著者

中西 剛

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.127, no.3, pp.491-500, 2007 (Released:2007-03-01)

参考文献数

38

被引用文献数

2 8

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Rodent models have great utility for evaluating the potential of environmental chemicals to alter human reproductive development. However, animal studies have some problems of species differences in extrapolating to human developmental toxicity induced by xenobiotics, because the placental endocrine functions in particular vary considerably among different species. For example, estrogen biosynthesis during pregnancy in humans is much different from that in rodents. In humans, ovarian function gradually declines after fertilization, as the placenta becomes the primary site of estrogen biosynthesis during pregnancy. In contrast to the process in humans, the ovary (not the placenta) is the main source of estrogen during pregnancy in rodents, because the placenta of rodents does not express the catalytic enzymes for estrogen biosynthesis, such as aromatase. The regulation of estrogen biosynthesis in the placenta is very important for human embryos because altering placental function can cause permanent effects on embryos. It has been suggested that rodents are therefore unsuitable for evaluating the potential effects of xenobiotics on the human reproductive system and developmental toxicity induced by the alteration of placental endocrine functions. Consequently, there is an urgent need to establish effective tools to evaluate the in vivo reproductive and developmental toxicity of environmental contaminants that disrupt the placental endocrine functions, including maintenance of local estrogen concentrations in the placenta. To resolve the problems, in this review we propose using transgenic mice, in which the transgene is controlled by placental-specific promoters, and local transgene systems into the placenta using viral vectors.

著者

岡田 壽太郎 森田 修之

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.100, no.5, pp.524-529, 1980-05-25 (Released:2008-05-30)

参考文献数

1

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To deal with missing data in clinical tests, three methods (A, B, and E) were considered. Drug efficacy was estimated by (A) using only actual data, (B) using a previous value for a missing datum, and (E) using the value estimated by the equation (1) for a missing datum. [numerical formula] where S is the symptomatic severity (S0 is at the beginning), b is the recovery rate constant, θ is the number of days after the initiation of medical treatment, and subscript i means the i-th judgment. Based on theoretical calculations and analyses of nine sets of real data in ophthalmology, orthopedics and dermatology, (i) drug efficacy estimated by B was always smaller than by E, (ii) the difference in estimated drug efficacy between A and E was very small.

著者

平澤 明 原 貴史 市村 敦彦 辻本 豪三

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.131, no.12, pp.1683-1689, 2011 (Released:2011-12-01)

参考文献数

44

被引用文献数

2 6

---

Free fatty acids (FFAs) are not only essential nutrient components, but they also function as signaling molecules in various physiological processes. In the progression of genomic analysis, many orphan G-protein coupled receptors (GPCRs) are found. Recently, GPCRs deorphanizing strategy successfully identified multiple receptors for FFAs. In these FFA receptors (FFARs), GPR40 (FFAR1) and GPR120 are activated by medium- to long- chain FFAs. GPR40 is expressed mainly in pancreatic β-cell and mediates insulin secretion, whereas GPR120 is expressed abundantly in the intestine and regulates the secretion of cholecystokinin (CCK) and glucagons-like peptide-1 (GLP-1), it promotes insulin secretion. Due to these biological activity, GPR40 and GPR120 are potential drug target for type 2 diabetes and selective ligands have been developed. In this review, we provide recent development in the field and discuss their physiological roles and their potential as drug targets.

著者

高橋 夏子 小林 正紀 板垣 史郎 平野 剛 武隈 洋 菅原 満 井関 健

出版者

日本薬学会

雑誌

Yakugaku Zasshi (ISSN:00316903)

巻号頁・発行日

vol.132, no.6, pp.777-783, 2012-06-01

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The most effective drugs based on the type of cancer are chosen for chemotherapy. Tumor cells can be targeted at the DNA, RNA or protein level, and most of the classical anticancer drugs interact with tumor DNA in a time-dependent manner or a concentration-dependent manner. However, it has been unclear to date whether a combination therapy is carried out by using exact classification. Thus it is necessary to reclassify a great number of anticancer drugs. We propose a new classification system based on pharmacological effects of anticancer drugs. Classification of four anticancer drugs (cisplatin, carboplatin, paclitaxel and gemcitabine) was performed by the 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The four anticancer drugs were grouped by IC50 values (inhibitory concentration, 50%) in a time-dependent manner and a concentration-dependent manner. The present approach may be combined to enhance the chemosensitivity, improve the dose of cytotoxic drugs and evaluate the effects of novel anticancer drugs.

