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101.
Koichi Yamada Hiroko Inoue Satoshi Kida Shoichi Masushige Tatsuaki Nishiyama Kenji Mishima Ichiro Saito 《Pathobiology》2006,73(1):1-7
OBJECTIVE: Saliva secretion is mediated by cAMP and the calcium signaling pathway in salivary acinar cells. The PKA signaling pathway plays an important role in protein secretion through the activation of cAMP, in fluid secretion through the elevation of intracellular calcium and in the activation of cAMP response element-binding protein (CREB), which is involved in these signaling cascades. In this study, we investigated whether the activation of CREB plays a part in the salivary secretion in mice. METHODS: We examined CREB activation by assessing phosphorylation at the serine-133 position using Western blotting. RESULTS: Carbachol (a muscarinic acetylcholine agonist) and isoproterenol (a beta-adrenergic agonist) markedly activated CREB in parotid acinar cells. Carbachol and isoproterenol-induced CREB phosphorylation was blocked by atropine (a muscarinic acetylcholine antagonist) and propranolol (a beta-adrenergic antagonist), respectively. The PKA inhibitor H89 inhibited CREB activation, but the PLC inhibitor U73122 did not. Moreover, carbachol- and isoproterenol-stimulated amylase secretion from parotid acinar cells was inhibited by H89 and adenoviral dominant-negative CREB. CONCLUSION: These results indicate that the muscarinic and beta-adrenergic activation of CREB was mediated through the PKA pathway and that CREB is involved in protein secretion from parotid acinar cells. 相似文献
102.
H. Jay Rubenstein Thomas Kenner Koichi Ono 《Pflügers Archiv : European journal of physiology》1973,343(4):309-316
Summary In order to investigate the low frequency properties of renal and femoral hemodynamic variables, pseudorandom testing techniques were used. The arterial flow of each bed, in separate experiments, was modulated by a low amplitude signal based on a pseudorandom binary sequence (PRBS) generated by digital computer.The cross-correlation functions between input flow and arterial pressure, venous pressure, and venous flow exhibit damped oscillations in all cases. These responses are parameterized in terms of a damping ratio () and an undamped natural frequency
n
for a second order model. The parameters of the model are dependent upon the state of the bed as defined by mean arterial and venous pressures, mean flow through the bed, resistance, and oxygen consumption.The results of this study offer further insight into the dynamic low frequency autoregulation phenomenon for the renal and femoral beds of the dog.Supported by NIH Grant HE 11747. 相似文献
103.
Modulation during sleep of the cat trigeminal neurons responding to tooth pulp stimulation 总被引:1,自引:0,他引:1
Sleep-induced changes in the trigeminal neuron responses to electrical stimulation of the cat tooth pulp were studied. Two parameters were adopted: One was the evoked spike number at two times the threshold intensity (2 X T response magnitude), which would reveal the level shifting of the neuronal response by the sleep-regulatory system. Another was the rate of change in the response intensity when the stimulus was raised to a level of 0.7 time the arousal threshold during light slow wave sleep (sensitivity gradient), which would reflect the influences of the pain-modulatory system driven by strong noxious inputs. It was found that during sleep the two indexes tended to show a correlated change; the neurons which came to have a greater 2 X T response magnitude tended to have a smaller sensitivity gradient than during wakefulness, and vice versa. It was suggested that two contrasting populations of tooth pulp neurons might be differentiated, and that the sleep-regulatory system and the pain-modulatory system would have differential but correlated controls over these two kinds of neurons. 相似文献
104.
Hiroyuki Kageyama Yoko Hayashi Shigeharu Harada Yasushi Kai Nobutami Kasai Yoshio Okamoto Koichi Hatada 《Macromolecular chemistry and physics.》1985,186(1):203-214
The molecular structures of 1,1-diphenylethyl methacrylate (1,1-DPEMA) and triphenylmethyl methacrylate (TrMA) were determined by means of X-ray diffraction. 1,1-DPEMA: monoclinic, space group P21/a,a = 9,666(6), b = 19,94(2), c = 8,132(6) Å, β = 104,49(7)°, and Z = 4; TrMA: monoclinic, space group P21/n, a = 17,349(3), b = 9,487(2), c = 11,254(2) Å, β = 102,30(2)°, and Z = 4. Both structures were solved by the direct method and refined by the block-diagonal least-squares procedure to R = 0,175 and 0,056 for non-zero reflections, respectively. In both molecules, conformations about the C(1)? C(2) and C(1)? O(1) bonds are all synperiplanar and one of the two or three phenyl groups attached to the C(5) atom is in trans to the O(2). 相似文献
105.
