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Biomedical subjects

Fumio Mizuno

Publications and source records attributed to Fumio Mizuno.

9 recordsLinked to original sources

Clinicopathologic study of non-Hodgkin lymphoma in sinonasal and hard palate regions in 15 Japanese cases.

Non-Hodgkin lymphomas of the sinonasal region have been the subject of numerous studies. Previous reports have suggested that nasal lymphomas occurring in Orientals are mostly of the natural killer cell (NK)/T-cell phenotype which contrasts with the preponderance of the B-cell type in western populations. Recent studies indicated that NK/T-cell lymphoma constitutes the clinical condition of lethal midline granuloma. These reports led us to question whether all NK/T lymphomas are always lethal midline granuloma. We have investigated a series of 15 cases of non-Hodgkin lymphomas in the nasal and/or paranasal sinuses clinically, immunohistochemically and for the presence of Epstein-Barr virus (EBV). This study showed that the presence of EBV was common in nasal NK/T lymphoma, and this type of lymphoma was clearly highly frequent in other types of nasal lymphoma in our department. Moreover, in 4 cases of NK/T-cell lymphomas, the clinical features of lethal midline granuloma did not appear, indicating that NK/T lymphomas are not always lethal midline granuloma.

Adult↗

Effects of smoking and age on chronic obstructive pulmonary disease in Japan.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease guidelines recommended a forced expiratory volume at one second per forced vital capacity as a standard diagnostic criterion of chronic obstructive pulmonary disease (COPD). A few reports on the risk factors of COPD have used the standard diagnostic criteria. In our study, the effects of age and smoking on COPD in Japan under the standard diagnosis criteria were evaluated. METHODS: Subjects were 11,460 participants aged 25-74 years during health check-ups including spirometry at the Toyota Community Medical Center in Japan. Logistic regression analyses with or without COPD as a dependent variable and age as an independent variable were conducted among non-smokers. The ratio of the observed number of COPD cases in former and current smokers to the number expected for non-smokers with the same distribution of age (O/E) was calculated. RESULTS: The proportion of males incurring COPD significantly increased with age, and the O/E for former and current male smokers was significantly higher than one, i.e., O/E (95% confidence interval) for current smokers with a Brinkman Index of <400, 400-799, and 800+ were 3.10 (2.00-4.81), 2.78 (2.05-3.73), and 4.76 (3.65-6.19), respectively. Among females, the O/E for current smokers with a Brinkman Index of <400, and 400-799 were significantly higher than one. CONCLUSION: Age and smoking were shown to constitute strong risk factors for COPD under the standard diagnostic criteria.

Adult↗

Activation of Epstein-Barr virus by saliva from Sjogren's syndrome patients.

The aim of this study was to examine the mechanism of Epstein-Barr virus (EBV) activation by soluble factors from the inflamed salivary glands of patients with Sjogren's syndrome (SS). Saliva from SS patients was used to examine the regulation of EBV activation by an inflammatory salivary microenvironment. Transient transfection of the EBV-negative salivary gland cell line (HSY) with BZLF1, a trans-activating EBV gene promoter-fusion construct (Zp-luc), was used in this study. The results showed that under conditions where the BZLF1 promoter is activated by potent stimuli, SS saliva (from eight of 12 patients) exerts a significant effect on expression of the luciferase gene. A specific inhibitor of protein kinase C did not affect the SS saliva-induced Zp-luc activity, whereas treatment with inhibitors of calmodulin, calcineurin and IP3, dose-dependently decreased this induction. Transforming growth factor beta1 (TGF-beta1), which is known to be expressed in SS salivary glands, dose-dependently induced Zp-luc activity. Hence, these results demonstrate the activation of EBV by SS saliva and suggest that EBV activation at the inflammatory site may occur in the presence of TGF-beta1 via triggering of the mitogen-activated protein kinase (MAPK) kinase signalling pathway.

Adult↗

No effects of extremely low frequency magnetic fields found on cytotoxic activities and cytokine production of human peripheral blood mononuclear cells in vitro.

Several epidemiologic studies have suggested an association between exposure to extremely low frequency (ELF) magnetic fields (MFs) and cancer in adults and children. A possible target of MFs is the immune system. The effects of the exposure to ELF MFs on the immunological functions of human peripheral blood mononuclear cells (PBMCs) obtained from healthy male volunteers were assessed by measuring the natural killer (NK) and lymphokine activated killer (LAK) activities and the production of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), and interleukin-10 (IL-10). The PBMCs were exposed to three different MF: linearly polarized (vertical), circularly polarized, and elliptically polarized, at 50 and 60 Hz. Magnetic flux densities were set at 500, 100, 20, and 2 microT (rms) for vertical field and at 500 microT (rms) for the rotating fields. Using cytotoxicity assay and enzyme-linked immunosorbent assay (ELISA) for cytokine production, we could not find any effects of ELF MFs on the cytotoxic activities and the cytokines production of human PBMCs.

