著者

沢田 誠吾 野方 健一郎 古田 富雄 横倉 輝男 宮坂 貞

出版者

公益社団法人 日本薬学会

雑誌

CHEMICAL & PHARMACEUTICAL BULLETIN (ISSN:00092363)

巻号頁・発行日

vol.39, no.10, pp.2574-2580, 1991

被引用文献数

56

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A radical substitution reaction of 20(S)-camptothecin (1) with methanol furnished 7-hydroxymethylcamptothecin (2). Reaction of 1 with primary alcohols higher than methanol gave 7-alkylcamptothecins (4), of which alkyl groups were one carbon less than the alcohols used and also 7-hydroxyalkylcamptothecins (5). For the preparation of 7-alkylcamptothecin (4), aldehydes were used as a radical source and several alkylated derivatives were synthesized. 7-Acyloxymethyl derivatives (6), 7-carbaldehyde (7), iminomethyl derivatives (10), acid (11), esters (12) and amides (13) were synthesized starting from 2. 7-Ethyl-(4b) and 7-propylcamptothecin (4c), acyloxymethyl compounds 6a, 6c and ethyl ester (12b) exhibited higher antitumor activity than 1 against L1210 in mice.

著者

沢田 誠吾 松岡 俊一 野方 健一郎 永田 洋 古田 富雄 横倉 輝男 宮坂 貞

出版者

公益社団法人 日本薬学会

雑誌

CHEMICAL & PHARMACEUTICAL BULLETIN (ISSN:00092363)

巻号頁・発行日

vol.39, no.12, pp.3183-3188, 1991

被引用文献数

57

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20(S)-Camptothecin derivatives having nitro, amino, chloro, bromo, hydroxyl and methoxyl groups in the A-ring were synthesized. B-Ring hydrogenated camptothecin (2a) was converted into 10-hydroxycamptothecin (6e) by treatment with lead tetraacetate in trifluoroacetic acid. 10-Substituted derivatives (6) were obtained by a photoreaction of N-oxides (9). The cytotoxicity o the A-ring modified camptothecins was evaluated against KB cells in vitro and leukemia L1210 in mice. 7-Ethyl-10-hydroxycamptothecin (6i) was identified as a potential derivative for further modification.

著者

八重樫 隆 沢田 誠吾 永田 洋 古田 富雄 横倉 輝男 宮坂 貞

出版者

公益社団法人 日本薬学会

雑誌

CHEMICAL & PHARMACEUTICAL BULLETIN (ISSN:00092363)

巻号頁・発行日

vol.42, no.12, pp.2518-2525, 1994

被引用文献数

42

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Twenty-six novel A-ring-modified 7-ethylcamptothecins (6) were synthesized by Friedlander's condensation of the chiral tricyclic ketone (5) with aminopropiophenones (4). The compounds substituted with fluorine at the 11 position showed strong cytotoxicity to KB and L1210 cells. The 11-fluoro derivatives also exhibited strong inhibitory activity on DNA topoisomerase I. Nine compounds 6 with four to ten times stronger cytotoxicity than that of camptothecin were selected and converted into water-soluble 17-O-acyl amide derivatives (8). Compounds 8e (10-Me, O-COCH<SUB>2</SUB>CH<SUB>2</SUB>SCH<SUB>3</SUB>) and 8f (11-F, O-COC<SUB>2</SUB>H<SUB>5</SUB>) showed activity towards Meth A in mice that was comparable to that of CPT-11, at lower doses than CPT-11.