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 (Released:2012-05-01)

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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.

著者

岸本 桂子 福島 紀子

出版者

The Pharmaceutical Society of Japan

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.131, no.5, pp.685-695, 2011-05-01 (Released:2011-05-01)

参考文献数

28

被引用文献数

10 11

---

In this study, we investigated the status of researching drug information online, and the type of Internet user who uses anonymous Web communities and websites. A Web-based cross-sectional survey of 10875 male and female Internet users aged 16 and over was conducted in March 2010. Of 10282 analyzed respondents, excluding medical professionals, about 47% reported that they had previously searched the Internet for drug information and had used online resources ranging from drug information search engines and pharmaceutical industry websites to social networking sites and Twitter. Respondents who had researched drug information online (n=4861) were analyzed by two multivariable logistic regressions. In Model 1, the use of anonymous websites associated with age (OR, 0.778; 95% CI, 0.742-0.816), referring to the reputation and the narrative of other Internet users on shopping (OR, 1.640; 95% CI, 1.450-1.855), taking a prescription drug (OR, 0.806; 95% CI, 0.705-0.922), and frequent consulting with non-professionals about medical care and health (OR, 1.613; 95% CI, 1.396-1.865). In Model 2, use of only anonymous websites was associated with age (OR, 0.753; 95% CI, 0.705-0.805), using the Internet daily (OR, 0.611; 95% CI, 0.462-0.808), taking a prescription drug (OR, 0.614; 95% CI, 0.505-0.747), and experience a side effect (OR, 0.526; 95% CI, 0.421-0.658). The analysis revealed the profiles of Internet users who researched drug information on social media sites where the information providers are anonymous and do not necessarily have adequate knowledge of medicine and online information literacy.

著者

小林 利彦

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.12, pp.1743-1744, 2011-12-01 (Released:2011-12-01)

参考文献数

1

被引用文献数

3 3

---

In the 1990s, drug companies focused their resources on chemistry-based proprietary blockbuster compounds (small molecules) for chronic diseases that could bring in several billion dollars in a short period of time. Since then, the focus has turned to biologics (proteins/high MW molecules) such as anticancer agents, antibodies, and so on. Vaccines, in contrast, are a rather slow-growing market, administered only a few times per patient, low priced, and often undifferentiated. Due to the influenza scares of recent years, the above view has changed remarkably. According to some analysts, the annual growth of the current $2.2bn vaccine market will become almost 10 percent over the next 5 years. In 2009, Pfizer (US), in an effort to boost their small vaccine-related business, purchased Wyeth (US). In October 2010, Johnson & Johnson announced they were buying Crucell (Germany), the only vaccine maker who had remained independent. GSK (UK) holds the top spot in the vaccine market with a 25% share. Pfizer (US), Merck (US), Novartis (Switzerland), and Sanofi-Aventis (France) are next, while Johnson & Johnson has moved into the 6th position by purchasing Crucell. There is of course an essential therapeutic need for vaccines, however, why are major pharmaceutical companies now investing a significant amount of resources in the vaccine business? Vaccine development may take more time than that of small molecules, but they are less risky from an intellectual property standpoint, and complicated manufacturing processes create a high barrier to follow-on biologics/biosimilars. Also in Japan, since the recent influenza scares, there has been acceleration in movement and cooperation among industry and government, including lawmakers.

著者

酒井 一夫

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.126, no.10, pp.827-831, 2006 (Released:2006-10-01)

参考文献数

8

被引用文献数

10 18

---

“Hormesis” is defined, originally in the field of toxicology, as a phenomenon in which a harmful substance gives stimulating effects to living organisms when the quantity is small. The concept was extended and applied to ionizing radiation, high doses of which are harmful. Although radiation has been thought to be, based on findings in high dose ranges, harmful no matter low the dose is, recent investigation revealed that living organisms possess the ability to respond to low-dose radiation in very sophisticated ways. A good example of such responses is the so-called radiation adaptive response, a process in which acquired radioresistance is induced by low-dose radiation given in advance. The stimulation of certain bioprotective functions, including antioxidative capacity, DNA repair functions, apoptosis, and immune functions are thought to underly the adaptive response. The adaptive response is effective for chromosome induction, acute death, and tumorigenesis induced by high doses of radiation. Radiation hormesis and adaptive response provide a new scope in the risk assessment and medical application of ionizing radiation.

