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1.
Immunohistochemical detection of imidazolone, a novel advanced glycation end product, in kidneys and aortas of diabetic patients. 总被引:11,自引:0,他引:11
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T Niwa T Katsuzaki S Miyazaki T Miyazaki Y Ishizaki F Hayase N Tatemichi Y Takei 《The Journal of clinical investigation》1997,99(6):1272-1280
To investigate the role of the Maillard reaction in the pathogenesis of diabetic complications, we produced several clones of monoclonal antibodies against advanced glycation end products (AGEs) by immunizing mice with AGE-modified keyhole limpet hemocyanin, and found that one clone (AG-1) of the anti-AGE antibodies reacted specifically with imidazolones A and B, novel AGEs. Thus, the imidazolones, which are the reaction products of the guanidino group of arginine with 3-deoxyglucosone (3-DG), a reactive intermediate of the Maillard reaction, were found to be common epitopes of AGE-modified proteins produced in vitro. We determined the erythrocyte levels of imidazolone in diabetic patients using ELISA with the monoclonal anti-imidazolone antibody. The imidazolone levels in the erythrocytes of diabetic patients were found to be significantly increased as compared with those of healthy subjects. Then we studied the localization of imidazolone in the kidneys and aortas obtained from diabetic patients by immunohistochemistry using the antibody. Specific imidazolone immunoreactivity was detected in nodular lesions and expanded mesangial matrix of glomeruli, and renal arteries in an advanced stage of diabetic nephropathy, as well as in atherosclerotic lesions of aortas. This study first demonstrates the localization of imidazolone in the characteristic lesions of diabetic nephropathy and atherosclerosis. These results, taken together with a recent demonstration of increased serum 3-DG levels in diabetes, strongly suggest that imidazolone produced by 3-DG may contribute to the progression of long-term diabetic complications such as nephropathy and atherosclerosis. 相似文献
2.
Strain difference of susceptibility to 4-nitroquinoline 1-oxide (4NQO)-induced squamous cell carcinomas of the tongue among Dark-Agouti, Long-Evans, Sprague-Dawley, ACI/Ms, Fischer 344, Donryu and Wistar/Furth rats was surveyed by evaluating the survival times, incidences and sizes of developed tumors as markers of susceptibility. Administration of 4NQO dissolved in drinking water induced squamous cell carcinomas in various sites of the upper digestive tract mucosa of all the experimental male and female rats of the seven strains. Regarding the mean survival times, Wistar/Furth rats survived much longer than any other strain of rats, and Dark-Agouti showed the shortest survival. The incidence of large, mass-type carcinomas of the tongue of Dark-Agouti rats was higher than in any other strain of rats, while that of Wistar/Furth rats was the lowest. Subsequently the mitotic activity and bromodeoxyuridine incorporation in the tongue epithelium of Dark-Agouti and Wistar/Furth rats were estimated after a short-term administration of 4NQO. There was a pronounced difference between the two strains of rats, because the proliferative responses of the tongue epithelium of Dark-Agouti rats to the 4NQO stimulation were much higher than those of Wistar/Furth rats. These results indicated that there are marked differences in the susceptibility to 4NQO-induced tongue carcinoma among the seven strains of rats, and that Dark-Agouti and Wistar/Furth rats could be useful as models of highly and poorly susceptible strains, respectively, for further genetic analysis. 相似文献
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T Akita S Hayase Y Yano K Ogawa H Hiramatsu T Hattori 《Nihon Geka Gakkai zasshi》1990,91(12):1808-1811
Sixty-one and 51-year-old males had progressive walk disturbance after cardiac operations at the intervals of 1 and 2 years. They had received blood transfusion at their operations. Physical examination revealed spastic paraparesis, sensory disturbance of the lower and rectobladder disorder. High titers of anti-Human T-lymphotrophic Virus type-I (HTLV-I) antibody were found in sera and CNF in both cases. They were diagnosed as HTLV-I associated myelopathy (HAM). Because they lived in Aichi Prefecture where the virus is non-epidemic, they were possibly infected through the blood transfusion at their operations. For prevention of HAM, the anti-HTLV-I antibody of all donor blood should be checked before transfusion. 相似文献
5.
