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1.
Shigeji Matsumoto Mizuho Ikeda Toshimi Nishikawa Shinki Yoshida Takeshi Tanimoto Masahiro Ito Chikako Saiki Mamoru Takeda 《The Journal of pharmacology and experimental therapeutics》2002,300(2):597-604
The excitatory responses of deflationary slowly adapting pulmonary stretch receptor (SAR) activity to lung deflation ranging from approximately -15 to -25 cm of H(2)O for approximately 5 s were examined before and after administration of flecainide, a Na(+) channel blocker, and K(+) channel blockers, such as 4-aminopyridine (4-AP) and tetraethylammonium (TEA). The experiments were performed in anesthetized, artificially ventilated rats after unilateral vagotomy. The deflationary SARs increased their activity during lung deflation and its effect became more pronounced by increasing the degree of negative pressure. During lung deflation the average values for the deflationary SAR adaptation index (AI) were below 40%. Intravenous administration of veratridine (50 microg/kg), an Na(+) channel opener, stimulated deflationary SAR activity: one maintained excitatory activity mainly during deflation and the other receptors showed a tonic discharge during both deflation and inflation. Despite the difference in deflationary SAR firing patterns after veratridine administration, flecainide treatment (6.0 mg/kg) blocked veratridine-induced deflationary SAR stimulation and also caused strong inhibition of the excitatory responses of deflationary SARs to lung deflation. Under these conditions, the average values for deflationary SAR AI were over 90%. The responses of deflationary SARs and deflationary SAR AI to lung deflation were not significantly altered by pretreatment with either 4-AP (0.7 and 2.0 mg/kg) or TEA (2.0 and 6.0 mg/kg). These results suggest that the excitatory effect of lung deflation on deflationary SAR activity is mediated by the activation of flecainide-sensitive Na(+) channels on the nerve terminals of deflationary SARs. 相似文献
2.
S Saiki N Meguro T Morita Y Tomooka O Maeda T Kinouchi M Kuroda T Miki M Usami T Kotake 《Nihon Hinyōkika Gakkai zasshi. The japanese journal of urology》1990,81(10):1537-1542
Two hybridomas secreting two monoclonal antibodies IgG1 B1.4 and IgG2a B1.6 were obtained by immunizing BALB/c mice with human bladder cancer cell line EJ-1. In immunohistochemical staining of cryopreserved tissues, B1.4 reacted with 0 of 9 grade 1 TCC, 6 of 11 grade 2, all of 6 grade 3 and five metastatic specimens. The antigen recognized by B1.4 was not expressed by normal urothelial cells but were expressed by vascular endothelial cells and muscle of tunica media. The target antigen of B1.6 was expressed by normal urothelial cells and all grade of TCC. In this study, it was demonstrated that poorly differentiated bladder cancer and metastatic specimens of bladder cancer express a vascular carbohydrate antigen. Taking the escape mechanism of immune surveillance, into consideration, it is possible that the antigen recognized by B1.4 is an indicator of metastatic potential of bladder cancer. 相似文献
3.
Ikuo Saiki Jun Murataxd Junya Yoneda Hideo Kobayashi Ichiro Azuma 《International journal of cancer. Journal international du cancer》1994,56(6):867-873
We have examined the influence of fibroblasts on the invasive and migratory potential of highly metastatic melanoma B16-BL6 and weakly metastatic B16-FI cells in vitro. Co-culture of B16-BL6 cells with a fibroblast monolayer without cellular contact in a Transwell chamber more effectively induced tumor-cell invasion into Matrigel basement membrane than co-culture of B16-FI cells with a fibroblast monolayer. The activity was closely correlated with the chemotactic migration of tumor cells toward the fibroblast monolayer. We also found that the conditioned medium (CM) from the co-culture of fibroblasts with B16-BL6 cells without cellular contact, i.e., CM (B16-BL6/fibroblast), rather than from co-culture with B16-FI cells, could potentially promote the migration of tumor cells of both types. Tumor cells did not chemotactically migrate to the CM (B16-BL6), CM (B16-FI) or CM (fibroblast). Antibodies against TGF-β1 or FN almost completely abolished the chemotactic migration of B16-BL6 cells to the CM (B16-BL6/fibroblast) or CM (TGF-β1 -treated fibroblast) when these antibodies were c-incubated with fibroblasts and either B16-BL6 or TGF-β1. In contrast, the anti-EGF antibody did not show any inhibitory effects. Analysis of amounts of TGF-β1 or FN in various CM using ELISA plates, and using their specific antibodies, revealed that the concentration of TGF-β1 in the CM (B16-BL6) was slightly higher than in the CM (B16-FI), and the amount of FN in the CM (B16-BL6/fibroblast) was twice as high as in the CM (B16-FI /fibroblast). These results suggest that TGF-β1 released from B16-BL6 cells can stimulate fibroblasts to produce FN; consequently, the tumor cells were able to chemotactically migrate toward the released FN, and the differences in invasive and migratory activities towards fibroblasts in B16-BL6 and B16-FI cells may in part be due to the amounts of TGF-β1 from tumor cells and of FN from TGF-β1 -stimulated fibroblasts. 相似文献
4.
