著者
伊東 祐二
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.137, no.7, pp.823-830, 2017 (Released:2017-07-01)
参考文献数
15
被引用文献数
2

As an alternative to hybridoma technology, the antibody phage library system can also be used for antibody selection. This method enables the isolation of antigen-specific binders through an in vitro selection process known as biopanning. While it has several advantages, such as an avoidance of animal immunization, the phage cloning and screening steps of biopanning are time-consuming and problematic. Here, we introduce a novel biopanning method combined with high-throughput sequencing (HTS) using a next-generation sequencer (NGS) to save time and effort in antibody selection, and to increase the diversity of acquired antibody sequences. Biopannings against a target antigen were performed using a human single chain Fv (scFv) antibody phage library. VH genes in pooled phages at each round of biopanning were analyzed by HTS on a NGS. The obtained data were trimmed, merged, and translated into amino acid sequences. The frequencies (%) of the respective VH sequences at each biopanning step were calculated, and the amplification factor (change of frequency through biopanning) was obtained to estimate the potential for antigen binding. A phylogenetic tree was drawn using the top 50 VH sequences with high amplification factors. Representative VH sequences forming the cluster were then picked up and used to reconstruct scFv genes harboring these VHs. Their derived scFv-Fc fusion proteins showed clear antigen binding activity. These results indicate that a combination of biopanning and HTS enables the rapid and comprehensive identification of specific binders from antibody phage libraries.
著者
石原 慶一
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.137, no.7, pp.807-810, 2017 (Released:2017-07-01)
参考文献数
8

Down syndrome, caused by the triplication of human chromosome 21, is the most frequent genetic cause of mental retardation. Mice with a segmental trisomy for mouse chromosome 16, which is orthologous to human chromosome 21, exhibit abnormalities similar to those in individuals with Down syndrome and therefore offer the opportunity for a genotype-phenotype correlation. In the current review, I present several mouse lines with trisomic regions of various lengths and discuss their usefulness for elucidating the mechanisms underlying Down syndrome-associated developmental cognitive disabilities. In addition, our recent comprehensive study attempting to identify molecules with disturbed expression in the brain of a mouse model of Down syndrome in order to develop a pharmacologic therapy for Down syndrome is described.
著者
小島 正美
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.132, no.5, pp.555-559, 2012

A lot of healthcare professionals experienced annoyance with biased mass media news regarding medical and health issues. In this paper, I propose "news profiling method" and "media guideline" to improve the medical and health journalism.<br>
著者
杉本 八郎 山西 嘉晴 小倉 博雄 飯村 洋一 山津 清實
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.119, no.2, pp.101-113, 1999-02-01 (Released:2008-05-30)
参考文献数
28
被引用文献数
3 9

The most consistent change of neurotransmitter in the brain of Alzheimer's patients is the dramatic decrease of cholinergic innervation due to the loss of neurons in the basal forebrain. The most widely studied acetylcholinesterase inhibitors (AChEIs) have been physostigmine and tacrine. Physostigmine has very short duration, and tacrine has liability to hepatotoxicity. These are the defects of the inhibitors. Our objective was to find a new type of AChEIs that would overcome the disadvantages of physostigmine and tacrine. Through a random screening, we incidentally found an N-benzylpiperazine derivative which showed positive cholinergic behavior in rats. We replaced the N-benzylpiperazine moiety with N-benzylpiperidine moiety and found a dramatic increase in anti-AChE activity. Even after the replacement of an amide group with a ketone group the activity was held. Furthermore, the cyclic-amide derivative showed enhanced inhibitory activity. On the basis of these results, an indanone derivative was designed. Among these indanone derivatives, donepazil hydrochloride (E2020), brand name ARICEPT was found to be the most balanced compound. The clinical studies of donepezil hydrochloride demonstrated statistically significant effects on ADAS-cog (Alzheimer's Disease Assessment Scale cognitive sub.) and CIBIC Plus (Clinician's Interview-Based Impression of Change plus).
著者
池田 幸弘
出版者
公益社団法人 日本薬学会
雑誌
ファルマシア
巻号頁・発行日
vol.51, no.7, pp.700-701, 2015