著者

小菅 卓夫 神谷 弘子 足立 太平

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.82, no.1, pp.190-190, 1962-01-25 (Released:2010-02-19)

参考文献数

3

被引用文献数

10

著者

Masayoshi Yamaguchi Aki Igarashi Satoshi Uchiyama Seiichi Morita Kuniaki Sugawara Takashi Sumida

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.50, no.6, pp.619-624, 2004 (Released:2004-12-01)

参考文献数

21

被引用文献数

19 28

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A change in circulating biochemical markers of bone metabolism in normal individuals with the intake of juice prepared from Satsuma mandarin (Citrus unshiu MARC.) containing β-crypthoxanthin was investigated. Twenty-one volunteers (ten males and eleven females) were divided into two groups of ten volunteers (five males and five females) and eleven volunteers (five males and six females), and each group was given sequentially juice (192 ml) containing two different contents of β-crypthoxanthin once a day for 28 or 56 days as follows: either regular juice with naturally occurring 802 μg β-cryptoxanthin/100 ml or a reinforced juice containing 1500 μg β-cryptoxanthin/100 ml. As serum bone markers, bone-specific alkaline phosphatase, γ-carboxylated osteocalcin, bone tartrate-resistant acid phosphatase (TRAP), and N-telopeptide of type I collagen were assayed. The intake of regular juice for 28 or 56 days caused a significant increase in γ-carboxylated osteocalcin, a marker of bone formation, and the intake for 56 days produced a significant decrease in serum bone TRAP activity. Moreover, intake of the β-cryptoxanthin reinforced juice for 28 or 56 days caused a significant increase in serum β-carboxylated osteocalcin concentration and a corresponding decrease in serum bone TRAP activity and N-telopeptide of type I collagen, a marker of bone resorption. This study suggests that the intake of β-cryptoxanthin reinforced juice has a stimulatory effect on bone formation and an inhibitory effect on bone resorption in normal individuals.

著者

戸口 始 小川 泰亮 岡田 弘晃 山本 眞樹

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.111, no.8, pp.397-409, 1991-08-25 (Released:2008-05-30)

参考文献数

61

被引用文献数

10 14

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Leuprorelin (leuprolide, D-Leu6-(des-Gly10-NH2)-LH-RH ethylamide) acetate is a superactive agonist of luteinizing hormone-releasing hormone (LH-RH). We developed once-a-month injectable microcapsules of this agonist by our novel in-water drying method. This depot formulation can release the drug at an apparent zero-order rate over one month with bioerosion of copoly (lactic/glycolic acid) utilized as a wall material of the polycore microcapsules. A dramatic prolonged depression of pituitary-gonadal axis, chemical castration, was achieved by the once-a-month injection in experimental animals ; it expects a reliable effcacy for treating hormone-dependent prostatic, breast cancers and endometriosis. Studies on the dosage design of this new delivery system of leuprorelin are summarized.

著者

山口 智子 向井 志乃 魚谷 茂雄 大谷 壽一 澤田 康文

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.122, no.5, pp.331-338, 2002 (Released:2003-02-18)

参考文献数

10

被引用文献数

1

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Phenytoin (PHT) exhibits nonlinear pharmacokinetics in the therapeutic range. Therefore a slight increase in dose may lead to considerable elevation of the serum PHT level. Although its bioavailability is dependent on the formulation, bioequivalence is considered to be preserved between the three major formulations, of tablet, 97% fine granules, and 10% powder. However, we experienced many cases of increases serum PHT concentration after changes in formulation from 97% fine granules to 97/4% hospital-made fine granules, and from the latter to 10% powder. Retrospective analysis revealed that these alterations were accompanied by 55% and 16% increases in the serum concentration-to-dose ratio of PHT, respectively. We investigated the factors of this increase by analyzing the weight of remaining powder in a package and the PHT content of each formulation. Each package of PHT formulation prepared with 97% fine granules and 10% powder was unsealed, and the contents were weighed to calculate the rate of recovery. The rate of ingestion was estimated by correcting the rate of recovery by PHT strength (i. e., 1.0 for 10% powder and 0.97 for fine granules). The rates of recovery and ingestion for 10% powder were 13% and 16% higher than those for 97% fine granules, respectively (p<0.01). In conclusion, Changing the PHT formulation from 97% fine granules to 10% powder may lead to a considerable increase in the serum PHT concentration and possibly induce PHT toxicity.

