A Production/Transaction-Related Model Using Control Theory

In recent years, the need for wide-ranging kaizen/improvements has arisen in relationships with suppliers and other transaction partners in response to rising demands, including increases in profit and reductions in time. A method that results in such improvements is the application of a servo-mechanism control to manage inventory ordering. It is believed that if control theory is applied to the overall supply chain, it may enable an optimization of the supply chain, which fits the needs of modern society. This study proposes a prototype of the supply chain model of contemporary society, which applies the control theory and evaluates the validity of this model

Intra-Day Variation of Urinary Nuclear Matrix Protein 22

Nuclear Matrix Protein 22 (NMP22), a urinary tumor marker for urothelial cancers, is directly released into the urine from the nucleus after cell death, Accordingly, values of NMP22 do not requlre adjustment using other substances such as urinary creatinine. On the other hand, its values might vary according to urine concentration. This study investigated the intra-day variation in the urinary level of NMP22. NMP22 and urinary creatinine were measured in a 24-hour urine sample and 4 spot urine samples obtained from 20 inpatients (10 with bladder cancer, and 10 with non-urothelial cancer or benign tumors). The spot urine samples were collected at 6 a.m., 10 a.m., 2p.m. and 9 p.m. There were no significant differences in NMP22 values between the 24-hour and spot samples in all patients. Out of 10 bladder cancer patients, 6 had positive 24-hour samples. Among these 6 patients, only 3 had 4 positive spot samples (>12.O U/ml): one had 3 positive samples, and 2 had one positive sample. Among the controls, only one patient with renal cancer had a positive 24-hour sample. Only 3 controls, 2 With prostatic cancer and one with renal cancer, had a single positive spot sample. The highest margin between the maximum and minimum levels in the 4 spot samples was 237.8 U/ml in the bladder cancer patients and 16.6 U/ml in the controIs. When the ratios of NMP22 and urinary creatinine values for the 24-hour to spot samples were calculated in each patient, a significant correlation was observed between the ratios of NMP22 and urinary creatinine (r=0.575, p<0.001). The urinary level of NMP22 shows intra-day variation and might be affected by the extent of the concentration of urine samples. The measurement results must be judged with this in mind, especially when judging the results around the cut-off value

尿中Nerve Growth Factorは、過活動膀胱症状を呈する患児の治療効果の予測因子になる

Objective: To assess urinary nerve growth factor (NGF) in children with overactive bladder (OAB) and to investigate the relationship between urinary NGF/creatinine (Cr) levels and OAB. Patients and methods: Thirty-five children (27 boys and 8 girls) with OAB and 11 children (6 boys and 5 girls) without OAB or any other urinary symptoms, who served as controls, were included in this study. Urinary NGF levels were measured using enzyme-linked immunosorbent assay. The total urinary NGF levels were adjusted with the concentration of urinary creatinine (NGF/Cr level). Refractory OAB was defined as little improvement in OAB symptoms despite at least 3 months of urotherapy and anticholinergic agent treatment. Urinary NGF/Cr was compared between the children with OAB and the controls. The relationship between urinary NGF/Cr and treatment outcomes was also evaluated. Results: Urinary NGF/Cr was significantly higher in the children with OAB when compared with those in the control group (0.65 ± 0.82 vs 0.11 ± 0.09, P = .0007). Improvement of OAB symptoms was observed in 26 out of 35 children (74%). The remaining 9 children showed refractory OAB symptoms (the refractory group). Urinary NGF/Cr was significantly higher in the refractory group than in the improved group (1.28 ± 1.34 vs 0.44 ± 0.39, P = .027). Conclusion: Urinary NGF/Cr was significantly higher in the children with OAB than in the controls, and was significantly higher in the refractory group than in the improved group. Urinary NGF/Cr could not only be a potential biomarker for children with OAB, but also a predictor of therapeutic efficacy in children with OAB.博士（医学）・乙第1454号・令和2年3月16日Copyright © 2017 Elsevier Inc. All rights reserved

