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41.
Covalent binding of rofecoxib, but not other cyclooxygenase-2 inhibitors, to allysine aldehyde in elastin of human aorta. 总被引:1,自引:0,他引:1
Masataka Oitate Takashi Hirota Takahiro Murai Shin-Ichi Miura Toshihiko Ikeda 《Drug metabolism and disposition》2007,35(10):1846-1852
In rats, it has been reported that rofecoxib, a cyclooxygenase-2 (COX-2) inhibitor, reacts with the aldehyde group of allysine in elastin to give a condensation covalent adduct, thereby preventing the formation of cross-linkages in the elastin and causing degradation of the elastic fibers in aortas in vivo. Acid, organic solvent, and proteolytic enzyme treatments of human aortic homogenate after incubation with [(14)C]rofecoxib demonstrated that most of the radioactivity is covalently bound to elastin. The in vitro covalent binding was inhibited in the presence of beta-aminopropionitrile, D-penicillamine, and hydralazine, which suggested that the aldehyde group of allysine in human elastin was relevant to the covalent binding. The in vitro covalent binding of [(14)C]rofecoxib was significantly decreased by the addition of only nonradiolabeled rofecoxib but not the other COX-2 inhibitors, celecoxib, valdecoxib, etoricoxib, and CS-706 [2-(4-ethoxyphenyl)-4-methyl 1-(4-sulfamoylphenyl)-1H-pyrrole], a novel selective COX-2 inhibitor. All the above COX-2 inhibitors except for rofecoxib had no reactivity with the aldehyde group of benzaldehyde used as a model compound of allysine aldehyde under a physiological pH condition. On the other hand, no retention of the radioactivity of [(14)C]rofecoxib was observed in human aortic endothelial cells in vitro, suggesting that rofecoxib is not retained in aortic endothelial cells in vivo. These results suggest that rofecoxib, but not other COX-2 inhibitors, is capable of covalently binding to the aldehyde group of allysine in human elastin. This might be one of the main causes of cardiovascular events by rofecoxib in clinical situations. 相似文献
42.
Mitsuo Miyazawa Takahiro Torii Yasuko Toshimitsu Katsuya Okada Isamu Koyama Yoshito Ikada 《American journal of transplantation》2005,5(6):1541-1547
The aim of this study was to fabricate an artificial bile duct for the development of a new treatment for biliary diseases. Eighteen hybrid pigs were implanted with a bile duct organoid unit (BDOU) made of a bioabsorbable polymer. Twelve of the transplanted BDOUs had been seeded with autologous bone marrow cells (BMCs) in advance. Six animals, the controls, were grafted with the scaffold alone with no BMCs seeded. The common bile duct was cut, the hepatic cut end of the native common bile duct was anastomosed to the BDOU and the other end was anastomosed to the duodenum. The controls underwent a similar operation. The neo-bile duct was removed at pre-determined time points and investigated histologically. All 18 recipient pigs survived until their sacrifice at 6 weeks, 10 weeks or 6 months. Histological examination revealed incomplete epithelialization of the neo-bile duct at 6 weeks and 10 weeks after transplantation. At 6 months, the organoid exhibited a morphology almost identical to that of the native common bile duct. No differences were found between the controls and BMC-seeded pigs. These results show that the artificial bile duct thus fabricated can serve as a substitute for the native bile duct. 相似文献
43.
Yasushi Sano Hirohisa Machida Kuang‐I. Fu Hiroaki Ito Takahiro Fujii 《Digestive endoscopy》2004,16(Z1):S93-S96
The goal of endoscopic mucosal resection (EMR) is to allow the endoscopist to obtain tissue or resect lesions not previously amenable to standard biopsy or excisional techniques and to remove malignant lesions without open surgery. In this article, we describe the results of conventional EMR and EMR using an insulation‐tipped (IT) electrosurgical knife (submucosal dissection method) for large colorectal mucosal neoplasms and discuss the problems and future prospects of these procedures. At present, conventional EMR is much more feasible than EMR using IT‐knife from the perspectives of time, money, complication, and organ preservation. However, larger lesions tend to be resected in a piecemeal fashion; and it is difficult to confirm whether EMR has been complete. For accurate histopathological assessment of the resected specimen en bloc EMR is desirable although further experience is needed to establish its safety and efficacy. Further improvements of in EMR with special knife techniques are required to simply and safely remove large colorectal neoplasms. 相似文献
44.
Hiroyuki Oka Taiji Kondoh Atsushi Seichi Takahiro Hozumi Kozo Nakamura 《Journal of orthopaedic science》2006,11(1):13-19
Background Few previous studies have analyzed the incidence of bone metastases in a defined population of Japanese breast cancer patients
and their prognosis after chemotherapy.
