局所進行膵癌に対する放射線治療成績の向上を目的とした消化管位置の変動解析と即時適応放射線治療の有用性に関する研究

京都大学新制・課程博士博士(医学)甲第24884号医博第5018号京都大学大学院医学研究科医学専攻(主査)教授 鈴木 実, 教授 小濱 和貴, 教授 中島 貴子学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Potential utility of cone‐beam CT‐guided adaptive radiotherapy under end‐exhalation breath‐hold conditions for pancreatic cancer

[Purpose] The purpose of this study was to demonstrate the potential utility of cone-beam computed tomography (CBCT)-guided online adaptive radiotherapy (ART) under end-exhalation breath-hold (EE-BH) conditions for pancreatic cancer (PC). [Methods] Eleven PC patients who underwent 15-fraction volumetric-modulated arc therapy under EE-BH conditions were included. Planning CT images and daily 165 CBCT images were imported into a dedicated treatment planning system. The prescription dose was set to 48 Gy in 15 fractions. The reference plan was automatically generated along with predefined clinical goals. After segmentation was completed on CBCT images, two different plans were generated: One was an adapted (ADP) plan in which re-optimization was performed on the anatomy of the day, and the other was a scheduled (SCH) plan, which was the same as the reference plan. The dose distributions calculated using the synthetic CT created from both planning CT and CBCT were compared between the two plans. Independent calculation-based quality assurance was also performed for the ADP plans, with a gamma passing rate of 3%/3 mm. [Results] All clinical goals were successfully achieved during the reference plan generation. Of the 165 sessions, gross tumor volume D98% and clinical target volume D98% were higher in 100 (60.1%) and 122 (74.0%) ADP fractions. In each fraction, the V3 Gy < 1 cm³ of the stomach and duodenum was violated in 47 (28.5%) and 48 (29.1%), respectively, of the SCH fractions, whereas no violations were observed in the ADP fractions. There were statistically significant differences in the dose–volume indices between the SCH and ADP fractions (p < 0.05). The gamma passing rates were above 95% in all ADP fractions. [Conclusions] The CBCT-guided online ART under EE-BH conditions successfully reduced the dose to the stomach and duodenum while maintaining target coverage

病原性 Candida 酵母から調製した粗抽出物の 1H-NMR 分析によって得られる細胞壁ﾏﾝﾅﾝの構造情報について

病原性 Candida 酵母の乾燥菌体から精製されたﾏﾝﾅﾝのﾌﾟﾛﾄﾝ核磁気共鳴(1H-NMR)分析(測定温度45℃)において､ﾏﾝﾉｰｽ残基に基づくｱﾉﾒﾘｯｸﾌﾟﾛﾄﾝｼｸﾞﾅﾙ領域(4.5～6.0ppm)に観察されるｼｸﾞﾅﾙは極めて明瞭であった｡一方､同一酵母の粗抽出物の 1H-NMR 分析(測定温度70℃)におけるこの領域のｼｸﾞﾅﾙは､僅かに不明瞭な部分が観察されるものの､ほぼ精製ﾏﾝﾅﾝに匹敵するｼｸﾞﾅﾙﾊﾟﾀｰﾝを観察することができた｡従って､酵母細胞壁ﾏﾝﾅﾝの化学構造に関して､ﾏﾝﾅﾝを精製する前段階である粗抽出物の NMR 分析によって､精製ﾏﾝﾅﾝの NMR 分析とほぼ同等の情報が得られることが明らかになった｡In the measurement of 1H-NMR of purified mannan obtained from dried cells of pathogenic Candida yeast, the extremely clear signal is observed anomeric proton region(4.5～6.0ppm)based on mannose residues. On the other hand, in the 1H-NMR analysis of the crude extract obtained from the same yeast, part obscured slightly observed, but the signal pattern equivalent to purified mannan substantially was observed. Therefore, it was demonstrated that 1H-NMR analysis of the crude extract obtained in the previous step of purification of mannan give the rough information for the chemical structure of the yeast cell wall mannan

Development of alkoxy styrylchromone derivatives for imaging of cerebral amyloid-β plaques with SPECT