著者

野田 幸裕 鍋島 俊隆

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.120, no.8, pp.677-682, 2000-08-01 (Released:2008-05-30)

参考文献数

24

被引用文献数

1 9

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To develop an animal model for negative symptoms, in particular avolition, of schizophrenia, the effect of phencyclidine (PCP) on immobility (regarded as avolition) in the forced swimming test was investigated in mice, since PCP produces negative symptoms in humans. Unlike single, repeated treatment with PCP prolonged the immobility time in the forced swimming test 24 h after the final injection compared with saline treatment. The enhancing effect of PCP on the immobility persisted for 21 d after the withdrawal of the drug. Atypical antipsychotics attenuated the enhancing effect of PCP on the immobility. Since these attenuating effects were antagonized by a serotonin-S2 receptor agonist, (±)-2, 5-dimethoxy-4-iodamphetamine (DOI), the effects may be mediated via serotonin-S2 receptors. In contrast with atypical antipsychotics, typical antipsychotics, antidepressants and anxiolytics had no effect. No functional changes in post-synaptic serotonin-S2 reseptors were observed in PCP-treated mice following the forced swimming test. Serotonin utilization in the prefrontal cortex was increased, but dopamine utilization was decreased in PCP-treated mice showing the enhancement of immobility. The enhancing effect of PCP was significantly attenuated by D-cycloserine, an agonist for glycine binding site of N-methyl-D-aspartate (NMDA) receptor ionophore complex. Decreases of NMDA receptor function or of the cortical glutamate and glycine levels were observed in PCP-treated mice showing the enhancement of immobility. These results suggest that the enhancing effect of PCP on immobility is mediated by the imbalance of the cortical serotonergic, dopaminergic and glutamatergic systems and could be used as an animal model for negative symptoms of schizophrenia.

著者

金岡 祐一

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.50, no.4, pp.354-354, 2014 (Released:2016-06-01)

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無限ともいえる生命科学の将来に対し「有機化学システム」応用の可能性も,限りなく有望である.最近のこの分野の代表例として,畑中保丸博士は「光アフィニティーラベリングの画期的高速化と生命科学上のブレークスルーへの応用」研究により,平成26年度日本薬学会賞を受賞された.心からお祝いするとともに,推薦者として同氏の業績と併せて,アメリカで生まれ日本で育った「光アフィニティーラベリング」を概説する.

著者

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.130, no.4, pp.521-526, 2010 (Released:2010-04-01)

参考文献数

8

被引用文献数

6 6

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Currently, there are five anti-Alzheimer's disease drugs approved. These are tacrine, donepezil, rivastigmine, galantamine, and memantine. The mechanism of the first four drugs is acetylcholinesterase inhibition, while memantine is an NMDA-receptor antagonist. However, these drugs do not cure Alzheimer's, but are only symptomatic treatments. Therefore, a cure for Alzheimer's disease is truly needed. Alzheimer's disease is a progressive neurodegenerative disease characterized by cognitive deficits. The cause of the disease is not well understood, but research indicates that the aggregation of β-amyloid is the fundamental cause. This theory suggests that β-amyloid aggregation causes neurotoxicity. Therefore, development of the next anti-Alzheimer's disease drug is based on the β-amyloid theory. We are now studying natural products, such as mulberry leaf extracts and curcumin derivatives, as potential cure for Alzheimer's disease. In this report, we describe some data about these natural products and derivatives.

