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排序方式: 共有128条查询结果,搜索用时 15 毫秒
1.
M Yamato J Ando K Sakaki K Hashigaki Y Wataya S Tsukagoshi T Tashiro T Tsuruo 《Journal of medicinal chemistry》1992,35(2):267-273
Bistropolone derivatives (4-12) containing differing lengths of linkage between the two tropolone rings were prepared and examined for their antitumor activity in in vitro (KB cell) and in vivo (leukemia P388 in mice) systems. Parent compound 3, related compounds previously prepared, and the new compounds 4-12 were evaluated for inhibitory activity against ribonucleotide reductase by indirect means to measure their effects on the dNTP pool imbalance. Present structure-activity relationship results would suggest that potently active bistropolones in vivo inhibit intracellular ribonucleotide reductase through chelating with the two irons at the two active sites of the enzyme. 相似文献
2.
Kinuko Iwasa Yumi Nishiyama Momoyo Ichimaru Masataka Moriyasu Hye-Sook Kim Yusuke Wataya Takao Yamori Turuo Takashi Dong-Ung Lee 《European journal of medicinal chemistry》1999,34(12):1077
Seventeen quaternary protoberberine alkaloids related to berberine 1 were tested for antimalarial activity in vitro against Plasmodium falciparum and structure-activity relationships are proposed. The activity of the protoberberine alkaloids was influenced by the type of the oxygen substituents on rings A, C and D and the position of the oxygen functions on ring D. The position of the oxygen functions on ring D and the type of the oxygen substituents at the C-13 position (ring C) strongly influenced the activity. Shifting the oxygen functions at C-9 and C-10 to C-10 and C-11 on ring D resulted in a significant increase in the activity. Compounds bearing a methylenedioxy function at C-2 and C-3 (ring A) or C-9 and C-10 (ring D) showed higher activity than those which have methoxy groups at the same positions. Introduction of a methoxy group into the C-1 position (ring A) decreased the activity. Replacement of a hydroxy group at C-2 or C-3 (ring A) by a methoxy group led to a reduction in the activity. Displacement of a hydroxy function at C-13 (ring C) by the oxygen substituents such as OMe, OEt, OCOOEt, and OCON(Me)2 reduced the activity. In the same replacement at C-9 (ring D), the activity depended upon the type of the oxygen function. Six protoberberines displayed more potent activity than berberine 1. The activity decreased in the order: 10, 11, 17 and 18 > 7 and 8 > 1. 相似文献
3.
Setsuo Takeda Jun-ichi Yamashita Hitoshi Saito Junji Uchida Hiroyasu Satake Yuji Yamada Norio Unemi Yusuke Wataya Hikoya Hayatsu 《Cancer chemotherapy and pharmacology》1991,29(2):122-126
Summary 1-(3-O-Benzyl-2-deoxy--d-ribofuranosyl)-5-trifluoromethyl-2,4(1H,3H)-pyrimidinedione (FTC-092), a fluorinated pyrimidine derivative, appeared to be effective against various transplantable tumors in mice following oral administration, and its activity was superior to that of several other antitumor fluorinated pyrimidines. The ED50 value for FTC-092 the dose effective in achieving 50% inhibition of tumor growth against the solid form of sarcoma 180 was 13.3 mg/kg daily, whereas those for 5-trifluoromethyl-2-deoxyuridine (CF3dUrd), the parent compound of FTC-092, for 1-(2-tetrahydrofuryl)-5-fluorouracil (Tegafur, FT), the prodrug of 5-fluorouracil (FUra), and for FUra were 64.1, 122, and 28 mg/kg daily, respectively. The therapeutic indices (LD10/ED50) of FTC-092, CF3dUrd, FT, and FUra were 4.39, 1.7, 1.35, and 1.65, respectively. FTC-092 itself is not an active agent. After it has been absorbed from the gastrointestinal tract, FTC-092 undergoes a gradual biotransformation, mainly via the action of liver microsomes, releasing CF3dUrd over a long period. The levels of CF3dUrd in the stomach and small intestine of mice after the oral administration of FTC-092 were undetectable, whereas those following the administration of CF3dUrd at the same dose were high for a period of several hours. In contrast, the CF3dUrd level generated in plasma after the administration of FTC-092 remained at a high level for a longer period than did that observed on the administration of CF3dUrd. The low levels of CF3Urd measured in stomach and small-intestine tissues and the maintenance of CF3dUrd in blood over long periods after the administration of FTC-092 are features that favor the possible clinical application of FTC-092.Abbreviations used FTC-092
1-(3-O-benzyl-2-deoxy--d-ribofuranosyl)-5-trifluoromethyl-2,4(1H,3H)-pyrimidinedione
- CF3dUrd
5-trifluoromethyl-2-deoxynridine
- FT
1-(2-tetrahydrofuryl)-5-fluorouracil
- FUra
5-fluorouracil
- F3Thy
5-trifluorothymine
- ILS
increase in life span 相似文献
4.
