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31.
E Ohshima H Takami H Sato S Mohri H Obase I Miki A Ishii S Shirakura A Karasawa K Kubo 《Journal of medicinal chemistry》1992,35(18):3402-3413
A series of 11-[2-(1-benzimidazolyl)ethylidene]-6,11-dihydrodibenz[b,e]oxep in-2- carboxylic acid derivatives and related compounds were synthesized and found to be potent TXA2/PGH2 receptor antagonists. Each compound synthesized was tested for its ability to displace [3H]U-46619 binding from guinea pig platelet TXA2/PGH2 receptors. Structure-activity relationship studies revealed that the following key elements were required for enhanced activities: (1) an (E)-2-(1-benzimidazolyl)ethylidene side chain in the 11-position of the dibenzoxepin ring system and (2) a carboxyl group in the 2-position of the dibenzoxepin ring system. The studies also indicated that the TXA2/PGH2 receptor binding affinities of this series of compounds in guinea pig platelet were poorly correlated with those in human platelet. Introduction of substituent(s) to the benzimidazole moiety was effective and sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl)ethylidene]- 6,11-dihydrodibenz[b,e]oxepin-2-carboxylate monohydrate (57) recorded the highest affinity for human platelet TXA2/PGH2 receptor with a K(i) value of 1.2 +/- 0.14 nM. It demonstrated potent inhibitory effects on U-46619-induced guinea pig platelet aggregation (in vitro and ex vivo) and human platelet aggregation (in vitro). Compound 57, now designated as KW-3635, is a novel, orally active, and specific TXA2/PGH2 receptor antagonist with neither TXA2/PGH2 receptor agonistic nor TXA2 synthase inhibitory effects. It is now under clinical evaluation. 相似文献
32.
Eiji Fukuyama Susumu Omura Kiyohide Fujita Kunimichi Soma Katsuyuki Torikai 《The Cleft palate-craniofacial journal》2006,43(6):673-677
OBJECTIVE: This article reports a case of bilateral cleft lip and alveolus (BCLA) for which excessive rapid palatal expansion with a Latham appliance was performed for preoperative alignment of the protruded premaxilla. Postoperative changes of maxillary width were investigated with serial plaster casts. PATIENT AND RESULTS: A 3-month-old girl presented with complete BCLA in which the premaxilla was markedly protruded. Preoperative alignment of the protruded premaxilla with a Latham appliance was planned to facilitate primary lip repair. The appliance was placed when the patient was 4.5 months old. The necessary palatal expansion was estimated to be 7.0 mm in order to move the premaxilla backward into the ideal position. After palatal expansion and posterior repositioning of the protruded premaxilla, the primary operation, including cheiloplasty and gingivoperiosteoplasty, was performed when the patient was 7 months old. Excessive maxillary expansion might be a cause of transverse maxillomandibular discrepancy. Measurement with serial plaster casts demonstrated that maxillary widths increased from 42.3 mm pretreatment to 49.0 mm after orthopedic treatment but relapsed markedly to 43.5 mm at 3 months after the primary operation. Therefore, the net change of maxillary widths was only 1.2 mm. After alignment of the protruded premaxilla, tension-free soft tissue repairs were performed, and a harmonious alveolar arch was obtained without change in maxillary width. CONCLUSION: These results indicate that this method is useful for preoperative management of BCLA with protruded premaxilla. 相似文献
33.
