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Aliphatic ketones, such as 2-butanone and 3-hexanone, with only one carbon difference among side chains adjacent to the carbonyl carbon are difficult to be reduced enantioselectively. In this study, we utilized an acetophenone reductase from Geotrichum candidum NBRC 4597 (GcAPRD) to reduce challenging aliphatic ketones such as 2-butanone (methyl ethyl ketone) and 3-hexanone (ethyl propyl ketone) to their corresponding (S)-alcohols with 94% ee and > 99% ee, respectively. Through crystallographic structure determination, it was suggested that residue Trp288 limit the size of the small binding pocket. Docking simulations imply that Trp288 plays an important role to form a C-H⋯π interaction for proper orientation of ketones in the pro-S binding pose in order to produce (S)-alcohols. The excellent (S)-enantioselectivity is due to a non-productive pro-R binding pose, consistent with the observation that the (R)-alcohol acts as an inhibitor of (S)-alcohol oxidation.

Chylothorax has been reported to be caused by accidental injuries in half of all cases in Japan, and10% of these cases have been associated with malignant tumors, including lymphoma. Chylothorax is a rare complication of gastric carcinoma. We successfully treated a 58-year-old man with gastric carcinoma, chylothorax, and ascites using a combination of talc pleurodesis and a lipid-limited diet. Case: A 58-year-old man with advanced stage of poorly differentiated gastric adenocarcinoma presented to our hospital with complaints of shortness of breath. Whole-body computerized tomographic images suggested massive pleural effusion and ascites. Examination of pleural fluid and ascites revealed elevated serum triacylglycerol levels of up to 913mg/dL with numerous free-floating cancer cells. Malignant chylothorax was diagnosed. A lipid-limited diet and octreotide were started, followed by talc pleurodesis for pleural effusion. The patient with controlled pleurisy died of gastric cancer on day 55 after pleurodesis.

Pemetrexed is an antifolate agent that is regarded as an alternative second-line chemotherapy against advanced or metastatic urothelial carcinoma (UC). However, there is limited information on pemetrexed in a third-line setting. We report a case of metastatic UC treated with pemetrexed as third-line chemotherapy following gemcitabine and cisplatin (GC) and gemcitabine and docetaxel (GD) therapies. A 73-year-old man with a history of transurethral resection of bladder carcinoma presented with pollakiuria. CT revealed a mass in the left renal pelvis that had invaded into the parenchyma of the left kidney, as well as para-aortic and mediastinum lymph node enlargement. Urinary cytology of the lesion in the left renal pelvis revealed UC. Thus, the patient was diagnosed with left renal pelvic carcinoma (cT3N2M0). After having received 4 courses of GC therapy, another mediastinum lymph node was enlarged. He subsequently received 3 courses of GD therapy as second-line chemotherapy, which showed little efficacy against the metastatic lesions. The patient was administered 3 courses of pemetrexed as third-line chemotherapy; however, its effect on tumor reduction was not sufficient. Finally, metastasis to the liver was observed, and he died 21 months after initiation of chemotherapy. For pathological confirmation, needle biopsy of a metastatic lymph node performed after death revealed high-grade UC and a high positivity of programmed death ligand 1 (PD-L1) in the tumor, which suggested that he could have benefited from anti-PD-L1 antibody immunotherapy. This report describes the outcome of pemetrexed treatment and proposes another possible candidate as third-line chemotherapy against metastatic UC.