1006-44 A Prognostic Factor in Coronary Artery Disease (CAD): Platelet-Dependent Thrombin Generation in Patients with CAD

We examined platelet-dependent thrombin generation in patients with coronary artery disease (CAD). Thrombin generation was measured according to the method of Aronson et al (Circulation, 1992). 0.5ml of platelet rich plasma (PRP, 15×104/ml) was prepared, and 40mM of CaCl, was added to start clotting. 0.5mM of S-2238 was added to each sample in a microtiter plate every 10min, and the plate was read kinetically at a wavelength of 405nm on a microtiter plate reader. The patients with CAD devided into 3 groups.Thrombin generation 20 min after CaCI2, additon is:Control (n=12)48±10(mOD)Stable angina (SAP) (n=15)79±27Unstable angina (UAP) (n=15)**562±155Acute myocardial infarct (AMI) (n=43)**440±269**p&lt;0.01 compared to SAPThe patients with UAP and AMI showed marked increase in thrombin generation compared to SAP and control subjects. AMI patients with severe coronary artery disease (Group B) showed higher levels of thrombin generation (Group A, Gensini score&lt;32: 382±248 mOD vs Group B, Gensini score&gt; 31: 578±238, P&lt;0.05). LVEF of group A is significantly higher than that of group B (P &lt; 0.05). These findings indicate that patients with UAP and AMI have an evidence of hypercoagulable states and that platelet-dependent thrombin generation may play an important role in pathophysiology of UAP or AMI, and may be a prognostic factor in CAD

Hepatocyte growth factor and Met in drug discovery

Activation of the hepatocyte growth factor (HGF)-Met pathway evokes dynamic biological responses that support the morphogenesis, regeneration and survival of cells and tissues. A characterization of conditional Met knockout mice indicates that the HGF-Met pathway plays important roles in the regeneration, protection and homeostasis of cells such as hepatocytes, renal tubular cells and neurons. Preclinical studies in disease models have indicated that recombinant HGF protein and expression plasmid for HGF are biological drug candidates for the treatment of patients with diseases or injuries that involve impaired tissue function. The phase-I and phase-I/II clinical trials of the intrathecal administration of HGF protein for the treatment of patients with amyotrophic lateral sclerosis and spinal cord injury, respectively, are ongoing. Biological actions of HGF that promote the dynamic movement, morphogenesis and survival of cells also closely participate in invasion-metastasis and resistance to the molecular-targeted drugs in tumour cells. Different types of HGF-Met pathway inhibitors are now in clinical trials for treatment of malignant tumours. Basic research on HGF and Met has lead to drug discoveries in regenerative medicine and tumour biology. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved

Cellular Responses of Human Lymphatic Endothelial Cells to Carbon Nanomaterials

One of the greatest challenges to overcome in the pursuit of the medical application of carbon nanomaterials (CNMs) is safety. Particularly, when considering the use of CNMs in drug delivery systems (DDSs), evaluation of safety at the accumulation site is an essential step. In this study, we evaluated the toxicity of carbon nanohorns (CNHs), which are potential DDSs, using human lymph node endothelial cells that have been reported to accumulate CNMs, as a comparison to fibrous, multi-walled carbon nanotubes (MWCNTs) and particulate carbon black (CB). The effect of different surface characteristics was also evaluated using two types of CNHs (untreated and oxidized). In the fibrous MWCNT, cell growth suppression, as well as expression of inflammatory cytokine genes was observed, as in previous reports. In contrast, no significant toxicity was observed for particulate CB and CNHs, which was different from the report of CB cytotoxicity in vascular endothelial cells. These results show that (1) lymph endothelial cells need to be tested separately from other endothelial cells for safety evaluation of nanomaterials, and (2) the potential of CNHs as DDSs.ArticleNANOMATERIALS. 10(7):1374 (2020)journal articl

