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Biomedical subjects

S Naito

Publications and source records attributed to S Naito.

At least 145 records · Page 8Linked to original sources

[Clinicopathological analysis of transition zone cancer of the prostate: the clinical significance of coexistent non-transition zone cancer foci].

BACKGROUND: Dominant cancer of transition zone origin of the prostate (TZ cancer) has been frequently detected, because ultrasound-guided systematic biopsies have been generalized. In cases of TZ cancer, we attempted to determine clinical significance of coexistent non-TZ cancer foci. MATERIALS AND METHODS: Twenty cases with TZ cancer who underwent radical prostatectomy or cystoprostatectomy were clinicopathologically evaluated using step-sectioned specimens. RESULTS: In TZ cancer foci, there were extraprostatic extension in 5 cases (25%), seminal vesicle invasion in 2 cases (10%), positive surgical margin in 6 cases (30%) and bladder neck invasion in 4 cases (20%). The extraprostatic extension and the positive surgical margin occurred at the anterior or anterioapical portion of the prostate in all the cases. On the other hand, 17 (85%) had coexistent non-TZ cancer foci. In non-TZ cancer foci, there were extraprostatic extension in 3 cases (15%), seminal vesicle invasion in 1 case (5%) and positive surgical margin in 1 case (5%). The extraprostatic extension and the positive surgical margin occurred at the posteriolateral portion of the prostate in all the cases. In 3 cases a coexistent non-TZ cancer focus showed the extraprostatic extension, the seminal vesicle invasion or the positive surgical margin, although a TZ cancer focus were organ-confined. CONCLUSION: We should add attention to coexistent non-TZ cancer foci in TZ cancer cases. Particularly, we believe that pre-operative evaluation of non-TZ cancer foci is needed in TZ cancer cases of the candidates for nerve-sparing radical prostatectomy.

Aged↗

[Mapping-guided focal cryoablation and endoaneurysmorrhaphy for a case of ischemic ventricular tachycardia with left ventricular aneurysm].

A 74-year-old woman admitted with exertional dyspnea. Echocardiography revealed the giant left ventricular aneurysm. In the hospital course, she fell into sustained monomorphic ventricular tachycardia. Coronary angiogram showed complete obstruction of the LAD. Left ventricular ejection fraction was 20%. The origin of tachycardia seems to be at infero-apicallateral area of LV by electrophysiology study. Because of the failure of RF energy ablation, we planned mapping-guided cryoablation, CABG and endoaneurysmorrhaphy. To prevent air embolism and myocardial ischemic damage for long aortic cross clamp, intraoperative endocardial mapping was carried out on beating heart due to continuous normothermic coronary blood perfusion (300 ml/min) from the aortic root cannula under aortic clamping. Cold crystalloid cardioplegia changed into the root cannula after EPS, focal cryoablation (-100 degrees C) was performed 3 times on cardiac arrest. Sustained VT was not inducible in the following study. CABG and endoaneurysmorrhaphy was performed on repeated cardiac arrest during single aortic clamp. Postoperative course was uneventful, and she discharged 8 weeks after the operation.

Aged↗

Ets-1 transcription factor-mediated urokinase-type plasminogen activator expression and invasion in glioma cells stimulated by serum and basic fibroblast growth factors.

