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Volume 110, Issue 6
Displaying 1-7 of 7 articles from this issue
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Tetsuro URUSHIDANI, Taku NAGAO1997 Volume 110 Issue 6 Pages 303-313
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSThe parietal cell has three types of activating receptors for acid secretion on its basolateral membrane, i.e., histamine H2, acetylcholine M3, and gastrin CCKB. Activation of acid secretion is achieved by two concomitant functional changes namely: (i) tubulovesicles fuse with the apical secretory membrane, thus recruiting functional pumps to the expanded microvillar surface, and (ii) the apical membrane acquires a permeability to KCl. The major path for parietal cell stimulation is via H2-receptor-mediated adenylate cyclase and elevation of cAMP to activate protein kinase A (PKA), which phosphorylates key effector proteins, e.g., ezrin, a membrane-cytoskeletal linker, apical Cl- or K+-channels. Ca2+ is liberated from intracellular stores by IP3, which in turn is the result of M3-, CCKB-, or possibly H2-coupled activation of phospholipase C. The resulting protein kinase C activation may have both inhibitory and excitatory roles. Elevated Ca2+ activates calmodulin-dependent kinases, e.g., calmodulin kinase II and myosin light chain kinase, that could promote vesicular motor activity. Ezrin is considered to play a main role in the vesicular transport system of the parietal cell. The regulation might be conducted through the phosphorylation of the molecule to modify its property to interact with the cytoskeletal components, membranes or membrane proteins.View full abstractDownload PDF (9020K) -
Kensuke KISARA, Koichi TAN-NO, Tsukasa SAKURADA1997 Volume 110 Issue 6 Pages 315-324
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSProgress in the characterization of tachykinin receptors and the understanding of the physiological and pathological roles of tachykinins is highly dependent on the discovery of potent and selective antagonists with metabolic stability. We have recently described a peptidic antagonist of the tachykinin NK 1 receptor, sendide (Tyr-D-Phe-Phe-D-His-Leu-Met-NH2), that is a selective and extremely potent antagonist of NK-1 receptors, but displays no antagonistic activity on the response induced by NK-2 or NK-3-receptor agonists in the mouse spinal cord. When coadministered with substance P (SP) intrathecally (i.t.), sendide markedly inhibited the scratching, biting and licking behavior induced by SP in a dose-dependent manner. The antagonistic effect of sendide on the SP-induced behavioral response was approximately 7300 times more potent than that of CP-96, 345, a non-peptidic NK-1-receptor antagonist. The duration of the antagonistic effect of sendide was longer than that of CP-96, 345. The behavioral response elicited by other NK-1-receptor agonists, septide, physalaemin and [Sar9, Met (O2)11]-SP, was reduced significantly by a small dose of sendide. In the [3H]-SP binding assay using mouse spinal cord membranes, sendide potently displaced [3H]-SP binding, with a potency approximately 5.4×104 times greater than that of CP-96, 345. Moreover, Lt. administration of sendide was found to produce the antinociceptive effect through the blockage of NK-1 receptors in the mouse formalin and capsaicin tests. Sendide is therefore likely to become a powerful pharmacological tool for studying the functional roles of NK-1 receptors in the central nervous system.View full abstractDownload PDF (8396K) -
Shuji HASHIMOTO1997 Volume 110 Issue 6 Pages 325-332
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSProblems of multiple comparison were discussed without assuming technical knowledge of statistics. For the first question concerning why to use multiple comparison procedures, theoretical bases of statistical inference and multiple comparison (including type I error rate and familywise error rate) were briefly outlined. For the second question concerning how to properly use multiple comparison procedures, multiple comparison procedures were introduced, and their characteristics were compared. Families of comparisons are different among Dunnett's, Tukey's and Scheffe's tests. Assumptions of dose-response relationship are different among Dunnett's, Williams' tests and linear regression analysis. Duncan's test does not control familywise error rate at a fixed level. For the last question concerning what is remarked for multiple comparison, approaches to several problems such as abnormality and heteroscedasticity were provided. Philosophy and strategy to multiple comparison problems were discussed.View full abstractDownload PDF (5915K) -
Isao YOSHIMURA, Takashi OMORI1997 Volume 110 Issue 6 Pages 333-340
