The prevalence and mortality of chronic obstructive pulmonary disease (COPD) is expected to increase in the future throughout the world. Little data is avail- able on the prevalence of airflow limitation in Japan, especially on medical check-up. The purpose of this study was to assess the prevalence of airflow limitation in Japanese subjects during medical check-ups. The study subjects were 13,534 Japanese subjects (8,583 males and 4,951 females) aged 40 - 69 years who underwent medical check-ups at the Japanese Red Cross Kumamoto Health Care Center. Pulmonary function data were analyzed according to smoking habits in each age group. The spirometric criteria for diagnosis of airflow limitation were forced expiratory volume in 1 second (FEV₁) / forced vital capacity (FVC) < 70%. The severity of COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. People with a medical diagnosis of asthma or individuals who had other pulmonary diseases were excluded from a diagnosis of COPD. The prevalence of airflow limitation was 7.0% in all subjects, 9.1% in males and 3.3% in females. Using the GOLD system, the prevalence of mild, moderate, severe and very severe airflow limitation was 7.06, 1.92, 0.10 and 0.00%, respectively, in males. In females, the prevalence of mild, moderate, severe and very severe airflow limitation was 2.67, 0.63, 0.02 and 0.00%, respectively. Only 10 cases with airflow limitation reported a previ- ous diagnosis of COPD. These results suggest that screening spirometry dur- ing medical check-ups can identify many COPD patients not aware of this disease and highlight the need for enhanced screening efforts, intervention and treatment.

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An endocrine disruptor, para-nonylphenol (NP), caused a dose-dependent stimulatory effect on the generation of reactive oxygen species (ROS) in human whole blood from 50 to 1000 μM, which was measured by chemiluminescence generation. ROS-scavenging enzymes such as catalase and superoxide dismutase, and the lipophilic antioxidative agents, α-tocopherol and β-carotene, showed preventive effects on NP-induced ROS generation. To analyze the biochemical mechanism of NP-induced ROS generation in human blood, we investigated the effects of different types of metabolic inhibitors on the activation pathways of ROS generation. An NADPH-dependent oxidase inhibitor, diphenyl iodonium chloride (DPI), and a myeloperoxidase inhibitor, sodium azide (NaN₃), showed remarkable inhibitory effects on ROS generation induced by NP, but an inhibitor against mitochondrial respiratory function, potassium cyanide (KCN), did not exhibit a significant effect. Furthermore, a phosphatidylinositol-3 (PI3) kinase inhibitor, wortmannin, and a tyrosine kinase inhibitor, protein phosphorylation inhibitor 1 (PP1), caused a strong suppression of NP-induced ROS generation. Selective protein kinase C inhibitor, Ro-32-0432, p38 MAP kinase inhibitor, SB-203580, and ERK MAP kinase inhibitor, PD 98059, showed significant suppressive effects on NP-induced ROS generation. In addition, when human blood was exposed to lower concentrations (5 - 50 μM) of NP, they did not cause the significant ROS generation by themselves, but the priming and synergistic effects of NP were detected by the addition of secondary stimulants, opsonized zymosan (OZ) or phorbol myristate acetate (PMA). The analysis of the priming and synergistic effects of NP on OZ- or PMA-dependent ROS generation by antioxidative substances and metabolic inhibitors showed similar results compared with those of human blood treated with NP alone. These results suggest that NP causes an enhancing effect by itself, or priming and synergistic effects on ROS generation in human blood with other inflammatory stimulants through the activation of signal transduction pathways such as protein kinase cascades.

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Lower body negative pressure (LBNP) induces venous pooling in the legs and a decrease of blood volume (BV). The present study was designed to investigate the dynamic changes in BV and limb volume during LBNP. We made continuous measurements of blood density (ρ_b) during LBNP at two different levels (-15 and -30 mmHg) in eight healthy male volunteers. Blood was withdrawn continuously from the antecubital vein to measure ρ_b during an experimental period of 40 min (a 10-min control period, a 10-min LBNP and a 20-min recovery period). The density was measured by the mechanical oscillator technique. The changes of circumference in the upper arm and calf were measured by strain gauge plethysmography. ρ_b decreased rapidly in the early phase of LBNP followed by an increase, as expected. The peak reduction (-0.35 ± 0.04 g/ℓ) of ρ_b at -15 mmHg did not differ (P = 0.47) from that (-0.42 ± 0.05 g/ℓ) at -30 mmHg. The time (2.9 ± 0.3 min) from onset of LBNP to the peak reduction of ρ_b was not significantly different between -15 and -30 mmHg (P = 0.50). After LBNP, a further ρ_b increase was continued for 2.5 ± 0.2 min at both intensities, followed by the return toward control levels. The maximal increase (1.34 ± 0.07 g/ℓ) of ρ_b after LBNP at -30 mmHg was greater (P < 0.001) than that (0.57 ± 0.06 g/ℓ) at -15 mmHg. LBNP decreased the arm circumference and increased the calf circumference in an intensity-dependent manner. These results suggest that LBNP induces an intensity-dependent decrease in BV with no difference in the time peak reduction occurring after LBNP. We found no significant difference between the intensities in the transient hemodilution effect during LBNP. It is suggested that LBNP also induces an intensitydependent mobilization of blood from the upper portion to the lower portion of the body.