Overexpression of urokinase plasminogen activator (uPA) has been proposed to be one of the mechanisms by which malignant glioma cells cause pericellular proteolysis of stromal structures during brain-tissue invasion. However, knowledge about the mechanisms that regulate uPA in glioma cells is still rather scant. Growth factors, particularly epidermal growth factor and basic fibroblast growth factor (bFGF), regulate uPA synthesis in various nonglial cells. Because these factors have been associated with glioma invasion, we thought that perhaps similar events may occur in glioma cells. In this study, we demonstrate that growth factors regulate uPA gene transcription in glioma cells by induction of Ets-1 transcription factor. Serum and bFGF treatment concomitantly stimulated baseline levels of Ets-1 and uPA mRNA and protein, and this was associated with a marked increase in the migration and invasion potentials of glioma cells in vitro. Treatment of cells with antisense Ets-1 but not the control sense oligonucleotides concurrently inhibited the expression of Ets-1 and uPA, and this blocked glioma cell migration and invasion by more than 50%. In addition, medium conditioned by antisense Ets-1 oligonucleotide-treated cells showed markedly reduced uPA activity, as determined by casein zymography. These results strongly suggest that serum and bFGF control glioma invasion by inducing synthesis of Ets-1 transcription factor, which directly up-regulates expression of uPA in glioma cells. Antisense inhibition of Ets-1 expression may therefore provide a potential and exciting therapeutic target for preventing invasion by glioma cells.

Blood↗

Expression of the Ets-1 proto-oncogene correlates with malignant potential in human astrocytic tumors.

The protein encoded by the Ets-1 proto-oncogene is a transcription factor that regulates expression of matrix proteases. It has been associated with tumor invasion and angiogenesis. Glioma progression is characterized by increased invasiveness and neovascularization, so we hypothesized that expression of Ets-1 proto-oncogene might play a role in the progression of these tumors. Therefore, we examined the expression of Ets-1 protein by immunohistochemical means and in situ hybridization in tissues obtained from 81 primary and 20 recurrent astrocytic tumors. Twenty-eight (65%) of 43 glioblastomas (Grade IV astrocytomas) stained for Ets-1. The percentage of positive cells in glioblastomas varied from 10 to 90%. Of the 16 anaplastic astrocytomas (Grade III), 4 (25%) were moderately positive (<50% of cells) for Ets-1. None of 22 cases of low-grade astrocytomas (Grade II) expressed endogenous Ets-1. The staining score was significantly associated with tumor grade (P < .0001). Normal brain tissues did not express Ets-1 protein, whereas recurrent astrocytoma cases expressed significantly more positivity for Ets-1 than did primary tumors (P = .03). The Ets-1 protein was observed mainly in the nucleus and corresponded to the cytoplasmic Ets-1 mRNA localization by in situ hybridization. Western and Northern blot analyses confirmed overexpression of Ets-1 protein and mRNA in high-grade tumors. We conclude that Ets-1 protein expression correlates with the malignant potential of tumors of astroglial origin.

Adolescent↗

Expression of the MMP-1 in human pancreatic carcinoma: relationship with prognostic factor.

Matrix metalloproteinases (MMPs) have been implicated in the invasion and metastasis of tumor cells. To elucidate the involvement of MMP-1 in human pancreatic ductal adenocarcinoma, we performed immunohistochemical analysis on tissues from 2 fetal pancreases, 5 normal pancreases, 6 cases of chronic pancreatitis, and 46 pancreatic ductal adenocarcinomas. In addition, among the pancreatic carcinomas, we compared MMP-1 expression in relation to the degree of differentiation, lymph node metastasis, and depth of invasion of the carcinoma. MMP-1 was expressed faintly in fetal and normal pancreatic tissues. Among the 46 pancreatic carcinomas, 33 (72%) showed positive staining for the MMP-1 protein. There was no difference in the degree of differentiation. In situ hybridization confirmed the presence of MMP-1 mRNA in the pancreatic carcinomas. Expression of MMP-1 mRNA was also detected in two human pancreatic carcinoma cell lines and three pancreatic carcinoma tissues by the reverse transcription polymerase chain reaction method. MMP-1 was expressed in the carcinoma cells themselves and in stromal fibroblasts. Patients with MMP-1 positivity in the primary site had a significantly poorer prognosis than patients who were MMP-1 negative (P < .05). MMP-1 expression, however, had no relation to the presence of lymph node metastasis, tumor size, or tumor-node-metastasis stage in pancreatic carcinomas. These findings suggest that MMP-1 expression is related to the carcinogenesis and prognosis of human pancreatic ductal adenocarcinoma.

