We investigated the effects of

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-saiko-to, the most commonly used herbal medicine in Japan, on the production of interleukin (IL)-la by cultured human epidermal keratinocytes. IL-lα production was significantly promoted by treatment with 100 or 500 μg/ml -saiko-to for 24 or 48 hr. Expression of IL-lα receptors was the most markedly upregulated after treatment with 500 μg/ml

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-saiko-to for 24 hr and with 100 or 500 μg/ml for 48 hr; these cells showed the characteristics of multilayered differentiated keratinocytes. The presence of an anti-IL-lα antibody during the treatment with 500 μg/ml of

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-saiko-to for 24 or 48 hr or with 100 μg/ml for 48 hr significantly down-regulated the synthesis by the keratinocytes and induced damages in them. Keratinocytes treated with

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-saiko-to might produce IL-lα and express IL-lα receptors. IL-lα may regulate the proliferation and differentiation of keratinocytes after

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-saiko-to treatment. These findings suggest that

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-saiko-to enhances the autocrine growth mediated by IL-lα.

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In calligraphy Lin- is to copy original works in a freehand manner. Lin- is not only an important method to learn the technique of calligraphy but also an essential condition for its expression. In this paper, my attempt is to clarify the characteristic of calligraphy as a traditional art in China and Japan through the consideration of Lin-. First I inquire into the meaning of "copying" in calligraphy, then analyze the technique of works by Lin-. Most important in Lin- is the attitude to read the artistic mind of a calligrapher. Lin- is not merely to copy a preconceived form of letters but to enter into the ancient calligrapher's artistic intention concerning an original work of his. Calligrapher in Lin- introduces the mind of the ancients through the exemplary traces of the brush into himself, and at the same time expresses his mind. Lin- can be seen as the realization of the artistic intention. Lin- is one form of interpretative act that is essentially based on the dialogue between the ancient masters and calligraphers in copying. Through this dialogue calligraphers have created their own styles. Thus Lin- can open the way to creativity in calligraphy.

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-ju-sen is a Japanese herbal medicine which has been used as a nourishing tonic. It is composed of a water extract of Kumazasa leaves (Sasa kurinensis Makino et Sibata) and ethanol extracts of Japanese red pine needles (Pinus densiflora Sieb. Et Zucc) and ginseng roots (Panax ginseng C. A. Meyer). Previous studies showed that -ju-sen has antidepressant and anxiolytic effects in mice (Phytother Res., 15: 142-147, 2001 and 18: 173-176, 2004). Here we report that the effects of -ju-sen on catecholamine secretion in cultured bovine adrenal medullary cells. Adrenal medullary cells have provided a good material for the detailed analysis of a drug's actions on catecholamine secretion and have been used as a model of the sympathetic neurons. We found that -ju-sen (0.5 - 1 %) and extract of Kumazasa leaves (0.5-1 %), but not ethanol extract of Japanese red pine needles or ginseng roots, concentration-dependently inhibited the secretion of catecholamines induced by acetylcholine, a physiological secretagogue and agonist of nicotinic acetylcholine receptors. In Xenopus oocytes expressing α3β4 nicotinic acetylcholine receptors, -ju-sen (0.5 - 1 %) directly inhibited Na⁺ current evoked by acetylcholine. -ju-sen (0.3 - 1 %) also inhibited catecholamine secretion induced by veratridine, an activator of voltage-dependent Na⁺ channels, but not by 56 mM K⁺ which depolarizes cell membranes. The present findings demonstrate that -ju-sen inhibits acetylcholine- and veratridine-induced catecholamine secretion by suppression of nicotinic acetylcholine receptor-ion channels and voltage-dependent Na⁺ channels in adrenal medulla cells and probably sympathetic neurons, and also suggest that -ju-sen has an anti-stress effect.

