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Y Saijo

Publications and source records attributed to Y Saijo.

At least 19 recordsLinked to original sources
PubMed2001

Altered sensitivity to a novel vasoconstrictor endothelin-1 (1-31) in myometrium and umbilical artery of women with severe preeclampsia.

We have suggested that a novel endothelin-1 with 31 amino acids [ET-1 (1-31)] plays an important role in fetal circulation, owing to a strong contractile activity on the umbilical artery. To clarify the pathophysiological significance of ET-1 (1-31) in the development of severe preeclampsia, its contractile activities on human umbilical arteries and uterine smooth muscle from patients with preeclampsia were studied. The contraction by ET-1 (1-31) was stronger in uterine smooth muscle of the patients with severe preeclampsia than that of normal subjects. On the contrary, the constriction of umbilical artery of the patients with eclampsia was significantly weaker than that of normal pregnant women. The stronger contraction of myometrium by ET-1 (1-31) in patients with severe preeclampsia observed for the first time in the present study suggests that ET-1 (1-31) might be involved in the development of preeclampsia.

Case-Control Studies↗
PubMed2001

Ultrasonic tissue characterization of collagen in lipid-rich plaques in apoE-deficient mice.

Mechanical failure of the fibrous cap of a vulnerable atherosclerotic plaque may lead to sudden plaque rupture and thus precipitate arterial thrombosis. Because ultrasound correlates strongly with mechanical features of tissues it might provide information on the stability of fibrous caps. The acoustic properties of the normal vessel wall and plaques, particularly fibrous caps of lipid-rich plaques, were evaluated in the aortic roots of six normal C57BL mice and 12 atherosclerosis-prone apoE-deficient (apoE(-/-)) mice by scanning acoustic microscopy (SAM). After processing, the attenuation of high-frequency (1.1 GHz) focused ultrasound was measured in unstained tissue sections by SAM followed by quantification of the amount and type of collagen in picrosirius red stained sections by means of polarized light microscopy (PLM). The acoustic and optical images were superimposed and ultrasonic attenuation was measured in different tissue components. Pertinent plaque features, particularly fibrous caps covering lipid-rich pools, were clearly visualized by both SAM and PLM. Collagen appeared green in thin fibrous caps and bright orange in thick caps by PLM. The attenuation of ultrasound was significantly higher in the collagen fibers with orange color compared to those with green color (17.2 versus 6.6 x 10(3) dB/mm). SAM has shown the possibility to characterize the types of collagen by high frequency intravascular ultrasound in vivo and it might improve our understanding of the vulnerable plaque and its sudden rupture from micro-mechanical point of view.

Animals↗
PubMed2001

Expression of nucleolar protein p120 predicts poor prognosis in patients with stage I lung adenocarcinoma.

BACKGROUND: P120 is a proliferation-associated nucleolar protein found in most human malignant tumors, but not in resting normal cells. In our previous studies, the expression of p120 was statistically correlated with the proliferation capacity in human lung cancer cells and could be a prognostic marker for resected lung adenocarcinoma. PATIENTS AND METHODS: The expression levels of p120 in tumors were assessed by immunohistochemistry in 59 patients with stage I lung adenocarcinoma who underwent radical resection. Using clinical follow-up data, the prognostic significance of p120 calculated by labeling indices was evaluated using Cox's proportional hazard model. RESULTS: A mean +/- SD of the labeling index of p120 was 35.3+/-14.4%. No significant correlation was found between the expression levels of p120 and clinicopathological factors. Using a cutoff value of 35% in the labeling index of p120, patients with high expression of p120 experienced early recurrence and shorter survival compared with those having low expression of p120 (P = 0.04). Multivariate analysis revealed that p120 served as an independent and strongest prognostic factor for resected lung adenocarcinoma (P = 0.033). CONCLUSION: This article provides the first evidence that the expression levels of p120 in tumor tissues can be used as an independent and powerful prognostic marker for resected stage I lung adenocarcinoma.

Adenocarcinoma↗
PubMed2001

Replication-deficient adenovirus-mediated transfer of B7-1 (CD80) cDNA induces anti-tumour immunity in isolated human lung cancer.

