Using the Sum of Roots and Its Application to a Control Design Problem

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酸性尿酸アンモニウム結石を伴ったEncrusted cystitisの1例

88歳男, 間質性肺炎に対し他院で治療中血膿尿を認め紹介転院した.KUB・CT・膀胱鏡にて膀胱内面ほぼ3分の2に石灰化を認め病理所見にてbacterial colonyとそれに伴う炎症細胞の浸潤・石灰化を認めた.またその際の結石分析で酸性尿酸アンモニウム結石と診断されたWe present a case of encrusted cystitis with ammonium acid urate calculi. An 88-year-old man was referred to our hospital to determine the cause of hematopyuria. He was a patient at another hospital for treatment of interstitial pneumonia with predonisolone. After admission to our hospital, kidney, ureter, bladder X-ray, computed togography and cystoscopy revealed calcification of about two-thirds of the mucosa of the bladder, and biopsy of the bladder revealed bacterial colonies with inflammation and calcification. Calculographic analysis revealed ammonium acid urate calculi. After treatment with antibiotics and irrigation with solita T1, an acidic solution of pH 3.5-6.5, inflammation and calcification were significantly reduced

Application of precise neutron focusing mirrors for neutron reflectometry: latest results and future prospects

超精密中性子集束ミラーによる電極界面のナノ構造解析技術の実用化 --測定精度の劇的な向上に向けた大きなマイルストーン--. 京都大学プレスリリース. 2020-10-28.Neutron reflectometry (NR) is a powerful tool for providing insight into the evolution of interfacial structures, for example via operando measurements for electrode–electrolyte interfaces, with a spatial resolution of nanometres. The time resolution of NR, which ranges from seconds to minutes depending on the reflection intensity, unfortunately remains low, particularly for small samples made of state-of-the-art materials even with the latest neutron reflectometers. To overcome this problem, a large-area focusing supermirror manufactured with ultra-precision machining has been employed to enhance the neutron flux at the sample, and a gain of approximately 100% in the neutron flux was achieved. Using this mirror, a reflectivity measurement was performed on a thin cathode film on an SrTiO3 substrate in contact with an electrolyte with a small area of 15 × 15 mm. The reflectivity data obtained with the focusing mirror were consistent with those without the mirror, but the acquisition time was shortened to half that of the original, which is an important milestone for rapid measurements with a limited reciprocal space. Furthermore, a method for further upgrades that will reveal the structural evolution with a wide reciprocal space is proposed, by applying this mirror for multi-incident-angle neutron reflectometry

Angiotensin II produces nociceptive behavior through spinal AT1 receptor-mediated p38 mitogen-activated protein kinase activation in mice

Background: It has been demonstrated that angiotensin II (Ang II) participates in either the inhibition or the facilitation of nociceptive transmission depending on the brain area. Neuronal Ang II is locally synthesized not only in the brain, but also in the spinal cord. Though the spinal cord is an important area for the modulation of nociception, the role of spinal Ang II in nociceptive transmission remains unclear. Therefore, in order to elucidate the role of Ang II in nociceptive transmission in the spinal cord, we examined the effect of intrathecal (i.t.) administration of Ang II into mice.Results: I.t. administration of Ang II produced a behavioral response in mice mainly consisting of biting and/or licking of the hindpaw and the tail along with slight hindlimb scratching directed toward the flank. The behavior induced by Ang II (3 pmol) was dose-dependently inhibited by intraperitoneal injection of morphine (0.1-0.3 mg/kg), suggesting that the behavioral response is related to nociception. The nociceptive behavior was also inhibited dose-dependently by i.t. co-administration of losartan (0.3-3 nmol), an Ang II type 1 (AT1) receptor antagonist, and SB203580 (0.1-1 nmol), a p38 MAPK inhibitor. However, the Ang II type 2 (AT2) receptor antagonist PD123319, the upstream inhibitor of ERK1/2 phosphorylation U0126, and the JNK inhibitor SP600125 had no effect on Ang II-induced nociceptive behavior. Western blot analysis showed that the i.t. injection of Ang II induced phosphorylation of p38 MAPK in the lumbar dorsal spinal cord, which was inhibited by losartan, without affecting ERK1/2 and JNK. Furthermore, we found that AT1 receptor expression was relatively high in the lumbar superficial dorsal horn.Conclusions: Our data show that i.t. administration of Ang II induces nociceptive behavior accompanied by the activation of p38 MAPK signaling mediated through AT1 receptors. This observation indicates that Ang II may act as a neurotransmitter and/or neuromodulator in the spinal transmission of nociceptive information. © 2013 Nemoto et al.; licensee BioMed Central Ltd

RAW 264.7細胞におけるLPSで誘導される誘導型NO合成酵素の発現に対するCaffeic Acid Undecyl Esterの阻害について

We synthesized caffeic acid undecyl ester (CAUE),and found that it exhibited strong inhibitory effect of lipopolysaccharide (LPS) -induced nitric oxide (NO) production in murine macrophage-like RAW 264.7 cells.We examined the effect of CAUE on the expression inducible nitric oxide synthase (iNOS) in LPS-stimulated RAW 264.7 cells.Western blot analysis performed with specific anti-iNOS antibody showed that a decrease in NO was accompanied by a decrease in the level of iNOS protein with dose-dependent manner (CAUE:0.1～1.0μM).To clarify the mechanistic basis for CAUE\u27s ability to inhibit the induction of iNOS,we examined the effect of CAUE on nuclear factor (NF)-κB,Inhibitor-κB (IκB) degradation and phosphorylation of extracellular-signaling regulated Kinases,ERK 1/2.CAUE potently suppressed the transcriptional activity of NF-κB,IκB degradation and activation of ERK.Since NF-κB was activated by following IκBα degradation,the recovery of IκBα protein indicating that CAUE inhibited the activation of degradation following NF-κB.These finding suggest that CAUE has the inhibitory effect on LPS-induced NO production and expression of iNOS in macrophage by the inhibition of IκB degradation and NF-κB activation,which may be mediated through blockage in the phospholylation ERK