鶴橋の焼肉で腹ごしらえを済ませ,近鉄大阪線青山町行きの急行に乗車した.50分ほど乗っただろうか,ずいぶん山深いところまで来た.榛原で下車すると,ちょうど大宇陀行きのバスが待ち構えているかのように停車しており,乗車して20分ほどで終着の大宇陀に到着した.
著者
谷村 顕雄 秦 邦男 竹下 隆三
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.84, no.7, pp.652-655, 1964-07-25 (Released:2010-02-19)
参考文献数
11

Analysis was made on the composition of torula yeast, prepared from sulfite pulp waste liquor, using Torulopsis utilis, in order to elucidate the factor accelerating animal growth. Ethanol extract of torula yeast was fractionated and examination was made on several crystalline substances obtained. Besides D-galactose, ergosterol, and myristic acid, 1, 2, 3, 5, 6-penta-O-acetyl-α-D-galactofuranose was obtained in 0.11% yield. This is the first example of its presence in a natural product and it is interesting that a substance with so many acetyl groups had been found in nature.
著者
Yuji Takao Ho Chul Lee Shinya Kohra Koji Arizono
出版者
公益社団法人 日本薬学会
雑誌
Journal of Health Science (ISSN:13449702)
巻号頁・発行日
vol.48, no.4, pp.331-334, 2002 (Released:2002-08-01)
参考文献数
19
被引用文献数
26 48

Nine different food cans, packed with water, were heat-treated for 30 min at 80 or 100°C in order to elucidate the trends associated with the leaching of bisphenol A (BPA) from internal coatings. Low levels of BPA were detected in water from all unheated cans, rising to 0.06 to 32 ng/cm2 after heating at 100°C. Reducing the heat-treatment temperature to 80°C was found to reduce the BPA concentration in the contained water by up to two-thirds. The cans that recorded the highest BPA concentrations in water after heating were found to have components (lid, bottom or body) with high available BPA contents.
著者
宗像 達夫
出版者
公益社団法人 日本薬学会
雑誌
ファルマシア (ISSN:00148601)
巻号頁・発行日
vol.52, no.5, pp.436-436, 2016

梅雨の季節も近づく中,青や赤といった様々な色彩で私たちの心をそっと和ませてくれる身近な花といえば,アジサイ(Hydrangea macrophylla)だろう.アジサイの色は自生している土壌の酸性度によって変化するが,これは酸性土壌において土壌中にアルミニウムイオン(Al3+)が溶け出し,それが根から吸収されることに起因する.またアジサイの様々な色彩はアントシアンに由来するものであるが,赤色色素としては着色料などに広く利用されているものの,青色色素としては安定性の問題もあり使用が限定的である.本稿では,アジサイの青色色素の多様性の解明について積極的に取り組んでいるOyamaらの研究を紹介する.なお,本稿は下記の文献に基づいて,その研究成果を紹介するものである.1) Oyama H. et al., J. Agri. Food Chem., 63, 7630-7635 (2015).2) Takeda K. et al., Phytochemistry, 24, 1207-1209 (1985).3) Takeda K. et al., Phytochemistry, 24, 2251-2254 (1985).
著者
芝 清隆
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.129, no.11, pp.1295-1302, 2009 (Released:2009-11-01)
参考文献数
26
被引用文献数
1 1

