Meiwa Idoshi Gohyogi Kakinuki (1): Transcription and Analysis of Historical Sources about Kyoto Machi Bugyosho in Meiwa Period

JSPS科研費26870726, 25285006,26284095平成28年度関西大学若手研究者育成経費（個人研究）研究課題「江戸幕府の京都における法令・裁判に関する実証的研究

江戸時代後半の上方における幕府代官と幕領

平成28年度関西大学若手研究者育成経

Infrared and Raman spectroscopic investigation of the reaction mechanism of cytochrome c oxidase

AbstractRecent progress in studies on the proton-pumping and O2 reduction mechanisms of cytochrome c oxidase (CcO) elucidated by infrared (IR) and resonance Raman (rR) spectroscopy, is reviewed. CcO is the terminal enzyme of the respiratory chain and its O2 reduction reaction is coupled with H+ pumping activity across the inner mitochondrial membrane. The former is catalyzed by heme a3 and its mechanism has been determined using a rR technique, while the latter used the protein moiety and has been investigated with an IR technique. The number of H+ relative to e− transferred in the reaction is 1:1, and their coupling is presumably performed by heme a and nearby residues. To perform this function, different parts of the protein need to cooperate with each other spontaneously and sequentially. It is the purpose of this article to describe the structural details on the coupling on the basis of the vibrational spectra of certain specified residues and chromophores involved in the reaction. Recent developments in time-resolved IR and Raman technology concomitant with protein manipulation methods have yielded profound insights into such structural changes. In particular, the new IR techniques that yielded the breakthrough are reviewed and assessed in detail. This article is part of a Special Issue entitled: Vibrational spectroscopies and bioenergetic systems

骨転移を有しない前立腺がん患者へのアンドロゲン除去療法による骨粗鬆症に対する経口ビスフォスフォネート製剤の予防効果について

We studied the short-term efficacy of alendronate, an oral bisphosphonates, on bone mineral density (BMD) during androgen deprivation therapy (ADT) in 45 nonmetastatic prostate cancer patients at the beginning of ADT (treatment group). All received alendronate five mg daily from the initiation of ADT. Lumber BMD was evaluated by dual energy X-ray absorptiometry, at baseline and after six months of treatment. Historical data on 24 patients with prostate cancer who received ADT without bisphosphonate administration were studied as controls (control group). BMD decreased in 13.9 and 45.8% of the patients in the treatment and control groups, respectively. Mean BMD changes in the lumber spine were +1.6 +/- 3.0% in the treatment group and -1.1 +/- 2.7% in the control group (p = 0.006). No pathological fractures occurred during the study period. No severe adverse effects were observed, but three patients could not continue alendronate treatment because of adverse events. Despite the short-term of this evaluation, our results showed that oral alendronate is an effective and safe treatment for preventing bone loss and increasing BMD in patients receiving ADT for prostate cancer.目的:アンドロゲン除去療法は骨塩減少とそれに伴う病的骨折の潜在的な危険因子である。点滴ビスフォスフォネート製剤はアンドロゲン除去療法を受けている前立腺がん患者に対する骨塩量の減少を予防することが示されているが経口ビスフォスフォネート製剤については評価されていない。今回, われわれは経口ビスフォスフォネート製剤の1つであるアレンドン酸を骨転移を有しない前立腺がん患者に投与して骨塩量を測定し短期間での効果を検討した。対象と方法:治療群として45人の骨転移を有しない前立腺がん患者について検討した。アレンドロン酸を1日5mg経口投与し治療前, 治療半年後に腰椎の骨塩量を測定し比較検討した。対照群として24人の骨転移を有しない前立腺がん患者についても同様に検討を行った。結果:骨塩量の減少は治療群で13.9%, 対照群で45.8%に見られた。腰椎における骨塩量の変化は治療群で平均1.6%, 対照群で-1.1%であった(p=0.006)。治療期間内において病的骨折は認められず, 有害事象として重篤なものは認めなかったが副作用のため3例が内服継続困難であった。結語:短期間の検討であるにもかかわらず経口ビスフォスフォネート製剤であるアレンドロン酸は前立腺がん患者に対するアンドロゲン除去療法による骨塩量減少を予防するのに有効で安全な治療法であることが示唆された。(著者抄録

Interfractional target changes in brain metastases during 13-fraction stereotactic radiotherapy

[Background] The risk for radiation necrosis is lower in fractionated stereotactic radiotherapy (SRT) than in conventional radiotherapy, and 13-fraction SRT is our method of choice for the treatment of brain metastases ≥ around 2 cm or patients who are expected to have a good prognosis. As 13-fraction SRT lasts for at least 17 days, adaptive radiotherapy based on contrast-enhanced mid-treatment magnetic resonance imaging (MRI) is often necessary for patients undergoing 13-fraction SRT. In this study, we retrospectively analyzed interfractional target changes in patients with brain metastases treated with 13-fraction SRT. [Methods] Our analyses included data from 23 patients and 27 metastatic brain lesions treated with 13-fraction SRT with dynamic conformal arc therapy. The peripheral dose prescribed to the planning target volume (PTV) was 39–44.2 Gy in 13-fractions. The gross tumor volume (GTV) of the initial SRT plan (initial GTV), initial PTV, and modified GTV based on the mid-treatment MRI scan (mid-treatment GTV) were assessed. [Results] The median initial GTV was 3.8 cm3 and the median time from SRT initiation to the mid-treatment MRI scan was 6 days. Compared to the initial GTV, the mid-treatment GTV increased by more than 20% in five lesions and decreased by more than 20% in five lesions. Interfractional GTV volume changes of more than 20% were not significantly associated with primary disease or the presence of cystic components/necrosis. The mid-treatment GTV did not overlap perfectly with the initial PTV in more than half of the lesions. [Conclusions] Compared to the initial GTV, the mid-treatment GTV changed by more than 20% in almost one-third of lesions treated with 13-fraction SRT. As SRT usually generates a steep dose gradient as well as increasing the maximum dose of PTV compared to conventional radiotherapy, assessment of the volume and locational target changes and adaptive radiotherapy should be considered as the number of fractions increases

