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Volume 58 (2003)
- Issue 3 Pages 311-
- Issue 2 Pages 243-
Volume 58, Issue 2
Displaying 1-9 of 9 articles from this issue
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Hidekuni INADERA, Kouji MATSUSHIMA2003 Volume 58 Issue 2 Pages 243-247
Published: May 15, 2003
Released on J-STAGE: February 17, 2009
JOURNAL FREE ACCESSA revolution in biology and medicine is taking place as a direct consequence of rapid developments in the field of molecular biology. The tremendous advances in our knowledge of basic molecular genetics and cell biology have opened the door for new methods of diagnosis, assessment of individual susceptibility to disease, and elucidation of the pathogenesis of disease. These advances will have a profound impact on the practice of occupational and environmental medicine. In this review, we intend to summarize the approaches we have applied in order to deal with the environmental problems we have faced.View full abstractDownload PDF (860K) -
Hiroyoshi FUJITA, Chiaki NISHITANI, Mineba NAKAJIMA2003 Volume 58 Issue 2 Pages 248-253
Published: May 15, 2003
Released on J-STAGE: February 17, 2009
JOURNAL FREE ACCESSIron is regarded as one of the most important nutriments, and many diseases are related to iron deficiency or its overload. Approximately 70% of iron in the body is located in heme, functioning as hemoglobin, myoglobin, and cytochrome P450. Iron itself also has many catalytic functions through the iron-sulfa cluster. It is believed that iron and/or heme plays significant roles in regulation of genes, however, little about the mechanism has been elucidated.
Recently, not only iron but also heme has been identified as important regulators of gene activation via oxygen sensing. For example, iron controls the oxygen response of HIF-1 activity by two mechanisms; in cytosol, the half life of HIF-1α is determined by hydroxylation of Pro564, and transcriptional activity of HIF1α in nuclei is disturbed by hydroxylation of Asn803. Hemoproteins in prokaryotes such as FixL, Dos, and HemAT were found to be oxygen sensors, however, little has been reported in eukaryotes. Our finding on Bach1 seems to be the first report of heme and oxygen-mediated regulation of genes in vertebrates.
Understanding of these newly identified mechanisms in iron- and heme-controlled genes is essential in the field of nutritional science. We therefore summarize here the recent findings indicating mechanisms of iron as transcriptional regulators.View full abstractDownload PDF (2655K) -
Contributions of Molecular Biology to Behavior ModificationsTatsuya TAKESHITA2003 Volume 58 Issue 2 Pages 254-259
Published: May 15, 2003
Released on J-STAGE: February 17, 2009
JOURNAL FREE ACCESSHigh alcohol sensitivity among Asians is mainly due to a genetic polymorphism in the low Km aldehyde dehydrogenase (ALDH2) gene. Strong correlations between the ALDH2 genotype and alcohol sensitivity or alcohol drinking habits have been reported.
Another prevalent polymorphism in the alcohol dehydrogenase β-subunit(ADH2 gene) among Asians appears to modify skin flushing reactions after exposure to ethanol but does not influence alcohol drinking behavior. Both the ADH2 and ALDH2 genotypes have been significantly correlated with the risk of alcoholism. In a Japanese occupational population, a gene-environment interaction of the ALDH2 genotype and daily hassles scores for development of problem drinking behavior was observed. Habitual drinkers with the ALDH2*1/*2 genotype had higher frequencies of sister-chromatid exchange in cultured lymphocytes and higher 8-OHdG levels in polymorphonuclear leukocytes than those with the ALDH2*1/*1 genotype. Alcoholics and heavy drinkers with the ALDH2*1/*2 genotype have been shown to have significantly elevated risks for esophageal and multiple cancers in upper digestive organs than those with the ALDH2*1/*1 genotype. In Japan, bronchial asthma patients with the ALDH2*1/*2 genotype have been shown to have a significantly elevated risk for experiencing alcohol-induced asthma compared with the ALDH2*1/*1 genotype. Providing services to determine these genotypes would be of great help for each individual to make a plan for tailor-made health promotion.View full abstractDownload PDF (1022K) -
Akio KOIZUMI2003 Volume 58 Issue 2 Pages 260-266
Published: May 15, 2003
Released on J-STAGE: February 17, 2009
JOURNAL FREE ACCESSWith the end of the Human Genome Project, we can foresee on the horizon the molecular dissection of common diseases, although we could not have imagined such a possibility even 10 years before. As byproducts of the human genome project, molecular dissection enables us to provide evidence-based health care against common diseases: therapies will become more specific and effective than before against individual health risks associated with genetic diversities. In the present paper, I will briefly sketch state-of-the-art genetic linkage analysis for common diseases and discuss inherent difficulties which hamper our approach. Emphasis should be put on some advantages of our country for genetic studies, where our local communities still preserves old genetic backgrounds. Such a unique feature will facilitate genetic dissections of not only rare hereditary diseases but also common diseases, paving the way for genetic epidemiology in the next 10 years.View full abstractDownload PDF (1246K) -
As a Model for “Molecular-Targeting Prevention” of CancerYoshihiro SOWA, Toshiyuki SAKAI2003 Volume 58 Issue 2 Pages 267-274
Published: May 15, 2003
Released on J-STAGE: February 17, 2009
JOURNAL FREE ACCESSRecent progress in molecular biology and genetics has improved understanding of the mechanisms of carcinogenesis. However, there are few effective methods for prevention or therapies against cancer based on such elucidated molecular mechanisms of carcinogenesis. We therefore tried to develop novel methods of cancer prevention and therapy based on them.
