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991.
Takayuki Matsumoto Tsuneo Kobayashi Toyohiko Kikuchi Toshio Honda Katsuo Kamata 《Journal of Smooth Muscle Research》2005,41(1):23-33
Protein tyrosine kinases and nitric oxide (NO) play important roles in several cardiovascular diseases. In this study, we examined the actions of two compounds, each has structure of genistein (a tyrosine kinase inhibitor) and an NO donor, on endothelium-independent relaxation responses in the isolated rat aorta. By rational drug design, genistein was modified to acquire an NO donor, and we synthesized two such compounds (G-II, G-VI). These compounds and genistein induced dose-dependent relaxation responses in endothelium-denuded aortic strips, the rank order of potencies being G-VI > G-II > genistein. Incubation of endothelium-denuded strips with 1H-[1,2,4] oxadiazolo[4,3-a]-quinoxalin-1-one (ODQ, 10 microM), a guanylyl cyclase inhibitor, inhibited both the G-II- and G-VI-induced relaxations, but not the genistein-induced relaxation. The residual relaxations induced by these two compounds were similar to the genistein-induced relaxation. Incubation of endothelium-denuded strips with lysophosphatidylcholine (LPC, 20 microM)-which is a major atherogenic lysophospholipid component of oxidized low-density lipoprotein and is known to activate tyrosine kinase-caused a significant rightward shift in the dose-response curve for genistein. LPC also shifted the G-II- and G-VI-induced relaxation curves to the right; however, these relaxations in the presence of LPC were greater than that induced by genistein. The sodium nitroprusside-induced relaxation in endothelium-denuded strips was similar between in the absence and presence of LPC. These results suggest that each of our newly developed G-II and G-VI compounds has a dual action, as an NO donor and a tyrosine kinase inhibitor. These compounds may be useful against certain cardiovascular diseases. 相似文献
992.
Takahashi T Ogawa Y Kitaoka K Tani T Uemura Y Taguchi H Kobayashi T Seguchi H Yamamoto H Yoshida S 《International journal of molecular medicine》2005,15(2):213-219
The purpose of this study was to examine the effect of cyclooxygenase-2 (COX-2) inhibitors on the mitogen-activated protein (MAP) kinase signaling pathway and synthesis of glucosaminoglycan after nitric oxide (NO) induction in articular human chondrocytes. After NO induction, the cells were divided into three groups that were treated with either ethanol (control); a selective COX-2 inhibitor (Celecoxib), or no additive, and evaluated. There were no differences in the effect of the selective COX-2 inhibitor on mitochondrial membrane potential or Annexin V levels. However, Celecoxib significantly decreased prostaglandin E2 (PGE2) production. Celecoxib also decreased the phosphorylation state of p38 and p44/42 of MAP kinase. The ratio of chondroitin-6 sulfate (C6S)/C4S was increased in response to the exposure to Celecoxib. Celecoxib did not affect apoptosis, but decreased the activation of MAP kinase in osteoarthritic chondrocytes after NO induction. NO-induced OA chondrocytes were associated with the p38 and the p44/42 MAPK signaling pathways, in a pathway that is distinct from PGE2-mediated apoptosis. 相似文献
993.
994.
Use of Glycopeptidolipid Core Antigen for Serodiagnosis of Mycobacterium avium Complex Pulmonary Disease in Immunocompetent Patients 下载免费PDF全文
Seigo Kitada Ryoji Maekura Naomi Toyoshima Takashi Naka Nagatoshi Fujiwara Masami Kobayashi Ikuya Yano Masami Ito Kazuo Kobayashi 《Clinical and Vaccine Immunology : CVI》2005,12(1):44-51
We report the development of a serodiagnostic method for Mycobacterium avium complex (MAC) disease with an enzyme immunoassay (EIA) with the MAC-specific glycopeptidolipid (GPL) core as the antigen. In this study, we confirmed by EIA that the GPL core antibody was in the sera of immunocompetent patients with MAC disease. The EIA for quantifying the GPL core antibody was evaluated as a clinical tool for serodiagnosis of pulmonary MAC disease. A significant increase in GPL core antibodies (immunoglobulins G, A, and M) was detected in sera of patients with MAC pulmonary diseases when they were compared to patients who were colonized with MAC, patients with Mycobacterium kansasii disease or tuberculosis, and healthy subjects. The sensitivities and specificities of the GPL core-based EIA for diagnosis of MAC pulmonary disease were 72.6% and 92.2%, respectively, for IgG, 92.5% and 95.1%, respectively, for IgA, and 78.3% and 91.0%, respectively, for IgM. The best sensitivity and specificity were obtained by measuring immunoglobulin A antibodies against GPL core antigen. The level of GPL core antibodies reflected disease activity, since it decreased in cured MAC patients who had responded to chemotherapy. Measurement of serum antibodies against GPL core is useful for both diagnosis and assessment of disease activity in MAC disease of the lung. 相似文献
995.
