Pita Effector Gene among Chromosomes of the Rice Blast Fungus Magnaporthe oryzae and Related Species
Magnaporthe oryzae is the causal agent of rice blast disease, a devastating problem worldwide. This fungus has caused breakdown of resistance conferred by newly developed commercial cultivars. To address how the rice blast fungus adapts itself to new resistance genes so quickly, we examined chromosomal locations of AVR-Pita, a subtelomeric gene family corresponding to the Pita resistance gene, in various isolates of M. oryzae (including wheat and millet pathogens) and its related species. We found that AVR-Pita (AVR-Pita1 and AVR-Pita2) is highly variable in its genome location, occurring in chromosomes 1, 3, 4, 5, 6, 7, and supernumerary chromosomes, particularly in rice-infecting isolates. When expressed in M. oryzae, most of the AVR-Pita homologs could elicit Pita-mediated resistance, even those from non-rice isolates. AVR-Pita was flanked by a retrotransposon, which presumably contributed to its multiple translocation across the genome. On the other hand, family member AVR-Pita3, which lacks avirulence activity, was stably located on chromosome 7 in a vast majority of isolates. These results suggest that the diversification in genome location of AVR-Pita in the rice isolates is a consequence of recognition by Pita in rice. We propose a model that the multiple translocation of AVR-Pita may be associated with its frequent loss and recovery mediated by its transfer among individuals in asexual populations. This model implies that the high mobility of AVR-Pita is a key mechanism accounting for the rapid adaptation toward Pita. Dynamic adaptation of some fungal plant pathogens may be achieved by deletion and recovery of avirulence genes using a population as a unit of adaptation
Effects from Spatial Cues on Detectability of Alarm Signals in Car Environments
It is crucial to correctly detect alarm signals in noise conditions, for instance, especially in car environments. However, alarm signals are possibly masked by noises from engine, friction between tires and road, etc., in car environments. To design the alarm signals that can be easily detected,it is necessary to first understand the perceptual characteristics of alarm signals in noisy environments. In this paper, the masked thresholds of alarm signals in the presence of car noise were measured in the virtual acoustic environmentsgenerated by using head-related transfer functions (HRTFs). The main conclusions are: a) when the frequency component of alarm signals is 1.0 kHz, interaural time difference (ITD) and interaural phase difference (IPD) have great effect on the detectability of alarm signals in car noise; b) when the frequency component of alarm signals is 2:5 kHz, interaural level difference (ILD) except ITD and IPD also plays an important role in alarm signal detection when the signal is fixed in the front of listener
Effect of dose-delivery time for flattened and flattening filter-free photon beams based on microdosimetric kinetic model.
The effect of dose-delivery time with flattening filter (FF) and flattening filter-free (FFF) photon beams based on microdosimetric kinetic model (MKM) was investigated in this study. Monte Carlo simulation with the particle and heavy ion transport code system (PHITS) was performed to calculate the dose-mean lineal energy yD (keV/μm) of FF and FFF 6 MV photon beams using the IAEA phase-space files of Varian TrueBeam linear accelerator. Human non-small cell lung cancer NCI-H460 cells were used to determine the MKM parameters under the condition that dose-delivery times with continuous irradiation were 1, 5, 10, 30, and 60 min, and the adsorbed dose was 2, 4, and 8 Gy in this study. In addition, the relative biological effectiveness (RBE) of FF and FFF photon beams were calculated for evaluating the effect of dose delivery time. The RBE of FF decreased to 99.8% and 97.5% with 5 and 60 min for 2 Gy in comparison to 99.6% and 95.1% for 8 Gy, respectively. Meanwhile, that of FFF decreased to 99.5% and 94.9% with 5 and 60 min for 2 Gy in comparison to 99.5% and 94.9% for 8 Gy, respectively. Dose-delivery time has an effect on the RBE with photon beams. In other words, the dose-delivery time should be considered during radiation therapy. Furthermore, FFF photon beams were an effective irradiation method compared to FF in dose-delivery time on account of improving clinic throughput
Treatment‐related neuroendocrine prostate cancer with BRCA2 germline mutation treated with olaparib
Introduction The efficacy of olaparib for treatment‐related neuroendocrine prostate cancer is unknown. Here, we report a case of treatment‐related neuroendocrine prostate cancer with a BRCA2 mutation that was treated with olaparib with 1‐year efficacy. Case presentation A 75‐year‐old man initially diagnosed with prostate adenocarcinoma developed treatment‐related neuroendocrine prostate cancer after 10‐year androgen deprivation therapy. Despite the initial temporary effects of etoposide and carboplatin, the patient experienced prostate bed tumor recurrence 1 year after chemotherapy cessation. FoundationOne® detected a BRCA2 gene mutation, and olaparib was initiated after repeating one chemotherapy course using the same chemotherapeutic agents. The patient received olaparib with sustained tumor regression for 1 year without severe side effects. Conclusion Olaparib may be the treatment of choice for treatment‐related neuroendocrine prostate cancer in patients with BRCA mutations