5.
Antimetastatic Activity of Polymeric RGDT Peptides Conjugated with Poly(ethylene glycol) 总被引:1,自引:0,他引:1
Ikuo Saiki Junya Yoneda Yu Igarashi Miho Aoki Naoto Kusunose Kei-ichi Ono Ichiro Azuma 《Cancer science》1993,84(5):558-565
Polymeric peptides containing defined repetitive or cyclic structures of RGDT sequence, (RGDT)n (n = 1 to 11) and cyclo(RGDT)n (n=2 to 4), at a dose of 500 μg exhibited an inhibitory effect on experimental lung metastasis upon co-injection with tumor cells and the magnitude of the effect increased in parallel with the increase of degree of repetition of the RGDT sequence. The conjugation of (RGDT)n (n = 1, 5, 11) with poly(ethylene glycol), PEG as a polymeric carrier led to enhanced inhibition of lung metastasis in proportion to the degree of RGDT sequence repetition and in a dose-dependent manner. Multiple i.v. administrations of PEG-(RGDT)11, at 2-day and 3-day intervals before the excision of primary tumors, effectively inhibited spontaneous lung metastasis by s.c. inoculation of tumors, whereas (RGDT)11 exhibited inhibition of lung metastasis only when given at 2-day intervals. This indicates that the conjugation of PEG with (RGDT)n allowed the prolongation of administration interval, implying a sustained inhibitory effect on tumor metastasis. In support of this supposition, a decrease in the arrest of radiolabeled tumor cells in the lungs was observed when PEG-(RGDT)11 was co-injected i.v. with tumor cells, or injected i.v. one day before tumor inoculation. In contrast, (RGDT)11 significantly inhibited the tumor cell arrest in the lungs only upon co-injection with tumor cells. We also noted that (RGDT)n, cyclo(RGDT)n and PEG-(RGDT)11 inhibited tumor cell invasion into Matrigel in a concentration-dependent manner and in proportion to the degree of RGDT sequence repetition, indicating that the peptide-mediated antimetastatic effect is partly associated with the anti-invasive potential. Thus, the conjugation of anti-cell adhesive and antimetastatic RGDT peptide with PEG might provide a therapeutically promising basis for the prevention of cancer metastasis (“anti adhesion therapy”). 相似文献
6.
S H Embury S J Scharf R K Saiki M A Gholson M Golbus N Arnheim H A Erlich 《The New England journal of medicine》1987,316(11):656-661
We have used a new method of DNA analysis for the rapid prenatal diagnosis of sickle cell anemia in two fetuses at risk for this disease. This method of detecting the sickle gene is a modification of standard restriction-enzyme techniques and requires only a small amount of DNA. The first step involves a 200,000-fold enzymatic amplification of the specific beta-globin DNA sequences that may carry the sickle mutation. This provides a sufficient quantity of DNA for the analysis. Next, a short radiolabeled synthetic DNA sequence homologous to normal beta A-globin gene sequences is hybridized to the amplified target sequences. The hybrid "duplexes" are then digested sequentially with two restriction endonucleases. The presence of beta A- or beta S-globin gene sequences in the amplified target DNA from the patient determines whether the beta A-hybridization probe anneals perfectly or with a single nucleotide mismatch. This difference affects the restriction-enzyme digestion of the DNA and the size of the resulting radiolabeled digestion products, which can be distinguished by electrophoresis followed by autoradiography. This method is sufficiently sensitive and rapid that the prenatal diagnosis of sickle cell anemia can be made on the same day that the fetal DNA is made available. It can also be applied to the diagnosis of hemoglobin C disease. 相似文献
7.