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健康なビーグル犬各7頭に, 消風散, 当帰飲子, 小柴胡湯および小青龍湯の漢方方剤1.25g (小青龍湯は1.5g) を朝, 夕2回に分割して連続7日間経口投与したところ, 消風散を除く3方剤により, Compound 48/80に対する皮内反応を指標とした肥満細胞脱顆粒作用は有意に抑制され, 当帰飲子を除く3方剤により, リン酸ヒスタミンに対する皮内反応を指標とした抗ヒスタミン作用は有意に増強された. また, 小青龍湯および小柴胡湯投与開始後7日には, 血中Cortisol濃度が投与開始前に比べて有意に増加した.

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-saiko-to, one of the most frequently prescribed Kampo medicines, is used clinically to treat chronic hepatitis and has shown confirmed clinical efficacy. The present study investigated whether -saiko-to can suppress cytotoxicity and tumor necrosis factor (TNF)-α production in endotoxin-treated J774A.1 cells. -saiko-to (10—20 μg/ml) did not affect the proliferation of J774A.1 cells, while a high concentration (50 μg/ml) of -saiko-to induced a slight reduction in cell viability. Treatment with -saiko-to (10—50 μg/ml) significantly inhibited endotoxin (10 μg/ml)-induced cytotoxicity in J774A.1 cells. In addition, -saiko-to (20 μg/ml) suppressed TNF-α production by endotoxin (1 μg/ml)-activated J774A.1 cells. These findings suggest that the Kampo prescription -saiko-to suppresses cytotoxicity or TNF-α production in macrophages treated with endotoxin and that it may be useful in improving septic shock symptoms. -saiko-to may therefore protect against some of the various disturbances caused by endotoxins through its ability to inhibit TNF-α production in septic shock.

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A scientific evaluation to several oriental handwritting "" was performed using a thermography. Probably this kind of experiment was first trial. Usually, a part of "" was treated as an art. A trial test was performed for articles written by an authority ("" s were written in 29, 19, 8 years and one year before by Mr. Tanchu Terayama). The test was performed as follows; after a "SYO" was excited with a single light pulse (10 seconds excitation) from a halogen lamp, carbon of a character absorbs the light energy and the temperature goes up. About ten measureing points were set in one character. After the light pulse excitation was stopped, the temperature of the points goes down. These temperature change can measured non-distractively and without touch by the thermography. In this temperature experiment, we found the characters of temperature decay were different in each measureing points. We understood these differences came from the thickness due to Chinese ink and the thermal conductivity. From these temperature experiments, decay times of the half height in each measuring points were scattered especially in old "" and were not scattered in his recent articles written in 8 years and last year before. By his comments of Mr. Terayama, good "" s do not scattered so much and also older samples had large scattering value. Probably, recent articles were written under a strong Qi (concentrated) condition. Therefore our trial method was useful to distinguish good "" in Mr. Terayama articles. This method must be tested in his many works and more researches are needed for cheching the availability.

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-saiko-to extract, a Chinese herbal medicine, is widely used for treatment of chronic hepatitis in Japan. However, it is not clear what conditions -saiko-to extract improves hepatic inflammation and fibrosis. We therefore induced various stages of liver injury in model rats and administered -saiko-to extract. We then evaluated the liver inflammation and liver fibrosis-improving effects of -saiko-to extract. The liver injury model rats were produced by administration of various doses of dimethylnitrosamine (DMN) and -saiko-to extract was administered to these rats. Then the liver inflammation and fibrosis-improving effects of -saiko-to extract were evaluated according to L-asparate aminotransferase (AST), L-alanine aminotransferase (ALT), liver retinoid levels, levels of hydroxyproline, Transforming Growth Factor-β (TGF-β), and the liver fibrosis area. These indicators depended on the total doses of DMN. The ability of -saiko-to extract to improve liver inflammation and fibrosis was limited to the following levels of the respective parameters: AST levels (234—264 U/l), ALT levels (208—232 U/l), TGF-β levels (1102—1265 pg/g liver tissue), hydroxyproline levels (633—719 nmol/g liver tissue), and liver fibrosis area (9.7—10.6 times for normal rat). These findings suggested that -saiko-to extract is effective in the treatment of liver inflammation and fibrosis up to a certain degree of severity, but it produces no improvement in more severe cases.