OBJECTIVE: Interaction between the co-stimulatory molecule B7-1 (CD80) on antigen-presenting cells and its counter-receptor CD28 on T lymphocytes plays a key role in the induction of cell-mediated immune responses. Many tumours, including lung cancer, lack expression of B7-1 and this has been suggested to contribute to the failure of immune recognition of these diseases. Based on this knowledge, we hypothesized that the co-stimulatory signal delivered through the B7-1 molecule expressed on lung cancer cells using replication deficient adenovirus vector would induce efficient tumour immunity in T lymphocytes. METHODOLOGY: To evaluate this hypothesis, we constructed two adenovirus vectors: AdCMVhB7 (an E1-deleted-Ad5-based vector containing human B7-1 cDNA driven by cytomegalovirus immediate early promoter and enhancer) and AdNull (same vector as above without expression of exogenous gene) as control. Using these adenovirus vectors, efficient generation of tumour immunity in T lymphocytes was studied using primary cultured lung cancer cells and peripheral blood lymphocytes (PBL) obtained from patients with lung cancer. RESULTS: Inoculation of lung cancer cells with 10 multiplicity of infection of AdCMVhB7 resulted in rapid and efficient cell surface expression of B7-1 molecule (> 90% of cells at 24 h). Cytolytic activity of PBL in 51Cr-release assay (E/T = 40) demonstrated that effector lymphocytes induced by hB7-1 (+) lung cancer cells treated with AdCMVhB7could lyse parental lung cancer cells hB7-1 (-). In contrast, effector lymphocytes induced by lung cancer cells treated with AdNull as control virus or PBS as control could not lyse parental lung cancer cells at all. Furthermore, cytolytic activity of the effector lymphocytes induced by B7-1-transduced lung cancer cells was inhibited by addition of anti-CD3 antibody. CONCLUSIONS: These data demonstrate that primary-cultured lung cancer cells treated with AdCMVhB7 would efficiently generate tumour immunity in T lymphocytes. Adenovirus-mediated-hB7-1 gene transfer may be a useful means for gene therapy of lung cancer using adoptive immunotherapy.

Adenoviridae↗
PubMed2001

A Ca(2+)-dependent protein kinase that endows rice plants with cold- and salt-stress tolerance functions in vascular bundles.

A rice Ca(2+)-dependent protein kinase, OsCDPK7, is a positive regulator commonly involved in the tolerance to cold and salt/drought. We carried out in situ detection of the transcript and immunolocalization of the protein. In the wild-type rice plants under both stress conditions, OsCDPK7 was expressed predominantly in vascular tissues of crowns and roots, vascular bundles and central cylinder, respectively, where water stress occurs most severely. This enzyme was also expressed in the peripheral cylinder of crown vascular bundles and root sclerenchyma. Similar localization patterns with stronger signals were observed in stress-tolerant OsCDPK7 over-expressing transformants with the cauliflower mosaic virus 35S promoter. The transcript of a putative target gene of the OsCDPK7 signaling pathway, rab16A, was also detected essentially in the same tissues upon salt stress, suggesting that the OsCDPK7 pathway operates predominantly in these regions. We propose that the use of the 35S promoter fortuitously strengthened the localized expression of OsCDPK7, resulting in enhancement of the stress signaling in the inherently operating regions leading to improved stress tolerance.

Adaptation, Physiological↗
PubMed2001

Application of scanning acoustic microscopy for assessing stress distribution in atherosclerotic plaque.

Scanning acoustic microscopy (SAM) was equipped to assess the acoustic properties of normal and atherosclerotic coronary arteries. The SAM image in the atherosclerotic lesion clearly demonstrated that the sound speed was higher than that in the normal intima, and that the variation of elasticity was found within the fibrous cap of the plaque. Young's elastic modulus of each region was calculated and the finite element analysis was applied to derive the stress distribution in these arterial walls. In a case of normal coronary artery, the stress was dominant in the intima and the distribution was rather homogeneous and in a case of atherosclerosis, high stress was concentrated to the relatively soft lesion in the fibrous cap overlying lipid pool. SAM provides information on the physical properties, which cannot be obtained by the optical microscope. The results would help in understanding the pathological features of atherosclerosis.

Acoustics↗
PubMed2001

[Perspectives on postgenome medicine: Gene therapy for lung cancer].

The gene therapy or the immunotherapy targeting specific molecule(s) have just introduced into the clinical field in Japan. The first gene therapy for the human lung cancer is underway; an adenoviral vector harboring wild type p53 gene is intratumorally injected. A cancer immunotherapy using the Cyclophilin B derived peptide is in the phase I clinical trial. As the next generation cancer therapies, a variety of strategies are planned and investigated at the laboratory level. They range from the usage of a new viral vector to the introduction of genes with specific biological functions into the cells. In this article, by reviewing the possible approach, an ideal combination of the future remedies is discussed.

Adenoviridae↗
PubMed2001

[Non-small-cell lung cancer (NSCLC) in an elderly patient--a case of squamous cell carcinoma successfully treated with chemotherapy using vinorelbine].

