乳房領域における高速造影検査法(KWIC)を用いたMRI血流動態パラメータ:Maximum slopeの診断能評価

京都大学0048新制・課程博士博士(医学)甲第22741号医博第4659号新制||医||1046(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 辻川 明孝, 教授 伊達 洋至, 教授 羽賀 博典学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

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

Synthesis and Evaluation of 1,3a,6a-triazapentalene (TAP)-bonded system

A method of synthesizing a directly connected 1,3a,6a-triazapentalene (TAP) ring system as a linearly bonded aromatic system with a planar form was established. Various TAP-dimers and a 2-alkyl-TAP-trimer were synthesized and their fluorescence properties were evaluated. Although the direct connection of the TAP ring with other TAP rings did not affect the fluorescence properties in diluted solvent, TAP-dimers showed unique fluorescence properties derived from the aggregation state under highly concentrated conditions. In particular, TAP-dimer 5f showed aggregation-induced emission in highly concentrated solution, and 5b showed typical mechanochromic fluorescence in the solid state despite their compact molecular size

Support for UNRWA's survival

The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) provides life-saving humanitarian aid for 5·4 million Palestine refugees now entering their eighth decade of statelessness and conflict. About a third of Palestine refugees still live in 58 recognised camps. UNRWA operates 702 schools and 144 health centres, some of which are affected by the ongoing humanitarian disasters in Syria and the Gaza Strip. It has dramatically reduced the prevalence of infectious diseases, mortality, and illiteracy. Its social services include rebuilding infrastructure and homes that have been destroyed by conflict and providing cash assistance and micro-finance loans for Palestinians whose rights are curtailed and who are denied the right of return to their homeland

Malfunctioning CD106-positive, short-term hematopoietic stem cells trigger diabetic neuropathy in mice by cell fusion.

Diabetic neuropathy is an incurable disease. We previously identified a mechanism by which aberrant bone marrow-derived cells (BMDCs) pathologically expressing proinsulin/TNF-α fuse with residential neurons to impair neuronal function. Here, we show that CD106-positive cells represent a significant fraction of short-term hematopoietic stem cells (ST-HSCs) that contribute to the development of diabetic neuropathy in mice. The important role for these cells is supported by the fact that transplantation of either whole HSCs or CD106-positive ST-HSCs from diabetic mice to non-diabetic mice produces diabetic neuronal dysfunction in the recipient mice via cell fusion. Furthermore, we show that transient episodic hyperglycemia produced by glucose injections leads to abnormal fusion of pathological ST-HSCs with residential neurons, reproducing neuropathy in nondiabetic mice. In conclusion, we have identified hyperglycemia-induced aberrant CD106-positive ST-HSCs underlie the development of diabetic neuropathy. Aberrant CD106-positive ST-HSCs constitute a novel therapeutic target for the treatment of diabetic neuropathy

Subcategory classifications of Breast Imaging and Data System (BI-RADS) category 4 lesions on MRI

[Purpose]Category 4 in BI-RADS for magnetic resonance imaging (MRI) has a wide range of probabilities of malignancy, extending from > 2 to  0%,  ≤ 2%), 4 (> 2%,   2%,  ≤ 10%), 4B (> 10%,  ≤ 50%) and 4C (> 50%,  < 95%) at the time of diagnosis. Radiological and pathological reports were retrospectively analyzed, and the PPVs were calculated. [Results] We included 149 malignant and 285 benign lesions. The PPVs of subcategories 4A, 4B and 4C were 1.8%, 11.8% and 67.5%, respectively. The PPVs were higher for lesions coexisting with category 5 or 6 lesions compared with those for isolated lesions. [Conclusion] Category 4 lesions can be classified into three subcategories depending on the likelihood of malignancy. Lesions coexisting with category 5 or 6 lesions are more likely to be malignant

The role of breast tomosynthesis in a predominantly dense breast population at a tertiary breast centre : breast density assessment and diagnostic performance in comparison with MRI

Objectives: To compare breast density measured on digital breast tomosynthesis (DBT) (BI-RADS-based breast composition and fully-automatic estimation) and magnetic resonance imaging (MRI) (BI-RADS amount of fibroglandular tissue), and to evaluate the diagnostic performance in terms of sensitivity and specificity of DBT and MRI in a predominantly dense breast population. Methods: Between 2015 and 2016, 152 women with 103 breast malignancies, who underwent 3-T breast MRI and DBT within 2 months’ time, were enrolled in this study. Breast composition/fibroglandular tissue and findings on DBT (two readers) and MRI were reported using BI-RADS 5th edition. Digital mammography images were analysed for breast percent density (PD) using the Libra software tool. Results: A majority of women had dense breasts as categorised by breast composition c (heterogeneously dense) (68%) and d (extremely dense) (15%). The mean PD was 44% (range, 18-89%) and the correlation between breast composition and PD was r = 0.6. The diagnostic performance of MRI was significantly higher compared to DBT for one reader as described by the area under the receiver operating characteristic (ROC) curve (p = 0.004) and of borderline significance for the other reader (p = 0.052). Conclusions: MRI had higher diagnostic performance than DBT in a dense breast population in the tertiary setting. Key Points: • MRI had higher diagnostic performance than DBT in a dense breast population• Diagnostic performance of DBT was comparable to MRI in women with fatty breasts• MRI was superior to DBT in preoperative breast cancer size assessmen

