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Biomedical subjects

K Nagano

Publications and source records attributed to K Nagano.

At least 217 records · Page 12Linked to original sources

Lack of a disulfide bond in the large subunit of (Na, K)ATPase.

Subunit distribution of disulfide bonds in the dog kidney (Na, K)ATPase was examined. It was estimated that there were no disulfide bonds in the alpha subunit and possibly one in the beta subunit. The disulfide bond located in the beta subunit would be a good probe for elucidation of the role of the beta subunit. Our previous overestimation was presumably due to the phospholipid attached to the subunits.

Animals↗

Evidence for essential disulfide bonds in the beta-subunit of (Na+ + K+)-ATPase.

(Na+ + K+)-ATPase from dog kidney lost its activity when heated at 55 degrees C in the presence of 0.3 M 2-mercaptoethanol. Either heat treatment alone or addition of reducing agent at around 25 degrees C caused little inactivation. One disulfide bond per protomer (mol. wt. 146 000) was reduced in the inactivated sample but in active samples no reduction occurred. Neither K+-dependent phosphatase activity nor phosphoenzyme formation in the presence of Na+ was detected in the inactivated sample, suggesting that the disulfide bond was essential for the catalytic cycle of (Na+ + K+)-ATPase. This essential disulfide bond belonged to the beta-subunit, the glycoprotein component of the enzyme, indicating that the beta-subunit may be an integral component of the (Na+ + K+)-ATPase system.

Animals↗

Low density lipoprotein-lowering and high density lipoprotein-elevating effects of nicardipine in rats.

Oral administration of a calcium antagonist, nicardipine hydrochloride (simply designated as nicardipine), in doses of 10-100 mg/kg tended to decrease total serum cholesterol and to increase high density lipoprotein (HDL) cholesterol in the normal rat. These effects of nicardipine were much greater than those of clofibrate, a standard cholesterol-lowering drug. Neither nicardipine nor clofibrate caused significant alteration in serum triglyceride and phospholipid. In hypercholesterolemic rats, nicardipine increased significantly HDL cholesterol with a reduction of total serum cholesterol, whereas clofibrate did not change HDL cholesterol. Separation of serum lipoproteins either by ultracentrifugation in various densities of KBr-NaCl solution or by polyacrylamide gel electrophoresis demonstrated that nicardipine increased preferentially HDL2 (density: 1.063-1.125), with a reduction of the low density lipoprotein (LDL) (density: 1.006-1.063) level in hypercholesterolemic rats. Serum triglyceride and liver phospholipid were increased slightly by nicardipine with no clear dose-dependency. Clofibrate also increased serum triglyceride. In normal rats, neither nicardipine nor nicotinic acid inhibited sterol biosynthesis from [1-14C]acetate in the liver, whereas clofibrate inhibited sterol production. Oral administration of [4-14C]cholesterol to hypercholesterolemic rats indicated that nicardipine had no inhibitory effect on the intestinal absorption of cholesterol.

Acetates↗

Differential coupling efficiency of chemically activated amino acid to tRNA.

Interaction based on possible chemical affinity of an amino acid for tRNA was examined as a model for the aminoacylation of primitive tRNA without aid of an enzyme system. Two types of reaction were carried out and compared. One was the acyl linkage of amino acid to the 5'-terminal phosphate of a tRNA activated as an imidazolide. The other was the incorporation of an amino acid activated as an imidazolide into 2'(3')-hydroxyl groups of intact tRNA. Both types of reaction indicated that none of the amino acids tested had any selectivity for the tRNAs examined. However, the rates of reaction with a given tRNA were different among amino acids. In the second type of reaction, amino acids were found mainly at loop-out regions of tRNA, but not at either its 5'- or 3'-terminal sites.

Amino Acids↗

Prediction of packing of secondary structure.

An improved method of picking up candidates for predicting the packing arrangement of beta-strands and alpha-helices of the alpha/beta type domains is described here. The method of judging whether the region of the protein would fold into the alpha/beta type or not is also described. The folding constraints of globular proteins are analysed and presented in this article for application to the prediction of packing of secondary structure. The analysis of the residue-fluctuations is also applicable for the purpose.

Arabinose↗

Pathogenesis of paraquat-induced pulmonary hemorrhage in hamsters with special reference to arterial constriction.

Three dimensional reconstructions of pulmonary arteries and the bronchial tree were made to evaluate the cause of hemorrhage in the lungs of hamsters treated with a single intraperitoneal injection of paraquat at a dose of 15 mg/kg b.w. The hemorrhage corresponding to the respiratory bronchiolar segment formed the minimum hemorrhagic unit; larger hemorrhages were composed of conglomerations of such units. The respiratory bronchiolar segment was fed by a single respiratory bronchiolar arteriole which had a distinct muscular medial coat. No evidence of breakage of the arterial wall passing through the hemorrhagic lesion could be detected even by careful observation with serial histological sections. Accordingly, the cause of the lung hemorrhage was sought in the combined effects of paraquat toxicity to the capillary endothelium and vasoconstriction of the respiratory bronchiolar arterioles.

