浸潤性乳癌の術前薬物療法後のMRIによる治療効果判定：拡散強調画像とダイナミック造影の比較検討

京都大学新制・課程博士博士(医学)甲第24969号医博第5023号新制||医||1069(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 溝脇 尚志, 教授 小濱 和貴, 教授 鈴木 実学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Nitrosomonas europaea MazF Specifically Recognises the UGG Motif and Promotes Selective RNA Degradation

Toxin-antitoxin (TA) systems are implicated in prokaryotic stress adaptation. Previously, bioinformatics analysis predicted that such systems are abundant in some slowly growing chemolithotrophs; e.g., Nitrosomonas europaea. Nevertheless, the molecular functions of these stress-response modules remain largely unclear, limiting insight regarding their physiological roles. Herein, we show that one of the putative MazF family members, encoded at the ALW85_RS04820 locus, constitutes a functional toxin that engenders a TA pair with its cognate MazE antitoxin. The coordinate application of a specialised RNA-Seq and a fluorescence quenching technique clarified that a unique triplet, UGG, serves as the determinant for MazF cleavage. Notably, statistical analysis predicted that two transcripts, which are unique in the autotroph, comprise the prime targets of the MazF endoribonuclease: hydroxylamine dehydrogenase (hao), which is essential for ammonia oxidation, and a large subunit of ribulose 1,5-bisphosphate carboxylase/oxygenase (rbcL), which plays an important role in carbon assimilation. Given that N. europaea obtains energy and reductants via ammonia oxidation and the carbon for its growth from carbon dioxide, the chemolithotroph might use the MazF endoribonuclease to modulate its translation profile and subsequent biochemical reactions

Biomarkers Predictive of Distant Disease-free Survival Derived from Diffusion-weighted Imaging of Breast Cancer

Purpose: To investigate whether intravoxel incoherent motion (IVIM) and/or non-Gaussian diffusion parameters are associated with distant disease-free survival (DDFS) in patients with invasive breast cancer. Methods: From May 2013 to March 2015, 101 patients (mean age 60.0, range 28-88) with invasive breast cancer were evaluated prospectively. IVIM parameters (flowing blood volume fraction [ɪᴠɪᴍ] and pseudodiffusion coefficient [D*]) and non-Gaussian diffusion parameters (theoretical apparent diffusion coefficient [ADC] at a b value of 0 s/mm² [ADC₀] and kurtosis [K]) were estimated using a diffusion-weighted imaging series of 16 b values up to 2500 s/mm². Shifted ADC values (sADC₂₀₀-₁₅₀₀) and standard ADC values (ADC₀-₈₀₀) were also calculated. The Kaplan-Meier method was used to generate survival analyses for DDFS, which were compared using the log-rank test. Univariable Cox proportional hazards models were used to assess any associations between each parameter and distant metastasis-free survival. Results: The median observation period was 80 months (range, 35-92 months). Among the 101 patients, 12 (11.9%) developed distant metastasis, with a median time to metastasis of 79 months (range, 10-92 months). Kaplan-Meier analysis showed that DDFS was significantly shorter in patients with K > 0.98 than in those with K ≤ 0.98 ( = 0.04). Cox regression analysis showed a marginal statistical association between K and distant metastasis-free survival ( = 0.05). Conclusion: Non-Gaussian diffusion may be associated with prognosis in invasive breast cancer. A higher K may be a marker to help identify patients at an elevated risk of distant metastasis, which could guide subsequent treatment

シンフゼン オ ガッペイ シタ ジンケッカンセイ コウケツアツ ニ タイスル ケイヒテキ ジンドウミャク ケイセイジュツ ノ ユウコウセイ

【Background】 Percutaneous transluminal renal angioplasty （PTRA） is recommended for patients with heart failure due to renovascular hypertension ; however, the clinical characteristics of the patients and the effects of PTRA on heart failure and cardiorenal function have not been elucidated. 【Methods】 We retrospectively analyzed data for 4 PTRA-treated patients （male/female, 1/3 ; mean age, 70.0±10 years ; mean left ventricular ejection fraction, 51.5±15.2％） with heart failure due to renovascular hypertension and evaluated the effects of PTRA on heart failure and cardiorenal function 6 months after treatment. 【Results】 All patients had pro-arteriosclerotic diseases including diabetes mellitus, essential thrombocythemia, heparin cofactor II deficency, metabolic syndrome, and familial hypercholesterolemia, and 3 patients had ischemic heart disease. No abdominal bruit was heard and mean plasma renin activity was 4.5±3.6 ng/ml/hr, which was not elevated, contrary to expectation. All contralateral kidneys of PTRA were nonfunctioning, suggesting bilateral kidneys were disturbed in all patients. In all patients, PTRA was successfully performed and resolved heart failure. PTRA resulted in decreases in systolic blood pressure from 157±18 to 124±8.6 mmHg, mean serum creatinine from 3.2±2.6 to 2.7±2.2 mg/dl, and mean BNP from 919±998 to 243±291 pg/ml at 6 months after treatment. PTRA did not change left ventricular ejection fraction, a parameter of systolic fraction evaluated by an echocardiogram ; however, PTRA improved E/e’, a parameter of left ventricular diastolic fraction, from 16.1±5.2 to 9.7±3.7. None of the patients were hospitalized due to heart failure during the 6-month period after PTRA. 【Conclusions】 Patients with heart failure with cardiovascular risk factors should be screened for renovascular hypertension regardless of abdominal bruit or plasma renin activity. PTRA is effective for resolving heart failure and for improving renal and cardiac diastolic functions in patients with renovascular hypertension complicated with heart failure

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