著者

岡﨑 敬之介 渡邊 徹 齋藤 勲 村山 純一郎

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.132, no.2, pp.231-236, 2012 (Released:2012-02-01)

参考文献数

10

被引用文献数

2 2

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Our aim was to clarify the side effects of irinotecan which occurred in patients admitted to Showa University Hospital to investigate whether the UGT1A1 genetic polymorphism status was reflected in the discontinuation or dose reduction of irinotecan. We retrospectively investigated UGT1A1 genetic polymorphisms, irinotecan dosage, dose discontinuance or reduction, and laboratory results from May 1 2009 to April 30 2010. The analysis of UGT1A1 genetic polymorphisms in 23 patients showed that frequencies of the UGT1A1*6 and UGT1A1*28 polymorphisms were 35% (eight patients) and 22% (five patients), respectively, and 17% (three patients) were UGT1A1*6/UGT1A1*28 compound heterozygotes. Of all patients who received irinotecan, dose reduction occurred in six patients (38%) and discontinuance in two patients (13%) due to neutropenia and other factors. Of these eight patients, seven (88%) had the UGT1A1*6 and/or *28 polymorphism. The most common irinotecan dose reduction was about 25% of the initial dose. Grade 4 neutropenia was observed in two patients who had the UGT1A1*6 and/or *28 mutation (13%), and one patient was a compound heterozygote. Our investigation confirmed that the UGT1A1 genetic polymorphism status of the patients was reflected in the discontinuance or dose reduction of irinotecan. Our results suggest that Grade 4 neutropenia may occur in patients who are compound heterozygotes and that these patients may need careful selection of treatment regimens possibly involving discontinuance or reduction in irinotecan dosage.

著者

富松 利明 松井 又夫 宇治 昭 加納 蓉子

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.82, no.11, pp.1560-1563, 1962-11-25 (Released:2010-02-19)

参考文献数

5

被引用文献数

6

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Experimental evidences suggest that the bases contained in Thalictrum thunbergii DC. (Japanese name “Akikaramatsu”) differs slightly by its habitat. In order to elucidate this point, the root of this plant collected in Nagano Prefecture was processed and a comparatively large amount of magnoflorine (I) was obtained, while its leaves and stems yielded takatonine (II). The leaves and stems of the same plant collected in Kochi Prefecture yielded magnoflorine (I) and berberine (III). These results are summarized in Table I.

著者

佐井 君江 澤田 純一 南 博信

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.128, no.4, pp.575-584, 2008 (Released:2008-04-01)

参考文献数

42

被引用文献数

10 19

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Recent progress in pharmacogenetic research has made “personalized medicine” a reality, where a suitable drug at the appropriate dosage is prescribed based on individual genetic factors. Irinotecan, an anticancer drug, is one of the models for personalized medicine, and a number of clinical studies have revealed significant associations between UGT1A1*28 and irinotecan toxicity. Based on the cumulative evidence, clinical tests for the UGT1A1*28 marker have started in the United States since 2005. However, the appropriate criteria for irinotecan dose adjustments have not yet been fully established. Since there are considerable differences in genetic polymorphisms among different ethnic groups and in approved irinotecan-containing regimens between countries, the criteria for the choice of suitable genetic markers and dose adjustments should be standardized in each country. This mini-review outlines our recent studies on irinotecan pharmacogenetics and discusses the clinical significance of UGT1A1*6 and *28 markers for personalized irinotecan therapy in Japanese cancer patients.

著者

林 恭子 大津 史子 矢野 玲子 榊原 仁作 後藤 伸之

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.131, no.1, pp.139-152, 2011 (Released:2011-01-01)

参考文献数

32

被引用文献数

3 3

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The present study investigated risk factors and subjective symptoms associated with drug-induced leucopenia. We selected 248 patients with drug-induced leucopenia from the Case Reports of Adverse Drug Reactions and Poisoning Information System (CARPIS) database of over 47000 case reports of adverse drug reactions and assigned them to a case group. We also randomly selected 743 cases of adverse drug reactions not associated with leucopenia as a control group. A comparison of patient characteristic data between the two groups using logistic-regression analysis revealed that female sex, autoimmune disease and renal damage were background risk factors for drug-induced leucopenia. In addition, thiamazole, ritodrine, propylthiouracil, ticlopidine, allopurinol, minocycline and captopril administration significantly increased the risk of drug-induced leucopenia. A significant association was also found for fever, chills and pharyngeal abnormalities. Based on these findings, we developed two estimated regression equations to help prevent drug-induced leucopenia in the community pharmacy setting.