Physical work capacity and effect of endurance training in visually handicapped boys and young male adults 总被引:1,自引:0,他引:1
Munehiro Shindo Shuzo Kumagai Hiroaki Tanaka 《European journal of applied physiology》1987,56(5):501-507
Summary The purpose of the present study was to evaluate the relationship between several physical fitness parameters and eyesight divided into 3 grades in visually handicapped boys and young male adults, and to investigate the effect of mild exercise training on physical and psychic symptoms as well as cardiorespiratory fitness. Four subjects were totally blind (TB), 6 were semi-blind (SB) and 27 had amblyopia (AM). Physical fitness tests consisted of maximal oxygen uptake (V
O
2max), maximal pedalling speed and power, maximal stepping rate, and isometric knee extention strength. Compared with AM and SB groups, the TB group was inferior in all physical fitness parameters. Especially,V
O
2max in TB (26 ml · kg–1 · min–1) was about 56% of that in agematched Japanese sighted subjects and was significantly low compared with the AM and SB groups. Both muscle strength and maximal pedalling power corresponded to about 50% that of the age-matched sighted group. Six SB and 4 TB students (¯x=17.7 years) were trained for 6 weeks on a bicycle ergometer at an intensity of 50%V
O
2max. Training was undertaken for 3 days per week and maintained for 60 min per session. After training, physical and psychic symptoms determined by the Cornell Medical Index improved significantly. These results indicate that low physical work capacity in visually handicapped boys and young male adults is due to the lack of physical activity, and that mild endurance training is effective in improving physical and psychic symptoms as well as cardiorespiratory fitness. 相似文献
8.
Social isolation stress augments angiogenesis induced by colon 26-L5 carcinoma cells in mice 总被引:3,自引:0,他引:3
Wu W Murata J Murakami K Yamaura T Hayashi K Saiki I 《Clinical & experimental metastasis》2000,18(1):1-10
We have previously shown that tumor necrosis factor-α (TNF-α), which is an important angiogenesis-related factor, was over-secreted in male BALB/c mice under social isolation stress as compared with the control, and closely associated with a remarkable elevation of tumor invasion and metastasis of colon 26-L5 carcinoma cells. In the present study, we explored the effect of isolation stress on the angiogenesis caused by colon 26-L5 carcinoma cells in vivo and in vitro. Social isolation lead to the enhancement of tumor growth after intrahepatic implantation with a fragment of colon 26-L5 tumor. Angiogenic response (number of vessels oriented towards tumor mass) and tumor growth (size) were significantly increased in the socially isolated mouse relative to that in the group-housed mice. Furthermore, higher protein level of hepatic TNF-α was found in the stressed mice than that in the control. Expression of mRNA for vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were also elevated in the tumor regions and liver tissues of the stressed mice in comparison with that in group-housed mice. On the other hand, hepatic sinusoidal endothelial (HSE) cells treated with TNF-α exhibited a marked promotion of the migration, invasion, expression of mRNA for matrix metalloproteinase (MMP)-9, and tube-like formation, but no cytotoxicity against the cells in vitro. The above data suggest that the social isolation stress augmented the tumor-induced angiogenesis probably by up-regulating the angiogenesis-related factors, including TNF-α, VEGF and HGF, and consequently mediating the functions of endothelial cells such as migration, invasion, and tube-like formation. 相似文献
9.
10.
Junya Yoneda Ikuo Saiki Hideji Fujii Fuminori Abe Yutaka Kojima Ichiro Azuma 《Clinical & experimental metastasis》1992,10(1):49-59
We have investigated the effect of the immunomodulator ubenimex (hereafter referred to as bestatin) on the enzymatic degradation
of the extracellular matrix by human renal cell carcinoma SN12M cells during the invasive process. The invasion of SN12M cells
into reconstituted basement membrane (Matrigel) was inhibited by the presence of bestatin in a concentration-dependent manner.
However, bestatin did not have any effect on tumor cell adhesion and migration to the extracellular matrices which may be
involved in tumor cell invasion. Bestatin inhibited the degradation of type IV collagen by tumor cells, but not by tumor-conditioned
medium (TCM), in a concentration-dependent manner. We also found that bestatin inhibited hydrolysing activities towards substrates
of aminopeptidases in SN12M cells. Since bestatin was found to inhibit aminopeptidase activity, the inhibition of tumor invasion
by bestatin is likely to be associated with its action as an enzyme inhibitor. Bestatin only slightly inhibited tumor cell
plasmin activity, which can lead to the conversion of the latent collagenase to the active form, but this slight effect was
not significant. The zymography of TCM from SN12M cells showed that the treatment of tumor cells with bestatin resulted in
the disappearance of the 68 kDa type IV collagenase-enzyme level (active form) and slight reduction of the 72 kDa type IV
collagenase-enzyme level (latent form). These results indicated that bestatin may inhibit tumor cell invasion through a mechanism
involving its inhibitory action on aminopeptidases in tumor cells, suggesting that the aminopeptidase may partly be associated
with the conversion of a latent form of type IV procollagenase to an active form or the secretion of the collagenases from
tumor cells. 相似文献