Adult↗

Physical interaction of Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) with human oestrogen-related receptor 1 (hERR1): hERR1 interacts with a conserved domain of EBNA-LP that is critical for EBV-induced B-cell immortalization.

Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) consists of W1W2 repeats and a unique C-terminal Y1Y2 domain and plays a critical role in EBV-induced transformation. To identify the cellular proteins associating with EBNA-LP, we performed a yeast two-hybrid screen using EBNA-LP cDNA containing a single W1W2 domain as bait and an EBV-transformed human peripheral blood lymphocyte cDNA library as the source of cellular genes. Our results were as follows. (i) A cDNA in the positive yeast colony was found to encode a cellular protein, human oestrogen-related receptor 1 (hERR1), which is a constitutive transcriptional activator of the various types of oestrogen response elements. (ii) A purified chimeric protein consisting of glutathione S-transferase (GST) fused to hERR1 specifically formed complexes with EBNA-LPs containing one (EBNA-LPR1), two (EBNA-LPR2) or four W1W2 repeats (EBNA-LPR4) transiently expressed in COS-7 cells. Reciprocally, GST fused to EBNA-LPR1 or EBNA-LPR2 pulled down hERR1 transiently expressed in COS-7 cells. (iii) Mutational analyses of EBNA-LP revealed that the Y2 domain of EBNA-LP is responsible for the interaction with hERR1 and two leucines in the Y2 domain (Leu-78 and -82), which are conserved among a subset of primate gammaherpesviruses, are interactive sites for hERR1. So far, it has been reported that the only domain of EBNA-LP critical for EBV-induced transformation is the Y1Y2 domain. Potential roles of hERR1 in EBV-induced transformation are discussed.

Amino Acid Sequence↗

No effect of extremely low-frequency magnetic field observed on cell growth or initial response of cell proliferation in human cancer cell lines.

An effect on the tumor promotion process, as represented by accelerated cell growth, has been indicated as one example of areas that demonstrate the possibility of biological effects of extremely-low frequency magnetic fields. We, therefore, exposed the five cell lines (HL-60, K-562, MCF-7, A-375, and H4) derived from human tumors to a magnetic field for 3 days to investigate the effects on cell growth. Prior to exposure or sham exposure, the cells were precultured for 2 days in low serum conditions. The number of growing cells was counted in a blind manner. To investigate the effect on the initial response of cell proliferation, two cell lines were synchronized in G1 phase by serum starvation and then exposed to a magnetic field for 18 h (H4 cells) or 24 h (MCF-7 cells), both with and without serum stimulation. The rate of DNA synthesis, taken as a measure of the cell proliferation, was determined by following the incorporation of [(3)H]-thymidine into the DNA. Three different magnetic field polarizations at both 50 and 60 Hz were used: linearly polarized (vertical); circularly polarized; and an elliptically polarized field. Magnetic field flux densities were set at 500, 100, 20 and 2 microT (rms) for the vertical field and at 500 microT (rms) for the rotating fields. No effect of magnetic field exposure was observed on either cell growth or the initial response of cell proliferation.

Cell Division↗

Comparison of four microbial enzymes in Clostridia and Bacteroides isolated from human feces.

The activities of four microbial enzymes (azoreductase, nitroreductase, beta-glucuronidase, and beta-glucosidase) in major anaerobic members of human fecal microflora were quantified and the influence of the host factors on expression of these microbial enzyme activities was also investigated. Clostridium paraputrificum and C. clostridiiforme showed much higher activities than other fecal anaerobes tested. Nitroreductase activity in C. paraputrificum isolated from fecal specimens of patients with colon cancer was significantly (P < 0.05) higher than that in the clostridia isolated from healthy subjects and the subjects given high beef diets. However, the activities of some microorganisms tested showed marked differences in each strain.

Aerobiosis↗

Effects of power frequency alternating magnetic fields on reproduction and pre-natal development of mice.

Three groups of ICR male and female mice were exposed to 50-Hz, sinusoidal, alternating, horizontal magnetic fields of 0.0 mT (sham), 0.5 mT and 5.0 mT (rms) for 9 and 2 weeks prior to mating for males and females, respectively, through fertilization and until cesarean sectioning. Fetuses were collected by cesarean section on the 18th day of gestation. Approximately half were randomly selected for skeletal examination and the remainder used for visceral examination. No significant differences were found between the field- and the sham-exposed groups in pre-, post- and total implantation losses; number of live fetuses; sex ratio; live fetal weight; number of externally abnormal fetuses; and numbers of fetuses with skeletal and visceral anomalies. These results suggest that exposure to power-frequency magnetic fields has no major effects on reproduction and development in mice, and do not support the association of EMF exposure with adverse reproductive effects suggested by epidemiology.

Abnormalities, Radiation-Induced↗