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Biomedical subjects

S Nishimoto

Publications and source records attributed to S Nishimoto.

At least 73 records · Page 4Linked to original sources
PubMed1988

[Mechanism of action and molecular design of hypoxic cell sensitizer].

Fluorine modification of nitroazoles has been characterized as a useful method of molecular design of hypoxic cell sensitizers. In vitro sensitizing activities were correlated to the promotion efficiency of radiolytic hydroxylation of thymine to thymine glycol and to the one-electron reduction potential of a variety of fluorinated and non-fluorinated nitroazole derivatives. The absolute activity of sensitizers, which was evaluated from the enhancement ratio in vivo (SERvivo) and the tumor affinity, showed a linear relationship with the in vitro sensitizing activity. The sensitizer dose required to achieve an SERvivo of 1.5 decreased as the tumor affinity became greater. The fluorine modification of nitroazole sensitizers could enhance both the absolute activity and the tumor affinity.

Animals↗
PubMed1987

Advanced glycosylation endproducts on erythrocyte cell surface induce receptor-mediated phagocytosis by macrophages. A model for turnover of aging cells.

Glucose can react nonenzymatically with amino groups of proteins to form covalent Amadori products. With time these adducts undergo further rearrangements to form irreversible advanced glycosylation endproducts (AGE), which accumulate with protein age. A specific AGE, 2-(2-furoyl)-4(5)-(2-furanyl)-1H-imidazole (FFI), has been identified on proteins in vivo. We have recently shown that a macrophage receptor specifically recognizes and internalizes proteins modified by AGE such as FFI, thus preferentially degrading senescent macromolecules. Reasoning that cellular turnover may be mediated by macrophage recognition of AGE-membrane proteins, we prepared human RBCs with FFI attached chemically. Human monocytes were incubated with either FFI-RBCs, IgG-opsonized RBCs, or PBS-treated RBCs. Erythrophagocytosis of FFI-RBCs was significantly higher than that of PBS-RBCs (55 vs. 4%; p less than 0.0025) and almost as high as that of IgG-RBCs (70%), and was competitively inhibited by AGE-BSA. AGE-RBCs were also prepared by incubating RBCs with various sugars. Human monocytes showed a 15% ingestion of glucose-RBCs, and a 26% ingestion of glucose-6-phosphate-RBCs, compared to 6% for PBS-RBCs. Similarly, diabetic mouse RBCs were phagocytosed by nearly three times more cells (21%) than normal mouse RBCs when exposed to syngeneic mouse macrophages. This phagocytosis was competitively inhibited (70%) by addition of excess AGE-BSA. The in vivo half-life of 51Cr-labeled mouse FFI-RBCs injected into syngeneic mice was reduced to 7 d, as compared to a half-life of 20 d for the controls. These data suggest that the macrophage receptor for the removal of glucose-modified proteins may also mediate the endocytosis of RBCs with AGE formed on their surface, and thus be responsible in part for the removal of some populations of aging cells.

Animals↗
PubMed1987

Evaluation of various types of new hypoxic cell sensitizers using the EMT6 single cell-spheroid-solid tumour system.

Eleven new hypoxic cell sensitizers representative of those developed in Japan between 1980 and 1985 were evaluated in vitro and in vivo in comparison with misonidazole (MISO), SR-2508, Ro 03-8799, and ANT (2-amino-5-nitrothiazole). The new compounds included 2-nitroimidazole nucleoside analogues, nitrotriazoles and other nitroaromatics, non-nitro compounds, and electron-affinic compounds that readily intercalate DNA. The sensitizing activity in the EMT6 single cells correlated not only with the reduction potential but, for some compounds, also with the reactivity with non-protein sulphydryls. The sensitizers were also tested using the EMT6 spheroids and solid tumours. The patterns of changes in sensitizer enhancement ratios (SERs) for single cells, spheroids, and solid tumours were classified into two types: (1) SERs for the three testing systems were similar; and (2) SERs decreased in the order of: single cells, spheroids, and solid tumours. Only nitroimidazole and nitrotriazole derivatives belonged to the former type. RK-28 and RK-29, 2-nitroimidazoles with sugar analogue components, had in vivo effects almost equal to those of MISO. Also 3- and 4-nitrotriazole derivatives had definite in vivo effects.

Animals↗
PubMed1986

Radiosensitization in vitro and in vivo by 3-nitrotriazoles.

A series of 3-nitro-1,2,4-triazole derivatives bearing various types of side chain (R) at the N1-position (AK-2000 series) were synthesized and their radiosensitizing effect and toxicity in vitro and in vivo were investigated, in comparison with those of Misonidazole (MISO), SR-2508, and RSU-1069. Of the fifteen 3-nitrotriazoles tested, all had sensitizing effects in vitro on hypoxic V79 cells. Also, all but one had definite effects on solid EMT6/KU and SCCVII tumors in vivo. For many of the triazole compounds, the degree of radiosensitization in vitro and in vivo appeared identical. However, they were generally less efficient, both in vitro and in vivo, than the corresponding 2-nitroimidazoles, whereas their aerobic cytotoxicity and toxicity to mice (LD50/7) were comparable to those of the 2-nitroimidazoles. Considering the sensitizing effect and toxicity, AK-2123 (R = CH2CONHC2H4OCH3) may be as useful as MISO, but none of the triazoles have been proved to be superior to SR-2508.

Animals↗
PubMed1986

Increased fructose-lysine of nail protein and blood glucose control in diabetic patients.

Furosine, which was formed by acid hydrolysis of fructose-lysine, was determined and used as an indicator of glycosylated protein. The diabetic patients had significantly higher fructose-lysine levels in finger nails than healthy subjects [10.8 +/- 4.6% (mean +/- S.D.) vs 4.2 +/- 1.1%]. The best correlation was found between the fructose-lysine value and the fasting blood glucose level determined 3 to 5 months before sampling nails in diabetics. These results suggest that the furosine derived from fructose-lysine in finger nails may become an indicator of blood glucose control during the past 3 to 5 months in diabetics.

Adult↗
PubMed1986

Age-related acceleration of glycation of tissue proteins in rats.

The Maillard reaction on proteins is a nonenzymatic glycosylation that is now termed glycation and produces a ketoamine linkage on the protein. The extent of this glycation was estimated by determining furosine (epsilon-N-(2-furoylmethyl)-L-lysine), which is derived from glycated lysine residues. Glycation of rat sciatic nerve and aorta increased with advancing age for up to 50 weeks and the high degree of glycation was maintained thereafter. The level of hemoglobin did not change significantly after 14 weeks. These results suggest that tissue glycation may increase with aging and may be involved in the mechanism of aging.

Aging↗
PubMed1985

Increased fructose-lysine of hair protein in diabetic patients.

Fructose-lysine, which is formed by binding glucose to lysine, is changed by acid hydrolysis into furosine. Furosine derived from fructose-lysine of hair was determined by high-performance liquid chromatography according to the method of Schleicher et al. Furosine values were significantly higher in diabetic patients than in healthy subjects, and significantly correlated with the stable components of hemoglobin A1 (HbA1) values. These results suggest that furosine, like HbA1, may become an indicator of past blood glucose control at any time in diabetic patients and be useful in investigating diabetic complications on the level of tissue.

Adult↗