Neocarzinostatin: carboxyl-terminal-43-peptide residue of apo-neocarzinostatin as the binding site of neocarzinostatin-chromophore.
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Amino Acid Sequence↗
Biomedical subjects
Y Koide
Publications and source records attributed to Y Koide.
[Secretory control of pituitary hormones--mechanism of TSH secretory control].
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Animals↗
Evaluation of treatment for gastric cancer with liver metastasis.
In 161 cases of gastric cancer with liver metastasis but without peritoneal dissemination, evaluations were executed to find effective treatment. The most favorable results with best prognosis were obtained in the group receiving gastrectomy + hepatectomy + chemotherapy, followed by gastrectomy + chemotherapy, and gastrectomy alone. The most unfavorable outcome was in nonresected cases. Chief chemotherapy to be used after gastrectomy was FML (5-fluorouracil (5-FU) + mitomycin C [MMC] + lentinan) continuous intra-arterial infusion. Hepatectomy was found to be effective as an active measure for tumor reduction in cases of liver metastasis so far as the metastatic lesions are only a few scattered ones in both lobes.
Adult↗
Anti-tumour effect of humoral and cellular immunities mediated by a bacterial immunopotentiator, Lactobacillus casei, in mice.
Administration of a mixture containing Lactobacillus casei YIT 9018 (LC9018) and methylcholanthrene-induced fibrosarcoma (Meth A) cells into the peritoneum of syngeneic BALB/c mice suppressed the tumour growth and protected the mice from tumour death. With the appearance of the anti-tumour activity, serum complement-dependent tumour cytotoxic (CDC) antibody was induced on the 5th day after the administration as a result of the adjuvant effect. The cytotoxic antibody was not found in serum on the 5th day after inoculation of Meth A cells alone, but it was induced before the mice died of the tumours. Adjuvant induction of the cytotoxic serum antibody at an early time was also observed using Kirsten murine sarcoma virus-transformed tumour (K234) cells. Both of these cytotoxic antibodies in sera from Meth A-suppressed and the tumour-bearing mice were specific for the tumour cells and were IgM class, since they were absorbed with rabbit anti-mouse IgM antibody. However, the cytotoxic antibody was not found in the peritoneal cavity which was the tumour inoculation site, but binding antibody against the tumour cells was faintly detected in the region using an enzyme-linked immunoabsorbent assay (ELISA). In neutralization tests, the cytotoxic antibody did not exert anti-tumour activity in recipient mice when it was administered to the mice along with the tumour cells or when it was administered i.v. at the time of tumour inoculation. Moreover, the cytotoxic antibody was not available for the antibody-dependent cell-mediated cytotoxicity (ADCC). These results suggest that the cytotoxic antibody did not exert anti-tumour activity in the tumour-suppressed mice. In contrast, peritoneal exudate cells (PEC) on the 5th day, and PEC and spleen cells on the 15th day after i.p. administration of the mixture exerted strong anti-tumour activity as measured by the Winn test. In conclusion, the adjuvant effect of LC9018 induced tumour-specific humoral and cellular immunities but the anti-tumour activity was dependent only on the cellular effectors of the host. The possible use of LC9018 in tumour immunotherapy is discussed.
Adjuvants, Immunologic↗
Protection against suture insufficiency in ante-thoracic esophagogastrostomy.
In attempts to decrease suture insufficiency in case of ante-thoracic esophagogastrostomy, a gastric tube was so specially prepared that the short gastric vessels as well as the splenic vessels were severed very adjacent to the spleen. The anastomosis of the gastric tube thus prepared to the cervical esophagus was made using EEA-autosuture instruments. The suture insufficiency rate was thus markedly improved, with a value of approximately 10 per cent. Even cases of suture insufficiency with minor leakage, control was complete with simple pressure with gauze.
Adult↗
Influence of extracellular phosphate concentrations on the regulation of hepatic glucose output.