著者

国分 秀也 的場 元弘 山田 安彦 矢後 和夫

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.131, no.1, pp.113-127, 2011-01-01 (Released:2011-01-01)

参考文献数

89

被引用文献数

1 1

---

The pain experienced by cancer patients can be managed in 70-90% of cases by the World Health Organisation protocol for cancer pain. However, cancer pain treatment in Japan is not sufficiently effective. To use medicine safely and effectively, various problems must be solved. Therefore, in this study, appropriate usage of cancer pain treatment was examined. We were able to use acetaminophen suppositories (800 mg each) in cancer pain patients. It was suggested that high serum concentrations of oxycodone and hydrocotarnine might be observed in geriatric patients or in the state of decreased hepatic blood flow, making dose adjustment is necessary for such patients. We also clarified that the conversion ratio from oral oxycodone to intravenous ocycodone/hydrocotarnine was 0.71±0.12. In addition, we clarified the pharmacokinetics of controlled-release oxycodone in patients with cancer pain. Moreover, the findings of our study indicate that in the steady state, the serum concentrations of fentanyl are not maintained at a constant level for 3 days following the use of transdermal fentanyl. We established a method of appropriately passing a nasal duct for sustained release of fine granules of morphine sulfate. Resolution of the clinical problems associated with cancer pain treatments is anticipated to allow the proper use of cancer pain treatments in Japan.

著者

辻 彰

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.12, pp.1037-1058, 2002 (Released:2003-02-18)

参考文献数

148

被引用文献数

11 11

---

By incorporating the transporter-mediated or receptor-mediated transport process in physiologically based pharmacokinetic models, we succeeded in the quantitative prediction of plasma and tissue concentrations of β-lactam antibiotics, insulin, pentazocine, quinolone antibacterial agents, and inaperizone and digoxin. The author's research on transporter-mediated pharmacokinetics focuses on the molecular and functional characteristics of drug transporters such as oligopeptide transporter, monocarboxylic acid transporter, anion antiporter, organic anion transporters, organic cation/carnitine transporters (OCTNs), and the ATP-binding cassette transporters P-glycoprotein and MRP2. We have successfully demonstrated that these transporters play important roles in the influxes and/or effluxes of drugs in intestinal and renal epithelial cells, hepatocytes, and brain capillary endothelial cells that form the blood-brain barrier. In the systemic carnitine deficiency (SCD) phenotype mouse model, juvenile visceral steatosis (jvs) mouse, a mutation in the OCTN2 gene was found. Furthermore, several types of mutation in human SCD patients were found, demonstrating that OCTN2 is a physiologically important carnitine transporter. Interestingly, OCTNs transport carnitine in a sodium-dependent manner and various cationic drugs transport it in a sodium-independent manner. OCTNs are thought to be multifunctional transporters for the uptake of carnitine into tissue cells and for the elimination of intracellular organic cationic drugs.

著者

長島 弘明 増保 安彦

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.1, pp.49-54, 2010-01-01 (Released:2010-01-01)

参考文献数

19

被引用文献数

1 1

---

Monoclonal antibodies are being used as therapeutics for a number of cancers, such as leukemia, breast and colon cancers, and a lot of monoclonal antibodies specific for tumor-related antigens have been on clinical trials. Antibody-dependent cellular cytotoxicity (ADCC) is one of the major mechanisms by which antibodies exert anti-tumor effects. ADCC occurs through interaction between the Fc domains of IgG antibodies bound to target cells and Fcγ receptors on the surface of effector cells. In our study, a chimeric antibody, designated M-Ab, was constructed with the V regions from mouse anti-CD20 mAb 1F5 and the C regions from human IgG1 and κ chain. Two or three Fc domains were tandemly repeated downstream of the C-terminus of the M-Ab to give D0-Ab (Fc dimer Ab without a linker), T0-Ab (Fc trimer Ab without a linker), and T3-Ab (Fc trimer Ab with a (GGGGS)3 linker in front of the second and third hinge regions). Here, we show that Fc tandem repeat antibodies bind to all the low-affinity Fcγ receptors with very potent avidities and have greatly enhanced ADCC activity. T3-Ab is about 100 times more potent than the parental 1F5 chimeric antibody in terms of both Fcγ receptor binding and exerted ADCC activity at a 50-100 times less concentration as compared with the parental antibody. Thus, Fc tandem repeat antibodies are anticipated to be candidates for anti-tumor therapeutics and useful tools to elucidate the biological roles of Fcγ receptors.

