巻号一覧
129 巻, 6 号
選択された号の論文の17件中1～17を表示しています
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誌上シンポジウム
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山村 隆, 千葉 健治2009 年 129 巻 6 号 p. 647-648
発行日: 2009/06/01
公開日: 2009/06/01
ジャーナル フリーPDF形式でダウンロード (204K) -
三宅 幸子2009 年 129 巻 6 号 p. 649-653
発行日: 2009/06/01
公開日: 2009/06/01
ジャーナル フリーNKT cells are defined as cells co-expressing of the natural killer receptors such as NK1.1 or NKR-P1A (CD161) and a T cell receptor (TCR). Although NK1.1+ TCR+ lymphocytes are heterogeneous, we focus on two distinct T cell subsets express invariant T cell receptor α chains, Vα14-Jα18(Vα14i) and Vα19-Jα33(Vα19i). Vα14i NKT cells (Vα24i NKT cells for human) are restricted by CD1d and Vα19i NKT cells (Vα7.2i NKT cells for human) are restricted by MR1 molecule. These cells emerge as an unique lymphocytes subset to bridge innate and acquired immunity. Here in this review, we discuss on the role of these cells in the regulation of autoimmunity and on the potential of therapeutic target for autoimmune diseases.
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千葉 健治2009 年 129 巻 6 号 p. 655-665
発行日: 2009/06/01
公開日: 2009/06/01
ジャーナル フリーFingolimod (FTY720) is the first substance in the new immunomodulator class called sphingosine 1-phosphate (S1P) receptor modulators. We isolated an immunosuppressive natural product, myrocin, from the culture broth of Isaria sinclairii, a kind of vegetative wasp. The chemical modification of myriocin yielded a new compound, FTY720, which has more potent immunosuppressive activity and less toxicity than myriocin. FTY720 has been shown to be highly effective in experimental allograft models and autoimmune disease models such as autoimmune encephalomyelitis, collagen-induced arthritis, and lupus nephritis. The most striking feature of FTY720 is the induction of a marked decrease in peripheral blood lymphocytes at doses that show immunosuppressive activity in these models. FTY720 is rapidly converted to FTY720-phosphate (FTY720-P) by sphingosine kinases. FTY720-P acts as a potent agonist at S1P receptor type 1 (S1P1), internalizes S1P1 on lymphocytes, and inhibits the migration of lymphocytes toward S1P. It is highly likely that the reduction of peripheral blood lymphocytes by FTY720 is due to the inhibition of S1P1-dependent lymphocyte egress from secondary lymphoid organs and thymus. Recently, it has been reported that FTY720 exerted considerable therapeutic effects in a placebo-controlled clinical trail involving patients with relapsing multiple sclerosis. Patients who received FTY720 orally had a significant reduction in the clinical disease activity, the number of lesions in the central nervous system, and the relapse rates. Since FTY720 possesses a new mechanism of action that has not been observed with other immunosuppressive agents, it is believed that FTY720 provides a new therapeutic approach for autoimmune diseases including multiple sclerosis.
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吉崎 和幸2009 年 129 巻 6 号 p. 667-674
発行日: 2009/06/01
公開日: 2009/06/01
ジャーナル フリー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.
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田中 良哉2009 年 129 巻 6 号 p. 675-679
発行日: 2009年
公開日: 2009/06/01
ジャーナル フリーSystemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are representative autoimmune diseases thought to involve disturbances in T and B cell functions. Immune complexes consisting of antigens and autoantibodies secreted from activated B cells cause severe inflammation in various organs. Since often patients with RA and SLE are refractory to these conventional treatments such as immunosuppressants and corticosteroids, innovative approaches need to be developed. CD20 is a surface molecule specific for B cells and rituximab is a chimeric antibody specific for human CD20 and is known to deplete B cells. Recently, the potential efficacy of B-cell depletion therapy with rituximab has been reported in several autoimmune diseases. Rituximab is now approved for use in combination with methotrexate in refractory RA patients in the United States and EU. We reported that SLE patients with organ-threatening disorders that are resistant to intensive conventional therapies, were treated by once a week administration of anti-CD20 antibody rituximab, and that sufficient evidence concerning the excellent tolerability and high efficacy of rituximab therapy was obtained in both a pilot study and a nation-wide phase I/II clinical examination Moreover, a rapid and marked reduction in the expression of the co-stimulatory molecules CD40 and CD80 on B-cells was found in SLE patients, implying that reduction of both the quantity and the quality of B-cells by rituximab could improve the disease course in refractory SLE. Therefore, targeting B-cells may have potential interests by bringing about a breakthrough in the treatment of RA, SLE and other autoimmune diseases.