Osaki S Nakanishi Y Wataya H Takayama K Inoue K Takaki Y Murayama S Hara N 《Respiration; international review of thoracic diseases》2000,67(4):412-416
BACKGROUND: Bronchial artery embolization (BAE) is a well-accepted and widely used treatment modality for the management of massive and recurrent hemoptysis. However, few reports have previously investigated the long-term results. OBJECTIVES: To investigate the prognosis of patients with hemoptysis who had undergone BAE. METHODS: Twenty-two patients with hemoptysis underwent BAE. The underlying diseases included bronchiectasis in 9, aspergillosis in 3, chronic bronchitis in 2, idiopathic bronchial bleeding in 4, and other diseases in 4. The follow-up period ranged from 25 to 88 months (median 47 months). RESULTS: After the initial BAE, 11 of 22 (50%) patients had re-bleeding (5 patients with hemoptysis and 6 patients with minor hemosputa). Among them, 1 patient suffered from recurrent massive hemoptysis and died from airway obstruction within 1 month after BAE. In addition, 10 of these 11 (90.9%) patients experienced recurrent airway bleeding within 3 years after BAE. Recurrent cases of hemoptysis were seen in 6 of 22 patients (27.3%) within 3 years and no case recurred later than 3 years after BAE. A recurrence of hemoptysis was frequently seen in patients with either bronchiectasis or pulmonary-bronchial artery (P-B) shunt. Although BAE is an effective treatment for the immediate control of hemoptysis, 5 of the patients experienced recurrent bleeding in the long-term follow-up. CONCLUSIONS: It is important to follow-up such patients until 3 years after initial BAE, especially when either ectatic changes of the bronchi on a CT scan or a P-B shunt on angiographic findings are detected. 相似文献
5.
Keisuke Endo Takayuki Miki Takahito Itoh Hirofumi Kubo Ryosuke Ito Kouhei Ohno Hiroyuki Hotta Nobuo Kato Tomoaki Matsumoto Aya Kitamura Mai Tamayama Takako Wataya Ayaka Yamaya Rei Ishikawa Hitoshi Ooiwa 《Internal medicine (Tokyo, Japan)》2022,61(1):37
Objective In this study, we investigated whether and how the COVID-19 pandemic affected glycemic control and blood pressure (BP) control in patients with diabetes mellitus (DM). Methods DM patients whose HbA1c level was measured regularly before and after the declaration of a state of emergency were included in this study. Some patients were given questionnaires about changes in their lifestyle to determine the factors affecting glycemic control and BP control. Results The median HbA1c level of the 804 patients increased significantly from 6.8% before the state of emergency to 7.1% and 7.0% during and after the state of emergency, respectively. This was in contrast to the decrease one year earlier due to seasonal variations. In the 176 patients who responded to the questionnaire, the HbA1c level also increased significantly during and after the state of emergency. The worsening of glycemic control was more pronounced in the group that had achieved HbA1c of <7% before the state of emergency than in those with higher values. Unlike the rise in HbA1c, the BP did not rise during the state of emergency but did rise significantly afterwards. There was no marked decrease in HbA1c or BP after the state of emergency, even in patients who responded that they were much more careful with their diet, ate less, or exercised more. Conclusions The COVID-19 pandemic worsened glycemic control and BP control, even in patients who perceived no marked change in their diet or exercise, suggesting that more active lifestyle guidance is necessary for good treatment of DM patients. 相似文献
6.
7.
