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ABSTRACT: Consumed substances, including food, drink, and tobacco, produced in the environment are exposure sources of Cd. The object
of the present study was to estimate Cd exposure and absorption amount from smoking cigarettes, one exposure source of Cd,
using recent findings from Japan. The market share of cigarettes produced in foreign countries has increased in Japan, the
proportion of tobacco leaves harvested in foreign countries has increased in cigarettes produced in Japan, and the percentage
of smokers in Japan has changed. Therefore, obtaining the absorption value of Cd from smoking cigarettes using recent findings
from Japan is significant.
We collected information on (1) the concentrations of Cd in tobacco leaves by country of harvest and in cigarettes by country
of production, (2) the concentrations of Cd in cigarette smoke, (3) the proportion of tobacco leaves harvested in foreign
countries used in cigarettes made and sold in Japan, (4) the absorption rate of Cd in the airways for cigarette smoke, (5)
the smoking rate by gender, age, and year in Japan, (6) the number of cigarettes sold in Japan by year and country of production,
(7) the number of cigarettes smoked by smokers per day according to gender and age in Japan, and (8) the population size in
1998 by gender and age in Japan. The mean amount of Cd absorbed via the airways by smoking for smokers in Japan was calculated
to be 0.89–1.78 μg/day from the above information. The values are not small in comparison with the amount of Cd absorbed from
the digestive organs.
The concentration of Cd in tobacco leaves harvested in Japan and cigarettes produced in Japan is generally higher than that
of leaves harvested and cigarettes produced in foreign countries. The increase in the market share of cigarettes produced
in foreign countries and sold in Japan and the increase in the proportion of tobacco leaves harvested in foreign countries
used in cigarettes made and sold in Japan have decreased the amount of Cd absorbed by smoking for smokers in Japan.
Environmental Health and Preventive Medicine 04/2012; 6(3):154-159.
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ABSTRACT: Using a population approach, we investigated whether a group health education program exerted a preventive effect on checkup items at five years later. Workers turning 35 years old before the initial implementation of the program were entered in the control group (n = 422) and those turning 35 years on this date or after were entered in the intervention group (n = 206). These groups were compared using data obtained from routine health checkups at 35 and 40 years of age. In the intervention group, self-management ability prior to and after completion of the program was compared using a 2 item questionnaire based on the General Self-Efficacy Scale (GSES) and the Health Locus of Control (HLC). In males, the intervention group showed significant inhibition of increases in body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP), and gamma-glutamyl transpeptidase (gamma-GTP) compared to the control group. In females, however, a similar outcome was seen for gamma-GTP only. The evaluation index of self-management ability for both GSES and HLC significantly improved among males but did not significantly change among females at five years post-completion of the program. In particular, the group with a high GSES evaluation index experienced significant inhibition of weight gain. As a population approach, adoption of this program in the workplace for males aged 35 years may have an inhibitory effect on five-year weight gain. Further, programs which improve GSES appear effective in inhibiting weight gain.
Journal of UOEH 03/2011; 33(1):23-34.
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ABSTRACT: Cyclodextrin (CD) is widely used in the pharmaceutical and nutritional fields to form an inclusion complex with lipophilic compounds for the improvement of their aqueous solubility, stability and diffusibility under physiological conditions. In this study, we investigated the effect of the γ-tocotrienol (γT3) inclusion complex with CD on its oral bioavailability. Five-week-old C57BL6 mice were fed a vitamin E-free diet for 28 days, followed by the oral administration of 2.79 mg of γT3-rich fraction (TRF) extracted from rice bran or the equivalent dose (14.5 mg) of a CD inclusion complex with TRF (TRF/CD). The levels of γT3 in sequentially collected plasma were determined by LC-MS/MS. The pharmacokinetic study revealed that the plasma concentrations of γT3 were increased and peaked at 6 or 3 h after the oral administration of TRF or TRF/CD, respectively (C(max) values of 7.9±3.3 or 11.4±4.5 μM, respectively). The area under the curve of plasma γT3 concentration also showed a 1.4-fold increase in the group administered with TRF/CD compared with the TRF-only group. Furthermore, the mice that had received the TRF/CD tended to reduce the endotoxin shock induced by injection with lethal amounts of Escherichia coli lipopolysaccharide, compared with the mice that had received TRF alone. Taken together, our results suggest that the CD inclusion improved γT3 bioavailability, resulting in the enhancement of γT3 physiological activity, which would be a useful approach for the nutrition delivery system.