Apomorphine is a non-selective dopamine D1/D2 receptor agonist, which has been used for patients with Parkinson's disease and reported to induce QT interval prolongation and cardiac arrest. To clarify their causal link, we assessed the cardiovascular and pharmacokinetic profile of apomorphine with the halothane-anaesthetized canine model (n = 4), whereas pro-arrhythmic potential of apomorphine was analysed with the chronic atrioventricular block canine model (n = 4). In the halothane-anaesthetized model, 0.01 mg/kg, i.v. of apomorphine hydrochloride over 10 min., providing about 10 times of its therapeutic concentration, increased the heart rate and ventricular contraction; 0.1 mg/kg over 10 min., providing about 100 times of the therapeutic, prolonged the ventricular effective refractory period; and 1 mg/kg over 10 min., providing about 1000 times of the therapeutic, decreased the ventricular contraction, mean blood pressure and cardiac output together with the intraventricular conduction delay and prolongation of the effective refractory period, whereas the left ventricular end-diastolic pressure, atrioventricular nodal conduction or ventricular repolarization were hardly affected. Meanwhile, in the atrioventricular block model, 1 mg/kg, i.v. of apomorphine hydrochloride over 10 min. neither prolonged the QT interval nor induced torsade de pointes. These results suggest that apomorphine may possess a wide margin of cardiovascular safety contrary to our expectations.

Background: Cancer-related neuropathic pain is resistant to treatment with multiple medications and results in reduced patient quality of life. Objective: The aim was to find a new curative to treat neuropathic pain without using adjuvant analgesics. Design: This was a retrospective study that used the FACES Pain Scale (FPS) to measure pain intensity and pain relief. Setting/Subjects: Twenty-eight inpatients who were treated with other strong opioids and who consulted the palliative care team about their pain relief. Results: In 22 (78.6%) out of 28 patients who successfully switched to methadone from other strong opioids, such as oxycodone and fentanyl, within two weeks, the mean FPS score was significantly reduced from 4.43 to 1.86, and methadone switching either reduced the number of prescriptions or stopped them entirely in 12 out of 17 (70.5%) patients who had used adjuvant analgesics before switching to methadone. Conclusions: These results suggest that opioid switching to oral methadone no...

Background Patients with a primary pure seminoma in the testis who have elevated serum alpha-fetoprotein are rare and should be treated as patients with nonseminomatous germ cell tumors. However, nonpalpable testicular tumors in this condition have never been reported. We describe a case of nonpalpable pure testicular seminoma with elevated serum alpha-fetoprotein presenting retroperitoneal metastasis. Case presentation A 29-year-old Asian man was referred to our hospital with right flank pain. Computed tomography showed a mass located between his aorta and inferior vena cava, but a testicular tumor was not detected. His serum levels of lactate dehydrogenase, alpha-fetoprotein, and DUPAN-2 were high. Although no tumor or nodule was palpable in his testis, ultrasonography revealed multiple low echoic lesions in his right testicular parenchyma. He was diagnosed with right testicular cancer with retroperitoneal lymph node metastasis and underwent right high orchiectomy. A pathological examination revealed pure seminoma and no nonseminomatous components were found in the specimen. Three courses of induction systemic chemotherapy (cisplatin, etoposide, and bleomycin) normalized his serum alpha-fetoprotein and DUPAN-2 levels. Three additional courses of chemotherapy (etoposide and bleomycin) were performed, and treatment was completed with laparoscopic retroperitoneal lymph node dissection. Pathology of the dissected specimen showed fibrous and necrotic tissue with no viable cells. He is alive without recurrence 54 months after orchiectomy. Conclusions We report a case of pure testicular seminoma with elevated serum alpha-fetoprotein and DUPAN-2 presenting retroperitoneal metastasis. We recommend an ultrasound examination of bilateral testes when large retroperitoneal tumors are detected in young men, even if a mass is not palpable in the scrotum.