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Exposure to a large number of environmental toxins can induce damage to DNA and may play an important role in the pathophysiological processes of atherosclerosis. To examine the effect of some specific environmental conditions that predispose to sudden coronary atherosclerotic death on the level of 8-OHdG, urine samples were collected from cases of certain occupations and polluted regions that showed a high prevalence of premature deaths. The samples were then analyzed for 8-OHdG. Analysis of 108 cases and 45 controls showed a significant high level of 8-OHdG in relation to occupations, habits, residency and work shift. The mean ± standard deviation (M±SD) for the control group was 4.5 ± 2.3 ng 8-OHdG/mg creatinine (n=45), compared to 9.1 ± 3.1 ng/mg in taxi drivers (n=9), 10 ± 5.5 ng/mg in chemical factory workers (n=16), 12.0 ± 8.9 ng/mg in paint workers (n=9), 14.6 ±11.1 ng/mg in gasoline station workers (n=15), 15 ± 6.1 ng/mg in cement factory workers (n=12), 16.4 ± 3.2 ng/mg in city center inhabitants (n=18) and 18.6 ± 3.2 ng/mg in smokers (n=15). These conditions at least in the pilot study done by the author, showed some form of precipitation of sudden atherosclerotic coronary death. This work proved that the recently used 8-OHdG DNA damage biomarker may be an important marker of environmental conditions that are expected to have a serious long-term impact on the cardiovascular system.

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A 52-year-old man underwent lung cancer screening with low-dose spiral computed tomography (CT) in a medical check-up at the Japanese Red Cross Kumamoto Health Care Center. He was asymptomatic. Chest x-ray on a medical check-up showed no abnormal shadows. CT scans revealed a nodule in the right lower lung, suggestive of its connection to the descending thoracic aorta. A diagnosis of pulmonary sequestration was considered. He was transferred to Kumamoto University Hospital for further examination. Contrast enhanced multidetector CT images demonstrated that a nodule in the right lower lobe and an anomalous artery ran from the descending thoracic aorta, flowed through the right lower lobe and returned to the right inferior pulmonary vein. Intralobar pulmonary sequestration was confirmed by contrast enhanced multidetector CT. We report this case of asymptomatic intralobar pulmonary sequestration diagnosed using contrast enhanced multidetector CT.

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Tobacco smoking is the main cause of human urothelial cancer. It has been suggested that genetic susceptibility may contribute to the risk, because only a small portion of smokers develops urothelial cancer. Tobacco smoke contains many carcinogens which are activated or detoxified by phase-I or phase-II enzymes. The concentration of the ultimate carcinogen, which will react with DNA, is determined by the rate of activation and detoxification. Individuals with an increased rate of activation or a decreased rate of detoxification have a slightly higher level of bulky carcinogen-DNA adduct in the urothelial mucosa. Thus metabolic polymorphisms have been recognized as important determinants of carcinogen susceptibility, and recent efforts have shown that inter-individual differences in specific cytochrome P450 enzymes (CYPs), N-acetyltransferases (NAT), glutathione S-transferases (GST) and sulfotransferases (SULT) are often disproportionately represented in epidemiological studies between urothelial cancer cases and controls. It has been revealed that GSTM1 null genotype or NAT2 slow acetylator genotype may be associated with a small increase in urothelial cancer risk. Associations between other polymorphisms of metabolic enzymes and urothelial cancer are not well-known or are inconsistent. To reveal these associations, further well-designed and large-scale studies are needed.

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The starting point of reproductive immunology is the understanding of the immunological mechanism for maintenance of pregnancy; why the fetus, which is a semi-allograft for the mother, is not rejected by the maternal immune system. Since Medawar pointed out this immunological contradiction in 1953, many investigators have addressed this question. As a result, we are coming to understand that not only a mere immunological tolerance but also immunotrophism, by which the immune system recognizes the fetal antigen actively, is important for the formation and maintenance of pregnancy. In addition, we are also coming to understand the importance of cytokines such as LIF and the cytokine environment of Th2 dominant. However, the cellular and microbiological mechanisms of these cytokines in the reproductive phenomenon are not well known. It is considered that the understanding of these mechanisms is useful for the clinical application to infertility or habitual abortion.

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Some occupational and environmental chemicals cause allergic diseases. To prevent chemical allergies, it is essential to identify the chemical substances that cause sensitization and to eliminate such sensitizers from daily life. As an occupational countermeasure, information for evaluating sensitization of chemical substances is needed. The aims of this article are to compare the criteria for sensitizers among national organizations in various countries and international organizations, and to make out a list of these chemical substances. The definition of sensitizing chemicals and the designation of respective sensitizers according to the PRTR law, Japan Society for Occupational Health (JSHO), American Conference of Governmental Industrial Hygienists (ACGIH), European Union (EU), Deutsche Forschungsgemeinshaft (DFG) and Japanese Society of Occupational and Environmental Allergy were studied. There are 1,389 chemical substances which are designated as sensitizers by any of the laws and five organizations. We specify each chemical substance in the list.

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