The Journal of nutritional biochemistry 02/2011; 22(12):1121-6. · 4.29 Impact Factor
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ABSTRACT: Recently studies have shown that ectopic expression of activation-induced cytidine deaminase (AID) plays an important role in carcinognesis and cancer progression of inflammatory-associated cancers. Here, we examined the molecular mechanism of ectopic expression of AID in cancer cells, and whether or not nitric oxide (NO) modulates this expression, as NO is known to cause chemical deamination of the cytidine. In several cancer cell lines, treatment with the DNA methyltransferase (Dnmt) inhibitor 5-Aza-dC effected expression of AID by TNF-α, and expression was further induced by additional treatment with histone deacetylase (HDAC) inhibitors with no stimulation. The CpG sites located in the promoter and exon 1 region of the AID gene in cancer cells were found to be hypomethylated in correlation with AID expression levels. Further, administration of HDAC inhibitors also induced expression of inducible nitric oxide synthase (iNOS) in cancer cells treated with 5-Aza-dC. Interestingly, administration of S-nitroso-L-glutathione (GSNO) a nitric oxide (NO) donor, was found to enhance AID and iNOS expression in LoVo cells treated with 5-Aza-dC. Our findings suggest that AID and iNOS expression in cancer cells may be modified by epigenetic mechanisms, and that NO may further enhance AID and iNOS expression. Given recent plans to introduce Dnmt and HDAC inhibitors as novel cancer treatments, these findings regarding the potential for Dnmt and HDAC inhibitors to enhance expression of AID and iNOS, resulting in further cancer progression, might be taken into consideration.
Oncology Reports 01/2011; 25(1):153-8. · 1.84 Impact Factor
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Akira Mizuki, Masayuki Tatemichi,
Nobuhiro Tsukada,
Ryousuke Nagamatsu,
Mitsuhiko Kawaguchi,
Tatsuya Itoshima,
Shigeki Maruyama,
Atsuhiko Satou,
Yasuhisa Imari,
Toshiharu Kawatoko,
Junya Shimono,
Hiroshi Nagata
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ABSTRACT: To assess the efficacy of the additional treatment of transcatheter arterial chemoembolization (TACE) to percutaneous ethanol injection (PEI) therapy for relatively small hepatocellular carcinomas (HCCs), a multicenter randomized control study (RCT) was performed. We conducted an RCT and follow-up study during the enrollment period from 1997 to 1999. Newly diagnosed patients with one to three HCC tumors measuring from 2 to 4 cm (4 cm maximum) in diameter were enrolled. A total of 30 patients initially underwent a combination TACE-PEI or PEI-alone therapies at eight randomly assigned Japanese hospitals. However, 3 patients withdrew. Of the 27 remaining patients, 13 were treated with the combination TACE-PEI therapy and 14 with PEI therapy alone. The patients were observed over several months [median (interquartile range) 33.2 (24.6) months]. There were no significant differences in the background of the patients between the two groups. Among the patients treated with TACE-PEI, the development of a local residual tumor was of significantly lower occurence, compared to the group receiving PEI alone (7.6 and 42.9%, respectively; P=0.024). However, the mean cancer-free time (absence of local or multiple nodule recurrence) or patient survival time was not significantly different between the two groups [PEI alone vs. TACE-PEI: cancer-free time 16.7 (95% CI 7.3-26.0) vs. 22.9 months (95% CI 12.4-33.4); survival time 57.2 (95% CI 37.2-77.2) vs. 42.4 months (95% CI 29.2-55.6)]. Although the combination of TACE and PEI had significant effects on the local tumor control, no efficacy of the addition of TACE to PEI was noted in the prognosis among patients with relatively small HCC tumors.