著者

菅谷 幸子 吉葉 孝子 梶間 隆 石濱 泰

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.122, no.3, pp.237-246, 2002 (Released:2003-02-18)

参考文献数

15

被引用文献数

12 21

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We developed two methods for solubility screening of drug candidates in drug discovery. The first is a solution-precipitation (SP) method, in which the sample solutions are prepared by adding the drug solution in dimethylsulfoxide (DMSO) to buffers followed by filtering off the precipitate using 96-well filterplate. The second is a powder-dissolution (PD) method, in which the solid samples are dissolved to the buffer in the HPLC vial equipped with the filter membrane in the HPLC autosampler. An HPLC equipped with a photodiode array detector is used to measure the concentration of the sample solutions in both methods. The SP method was used for high throughput screening the solvating process of the candidates in aqueous solutions with lower sample consumption, and the PD method was used for screening both inter-molecular interaction in solid state and solvation in aqueous solution with more sample amount than that of SP method. Therefore, the solubility screening from early to final stage of lead optimization process would be successfully accomplished by using both methods complementarily.

著者

潮平 英郎 仲松 正司 喜瀬 勇也 比嘉 太 健山 正男 外間 惟夫 国吉 幸男 植田 真一郎 中村 克徳 藤田 次郎

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.136, no.9, pp.1313-1317, 2016 (Released:2016-09-01)

参考文献数

16

被引用文献数

1 2

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Teicoplanin, a glycopeptide antibiotic for methicillin-resistant Staphylococcus aureus, is recommended for therapeutic drug monitoring during treatment. Maintaining a high trough range of teicoplanin is also recommended for severe infectious disease. However, the optimal dose and interval of treatment for severe renal impairment is unknown. We report a 79-year-old man who received long-term teicoplanin treatment for methicillin-resistant Staphylococcus aureus bacteremia due to postoperative sternal osteomyelitis with renal impairment. Plasma teicoplanin trough levels were maintained at a high range (20-30 μg/mL). Although the patient required long-term teicoplanin treatment, a further decline in renal function was not observed, and blood culture remained negative after the start of treatment. Teicoplanin treatment that is maintained at a high trough level by therapeutic drug monitoring might be beneficial for severe methicillin-resistant Staphylococcus aureus infection accompanied by renal impairment.

著者

千葉 寛

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.31, no.9, pp.992-996, 1995

参考文献数

9

被引用文献数

21

著者

香川 靖雄

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.107, no.11, pp.835-848, 1987-11-25 (Released:2008-05-30)

参考文献数

38

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Adenosinetriphosphate (ATP) synthase (FoF1) is a major energy supplying enzyme of cells utilizing the proton motive force. It consists of a catalytic portion called F1 and a proton channel portion called Fo. In order to elucidate the chemical reaction of FoF1, thermophilic FoF1 (TFoF1) was used, because it is stable and could eb reconstituted without Mg-ATP. In contrast to the previous hypotheses on the ATP synthesis, direct measurement of H+ current through TFoF1 incorporated into a planar lipid bilayer, 3H+/ATP stoichiometry was obtained. The primary structure of TFoF1 was established by sequencing its operon deoxyribonucleic acid and subunit peptides. The stereochemistry of the reaction using [16O, 17O, 15O, 35S] thiophosphate supported the a pathway for associative nucleophilic displacement on a phosphoric ester without pseudorotation. The diastereoisomeric preference of Cd-ATPγS revealed that the true substrate of TFoF1 is Δ, β, γ, bidentate Mg-ATP, like adenylate kinase. The site directed mutagenesis of the residues of F1 homologous to Mg-ATP binding site of adenylate kinase revealed their essential role in the reaction. Mitchell's chemiosmotic theory was refined by these results.