Mitochonic Acid 5 (MA-5) Facilitates ATP Synthase Oligomerization and Cell Survival in Various Mitochondrial Diseases

Mitochondrial dysfunction increases oxidative stress and depletes ATP in a variety of disorders. Several antioxidant therapies and drugs affecting mitochondrial biogenesis are undergoing investigation, although not all of them have demonstrated favorable effects in the clinic. We recently reported a therapeutic mitochondrial drug mitochonic acid MA-5 (Tohoku J. Exp. Med., 2015). MA-5 increased ATP, rescued mitochondrial disease fibroblasts and prolonged the life span of the disease model “Mitomouse” (JASN, 2016). To investigate the potential of MA-5 on various mitochondrial diseases, we collected 25 cases of fibroblasts from various genetic mutations and cell protective effect of MA-5 and the ATP producing mechanism was examined. 24 out of the 25 patient fibroblasts (96%) were responded to MA-5. Under oxidative stress condition, the GDF-15 was increased and this increase was significantly abrogated by MA-5. The serum GDF-15 elevated in Mitomouse was likewise reduced by MA-5. MA-5 facilitates mitochondrial ATP production and reduces ROS independent of ETC by facilitating ATP synthase oligomerization and supercomplex formation with mitofilin/Mic60. MA-5 reduced mitochondria fragmentation, restores crista shape and dynamics. MA-5 has potential as a drug for the treatment of various mitochondrial diseases. The diagnostic use of GDF-15 will be also useful in a forthcoming MA-5 clinical trial

Feasibility of methotrexate discontinuation following tocilizumab and methotrexate combination therapy in patients with long-standing and advanced rheumatoid arthritis: a 3-year observational cohort study

Objectives: Methotrexate (MTX) is associated with extensive side effects, including myelosuppression, interstitial pneumonia, and infection. It is, therefore, critical to establish whether its administration is required after achieving remission with tocilizumab (TCZ) and MTX combination therapy in patients with rheumatoid arthritis (RA). Therefore, the aim of this multicenter, observational, cohort study was to evaluate the feasibility of MTX discontinuation for the safety of these patients. Methods: Patients with RA were administered TCZ, with or without MTX, for 3 years; those who received TCZ+MTX combination therapy were selected. After remission was achieved, MTX was discontinued without flare development in one group (discontinued [DISC] group, n = 33) and continued without flare development in another group (maintain [MAIN] group, n = 37). The clinical efficacy of TCZ+MTX therapy, patient background characteristics, and adverse events were compared between groups. Results: The disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 3, 6, and 9 months was significantly lower in the DISC group (P < .05, P < .01, and P < .01, respectively). Further, the DAS28-ESR remission rate at 6 and 9 months and Boolean remission rate at 6 months were significantly higher in the DISC group (P < .01 for all). Disease duration was significantly longer in the DISC group (P < .05). Furthermore, the number of patients with stage 4 RA was significantly higher in the DISC group (P < .01). Conclusions: Once remission was achieved, MTX was discontinued in patients who responded favorably to TCZ+MTX therapy, despite the prolonged disease duration and stage progression

Applicability of Preoperative Nuclear Morphometry to Evaluating Risk for Cervical Lymph Node Metastasis in Oral Squamous Cell Carcinoma

Background: We previously reported the utility of preoperative nuclear morphometry for evaluating risk for cervical lymph node metastases in tongue squamous cell carcinoma. The risk for lymph node metastasis in oral squamous cell carcinoma, however, is known to differ depending on the anatomical site of the primary tumor, such as the tongue, gingiva, mouth floor, and buccal mucosa. In this study, we evaluated the applicability of this morphometric technique to evaluating the risk for cervical lymph node metastasis in oral squamous cell carcinoma. Methods: A digital image system was used to measure the mean nuclear area, mean nuclear perimeter, nuclear circular rate, ratio of nuclear length to width (aspect ratio), and nuclear area coefficient of variation (NACV). Relationships between these parameters and nodal status were evaluated by t-test and logistic regression analysis. Results: Eighty-eight cases of squamous cell carcinoma (52 of the tongue, 25 of the gingiva, 4 of the buccal mucosa, and 7 of the mouth floor) were included: 46 with positive node classification and 42 with negative node classification. Nuclear area and perimeter were significantly larger in node-positive cases than in nodenegative cases; however, there were no significant differences in circular rate, aspect ratio, or NACV. We derived two risk models based on the results of multivariate analysis: Model 1, which identified age and mean nuclear area and Model 2, which identified age and mean nuclear perimeter. It should be noted that primary tumor site was not associated the pN-positive status. There were no significant differences in pathological nodal status by aspect ratio, NACV, or primary tumor site. Conclusion: Our method of preoperative nuclear morphometry may contribute valuable information to evaluations of the risk for lymph node metastasis in oral squamous cell carcinoma