Chai JY Park YK Guk SM Oh KH Oh MD Lee SH Kim HS Wataya Y 《The American journal of tropical medicine and hygiene》2000,63(1-2):80-84
The polymerase chain reaction-based microtiter plate hybridization (PCR-MPH) assay was utilized for a DNA diagnosis of Plasmodium vivax malaria, which has recently reemerged in the Republic of Korea. The subjects were 18 parasite-proven patients and 5 healthy controls. Follow-up blood samples were collected from 4 patients after a standard course of treatment. Polymerase chain reaction and electrophoresis of all the patients' blood showed a prominent band at the 138 base pair area, but not in the controls or after treating the patients. Hybridization of the PCR products with known species-specific probes of the 18S rRNA of various malaria species revealed strong positive reactions against the Plasmodium vivax-specific probe (absorbance 1.30-1.90 at 405 nm) in all of the patients. The absorbance was positively correlated with the degree of blood parasitemia, but with a borderline significance. Sequencing of the probe region of the Korean P. vivax revealed no significant variations from the typical P. vivax. The results show that the PCR-MPH is a highly useful technique for the DNA diagnosis of Korean vivax malaria. 相似文献
8.
Perry G Nunomura A Cash AD Taddeo MA Hirai K Aliev G Avila J Wataya T Shimohama S Atwood CS Smith MA 《Journal of neural transmission. Supplementum》2002,(62):69-75
Over the past decade, oxidative stress has been established as the earliest cytological feature of Alzheimer disease and an attractive therapeutic target. The major challenges now are establishing the source of the reactive oxygen and what oxidative stress tells us about the etiology of Alzheimer disease. These are complex issues since a variety of enzymatic and non-enzymatic processes are involved in reactive oxygen formation and damage to macromolecules. In this review, we consider disease mechanisms that show the greatest promise for future research. 相似文献
9.
Ishikawa M Matsuura T Okuaki T Imai Y Tsukamoto A Ide T Shinohara F Miyazaki S 《Nihon Hoshasen Gijutsu Gakkai zasshi》2002,58(8):1091-1100
X-ray equipment has seen advances in inverters and the digitalization of reception systems. The X-ray Systems Study Group, in order to examine changes in the conditions of radiography, including pediatric radiography, variations in shortest irradiation time, and standardization of the conditions of radiography, carried out investigative research using a questionnaire survey that was sent to 400 facilities. The recovery rate was 33%. In terms of the reception system, half of the general radiography systems were using computed radiography (CR). Seventy percent of respondents used an intensifying screen and film(S EF)in stomach double-contrast radiography. About 80% used digital radiography (DR) and digital subtraction angiography (DSA) in aorta abdominalis angiography. At least 70% of high-voltage generators were of the inverter type. The conditions of radiography were not greatly influenced by changes in reception systems and X-ray equipment. Many pediatric radiographies were carried out by radiological technologists. We consider it useful to conduct such survey investigations. 相似文献
10.
Oxidative damage is the earliest event in Alzheimer disease 总被引:32,自引:0,他引:32
Nunomura A Perry G Aliev G Hirai K Takeda A Balraj EK Jones PK Ghanbari H Wataya T Shimohama S Chiba S Atwood CS Petersen RB Smith MA 《Journal of neuropathology and experimental neurology》2001,60(8):759-767
Recently, we demonstrated a significant increase of an oxidized nucleoside derived from RNA, 8-hydroxyguanosine (8OHG), and an oxidized amino acid, nitrotyrosine in vulnerable neurons of patients with Alzheimer disease (AD). To determine whether oxidative damage is an early- or end-stage event in the process of neurodegeneration in AD, we investigated the relationship between neuronal 8OHG and nitrotyrosine and histological and clinical variables, i.e. amyloid-beta (A beta) plaques and neurofibrillary tangles (NFT), as well as duration of dementia and apolipoprotein E (ApoE) genotype. Our findings show that oxidative damage is quantitatively greatest early in the disease and reduces with disease progression. Surprisingly, we found that increases in A beta deposition are associated with decreased oxidative damage. These relationships are more significant in ApoE epsilon4 carriers. Moreover, neurons with NFT show a 40%-56% decrease in relative 8OHG levels compared with neurons free of NFT. Our observations indicate that increased oxidative damage is an early event in AD that decreases with disease progression and lesion formation. These findings suggest that AD is associated with compensatory changes that reduce damage from reactive oxygen. 相似文献