We report an elderly patient with squamous cell carcinoma who was successfully treated with chemotherapy using vinorelbine. A 76-year-old man was referred to our hospital for evaluation of a nodular shadow in the left lung. Chest CT scam showed a 3-cm tumor shadow in left S9 and a 1-cm small nodule in right S2. Transbronchial lung biopsy yielded a diagnosis of squamous cell carcinoma. The clinical stage was IV (cT2N2M1). The patient first underwent chemotherapy consisting of cisplatin (CDDP) 80 mg/m2 on day 1 and vinorelbine (VNB) 20 mg/m2 on days 1, 8, and 15, which generated tumor shrinkage of 48% as well as transient elevation of grade 1 in serum creatinine. The 2 cycles of chemotherapy using vinorelbine only (VNB 20 mg/m2 on days 1, 8, 15) produced a tumor reduction of 70% with grade-1 decrease of granulocytes. The low grade of toxicity enabled us to treat the patient in our outpatient office for the second cycle of the regimen. This case suggests that chemotherapy using low-dose vinorelbine might be suitable to treat elderly patients with NSCLC in outpatient settings.

Aged↗
PubMed2000

Administration of wild-type p53 adenoviral vector synergistically enhances the cytotoxicity of anti-cancer drugs in human lung cancer cells irrespective of the status of p53 gene.

Recombinant adenovirus mediated p53 gene transfer combined with anti-cancer drugs has clinical potential for gene therapy of lung cancer. We constructed a recombinant adenoviral vector expressing wild-type p53 cDNA (Ad-p53), and assessed the efficacy of a combined treatment with Ad-p53 and six anti-cancer drugs (cisplatin, 5-fluorouracil, doxorubicin, docetaxel, irinotecan, and etoposide) for human lung cancer cell lines, H1299 (with deleted p53), RERF-LC-OK (with mutant p53), and A549 (with wild-type p53). The infection of the Ad-p53 vector into H1299 cells, RERF-LC-OK cells, or A549 cells increased the sensitivity to all six drugs regardless of the cellular p53 status, and a synergism was observed by the isobolic method in combination studies (D<1). We conclude that our strategy using adenoviral mediated p53 gene transfer to cancer cells can enhance the cytotoxic effect of anti-cancer drugs, which leading to an improvement of lung cancer chemotherapy.

Adenoviruses, Human↗
PubMed2000

Expression of the 37-kDa laminin binding protein in murine lung tumor cell correlates with tumor angiogenesis.

Expression of the 37-kDa laminin binding protein (37LBP), a precursor protein of the 67-kDa laminin receptor, correlates well with the biological aggressiveness of cancer cells. Previously, we have established murine lung cancer cell lines T11 and T15, in which 37LBP expression was remarkably diminished, and reported that the mean survival time of the T11 and the T15-recipients was significantly prolonged compared with that of the control cell lines (P29 and T42). In the present study, immunohistochemical findings of the tumors demonstrated that the microvessel density in the T11 (28. 1+/-7.2/mm(2)) and in the T15 tumor (29.7+/-6.5/mm(2)) were significantly lower than that observed in P29 (46.3+/-8.7/mm(2)) or in T42 (50.5+/-4.4/mm(2)). Expression of vascular endothelial growth factor (VEGF) was repressed in T11 and T15 compared with its expression in P29 and T42. It was also shown that conditioned media of T11 and T15 cells exhibited significantly reduced proliferation and migration of the capillary endothelial cells. These results suggest that decreased expression of 37LBP in antisense-RNA transfectant may relate to its low tumorigenicity, and that this effect may be partly caused by the diminished tumor angiogenesis of murine lung cancer.

Animals↗
PubMed2000

Effect of a novel vasoconstrictor endothelin-1 (1-31) on human umbilical artery.

To clarify the action of a novel endothelin-1 with 31 amino acids, ET-1 (1-31), on fetal circulation, its vasoconstrictive activity on human umbilical and uterine arteries was investigated in comparison with that of a conventional ET-1 (1-21). UFER micro-easy magnus was used for determination of vasoconstriction. The contraction of umbilical artery by KCl was significantly weaker than that of the uterine artery. In ETs, constriction by KCl was set as control, and the rate of constriction of uterine and umbilical arteries was used for comparison. The constriction of human uterine artery induced by ET-1 (1-31) was also significantly weaker than that by ET-1 (1-21). On the contrary, ET-1 (1-31) was a potent constrictor on the umbilical artery equally to ET-1 (1-21). The present study is the first to demonstrate that ET-1 (1-31) has a contractile activity on human vessels. Furthermore, the regulatory mechanism on constriction of umbilical artery is different from that observed in a systemic vessel, indicating a particularly important role of ET-1 (1-31) in fetal circulation.

Adult↗
PubMed2000

Visualization of human umbilical vein endothelial cells by acoustic microscopy.