著者

西村 信弘 土井 教雄 上村 智哉 竹谷 健 林 丈二 葛西 武司 金井 理恵 山口 清次 岩本 喜久生 直良 浩司

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.6, pp.759-766, 2009 (Released:2009-06-01)

参考文献数

21

被引用文献数

4 5

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A traditional Chinese herbal medicine, Kampo medicine, maoto, has been widely used in the treatment of febrile symptoms caused by viral infection. This herbal extract granule for oral use, however, is not well accepted by infants or young children due to its unpleasant taste and odor. Therefore, we prepared Kampo medicine, maoto, suppository and investigated the pharmaceutical and clinical efficacy of the suppository. Kampo medicine, maoto, granules were micro-pulverized and homogeneously dispersed into Hosco-H15 to prepare suppositories containing 0.25 to 1.0 g herbal extract by the conventional fusion method. Content of l-ephedrine, an index compound of Kampo medicine, maoto, in the extract granules and suppositories was determined by using a high performance liquid chromatographic method. Physicochemical experiments revealed that the suppository containing 0.5 g herbal extract had the most suitable melting point of 34°C. Contents of l-ephedrine in the suppository were constant, 93-96% of those in the same amount of the extract granules in different three lots. Upper and lower portions of the suppository had the same content of l-ephedrine. The suppository maintained more than 95% of l-ephedrine content through 6 months at 4°C, room temperature and 40°C, although maldistribution of the extract constituent was observed after storage at 40°C. The suppository was administered to 21 pediatric febrile patients at a dose of 1/3 to 2 full pieces depending on their body weight and physical status. Significant reduction (p<0.001) of body temperature from 39.5 to 37.5°C without serious adverse effects was observed in 17 patients who were monitored the clinical effects on the febrile symptoms. In conclusion, Kampo medicine, maoto, suppository was found to satisfy the physicochemical quality and quantity standards as well as to be clinically applicable to neonates, infants and children with viral febrile symptoms without any adverse effects.

著者

河邉 香月

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.126, no.Special_Issue, pp.199-206, 2006 (Released:2006-03-01)

参考文献数

32

被引用文献数

6 12

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α1-Adrenoceptor antagonists, called α1-blockers, are the first-line treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH). Nonselective α1-blockers like prazosin were mainly used in the past, but prostate-specific α1-blockers such as tamsulosin or naftopidil are now the mainstream agents for the management of BPH, based on the function of α1-adrenoceptor subtypes. Recent studies on voiding dysfunction have clarified the association between BPH and overactive bladder (OAB), underlining the use of OAB treatment in the management of BPH, inducing the simultaneous administration of antimuscarinic agents. Every aspect of diversified BPH symptom can be controlled individually in a short period.

著者

吉崎 和幸

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.6, pp.667-674, 2009-06-01 (Released:2009-06-01)