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総説
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竹田 忠紘2009 年 129 巻 6 号 p. 681-698
発行日: 2009/06/01
公開日: 2009/06/01
ジャーナル フリーThis review describes the carbohydrate study and the natural product related to the glycoside chemistry. What shall the people in the field of pharmacognosy and natural products chemistry search in scene in future? Forty years before while isolating dimeric compound having naphthoquinonepyrone skeleton from the coloring material produced by the pathogen that hosted in wheat and caused rotten root disease, silica gel has to be treated with oxalic acid to reduce the absorbency before separation. However now a days, availability of reversed phase adsorbents for liquid chromatography has made the separation and isolation of complex compounds possible, easy and rapid. With the advancement of mechanical/physicochemical analytic methods, it has even been possible to isolate traces of compounds present in complex. This advancement has made it possible to determine structure of saponins and complex polysaccharides without decomposition and carry out in vitro bioassay at the same time using various cells on-line. Further, this review describes the oligosaccharide syntheses and biological activities of glycosphingolipids, focusing especially on those found in invertebrates.
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大久保 孝義2009 年 129 巻 6 号 p. 699-708
発行日: 2009/06/01
公開日: 2009/06/01
ジャーナル フリーAmbulatory and home blood pressure (BP) measurements more accurately and reliably reflect the true BP levels of individuals than conventional BP measurement. Moreover, they can be measured over an extended period, thus generating information about BP variability. We conducted a population-based prospective study in Japan (the Ohasama study), demonstrating their superior predictive power for cardiovascular mortality/morbidity over conventional BP measurements as well as unique prognostic significance of variability in their values. Masked hypertension defined as normal conventional BP and high ambulatory or home BP was associated with worse prognosis. A disturbed nocturnal decline in BP was associated with cerebral infarction and heart diseases, whereas a large morning surge in BP was associated with cerebral hemorrhage. Morning hypertension at home, a reflection of a disturbed nocturnal decline or a large morning surge in BP, was a good predictor of stroke, particularly among individuals using anti-hypertensive medication. The J-HOME (Japan Home versus Office Measurement Evaluation) study among hypertensive patients receiving antihypertensive treatment revealed that morning home BP levels were not adequately controlled among approximately 60% of the patients. Interim analysis of the HOMED-BP (Hypertension Objective treatment based on Measurement by Electrical Devices of Blood Pressure) study, a randomized controlled trial to determine optimal target of morning home BP, demonstrated effectiveness of systematic antihypertensive drug regimen to lower morning home BP levels. The diagnosis and treatment of hypertension can be managed effectively by considering information from home and ambulatory BP monitoring.