Abstract We report here the development of radioiodinated styrylchromone derivatives with alkoxy groups as single photon emission computed tomography (SPECT) imaging probes for cerebral amyloid-β (Aβ) plaques. Among the derivatives, the methoxy derivative 14 and the dimethoxy derivative 15 displayed relatively high affinity for the Aβ(1-42) aggregates with Ki values of 22 and 46 nM, respectively. Fluorescent imaging demonstrated that 14 and 15 clearly labeled thioflavin-S positive Aβ plaques in the brain sections of Tg2576 transgenic mice. In the in vivo studies, [125I]14 and [125I]15 showed high initial brain uptake expressed as the percentage of the injected dose per gram (2.25% and 2.49% ID/g at 2 min, respectively) with favorable clearance (0.12% and 0.20% ID/g at 180 min, respectively) from the brain tissue of normal mice. Furthermore, in vitro autoradiography confirmed that [125I]15 binds thioflavin-S positive regions in Tg2576 mouse brain sections. The derivative 15 may be a potential scaffold for the development of in vivo imaging probes targeting Aβ plaques in the brain. In particular, further structural modifications are required to improve the compounds binding affinity for Aβ

Functional tooth restoration by next-generation bio-hybrid implant as a bio-hybrid artificial organ replacement therapy

Bio-hybrid artificial organs are an attractive concept to restore organ function through precise biological cooperation with surrounding tissues in vivo. However, in bio-hybrid artificial organs, an artificial organ with fibrous connective tissues, including muscles, tendons and ligaments, has not been developed. Here, we have enveloped with embryonic dental follicle tissue around a HA-coated dental implant, and transplanted into the lower first molar region of a murine tooth-loss model. We successfully developed a novel fibrous connected tooth implant using a HA-coated dental implant and dental follicle stem cells as a bio-hybrid organ. This bio-hybrid implant restored physiological functions, including bone remodelling, regeneration of severe bone-defect and responsiveness to noxious stimuli, through regeneration with periodontal tissues, such as periodontal ligament and cementum. Thus, this study represents the potential for a next-generation bio-hybrid implant for tooth loss as a future bio-hybrid artificial organ replacement therapy

Unique structure of ozoralizumab, a trivalent anti-TNFα NANOBODY® compound, offers the potential advantage of mitigating the risk of immune complex-induced inflammation

Biologics have become an important component of treatment strategies for a variety of diseases, but the immunogenicity of large immune complexes (ICs) and aggregates of biologics may increase risk of adverse events is a concern for biologics and it remains unclear whether large ICs consisting of intrinsic antigen and therapeutic antibodies are actually involved in acute local inflammation such as injection site reaction (ISR). Ozoralizumab is a trivalent, bispecific NANOBODY® compound that differs structurally from IgGs. Treatment with ozoralizumab has been shown to provide beneficial effects in the treatment of rheumatoid arthritis (RA) comparable to those obtained with other TNFα inhibitors. Very few ISRs (2%) have been reported after ozoralizumab administration, and the drug has been shown to have acceptable safety and tolerability. In this study, in order to elucidate the mechanism underlying the reduced incidence of ISRs associated with ozoralizumab administration, we investigated the stoichiometry of two TNFα inhibitors (ozoralizumab and adalimumab, an anti-TNFα IgG) ICs and the induction by these drugs of Fcγ receptor (FcγR)-mediated immune responses on neutrophils. Ozoralizumab-TNFα ICs are smaller than adalimumab-TNFα ICs and lack an Fc portion, thus mitigating FcγR-mediated immune responses on neutrophils. We also developed a model of anti-TNFα antibody-TNFα IC-induced subcutaneous inflammation and found that ozoralizumab-TNFα ICs do not induce any significant inflammation at injection sites. The results of our studies suggest that ozoralizumab is a promising candidate for the treatment of RA that entails a lower risk of the IC-mediated immune cell activation that leads to unwanted immune responses

Risk factors predicting subtypes of physical frailty incidence stratified by musculoskeletal diseases in community-dwelling older adults: The SONIC study