Kazuhiko Suzuki Hiroshi Tanaka Satoshi Kaneko Motoi Nishi Shin Teramoto Susumu Itoh Shosaku Abe 《The Journal of asthma》2003,40(3):243-250
The relation between smoking and risk of asthma has been well-examined; however little attention has been paid to the correlation between smoking and asthma symptoms. The aims of this study were to examine respiratory symptoms in asthmatics with a highly prevalent use of inhaled corticosteroid (ICS) and to assess the effects of smoking and its cessation. A cross-sectional study of pulmonologist-based 3197 asthmatics (men 45.2%, ages 20-97) was performed using a questionnaire about smoking habits, the incidence and frequency of symptoms (sputum, cough and wheezing, night symptoms, and shortness of breath), physical activity interference, and medication. Although 81.4% of the patients used ICS according to the international guideline, 14.9% had activity interference, and daily symptoms remained in 43.3%. At the time of the questionnaire, 21.6% were current and 25.1% were ex-smokers. In multiple logistic regression analysis, the factors of significance (p < 0.0001) were (1) smoking; for all four symptoms, (2) age and duration of asthma; for shortness of breath. Current smokers were at a risk of sputum (age-adjusted odds ratio 2.32 [95% confidence interval 1.73-3.11]; 2.09 [1.57-2.79]), of cough and wheezing (2.38 [1.81-3.14]; 1.78 [1.35-2.36]), of night symptoms (1.95 [1.41-2.60]; 1.47 [1.09-1.98]), and of shortness of breath (1.70 [1.26-2.28]; 1.30 [0.97-1.75]) in men and women, respectively. These ratios in ex-smokers decreased to the level similar to nonsmokers. Although 81.4% of asthmatic patients used ICS, 43.3% complained of daily respiratory symptoms, especially sputum. It is suggested that the effects of ICS on asthma symptoms may be interfered with by smoking and therefore more emphasis should be placed on cessation of smoking. 相似文献
34.
Itsuro Tomita Katsuya Sato Susumu Shirabe Kunihiko Nagasato Akira Satoh Mitsuhiro Tsujihata 《Clinical neurology》2004,44(3):182-186
Serial DWIs were performed in a patient with CJD who developed symptoms acutely and progressed rapidly. DWI discloed an increased signal in the frontal and parietal inner cortical areas, and in the caudate nuclei and putamina 20 days after the onset of symptoms. T2-weighted images showed only signal abnormality in the caudate nuclei and putamina, but not in the cerebral cortex. In the CSF obtained 15 days after the onset of symptoms, total tau protein was markedly elevated and 14-3-3 protein was positive. Measurement of these proteins are highly specific and sensitive for the diagnosis of CJD, but not available as a rapid routine examination at present. DWI is not specific, but useful for making the diagnosis of CJD in the early stage of the disease. 相似文献
35.
Serial in vivo MR tracking of magnetically labeled neural spheres transplanted in chronic EAE mice. 总被引:5,自引:0,他引:5
Tamir Ben-Hur Ruud B van Heeswijk Ofira Einstein Michal Aharonowiz Rong Xue Emma E Frost Susumu Mori Benjamin E Reubinoff Jeff W M Bulte 《Magnetic resonance in medicine》2007,57(1):164-171
Neural stem cell (NSC) transplantation has been shown to attenuate the severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Central to the future success of NSC transplantation in MS is the ability of transplanted cells to migrate from the site of transplantation to relevant foci of disease. Using magnetically labeled mouse neurospheres and human embryonic stem cell (hESC)-derived neurospheres, we applied serial magnetic resonance imaging (MRI) to assess the biodynamics of transplanted cell migration in a chronic mouse EAE model. Magnetic labeling did not affect the in vitro and in vivo characteristics of cells as multipotential precursors. Cell migration occurred along white matter (WM) tracts (especially the corpus callosum (CC), fimbria, and internal capsule), predominantly early in the acute phase of disease, and in an asymmetric manner. The distance of cell migration correlated well with clinical severity of disease and the number of microglia in the WM tracts, supporting the notion that inflammatory signals promote transplanted cell migration. This study shows for the first time that hESC-derived neural precursors also respond to tissue signals in an MS model, similarly to rodent cells. The results are directly relevant for designing and optimizing cell therapies for MS, and achieving a better understanding of in vivo cell dynamics and cell-tissue interactions. 相似文献
36.
