OBJECTIVESTo assess the validity of the criterion of overweight for Asian people that is recommended by Western Pacific Region of the World Health Organization.

METHODSWe carried out a cross-sectional analysis of the association between the criterion of overweight for ethnic Asian people--body mass indices (BMI) of 23.0-24.9 kg/m(2)--and the presence of obesity-related metabolic disorders among middle-aged Japanese men (n = 974, age range 51-59).

RESULTSThe odds ratios (95% confidence interval) of overweight to those with normal weight (BMI < 23.0 kg/m(2)) were 1.61 (1.11-2.33) for the presence of impaired glucose tolerance, 1.95 (1.30-2.93) for hypertension, 2.22 (1.63-3.03) for hypercholesterolemia, 2.83 (2.02-3.97) for hypertriglyceridemia, and 2.06 (1.06-4.00) for hyperuricemia. Overweight was not associated with the presence of type 2 diabetes or with high gamma-glutamyl transferase in the present study (odds ratios: 1.09 and 1.05, respectively). Adjustment for age, rank, and lifestyle factors affected the results only slightly.

CONCLUSIONSBased on these results, we conclude that the Asian criterion of overweight appears to be rational in terms of its association with obesity-related metabolic disorders in male personnel of the Japan Self-Defense Forces in their fifties.

OBJECTIVESTo estimate the degree to which low back pain (LBP) deprives the Japanese adult population of their quality of life (QOL) in terms of quality-adjusted life-years (QALYs).

METHODSA questionnaire survey was conducted among participants of health examinations at five healthcare facilities in Japan. Age- and sex-specific mean values of the EQ-5D score were calculated for (1) those who reported LBP and interference with daily activities (IDA) due to the pain (n = 251), (2) those who reported LBP but no IDA (n = 955), and (3) those who reported no musculoskeletal pain (n = 2887). To estimate the loss of QALYs due to LBP in the Japanese adult population, we multiplied the age- and sex-specific mean differences of the EQ-5D scores between the LBP with (or without) IDA group and the no pain group by the corresponding age- and sex-specific numbers of people with LBP with (or without) IDA in Japan.

RESULTSAmong the entire Japanese adult population of 103 million people, 11,800,000 (4,910,000 men and 6,890,000 women) were estimated to suffer from LBP, and 2,403,000 (976,000 men and 1,427,000 women) people were estimated to encounter IDA due to the pain. The loss of QALYs due to LBP in the Japanese adult population was estimated at 947,000 (9.18 per 1000 population). The loss of QALYs due to IDA in the LBP people was estimated at 139,000 (1.35 per 1000 population).

CONCLUSIONSThe estimated loss of QALYs due to LBP suggests that LBP substantially deprives the Japanese adult population of their QOL.

Selenium (Se) is an essential trace element, and its low status in humans has been linked to increased risk of various diseases, such as cancer and heart disease. In recent years, Se research has attracted tremendous interest because of its important role in antioxidant selenoproteins for protection against oxidative stress initiated by excess reactive oxygen species (ROS) and reactive nitrogen species (NOS). The synthesis of selenoproteins requires a unique incorporation of amino acid selenocysteine (Sec) into proteins directed by the UGA codon, which is also a termination codon. Interest in Se research has led to the discovery of at least 30 selenoproteins; however, the biochemical functional roles of some of these selenoproteins are still unknown. Besides in the form of selenoproteins, Se can exist in many different chemical forms in biological materials either as organic Se compounds, such as selenomethionine and dimethylselenide, and inorganic selenites and selenates. In foods, Se is predominantly present as selenomethionine, which is an important source of dietary Se in humans, and also as a chemical form that is commonly used for Se supplements in clinical trials. Concern for potential deficiency diseases associated with low Se status has led to the establishment of the recommended daily requirements for Se in many countries. However, excess Se intakes through supplementation and its potential misuse as health therapy could also pose a risk of adverse health effects if its use is not properly regulated.

"Air pollution and population health" is one of the most important environmental and public health issues. Economic development, urbanization, energy consumption, transportation/motorization, and rapid population growth are major driving forces of air pollution in large cities, especially in megacities. Air pollution levels in developed countries have been decreasing dramatically in recent decades. However, in developing countries and in countries in transition, air pollution levels are still at relatively high levels, though the levels have been gradually decreasing or have remained stable during rapid economic development. In recent years, several hundred epidemiological studies have emerged showing adverse health effects associated with short-term and long-term exposure to air pollutants. Time-series studies conducted in Asian cities also showed similar health effects on mortality associated with exposure to particulate matter (PM), sulfur dioxide (SO(2)), nitrogen dioxide (NO(2)) and ozone (O(3)) to those explored in Europe and North America. The World Health Organization (WHO) published the "WHO Air Quality Guidelines (AQGs), Global Update" in 2006. These updated AQGs provide much stricter guidelines for PM, NO(2), SO(2) and O(3). Considering that current air pollution levels are much higher than the WHO-recommended AQGs, interim targets for these four air pollutants are also recommended for member states, especially for developing countries in setting their country-specific air quality standards. In conclusion, ambient air pollution is a health hazard. It is more important in Asian developing countries within the context of pollution level and population density. Improving air quality has substantial, measurable and important public health benefits.