INTRODUCTION AND OBJECTIVES: There is no standard second line treatment for patients with metastatic urothelial carcinoma (mUC) after the failure of platinum based first line chemotherapy. In previous study, we reported the efficacy of gemcitabine docetaxel (GD) combination as a second line treatment strategy for patients with mUC after failure of the first line treatment with platinum based chemotherapy. However, the efficacy of GD was not sufficient to be established as a standard second line treatment. The treatment options are limited for patients who demonstrate good performance status following GC or GD therapy. This study was conducted to evaluate the effectiveness of a combination of gemcitabine and paclitaxel (GP) therapy for patients with mUC that was previously treated with two lines of chemotherapy. METHODS: Between January 2006 and May 2015, 91 patients were treated with GD as second line chemotherapy. All had received first line chemotherapy consisting of cisplatin. After the failure of the second line GD therapy, 13 patients received GP therapy as a third line treatment. This consisted of gemcitabine (1000 mg/m2) on days 1, 8, and 15 and paclitaxel (200 mg/m2) on day 1 of each 21 day cycle. All patients were evaluated for toxicity and tumor responses. In addition, quality of life (QOL) was estimated by using the Short Form Health Survey (SF36) questionnaire. We analyzed the efficacy of GP as third line chemotherapy in followup study. RESULTS: The median number of GP treatment cycles was 4 (range 2 to 8). The objective response rate was 23.1%. The overall survival in third GP group after the end of second line GD therapy was longer than in untreated group. Univariate and multivariate analyses showed that good performance status was the only prognostic factor for tumor response. Grade 3 treatment related toxicity included neutropenia (77%) and thrombocytopenia (62%), and none of the patients showed grade 4 toxicity. The QOL score after 2 cycles of GP therapy was not significantly decreased compared to the pretreatment scores. CONCLUSIONS: GP combination chemotherapy as a third line regimen is a favorable option for patients with metastatic UC. Given the safety and benefit profile including QOL observed in this study, further prospective trials are warranted to evaluate this strategic chemotherapy approach for patients with mUC.

帯鋼補強土壁工法において，補強材との摩擦抵抗が小さく，盛土材として不適とされる粘性土やシルトを固化処理して利用することが望まれている．しかし，固化処理に特有の粘着力の増加効果を反映した設計方法はまだ確立されていない．本論文では，その設計のための基礎的データを得ることを目的にして，土槽からの補強材の引抜き試験装置を作製し，土試料・上載圧・固化材添加量・養生時間・補強材長・補強材種類などの諸条件を変えた実験を行った．そして補強材の引抜き抵抗に及ぼす固化処理の効果を上記要因別に調べた．また，固化処理土の一軸圧縮強さと固化処理土中の補強材の最大引抜き抵抗の関係を検討し，それを基にした所要補強材長の設計式の一例を示した．

Acetophenone reductase (APRD) fromGeotrichum candidiumNBRC 4597 was crystallized by the hanging-drop vapour-diffusion method using PEG 3350 as a precipitant. The crystal belonged to space groupP6522, with unit-cell parametersa=b= 104.5,c= 273.7 Å, and diffracted to 2.6 Å resolution. Phasing using the single-wavelength anomalous diffraction method was successful. Model building and crystallographic refinement are in progress.

In the retail business under the evolving market, the users solicit continuously to utilize the appropriate services based on their preferences and situations. Such requirements can not be satisfied with the conventional centralized system, due to the dynamic changes of user requirements. Autonomous Decentralized Community System (ADCS) has been proposed to realize a system that satisfies such requirements. The system realizes flexibility to cope with dynamic changes in the environment, but since ADCS is a pure decentralized system, the system has no existence that monitors the whole system to maintain timeliness, which is an essential factor for assurance. In this paper, Autonomous Construction Technology is proposed to improve the response time, which integrates and divides a community in order to achieve the optimal size depending on the changes in environment. The effectiveness is verified through simulation.

Given an edge-weighted digraph G with a designated vertex r, and a vertex capacity ?, we consider the problem of finding a shortest path tree T rooted at r such that for each vertex v the number of children of v in T does not exceed the capacity ?(v). The problem has an application in designing a routing for transferring files from the source node to other nodes in an information network. In this paper, we first present an efficient algorithm to the problem. We then introduce extensions of the problem by relaxing the degree constraint or the distance constraint in various ways and show polynomial algorithms or the computational hardness of these problems.