For example, the tumor-suppressor gene p53 is mutated in about 50% of human malignancies or in a cancer-prone family with Li-Fraumeni syndrome. It is known that p53 stimulates the promoter activities of p21/WAF1, gadd45 and bax genes to enhance their expression as a transctiptional factor, resulting in cell cycle arrest, DNA repair and apoptosis, respectively. Therefore, chemical compounds or food factors that can stimulate these genes might compensate for part of the p53 function. As a model of our hypothesis, we found that histone deacetylase inhibitors such as butyrate and trichostatin A dramatically stimulate the p21/WAF1 gene promoter through the Sp1 sites, resulting in cell cycle arrest. We therefore hypothesized that a strategy for up-regulating p53-target genes such as p21/WAF1, gadd45 and bax might be useful for cancer prevention or therapy, and termed this method “Gene-regulating chemoprevention” or “Gene-regulating chemotherapy” against cancer. In fact, butyrate, a short chain fatty acid, exists in colon lumen as a metabolite of dietary fiber, and is believed to be preventive against colon cancer.
In conclusion, we proposed that “Gene-regulating chemoprevention” and “Gene-regulating chemotherapy” may be new promising strategies for cancer prevention or therapy, and histone deacetylase inhibitors are good candidates for these strategies. “Gene-regulating chemoprevention” is a particularly suitable model for “Molecular-targeting prevention”, which we have proposed recently. We believe that “Molecular-targeting prevention” will become one of the most important concepts in the 21st century for general prevention of a variety of common hereditary or non-hereditary common diseases.View full abstractDownload PDF (1501K) -
Kazuko HIRAI, Yasuyo ASANO, Minako KAKESU, Hisa HIGUCHI, Mamoru NAKANI ...2003 Volume 58 Issue 2 Pages 275-280
Published: May 15, 2003
Released on J-STAGE: February 17, 2009
JOURNAL FREE ACCESSObjectives: The effects of 3 months of desert travel in China on serum fatty acids and tocopherol were studied.
Methods: In project staff members (6 males, 3 females, aged 19-27 years), serum levels of fatty acids and α-tocopherol were analyzed before and after travel by gas liquid chromatography and high-performance liquid chromatography, respectively.
Results: Comparison of the levels before and after the trip showed no differences in serum total cholesterol, triglycerides, total protein or α-tocopherol. There were no changes in the levels of total fatty acids, while the percentage of polyunsaturated fatty acids increased (p<0.05). Levels of n-3 PUFA lowered form 166μg/ml to 103μg/ml, and those of n-6 PUFA had increased from 988μg/ml to 1140μg/ml after the trip (p<0.01 and p<0.001, respectively). No change was observed in the serum levels of α-linolenic acid (C18: 3n-3), but lowering of the levels of eicosapentaenoic acid (EPA, C20: 5n-3) from 41.4μg/ml to 16.3μg/ml and docosahexaenoic acid (DHA, C22: 6n-3) from 107.8μg/ml to 71.7μg/ml was found after the trip (p<0.05 and p<0.01, respectively). Serum levels of linoleic acid (LA, C18: 2n-6) increased from 832μg/ml to 958μg/ml (p<0.001), and arachidonic acid (AA, C20: 4n-6) tended to increase. The ratios of n-3/n-6 PUFA and EPA/AA decreased from 0.171 to 0.091 and from 0.258 to 0.096 after the trip, respectively (p<0.01 for both).