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSThis paper considers the method of data analysis for a pharmacological experiment with multiple dose groups, in which a response variable is observed repeatedly at several time periods. The inappropriateness of conventionally used statistical methods such as the t-test, Dunnett's multiple comparison procedure and analysis of variance method is pointed out. We recommended that the dose-response relationship should be estimated as a response function of time incorporating the dose effect as parameters. We also propose to adopt a strategy that the researcher tests some hypotheses on the parameters in the response function appropriate to the objective of the experiment after estimating parameters of the response function based on the observed data. A numerical example applying the strategy to real data is presented.View full abstractDownload PDF (6389K) -
Kazuhiko MATSUMOTO1997 Volume 110 Issue 6 Pages 341-346
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSThe cumulative chi-squared statistic has been proposed for testing against ordered alternatives in various statistical models. As usual statistical tests of ordered column categorical data, the χ2 test, Fisher's exact test and Wilcoxon test are used. Pharmacological studies often are performed by multiple dosing. Data obtained from these studies are called ordered categorical data. The cumulative chi-squared statistic, which has been proposed by Hirotsu and Shibuya for testing against ordered alternatives in various statistical models, is little used in spite of its good applicability in the field of pharmacology. This method was too difficult for the general pharmacologist and biological scientists because it requires the use of a complex matrix and a powerful computer to carry out the analysis. However since a more simple method was proposed by Matsumoto and Yoshimura this method has been used more frequently in the biological sciences. In this paper, the one way cumulative chi-squared statistic test and two way chi-squared statistic test are compared with the chi-squared statistic test and Wilcoxon test.View full abstractDownload PDF (3438K) -
Mitsushi YOSHIOKA, Pao-Li WANG, Kiyoshi OHURA1997 Volume 110 Issue 6 Pages 347-355
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSPorphyromonas gingivalis (P. gingivalis) has been implicated as an important pathogen in periodontal diseases, and its protease (Arg-gingipain) is one of the most important disease-causing factors. We have examined the effect of Arg-gingipain on the cell adhesion molecules of human periodontal ligament fibroblasts (HPLF). The Arg-gingipain was purified from the culture supernatant of P. gingivalis. Confluent monolayer cultures of HPLF were incubated for up to 24 hr with Arg-gingipain. As for the morphological changes, HPLF detached from the dish at 16 hr. The growth rate as evaluated by the MTT assay increased at 12 hr, and then the rate decreased. The cell adhesion molecules (ICAM 1, intercellular adhesion molecule-1; CD54, VCAM 1, vascular cell adhesion molecule-1; CD106, and VLA-4, very late antigen-4; CD49d/cd29) were constitutively expressed on HPLF by flow cytometric analysis. The amounts of fibronectin were increased at 12 hr and then, its production was decreased. The levels of ICAM-1, VCAM-1 and VLA-4 expressions were increased; however, after 16 hr, the levels of expression of all cell adhesion molecules were decreased. Our experiments showed that adhesion decreases as a result of destruction of the extracellular matrix when bacterial protease brings about rapid cell destruction. This may suggest that the increase of expression of cell adhesion molecules is due to a mechanism that compensates for the decreased cellular-extracellular matrix. Alternatively, it may suggest that after the expression is activated, cell adhesion molecules help to increase bacterial adhesion to cells.View full abstractDownload PDF (7339K) -
Jun KUSUNOKI, Katsumi ARAGANE, Tetsuya KITAMINE, Tetsuaki YAMAURA, Har ...1997 Volume 110 Issue 6 Pages 357-365
Published: 1997
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSThe present study was conducted to investigate the inhibitory effect of F-1394, a potent and selective inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), on incorporation of 14C-oleic acid into cholesteryl ester in cultured Caco-2 cells, a human intestinal cell line, and compare its effect to those of other ACAT inhibitors and hypolipidemic agents. The cholesterol esterification in Caco-2 cells was strongly inhibited by F-1394 in a concentration-dependent manner with the estimated IC50 value of 71 nM. In contrast, the estimated IC50 values of the other ACAT inhibitors such as YM-17E, CI-976, CL-277, 082 and DL-melinamide are 121 nM, 702 nM, 21.5 μM and 20.9 μM, respectively. Simvastatin, a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, also inhibited the ACAT activity in Caco-2 cells with an IC50 value of 22.5 μM, whereas pravastatin Na, probucol and clofibrate did not affect the activity. Furthermore, F-1394 at a concentration of 100 nM inhibited the basolateral secretion of cholesteryl ester by 90 % from differentiated Caco-2 cells that were cultured on a membrane filter. These results demonstrate that F-1394 strongly inhibits human intestinal ACAT activity and basolateral secretion of cholesterol from Caco-2 cells. Therefore, F-1394 may have a therapeutic potential for dietary hyperlipidemic subjects.View full abstractDownload PDF (6419K)
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