Experiments were carried out to investigate the role of extracellular phosphate in the hormonal regulation of glycogenolysis in perfused fed-rat liver. Omission of phosphate from the perfusate did not affect the ATP, ADP and AMP contents of the tissue and the basal glucose output from the perfused liver. However, it inhibited significantly the glycogenolysis induced by glucagon, cyclic AMP, phenylephrine and vasopressin but not that induced by 2,4-dinitrophenol. In the absence of perfusate phosphate, the increase in phosphorylase a activity caused by the addition of glucagon, phenylephrine and vasopressin was significantly less than that observed in the presence of perfusate phosphate. Insulin inhibition of the glucagon- or cyclic AMP-induced glycogenolysis was abolished when the perfusion was carried out with the phosphate-free buffer. However, the inhibitory effect of insulin on phenylephrine-induced glycogenolysis was clearly demonstrated even when the perfusate contained no phosphate. These data indicate that in the phosphate-depleted liver, the hormonal control of phosphorylation and dephosphorylation of phosphorylase is impaired. The difference in the phosphate dependency of insulin action on glucagon-and alpha-adrenergic agonist-induced glycogenolysis suggests that the mechanism or site of insulin action on glucagon and phenylephrine is different.
Adenine Nucleotides↗
Relationship between serum free thyroxine, total thyroxine and thyroxine-binding globulin concentrations in patients with Graves' disease.
Statistical analysis of relationship between free thyroxine (FT4) and thyroxine (T4) in patients with Graves' disease has revealed that serum FT4 values correlated well with serum T4 values at variable thyroid states before and during treatment with anti-thyroid drugs. However, the ratio of FT4 concentration to T4 concentration at hyperthyroid state was more than twice as large as the ratio at euthyroid and hypothyroid states. These findings are considered to denote the elevation of per cent of FT4 to T4 (% FT4) in thyrotoxicosis. Nevertheless, thyroxine-binding globulin (TBG) concentrations in hyperthyroid patients were slightly, but significantly lower by 7.3% than those in normal euthyroid volunteers. These results indicate the minimal contribution of the slight decrease in TBG concentrations to the marked elevation of %FT4 in patients with thyrotoxicosis.
Adolescent↗
Establishment of an efficient purification method and further characterization of 32K calmodulin-binding protein in testis.
A heat-stable 32K calmodulin-binding protein has been purified approximately 3,670-fold from porcine testis to apparent homogeneity as judged by both sodium dodecyl sulfate polyacrylamide gel electrophoresis and polyacrylamide gel electrophoresis under native conditions. The purification employed calmodulin-Sepharose 4B affinity chromatography; elution was performed with a free Ca2+ gradient. This provided a simple and efficient procedure, and approximately 1.62 mg of pure heat-stable calmodulin-binding protein was obtained from 390 g of porcine testis with a yield of 47% in activity. The purified protein was asymmetric (f/fo = 1.89) and consisted of a single polypeptide of Mr = 32,000. It is a highly acidic protein (pI = 3.9) with a diffusion coefficient of 5.4 X 10(-7) cm2/s, a sedimentation coefficient of 1.43 S, and a Stokes radius of 39.5 A in its free form and 41.3 A in its complex form with calmodulin. The extent of inhibition of phosphodiesterase by the calmodulin-binding protein was affected by the order of addition of the agents to the reaction mixture. The extent of inhibition was maximal when phosphodiesterase was added last, while it was minimal when the calmodulin-binding protein was added last. This protein was indistinguishable from a heat-stable calmodulin-binding protein in rat testis (Ono, T., Koide, Y., Arai, Y., & Yamashita, K. (1984) J. Biol. Chem. 259, 9011-9016).
3',5'-Cyclic-AMP Phosphodiesterases↗
Difference in the mechanism of action of alpha-adrenergic agonists and vasopressin or angiotensin II in stimulating hepatic glycogenolysis; a role of extracellular calcium concentration.