Hayase N Fukumoto M Yoshida D Kariya S Akagi N Kurohara A Hisa N Yoshida S 《Clinical nuclear medicine》1999,24(5):326-329
Owing to recent advances in imaging technology and radiologic intervention, survival rates in patients with hepatocellular carcinoma have improved markedly. However, such prolonged survival has resulted in an increase in extrahepatic metastases. Tc-99m (Sn)-N-pyridoxyl-5-methyltryptophan (Tc-99m PMT), developed for hepatobiliary scintigraphy, has been used to visualize extrahepatic metastases, with most related reports limited to osseous metastases. The authors report two cases of hepatocellular cancer presenting as a hypopharyngeal metastasis and intraperitoneal dissemination along the tract of a fine-needle biopsy. Lesions undetectable on planar imaging could be visualized by Tc-99m PMT SPECT. 相似文献
6.
Murakami M Kashiwakura I Hayase Y Takagi Y 《Biological & pharmaceutical bulletin》1999,22(11):1153-1157
We examined the effect of murine kidney extract (MKE) on the clonal growth of mast cells from murine peritoneal cells. Adding MKE resulted in a 40% inhibition of colony formation of mast cells in a methylcellulose culture, and a 90% decrease in mast cell numbers and histamine content in mast cells in a liquid culture containing stem cell factor and interleukin-3. The mast cell inhibitory factors in MKE were heat sensitive proteins of approximately 560 and 24 kDa. These results suggest that MKE contains regulators that suppress the growth of murine mast cells and histamine synthesis. 相似文献
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Long-term effects of diet and colestipol (a bile acid sequestrant) were studied in 25 patients with familial type II hyperlipoproteinemia. Serum lipids and body weights of an initial group of 30 patients were stabilized by low cholesterol-saturated fat-refined carbohydrate diet and the patients were then randomized into placebo and drug-treatment groups. After explaining that the drug is nontoxic and effective in lowering serum lipids, total cholesterol (C) and low-density lipoprotein cholesterol (LDL-C), colestipol (30 g/day) and diet were given to the 25 patients who remained in the long-term follow-up program. The treatment resulted in highly significant lowering of serum lipids (mg/dl, mean +/- SEM): C and LDL-C from 412.7 +/- 24.4 and 331.1 +/- 22.8 to 270 +/- 11.0 and 188.1 +/- 13.8, respectively (p less than 0.001 in each instance) over 7--7 1/2 years. Although we observed no absolute increase in high density lipoprotein (HDL), the HDL/LDL ratio was elevated. Long-term colestipol and diet treatment reduced the xanthoma size and stabilized serially angiographically visualized atherosclerotic lesions in 21 of the 25 patients who showed a satisfactory hypolipemic response. It did not cause nutritional or metabolic disturbances. 相似文献
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Effects of amifostine on the proliferation and differentiation of megakaryocytic progenitor cells 总被引:3,自引:0,他引:3
Kashiwakura I Murakami M Inanami O Hayase Y Takahashi TA Kuwabara M Takagi Y 《European journal of pharmacology》2002,437(1-2):19-25
This study investigated the effects of amifostine, a clinically usable radioprotector or chemoprotector, on the proliferation and differentiation of normal and X-irradiated cluster of differentiation 34 positive (CD34+) megakaryocytic progenitor cells (colony-forming unit in megakaryocytes, CFU-Meg) from human placental and umbilical cord blood (CB) in vitro. Amifostine significantly accelerated megakaryocyte colony formation in a plasma clot culture supplemented with recombinant human thrombopoietin because of an increase in immature CFU-Meg-derived large megakaryocyte colony formation. An analysis of the cells that were harvested from the culture showed that amifostine induced a 70- and an 83-fold increase in the total cell and CFU-Meg numbers, respectively, and produced hyperploid megakaryocytes of more than 8 N ploidy. The radioprotective effect of amifostine on the clonal growth of X-irradiated CD34+ CFU-Meg was observed by treatment before or after irradiation. These findings suggest that the action of amifostine extends from immature CFU-Meg to the terminal differentiation of megakaryopoiesis, and its radioprotective effect is shown in megakaryopoiesis and thrombopoiesis. 相似文献