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Biomedical subjects

K Kitagawa

Publications and source records attributed to K Kitagawa.

At least 289 records · Page 16Linked to original sources

Berberine sulfate inhibits tumor-promoting activity of teleocidin in two-stage carcinogenesis on mouse skin.

Berberine sulfate, an isoquinoline alkaloid isolated from Hydrastis canadensis L., inhibited the effects of the tumor promoters 12-O-tetradecanoylphorbol-13-acetate and teleocidin, such as increased 32Pi-incorporation into phospholipids of cell membrane and hexose transport. Berberine sulfate also markedly suppressed the promoting effect of teleocidin on skin tumor formation in mice initiated with 7,12-dimethylbenz[a]anthracene.

3-O-Methylglucose↗

Analysis of hexose transport in untransformed and sarcoma virus-transformed mouse 3T3 cells by photoaffinity binding of cytochalasin B.

The effect of simian virus 40 transformation on the hexose transport system in mouse embryo fibroblast Swiss 3T3 cells was examined. The concentration of hexose transporters was estimated by measuring D-glucose-inhibitable cytochalasin B binding. The binding of cytochalasin B to the plasma membranes of simian virus 40-transformed mouse 3T3 cells (SV3T3 cells) was significantly greater than that of 3T3 cells. On the other hand, cytochalasin B binding to the microsomal membranes of SV3T3 cells was decreased, and the total amount of binding to plasma and microsomal membranes was not significantly changed in both cell lines. The electrophoretic analysis demonstrated that both hexose-transporter components of Mr 46 000 and Mr 58 000 affinity labeled were responsible for an increase in the hexose transport by viral transformation. These results suggested that the higher hexose-transport activity of transformed cells is caused by a redistribution of transporter from intracellular membranes to plasma membranes.

Adenosine Monophosphate↗

Effect of tunicamycin on hexose transport in mouse embryo fibroblast Swiss 3T3 cells.

The role of glycosylation of the carrier in the transporting activity was investigated in Swiss 3T3 cells. Inhibition of protein glycosylation by tunicamycin resulted in the decrease of hexose uptake in a dose- and time-dependent manner without a cytotoxic effect. From kinetic analysis, a decrease in the number or availability of hexose carriers in the plasma membrane was suggested. This was in good correlation with the decrease in the amount of photoaffinity cytochalasin B binding in the plasma membrane by the treatment with tunicamycin. The rate of phorbol 12,13-dibutyrate-induced translocation of the hexose carrier from microsomal to plasma membrane was reduced in tunicamycin-treated cells, which may be correlated with the decrease in the number of the completely glycosylated carrier translocatable from the microsomal membrane. In both tunicamycin-treated and untreated cells, the stimulation of hexose transport by phorbol 12,13-dibutyrate was abolished by the removal of phorbol 12,13-dibutyrate, and upon its readdition the stimulation recovered to the same degree as before the removal. Thus, the recycling of the functionally mature hexose carrier appeared not to be affected by the treatment with tunicamycin. These results suggested that complete glycosylation of the carrier may be necessary for the translocation of the carrier from microsomal to plasma membrane to accomplish its function on the cell surface.

3-O-Methylglucose↗

Tumor promoter-stimulated translocation of glucose transport system in mouse embryo fibroblast Swiss 3T3 cell.

Assay for D-glucose-inhibitable 3H-cytochalasin B-binding was carried out to elucidate the action mechanism of the tumor promoter-induced enhancement of glucose transport activity in Swiss 3T3 cells. Incubation of the cells with 12-0-tetradecanoylphorbol-13-acetate (TPA) increased the amount of D-glucose-inhibitable cytochalasin B-binding sites in plasma membrane from 13.5 to 40.1 pmol/mg protein. On the other hand, TPA treatment resulted in the decrease of binding sites in microsomal membrane from 68.9 to 34.1 pmol/mg protein. The tumor promoter-induced translocation of hexose transport system from microsomal membrane to plasma membrane was inhibited by the treatment with 2,4-dinitrophenol before the addition of TPA but was not affected by the treatment with cycloheximide. By removal of the promoter from its receptor, the stimulatory effect of the promoter on the translocation of hexose transport system was decreased. The analysis by electrophoresis demonstrated that among the affinity labeled hexose transporter components of Mr 48,000 and Mr 55,000, the former was responsible for the TPA-induced increase in hexose transport activity in plasma membrane.

Animals↗

Ca2+-dependent stimulation of 3-O-methylglucose transport in mouse fibroblast Swiss 3T3 cells induced by phorbol-12,13-dibutyrate.

Binding of phorbol-12,13-dibutyrate (PDBu), a tumor promoter, to quiescent Swiss 3T3 cells increased the number of hexose carriers, resulting in stimulation of membrane transport of 3-O-methylglucose (3MeGlu) in a Ca2+-dependent fashion. Extracellular Ca2+ was necessary to initiate the binding of PDBu to its receptor, and intracellular Ca2+ was required to maintain it. The loss of PDBu-binding, caused by elimination of Ca2+, was accompanied by a loss of stimulation of hexose transport. These results indicated that Ca2+-dependent, continuous binding of PDBu to its receptor was essential to induce the stimulation of hexose transport.