参考文献数

11

被引用文献数

4 4

---

Remarkable clinical effects were observed by IL-6 blockage with a humanized anti IL-6 receptor antibody in patients with Castleman's disease, rheumatoid arthritis, and juvenile inflammatory arthritis. This evidence suggests that the hyper-function of IL-6 is an essential key cytokine in the pathogenesis of the above diseases, in which many cytokines, chemokines, and inflammatory molecules are activated. We found, for example, TNF-α blocking therapy showed a reduction of acute phase proteins, such as CRP and SAA, however, the IL-6 blockade induced not only reduction but also normalization of CRP and SAA serum levels. To elucidate this in vivo phenomenon, we analyzed the expression of cytokine inducing CRP and SAA mRNA with the intracellular signal transduction mechanism in vitro. The results, indicated that the IL-6 signal was essential though the activation of STAT3 for the induction and augmentation of CRP or SAA by the associated stimulation with TNF-α or IL-1. Recently, it is now known that IL-6 is a regulatory molecule in the induction of Th17 cells with TGF-β. Therefore, IL-6 blockage may potentially improve autoimmune diseases, beginning with the pathogenic initiation phase. We believe that unknown pathogenic inflammatory phenomena can be clarified using this analytical strategy and cytokine blocking therapy. Furthermore, in the future we hope to induce complete remission of autoimmune diseases by using cytokine blockage freely.

著者

嵜山 陽二郎 小宮山 靖 塚田 秀夫

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.127, no.12, pp.2079-2084, 2007-09-18 (Released:2007-12-01)

参考文献数

10

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Animal pain testing is essential for the development of new analgesic drugs, where appropriate data analyses as well as appropriate multi-factorial design of experiments are necessary to obtain meaningful results in an efficient fashion. The tail withdrawal experiment is one of the pain tests in which a rhesus monkey is restrained in a chair from which its tail hangs free by so it can be immersed in warm water. The monkeys consistently kept their tails in 38-40°C water for an extended period of time, and thus, the data were censored at 120 sec. The effect of temperature on the tail withdrawal latency was evaluated using three monkeys with a randomized block design. The effect of morphine on the thermal sensitivity was also evaluated. A Friedman-type two-way analysis of variance (Mack-Skillings test) demonstrated that the effects of both temperature and the animals were significant. The effect of repeated measurement in one animal was not significant using the Friedman test, indicating that the significance of the effect of animals could be attributed to the difference in the intrinsic thermal sensitivity between animals. This method, together with a graphical approach, may prove to be valuable for assessing the sensitivity and reproducibility of an experimental condition, as well as the pharmacological effects of analgesic drugs.

著者

和田 浩二

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.122, no.11, pp.929-956, 2002 (Released:2003-02-18)

参考文献数

116

被引用文献数

5 13

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The chemical constituents of Aconitum yesoense var. macroyesoense and Aconitum japonicum were examined using high-resolution spectral analysis. Twelve novel alkaloids were isolated from A. yesoense var. macroyesoense together with 20 known alkaloids. Eight novel alkaloids were isolated from A. japonicum together with 15 known alkaloids. An HPLC-atmospheric pressure chemical ionization-mass spectrometry (HPLC-APCI-MS) method was useful for the simultaneous determination of 21 Aconitum alkaloids found in A. yesoense var. macroyesoense and A. japonicum. These compounds were fairly stable under the conditions used, and the protonated molecules or fragment ions characteristic of the molecule appeared as base peaks in the mass spectra and were used for selected ion monitoring. HPLC-APCI-MS is a very promising approach for structural investigations of positional isomers and stereoisomers. This method was applied successfully to stereoisomeric Aconitum alkaloids differing in configuration at C-1, -6, or -12. Comparison of the APCI spectra showed that the abundance of fragment ions was significantly higher for the C-1, -6, or -12 β-form alkaloid than for C-1, -6, or -12 α-form alkaloid. The main alkaloid constituents in the root of A. yesoense var. macroyesoense, Aconitum alkaloids of the C20-diterpenoid type, kobusine and pseudokobusine, and their acyl derivatives were examined for their peripheral vasoactivities by measuring laser-flowmetrically the cutaneous blood flow in the hind foot of mice after intravenous administration. It is thought that the hydroxyl groups of alkaloids, especially a free OH group of pseudokobusine at C-6, were important for action on the peripheral vasculature leading to dilatation, and the results indicated that esterification of the hydroxyl group at C-15 with either anisoate, veratroate, or p-nitrobenzoate may contribute to enhancement of the activity of the parent alkaloids.