Oncology letters 09/2010; 1(5):855-859. · 0.11 Impact Factor
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Masayuki Tatemichi,
Tadashi Nakano,
Takeshi Hayashi,
Katsutoshi Tanaka,
Hisanori Hiro,
Toshiaki Miyamoto,
Miho Aratake,
Norihide Nishinoue,
Akira Yamazaki,
Toshio Nakadate,
Minoru Sugita
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ABSTRACT: Purpose: To identify symptoms potentially related to glaucomatous visual field abnormalities (VFAs) in a population-based setting, and to assess the applicability of using these symptoms to identify persons at risk of developing glaucoma. Methods: In this study, 10 214 Japanese male general workers (mean age, 45.3 ± 8.8 years) filled out a self-administered questionnaire and underwent frequency doubling technology (FDT) perimetry testing. The questionnaire inquired about whether the participant was suffering from any of nine symptoms, with scores for each response graded on a four-item Likert scale: 0 (none), 1 (rarely), 2 (sometimes), and 3 (always). Results from the questionnaire were compared among three groups: participants without any VFAs (9767), participants with VFAs as determined by the FDT test (FDT-VFA; 447), and 227 participants (of the 447 FDT-VFA participants) with glaucomatous VFAs who were newly diagnosed by ophthalmologic examinations. Results: The mean summed scores for the total items were significantly (p < 0.01) higher in FDT- and glaucomatous VFA groups than in normal subjects. In particular, responses citing the symptoms 'feeling of something in the front of the eye' and 'feeling of hardness to see in dark places' were significantly (p < 0.05) more frequent in subjects with FDT- and glaucomatous VFAs than among normal participants. However, the respective areas under the receiver operating characteristic curve of summed scores for the nine total items and for the two items which showed significant differences for the glaucoma groups were 0.57 (95% confidence interval = 0.53-0.60) and 0.58 (95% confidence interval = 0.54-0.61). Conclusion: Although the symptoms 'feeling of hardness to see in dark places' and 'feeling of something in the front of the eye' could be associated with glaucomatous VFA in a population-based setting, inquiring about symptoms is of little aid in identifying subjects with glaucomatous VFA as a strategy for public health.
Acta ophthalmologica 08/2010; 90(6):546-551. · 2.44 Impact Factor
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ABSTRACT: This study investigated the association between glutathione S-transferases (GST) polymorphisms and immunoglobin G (IgG) titer levels in serum against Helicobacter pylori (H. pylori). Out of a total 300 healthy subjects seropositive for H. pylori, we analyzed the relationship between 15 single-nucleotide polymorphisms (SNPs), namely two in GST-mu2 (GST-M2), five in GST-mu3 (GST-M3), four in GST-pi1 (GST-P1) and four in GST-theta2 (GST-T2), and IgG antibody titer levels in serum against cytotoxin-associated gene A (CagA) and the surface antigen of H. pylori (Hp), as well as the levels of pepsinogen I (PGI). Titer levels were classified by tertile. The age-sex adjusted odds ratios (ORs) and 95% confidence intervals (CIs) in the middle and low titer groups were calculated using a polytomous logistic regression model, with the high titer group considered as control. Results for GST-M3 showed a significant association between SNPs, CagA and Hp titers. In addition, the AA genotype (high enzyme activity) from SNP rs7483 (Val224Ile) in GST-M3 showed a significantly low risk for being in the low titer group (OR: 0.48, 95% CI: 0.27-0.86 and OR: 0.46, 95% CI: 0.26-0.83 for CagA and Hp, respectively). Furthermore, the AA genotype from the rs7483 SNP showed significantly (P<0.05) higher PGI levels than did the genotypes harboring a G allele (mean (s.d.)=66.9 (32.0) and 59.1 (30.7) microg ml(-1) for AA and AG+GG, respectively). Our results suggest that GST-M3 polymorphisms are associated with levels of IgG titer in serum against H. pylori. GST-M3 activity is possibly involved in protection against mucosal atrophy caused by H. pylori as the levels of IgG titer and PGI are linked to mucosal status.
