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令和3年度, The objective was to evaluate the long-term efficacy and safety of tacrolimus monotherapy in myasthenia gravis (MG) patients. Immunosuppressive drug-naïve MG patients were administered tacrolimus, followed by thymectomy in some of the cases according to the clinical guideline for MG. Additional aggressive immunosuppressive therapies were allowed if the patients without thymectomy did not achieve minimal manifestation (MM) or better status after 3 weeks of tacrolimus administration or in the thymectomized patients by 1-2 weeks after the operation (i.e., 1st evaluation). Of all 14 patients included in this study, 8 of them (57%) achieved MM or better status at the 1st evaluation, and the remaining 6 (43%), who had failed to gain MM or better status at the 1st evaluation, also achieved MM or better status with 1 course of aggressive immunosuppressive therapy. The quantitative MG (QMG) scores, MG-Activities of Daily Living (ADL) scales, and anti-acetylcholine receptor (AchR) antibody levels were significantly decreased at 6 months and maintained thereafter. At the end of the follow-up period (41-70 months), all patients were in MM or better status. None of the patients experienced severe adverse effects. Our small preliminary study indicates that long-term tacrolimus monotherapy is possibly effective and safe for MG patients.

An analysis combining SERS and current–voltage response measurements with DFT calculations has identified the molecular adsorption site in a single molecule junction., Single-molecule junctions are ideal test beds for investigating the fundamentals of charge transport at the nanoscale. Conducting properties are strongly dependent on the metal–molecule interface geometry, which, however, is very poorly characterized due to numerous experimental challenges. We report on a new methodology for characterizing the adsorption site of single-molecule junctions through the combination of surface enhanced Raman scattering (SERS), current–voltage (I–V) curve measurements, and density functional theory simulations. This new methodology discriminates between three different adsorption sites for benzenedithiol and aminobenzenethiol junctions, which cannot be identified by solo measurements of either SERS or I–V curves. Using this methodology, we determine the interface geometry of these two prototypical molecules at the junction and its time evolution. By modulating the applied voltage, we can change and monitor the distribution of adsorption sites at the junction.

We have investigated the effect of the bias voltage on the 1,4-benzenethiol (BDT) single-molecule junction using the surface-enhanced Raman scattering (SERS). By measuring the bias voltage dependen...

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Key clinical symptoms observed among individuals with psychiatric disorders include difficulty falling asleep or maintaining sleep, poor sleep quality and nightmares. Those suffering from sleep disorders often present with symptoms of discontent with regard to sleep quality, timing and quantity, and these symptoms have an adverse impact on function and quality of life. A minimally invasive technique would be preferable in patients with psychiatric disorders, who tend to be sensitive to environmental change. Accordingly, we evaluated the performance of Zmachine Insight Plus, an ambulatory electroencephalography sleep monitor, in patients with psychiatric disorders. One hundred and three patients undergoing polysomnography were enrolled in this study. Zmachine Insight Plus was performed simultaneously with polysomnography. Total sleep time, sleep efficiency, wake after sleep onset, rapid eye movement (REM) sleep, light sleep (stages N1 and N2) and deep sleep (stage N3) were assessed. Total sleep time, sleep efficiency, wake after sleep onset, REM sleep duration and non-REM sleep duration of Zmachine Insight Plus showed a significant correlation with those of polysomnography. Lower sleep efficiency and increased frequency of waking after sleep onset, the arousal index and the apnea-hypopnea index on polysomnography were significantly associated with the difference in sleep parameters between the two methods. Among patients with psychiatric disorders who are sensitive to environmental change, Zmachine Insight Plus would be a useful technique to objectively evaluate sleep quality.

