[Clinical significance of plasma c-AMP response to glucagon for the assessment of the prognosis in liver cirrhosis and hepatocellular carcinoma].
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Biomedical subjects
Publications and source records attributed to Y Muto.
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Using C3H/10T-1/2 mouse fibroblasts, we tested whether polyprenoic acid (E-5166) inhibits radiogenic and chemically induced transformation in vitro. Our results show that E-5166 markedly inhibits transformation by X rays and benzo[a]pyrene in a dose-related manner. Maximum inhibition was observed when cells were pretreated with E-5166 prior to carcinogen exposure, and lesser inhibition when E-5166 treatment followed carcinogen exposure. These results indicate that E-5166 can serve as a radio-protective and chemopreventive agent with anticarcinogenic potential.
The effects of the newly synthesized polyprenoic acid, 3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid (E-5166) on N-2-fluorenylacetamide (FAA)-initiated hepatocarcinogenesis were examined in 6 groups of male ACI rats. The numbers of altered hepatocellular foci in rats of group 1 given a basal diet containing 0.02% FAA for 13 weeks and in rats of group 2 which received E-5166 by gavage (40 mg/kg, 3 times/week) at the same time as receiving the FAA diet were almost the same, indicating that E-5166 had no effect at the stage of carcinogen exposure. However, the number of foci in group 4, in which rats were given the basal diet and E-5166 after the termination of the carcinogen exposure, and were sacrificed 16 weeks later, was significantly smaller than that in group 3 maintained on the basal diet alone (P less than 0.05). The results suggests some anticarcinogenic activity of E-5166, possibly involving the phenotypic expression of the preneoplastic foci. Furthermore, the number of altered foci in rats of group 6 (given the liver-tumor promoter phenobarbital with E-5166 for 16 weeks after the administration of carcinogen) was also significantly smaller than that in rats of group 5, which received the promoter (P less than 0.05). The incidence of neoplastic nodules of the liver in group 6 at the end of the experiment was also lower than in group 5 (P less than 0.0014). These results suggest an antipromoting effect of the polyprenoic acid E-5166 on rat chemical hepatocarcinogenesis.
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A proton nuclear magnetic resonance (NMR) study is reported of des-Arg-C3a, which is a 76-residue fragment obtained from the N-terminal portion of the alpha chain of the third component of human complement. A method of carboxypeptidase digestion/difference spectroscopy [Endo, S., & Arata, Y. (1985) Biochemistry 24, 1561-1568] was used for the spectral assignments for Ala-76, Leu-75, Gly-74, His-72, His-67, and Ala-48. On the basis of the NMR results obtained for these residues, we conclude that in aqueous solution (1) the C-terminal segment Leu-73-Ala-76 is free from interactions with the rest of the C3a molecule and (2) the major part of the C-terminal segment takes an ordered conformation. We also suggest that the presence of a core, which is formed by segment Tyr-15-Tyr-59 [Huber, R., Scholze, H., Paques, E. P., & Deisenhofer, J. (1980) Hoppe-Seyler's Z. Physiol. Chem. 361, 1389-1399], is essential for the C-terminal segment in maintaining the ordered structure in aqueous solution. 1H NMR spectral data were also obtained for the intact C3 from human and porcine sources. The resonances for the C2-H protons of His-67 and His-72, which exist in the C3a part of the human C3 molecule, were assigned. Comparisons of the results obtained with those for des-Arg-C3a demonstrate that upon cleavage of C3a very little change, if any, is induced in microenvironments of His-67 and His-72 and a piece of segment that contains His-72 is exposed to solvent and highly flexible.(ABSTRACT TRUNCATED AT 250 WORDS)
High-performance liquid chromatographic (HPLC) analysis of human serum albumin (HSA) on a GS-520 column with 0.03 M sodium phosphate buffer-0.15 M sodium sulphate (pH 6.87) showed three peaks, the principal component corresponding to human mercaptalbumin (HMA) and the secondary and tertiary components to nonmercaptalbumin (HNA). Using HPLC analysis, the nonmercapt----mercapt conversion of HSA during haemodialysis and the mercapt----nonmercapt conversion after haemodialysis in chronic renal failure were re-confirmed, indicating that HMA is a covalent carrier protein for sulphur-containing amino acids. Fractions of HMA in various liver diseases were significantly lower than those of healthy male adults.
Transport of Ca2+ in microsomal membrane vesicles of the Tetrahymena has been investigated using arsenazo III as a Ca2+ indicator. The microsomes previously shown to carry a Mg2+-dependent, Ca2+-stimulated ATPase (Muto, Y. and Nozawa, Y. (1984) Biochim. Biophys. Acta 777, 67-74) accumulated calcium upon addition of ATP and Ca2+ sequestered into microsomal vesicles was rapidly discharged by the Ca2+ ionophore A23187. Kinetic studies indicated that the apparent Km for free Ca2+ and ATP are 0.4 and 59 microM, respectively. The Vmax was about 40 nmol/mg protein per min at 37 degrees C. The calcium accumulated during ATP-dependent uptake was released after depletion of ATP in the incubation medium. Furthermore, addition of trifluoperazine which inhibited both (Ca2+ + Mg2+)-ATPase and ATP-dependent Ca2+ uptake rapidly released the calcium accumulated in the microsomal vesicles. These observations suggest that Tetrahymena microsome contains both abilities to take up and to release calcium and may act as a Ca2+-regulating site in this organism.