Journal of Human Genetics 08/2009; 54(10):557-63. · 2.57 Impact Factor
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ABSTRACT: We clarified the clinical significance of measurement of IgG antibody titers against Helicobacter pylori using data from a nested case-control study from a large-scale cohort study in Japan.
Participants included 36,745 subjects from the Japan Health Center-based Prospective Study who responded to the baseline questionnaire and provided a blood sample. Subjects were aged 40-69 years and were followed over 15 years after initial sampling. Controls were matched to 511 gastric cancer patients. Plasma surface antigen (Hp)-IgG titer was measured using ELISA, and mucosal atrophy was determined by measuring pepsinogen I and II levels.
Seropositive subjects with low Hp-IgG titer and mucosal atrophy showed a higher risk for gastric cancer than high-titer subjects. Odds ratio (OR) referred to cases with true negative IgG titers and no mucosal atrophy. In moderately atrophic subjects, the low titer OR was 19.0, with a 95% confidence interval (CI) of 7.7-46.9, and 12.5 for high titer, with a 95% CI of 5.2-30.0. In severely atrophic subjects, the low titer OR was almost double that of high-titer subjects (OR = 30.2, 95% CI = 12.4-73.7 and OR = 15.9, 95% CI = 6.3-40.3, respectively). These associations were observed more frequently for differentiated than undifferentiated gastric cancer.
Combination assay with Hp-IgG titer and pepsinogens may help identify groups at high risk for gastric cancer. Subjects with low Hp-IgG titer and mucosal atrophy were at extremely high risk for gastric cancer, particularly differentiated cancer. Subjects with this background may require ongoing observation and periodic endoscopic examination for early cancer detection.
Helicobacter 07/2009; 14(3):231-6. · 3.15 Impact Factor
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ABSTRACT: We investigated the involvement of the inducible nitric oxide synthase (iNOS) gene in tumor promotion and progression. In the first study, 1 week after subcutaneous injection of benzo(a)pyrene into iNOS-deficient (iNOS) and wild-type (iNOS) mice, a foreign body (plastic plate) was subcutaneously inserted into the carcinogen injection site to evoke chronic inflammation. In the second study, primarily cultured tumor cells (PCTc) with different iNOS gene status were prepared from tumors induced in the first study, and they were implanted into the subcutaneous space of iNOS and iNOS mice, making four different combinations of iNOS gene status. Although the mice that were subjected to plastic plate-induced inflammation [p-IN(+)] exhibited significantly shorter tumor latency than those with p-IN(-), iNOS gene status did not affect it in the p-IN(-) or p-IN(+) groups. The rate of microscopic invasion and expression levels of matrix metalloproteinase mRNA were, however, higher in iNOSp-IN(+) than iNOSp-IN(+) mice. In the second study, microscopic invasion was also observed in the subcutaneously implanted tumors only in the case of PCTc with iNOS gene into iNOS mice, although iNOS gene status in PCTc or host mice did not affect the tumor growth curve. These data suggest that the iNOS gene was associated with tumor progression, rather than tumorigenesis, in this experimental model. The iNOS gene in both the stromal and cancer cells played an important role in invasion. Inhibition of iNOS gene activity might be useful for local cancer control in inflammation-associated cancers.
European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 03/2009; 18(1):1-8. · 2.21 Impact Factor
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ABSTRACT: Microsatellite polymorphism in the promoter region of the heme oxygenase-1 (HO-1) gene was analyzed jointly with that of the inducible nitric oxide synthase (iNOS) gene among Japanese subjects (control and gastric cancer patients). A higher promoter activity genotype of the HO-1 gene was associated with increased risk for gastric cancer in women. Gastric cancer risk was notably increased in subjects carrying a higher promoter activity genotype for both HO-1 and iNOS compared to those with a lower promoter activity genotype for both genes. Our data suggest that genetic polymorphisms of HO-1 and iNOS modulate individual susceptibility to gastric cancer risk.