Ken-ichi Sasaki Yasuo Kokai Shin-ichi Atsumi Hirotoshi Tobioka Norimasa Sawada Koichi Hirata Michio Mori 《Medical Electron Microscopy》1998,31(2):61-67
Epithelioid disorganization is a hallmark of gastrointestinal cancers and is believed to be associated with malignant phenotypes such as invasiveness and the potentiality for metastasis. Although tight junctions (TJs) are known to be crucial for the maintenance of polarized organization of the gastrointestinal epithelium, changes in the TJ proteins in human cancers have not yet been fully elucidated. In this report, we investigated the expression and localization of three TJ proteins-barmotin (7H6 antigen), occludin, and ZO-1-in three phenotypically different human colon cancer cell lines exhibiting differnt grades of epithelioid organization. All three proteins were localized at the most apical part of the cell border corresponding to the site of TJs in T84 cells, in which epithelioid organization was well preserved. In contrast, in COLO320DM cells, which showed no epithelioid phenotypes, occludin was not detectable at either the protein or mRNA level, although barmotin and ZO-1 were present in the cytoplasm. In the third cell line, DLD-1, which showed an epithelioid phenotype intermediate between T84 and COLO320DM, aberrant expression of occludin was found in the basolateral cell membrane. On the other hand, barmotin was present in the cytoplasm, whereas ZO-1 was localized at the cell border. These observations showed that changes in the expression of TJ proteins occur in close correlation with epithelioid disorganization in human colon cancers. 相似文献
106.
Antitumor immune response by CX3CL1 fractalkine gene transfer depends on both NK and T cells 总被引:6,自引:0,他引:6
Xin H Kikuchi T Andarini S Ohkouchi S Suzuki T Nukiwa T Huqun Hagiwara K Honjo T Saijo Y 《European journal of immunology》2005,35(5):1371-1380
The CX3C chemokine fractalkine (CX3CL1) exists as both a membrane-bound form promoting firm cell-cell adhesion and a soluble form chemoattracting leukocytes expressing its receptor CX3CR1. When adenoviral vector expressing mouse fractalkine (AdFKN) was transduced to the tumor cells, fractalkine was expressed as both membrane-bound form on the tumor cells and soluble form in the supernatant in vitro. Intratumoral injection of AdFKN (1 x 10(9)PFU/tumor) into C26 and B16F10 tumors resulted in marked reduction of tumor growth compared to control (C26: 86.5%, p<0.001; B16F10: 85.5%, p<0.001). Histological examination of tumor tissues revealed abundant infiltration of NK cells, dendritic cells, and CD8(+) T lymphocytes 3 and/or 6 days after treatment with AdFKN. Splenocytes from mice treated by AdFKN developed tumor-specific cytotoxic T cells, and thereby protected from rechallenging with parental tumor cells. Antitumor effects by AdFKN were completely abrogated in both NK cell-depleted mice and CD8(-/-) mice, and partially blocked in CD4(-/-) mice. These data indicated that fractalkine mediates antitumor effects by both NK cell-dependent and T cell-dependent mechanisms. This study suggests that fractalkine can be a suitable candidate for immunogene therapy of cancer because fractalkine induces both innate and adaptive immunity. 相似文献
107.
Flavonoids such as luteolin, fisetin and apigenin are inhibitors of interleukin-4 and interleukin-13 production by activated human basophils 总被引:2,自引:0,他引:2
Hirano T Higa S Arimitsu J Naka T Shima Y Ohshima S Fujimoto M Yamadori T Kawase I Tanaka T 《International archives of allergy and immunology》2004,134(2):135-140
BACKGROUND: We have previously shown that fisetin, a flavonol, inhibits IL-4 and IL-13 synthesis by allergen- or anti-IgE-antibody-stimulated basophils. This time, we investigated the inhibition of IL-4 and IL-13 production by basophils by other flavonoids and attempted to determine the fundamental structure of flavonoids related to inhibition. We additionally investigated whether flavonoids suppress leukotriene C4 synthesis by basophils and IL-4 synthesis by T cells in response to anti-CD3 antibody. METHODS: Highly purified peripheral basophils were stimulated for 12 h with anti-IgE antibody alone or anti-IgE antibody plus IL-3 in the presence of various concentrations of 18 different kinds of flavones and flavonols. IL-4 and IL-13 concentrations in the supernatants were then measured. Leukotriene C4 synthesis was also measured after basophils were stimulated for 1 h in the presence of flavonoids. Regarding the inhibitory activity of flavonoids on IL-4 synthesis by T cells, peripheral blood mononuclear cells were cultured with flavonoids in anti-CD3-antibody-bound plates for 2 days. RESULTS: Luteolin, fisetin and apigenin were found to be the strongest inhibitors of both IL-4 and IL-13 production by basophils but did not affect leukotriene C4 synthesis. At higher concentrations, these flavonoids suppressed IL-4 production by T cells. Based on a hierarchy of inhibitory activity, the basic structure for IL-4 inhibition by basophils was determined. CONCLUSIONS: Due to the inhibitory activity of flavonoids on IL-4 and IL-13 synthesis, it can be expected that the intake of flavonoids, depending on the quantity and quality, may ameliorate allergic symptoms or prevent the onset of allergic diseases. 相似文献
108.