Despite growing evidence that infants and very young children can be infected with schistosomes, the epidemiological features and risk factors are not well described in this age group. We aimed to assess the prevalence of S. mansoni infection in children under two years of age from a population with a known high burden of infection in school-aged children and adults and thus inform the need for interventions in this potentially vulnerable age group. In a cross-sectional study in Mbita Sub-county, along the east coast of Lake Victoria, Western Kenya, we enrolled 361 children aged 6-23 months. The prevalence of S. mansoni infection was detected using the Kato-Katz stool examination and a point-of-care test for urinary circulating cathodic antigen (POC-CCA) (Rapid Medical Diagnostics, Pretoria, South Africa). Three-hundred and five (305) children had complete data of whom 276 (90.5%, 95%CI: 86.6-93.5) children were positive for S. mansoni by the POC-CCA test, while 11 (3.6%, 95%CI: 1.8-6.4) were positive by the Kato-Katz method. All Kato-Katz positive cases were also positive by the POC-CCA test. In multivariable analysis, only geographical area, Rusinga West (AOR = 7.1, 95%CI: 1.4-35.2, P = 0.02), was associated with S. mansoni infection using Kato-Katz test. Independent associations for POC-CCA positivity included age, (12-17 months vs 6-11 months; AOR = 7.8, 95%CI: 1.8-32.6, P = 0.002) and breastfeeding in the previous 24 hours (AOR = 3.4, 95%CI: 1.3-9.0, P = 0.009). We found a potentially very high prevalence of S. mansoni infection among children under two years of age based on POC-CCA test results in Mbita Sub-county, Kenya, which if confirmed strongly supports the need to include infants in public health strategies providing universal prophylactic treatment in high burden settings. Further research is required to determine the accuracy of diagnostic tools to detect light infection among very young children and possible long-term health impacts.

A GH67 α-glucuronidase gene derived from Bacillus halodurans C-125 was expressed in E. coli to obtain a recombinant enzyme (BhGlcA67). Using the purified enzyme, the enzymatic properties and substrate specificities of the enzyme were investigated. BhGlcA67 showed maximum activity at pH 5.4 and 45 °C. When BhGlcA67 was incubated with birchwood, oat spelts, and cotton seed xylan, the enzyme did not release any glucuronic acid or 4-O-methyl-glucuronic acid from these substrates. BhGlcA67 acted only on 4-O-methyl-α-D-glucuronopyranosyl-(1→2)-β-D-xylopyranosyl-(1→4)-β-D-xylopyranosyl-(1→4)-β-D-xylopyranose (MeGlcA3Xyl3), which has a glucuronic acid side chain with a 4-O-methyl group located at its non-reducing end, but did not on β-D-xylopyranosyl-(1→4)-[4-O-methyl-α-D-glucuronopyranosyl-(l→2)]-β-D-xylopyranosyl-(1→4)-β-D-xylopyranosyl-(1→4)-β-D-xylop- yranose (MeGlcA3Xyl4) and α-D-glucuronopyranosyl-(l→2)-β-D-xylopyranosyl-(1→4)-β-D-xylopyranosyl-(1→4)-β-D-xylopyranose (GlcA3Xyl3). The environment for recognizing the 4-O-methyl group of glucuronic acid was observed in all the crystal structures of reported GH67 glucuronidases, and the amino acids for discriminating the 4-O-methyl group of glucuronic acid were widely conserved in the primary sequences of the GH67 family, suggesting that the 4-O-methyl group is critical for the activities of the GH67 family.

平成29年度, To investigate the difference in results according to the mode of levodopa administration and the effect of zonisamide (ZNS), we analyzed the mRNA expression of dopaminergic and non-dopaminergic receptors in the striatum of Parkinson model rats in relation to the development of levodopa-induced dyskinesia (LID). Unilateral Parkinson model rats were subdivided into 4 groups and treated as follows: no medication (group N), continuous levodopa infusion (group C), intermittent levodopa injection (group I), and intermittent levodopa and ZNS injection (group Z). Two weeks after the treatment, LID was observed in group I and Z, but less severe in group Z. The level of both D1 and D2 receptor mRNAs was elevated in groups I and Z, but only D2 receptor mRNA expression was elevated in group C. Adenosine A2A receptor mRNA showed increased expression only in group I. The level of endocannabinoid CB1 receptor mRNA was elevated in groups N, C, and I, but not in group Z. Intermittent injection of levodopa caused LID, in association with elevated expression of D1 and A2A receptors. ZNS ameliorated the development of LID and inhibited up-regulation of A2A and CB1 receptors. Modulation of these receptors may lead to therapeutic approaches for dyskinesia.