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春日 淳一, 大山 拓次, 中込 泉, 青山 惇, 迫 久美子, 槇島 誠, 広野 修一, 森川 耿右, 橋本 祐一, 宮地 弘幸2009 年 129 巻 6 号 p. 709-718
発行日: 2009/06/01
公開日: 2009/06/01
ジャーナル フリーA series of 3-(4-alkoxypheny)propanoic acid derivatives was prepared as candidate peroxisome proliferator-activated receptor (PPAR) δ-selective agonists, based on our previously discovered potent human PPARα/δ dual agonist TIPP-401 as a lead compound. Structure-activity relationship studies clearly indicated the importance of the chain length of the alkoxy group at the 4-position, and the n-butoxy compound exhibited the most potent PPARδ transactivation activity and highest PPARδ selectivity. The (S)-enantiomer of a representative compound (TIPP-204) exhibited extremely potent PPARδ transactivation activity, comparable to that of the known PPARδ-selective agonist GW-501516. To understand why TIPP-204 shows high selectivity for hPPARδ among hPPAR subtypes, and why TIPP-401, a structurally related compound, is a hPPARα/δ dual agonist, computational docking of TIPP-401 to the ligand binding domains of hPPARα and hPPARδ and X-ray structure analysis of TIPP-204-hPPARδ ligand binding domain were carried out. The results allowed identification of certain amino acids as putative determinants of the hPPARδ selectivity of TIPP-204. To confirm the significance of these amino acids, GAL4-fusion proteins of mutated hPPARδs and hPPARαs were prepared, and the transactivation activity of TIPP-204 toward the mutants was evaluated. The amino acid(s) that predominantly influence the potency and selectivity of TIPP-204 are different from that of the well-known PPARδ-selective agonist GW-501516, which belongs to a different chemical class. The significance of these amino acids was confirmed by the examination of the complex structure between TIPP-204 and hPPARδ. The results revealed several interactions relevant to the hPPARδ-selectivity of the two ligands and will be useful for logical hPPARδ ligand design.
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一般論文
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河村 麻衣子, 花尻(木倉) 瑠理, 合田 幸広2009 年 129 巻 6 号 p. 719-725
発行日: 2009/06/01
公開日: 2009/06/01
ジャーナル フリーDirect Analysis in Real Time (DART) is a novel ionization technique that provides for the rapid ionization of small molecules under ambient conditions. To investigate the trend of non-controlled psychotropic plants of abuse in Japan, a rapid screening method, without sample preparation, was developed using DART-time of flight mass spectrometer (TOFMS) for plant products. The major psychotropic constituents of these products were determined using liquid chromatography-mass spectrometry (LC/MS). As a result of the DART-TOFMS analyses of 36 products, the protonated molecular ions [M+H]+, corresponding to 6 kinds of major hallucinogenic constituents (mescaline, salvinorin A, N,N-dimethyltryptamine, harmine, harmaline and lysergamide), were detected in 21 products. It was possible to estimate their accurate elemental compositions through exact mass measurements. These results were consistent with those of the LC/MS analyses and the contents of the 6 psychotropic constituents were in the range from 0.05 to 45 μg/mg. Typical controlled narcotic drugs, tetrahydrocannabinol, opioid alkaloids and psilocin were also directly detected in marijuana cigarette, opium gum and magic mushroom respectively. Although it is difficult to estimate the matrix effects caused by other plant ingredients, the DART-TOFMS could be useful as a simple and rapid screening method for the targeted psychotropic natural products, because it provides the molecular information of the target compounds without time-consuming extraction and pre-treatment steps.
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畑中 典子, 伊藤 貴文, 石幡 真澄, 小島 美里, 根本 英一, 大嶋 繁, 小林 大介2009 年 129 巻 6 号 p. 727-734
発行日: 2009年
公開日: 2009/06/01
ジャーナル フリーThis questionnaire study involved the cooperation of home helpers and community pharmacists to improve medication adherence of in-home patients. The survey form contained 18 items that are factors for adherence and a visual analog scale to record the predicted medication adherence (predicted adherence). Assisted by the 14 offices of the home-visit helper care system located in Niiza, Saitama prefecture, 140 in-home patients were surveyed. For 21 of the 140 patients, a pharmacist was able to measure medication adherence by counting the number of pills remaining in the patient's home (true adherence). Factors influencing the predicted and true adherence were analyzed by multivariate analysis and found to be different. Home helpers predicted the medication adherence based on a patient's everyday life such as “irregular meal”, “storing up drugs” and “one dose package”. On the other hand true adherence was influenced by “urging to take the medicine by the home helper” and “pharmacist-visit”. Furthermore, the medication adherence of patients who were not visited by a pharamacist and urged to take medicine by the home helper was low when the (1) age was high, (2) care or support level required was low, and (3) self-control of dosing was suspected. Therefore the home helper should encourage the patient to take the medicine and when the pharmacist is informed by the home helper about patients who fit the above (1)-(3), the pharamacist should visit the patient's home.