The role of extracellular calcium in hormone-induced glycogenolysis was examined in a rat liver perfusion system by manipulating the perfusate calcium concentration and by using calcium antagonistic drugs. When the perfusate contained 1 mM CaCl2, 5 microM phenylephrine, 20 nM vasopressin, and 10 nM angiotensin II caused a persistent increase in glucose output and phosphorylase activity as well as a transient increase in 45Ca efflux from 45Ca preloaded liver. Verapamil hydrochloride (20-100 microM) inhibited the activation of glucose output by these hormones in a dose-dependent manner. This inhibitory effect was also associated with the inhibition of hormone-induced activation of phosphorylase and 45Ca efflux. In the absence of CaCl2 in the perfusate, the glycogenolytic effect of phenylephrine and its inhibition by verapamil were obtained equally as in the presence of CaCl2. However, the effects of vasopressin and angiotensin II were markedly attenuated and were not inhibited any further by verapamil. The substitution of diltiazem hydrochloride for verapamil produced essentially identical results. Cyclic AMP concentrations in the tissue did not change under any of these test conditions. The results indicate that the glycogenolytic effect of alpha-adrenergic agonists depends on intracellular calcium but those of vasopressin and angiotensin II on extracellular calcium, and support the concept that calcium antagonistic drugs inhibit the glycogenolytic effects of calcium-dependent hormones at least by inhibiting the mobilization of calcium ion from cellular pools.
Angiotensin II↗
Role of extracellular calcium and calcium efflux in the activation of hepatic glycogenolysis by calcium-dependent hormones.
The role of extracellular calcium in the glycogenolytic effects of calcium-dependent hormones was examined in a rat liver perfusion system. Decreasing the perfusate CaCl2 concentration resulted in a concentration-dependent inhibition of glucose output by maximal concentrations of vasopressin (20 nM) and angiotensin II (10 nM), but not of glucagon (1.4 nM), cyclic AMP (100 microM), dibutyryl cyclic AMP (10 microM) or phenylephrine (5 microM). However, the effect of phenylephrine was inhibited when livers were perfused with CaCl2-free perfusate containing 0.5 mM EGTA in a duration-dependent manner. These effects were exerted through the inhibition of the maximal response of each hormone, and were associated with a parallel decrease in phosphorylase activation but not with changes in tissue cyclic AMP concentrations. When livers were preloaded with 45Ca for 45 min and then washed for either 15 min or 45 min, these hormones elicited a rapid and transient 45Ca efflux regardless of the perfusate calcium concentration. The sequential perfusion of two hormones resulted in the loss of 45Ca efflux by the second hormone. These results suggest that the glycogenolytic effects of vasopressin and angiotensin II depend on the extracellular calcium and that of phenylephrine primarily on the cellular calcium. It was also demonstrated that these calcium-dependent hormones mobilize calcium from the same pools. However, the mobilization of cellular calcium does not necessarily correlate directly with the glycogenolytic actions of vasopressin and angiotensin II.
Angiotensin II↗
Effect of o,p'-DDD on cortisol metabolism in Cushing's syndrome of various etiology.
Effects of o,p'-DDD on parameters of cortisol metabolism were studied in 3 patients with Cushing's syndrome (ectopic ACTH-syndrome, Cushing's disease, and adrenal cancer). Before o,p'-DDD treatment, plasma cortisol, urinary 17OHCS, and urinary free cortisol were elevated in all patients. These parameters correlated well with each other in ectopic ACTH-syndrome and Cushing's disease. However, in adrenal cancer, urinary 17OHCS did not correlate with either plasma cortisol or urinary free cortisol, while the latter two parameters did. During o,p'-DDD, urinary 17OHCS rapidly declined in a patient with ectopic ACTH syndrome and a patient with Cushing's disease before plasma cortisol or urinary free cortisol decreases. Consequently the positive correlations of urinary 17OHCS with the other parameters were lost. In a case of adrenal cancer, urinary 17OHCS again did not correlate with plasma cortisol or urinary free cortisol. In these conditions, plasma cortisol and urinary free cortisol still significantly correlated. The present results demonstrated the limit of urinary 17OHCS as the index of the cortisol secretion rate both in some cases of adrenal cancer and in patients taking o,p'-DDD. It is suggested that urinary free cortisol should be utilized as a more accurate index for the cortisol secretion rate in such circumstances.