Effect of galactose diet removal on the progression of retinal vessel changes in galactose-fed dogs
PURPOSE. Feeding dogs a diet containing 30% galactose induces experimental galactosemia and results in the formation of diabetes-like microvascular lesions of the retina. The appearance and progression of these retinal lesions can be arrested in a dose-dependent manner by treating these dogs with aldose reductase inhibitors from the onset of galactosemia. To determine whether the elimination of galactosemia can also reduce the progression of retinal lesions, the galactose diet was removed from the galactosemic dogs after either the appearance of pericyte ghosts or formation of microaneurysms. METHODS. Ten control dogs were fed a normal diet, and 50 dogs were fed a diet containing 30% galactose. The galactose diet was removed from 15 dogs after 24 months, the time at which pericyte ghosts had previously been observed to develop, and from another 15 dogs after 31 months, when microaneurysms had previously been observed to develop. Eighteen dogs were continued on a galactose diet. Beginning at 24 months, eyes from each group were enucleated at approximately 6-month intervals. Changes in retinal lesions were quantified by computer image analyses. RESULTS. Significant (P Ͻ 0.05-0.01) increases in the endothelium-pericyte (E-P) ratio and decreases in pericyte density were observed with increased duration of galactose feeding. Although no reversal of retinal lesions occurred, differences in the progression of retinal lesions between the galactose-fed and galactose-deprived groups became evident after 12 to 24 months. CONCLUSIONS. Discontinuation of galactose in the diet at the initial stages of background retinopathy beneficially delays the progression of retinal lesions. (Invest Ophthalmol Vis Sci. 2002;43:1916 -1921 D iabetic retinopathy, a leading cause of blindness, is a major long-term complication of diabetes mellitus that is characterized by vascular changes of the retinal capillary bed. In its early, nonproliferative stage, these changes include the formation of microaneurysms, intraretinal hemorrhages, exudates and altered blood flow. In the later, proliferative stage, neovascularization occurs as retinal vessels break through the inner limiting membrane and grow into the vitreous. 1 A hallmark of this disease is the destruction of pericytes (mural cells) from retinal capillaries and the formation of pericyte ghosts. 2,3 Their loss is associated with vessel dilation, formation of microaneurysm, and endothelial cell proliferation. Retinal vessel changes similar to human retinopathy have been observed to occur in diabetic 4 -6 and galactose-fed Galactosemia is associated with a number of diabetes-like lesions. 10 Galactosemia, both hereditary and experimentally induced with galactose feeding, is associated with the rapid formation of galactitol and, to a lesser extent, the formation of galactonic acid and/or galactonolactone. 11-14 Long-term galactosemia is also associated with increased nonenzymatic glycation, basement membrane thickening, and biochemical changes that include decreased glutathione, taurine, and myoinositol levels, decreased adenosine triphosphate (ATP) and amino acid transport activity, increased PKC and VEGF levels, and altered membrane permeability. Formation of galactitol is catalyzed by the enzyme aldose reductase, and its intracellular accumulation precedes the biochemical changes associated with long-term galactosemia. The administration of aldose reductase inhibitors to animals from the onset of galactose feeding has been observed to reduce galactitol formation and prevent the subsequent formation of diabetes-like lesions. 10 However, aldose reductase inhibitors do not inhibit gulonic acid or formation of galactonolactone, suggesting that the formation of these latter two metabolic intermediates, unlike galactitol, do not contribute to the formation of diabetes-like lesions. 14 Studies using the galactose-fed dog model indicate that degeneration of retinal capillary pericytes is linked to the aldose reductase-catalyzed production of galactitol and that their loss precedes further vascular changes associated with retinopathy. In beagles fed a 30% galactose diet for 36 to 38 months, the onset and progression of destruction of pericytes and the formation of microaneurysms was reduced by the concomitant administration of the aldose reductase inhibitors sorbinil (S-6-fluoro-spirochroman-4-5Ј-imidazolidine-2Ј,4Јdione), its more potent 2-methyl analogue M79175 (2-methyl-6-fluorospirochroman-4-5Ј-imidazolidine-2Ј,4Јdione), or a combination of both inhibitors