Cancer letters 06/2008; 269(1):78-84. · 4.86 Impact Factor
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ABSTRACT: The present study epidemiologically clarified the different roles of Helicobacter pylori (Hp) infection in carcinogenesis between two major histological types of noncardia gastric cancer (ncGC), intestinal (=differentiated) and diffuse (=undifferentiated), by analyzing IgG antibody titer against Hp surface antigen on the data set of a nested case-control study in a large cohort study conducted in Japan.
A total of 36,745 subjects aged 40 to 69 years in the Japan Health Center-based prospective study who responded to the baseline questionnaire and provided blood were followed over 15 years; 350 ncGC cases (differentiated=242, undifferentiated=108) matched to controls were used. Using baseline blood samples, plasma IgG titer was measured using ELISA. The level of IgG titer >10 U (cut-off value) was classified into three grades in groups of equal number: low, middle, and high.
IgG titer of Hp was significantly (p<0.01) higher in undifferentiated cases than in differentiated ones. Among the three grades of Hp IgG titer, the high titer was more closely associated with risk of undifferentiated ncGC (odds ratio (OR) for high=7.8, 95% confidence interval (CI)=2.4-24.9 vs. OR for low=6.4, 95% CI=2.1-19.6), while the low titer was a better predictor of differentiated ncGC (OR for high=3.2, 95% CI=1.6-6.4 vs. OR for low=5.9, 95% CI=3.0-11.6, trend p < 0.05). The high titer group had the lowest risk to develop differentiated ncGC with <7 years (OR=3.2, 95% CI=1.3-7.7), whereas the high titer group demonstrated the highest risk for undifferentiated ncGC developing (OR=11.6 95% CI=2.3-59.1).
Our study epidemiologically confirmed that atrophic changes caused by Hp infection determine the development of differentiated-type ncGC, and the inflammation itself induced by Hp infection promotes the development of undifferentiated-type ncGC.
Acta oncologica (Stockholm, Sweden) 01/2008; 47(3):360-5. · 2.27 Impact Factor
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ABSTRACT: Numerous epidemiologic studies have revealed that smoking is a significant risk factor of many diseases. Some studies reported increase in medical expenditure by smoking using odds or hazard ratios between smoking and diseases in epidemiologic studies. The purpose of the present study is to investigate the ratios of mean medical expenditures between smokers and nonsmokers from studies conducted observing medical expenditure directly in Japan. We collected 11 published articles of studies conducted observing medical expenditures of smokers and nonsmokers directly in Japan. The weighted geometric mean of ratios between age-adjusted mean medical expenditures for smokers and nonsmokers of National Health Insurance and Government-Managed Health Insurance beneficiaries which included many elderly individuals was somewhat greater than 1.0, while the value of Society-Managed Health Insurance that included a small number of elderly people was less than 1.0. Smoking and smokers' indifference to health increase the medical expenditure of the smokers, especially elderly smokers. It was not determined, however, whether the mean medical expenditure of smokers is actually greater than that of nonsmokers.
The Keio Journal of Medicine 07/2007; 56(2):53-60.