17-Hydroxycorticosteroids↗
Alterations of adrenergic systems in thyroid slices from patients with Graves' disease.
The responses to TSH of tissue cAMP levels in thyroid slices from patients with Graves' disease were significantly lower than those in normal thyroid slices. Conversely, tissue cAMP levels in thyroid slices from these patients were greatly increased by beta-adrenergic agonists, either isoproterenol or norepinephrine compared with those in normal thyroid slices. The elevation of cAMP levels induced by TSH in normal thyroid slices was significantly reduced by norepinephrine via alpha-adrenergic action as reported previously in canine thyroid slices, while such an elevation by TSH of cAMP levels in slices of Graves' disease thyroids was not inhibited, or rather increased by norepinephrine. These results indicate that, in addition to low responses to TSH, alpha- and beta-adrenergic systems were functionally altered in thyroid tissues of patients with Graves' disease.
Adrenergic alpha-Antagonists↗
Two mouse monoclonal antibodies detecting two different epitopes of an activated lymphocyte antigen on adult T-cell leukemia cells.
Mouse monoclonal antibodies were produced against MT-2 cell line derived from adult T-cell leukemia or human T-cell leukemia virus-rich fraction therefrom. Two IgG1 antibodies, Ta60a and Ta60b, were found to be reactive not only with cell lines derived from adult T-cell leukemia or cutaneous T-cell lymphomas, but also with activated peripheral blood lymphocytes, suggesting the similarity of Ta60 antigen group to Tac antigen which is present on interleukin 2 receptor. Thus, the relationship among these antigens was studied. Two Ta60 antibodies and Tac antibody immunoprecipitated the molecule with almost identical electrophoretic mobility, approximately a Mr 60,000 antigen from [3H]glucosamine-labeled activated peripheral blood lymphocytes or MT-2, MT-1, or ATN-1 cells from adult T-cell leukemia and a Mr 53,000 antigen from HUT-102 cells derived from cutaneous T-cell lymphomas. Further, Tac antibody was found to immunoprecipitate Ta60b molecule on 125I-labeled MT-2 cells by sequential immunoprecipitation, indicating that these two epitopes are on the same molecule. Antibody binding inhibition assays with either 3H-labeled Ta60a or Ta60b antibody demonstrated that Ta60a and Tac are the same epitope, but different from Ta60b. Thus, at least two epitopes were demonstrated to be present on interleukin 2 receptor molecule. However, Ta60b antibody showed almost no blocking effects on proliferation of an interleukin-2-dependent cell line, whereas Ta60a antibody did. Various hematopoietic tumor cells were typed with these two antibodies, but the results with Ta60b antibody were described, because they showed a similar specificity. Ta60b antibody reacted with all adult T-cell leukemia cases, but did not react with T-cell acute lymphoblastic leukemia, lymphoblastic lymphoma, or mature T-cell lymphoma. Interestingly, 3 of 12 acute myeloblastic leukemia and 2 of 5 chronic myelocytic leukemia in blastic crisis showed positive reactions. One-third of B-cell chronic lymphocytic leukemia and B-cell lymphoma as well as a few B-cell lines were also weakly reactive with this antibody. A part of the results with direct tests was confirmed by the absorption tests. The results obtained demonstrated the presence of Ta60b on a certain fraction of malignant hematopoietic cells of other than T-cell origin.
Antibodies, Monoclonal↗
[Screening for the antagonizing agents against lethal toxicity of neocarzinostatin. I. Inhibitory effects of various drugs on the toxicity of neocarzinostatin in vitro and in vivo].