Animals↗

Experimental studies on toxicity of ethylene glycol alkyl ethers in Japan.

Past studies on the toxicological effects of ethylene glycol alkyl ethers as well as the recent data on these chemicals in Japan are reviewed. Only a few researchers have participated in the study of ethylene glycol alkyl ethers in Japan. The effects of ethylene glycol alkyl ethers on testis and embryotoxic effects of ethylene glycol monomethyl ether (EGM) have been studied, as has the teratogenicity of ethylene glycol dimethyl ether (EGdM). Studies on ethylene glycol alkyl ethers and related compounds administered to mice by oral gavage revealed the occurrence of testicular atrophy and decreased white blood cell count by EGM, EGdM, ethylene glycol monomethyl ether acetate, ethylene glycol monoethyl ether and ethylene glycol monoethyl ether acetate, and the toxicity was related to their chemical structure. On the other hand, ethylene glycol, ethylene glycol monopropyl ether, ethylene glycol monobutyl ether, ethylene glycol monophenyl ether, ethylene glycol monoacetate or ethylene glycol diacetate showed no such an effect. Studies on EGM using hamsters or guinea pigs revealed the occurrence of testicular atrophy similar to that observed in mice. In regard to the methyl ethers of other glycols, there is no convincing evidence that propylene glycol monomethyl ether, diethylene glycol monomethyl ether or diethylene glycol dimethyl ether causes testicular atrophy in mice. Teratological studies of EGM and EGdM revealed embryotoxic effects in mice.

Abnormalities, Drug-Induced↗

A comparative histometrical analysis of renal inner medulla of man, swine, dog and hamster.

Quantitative estimations of the total circumference (in mm) of Henle's thin segment (TCH) and of the collecting tubules (TCC) in the renal inner medulla of man, swine, dog and hamster were made at different distances (X) from the papillary apex. The results were expressed as exponential functions of X, the distance in mm along the medullary ray from the papillary apex to a certain point of the inner medulla, as L = AeBX. In man and swine, TCH was greater than TCC towards the external border of the inner medulla. However, in dog and hamster TCH was less than TCC along the entire inner medulla. The exponents of TCH showed nearly constant values (hamster: 0.68, dog: 0.75, man: 0.55, swine: 0.56), but those of TCC had values (hamster: 0.92, dog: 0.57, man: 0.28, swine: 0.26) correlated with the ability for concentration of urine. These findings indicate a good correlation between the ability to concentrate urine and the structure of the collecting tubules of the inner medulla, suggesting that the structure of the collecting tubules in the inner medulla affects the mechanism of urinary concentration.

Animals↗

Determination of protonation sites in thermospermine and in some other polyamines by 15N and 13C nuclear magnetic resonance spectroscopy.

The pK values of thermospermine, a novel asymmetric tetraamine (4,8-diazadodecane-1,12-diamine), have been determined for the first time by the conventional titration method with subsequent data analyses. It was found to be the most basic polyamine among naturally occurring tetraamines. The 15N NMR titration method was applied to determine its protonation site. Natural-abundance 15N magnetic resonance spectra of the polyamine have been recorded as a function of pH from its free to the protonated form. Its apparent pK values, as well as the intrinsic chemical shifts for each stage of protonation, have been calculated from the NMR titration curve by using a nonlinear least-squares method. The four protonation sites of thermospermine have been successfully determined to be N12, N1, N-8, and N-4 in that order from the free to the completely protonated form. In a similar manner the protonation sites of spermidine and two symmetric tetraamines, thermine and spermine, have been established. 13C NMR experiments for the four polyamines were almost consistent with those of 15N NMR. Owing to the much higher concentration of the polyamines furnished for NMR titration experiments, the pK values obtained by NMR were larger than those derived by the conventional titration methods.

Binding Sites↗

Mutagenicity of coal-pyrolyzed products and their photochemical reaction products with nitrogen oxides in Salmonella typhimurium TA98 and TA100.

The chemical class separation of coal-pyrolyzed products and the photochemical reaction of these fractions with nitrogen oxides in the experimental chamber, and the application of a short-term mutagenicity test were investigated. The altered products from the fraction hydroxy polycyclic aromatic compounds in a simulated atmosphere containing a small volume of nitrogen oxides under irradiation with a xenon lamp were the most potent mutagenic fraction among all the fractions tested against Salmonella typhimurium, both TA98 and TA100, with or without S9.

Animals↗