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ABSTRACT: Chronic inflammation is a recognized risk factor for human cancer at various sites because of persistent oxidative and nitrative tissue damage. Trp53+/- mice show the predisposition to tumor development, such as sarcomas and lymphomas, compared with Trp53+/+ mice. We investigated the effects of chronic inflammation, especially oxidative and nitrative stress, induced by subcutaneous implantation of a plastic plate (10 x 5 x 1 mm) as a foreign body on tumorigenesis in Trp53+/- and Trp53+/+ mice. The plastic plates were implanted at the age of about 11 weeks. Thirty out of 38 Trp53+/- mice (79%) developed sarcomas around the implant (mean time of tumor appearance was 45.8 +/- 12.0 weeks of age), whereas only one of 10 Trp53+/+ mice with an implant (10%) developed a tumor, at 56 weeks. No sarcomas developed at a sham-operation site. Two of 10 Trp53+/- mice with no implant (20%) also developed three sarcomas spontaneously at 77, 81 and 84 weeks. Increased immunostaining for markers of oxidative and nitrative stress (8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-nitroguanine and 3-nitrotyrosine) and expression of inducible nitric oxide synthase in tumor cells and inflammatory cells were detected in implant-induced sarcomas compared with spontaneous sarcomas in Trp53+/- mice. Furthermore, p53 loss of heterozygosity was observed in 26 out of 29 implant-induced sarcomas (90%). These results indicate that implanted foreign bodies significantly enhanced sarcoma development in Trp53+/- mice, and this may be associated with increased oxidaive and nitrative stress. Loss of the remaining wild-type p53 allele and loss of p53 function appears to be, at least in part, underlying molecular mechanisms during the development of sarcomas at the implantation site in Trp53+/- mice. Such implant-induced sarcoma development in Trp53+/- mice could be useful for studying molecular mechanisms and developing new strategies for chemoprevention in human carcinogenesis induced by chronic inflammation and/or foreign bodies.
Carcinogenesis 02/2007; 28(1):191-8. · 5.70 Impact Factor
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Akira Mizuki, Masayuki Tatemichi,
Mitsuhiro Nikaido,
Naoki Hosoe,
Sinsuke Funakoshi,
Kazuto Fukui,
Norio Maeda,
Takeharu Shigematsu,
Hiromi Nishiya,
Tatsuhiko Hayashi,
Hiroshi Nagata,
Norifumi Hibi,
Nobuhiro Tsukada
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ABSTRACT: We devised and evaluated a clinical pathway (CP) protocol for patients with bleeding peptic ulcers (BPU). Patients without severe comorbidities, who had been diagnosed with BPU and who had undergone endoscopic treatment, were enrolled in our study. The CP adaptation rate for BPU patients was 78.8% (89/113). The variance rate was 13.5% (12/89). The median length of admission was 10.0 +/- 4.6 days (n = 78) before and 7.4 +/- 2.9 days (n = 77) after introducing CP. Our CP for BPU was safe and resulted in shorter hospital stays and, therefore, cost reductions. In elder patients, our CP was also successful, but the variance rate was higher than in younger patients.
Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 04/2006; 103(3):283-9.
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ABSTRACT: We have developed an analytical method to quantitate urinary 8-nitroguanine, a product of nitrative nucleic acid damage caused by reactive nitrogen species such as peroxynitrite and nitrogen dioxide. 8-Nitroguanine was purified from human urine using immunoaffinity columns with an anti-8-nitroguanine antibody, followed by quantitation by high-performance liquid chromatography-electrochemical detection. Four sequential electrodes were used to (a) oxidize interfering compounds (+250 mV), (b) reduce nitrated bases (two online electrodes at -1000 mV), and (c) quantitate reduced derivatives (+150 mV). Using this system 8-nitroxanthine can also be detected, with the detection limits being 25 and 50 fmol/injection for 8-nitroguanine and 8-nitroxanthine, respectively. The method was used to analyze both adducts in the urine of smokers (n=12) and nonsmokers (n=17). We found that smokers excrete more 8-nitroguanine [median, 6.1 fmol/mg creatinine; interquartile range (IQR), 23.8] than nonsmokers (0; IQR, 0.90) (p=0.018), and although 8-nitroxanthine was detected in human urine, its level was not related to smoking status. This is the first report to show that 8-nitroguanine is present in human urine and the methodology developed can be used to study the pathogenic roles of this adduct in the etiology of cancers associated with cigarette smoking and inflammation.
Free Radical Biology and Medicine 03/2006; 40(4):711-20. · 5.42 Impact Factor
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ABSTRACT: Although the intraocular pressure (IOP) is the most important factor related to the onset and progression of glaucoma, there is little evidence on long-term aging effects on IOP. This article examines the changes of IOP over 10 years in normal eyes to assess physiologic changes related to aging.
