Invited Review Article
Mechanisms of Asbestos-induced Carcinogenesis
SHINYA TOYOKUNI
pg(s) 1-11
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Respiratory exposure to asbestos fibers has been associated with diffuse malignant mesothelioma (DMM) in humans. Despite advancements in the molecular analyses of human DMM and the development of animal models, the carcinogenic mechanisms of the disease remain unclear. There are basically three hypotheses regarding the pathogenesis of asbestos-induced DMM, which may be summarized as follows: (1) the “oxidative stress theory” is based on the fact that phagocytic cells that engulf asbestos fibers produce large amounts of free radicals due to their inability to digest the fibers, and epidemiological studies indicating that iron-containing asbestos fibers appear more carcinogenic; (2) the “chromosome tangling theory” postulates that asbestos fibers damage chromosomes when cells divide; and (3) the “theory of adsorption of many specific proteins as well as carcinogenic molecules” states that asbestos fibers in vivo concentrate proteins or chemicals including the components of cigarette smoke. Elucidation of the major mechanisms underlying DMM would be helpful for the development of novel strategies to prevent DMM induction in people who have already been exposed to asbestos.
Original Papers
Involvement of DNA Fragmentation of Enterocytes in Mucosal Injury to a Mouse Jejunum Incubated in Ussing Chambers
EIKO INAGAKI-TACHIBANA, TAKAMITSU TSUKAHARA, KAZUHIKO KAJI, RYOJI EGUCHI, HIROAKI KANAZAWA, HISAYOSHI HAYASHI and YUICHI SUZUKI
pg(s) 11-18
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A mouse jejunum, when incubated in vitro in Ussing chambers, was found to exhibit morphological deterioration of the villi with denudation of the epithelia (J Nutr Sci Vitaminol, 51: 406, 2005). Our study examined the involvement of apoptosis in an intestinal injury model by a DNA ladder assay and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Electrophoresis of mucosal DNA revealed ladders, indicating the occurrence of DNA fragmentation. Cells with TUNEL-positive nuclei were detected among the villus epithelial cells (enterocytes), whereas they are rarely seen among crypt epithelial cells. These features were evident within 1 h after the start of incubation. Apoptotic death of the enterocytes was thus involved in the destruction of villi when incubated in Ussing chambers.
Multilevel Analyses of Effects of Variation in Body Mass Index on Serum Lipid Concentrations in Middle-Aged Japanese Men
TAKAAKI KONDO, AKIKO KIMATA, KANAMI YAMAMOTO, SAYOKO UEYAMA, JUN UEYAMA, HIROSHI YATSUYA, KOJI TAMAKOSHI and YOKO HORI
pg(s) 18- 28
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For the effective use of the annual workplace health checkup data, we tried to perform multilevel analyses to explore whether the year-to-year weight variation causes any concurrent effects on the lipid profiles among middle-aged Japanese workers. Subjects were 1,939 healthy male workers 40–59 in age from whom serial data of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) were collected during health checkups conducted in the years 1997–2000. The effects of body mass index (BMI) on serum concentrations of those lipids were investigated by statistical analysis with multilevel modeling to distinguish multiple levels of information with individual repeated measurements within individuals. A significant increase of TC and TG, and decrease of HDL-C with BMI increase were confirmed. Subanalyses according to both the baseline BMI status (< 25 kg/m2 or ≥ 25 kg/m2) and smoking status (never, former, or current) yielded the same BMI-dependent changes of lipid profiles, but obese never smokers failed to show significant effects of BMI on HDL-C concentrations. Multilevel analyses of annual health checkup data linked at individual levels indicated that year-to-year weight variation, though usually in a much narrower range than the between-individual variation, had a strong impact on the corresponding changes of serum concentrations of TC, HDL-C, and TG. This result supports the public health significance of intervention into weight control to prevent the development of atherogenic risks among a healthy workplace population.
Knowledge, Attitude and Practice Regarding Dengue among People in Pakse, Laos
SOODSADA NALONGSACK, YOSHITOKU YOSHIDA, SATOSHI MORITA, KEO SOSOUPHANH and JUNICHI SAKAMOTO
pg(s) 29-37
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Dengue fever (DF) is an acute febrile disease, caused by infection of dengue virus transmitted by the female Aedes mosquito. This is the second leading cause of deaths in Champasack Province, where Pakse district has the highest number of this outbreak. This cross-sectional study was designed to assess the knowledge, attitude, and practice of people regarding dengue disease in 9 villages of the Pakse district from July to September 2006. Purposive sampling was done to collect data from 230 subjects. They had a fair knowledge about the vector 163 (70.9%). For 101 (43.9%) respondents, their main source of information about dengue was their friends or relatives. It is encouraging that 217 (94.3%) respondents had a positive attitude that DF can be treated, and that 222 (96.5%) knew they should visit a doctor when they suffer from it. About 196 (85.2%) people stored water at home but infrequently changed it. The study indicated that the community was quite familiar with Dengue, but that there was some confusion about vaccination and water storage for domestic use. Dengue awareness activity should be included at the school and college level. Radio and television should play an important role in conveying health information to the public, and regular visits of health personnel to the villagers should be ensured.