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 Chapter 1: The purpose of this study is to examine some of Okura- owned by the Tottori Domain used for shipment of rice, and to clarify the regularity of spatial structures and the effects on spatial structures by environmental conditions. Okura- subject to this study are nine "Nadaokura", and four Okura- located in the central area such as Yonago Castle and Kurayoshi Jinya-machi. Among these Okura-, the architectural remains were found only in Hashizu Okura-. However, the drawings were presented for each Okura-.
 Chapter 2: It shows past studies and procedures of the study.
 Chapter 3: It clarifies the formation of each Okura- and shows the building arrangement in a later stage of domain administration. "Nadaokura" consisted of main buildings such as Okura, Hakariya (inspection station), Bugyo-goya (station for magistrates) and Metsuke-goya (station for inspectors). In Okura- located in the central area, there were also Okura and Hakariya, however, not Bugyo-goya or Metsuke-goya necessarily. In almost all of Okura-, Okura was arranged in a form like an one-stroke sketch, located closer to the border of the site. When focusing on the location of Hakariya, there were two types of arrangement: some Hakariya were located in the garden surrounded by a group of Kura (type A) while others were located closer to the border of the site (type B). Type A accounted for most.
 Chapter 4: The type A was the spatial structures that was advantageous to conveyance of materials and to fire prevention. On the other hand, ‹Akasaki› of the type B faced the sea, and building placement had a condition for a slim site shape. ‹Iwamoto› of the type B did not have it, but was affected by the excavation of the river which was planned to prevent sedimentation of the sand caused by the sea breeze. The hakariya and storehouses of the type B had the roles that were prevented window. Also these formed a defense line on the sea side of the okura- . The above-mentioned thing became clear. Furthermore, I added consideration to the ‹Hashizu› of the type A that was a base of shipment of rice.
 Chapter 5: In conclusion, I stated that although there was a basic style for Okura- owned by the Tottori Domain, two types were formed as a result of adaptation to the site shape and special environmental condition.

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"Higan-" were very important establishments for Hie-sha Shrine in the medieval ages. However their function is unclear to us now. This paper attempts to clarify their function and character. (1) "Higan-" were administrated by priests (so called "Higan-shu") of Enryaku-ji Temple. (2) There were many manors serving "Higan-" and "Higan-e" (the Buddhist ceremony held in spring and autumn) (3) The president of Tendai-shu stayed at "Omiya Higan-" whenever he came to Hie-sha Shrine. (4) Fundamentally the purpose of "Higan-" was to be used for "Higan-e". This paper will hypothesize what kind of ceremonies were held during "Higan-e".

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The effects of a traditional Chinese medicine -saiko-to (Kampo prescription) were investigated on the various metabolic disorders and antitumor activity of recombinant human tumor necrosis factor (rhTNF) administered to mice. The glycogen level in liver of rhTNF (5×10⁴ units/mouse, i.v.)-injected mice was markedly lower at 4 h post-intoxication than that in the control, whereas the administration of rhTNF to -saiko-to (500 mg/kg/d, p.o.)-pretreated mice resulted in a greater level of glycogen than that in rhTNF alone-treated mice. In mice pretreated with -saiko-to, the level of fibrinogen 4 h after rhTNF injection markedly increased as compared to that in mice treated with rhTNF alone. We also estimated the NO^-₂ in murine macrophage cell line J774A.1 using mice serum after administration of -saiko-to. Our results clearly demonstrated that J774A.1 cells stimulated with endotoxin (1 μg/ml) and rhTNF (1×10⁴ units/ml) can effectively produce nitric oxide (NO), and ascertained the suppressive effect of -saiko-to (500 mg/kg/d, p.o.)-pretreated serum on NO generation by endotoxin/TNF-activated J774A.1 cells. When the cells were incubated with endotoxin/TNF and -saiko-to pretreated serum (10-100 μl), the NO level was significantly lower than that in control serum incubated with endotoxin/TNF alone. The effect of -saiko-to (1 and 10 μg/ml) on in vitro cytotoxicity by rhTNF in Meth-A Sarcoma cells was observed to be in a dose dependent fashion. In addition, there was a remarkable enhancement of antitumor activity of rhTNF by -saiko-to pretreatment in mice. These findings suggest that the Kampo prescription -saiko-to may protect mice from severe shock syndrome by rhTNF, and that it may enhance rhTNF-induced antitumor activity.