著者

岡崎 研太郎

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.3, pp.351-355, 2015 (Released:2015-03-01)

参考文献数

8

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The empowerment approach to patients with diabetes is a philosophy that was introduced by Robert M. Anderson and Martha M. Funnell of Michigan Diabetes Research and Training Center in the 1990s. This approach is based on the observation that more than 98% of diabetes care is performed by patients themselves. Dr. Anderson, Ms. Funnell, and their colleagues found that every patient has a right and an ability to solve his/her own problem in his/her own diabetes. Therefore healthcare providers should provide support for patients own endeavors. Empowerment has three essential elements: 1) the patient is centered, they make a final decision of their daily self-management, and are responsible for those decisions and the results; 2) patient support is the main role of healthcare providers; and 3) patient and healthcare providers should collaborate. In this author's opinion, it is important for healthcare providers to improve their communication skills to use the empowerment approach to help patients change their behaviors in the real world. To encourage empowerment, we created a unique learning program for healthcare providers, named “Diabetes Theater”. This program is an interactive workshop comprising two parts: drama and discussion.

著者

酒井 弘憲

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.50, no.2, pp.151-153, 2014

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世の中,統計ブームである.2012年10月,トーマス・ダベンポートがハーバード・ビジネス・レビュー誌で「データサイエンティストは21世紀で最もセクシーな職業である(Data Scientist:The Sexiest Job of the 21st Century)」というセンセーショナルな記事を書いて以来,新聞やニュースを見てもビッグデータ,データサイエンティスト,統計(なかには,データねつ造,改ざんといった好ましくない報道もあるが)といった言葉を目にし,耳にしない日はないと言えるだろう.書店を覗いても,ビジネス誌で「統計」の特集が幾つも組まれているし,それまで一部の専門家だけのものであった「統計」の本がベストセラーになったりしている.ややブームが行き過ぎの感もあるが,データを扱う業務に携わっている立場からすると,脚光が当たるのは有難いことには違いない.こうやって見てみると,我々の身の回りには「統計」「データ」に関する情報が満ち溢れている.しかし,多くの人がそれらの言葉や情報を正しく理解できているとは言い難い.ビッグデータは無限の可能性を持った宝の山であるかのようにもてはやされ,データサイエンティストはハリー・ポッターのように玉石混交の巨大データから,いとも簡単にダイヤモンドのように有用な情報を掘り出すことができるかのような漠然とした幻想が世の中に充満している.もちろん,マスコミの情報操作も(意図するか否かは別として)多分にあるし,不親切な公的統計の提供方法などにも問題があることは確かである.なお,府・行政の名誉のため一言申し添えるならば,安倍内閣の日本再興計画(2013年6月14日公表)の1項目であるIT戦略で,一般国民が公的統計データをより使いやすくするための取り組み(どんな情報がどこにあるかというインデックス作りと検索窓口の一本化)を始めており,2014年度からはそれが実現化しはじめるはずである.常に物事を悲観的に見る必要はないが,楽観的に見すぎることも危険なことである.正しい統計リテラシーを身に付け,マスメディアに流れるデータや情報を冷静に客観的に見つめ分析することは,現代に生きる我々には必要不可欠な常識といってもよいのかもしれない.このたび縁あって,ファルマシア誌から「6 回の予定で,気楽に読める統計に関する話題提供を」ということで依頼を受けた.本誌を目にされる大方の読者は統計にはあまり馴染みがなく,数式アレルギーの方も少なくないと拝察する.著者自身も正直なところ,好きか嫌いかと問われれば,数式は苦手な方である.そのため,タイトルも「数式なしの統計のお話」とし,データを見る目を養うヒントや,統計にかかわりを持った人物のお話などを中心に紹介することにした.本誌の専門記事に目を通したあとで気分転換の気軽な気持ちで読んでいただき,多少でも統計に興味を抱いていただければ望外の喜びである.