PDE5阻害薬であるタダラフィルは糖尿病ラットの膀胱血流を改善し、初期段階に低下する下部尿路機能を回復する

AIMS: To investigate the effect of tadalafil on bladder blood flow and lower urinary tract function in a rat model of diabetes. MATERIALS AND METHODS: We studied female Sprague-Dawley rats and induced diabetes in some using a single intraperitoneal injection of streptozotocin. We divided the rats into nondiabetes (ND), diabetes (D), and diabetes with tadalafil (DT) groups. The rats were raised for an additional 7 weeks after diabetes induction. The DT group received oral tadalafil (2 mg/kg/day) for 7 days before the experiments. At 7 weeks after diabetes induction, we performed cystometry, resected the bladders for immunohistochemistry (hypoxia-inducible factor-1α [HIF-1α] and 8-oxo-2'-deoxyguanosine [8-OHdG] staining), and measured bladder blood supply using a laser blood flow meter. RESULTS: The opening pressure, when the urethra opens and urine flow starts, was significantly lower in the DT group than in the D group (24.9 ± 5.9 vs 43.6 ± 12.3 cmH2 O). The inter-contraction interval was significantly longer in the D group than in the ND and DT groups (1566.2 ± 168.7 vs 702.9 ± 165.2 and 787.4 ± 148.8 s). Immunohistochemistry showed positive staining of the urothelial layer for both HIF-1α and 8-OHdG in the D group, but not in the ND or DT groups. Bladder blood flow was significantly lower in the D group than in the ND or DT groups. CONCLUSIONS: Tadalafil improves bladder blood supply and lower urinary tract function in diabetic rats. Tadalafil may be a promising drug that restores lower urinary tract dysfunction in the early phase of diabetes.博士（医学）・甲第677号・平成30年3月15日© 2017 Wiley Periodicals, Inc.This is the peer reviewed version of the following article: "http://dx.doi.org/10.1002/nau.23372", which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

Clinical impact of postoperative loss in psoas major muscle and nutrition index after radical cystectomy for patients with urothelial carcinoma of the bladder

Figure S3. Comparison of changes after radical cystectomy between neoadjuvant chemotherapy-treated group and non-treated group. Time-course changes in cross-section area of the psoas major muscle at the level of L3 (a), abdominal skeletal muscle area at the level of L3 (b), the PNI (c) and, the CONUT score (d). Data of neoadjuvant chemotherapy-treated group (red) and non-treated group (blue) are plotted by means ¹ SD. Scores of two groups compared in each time point by the Mann-Whitney U-test. ns, not significant. (TIFF 7424 kb

Anti-PD-1 antibody decreases tumour-infiltrating regulatory T cells

Background There are many types of therapies for cancer. In these days, immunotherapies, especially immune checkpoint inhibitors, are focused on. Though many types of immune checkpoint inhibitors are there, the difference of effect and its mechanism are unclear. Some reports suggest the response rate of anti-PD-1 antibody is superior to that of anti-PD-L1 antibody and could potentially produce different mechanisms of action. On the other hand, Treg also express PD-1; however, their relationship remains unclear. Methods In this study, we used osteosarcoma cell lines in vitro and osteosarcoma mouse model in vivo. In vitro, we analyzed the effect of IFN gamma for expression of PD-L1 on the surface of cell lines by flowcytometry. In vivo, murine osteosarcoma cell line LM8 was subcutaneously transplanted into the dorsum of mice. Mouse anti-PD-1 antibody was intraperitoneally administered. we analysed the effect for survival of anti-PD-1 antibody and proportion of T cells in the tumour by flowcytometry. Results We discovered that IFN gamma increased PD-L1 expression on the surface of osteosarcoma cell lines. In assessing the relationship between anti-PD-1 antibody and Treg, we discovered the administration of anti-PD-1 antibody suppresses increases in tumour volume and prolongs overall survival time. In the tumour microenvironment, we found that the administration of anti-PD-1 antibody decreased Treg within the tumour and increased tumour-infiltrating lymphocytes. Conclusions Here we clarify for the first time an additional mechanism of anti-tumour effect-as exerted by anti-PD-1 antibody decreasing Treg- we anticipate that our findings will lead to the development of new methods for cancer treatment.ArticleBMC CANCER. 20(1):25 (2020)journal articl