Peter Szigligeti Lisa Neumeier Eugene Duke Claire Chougnet Koichi Takimoto Susan Molleran Lee Alexandra H. Filipovich Laura Conforti 《The Journal of physiology》2006,573(2):357-370
T lymphocytes encounter hypoxia when they migrate to pathological sites such as tumours and wounds. The inability of T cells to provide an efficient defence at these sites can in part be explained by the hypoxic environment. Kv1.3 channels, important components of the T cell activation process are inhibited by hypoxia and their inhibition accounts for a hypoxia-induced decrease in T cell proliferation. Although Kv1.3 channels play a key role in T cell O2 sensing, the signalling mechanisms mediating their response to hypoxia are still not understood. In this study, we show that the src-protein tyrosine kinase p56Lck (Lck) is required for Kv1.3 channel response to hypoxia. Pre-exposure to the src inhibitor PP2 abolished the hypoxia-induced inhibition of Kv1.3 channels in primary human T lymphocytes. Moreover, Kv1.3 channel sensitivity to hypoxia was lost in Lck-deficient Jurkat T cells. Further studies with recombinant Kv1.3 channels showed that Kv1.3 channels lack intrinsic O2 sensitivity, but delivery of Lck into the cells and transfection of a constitutively active Lck (Y505FLck) restored their sensitivity to hypoxia. Although Lck is necessary for the Kv1.3 channel response to hypoxia, it does not directly inhibit Kv1.3 channels. Indeed, under normal oxygen tension, delivery of active Lck into L929 cells and overexpression of Y505FLck did not decrease recombinant Kv1.3 currents. On the contrary, activation of endogenous src kinases increased wild-type Kv1.3 currents in T lymphocytes. Our findings indicate that Lck is required for the acute response to hypoxia of human T lymphocytes as it is necessary to confer O2 sensitivity on Kv1.3 channels. 相似文献
109.
Lipocalin-type prostaglandin D synthase (L-PGDS) is dominantly expressed in the leptomeninges surrounding the brain and secreted into the cerebrospinal fluid as β-trace, a major cerebrospinal fluid protein. To examine the interaction between the leptomeninges and the brain parenchyma, we co-cultured rat leptomeningeal cells with cells dissociated from the neonatal rat cortex and found that the production of L-PGDS was remarkably increased after the co-cultivation. A similar increase in L-PGDS production was observed by the co-culturing of the leptomeningeal cells with cells dissociated from astrocyte-rich cultures or with 1321-N1 astrocytoma cells. When a crude membrane fraction prepared from 1321-N1 cells was added to leptomeningeal cell cultures, L-PGDS gene expression was slowly increased up to 48 h after the addition. These results indicate that leptomeningeal cells enhance their L-PGDS production by a slow activation of L-PGDS gene expression through their contact with astrocytes. 相似文献
110.
Takasuka N Fujii H Takahashi Y Kasai M Morikawa S Itamura S Ishii K Sakaguchi M Ohnishi K Ohshima M Hashimoto S Odagiri T Tashiro M Yoshikura H Takemori T Tsunetsugu-Yokota Y 《International immunology》2004,16(10):1423-1430
The recent emergence of severe acute respiratory syndrome (SARS) was caused by a novel coronavirus, SARS-CoV. It spread rapidly to many countries and developing a SARS vaccine is now urgently required. In order to study the immunogenicity of UV-inactivated purified SARS-CoV virion as a vaccine candidate, we subcutaneously immunized mice with UV-inactivated SARS-CoV with or without an adjuvant. We chose aluminum hydroxide gel (alum) as an adjuvant, because of its long safety history for human use. We observed that the UV-inactivated SARS-CoV virion elicited a high level of humoral immunity, resulting in the generation of long-term antibody secreting and memory B cells. With the addition of alum to the vaccine formula, serum IgG production was augmented and reached a level similar to that found in hyper-immunized mice, though it was still insufficient to elicit serum IgA antibodies. Notably, the SARS-CoV virion itself was able to induce long-term antibody production even without an adjuvant. Anti-SARS-CoV antibodies elicited in mice recognized both the spike and nucleocapsid proteins of the virus and were able to neutralize the virus. Furthermore, the UV-inactivated virion induced regional lymph node T-cell proliferation and significant levels of cytokine production (IL-2, IL-4, IL-5, IFN-gamma and TNF-alpha) upon restimulation with inactivated SARS-CoV virion in vitro. Thus, a whole killed virion could serve as a candidate antigen for a SARS vaccine to elicit both humoral and cellular immunity. 相似文献