Iron and Iodine Deficiencies among Under-2 Children, Adolescent Girls, and Pregnant Women of Bangladesh: Association with Common Diseases
MD. HARUN-OR-RASHID, UH FARIDA KHATUN, YOSHITOKU YOSHIDA, SATOSHI MORITA, NURUDDIN CHOWDHURY and JUNICHI SAKAMOTO
pg(s) 39- 49
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We examined the frequency of iron and iodine deficiencies and associations of iron and iodine deficiencies with common diseases among under-2 children, adolescent girls, and pregnant women of Bangladesh. We assayed the blood hemoglobin concentration in 395 under-2 children, 355 adolescent girls, and 263 pregnant women, the urinary iodine concentration of those adolescent girls and pregnant women, and the iodine level of all household salt specimens. The history of common diseases within their previous 2 weeks were also obtained from recall to explore the associations of iron and iodine deficiencies with common diseases. Anemia was found in 49.1% of children, 24.8% of adolescent girls, and 44.4% of pregnant women using defined cut-off values (Hb<11.0 g/dL for under-2 children and pregnant women; <12.0 g/dL for adolescent girls). Prevalence of iodine deficiencies (urinary iodine <100 mg/L) was 38.4% in adolescent girls and 39.4% in pregnant women, and 39.4% of salt specimens had inadequate iodine (<15 ppm). The relative risk (RR) and 95% confidence intervals (CI) were estimated and adjusted for age, sex, and gestational age to explore the associations of iron and iodine deficiencies with common diseases. The RR of anemia was increased for fever (RR=1.7, 95% CI=1.3–2.3), ear infection (RR=3.4, 95% CI=1.3–8.5), skin disease (RR=1.4, 95% CI=0.9–2.2), and pneumonia (RR=3.7, 95% CI=0.7–19.5). The RR of iodine deficiency was elevated for diarrhea/dysentery (RR=2.2, 95% CI=1.1–4.4) and eye infection (RR=2.1, 95% CI=0.5–9.4). We concluded that iron and iodine deficiencies are quite high among the Bangladeshi population. Observed associations of iron and iodine deficiencies with common diseases indicated the necessity of eliminating iron and iodine deficiencies from this vulnerable population through strengthening of iron and iodine supplementation, in order to prevent diseases and promote health conditions.
The Induction of Dentin Bridge-Like Structures by Constructs of Subcultured Dental Pulp-Derived Cells and Porous HA/TCP in Porcine Teeth
YUSUKE ANDO, MASAKI J. HONDA, HAYATO OHSHIMA, AKIKO TONOMURA, TAKAYUKI OHARA, TOSHIMITSU ITAYA, HIDEAKI KAGAMI and MINORU UEDA
pg(s) 51- 62
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The purpose of this study was to investigate dentin-bridge formation in teeth following the transplantation of dental pulp-derived cells seeded on hydroxyapatite/tricalcium phosphate (HA/TCP) scaffolds. The dental pulp tissues were removed from the extracted first molar teeth of miniature pigs and single cell populations were subcultured. Second-passage cells that had alkaline phosphatase activity were combined with scaffolds. Cell-scaffold constructs were placed in contact with the exposed pulp tissue. The dimensions of the exposed pulp site were approximately 1–2.5 mm in diameter and 2–3 mm in depth from the tooth surface. After placing the constructs, the tooth was restored with composite resin. Six weeks after transplantation, hard tissue formation was observed on the pulp tissue in histology. Dentinal tubule-like structures were observed in most of the hard tissue generated, and columnar cells, which showed positive immunoreactions with dentin sialoprotein (DSP) and heat shock protein (HSP)-25, were aligned beneath the hard tissues. When only scaffolds were placed on the pulp tissues, particles of hard tissue were formed, however dentinal tubule-like structures and odontoblasts were not observed despite the formation of hard tissue. In conclusion, the implantation of dental pulp constructs into pulp exposed stimulates the formation of calcified dentin-like structures.
Note
Risk Disclosure in Securities Exchange and Medical Treatment Contracts
YOSHIHIKO IIJIMA
pg(s) 63-69
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The duty of risk disclosure in medical treatment contracts is examined first through comparison with securities exchange contracts, second, by examining the contract as dealt in judicial precedent, ensued by an analysis and proposal by the author. In both types of contracts, the number of judicial judgments finding for the plaintiff based solely on violation of the duty of risk disclosure is increasing. Different explanations, however, should apply for the increase. In the case of the securities exchange contracts, the duty to inform is understood as a means of providing material for informed choice and self-determination, thus supporting the argument for self-discipline. Whereas, in the case of medical treatment contracts, adding to the argument for self-determination, another line of reasoning is given: disclosure of relevant information as a means by which the medical services secure the life and physical well-being of the patient. The reason the principle of self-determination is not in full play is analyzed as a case in which higher norms of the professional ethics of the medical staff is functioning. Thus, in providing medical information of possible treatments to the patient, the physician is exonerated from legal liability, but remains burdened with the ethical responsibility to provide appropriate care. As the overlap of the two types of responsibility seems not to be fully realized, further investigation and dissemination of findings of this issue is proposed.