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High magnesian andesites from Kume-jima and Iriomote-jima, the Ryukyu islands were dated by the K-Ar method with the basalts from Kobi- and Sekibi-, the Senkaku islands. The obtained K-Ar ages of the high magnesian andesites are 6.08 ± 0.46 Ma and 13.1 ± 1.1 Ma for the sample (s) from Kume-jima and Iriomote-jima, respectively. The volcanic activity of the high magnesian andesite magma continued intermittently for at least 6 Ma. The K-Ar age of the basalt from Sekibi- is 2.59 ± 0.19 Ma. The age of the basalt lava from Kobi- is as young as 0.2 Ma or even younger, and indicates that Kobi- is a Quaternary volcano.

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-saiko-to, one of the the most frequently prescribed Kampo medicines, is used to treat chronic hepatitis and has shown confirmed clinical efficacy. The present study was performed with respect to heme metabolism to study the preventive effects of -saiko-to against endotoxemia. Endotoxin was injected intraperitoneally at a dose of 6 mg/kg into -saiko-to (500 mg/kg/d, p.o.)-pretreated rats, and its administration clearly prevented the endotoxin-induced hypoferremia. In rats pretreated with -saiko-to, the activity of hepatic δ-aminolevulinate synthetase and cytochrome P-450 level 18 h after endotoxin injection were significantly increased as compared to rats treated with endotoxin alone. Similarly, -saiko-to significantly depressed the endotoxin-induced increase in heme oxygenase activity in liver microsomes. These findings suggested that the extent of shock syndrome caused by endotoxin may be due, at least in part, to changes in heme metabolic disturbance during endotoxemia. -saiko-to may therefore protect rats against lethality caused by endotoxin through its ability to regulate the heme metabolism in septic shock.

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Background:The Yo/Yin concept is fundamental to making a Kampo () diagnosis and may be deeply related to the autonomic nervous system. There is, however, little objective data to confirm the validity of these concepts.Methods and Results:After diagnosis using standardized Kampo techniques, 20 men and 67 women (mean age, 52.4 years) for whom the prescribed Kampo medication was effective were judged to be correctly classified as Yo- (n=49) or Yin- (n=38) and enrolled. Autonomic nervous function was assessed at first visit using HRV obtained from 24-h Holter ECG. Nocturnal ultra low frequency-1 (ULF-1, 0.0001–0.0003 Hz) and ULF-2 (0.0003–0.003 Hz) were significantly higher in the Yin- than in the Yo- group (P=0.030, P=0.016), suggesting a higher variation of autonomic nervous activity according to sleep stage. On multivariate analysis BMI (≥23.0 kg/m²) and ULF-1 (≥1,150 ms²) were identified as independent factors associated with a differential diagnosis of Yo- or Yin- (odds ratio [OR], 11.63, P=0.002; OR, 0.30, P=0.038, respectively). When the sleep period was divided into 3 phases, the ULF-1 of the Yin- group was significantly higher than that of the Yo- group in the late phase of sleep (P=0.023).Conclusions:On heart rate variability analysis there was a sleep stage-related difference in the autonomic nervous activity of patients treated with standard Yo- and Yin- Kampo medicines. (Circ J 2014; 78: 1924–1927)

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Fifty-four patients with globus pharyngeus were classified by Jitsu scores and the Cornell Medical Index (CMI) health questionnaire. Three different Kampo medicines, saiboku-to (TJ-96), bukuryoin-go-hangekoboku-to (TJ-116), and kamikihi-to (TJ-137) were given, and their clinical usefulness was evaluated.
The number of patients showing Jitsu , Kyo/Jitsu Chukan , and Kyo was 9, 33, and 12, respectively. In regions I, II, III, and IV of CMI there were 16, 18, 17, and 3 patients, respectively.
The overall therapeutic efficacy was marked in 20%, moderated in 41%, and slight in 15%. TJ-116 was found to be most effective in patients with Jitsu and Kyo/Jitsu Chukan , while TJ-96 was most useful for patients with Kyo . The highest efficacy was obtained in TJ-116 for patients with regions I and II, and in TJ-96 for those with region III.