Adenocarcinoma↗

[Effect of exercise therapy on oxygen consumption in patients with chronic heart failure].

The effect of exercise training on delta Vo2/delta WR was studied in 12 patients(11 men, one woman, mean age 62 +/- 9 yr)with chronic heart failure(old myocardial infarction, dilated cardiomyopathy, patients after coronary arterial bypass graft surgery and patients after aortic valve replacement). Cardiopulmonary exercise testing was performed to decide the exercise tolerance and assess the delta Vo2/delta WR. Patients underwent physical training at the anaerobic threshold for 3 months. Cardiopulmonary exercise testing was performed after the second week and after the third month. The anaerobic threshold increased at the third month compared with before exercise testing and the second week(p < 0.05, respectively) (before exercise testing: 13.6 +/- 2.0 ml/min/kg, the second week: 14.7 +/- 2.5 ml/min/kg, the third month: 16.2 +/- 2.1 ml/min/kg). The delta Vo2/delta WR increased at the second week compared with before exercise testing(before exercise testing: 8.9 +/- 1.9 ml/min/W, the second week: 10.6 +/- 1.9 ml/min/W, p < 0.05), but significantly decreased at the third month compared with the second week(the third month: 9.4 +/- 1.7 ml/min/W, p < 0.05). Serial increase of the anaerobic threshold and the peak Vo2/heart rate suggests that the exercise tolerance and cardiac function of the patients improved significantly. The increase of the delta Vo2/delta WR after the first 2 weeks seemed to depend on the luxury blood supply to both working and non-working muscles. The decrease of delta Vo2/delta WR at the third month may be due to the redistribution of the blood flow to the working muscles.

Chronic Disease↗

[High-dose chemotherapy with peripheral blood stem cell autotransplantation for patients with poor-risk testicular germ cell tumors--pilot study of the Japan Blood Cell Transplantation Study Group].

The efficacy and toxicity of a single cycle of high-dose chemotherapy with peripheral blood stem cell autotransplantation (PBSCT) in patients with poor-risk testicular germ cell tumors (GCT) enrolled in the Japan Blood Cell Transplantation Study Group was investigated. Previously untreated poor-risk testicular GCT patients were treated with BEP therapy (cisplatin, etoposide and bleomycin) with or without high-dose chemotherapy (carboplatin, etoposide and ifosphamide) followed by PBSCT. Patients were qualified for a change to high-dose chemotherapy if elevated serum tumor markers (human chorionic gonadotropin-beta, alpha-fetoprotein and lactate dehydrogenase) was observed after 3 cycles of BEP therapy. Eighteen patients were treated with BEP therapy alone and 16 with BEP and high-dose chemotherapy. At the completion of high-dose chemotherapy, all tumor markers had returned to normal in 6 patients. Among them, 1 had only teratoma found at resection and 5 had carcinoma resected. Nine patients who had persistent elevation of any tumor marker were treated with high-dose chemotherapy or another anticancer drug. Thirteen are alive (81%) and 9 (56%) are continuously disease-free at a median follow up of 11 months. The median time from PBSCT to a granulocyte count > 500/microL was 9.5 days and to a platelet count > 50,000/microL was 13 days.

Adolescent↗

Expression of the ets-1 proto-oncogene in human thyroid tumor.

The proto-oncogene ets-1 is a transcription factor known to control the expression of a number of genes involved in extracellular matrix remodeling. To elucidate the involvement of ets-1 in human thyroid carcinoma, we examined 68 cases of thyroid carcinoma and 38 cases of benign tumors by immunohistochemical means. ets-1 was not expressed in normal thyroid follicular cells. Among the 69 cases of thyroid carcinoma, 61 (89.7%) showed positive staining for the ets-1 protein. According to histologic classification, 47 (97.9%) of 48 papillary carcinomas, 7 (87.5%) of 8 follicular carcinomas, 3 (60.0%) of 5 medullary carcinomas, and 4 (50.0%) of 8 anaplastic carcinomas showed positive staining of ets-1. Among the benign tumors, staining was positive for ets-1 in 8 (40.0%) of 20 adenomas and 3 (16.7%) of adenomatous goiters. In situ hybridization also confirmed the expression of ets-1 mRNA in thyroid carcinoma. Expression of ets-1 mRNA was seen in three kinds of cultured human thyroid carcinoma cell lines and carcinoma tissue obtained at surgery by reverse transcription-polymerase chain reaction. These findings suggest that ets-1 is deeply involved in thyroid carcinogenesis.