経済・社会のグローバル化が加速的に進む中、大学を取り巻く環境や社会的要請を背景とし、本学においてもグローバル化の推進は喫緊の課題となっている。本稿は、京都産業大学における事務組織及び事務職員のグローバル化推進を目指し取り組みを行った「国際業務力向上ワーキング・グループ（WG）」の活動を報告するものである。本WGの最終到達目標は、京都産業大学の事務組織において、かつて「英語」・「国際」といったキーワードに関係することは、全て国際交流センターで対応することが当然とされていたが、これを全学的な取り組みとして展開していくこと、すなわち、「国際交流センター牽引型」から「部局イニシアティブ型」への転換をはかることである。本稿では、本学における国際関連業務の現状を知るための調査、職員交流プログラムの試行、事務手続き文書の英文化を含め、WGでの代表的な取組成果を報告する。また、WGで実施した調査・分析により、本学の国際化への課題が浮き彫りとなったことを主要な成果として論じる。さらに、調査の分析や実施した取組の結果に基づき、国際交流センター以外の部署が、主体的に国際業務を展開していくために何が重要かについて提言を行う。

A water molecule exhibits characteristic properties on the basis of hydrogen bonding. In the past decade, single water molecules placed in non-hydrogen-bonding environments have attracted growing attention. To reveal the fundamental properties of a single water molecule, endohedral fullerene H2 O@C60 is an ideal and suitable model. We examined the electronic properties of H2 O@C60 by performing single-molecule measurements. The conductance of a single molecular junction based on H2 O@C60 was found to be comparable to that of empty C60 . The observed values were remarkably higher than those obtained for conventional molecular junctions due to the effective hybridization of the π-conjugated system to the metal electrode. Additionally, the results undoubtedly exclude the possibility of electrostatic contact of entrapped H2 O with the carbon wall of C60 . We finally concluded that H2 O entrapped inside a C60 cage can be regarded as an electrostatically isolated molecule.

平成29年度

令和3年度, Glutamate, GABA, acetylcholine, dopamine, and serotonin interact with each other to regulate the flow of neural information in the striatum. Serotonin type 1A receptor (5HT1A) is primarily expressed on glutamatergic nerve terminals, and 5HT1B is expressed on GABAergic medium spiny neurons (MSNs). Zonisamide (ZNS) reportedly improves the off period without worsening levodopa-induced dyskinesia (LID) in patients with advanced Parkinson's disease. In this study, LID model rats were prepared by administrating levodopa to unilaterally 6-OHDA-lesioned rats. We analyzed changes in serotonergic neurotransmission of LID model rats to elucidate the relationship between LID and the serotonergic system and pathomechanism of the anti-dyskinetic effects of ZNS. Abnormal involuntary movements (AIMs) were most severe in intermittently levodopa-treated rats but milder in rats intermittently medicated with levodopa and ZNS. Continuously levodopa-infused rats or intermittently ZNS-injected rats did not develop AIMs, and no differences in the expression of brain-derived neurotrophic factor, 5-HT transporter, 5HT1A, and 5HT1B mRNA between the lesioned striatum and normal side were observed. Expression of 5HT1B mRNA was elevated in the lesioned striatum of intermittently levodopa-treated rats, but this elevation was normalized by concomitant use of ZNS. The severity of AIMs was correlated with the ratio of 5HT1B to 5HT1A mRNA expression in the lesioned striatum, indicating that the anti-LID effect of ZNS is based on inhibition via 5HT1B receptors to direct pathway MSNs sensitized by intermittent levodopa treatment. Selectively acting serotonergic drugs, especially those that lower the 5HT1B to 5HT1A ratio, are promising new therapeutic agents to attenuate LID development.

Fabrication of oxygen molecular junctions was demonstrated for a series of single metal wires of Au, Ag, and Cu using the mechanically controllable break junction method at low temperature (10 K). On the basis of conductance measurement, vibrational spectroscopy, and current–voltage (I–V) response of the molecular junctions, we provide experimental evidence that the oxygen can incorporate into the metal wires to form single oxygen molecular junctions. Conductance behavior during the elongation process of the molecular junctions revealed the formation of single one-dimensional wire. The incorporation of oxygen into the metal wires was demonstrated in vibrational spectroscopy and I–V response measurements. Furthermore, detailed analysis of the I–V response based on the single channel transport model allowed us to quantitatively evaluate electronic properties of the molecular junctions as metal–molecule electronic couplings and an energy level of a transport channel. The present study demonstrated that oxyge...