Cytochrome P450s (CYPs) are one of the first steps in the metabolism of xenobiotics, such as polycyclic aromatic hydrocarbons (PAHs), which are bioactivated into carcinogens. As such, changes in CYP expression are potential biomarkers in human biomonitoring applications. For the proper biomonitoring of environmental toxicants, it is important to understand the biological relevance of each biomarker and the associations among the biomarkers for uses as exposure, effects, and susceptibility biomarkers. Here, we have reviewed various aspects of CYPs for biomonitoring environmental health in terms of the CYP substrates, such as PAHs, aromatic amines, benzene/toluene, and tobacco smoking-related nitrosamines. This review also includes association studies between CYP phenotypical alterations and other exposure, susceptibility, and effect biomarkers. The association studies were mainly performed in CYP gene-transfected cells and noninvasive human biospecies, such as urine and peripheral blood. In conclusion, we suggest that phenotypical alterations in CYPs with exposure to environmental toxicants are useful as susceptibility or effect biomarkers, particularly when the phenotype-related genotypes are unknown.

Mesothelioma is a highly lethal tumor derived from mesothelial cells, and its global incidence is increasing because of widespread exposure of numerous individuals to asbestos in the last 50 years. Mesothelioma is largely untreatable with any of the therapeutic modalities. Recently, a novel multitargeted antifolate pemetrexed has shown promising activity against malignant pleural mesothelioma, producing response rates of up to 40% when used in combination with cisplatin. In a large phase III study, use of a combination of pemetrexed and cisplatin was associated with significantly improved survival time and with greater antitumor activity compared with cisplatin alone. This combination also gave a significant response rate of approximately 50% in patients with epithelioid malignant pleural mesothelioma. These clinical benefits of pemetrexed-cisplatin doublet have changed the perception of mesothelioma chemotherapy. Other combinations, including gemcitabine in combination with cisplatin, have also shown encouraging response rates. Prognosis depends on gender, clinical stage of the tumor, histological subtype, platelet count, leukocyte counts, and performance status. Radiotherapy can palliate mesothelioma patients with chest pain, and has been indicated to be of benefit for the prevention of malignant seeding along the tract of a chest tube or needle biopsy. Trimodality treatment using extrapleural pneumonectomy, radiation and chemotherapy has shown promising therapeutic value. The development of chemotherapeutic regimens and the favorable outcomes of trimodality have led to new combined modality trials. In Japan, multicenter national trials against mesothelioma will begin in the near future.

Mesothelioma is an aggressive tumor arising from the mesothelium, and is usually associated with previous exposure to asbestos. The incubation period of the tumor may be described as 30-40 years, and the prognosis is dismal. We previously discovered the Erc (Expressed in renal carcinoma) gene in the Eker rat model (Tsc2 gene mutant) and it was a homolog of the human mesothelin/MPF gene. We developed a novel ELISA system (N-ERC/mesothelin). Recently, we found that N-ERC/mesothelin was a potentially useful diagnostic marker for asbestos-related mesothelioma.

Human malignancies develop via a multi-step that involves the accumulation of several key gene alterations with associated genetic and epigenetic events. Although malignant mesothelioma (MM) has been demonstrated to be clearly correlated with asbestos exposure, it remains poorly understood how asbestos fibers confer key gene alterations and induce cellular transformation in normal mesothelial cells, which results in the acquisition of malignant phenotypes, including deregulated cell proliferation and invasion. Malignant mesothelioma presents with the frequent inactivation of tumor suppressor genes of p16(INK4a)/p14(ARF) on chromosome 9p21 and neurofibromatosis type 2 (NF2) on chromosome 22q12, with the latter being responsible for the NF2 familial cancer syndrome. In contrast, MM shows infrequent mutation of the p53 gene, which is one of the most frequently mutated tumor suppressor genes in human malignancies. Genetic abnormalities of oncogenes have also been studied in MM, but no frequent mutations have been identified, including the epidermal growth factor receptor (EGFR) and K-RAS genes. Recent studies have suggested the activation of other receptor tyrosine kinases, including Met, and the deregulations of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K)-AKT signaling cascades, although the alterations responsible for their activation are still not clear. Thus, further genome-wide studies of genetic and epigenetic alterations as well as detailed analyses of deregulated signaling cascades in MM are necessary to determine the molecular mechanisms of MM, which would also provide some clues for establishing a new molecular target therapy for MM.

The incidence of mesothelioma has been gradually increasing in Japan, and the underlying factor for this is considered to be the increase in the amount of asbestos imported into Japan between 1960 and 1975. Mesothelioma can be roughly divided into localized and diffuse types, but the former is extremely rare. In making a diagnosis of mesothelioma, it is important to confirm the location of tumor and the specific gross findings before histological examination. Mesothelioma can be categorized histologically as epithelioid type, sarcomatoid type, biphasic type, desmoplastic type, among others. It can take many forms; consequently, there are many diseases to be differentiated when the diagnosis of mesothelioma is based on histological analyses. Immunohistochemical stains are useful for making a diagnosis, but the correct combination of antibodies as positive or negative markers should be selected and a comprehensive assessment of the staining results is necessary. The accuracy of the pathological diagnosis is very important to the patients because they can be receive official compensation or relief when the diagnosis of mesothelioma is confirmed. Under present conditions, both clinicians and pathologists must make a concerted effort to improve the accuracy of the diagnosis of mesothelioma.