In order to investigate the comparative fates of nivalenol (NIV) and 4-acetyl derivative of NIV (fusarenon-X, FX) in mice, 3H-FX or 3H-NIV was given p.o. to mice. Radioactivity was excreted mainly via the urine in mice given 3H-FX, but mainly via the feces in mice given 3H-NIV. The plasma radioactivity reached a peak at 30 or 60 min after the administration of 3H-FX or 3H-NIV, respectively. The plasma peak level was 5 times higher, and the area under curve (AUC) was 10 times higher, in 3H-FX-administered than 3H-NIV-administered mice. These findings clearly demonstrate that FX is absorbed from the gastrointestinal tract more rapidly and efficiently than NIV. The HPLC profile of radioactivity of acetonitrile extracts of urine and feces indicated that FX is rapidly metabolized to NIV after being absorbed from the gastrointestinal tract. In vitro incubation of tissue homogenates with 3H-FX demonstrated that the liver and kidney are the organs responsible for the FX-to-NIV conversion. Thus this study demonstrated that the higher oral toxicity of FX than NIV that has been observed in mice and rats is due to the efficient absorption of FX than NIV from the gastrointestinal tract, followed by its rapid conversion to NIV by the liver and kidney. 相似文献
37.
Koichi Nishimura Takashi Hajiro Toru Oga Mitsuhiro Tsukino Susumu Sato Akihiko Ikeda 《The Journal of asthma》2005,41(2):141-146
Simple and concise measures for health status are desirable in clinical practice. The Asthma Bother Profile (ABP), which consists of 23 items, has been developed to assess how much asthma bothers patients. The Airways Questionnaire 20 (AQ20) is a simple instrument which consists of 20 items. The purpose of this study was to investigate how the ABP and AQ20 evaluate the health status of patients with asthma. A total of 166 patients with chronic asthma (age: 48 ± 16 yr, 77 males) completed pulmonary function testing, measurement of airway hyperresponsiveness, dyspnea rating, assessments of their anxiety and depression (HADS; Hospital Anxiety and Depression Scale), and assessments of their health status. The health status was assessed using the ABP, AQ20, the short-form 36 health survey questionnaire (SF-36), the Living With Asthma Questionnaire (LWAQ) and the Asthma Quality of Life Questionnaire (AQLQ). The Japanese version of the ABP included only 15 'bother' items out of the original 23 items due to cultural differences. The scores on the ABP were widely distributed, whereas the scores on the AQ20 were skewed towards the milder end of the scale. The ABP had a strong correlation with the Avoidance and Distress constructs on the LWAQ, and Anxiety and Depression on the HADS (Rs = 0.56 ∼ 0.79), and its strongest correlation with the General Health (Rs = - 0.64) scale among the 8 subscales on the SF-36. The AQ20 had a less significant correlation with the LWAQ, AQLQ, and SF-36 than the ABP. The ABP and AQ20 were short and simple to complete, and both measures could easily be used in clinical practice. The ABP can evaluate patients more specifically with respect to distress and bother than the AQ20. 相似文献
38.
Hiroko Sasahara Susumu Sueyoshi Toshiaki Tanaka Hiromasa Fujita Kazuo Shirouzu 《The Japanese Journal of Thoracic and Cardiovascular Surgery》2004,52(5):231-239
Objective: The purpose of this experimental study was to investigate whether aortic stent grafting can be applied to the treatment of
an esophageal cancer involving the thoracic aorta. Methods: The canine thoracic aorta was partially resected without aorta being clamped after emplacement of an endovascular stent graft.
Study I; The aortic whole layer of 1 cm in length and 1/4 of the circumference was resected and was covered by a free fascia
patch of the abdominal rectal muscle immediately after stent graft placement. Study II; The aortic adventitia and the outer
half of the media of the same size was resected on day 3, 7,14, 21, and on day 28, after the stent graft placement. The resected
portion was covered by the free fascia patch in half experimental dogs, and was uncovered in the others. Study III; The aortic
adventitia and the outer half of the media of 1 cm in length and 1/2 of the circumference was resected and was uncovered on
day 7 after stent graft placement. Histological examinations were performed on day 28 and at one year after aortic resection.