Motif-programming is a method for creating artificial proteins by combining functional peptide motifs in a combinatorial manner. Motifs are often short amino acid sequences within natural proteins that are associated with particular biological functions. Motifs also can be created de novo using molecular engineering. In particular, peptide aptamers, which have been isolated as specific binders against various targets, are believed to be promising motif blocks for creating novel biomaterials through motif-programming. It is now known, however, that simple arithmetic addition does not always work with motif-programming-e.g., simple conjugation of motifs-A and -B does not always result in a bifunctional peptide-AB. To solve this nonlinearity in motif-programming, we have been employing a combinatorial approach, which we called MolCraft. In MolCraft, we prepare a library of artificial proteins that contain multiple motifs in various numbers and orders, from which clones having the desired functions are selected. In MolCraft, a microgene is first rationally designed so that the encoded peptides contain motifs, and then tandemly polymerized with insertion or deletion mutations at the junctions between microgene units. Because of junctional perturbations, proteins translated from a single microgene polymer are molecularly diverse, originating from the combinatorics of three reading frames, and are thus combinatorial polymers of three peptides. By embedding functional motifs into different reading frames of a single microgene, combinatorial polymers of functional motifs are easily prepared. Notably, repetitiousness retained in the overall structure of proteins contributes to the formation of ordered structures, and enhances the chances of reconstituting biological activity. This method is particularly well suited for developing liaison molecules that interface between cells and inorganic materials. Examples of multifunctional artificial proteins created from this method will be introduced.
著者
谷内 信彦 新留 徹広 杉本 八郎
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.135, no.2, pp.323-329, 2015-02-01 (Released:2015-02-01)
参考文献数
36
被引用文献数
1 1

In addition to cognitive decline, Alzheimer's disease patients also exhibit non-cognitive symptoms commonly referred to as behavioral and psychological symptoms of dementia, or BPSD. These symptoms have a serious impact on the quality of life of these patients, as well as that of their caregivers, but there are currently no effective therapies. The amyloid β-peptide (Aβ) is suspected to play a central role in the cascade leading to Alzheimer's disease, but the precise mechanisms are still incompletely known. To assess the influence of Aβ pathology on cognitive and non-cognitive behaviors, we examined locomotor activity, motor coordination, and spatial memory in male and female APPswePS1dE9 mice (Alzheimer's disease model, double transgenic mice expressing an amyloid precursor protein with Swedish mutation and a presenilin-1 with deletion of exon 9) at 5 months of age, when the mice had subtle Aβ deposits, and again at 9 months of age, when the mice had numerous Aβ deposits. Compared to wild-type mice, the male and female APPswe/PS1dE9 mice showed normal motor coordination in the rotarod test at both 5 and 9 months. In the Morris water maze test, male and female APPswe/PS1dE9 mice showed impaired spatial memory at 9 months; however, no such deficits were found at 5 months. In a locomotor activity test, male APPswe/PS1dE9 mice exhibited locomotor hyperactivity at 9 months, while females exhibited locomotor hyperactivity at both 5 and 9 months compared to the control mice. Together, these results indicate that APPswe/PS1dE9 mice developed spatial memory impairment and BPSD-like behavioral alterations resulting from Aβ accumulation.
著者
荒田 洋治
出版者
公益社団法人 日本薬学会
雑誌
ファルマシア
巻号頁・発行日
vol.52, no.12, pp.1153_1-1153_1, 2016

薬学と関りをもった50年の間,筆者が経験した事柄を,様々な観点から捉え,日本薬学会会員に向けて綴った短いエッセイ集です。
著者
古瀬 幹夫
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.134, no.5, pp.615-621, 2014 (Released:2014-05-01)
参考文献数
13
被引用文献数
1