Conclusions: Our findings indicated that 3 months of desert travel increased the serum levels of n-6 PUFA and LA and reduced the serum levels of n-3 PUFA and EPA and the ratios of n-3/n-6 PUFA and EPA/AA, possibly due to a relative essential fatty acid deficiency.View full abstractDownload PDF (959K) -
Comparison among Barley, Rice, and Corn StarchJue LI, Takashi KANEKO, Yuan WANG, Li-Qiang QIN, Akio SATO2003 Volume 58 Issue 2 Pages 281-286
Published: May 15, 2003
Released on J-STAGE: March 31, 2009
JOURNAL FREE ACCESSObjectives: In this study, the effects of a barley diet containing high dietary fiber on the onset and development of diabetes mellitus in spontaneously diabetic rats was investigated by comparing with a rice diet containing low dietary fiber and an α-corn starch diet containing very low dietary fiber.
Methods: 30 male Goto-Kakizaki (GK) strain rats (8 weeks of age) were randomly assigned to 3 groups; high barley (HB) group on a barley diet (dietary fiber intake, 1.79g/day/rat), rice (R) group on a rice diet (dietary fiber intake, 0.46g/day/rat), and α-corn starch (CS) group on an α-corn starch diet (dietary fiber intake, 0.24g/day/rat). The carbohydrate (70%), fat (10%), and protein (20%) contents of these 3 diets were equal, and the rats were pair-fed each diet for 3 months.
Results: Feeding for 3 months showed that fasting plasma glucose level in the HB group was significantly lower than in the R and CS groups; the glucose tolerance in the HB group was markedly improved. Moreover, the plasma cholesterol and triglyceride levels in the HB group were significantly lower than those of the R and CS groups.
Conclusions: Our findings demonstrated that barley enabled glycemic control and improved glucose tolerance compared with rice or α-corn starch.View full abstractDownload PDF (985K) -
Keiko NASU, Mieko NAKAMURA, Nobuo AOKI, Yoji IITOI, Imako KONDO, Yuji ...2003 Volume 58 Issue 2 Pages 287-297
Published: May 15, 2003
Released on J-STAGE: February 17, 2009
JOURNAL FREE ACCESSObjectives: To determine the effects of environmental factors on abnormalities in red blood cell deformability (RBCD), which may play an important role in the development of cardiovascular diseases, a cross-sectional epidemiological study was conducted in healthy subjects.
Method: The subjects were 350 males (mean age 52.7±10.3 SD) and 364 females (52.6±10.4) who participated in a health check program in the town of Akabane, Japan, in 1995-1998. Blood and serum were obtained to determine the values of RBCD and TP, TG, TCHOL, and HDLC. The inverse of RBCD (RBCDI, ms-1) was used as an indicator of RBCD. The subjects were also investigated for drinking and smoking habits, BMI, and SBP. Males and females were stratified into tertiles for each variable except drinking and smoking. For those exceptions, male subjects were stratified into three groups according to alcohol consumption (non-drinkers, moderate drinkers (up to 27ml pure ethanol per day), and habitual drinkers (28ml or more per day)) and according to tobacco use (non-smokers, mild smokers (equal or fewer than 20 cigarettes per day), and heavy smokers, (more than 20)). Each stratum was further divided into two groups according to age (younger, <50 years; older, ≥50 years).
Results: The mean value of RBCDI was significantly higher in males (1.041±0.135 SD) than in females (1.013±0.113). RBCDI declined with age in both genders. In analyses of variance, the averages of RBCDI decreased as TP increased in all ages and in both genders and as TCHOL increased in older males. With regard to alcohol consumption, the averages of RBCDI were the highest in moderate drinkers in younger males. Multiple linear regression analyses showed negative correlations between RBCDI values and age, TP or TCHOL values, and showed positive correlations between RBCDI values and BMI in males as well as negative correlations between RBCDI values and age and TP in females. When alcohol drinking was entered into the model, the statistical significance between TCHOL and RBCDI disappeared in males. No apparent relations between smoking habit and levels of SBP and TG to RBCDI were found.
Conclusions: RBCDI was higher in males than in females and higher in the younger group than in the older group. This study suggested that TCHOL may lower RBCDI and moderate drinking may improve it. Further epidemiological study is required to clarify these relationships.View full abstractDownload PDF (1751K) -
2003 Volume 58 Issue 2 Pages e1
Published: 2003
Released on J-STAGE: February 17, 2009
JOURNAL FREE ACCESSDownload PDF (57K)
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