Methods This is a retrospective cohort study. We investigated 695 patients who underwent surgery for breast cancer. The strategy of
adjuvant therapy was as follows. Patients with both estrogen receptors (ERs) and progesterone receptors (PgRs) had endocrine
therapy as initial adjuvant therapy (n = 239). Patients with neither ERs nor PgRs had chemotherapy. When metastasis to other organs, including bone, was identified,
patients received chemotherapy. The survival rates after surgery and after the onset of bone metastasis, as well as the incidence
of bone metastasis, were calculated. We also evaluated the prognostic and predictive factors.
Results Bone metastases developed in 148 of 695 patients. All 148 received chemotherapy, and 121 of them developed spinal metastases.
The 5-year survival rate after bone metastases was 26.1%. Prognostic factors for bone metastases were visceral metastases
and PgR status. Cord compression was observed in 17 of the 148 patients, with the thoracic spine being the most common. The
1-year survival rate for patients with bone metastases who received chemotherapy was 66.3%, whereas that of patients with
paralysis after spinal metastases was 17.6%. Within 6 months of the development of spinal cord compression, 70.6% of the patients
died.
Conclusions We reported the incidence and prognostic factors for a defined population of Japanese breast cancer patients with bone and
spinal metastases. Our results suggest that the expected survival time for patients with paralysis who received adequate endocrine
therapy or chemotherapy is generally poor. However, to detect a predictive factor of long survival after paralysis and establish
the indications for surgery, a comparative study among large groups of patients with paralysis and with different backgrounds
is necessary. 相似文献
45.
Takahiro Narishige Kensuke Egashira M.D. Yutaka Akatsuka Teisuke Takahashi Akira Takeshita 《Cardiovascular and interventional radiology》1993,16(6):343-347
The effects of an intracoronary administration of iomeprol, a new nonionic tri-iodinated water-soluble contrast medium, on
coronary circulation were compared to those of iopamidol and those of nitroglycerin in 6 chronically instrumented conscious
dogs. A pair of 10 MHz piezoelectric crystals and an electromagnetic flow probe were placed on the left circumflex coronary
artery (LCCA) to measure the epicardial coronary diameter (CD) and coronary blood flow (CBF). Polyethylene tubing for drug
administration was inserted into the LCCA proximal to the sonomicrometers. Iomeprol at the dose of 1 ml and 3 ml/min for 1
min significantly increased CD by 0.6±0.1% and 1.4±0.3%, respectively and CBF by 44.5±9% and 70±10%, respectively. Iopamidol
at the same rates also significantly increased CD by 0.8±0.1% and 1.5±0.3% and CBF by 50±11% and 82±14%, respectively. There
was no statistically significant difference between iomeprol-and iopamidol-induced increases in CD and CBF. However, the duration
of the increase in CD was significantly shorter (p<0.05) after iomeprol than after iopamidol. Nitroglycerin (10 μg/kg) significantly increased CD by 4.5±1% and CBF by 105±10%.
The increases in CD and CBF in response to iopamidol and iomeprol were significantly smaller (p<0.01) than to nitroglycerin. We conclude that vasodilating effects of iomeprol and iopamidol on the large epicardial coronary
artery and coronary blood flow are comparable in conscious dogs and significantly lower than after nitroglycerin in the doses
used by us.
This study was supported by a grant from the EI-ZA1 Pharmaceutical Co., Tokyo, Japan. 相似文献
46.
Magnetic resonance imaging (MRI) has greatly facilitated morphologic evaluation of spinal cord lesions. Eleven cases representative of inflammatory, demyelinating, neoplastic and vascular diseases, are presented which illustrate and summarize important abnormal features in spinal cord imaging, particularly MR findings. Recently, specialised techniques such as MR angiography, fat-inhibiting methods, dynamic MRI and functional imaging have been developed. These methods have facilitated not only lesion diagnosis but also qualitative assessment, and are being used to analyze pathophysiology. Comprehensive diagnoses based on such modalities may be important in determining indications for surgery or defining the extent of surgery or the intensity of other treatments. 相似文献
47.
Takahiro Nishida Hisanori Mayumi Yoshito Kawachi Shigehiko Tokunaga Yoshiyuki Maruyama Atsuhiro Nakashima Hisataka Yasui Kouichi Tokunaga 《Surgery today》1994,24(7):651-654
A case of active prosthetic valve infective endocarditis (PVE) due toCandida glabrata was successfully treated by the systemic administration of fluconazole. A 66-year-old Japanese man with infective endocarditis of unknown etiology underwent aortic and mitral valve replacement to treat severe aortic and mitral regurgitation associated with multiple organ failure. Postsurgical cultures of arterial blood were repeatedly positive forC. glabrata, and therefore fluconazole was administered either intravenously or orally at a dose of 400 mg/day for 46 days. During that time the signs of inflammation including fever such as an elevated white blood cell count and the presence of C-reactive protein (CRP) all improved while the blood cultures became negative. Fluconazole is thus considered to be effective in treating PVE caused byC. glabrata. When administering this treatment, it is also important to monitor the patient's renal and liver function. 相似文献
48.