Ito Y Yoshida H Tomoda C Miya A Kobayashi K Matsuzuka F Yasuoka H Kakudo K Inohara H Kuma K Miyauchi A 《Pathology》2005,37(4):296-298
AIMS: Galectin-3, a member of the beta-galactoside binding family of lectins, has been regarded as a useful tool for discriminating malignant tumours from benign nodules of the thyroid, including the distinction between follicular carcinoma and adenoma. However, there are follicular tumours with unclear vascular or capsular invasion, which makes diagnosis more difficult. In this study, we investigated the relationship between galectin-3 expression and the degree of vascular or capsular invasion of follicular tumours. METHODS: We immunohistochemically investigated galectin-3 expression in 260 cases of follicular tumour with various degrees of vascular or capsular invasion classified into four categories. RESULTS: The galectin-3 expression level significantly increased with the degree of vascular or capsular invasion (p<0.0001). However, its diagnostic value for follicular carcinoma was not high because the sensitivity and specificity were 68.7% and 57.5%, respectively. CONCLUSIONS: Our findings suggest that galectin-3 plays a role in the transformation of follicular tumours from benign to malignant; however, when diagnosing follicular tumours, the presence of this protein should not be required for diagnosing malignant transformation in all cases. Therefore, we must conclude that galectin-3 should only be considered an adjuvant marker for follicular carcinoma. 相似文献
996.
Recruitment of katanin p60 by phosphorylated NDEL1, an LIS1 interacting protein, is essential for mitotic cell division and neuronal migration 总被引:3,自引:0,他引:3
Toyo-Oka K Sasaki S Yano Y Mori D Kobayashi T Toyoshima YY Tokuoka SM Ishii S Shimizu T Muramatsu M Hiraiwa N Yoshiki A Wynshaw-Boris A Hirotsune S 《Human molecular genetics》2005,14(21):3113-3128
LIS1 is mutated in the human neuronal migration defect lissencephaly and along with NDEL1 (formerly NUDEL) participates in the regulation of cytoplasmic dynein function during neuronal development. Targeted disruption of Ndel1 suggested that NDEL1 could have other molecular targets that regulate microtubule organization for proper neuronal migration. To further understanding the molecular mechanism of LIS1 and lissencephaly, we identified the katanin p60 microtubule-severing protein as an additional molecular target of NDEL1. We demonstrate that phosphorylation of NDEL1 by Cdk5 facilitates interaction between NDEL1 and p60, suggesting that P-NDEL1 regulates the distribution of katanin p60. Abnormal accumulation of p60 in nucleus of Ndel1 null mutants supports an essential role of NDEL1 in p60 regulation. Complete loss of NDEL1 or expression of dominant negative mutants of p60 in migrating neurons results in defective migration and elongation of nuclear-centrosomal distance. Our results suggest that NDEL1 is essential for mitotic cell division and neuronal migration not only via regulation of cytoplasmic dynein function but also by modulation of katanin p60 localization and function. 相似文献
997.
Immune responses against a single CD8+-T-cell epitope induced by virus vector vaccination can successfully control Trypanosoma cruzi infection 下载免费PDF全文
Miyahira Y Takashima Y Kobayashi S Matsumoto Y Takeuchi T Ohyanagi-Hara M Yoshida A Ohwada A Akiba H Yagita H Okumura K Ogawa H 《Infection and immunity》2005,73(11):7356-7365
In order to develop CD8+-T-cell-mediated immunotherapy against intracellular infectious agents, vaccination using recombinant virus vectors has become a promising strategy. In this study, we generated recombinant adenoviral and vaccinia virus vectors expressing a single CD8+-T-cell epitope, ANYNFTLV, which is derived from a Trypanosoma cruzi antigen. Immunogenicity of these two recombinant virus vectors was confirmed by the detection of ANYNFTLV-specific CD8+ T cells in the spleens of immunized mice. Priming/boosting immunization using combinations of these two recombinant virus vectors revealed that the adenovirus vector was efficient for priming and the vaccinia virus vector was effective for boosting the CD8+-T-cell responses. Moreover, we also demonstrated that the ANYNFTLV-specific CD8+-T-cell responses were further augmented by coadministration of recombinant vaccinia virus vector expressing the receptor activator of NFkappaB (RANK) ligand as an adjuvant. By priming with the adenovirus vector expressing ANYNFTLV and boosting with the vaccinia virus vectors expressing ANYNFTLV and RANK ligand, the immunized mice were efficiently protected from subsequent challenge with lethal doses of T. cruzi. These results indicated, for the first time, that the induction of immune responses against a single CD8+-T-cell epitope derived from an intrinsic T. cruzi antigen was sufficient to control lethal T. cruzi infection. 相似文献
998.