Serum apolipoprotein (apo) A-IV levels were determined in patients receiving total parenteral nutrition (TPN) by an immunoassay using a specific antiserum against apo A-IV purified from human sera. The value was significantly lower than that of normal subjects (p less than 0.001), and the level correlated significantly with the duration of TPN. In a patient receiving TPN, serum apo A-IV concentration decreased during TPN and returned to normal levels after resuming oral intake of diet. This finding indicates that serum apo A-IV is a new parameter for nutritional assessment, since the protein is exclusively synthesized in the gut, being different from other rapid turnover proteins which are mainly synthesized in the liver.
Addition of bovine brain calmodulin and S-100 inhibited Tetrahymena calmodulin-induced stimulation of guanylate cyclase, but they did not affect enzymatic activity in the presence of calcium alone. Troponin C shows little effect on the cyclase activity regardless of the presence or absence of Tetrahymena calmodulin. The inhibitory effects of brain calmodulin and S-100 were overcome by the addition of Tetrahymena calmodulin, but not by calcium. Both calmodulins from Tetrahymena and bovine brain elicited stimulation of heart phosphodiesterase, while troponin C and S-100 did not affect the phosphodiesterase activity in the presence and absence of Tetrahymena calmodulin.
Agents such as 5'-guanylyl-imidodiphosphate(GppNHp), fluoride and forskolin did not activate adenylate cyclase from Tetrahymena. In addition, the cyclase was not stimulated by hormones including catecholamines and glucagon when assayed with or without GppNHp at conditions where they increased adenylate cyclase activity from rat heart. Sodium azide, NaNO2 or N-methyl-N'-nitro-N-nitroguanidine (MNNG) failed to activate Tetrahymena guanylate cyclase. Adenylate cyclase activity was activated at low free Ca2+ level and inhibited at high levels, while guanylate cyclase activity was activated by Tetrahymena calmodulin only at high physiological concn of Ca2+.
The calmodulin-dependent guanylate cyclase of Tetrahymena pyriformis was shown previously to be localized in surface membranes (ciliary and pellicular membranes) (Kudo, S, Nakazawa, K, Nagao, S & Nozawa, Y, Japan j exp med 52 (1952) 193) [21], whereas in a recent report Schultz et al, (Schultz, J E, Schonefeld, U & Klumpp, S, Eur j biochem 137 (1983) 89) [12] demonstrated the localization of this enzyme in ciliary membrane, arguing against its presence in pellicular membrane. To examine the discrepancy, the activities of guanylate and adenylate cyclases were examined in cilia and cell bodies of Tetrahymena pyriformis during transition from early log to stationary growth phase. The guanylate cyclase activity in the cell bodies increased significantly with growth of age, while in cilia the activity was rather consistent. In contrast, adenylate cyclase did not show any growth-dependent activity changes in both cilia and cell bodies. The increase of guanylate cyclase activity was not related to the increase of its activator calmodulin, because the change in enzyme activity could not be negated by addition of a saturating amount of calmodulin. These results suggest that the content of guanylate cyclase itself would be increased in the cell bodies during growth.
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The most characteristic phenomenon in patients with carcinoma of the gallbladder is frequent coexistence of gallstones. In this study, morphological differences of carcinoma of the gallbladder in between calculous and acalculous cases is investigated. This study involved fifty-three cases (eleven early carcinoma and forty-two advanced) that had been surgically treated at the Hamamatsu Medical Center Hospital during the past ten years. Nine of 11 early carcinomas were calculous and two, acalculous. All calculous carcinomas showed grossly superficial type and two acalculous, polypoid type. All of them were histologically differentiated adenocarcinoma. In advanced carcinoma, thirty-one of 42 cases were calculous and eleven, acalculous. Fifteen of 31 calculous cases showed polypoid type and sixteen, diffuse infiltrative type. In all cases with the latter type, the cystic duct was completely obstructed by impacted gallstones. All calculous carcinomas were histologically belonged to differentiated adenocarcinoma, mucinous carcinoma or adenosquamous carcinoma. On the other hand, six of 11 acalculous carcinomas revealed grossly polypoid type, and histologically differentiated adenocarcinoma or mucinous carcinoma. The remaining five were of diffuse infiltrative type, and of poorly-differentiated adenocarcinoma or signet-ring cell carcinoma. From these data, it may be highly suggestive that differentiated adenocarcinoma or adenosquamous carcinoma of histologic type irrespective of it's gross type is characteristic of calculous carcinoma, and poorly-differentiated adenocarcinoma or signet-ring cell carcinoma possessing primary diffuse infiltrative growth, of acalculous. The majority of the superficial type in early carcinoma and the diffuse infiltrative type in advanced are considered as a secondary modified gross appearance by direct or indirect effects of coexistent gallstones onto the main tumor.
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