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シリコンホロファイバー膜型人工肺はガス交換能に優れ, 血液成分に及ぼす影響も少なく開心術のみならず補助循環にも応用出来る優秀な膜型人工肺であり現在まで改良を重ね報告して来た。現在多用されている気泡型人工肺は熱交換器内蔵型が一般的でありFilter及びリザーバーの役目も兼ねるなど操作構造の機能性からみれば膜型人工肺よりも優れている。しかし高令者, 重症々例が増加し, より生理的な条件での体外循環が必要となり, さらにECMOの如く補助循環として体外循環を行なうには膜型人工肺は欠くべからざるものである。我々は今回ブラウンハリソン型熱交換器を内蔵したを開発し10例に臨床応用し従来のと比較した。その結果両者にはガス交換能, 血小板数, 血漿遊離ヘモグロビン値に有意の差はなく, 熱交換率においても従来使用のdisposable熱交換器よりも優れた熱効率を示し, compactとなり操作性も向上した。

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-seiryu-to, one of the traditional Chinese medicines was used in tracheostomy patients in an attempt to eradicate methicillin-resistant Staphylococcus aureus (MRSA).

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-seiryu-to was administered to 10 patients and eliminated MRSA in 6 of these. Another study was performed to determine the anti-MRSA activity of kampo medicines. The antibacterial activity of 4 kampo medicines (

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-seiryu-to,

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-saiko-to, Juzen-taiho-to and Ninjin-yoei-to) was measured.

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-seiryu-to had an anti-MRSA effect, but the other 3 kampo meds. had no effect. Investigation of the anti-MRSA activity due to the different components of

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-seiryu-to was performed by the dilution method. Ephedra herb was effective, glucyrrhiza root, cinnamon bark, schizandra fruit, peony root and dried ginger rhizome were slightly effective; while pinellia tuber and asiasarum root were not effective.

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　高等植物の形作りの主要な場である茎頂分裂組織は胚発生の過程で作られる。我々はイネの茎頂分裂組織の形成・維持機構を明らかにするために、イネ胚発生致死突然変異体shootless2 (shl2)および幼植物体致死突然変異体shoot organization1 ()の解析を行っている。shl2変異体は胚発生の段階で茎頂分裂組織を特異的に欠失する。変異体は茎頂分裂組織を形成するがその形態は扁平で野生型に比べ未分化な細胞が占める領域が小さくなっている。また、この茎頂分裂組織の異常に伴い変異体では葉の発生も異常になると考えられている。これらの変異体から原因遺伝子の単離を行ったところ、いずれもRNA interference (RNAi)への関与が示唆される遺伝子であった。これまでRNAiは外来遺伝子に対する生物の防御機構として解析されてきた。近年、線虫などでmicroRNA (miRNA)と呼ばれる小さなRNA分子がRNAiの機構の一部を介して生成され、発生の制御にも重要な役割を果たしていることが報告されている。今回、我々はSHL2, 遺伝子とmiRNA生成との関連性について検討した結果を報告する。

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Simplified differential display of mRNA was applied to isolate and identify genes transcriptionally regulated in mouse liver by -saiko-to administration. A cDNA fragment up-regulated by -saiko-to was isolated and characterized. cDNA sequencing and subsequent database analysis revealed that the fragment showed significant sequence similarity with mouse testosterone 16-alpha-hydroxylase (cytochrome P-450_16α) cDNA. The increased level of mRNA expression of cytochrome P-450_16α in association with -saiko-to administration suggests the molecular mechanism of the chemopreventive effect of -saiko-to. This result indicates the usefulness of the mRNA differential display technique to investigate the molecular mechanism of Kampo medicine.

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