Population-based long-term longitudinal study. STUDY POPULATION AND OBSERVATION PROCEDURE: Two thousand nine hundred eighty-seven Japanese male aircraft crew members underwent IOP measurement by Goldmann apparatus and received physical and complete ophthalmologic examinations every year for 10 years. A total of 2330 healthy persons (21-49 years; mean age, 35.9+/-6.8 [standard deviation]) who had no history of treatment for ophthalmic diseases, current illnesses, and no missing data for 10 consecutive years were analyzed.
For analysis of the longitudinal index (trend), the linear regression coefficients for 11 points of measurement were determined. Ophthalmologic and physiologic factors affecting the 10-year mean values and a trend of IOP were examined by multivariable linear regression analysis.
Intraocular pressure tended to decrease with age in all age groups. The mean linear regression coefficient (right eye/left eye) = -0.076/-0.060 (95% confidence interval [CI]: (-0.094 to -0.057)/(-0.078 to -0.041), -0.073/-0.060 [95% CI: (-0.084 to -0.062)/(-0.071 to -0.049)], and -0.060/-0.050 [95%CI: (-0.075 to -0.046)/(-0.064 to -0.036)] (mmHg/year) in the 20s, 30s, and 40s, respectively). In investigating correlations between the 10-year mean values of IOP and factors examined in this study, multivariate analysis showed a significantly inverse correlation with spherical power (partial regression coefficient [B] = -0.155/-0.144) and positive correlation with esophoria (B = 0.536/0.521), systolic blood pressure (B = 0.021/0.022), heart rate (B = 0.024/0.024), and hematocrit (B = 0.041/0.043) with IOP. The trend of IOP was significantly positively associated with the trends of systemic factors: body mass index (BMI) (B = 0.117/0.119), blood pressure (systolic) (B = 0.020/0.020), and hematocrit (B = 0.057/0.045), but not with any ophthalmologic factor.
The long-term observation clearly demonstrated that, in normal eyes, the IOP decreased with aging. The IOP value was negatively associated with spherical power and positively with esophoria, blood pressure, heart rate, and hematocrit. The change of IOP could be affected mainly by the change of body mas index, blood pressure, and hematocrit.
Ophthalmology 05/2005; 112(4):609-16. · 5.45 Impact Factor
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ABSTRACT: Tandem repeat number polymorphism of a CCTTT pentanucleotide in the promoter region of the inducible nitric oxide synthase gene (iNOS) and a polymorphism of the interleukin-1beta (IL-1B) promoter at position -31 were analyzed in DNA samples from 181 Japanese control subjects and 158 gastric cancer patients, including 96 intestinal type and 62 diffuse type. An association between the intestinal type of gastric adenocarcinoma and higher promoter activity of the iNOS gene was found in women, especially those having higher promoter activity of the IL-1B gene and without a history of smoking. Our results imply that chronic inflammation caused by excess nitric oxide generated by iNOS contributes to Helicobacter pylori-induced gastric cancer.
Cancer Letters 02/2005; 217(2):197-202. · 4.24 Impact Factor
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ABSTRACT: To study the association between computer use and visual field abnormalities (VFA) and to assess whether heavy computer users have an increased risk of glaucoma.
Cross sectional multicentre study. Subjects and observation procedures: A total of 10 202 randomly selected Japanese workers (mean (SD) age 43.2 (9.8) years) were screened for VFA using the frequency doubling technology perimetry (FDT-VFA), in addition to undergoing a general medical check up, and then ophthalmologically examined. Information about their computer use and refractive errors was obtained from a questionnaire and interview, respectively.
As a result of FDT test, 522 and 8602 subjects were positive and negative for FDT-VFA, respectively. A significant (p = 0.004) interaction was found between computer use and refractive errors regarding the risk of FDT-VFA. In stratified analysis, heavy computer users with refractive errors showed a significant positive association with FDT-VFA (odds ratio (OR) = 1.74, 95% confidence interval (CI) 1.28 to 2.37), while those without refractive errors did not. Comparison of 165 subjects with an ophthalmological diagnosis of glaucoma and 2918 controls showed that the OR for glaucoma of heavy computer users with refractive errors was 1.82 (95% CI 1.06 to 3.12). Of 165 subjects with glaucoma, 141 had refractive errors, especially myopia (96.4%, 136 of 141).