Evaluation of Malignant Breast Lesions Using High-resolution Readout-segmented Diffusion-weighted Echo-planar Imaging: Comparison with Pathology

PURPOSE: We aimed to investigate the performance of high resolution-diffusion-weighted imaging (HR-DWI) using readout-segmented echo-planar imaging in visualizing malignant breast lesions and evaluating their extent, using pathology as a reference. METHODS: This retrospective study included patients who underwent HR-DWI with surgically confirmed malignant breast lesions. Two radiologists blinded to the final diagnosis evaluated HR-DWI independently and identified the lesions, measuring their maximum diameters. Another radiologist confirmed if those lesions were identical to the pathology. The maximum diameters of the lesions between HR-DWI and pathology were compared, and their correlations were calculated using Spearman's correlation coefficient. Apparent diffusion coefficient (ADC) values of the lesions were measured. RESULTS: Ninety-five mass/64 non-mass lesions were pathologically confirmed in 104 females. Both radiologists detected the same 93 mass lesions (97.9%). Spearman's correlation coefficient for mass lesions were 0.89 and 0.90 (P < 0.0001 and 0001) for the two radiologists, respectively. The size differences within 10 mm were 90.3% (84/93) and 94.6% (88/93) respectively. One radiologist detected 35 non-mass lesions (54.7%) and another radiologist detected 32 non-mass lesions (50.0%), of which 28 lesions were confirmed as identical. Spearman's correlation coefficient for non-mass lesions were 0.59 and 0.22 (P = 0.0002 and 0.22), respectively. The mean ADC value of mass lesions and non-mass lesions were 0.80 and 0.89 × 10-3 mm2/s, respectively. CONCLUSION: Using HR-DWI, malignant mass lesions were depicted with excellent agreement with the pathological evaluation. Approximately half of the non-mass lesions could not be identified, suggesting a current limitation of HR-DWI

Mannose- and Mannobiose-Specific Responses of the Insect-Associated Cellulolytic Bacterium Streptomyces sp. Strain SirexAA-E

The cellulolytic insect symbiont bacterium Streptomyces sp. strain SirexAA-E secretes a suite of carbohydrate-active enzymes (CAZymes), which are involved in the degradation of various polysaccharides in the plant cell wall, in response to the available carbon sources. Here, we examined a poorly understood response of this bacterium to mannan, one of the major plant cell wall components. SirexAA-E grew well on mannose, carboxymethyl cellulose (CMC), and locust bean gum (LBG) as sole carbon sources in the culture medium. The secreted proteins from each culture supematant were tested for their polysaccharide-degrading ability, and the composition of secreted CAZymes in each sample was determined by liquid chromatography-tandem mass spectrometry (LC-MS/ MS). The results indicated that mannose, LBG, and CMC induced the secretion of mannan and cellulose-degrading enzymes. Interestingly, two alpha-1,2-mannosidases were abundantly secreted during growth on mannose and LBG. Using genomic analysis, we found a unique 12-bp palindromic sequence motif at 4 locations in the SirexAA-E genome, two of which were found upstream of the above-mentioned alpha-1,2-mannosidase genes, along with a newly identified mannose and mannobiose-responsive transcriptional regulator, SsManR. Furthermore, the previously reported cellobiose-responsive repressor, SsCebR, was determined to also use mannobiose as an effector ligand. To test whether mannobiose induces the sets of genes under the control of the two regulators, SirexAA-E was grown on mannobiose, and the secretome composition was analyzed. As hypothesized, the composition of the mannobiose secretome combined sets of CAZymes found in both LBG and CMC secretomes, and thus they are likely under the regulation of both SsManR and SsCebR. IMPORTANCE Streptomyces sp. SirexAA-E, a microbial symbiont of biomass-harvesting insects, secretes a suite of polysaccharide-degrading enzymes dependent on the available carbon sources. However, the response of this bacterium to mannan has not been documented. In this study, we investigated the response of this bacterium to mannose, mannobiose, and galactomannan (LBG). By combining biochemical, proteomic, and genomic approaches, we discovered a novel mannose and mannobiose responsive transcriptional regulator, SsManR, which selectively regulates three alpha-1,2-mannosidasecoding genes. We also demonstrated that the previously described cellobiose responsive regulator, SsCebR, could use mannobiose as an effector ligand. Overall, our findings suggest that the Streptomyces sp. SirexAA-E responds to mannose and mannooligosaccharides through two different transcriptional repressors that regulate the secretion of the plant cell wall-degrading enzymes to extract carbon sources in the host environment