The morphology and acoustic properties of the human umbilical vein endothelial cells (HUVECs) were evaluated using a scanning acoustic microscope system. HUVECs were cultured for 4 days and exposed to the endotoxin for 4 h. The frequency of the scanning acoustic microscope was variable between 100 and 210 MHz. By changing the measuring frequency, ultrasonic amplitude and phase were measured and the quantitative value of attenuation was calculated. Before and after endotoxin stimuli, HUVECs were observed by scanning acoustic microscopy and the attenuation was measured. The acoustic images were successfully obtained to identify the outer shape of the HUVEC and the location of the nucleus in the cell. The attenuation of the nucleus is higher than that of the cytoplasm. The attenuation of the cytoplasm was increased and became inhomogeneous after endotoxin exposure. This finding would be related to the change of F-actin filaments, which is the main component of the cytoskeleton. Scanning acoustic microscopy is useful for assessing the cellular viscoelastic properties since it can detect both the morphological and acoustic changes without contacting the cellular surface.

Acoustics↗
PubMed2000

Microscopy.

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Elasticity↗
PubMed2000

Induction of antitumor immunity by combined immunogene therapy using IL-2 and IL-12 in low antigenic Lewis lung carcinoma.

Interleukin-2 (IL-2) and interleukin-12 (IL-12) are crucial cytokines that induce potent antitumor responses in a variety of animal cancer models. Although single gene transfer of either IL-2 or IL-12 exhibits limited antitumor effects, the combination of IL-2 and IL-12 has been shown to induce a stronger antitumor response and to cure tumor-bearing mice. To examine the conditions necessary for tumor rejection, we varied the local concentration of IL-2 and IL-12 by introducing these genes into Lewis lung carcinoma (LLC) cells via retroviral vectors and/or an adenoviral vector and evaluated the growth of inoculated LLC cells (5 x 10(5) cells). In contrast to the result when using a stepwise dose increase of IL-2 either without or with a fixed production of IL-12 (4-5 ng/5 x 10(5) cells/24 hours, insufficient for tumor rejection by itself), rejection of the tumor was achieved in 75% of the mice when the IL-12 secretion was combined with high and transient IL-2 production (42 ng/5 x 10(5) cells/24 hours) using additional adenoviral vector transduction (100 multiplicities of infection). An abundant infiltration of both CD4+ (47.4/mm2) and CD8+ (85.6/mm2) T cells was a characteristic finding in the dual gene-transfected LLC tumors. Importantly, consistent with the rejection of rechallenged parental cells, tumor-specific cytotoxic T lymphocytes were induced only from the splenocytes of mice inoculated with the dual gene-transduced LLC cells, suggesting the existence of protective antitumor memory. In addition, only vaccination of dual gene-transduced LLC cells inhibited the growth of pre-established LLC tumors. These results indicate that generation of a pivotal antitumor response likely depends on the synergistic combination and concentration of IL-2 and IL-12 in the local milieu by which tumor-specific immune memory is established.

Adenoviridae↗
PubMed2000

Over-expression of a single Ca2+-dependent protein kinase confers both cold and salt/drought tolerance on rice plants.

A rice gene encoding a calcium-dependent protein kinase (CDPK), OsCDPK7, was induced by cold and salt stresses. To elucidate the physiological function of OsCDPK7, we generated transgenic rice plants with altered levels of the protein. The extent of tolerance to cold and salt/drought stresses of these plants correlated well with the level of OsCDPK7 expression. Therefore, OsCDPK7 was shown to be a positive regulator commonly involved in the tolerance to both stresses in rice. Over-expression of OsCDPK7 enhanced induction of some stress-responsive genes in response to salinity/drought, but not to cold. Thus, it was suggested that the downstream pathways leading to the cold and salt/drought tolerance are different from each other. It seems likely that at least two distinct pathways commonly use a single CDPK, maintaining the signalling specificity through unknown post-translational regulation mechanisms. These results demonstrate that simple manipulation of CDPK activity has great potential with regard to plant improvement.

Adaptation, Physiological↗
PubMed2000

Evaluation of the inner-surface morphology of an artificial heart by acoustic microscopy.

The total artificial heart (TAH) is being developed for permanent replacement of the natural heart instead of heart transplantation. The need for detecting the material fatigue in the TAH is increasing in order to guarantee long-term use. In this study, the inner surface morphology of the TAH was evaluated by a specially developed scanning acoustic microscope (SAM) system operating in the frequency range of 100-200 MHz. The inner sac of our TAH consisted of polyvinylchloride coated with polyurethane, and the SAM investigations were performed before and after the implantations in goats. The amplitude images of the SAM demonstrated protein adhesion on the inner surface of the TAH after the animal experiment, and the phase images showed distortion of the wall with spatial resolution of 0.2 microm. These results suggest the feasibility of a high-frequency ultrasound for evaluating the material fatigue of TAH.

Animals↗