3-O-Methylglucose↗

Unusual portosystemic collateral penetrating the liver parenchyma.

We present a case of an extremely rare portosystemic collateral pathway which arose from the right intrahepatic portal vein, passed through the liver parenchyma, and terminated into the inferior vena cava. We demonstrate the findings of diagnostic imaging and discuss the etiology of the collateral circulation in this unusual case.

Aged↗

Interaction between the A2 and A19 amino acid residues is of critical importance for high biological activity in insulin: [19-leucine-A]insulin.

The replacement of tyrosine at position A19 by leucine in the insulin molecule led to an analogue, [19-leucine-A]insulin [( Leu19-A]insulin), displaying insignificant receptor binding affinity and in vitro biological activity less than 0.1 and 0.05%, respectively, compared to the natural hormone. This analogue along with the previously reported [2-glycine-A]-, [2-alanine-A]-, and [2-norleucine-A]insulins is the least potent insulin analogue we have examined. Circular dichroic studies showed that all these analogues are monomeric at concentrations at which insulin is primarily dimeric. We conclude that an aromatic ring at position A19 and the presence of the side chain of isoleucine at position A2 are each of critical importance for high biological activity in insulin. It appears that the van der Waals interaction between the side chain of isoleucine A2 and tyrosine A19, present in crystalline insulin, is among the most important determinants for high biological activity in insulin.

Amino Acids↗

Critical role of the A2 amino acid residue in the biological activity of insulin: [2-glycine-A]- and [2-alanine-A]insulins.

We report the synthesis of [2-glycine-A]insulin ([ Gly2 -A]insulin) and [2-alanine-A]insulin ([ Ala2-A]insulin) in which the indicated amino acid has been substituted for isoleucine found in this position in the natural hormone. The circular dichroic (CD) spectra of the analogues were obtained, and their properties were examined in several biological assays. CD studies suggested that the analogues remain monomeric at concentrations at which insulin is partly or mostly dimeric. Both analogues are extremely weak full agonists. [ Gly2 -A]-insulin displays 0.05% of the potency of bovine insulin, whereas [Ala2-A]insulin assays at 0.4% of the activity of the natural hormone. We conclude that the presence of the side chain of isoleucine at position A2 is a critical requirement for high biological activity in insulin. The data, together with previous observations, are discussed in connection with an interaction between the side chain of isoleucine-A2 and the phenolic ring system of tyrosine-A19, which are in van der Waals contact in crystalline insulin. This interaction may be required to permit the molecule to assume a conformation consistent with dimerization and with binding to the insulin receptor.

Amino Acid Sequence↗

Inhibition of 12-O-tetradecanoylphorbol-13-acetate-stimulated 3-O-methyl-glucose transport in mouse Swiss 3T3 fibroblasts by glycyrrhetic acid.

12-O-Tetradecanoylphorbol-13-acetate (TPA), a potent tumor promoter, stimulated 3-O-methyl-glucose (3MeGlu) transport in Swiss 3T3 mouse fibroblasts. Application of glycyrrhetic acid, a terpenoid derivative, to cells prior to the treatment with TPA showed a time- and dose-dependent inhibitory effect on the TPA-stimulated 3MeGlu transport. From the kinetic analysis, it was suggested that the TPA-induced stimulation of hexose transport was due to the enhancement of the number of hexose carrier, which was completely inhibited by glycyrrhetic acid.

3-O-Methylglucose↗

Antitumor-promoting activity of glycyrrhetic acid in mouse skin tumor formation induced by 7,12-dimethylbenz[a]anthracene plus teleocidin.

Glycyrrhetic acid inhibited the action of tumor promoter in vitro and in vivo. Glycyrrhetic acid inhibited the increased phospholipid metabolism of cultured cells induced by tumor promoters, 12-O-tetradecanoylphorbol-13-acetate or teleocidin, and it markedly suppressed the promoting effect of teleocidin on skin tumor formation in mice initiated with 7,12-dimethylbenz[a]anthracene.

9,10-Dimethyl-1,2-benzanthracene↗

Segmental staining on hepatic arteriography as a sign of intrahepatic portal vein obstruction.

Peripheral obstruction of intrahepatic portal vein branches was detected by dynamic sequential computed tomography during arterial portography and subsequently confirmed surgically in 9 patients with hepatic neoplasm (7 hepatocellular carcinomas, 1 cholangiocarcinoma, and 1 metastatic lymphadenopathy from gastric carcinoma). In 1 patient, 2 obstructed segments were seen. Eight of these 10 segments showed more dense staining than other regions of the liver during infusion hepatic angiography. Retrograde opacification of the peripheral venules of the obstructed portion was seen in 2 of these 8 segments. This pattern was attributed to trans-sinusoidal or peripheral arterioportal shunting. In 5 cases, the segmental staining obscured the tumor stain, making the tumor appear larger than it actually was or causing it to be missed altogether.

Adenoma, Bile Duct↗