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内藤 結花, 石井 正和, 川名 慶治, 坂入 由貴, 清水 俊一, 木内 祐二2009 年 129 巻 6 号 p. 735-740
発行日: 2009/06/01
公開日: 2009/06/01
ジャーナル フリーPharmacists in a community pharmacy may recommend an over-the-counter (OTC) drug to patients with headache. However, it is not clear how pharmacists should distinguish the symptoms of patients and facilitate appropriate self-medication. Here, we investigated the role of pharmacists in a community pharmacy in recommending OTC drugs for self-medication by patients with headache and elucidated their future needs using a questionnaire intended for doctors and pharmacists. More than half of the pharmacists surveyed did not have any experience with recommending OTC drugs for patients with headache. To distinguish between patients for whom pharmacists should “recommend OTC drugs” and patients who should be encouraged “to consult a hospital or clinic,” doctors thought that pharmacists should use an “assistance tool to diagnosis headache, such as a screener for migraine” and “guidelines for chronic headache.” However, few pharmacists used these tools. About 68% of doctors indicated that it would be “meaningful” for pharmacists to distinguish patients with headache. Moreover, both doctors and pharmacists thought that pharmacists should provide patients not only with “instruction on the use of drugs” but also suggest “when to consult a hospital or clinic.” However, 32% of doctors indicated that it is “meaningless” for pharmacists to attempt to distinguish patients with headache and expressed concern about the increase of patients who overuse headache medication. These findings provide useful information to guide pharmacists in community pharmacy when recommending OTC drugs for self-medication by patients with headache.
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内藤 結花, 石井 正和, 坂入 由貴, 川名 慶治, 清水 俊一, 木内 祐二2009 年 129 巻 6 号 p. 741-748
発行日: 2009/06/01
公開日: 2009/06/01
ジャーナル フリーIt is often noted that the collaboration of hospital-to-hospital, hospital-to-clinic and clinic-to-clinic in medical care for patients with headache is important. However, the role of community pharmacies in the medical network for consultation of patients with headache is not clear. Here, we investigated the role of pharmacists in a community pharmacy in encouraging patients with headache to undergo medical examination and elucidated their future needs using a questionnaire intended for doctors and pharmacists. About 70% of pharmacists had experience with recommending that patients with headache consult a hospital. However, only 17% of doctors had experience with referral of patients with headache by pharmacists in a community pharmacy. About 22% of pharmacists had experiences in which the patient with headache refused to consult a hospital despite the recommendation, suggesting that many patients did not think that their headache symptoms were severe. In addition, 90% of doctors and 84% of pharmacists felt the need for collaboration between hospitals or clinics and community pharmacies. Doctors needed information from pharmacists on the “current state of drugs” taken by patients. However, pharmacists considered that they needed to provide not only “current state of drugs being taken” but also “symptoms of headache” to doctors. Although 67% of doctors considered the medication notebook to be useful for pharmacists to provide patient information to doctors, pharmacists preferred to provide the information by telephone. Moreover, 56% of pharmacists did not know how to search a website for medical specialists in headache. A medical network including not only hospitals or clinics but also community pharmacies might be useful for patients with headache.