著者

大谷 道輝 中井 達郎 大沢 幸嗣 金 素安 松元 美香 江藤 隆史 假家 悟 加野 象次郎 内野 克喜

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.12, pp.1153-1158, 2002-12-01 (Released:2003-02-18)

参考文献数

24

被引用文献数

10 12

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Twenty percent of dermatologists have experienced a separation of water or deterioration of topical corticosteroids mixed with commercially available ointments and/or creams. However, few investigations of this deterioration of admixtures have been reported. To assess the effects of preservatives in preventing microbial contamination of these admixtures, we attempted to investigate the concentration of preservative agents in admixtures and the microbial contamination of these admixtures with a topical corticosteroid ointment (Antebate®). The concentration of parabens was reduced by half using an admixture of corticosteroid ointment with four types of moisturizing creams, Urepearl, Pastaronsoft, Hirudoid, and Hirudoidsoft. After a further 3 months, no decrease in parabens was seen. No microbial contamination was found in any admixture stored at room temperature for 1 week and touched two times daily with a finger. The concentration and ratio of the parabens in the aqueous phase and oil phase were entirely different in the admixtures before being centrifuged. The aqueous phase of the admixtures of the oil/water (O/W)-type emulsions of Urepearl and Hirudoid was not found to have microbial contamination immediately after being centrifuged. All aqueous phases stored at room temperature or in a refrigerator for 1 week and touched with a finger twice daily exhibited microbial contamination. These experiments demonstrated that O/W-type emulsions, in which the water easily separates from the bases, should be thoroughly mixed to prevent microbial contamination.

著者

白井 宏樹 小堀 正人

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.127, no.1, pp.103-112, 2007-01-01 (Released:2007-01-01)

参考文献数

7

被引用文献数

1 1

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We describe the prospects of bioinformatics for drug discovery and discuss the current status, problems, and future direction of the interface between bioinformatics and docking studies. We also describe our recent work on sequence and structure analysis using the guanidino-modifying enzymes superfamily as a good example.

著者

上田 宏

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.127, no.1, pp.71-80, 2007 (Released:2007-01-01)

参考文献数

18

被引用文献数

4 6

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Proteins having multiple epitopes can be usually measured with sandwich ELISA employing two kinds of antibodies, which permits high sensitivity as well as a wide working range of more than three orders of magnitude. On the other hand, so-called monovalent antigens with MW less than 1000 are not susceptible to sandwich assays due to their small size and have almost always been measured in competitive assays. However, while a competitive assay needs only one antibody due to the principle of ratiometric measurement, optimization of the reaction conditions is necessary to attain suitable sensitivity and working range, which are often inferior to those of sandwich assays. As an alternative immunoassay for small antigens, here we propose a noncompetitive “open sandwich” immunoassay, which is based on the principle of stabilization of the antibody variable region Fv upon binding with antigen. Using ELISA to detect labeled VH fragments bound to immobilized VL in the presence of sample in microplate wells, various small molecules with MW around 200—300 can be measured with a superior detection limit and working range compared with those achieved with the corresponding competitive assays. The results indicate a common antigen recognition mode of anti-hapten antibody and wide applicability of the assay to the sensitive and handy analysis of low molecular-weight substances in areas such as environmental analysis and clinical diagnostics.

著者

石原 研治

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.125, no.9, pp.717-723, 2005-09-01 (Released:2005-09-01)

参考文献数

36

被引用文献数

2 2

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Eosinophils are one of the cells that play a critical role in the pathogenesis of allergic diseases. The increase in the number of eosinophils in such diseases is regulated by interleukin-5 (IL-5). The author have prepared recombinant rat IL-5 using a baculovirus expression system and examined its biological activities in rat eosinophils. It was demonstrated that recombinant rat IL-5 prolongs the survival of mature eosinophils and differentiates immature eosinophils into mature eosinophils, suggesting that rat IL-5 is a factor for eosinophilia in rats. Recombinant rat eosinophil-associated ribonuclease (Ear)-1 and Ear-2 were also prepared. Eosinophil granule proteins are thought to cause tissue damage due to their cytotoxic activity, but using recombinant rat Ear-1 and Ear-2, it was found that rat Ear-1 and Ear-2 have strong RNase A activity and bactericidal activity, suggesting that these proteins play critical roles in host defense. Finally, the important role of acetylation of histones was clarified in the differentiation of HL-60 clone 15 cells into eosinophils using the histone deacetylase inhibitors sodium n-butyrate, apicidin, and trichostatin A. These findings would be useful for further investigations of the role of eosinophils in allergic inflammation.