Ohata Y., Godai K., Kabayama M., et al. Risk factors predicting subtypes of physical frailty incidence stratified by musculoskeletal diseases in community-dwelling older adults: The SONIC study. Geriatrics and Gerontology International, (2024); https://doi.org/10.1111/ggi.14924.Aim: This study aims to identify the key risk factors that lead to subtypes of physical frailty assessed by walking speed and grip strength among community-dwelling Japanese individuals, stratified by the presence of musculoskeletal diseases (MSDs) and age group. Methods: We included 302 participants aged 70 or 80 years who did not exhibit subtypes of physical frailty at baseline through the Septuagenarians, Octogenarians, Nonagenarians, Investigation with Centenarians (SONIC) study. Our study was a longitudinal study. The outcome was the incidence of subtypes of physical frailty after 3 years. Subtypes of physical frailty were defined as a weak grip strength or slow walking speed, or both, based on the Japanese version of the Cardiovascular Health Study Index. The risk factors for subtypes of physical frailty incidence were examined by age group and MSD, using multivariate logistic regressions. Results: Of the 302 participants, 110 (36.4%) had MSD. Those with MSD were significantly more likely to have subtypes of physical frailty after 3 years compared with those without MSD. Among all participants, older age was a risk factor of subtypes of physical frailty (P < 0.05). Without MSD, older age and dissatisfied financial status were risk factors (P < 0.05). With MSD, older age was a risk factor (P < 0.05). By age group, in individuals aged 70 years old, a dissatisfied financial status was a risk factor for those without MSD (P < 0.05), and a higher BMI was one for those with MSD (P < 0.05). Conclusions: Older age was a risk factor for subtypes of physical frailty, but other risk factors differed according to the presence of MSD and age

Current status of a helicopter transportation system on remote islands for patients undergoing mechanical thrombectomy

Background: Mechanical thrombectomy (MT) is standard treatment for acute ischemic stroke (AIS) with large-vessel occlusion within 6 h of symptom onset to treatment initiation (OTP). Recent trials have extended the therapeutic time window for MT to within 24 h. However, MT treatment remains low in remote areas. Nagasaki Prefecture, Japan has many inhabited islands with no neurointerventionalists. Our hospital on the mainland is a regional hub for eight island hospitals. We evaluated clinical outcomes of MT for patients with AIS on these islands versus on the mainland. Methods: During 2014–2019, we reviewed consecutive patients with AIS who received MT at our hospital. Patients comprised the Islands group and Mainland group. Patient characteristics and clinical outcomes were compared between groups. Results: We included 91 patients (Islands group: 15 patients, Mainland group: 76 patients). Seven patients (46.7%) in the Islands group versus 43 (56.6%) in the Mainland group achieved favorable outcomes. Successful recanalization was obtained in 11 patients (73.3%) on the islands and 67 (88.2%) on the mainland. The median OTP time in the Islands was 365 min. In both the Islands and Mainland groups, the OTP time and successful recanalization were associated with functional outcome. The modified Rankin Scale (mRS) score at 90 days ≤2 was obtained in two patients and mRS = 3 in four patients among eight patients with OTP time >6 h. Conclusions: Few patients with AIS on remote islands have received MT. Although patients who underwent MT on the islands had longer OTP, the clinical outcomes were acceptable. OTP time on remote islands must be shortened, as this is related to functional outcome. In some cases with successful recanalization, a favorable outcome can still be obtained even after 6 h. Even if OTP exceeds 6 h, it is desirable to appropriately select patients and actively perform MT

異なる炊飯器を用いた米飯レジスタントスターチ含量の定量

米飯中のRSがヒトの栄養に及ぼす影響について検討する第一歩として,5種類の炊飯器を用いて米飯中のRS量の比較を行った。米飯のRSはパンのそれよりも高い値を示した。米飯中のRS量は炊飯器の加熱,加圧特性によって影響を受け,変化することが明らかとなった。IH式炊飯器のように高温を維持できるもの,釜肌からの加熱だけではなく,炊き上がった米飯表面にも高温スチームによる加温ができるもの,さらに加圧の場合には1.6気圧よりも1.2気圧のものでRS量が小さかった。これらの条件はまた,24時間冷蔵保存した場合にもRS量の変化が小さかった。以上のことから,炊飯器の加熱,加圧特性の違いによって,米飯中のRS量に差が生じることが明らかとなった。In order to elucidate the influence of resistant starch (RS) intake on our intestine, the RS contents in boiled rice prepared from five types of rice cookers were measured. Consequently, it was shown that 1) The RS content of boiled rice was higher than that of white bread. 2) The heating method and/or pressure treatment of the rice cooker were effective to the RS content of boiled rice. 3) The amount of the RS in boiled rice has decreased by induction heating system and the pressure processing of 1.2 atm. 4) These conditions also controlled the changes of the RS content in boiled rice during storage at 4℃. These results suggested that the RS content of boiled rice was influenced by the heating method and the pressurizing method of the rice cooker