Within an epithelial cellular sheet, the paracellular pathway can be divided into two routes: one between two adjacent cells and one at tricellular contacts, where the vertices of three cells meet. For epithelial barrier function, tight junctions restrict solute permeability through the paracellular pathway between two cells, while tricellular contacts contain specialized structures of tight junctions, named tricellular tight junctions (tTJs). Two types of membrane proteins, tricellulin and angulin family proteins (angulin-1/LSR, angulin-2/ILDR1 and angulin-3/ILDR2) have been identified as molecular components of tTJs. Angulins recruit triellulin to tTJs and these tTJ-associated proteins are required for normal tTJ formation as well as strong epithelial barrier function. Furthermore, mutations in tricellulin and angulin-2/ILDR1 genes cause autosomal recessive familial deafness, DFNB49 and DFNB42, respectively. Further analyses of the angulin-tricellulin system should lead to better understanding of the molecular mechanism and regulation of tTJs.
著者
宮田 興子
出版者
公益社団法人 日本薬学会
雑誌
ファルマシア (ISSN:00148601)
巻号頁・発行日
vol.52, no.7, pp.650-652, 2016 (Released:2016-07-01)
被引用文献数
1

薬学の6年制教育が開始されてから早いものでもう10年が経過した.更なるステップアップを目指して,6年制教育をより充実させることが求められている.そのような中で,薬学生および薬学部卒業生がより一層飛躍できるように,基礎薬学分野の1つである有機化学を専門にしている著者が,少しずつ実行していることを本稿で紹介させていただき,読者の方々のご意見を頂戴できたらと思う.さらにファーマシストであり,サイエンティストである優れた卒業生を輩出するためには,4年制博士課程の活性化が必要であると考えられる.このことについても,現在5人の博士課程学生の教育に携わっている立場より述べさせていただく.
著者
江本 憲昭
出版者
公益社団法人 日本薬学会
雑誌
ファルマシア (ISSN:00148601)
巻号頁・発行日
vol.53, no.4, pp.320-323, 2017 (Released:2017-04-01)
参考文献数
1

既存の薬学部教育では学生にとって臨床現場における基礎科学の重要性をイメージすることが難しいことが指摘されている。その理由のひとつとして、基礎科学研究と臨床現場との人事を含めた交流が希薄であることが挙げられる。本稿では、医学部での卒前・卒後教育を紹介し、薬学部における新たな基礎臨床統合科目の導入や基礎科学研究に詳しいpharmacist-scientist育成の重要性について概説する。
著者
伊藤 浩介
出版者
公益社団法人 日本薬学会
雑誌
ファルマシア (ISSN:00148601)
巻号頁・発行日
vol.51, no.7, pp.669-671, 2015 (Released:2017-03-22)

大阪大学大学院薬学研究科は,厚生労働省の「革新的医薬品・医療機器・再生医療製品実用化促進事業」に採択され,平成24年度より「核酸医薬の臨床有効性及び安全性の評価法」について研究を開始した.私は,当該事業における人材交流の一環で平成24年10月より2年半,医薬品医療機器総合機構(Pharmaceuticals and Medical Devices Agency:PMDA)において特任職員として勤務した.この事業は,革新的な技術等を応用した医薬品,医療機器および再生医療製品の実用化をスムーズに進めるために,薬事的な審査基準などの明確化が必要であるとの観点からスタートしている.その目的達成のために,革新的な医薬品等の開発に資する技術,科学的な知見などを有するアカデミアの参画を求めるわけであるが,実際のところ,大学等は単独で医薬品等の審査基準を検討できるノウハウや経験を有していないと思われる(少なくとも本事業開始時点において,大阪大学大学院薬学研究科にはそのような体制は整っていなかった).したがって,この事業では医薬品等の審査等に精通している規制当局(PMDAおよび国立医薬品食品衛生研究所)とアカデミアとの間で人材交流を行い,互いの知識と経験を共有することで,革新的な医薬品等の審査基準等の検討・確立が可能となることが期待されている.また,この事業の重要な副次的な成果として,アカデミアと規制当局間における人材交流などを通じて,アカデミアにレギュラトリーサイエンスに精通した人材を育成することも期待されている.本稿では,核酸医薬をキーワードとして行われた大阪大学大学院薬学研究科とPMDAの間の人材交流の当事者としての経験,および核酸医薬の審査基準等に関する検討の一端を紹介する.