Although there are limitations to this study, such as its cross sectional design, heavy computer users with refractive errors seem to have an increased risk of FDT-VFA. Glaucoma might be involved in an underlying disease and myopia in a risk factor for FDT-VFA.
Journal of Epidemiology & Community Health 01/2005; 58(12):1021-7. · 3.19 Impact Factor
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ABSTRACT: Trp53-deficient mice spontaneously develop lymphomas, mainly of thymic origin, although the molecular mechanism remains largely unknown. As several interaction effects between p53 and iNOS have been reported, we hypothesized that iNOS activity in the thymus is causally linked to lymphomagenesis in Trp53-deficient mice. We therefore created mouse strains with different combinations of the Trp53 and iNOS genes. Western blot and histologic analyses showed that the iNOS protein was constitutively expressed in the thymus independently of Trp53 status and its expression was enhanced in Trp53+/- and Trp53-/- mice compared to Trp53+/+ mice. Homozygous disruption of iNOS decreased the incidence of thymic lymphomas by almost 40% (p=0.087) and 90% (p<0.05) in Trp53-/- and Trp53+/- mice, respectively, compared to the respective iNOS wild-type mice but significantly (p<0.05) increased the development of nonthymic lymphomas in Trp53-/- and Trp53+/- mice. Although iNOS gene disruption did not affect the phenotype of thymic lymphomas, absence of the iNOS gene shifted the spectrum of nonthymic lymphoma from the B-cell to the T-cell lineage. RT-PCR analysis revealed enhanced expression of IL-10, which could have a promoting effect on lymphomagenesis, even without any stimulation, in the spleen of aging mice with the gene combinations Trp53-/-iNOS-/- and Trp53+/-iNOS-/- but not Trp53-/-iNOS+/+ or Trp53+/-iNOS+/+. These results suggest that iNOS could increase the development of thymic lymphomas in Trp53-deficient mice. While iNOS may have protective effects against nonthymic lymphomagenesis, the regulation of cytokine production by iNOS may be involved in the underlying mechanism of antilymphomagenesis effects in the peripheral lymphoid organ.
International Journal of Cancer 10/2004; 111(6):819-28. · 5.44 Impact Factor
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ABSTRACT: Basic fibroblast growth factor (bFGF) is a key factor in the healing of human and experimental peptic ulcers, but the behavior of bFGF in human giant gastric ulcer remains to be determined. We determined the bFGF content in the rim of giant ulcers (bFGF rim) and in non-ulcerated mucosa located opposite the ulcer (bFGF opposite) before and during treatment.
Biopsy specimens were endoscopically obtained from 31 patients with giant gastric ulcers and 17 patients with small ulcers before and 2, 4 and 8 weeks after treatment. The bFGF concentrations in the specimens were measured using a sandwich enzyme immunoassay.
Before treatment, the bFGF rim and bFGF opposite concentrations were not associated with ulcer size. The bFGF rim concentration before treatment in the rapid healing group was higher than that in the slow healing group, but no significant difference in bFGF opposite concentrations were found between the two groups. The bFGF rim concentration in the rapid healing patients decreased during treatment, while the slow healing patients showed an inverse response. The bFGF opposite concentration did not change during treatment and bFGF rim concentrations in Helicobacter pylori-positive stomachs were significantly lower than those in H. pylori-negative stomachs.
The bFGF rim concentration is not involved in the formation of giant gastric ulcers in humans. However, the bFGF rim concentration does appear to promote healing. The bFGF opposite concentration is not related to either the formation or healing of giant gastric ulcers.
Journal of Gastroenterology and Hepatology 06/2004; 19(5):528-34. · 2.87 Impact Factor