Kamigata Hachikakoku Tegiri Torihakarai Tome (1) : Transcription and Analysis of Historical Sources about Kamigata Daikan and Otsu Daikan in the Latter Half of the Edo Period

本研究は、JSPS科研費 JP19K01256、JP17H02448、JP20K00968 の助成を受けたものです

[Historical Materials] Gokokuin Narabini Gechijo Oboegaki No Tome : Transcription of Historical Sources about Ongoku Yakunin of the Shogunate in Kyoho Period

本研究は、二〇一九年度関西大学研究拠点形成支援経費において、研究課題「法の支配と法多元主義」として研究費を受け、その成果を公表するものです。また、本研究は、二〇二〇年度関西大学学術研究員として研究費を受け、その成果を公表するものです。さらに、本研究は、ＪＳＰＳ科研費ＪＰ一九Ｋ〇一二五六、ＪＰ二一Ｈ〇〇六五九、ＪＰ二〇Ｋ〇〇九六八の助成を受けたものです

Safety and efficacy of pirfenidone in idiopathic pulmonary fibrosis in clinical practice

SummaryBackgroudPrevious pirfenidone trials have only involved patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF). The aim of this study was to investigate the safety and efficacy of pirfenidone in patients with mild-to-severe IPF in clinical practice.MethodsThe clinical records of 76 patients who were diagnosed with IPF and received pirfenidone were reviewed.ResultsThe most frequent adverse event was anorexia, although the grade of anorexia in most patients was mild. Dose reduction of pirfenidone improved anorexia in 84% affected patients, which resulted in a high medication compliance rate. The mean forced vital capacity (FVC) at the initiation of pirfenidone therapy in this study was approximately 10% lower than that in previous clinical trials. The mean change in FVC during the 6-month period prior to the therapy initiation was −188 mL, which improved to −19 mL during the 6-month period after therapy. Significant attenuation in percentage predicted diffusion capacity of the lung for carbon monoxide decline was also achieved after pirfenidone therapy initiation. The efficacy of pirfenidone in attenuating the degree of FVC decline was higher in the group with FVC decline of ≥150 mL during the 6-month period prior to therapy initiation. The levels of serum markers, such as KL-6 and SP-D, were also lowered by the therapy.ConclusionsThese results showed that pirfenidone was well-tolerated and had beneficial effects in patients with mild-to-severe and/or progressive IPF. The degree of disease progression prior to the initiation of pirfenidone therapy had an impact on the response to the therapy

Observation of the FeO2 and FeIVO stretching Raman bands for dioxygen reduction intermediates of cytochrome bo isolated from Escherichia coli

AbstractReaction intermediates in dioxygen reduction by the E. coli cytochrome bo-type ubiquinol oxidase were studied by time-resolved resonance Raman spectroscopy using the artificial cardiovascular system. At 0–20 μs following photolysis of the enzyme—CO adduct in the presence of O2, we observed the FeO2 stretching Raman band at 568 cm−1 which shifted to 535 cm−1 with the 18O2 derivative. These frequencies are remarkably close to those of other oxyhemoproteins including dioxygen-bound hemoglobin and aa3-type cytochrome c oxidase. In the later time range (20–40 μs), other oxygen-isotope-sensitive Raman bands were observed at 788 and 361 cm−1. Since the 781 cm−1 band exhibited a downshift by 37 cm−1 upon 18O2 substitution, we assigned it to the FeIVO stretching mode. This band is considered to arise from the ferryl intermediate, but its appearance was much earlier than the corresponding intermediate of bovine cytochrome c oxidase (> 100 μs). The 361 cm−1 band showed the 16O/18O isotopic frequency shift of 14 cm−1 similar to the case of bovine cytochrome c oxidase reaction

Reconstitution of Mouse Spermatogonial Stem Cell Niches in Culture

SummarySpermatogonial stem cells (SSCs) reside in specific niches within seminiferous tubules. These niches are thought to secrete chemotactic factors for SSCs, because SSCs migrate to them upon transplantation. However, the identity of these chemotactic molecules remains unknown. Here, we established a testis feeder cell culture system and used it to identify SSC chemotactic factors. When seeded on testis cells from infertile mice, SSCs migrated beneath the Sertoli cells and formed colonies with a cobblestone appearance that were very similar to those produced by hematopoietic stem cells. Cultured cells maintained SSC activity and fertility for at least 5 months. Cobblestone colony formation depended on GDNF and CXCL12, and dominant-negative GDNF receptor transfection or CXCL12 receptor deficiency reduced SSC colonization. Moreover, GDNF upregulated CXCL12 receptor expression, and CXCL12 transfection in Sertoli cells increased homing efficiency. Overall, our findings identify GDNF and CXCL12 as SSC chemotactic factors in vitro and in vivo