Results: The aortic wall could be resected in all cases with no complication, except in resection of 1/2 the circumference where the
aorta had become narrow. There was no difference in healing of the resected portion of the aorta between with and without
fascia covering. Conclusion: An aortic endovascular stent graft could be applied to surgery for an esophageal cancer involving the aorta. 相似文献
39.
The anisotropy of the water diffusion tensor inside brain causes contrast in diffusion images, which depends on the relative orientation of the diffusion gradients and the subject. Because the trace of a tensor is invariant upon rotation, measurement of this trace can reduce the orientation effect. A family of imaging pulse sequences is presented in which the signal intensity is weighted by the trace of the diffusion tensor in a single scan. The methods are demonstrated for chicken gizzard in several orientations with respect to the gradient frame of reference, and for ischemic injury in cat brain after middle cerebral artery occlusion. The sensitivity of the techniques to the presence of background gradients is measured and discussed in detail. As a result, pulse sequences are suggested that provide reliable diffusion constants in both homogeneous and inhomogeneous magnetic fields. The efficiency of the techniques for clinical application is also evaluated. 相似文献
40.
Shiro Nakaike Takehiro Yamagishi Kazunori Samata Keiko Nishida Kouko Inazuki Tomoko Ichihara Yoshihiro Migita Susumu Otomo Hironaka Aihara Shigeru Tsukagoshi 《Cancer chemotherapy and pharmacology》1989,23(3):135-139
Summary A novel antitumor compound, N--dimethylaminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]-phenazine-6-carboxamide sodium salt (NC-190) was evaluated for its antitumor activity in experimental murine tumor systems. In the initial studies with P388 leukemia (i.p.-i.p.), NC-190 led to an increase of >200% in life span (ILS), and 75% of the mice were alive on day 30, when the optimal dose (50 mg/kg, days 1–5) was given. Additionally, the compound had significant activities against i.p. inoculated mouse L1210 leukemia, B16 melanoma, M5076 reticulum cell sarcoma, sarcoma 180, mouse hepatoma MH134, and rat Yoshida sarcoma and Yoshida ascites hepatoma AH130. The optimal dose resulted in a >280% ILS with a 30-day survival of 50% in mice with L1210 leukemia (100 mg/kg, days 1–5), a 156% ILS in mice with B16 melanoma (50 mg/kg, days 1–5), a 98% ILS with a 90-day survival of 25% in mice with M5076 reticulum cell sarcoma (25 mg/kg, days 1, 5, 9, and 13), a >300% ILS with a 60-day survival of 50% in mice with sarcoma 180 (50 mg/kg, days 3–10), a 148% ILS with a 60-day survival of 25% in mice with MH134 (25 mg/kg, days 1–5), a 129% ILS with a 60-day survival of 12.5% in rats with Yoshida sarcoma (12.5 mg/kg, day 3–10), and a >161% ILS with a 60-day survival of 50% in rats with AH130 (6.3 mg/kg, days 3–10). In the experiments with s.c. inoculated tumors, NC-190 not only inhibited tumor growth, but also increased the life span of mice with Lewis lung carcinoma or B16 melanoma. The 60-day survivors accounted for 60% and 30% in mice with Lewis lung carcinoma and B16 melanoma, respectively. The compound significantly inhibited the spontaneous lung metastasis of Lewis lung carcinoma by more than 90% when eight daily i.v. injections were given. NC-190 was active by the i.p., s.c., and i.v. routes. Five consecutive daily i.p. doses (days 1–5) were more effective than a single dose (day 1), two doses (days 1 and 5), or three doses (days 1, 5, and 9). NC-190 warrants further study as a potential antineoplastic agent against human neoplasms, as it has a broad spectrum of antitumor activity and inhibits metastasis.Abbreviations
ILS
increase in life span
-
MST
median survival time
-
MMC
mitomycin C
-
ADM
adriamycin
-
CPA
cyclophosphamide
-
5-FU
5-fluorouracil 相似文献