Neocarzinostatin (NCS) used for the chemotherapy of leukemia and cancers such as stomach, pancreas and bladder, has been pointed out to have the side effects mainly causing leukopenia. In order to prevent these side effects of NCS by systemic administration, we have attempted to inject NCS directly into the tumor tissues and to inactivate NCS leaked from the tissues by the treatment of antidotes for NCS. The present report deals with the influence of some antidotes on the toxicity of NCS in vitro and in vivo. The results demonstrated that; Four SH-compounds, such as thiopronin, glutathione (reduced form), sodium thioglycolate and L-cysteine monohydrochloride monohydrate were effective to inactivate antibacterial activity of NCS against M. luteus ATCC 9341 in vitro. It was recognized that acute toxicity of NCS was reduced by pretreatment of these SH-compounds and its action was dose related. The LD50 values of NCS intravenous administration in mice increased 5.8- to 24-fold when 150, 300, 500 and 1,000 mg/kg of thiopronin were administered intravenously 2 minutes prior to NCS. And 2.3- to 4.2-fold by 500 and 1,000 mg/kg of glutathione (reduced form), 1.6- to 4.2-fold by 50, 100 and 200 mg/kg of sodium thioglycolate, 1.9- to 4.2-fold by 100, 200 and 400 mg/kg of L-cysteine monohydrochloride monohydrate respectively. On the other hand, pretreatment of NCS didn't affect the acute toxicity of thiopronin.
Animals↗
[Bioavailabilities of three different phenytoin powders sold in Japan].
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Adolescent↗
Heat-stable calmodulin-binding protein in rat testis. Inhibition of calmodulin-stimulated cyclic nucleotide phosphodiesterase activity.
An inhibitor of procine brain calmodulin-dependent cyclic nucleotide phosphodiesterase was purified about 940-fold from rat testis. This inhibitor inhibited the calmodulin-induced activation of the enzyme without affecting its basal activity. The inhibitor activity was counteracted by a high concentration of calmodulin, but was not by a high concentration of Ca2+. The analysis on polyacrylamide disc gel electrophoresis demonstrated that the inhibitor and calmodulin form a complex in the presence of Ca2+ but not in the presence of excess amount of EGTA. This inhibitor also inhibited the calmodulin-induced activation of Ca2+, Mg2+ -ATPase of human erythrocytes. The inhibitor appeared to be a heat-stable protein, since the inhibitor activity was not attenuated by boiling up to 9 min but was completely abolished by tryptic or chymotryptic digestion. The molecular weights of the inhibitor determined by linear polyacrylamide gradient gel electrophoresis under nondenaturing conditions and sodium dodecyl sulfate-polyacrylamide gel electrophoresis were 40,000 and 32,000, respectively. Thus, the inhibitor is suggested to be a calmodulin-binding protein composed of a monomer which has unique properties different from those of other tissues.
2',3'-Cyclic-Nucleotide Phosphodiesterases↗
[Clinical studies on effective treatment for gastric cancer patients with synchronous hepatic metastasis].
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Adult↗
Developmental changes in the activity and substrate specificities of mouse brain monoamine oxidase.
Developmental changes in monoamine oxidase (MAO) activity in the mouse brain were investigated with the substrates beta-phenylethylamine (PEA), tryptamine, and 5-hydroxytryptamine (5-HT). In the newborn brain, MAO activity towards PEA was found to be much lower than the adult and to be inhibited by clorgyline in a double-sigmoidal fashion. The inhibition curve shifted to a single-sigmoidal pattern with age. MAO activity towards 5-HT as substrate was inhibited by 90% and in a single-sigmoidal manner by clorgyline throughout the postnatal life. Lineweaver-Burk plots with PEA as substrate presented two linear lines (apparent Km: 28.6 and 4.1 microM) for the newborn and one line (apparent Km: 11.4 microM) for the adult, respectively. The plot with high Km value for the newborn brain disappeared in a clorgyline-treated preparation. These findings suggest that age-dependent alterations in the ratio of MAO-A/MAO-B activity affect the substrate specificity of the enzyme.
Animals↗