Humans↗

Time-domain and spectral turbulence analyses of the signal-averaged electrocardiogram have different predictive values for sustained ventricular tachycardia in patients with myocardial infarction.

We performed signal-averaged ECG and programmed stimulation in 15 patients after myocardial infarction with ventricular tachycardia and 49 patients after myocardial infarction without ventricular tachycardia to compare the spectral turbulence analysis and time-domain analysis of signal-averaged ECG for prediction of clinical and induced ventricular tachycardia. Sustained monomorphic ventricular tachycardia was inducible in all 15 patients with clinical sustained monomorphic ventricular tachycardia (group 1) and in 9 patients without clinical sustained monomorphic ventricular tachycardia (group 2). Sustained monomorphic ventricular tachycardia was not inducible in 40 patients without clinical sustained monomorphic ventricular tachycardia (group 3). While there was no difference in time-domain variables between groups 1 and 2, there were significant differences between groups 2 and 3. Values obtained by spectral turbulence analysis differed significantly between groups 1 and 2, but not between groups 2 and 3. Time-domain analysis showed abnormal values in 87% of group 1 patients, 78% of group 2, and 35% of group 3. Spectral turbulence analysis showed abnormal values in 93% of group 1, 11% of group 2, and 30% of group 3. In conclusion, frequency-domain spectral turbulence analysis of signal-averaged ECG is more useful than the time-domain analysis in predicting the spontaneous occurrence of sustained monomorphic ventricular tachycardia in patients after myocardial infarction.

Aged↗

Microwave dielectric analysis of human stratum corneum in vivo.

The dielectric properties of the human skin stratum corneum (SC) in the frequency range higher than 107 Hz are not well understood because of the difficulty in selective scanning of the SC area in vivo. The present study was carried out to make clear factors responsible for the dielectric properties using a measuring system specially developed for the study of SC [S. Naito, M. Hoshi, S. Mashimo, Anal. Biochem. 251 (1997) 163-172]. We found that the dielectric properties of SC can be expressed by the linear combination of two relaxation processes and d.c. conduction. The faster relaxation is that of free water. The slower relaxation and d. c. conduction were analyzed using a model assuming interfacial polarization between dissimilar materials. We concluded that the polarization is the origin of the slower relaxation process because the experimental data could be well interpreted according to the above mechanism. We also concluded that the polarization of swelled SC locates at the interface between SC cells and the intercellular lipid layer, or at the interface between the lipophilic and the hydrophilic part of the lamellar structured intercellular lipid layer.

Biophysical Phenomena↗

Expression of Ets-1 transcription factor in relation to angiogenesis in the healing process of gastric ulcer.

Ets-1 is a transcription factor known to control the expression of genes involved in extracellular matrix remodeling. The purpose of this study is to evaluate the expression of Ets-1 in the process of healing of ulceration in the rats. The time-dependent changes and distribution of Ets-1 in the margins of ulcer were examined. Ets-1 did not express in the normal gastric mucosa. In the marginal granulation tissue, fibroblasts and endothelial cells of capillaries were immunopositive for Ets-1. Ets-1 expression was significantly increased at the early phase, and returned to normal levels at the scarred phase. Serial sectioning revealed that fibroblasts and endothelial cells also expressed MMP-1. Protein levels and mRNA expression of Ets-1 were confirmed by Western blotting and RT-PCR. These findings suggest that Ets-1 plays an important role in angiogenesis in the early phase of ulcer healing.