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小澤 和弘, 南 博信, 佐藤 均原稿種別: Regular Article
2009 年 129 巻 6 号 p. 749-757
発行日: 2009/06/01
公開日: 2009/06/01
ジャーナル フリーThis study was aimed to perform clinical trial simulations to evaluate the dose reduction strategy of docetaxel for Japanese patients with liver dysfunction, which we previously proposed. For this purpose, a log-binominal regression (LBR) was performed for febrile neutropenia (FN) induced by docetaxel in these patients. A LBR analysis was conducted using clinical data from cancer patients treated with docetaxel and incorporated in the subsequent trial simulation. Virtual patients with liver dysfunction were randomly assigned to receive the Japanese standard dose (60 mg/m2) or reduced dose (40 or 50 mg/m2) of docetaxel. The primary endpoint was overall survival of the reduced dose to the standard dose. The secondary endpoint was the number of patients who experienced FN in response to the two treatment regimens. From the LBR analysis, the performance status and the area under the plasma concentration-time curve (AUC) were selected as covariates associated significantly (p<0.05) with FN occurrence. From the results of the present trial simulation, the median proportion of patients who experienced FN was decreased by about 20% in the reduced dose arm. Non-inferiority criteria, the reduced dose group to the standard dose group were met in 85.5% of the simulated clinical trials with a decrease in the FN frequency. In conclusion, clinical trial simulation models for the efficacy (survival) and toxicity (FN) was first performed in Japanese patients, and the feasibility of docetaxel therapy for liver-dysfunction patients under the dose reduction strategy was supported.
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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2009 年 129 巻 6 号 p. 759-766
発行日: 2009/06/01
公開日: 2009/06/01
ジャーナル フリー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.
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ノート
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瀬尾 誠, 田近 賢二, 清水 久範, 浜田 真向, 土橋 保夫, 土橋 朗, 檀 和夫, 片山 志郎2009 年 129 巻 6 号 p. 767-771
発行日: 2009/06/01
公開日: 2009/06/01
ジャーナル フリーBusulfex®is a new type of busulfan which can be administered intravenously. Usually it is administered over 2 hours every 6 hours. Its injection should be finished within 8 hours after mixture with a saline, which may bring some troublesome in clinical practice. We, here, introduce the prefilled-syringe method; Busulfex® is filled into an injection syringe made of polypropylene beforehand under a sterile condition, and mixed with a saline just before the administration at the bed side. To evaluate the safety of this method we studied the stability of busulfan solution in the syringe physically and chemically. The drug solution was made with the same ingredients as Busulfex®, filled into a syringe, and stored at 4°C until use. Then, the transparency of this solution was studied with spectroscopy and the concentration of busulfan was analyzed directly by HPLC. Busulfan solution stored in non-colored injection syringe at 4°C was stable for up to 96 hours both physically and chemically. We concluded that prefilled-syringe method is ease and safe way to administer Busulfex® on scheduled time.
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朝比奈 泰子, 堀 里子, 大谷 壽一, 澤田 康文2009 年 129 巻 6 号 p. 773-780
発行日: 2009/06/01
公開日: 2009/06/01
ジャーナル フリーHerbs and dietary supplements (HDS) are widely used, and health professionals are in an ideal position to educate patients about them. However, it is sometimes difficult to evaluate their risks and benefits with limited information and what is worse, many health professionals in Japan are unconcerned with HDS. Therefore, we aimed to develop an internet-based educational system to periodically provide information about HDS to medical doctors and pharmacists in order to increase their awareness. Monographs about selected HDS, accompanied with educational quizzes, were prepared to meet pharmacists' needs. Examples of clinical Q&A cases about drug interactions involving HDS were prepared. The material was distributed weekly to registered health professionals by e-mail and via WWW pages. Two hundred and forty-four health professionals evaluated the system by questionnaire. The questionnaire results revealed that 1) more than 75% of responders evaluated the system as useful, 2) compilation of information into educational quizzes and cases encouraged health professionals to learn about HDS with less difficulty, and 3) e-mails led them to learn periodically and to be more concerned about the safety of HDS. In conclusion, the developed information system for HDS was proved to be useful and should serve to improve the understanding of health professionals about this issue.
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正誤表
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佐々木 圭子, 大林 真幸, 神山 紀子, 小林 靖奈, 山元 俊憲2009 年 129 巻 6 号 p. 781
発行日: 2009/06/01
公開日: 2009/06/01
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