Tadaki Yasumura MD Toshikazu Akami Manabu Mitsuo Takahiro Oka Kazuo Naitoh Takara Yamamoto Hideo Honjyo Hiroji Okada 《Surgery today》1990,20(4):369-375
The ovarian and pituitary functions of 64 operable breast cancer patients undergoing adjuvant therapy with cytotoxic chemotherapy
and/or tamoxifen were investigated. The post menopausal patients, divided into 3 treatment groups, one with tamoxifen alone,
one with tamoxifen and chemotherapy and the other with chemotherapy alone had serum estradiol 17-β (E2) and progesterone levels
lower than the evaluable limits. Although there was no significant difference in the level of estrone sulfate (E1-S) between
these three groups, the level of lutainizing hormone (LH) and follicle stimulating hormone (FSH) in the patients treated with
tamoxifen alone and tamoxifen and chemotherapy were significantly lower than those treated with chemotherapy alone. The decrease
in gonadotropin levels induced by tamoxifen treatment was reversible as it appeared after the initiation of tamoxifen and
recovered after its cessation. In the premenopausal patients, a group treated with tamoxifen and chemotherapy had significantly
higher E1-S, E2 and progesterone levels and significantly lower gonadotropin levels than a group treated with chemotherapy
alone or one treated with a cyclophosphamide regimen. These increases in the levels of estrogen and progesterone were also
reversible, and induced by tamoxifen. Thus, adjuvant endocrinochemotherapy causes profound alteration in the hypothalamo-pituitary-ovarian
axis and therefore, monitoring a variety of hormonal levels is thought to be necessary for assessing the consequences of adjuvant
therapy in breast cancer patients, especially in premenopausal patients using tamoxifen. 相似文献
49.
Yoshito Matsui Tomoatsu Kimura Noriyuki Tsumaki Haruhiko Nakahara Nobuhito Araki Natsuo Yasui Takahiro Ochi 《Journal of orthopaedic science》1996,1(2):130-135
Recent DNA studies performed by several groups have detected mutations of the gene encoding fibroblast growth factor receptor
3 (FGFR3) in patients with achondroplasia-group disorders, including achondroplasia (ACH), hypochondroplasia (HCH), and thanatophoric
dysplasia (TD). For this study, we analyzed theFGFR3 gene in 31 Japanese patients with typical ACH, four with HCH, three with a condition intermediate between ACH and HCH (ACH/HCH-intermediate),
and one with TD. Of the 31 typical ACH patients, 29 showed a G1138 to A transition and the other two a G1138 to C transversion,
both resulting in a common Gly380Arg substitution in the transmembrane domain of FGFR3. The one TD and the four HCH patients
did not display any mutations in the transmembrane domain of FGFR3. Of the three ACH/HCH-intermediate cases, one patient showed
the Gly380Arg substitution and one did not, and further analysis of the second patient revealed the presence of Asn540Lys
substitution. The first patient was, therefore, genotypically diagnosed as ACH and the second as HCH. Peripheral blood leukocyte
DNA analysis in the remaining ACH/HCH-intermediate patient indicated an unequal ratio of mutant to normal PCR products, possibly
representing a somatic mosaic for the Gly380Arg mutation. Analysis of the common FGFR3 mutation thus appears to help in the
molecular diagnosis of patients with achondroplasia-group disorders. 相似文献
50.
Tohru Hashimoto M.D. Hironobu Nakamura Shinichi Hori Kaname Tomoda Katsuyuki Nakanishi Takamichi Murakami Takahiro Kozuka Morito Monden Mitsukazu Gotoh Chikazumi Kuroda Kenichi Wakasa Masami Sakurai 《Cardiovascular and interventional radiology》1995,18(2):82-86
Purpose: To evaluate the efficacy of transcatheter oily chemoembolization (TOCE) for hepatoceliular carcinoma (HCC) on the basis
of microscopic and macroscopic findings postembolization.
Methods: HCCs ranging in size from 0.5 to 13 cm (mean 3.6 cm) were obtained from partial hepatectomies of 100 consecutive patients
who had undergone TOCE between 20 and 246 days (mean 59.5 days) prior to surgery. The efficacy of TOCE was assessed on the
basis of the necrotic to live cell ratio of the tumors. The microscopic pattern of tumor growth was grouped into expanding
type (complete capsule formation) and replacing type (incomplete or no capsule). There were five types of macroscopic groupings:
single nodule, single nodule with extranodular growth (SNE), contiguous and noncontiguous multinodular, and massive growth
type.
Results: Among 79 cases with the expanding type, 29 (37%) had 100% HCC necrosis, but none with 100% necrosis were in the replacing
type. By macroscopic grouping, the efficacy of TOCE decreased from the single nodule type (50% of patients had 100% necrosis)
to the SNE type (21%), and the other types (9%). 相似文献