Animals↗

The role of an inverted CCAAT element in transcriptional activation of the human DNA topoisomerase IIalpha gene by heat shock.

Expression of the DNA topoisomerase IIalpha (topoIIalpha) gene is highly sensitive to various environmental stimuli including heat shock. The amount of topoIIalpha mRNA was increased 1.5-3-fold 6-24 h after exposure of T24 human urinary bladder cancer cells to heat shock stress at 43 degreesC for 1 h. The effect of heat shock on the transcriptional activity of the human topoIIalpha gene promoter was investigated by transient transfection of T24 cells with luciferase reporter plasmids containing various lengths of the promoter sequence. The transcriptional activity of the full-length promoter (nucleotides (nt) -295 to +85) and of three deletion constructs (nt -197 to +85, -154 to +85, and -74 to +85) was increased approximately 3-fold 24 h after heat shock stress. In contrast, the transcriptional activity of the minimal promoter (nt -20 to +85), which lacks the first inverted CCAAT element (ICE1), the GC box, and the heat shock element located between nt -74 and -21, was not increased by heat shock. Furthermore, the transcriptional activity of promoter constructs containing mutations in the GC box or heat shock element, but not that of a construct containing mutations in ICE1, was significantly increased by heat shock. Electrophoretic mobility shift assays revealed reduced binding of a nuclear factor to an oligonucleotide containing ICE1 when nuclear extracts were derived from cells cultured for 3-24 h after heat shock. No such change in factor binding was apparent with an oligonucleotide containing the heat shock element of the topoIIalpha gene promoter. Finally, in vivo footprint analysis of the topoIIalpha gene promoter revealed that two G residues of ICE1 that were protected in control cells became sensitive to dimethyl sulfate modification after heat shock. These results suggest that transcriptional activation of the topoIIalpha gene by heat shock requires the release of a negative regulatory factor from ICE1.

Antigens, Neoplasm↗

Isolation of a mutant of Arabidopsis thaliana carrying two simultaneous mutations affecting tobacco mosaic virus multiplication within a single cell.

Tobacco mosaic virus strain Cg (TMV-Cg) infects A. thaliana systemically. In order to identify host factors involved in the multiplication of TMV-Cg, we isolated mutant of A. thaliana from an M2 population mutagenized by fast neutron irradiation, in which the accumulation of the coat protein in upper systemic leaves was reduced to low levels. The phenotype of the mutant, YS241, was controlled primarily by a single nuclear recessive mutation named tom2-1, which was distinct from tom1, a separate mutation which also affects TMV-Cg multiplication. The tom2-1 mutation affected the accumulation of TMV-related RNAs in protoplasts in a tobamovirus-specific manner, suggesting that the wild-type TOM2 gene product is necessary for efficient amplification of TMV-related RNAs within a single cell, through specific interaction with virus-coded factors. Furthermore, we found that YS241 contained a single dominant modifier named ttm1, which increased the efficiency of multiplication of TMV-Cg and a tomato strain of TMV in a tom2-1 genetic background, both in plants and in protoplasts. We propose that the ttm1 element might be a translocated form of the TOM2 gene.

Arabidopsis↗

Stimulation of nitric oxide synthase during oxidative endothelial cell injury.