Dendritic cells activated by cross-linking B7-DC (PD-L2) block inflammatory airway disease 总被引:3,自引:0,他引:3
Radhakrishnan S Iijima K Kobayashi T Kita H Pease LR 《The Journal of allergy and clinical immunology》2005,116(3):668-674
BACKGROUND: Allergic asthma is an increasing clinical problem that might be addressed with immunologically based interventions. A novel human antibody that activates human and mouse dendritic cells (DCs) by cross-linking B7-DC has strong immunomodulatory properties and blocks antigen-induced inflammatory lung disease in mice. OBJECTIVE: We sought to evaluate the ability of activated DCs to mediate an antibody-induced protective response against inflammatory lung disease. METHODS: An adoptive transfer strategy was used to test the ability of antibody treatments to activate DCs, inducing a protective response against inflammatory lung disease in mice presensitized to ovalbumin (OVA). After transfer of activated DCs, recipient mice were exposed repeatedly to airway antigen and evaluated for changes in immune reactivity and airway inflammatory disease. RESULTS: Animals presensitized to OVA receiving either systemic treatments with B7-DC cross-linking antibody (XAb) or adoptively transferred antibody-activated DCs were completely protected from airway inflammatory responses normally induced by repeated exposure to OVA. Lymphocytes isolated from spleens or lung-draining lymph nodes of treated animals were highly responsive to OVA and secreted TNF-alpha, IFN-gamma, and IL-10. In contrast, IL-4 was not produced by cells isolated from animals receiving B7-DC XAb. CONCLUSION: Activation of DCs with B7-DC XAb ex vivo before adoptive transfer into presensitized mice is sufficient to protect animals completely from inflammatory lung disease induced by subsequent repeated airway exposure to the offending antigen. This finding is consistent with our hypothesis that in vivo administration of B7-DC XAb modulates the immune response by activating endogenous DCs. 相似文献
999.
Yoshino H Futakuchi M Cho YM Ogawa K Takeshita F Imai N Tamano S Shirai T 《Clinical & experimental metastasis》2005,22(5):441-447
Previously, we established the in vivo lung metastasis model of rat HCC induced by two hepatocarcinogens, diethylnitrosamine (DEN) and N-nitrosomorpholine (NMOR)
at a dose of 120 ppm. This model allows us to investigate modifying factors leading to the inhibition of metastasis formation.
However, low survival rates made the evaluation of metastasis formation difficult. The current experiments were conducted
to modify the experimental protocol to improve survival and to establish a better animal metastasis model. Lower doses of
NMOR (80 or 40 ppm in drinking water) were given to F344 rats for 14 weeks after DEN treatment. Survival rates in the 80 ppm
group and in the 40 ppm group were 57% and 81%, respectively and these values were significantly higher than that in 120 ppm.
Incidences of lung metastasis in the 40 ppm group steadily increased up to 67% by week 36 while that in the 80 ppm increased
sharply up to 86% by week 24. Severity of lung metastases in the 40 ppm group at week 36 was mild compared with the 80 ppm
group at week 24. In the second experiment, in order to characterize HCC development and lung metastasis in the 40 ppm group,
rats given DEN and then followed with 40 ppm NMOR were killed sequentially. Development of HCC was observed at week 14 and
reached 100% incidence at week 20. First lung metastatic lesions were evident at week 22, and incidence of lung metastasis
reached 100%. Tumor cells were identified in the blood at week 20 by RT-PCR. The current study revealed that 40 ppm NMOR for
14 weeks after DEN treatment developed HCC without lung metastases at week 22, then HCC with a frequent lung metastasis at
week 40. Thus, it can be said that this system is a more appropriate model for elucidation of mechanisms of metastasis and
also for analysis of factors to inhibit natural metastasis. 相似文献
1000.