The purpose of this study was to determine changes in nitric oxide synthase (NOS) activity during the process of lethal oxidative cell injury following H2O2 treatment of endothelial cells. NOS activity was determined by measuring the conversion of [3H]arginine ([3H]Arg) to [3H]citrulline ([3H]Cit). Cell death was assessed by measuring the release of intracellular lactate dehydrogenase (LDH). Moreover, cell death and changes in cytosolic free Ca2+ (Ca(i)2+) were measured simultaneously using a confocal laser scanning system, and propidium iodide and fluo-3 as fluorescent indicators, respectively. Treatment with H2O2 (125-1000 microM) concentration dependently increased L-Cit formation from L-Arg, and a peak was obtained at 90 min after the addition of 500 or 1000 microM H2O2. The H2O2-induced increase in L-Cit formation was blocked completely by N(G)-nitro-L-arginine (L-NNA) or N(G)-methyl-L-arginine (L-NMA), both inhibitors of NOS. LDH release from endothelial cells was evoked from 120 min after the addition of H2O2 (125-1000 microM) in a concentration-dependent manner. Moreover, H2O2 increased Ca(i)2+ before cell death, and addition of Ca2+ chelator inhibited both the increase in L-Cit formation and LDH release by H2O2. The H2O2-induced LDH release was reduced by L-NNA, but not by L-NMA. These results suggest that H2O2 treatment of endothelial cells increases Ca(i)2+ before cell death, and stimulates NOS activity. The activation of NOS may be involved in oxidative endothelial cell death.

Animals↗

Prophylactic intravesical instillation chemotherapy against recurrence after a transurethral resection of superficial bladder cancer: a randomized controlled trial of doxorubicin plus verapamil versus doxorubicin alone. The Kyushu University Urological Oncology Group.

PURPOSE: We investigated whether verapamil (VR), a known chemosensitizing agent of P-glycoprotein-mediated multidrug resistance, could enhance the preventative effect of doxorubicin (Adriamycin, ADM) on both intravesical recurrence and disease progression after transurethral resection (TUR) of superficial bladder cancer. METHODS: The patients were randomized into two groups: one group received an intravesical instillation of ADM (30 mg) plus VR (15 mg) after TUR of superficial bladder cancer (19 times over 1 year), and the other group received ADM alone on the same treatment schedule. The nonrecurrence rate, the incidence of disease progression at the first recurrence and the side effects were compared over a median follow-up of 38.5 months. RESULTS: Of the 226 patients registered, 157 were evaluable. No significant differences were observed in the patients' characteristics between the two groups. Although the incidence of disease progression at the first recurrence was not significantly different between the two groups, the ADM plus VR instillation group did show a significantly higher nonrecurrence rate than the ADM-only instillation group, and such significance persisted even when any possible bias was allowed for in a multivariate analysis. In terms of side effects, the incidence and severity of bladder irritation symptoms were not significantly different between the two groups. CONCLUSIONS: Intravesical instillation chemotherapy with ADM plus VR was found to have a significantly greater beneficial effect than with ADM alone for preventing recurrence after TUR of superficial bladder cancer.

Administration, Intravesical↗

Newly synthesized dihydropyridine derivatives as modulators of P-glycoprotein-mediated multidrug resistance.

Newly synthesized 1,4-dihydropyridine derivatives possessing alkyl chains at the 4-position screened whether they could overcome P-glycoprotein-mediated multidrug resistance in cultured cancer cells and also leukemia-bearing animals. Of these derivatives, some could overcome drug resistance to doxorubicin and vincristine in multidrug resistant human cancer cell lines. Combined administration of vincristine and some of the derivatives significantly increased the life span of P-glycoprotein overexpressing multidrug-resistant P388 leukemia-bearing mice. The calcium antagonistic activities, an undesirable effects, were weaker than that of verapamil. These results suggested that the introduction of alkyl groups at the 4-position were effective for both overcoming multidrug resistance and reducing the calcium antagonistic activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Complete nucleotide sequence of the genomic RNA of tobacco mosaic virus strain Cg.

Tobacco mosaic virus (TMV)-Cg is a crucifer-infecting tobamovirus that was isolated from field-grown garlic. We determined the complete nucleotide sequence of the genomic RNA of TMV-Cg. The genomic RNA of TMV-Cg consists of 6303 nucleotides and encodes four large open reading frames, organized basically in the same way as that of other tobamoviruses. The nucleotide and deduced amino acid sequences are very similar to those of the other crucifer-infecting tobamoviruses that have been sequenced so far.

Amino Acid Sequence↗