Summary: Objective: The use of a novel 4-grade mouthpiece device to reproduce difficulty in breathing was assessed in healthy individuals.

Methods: A double-blind, randomized, crossover-controlled trial was conducted to investigate the efficacy and safety of the device with increasing mouth pressure. The modified Borg (mBorg) scale values, respiratory system resistance at 5 Hz (R5), and forced expiratory volume in one second (FEV₁) were assessed while using the device.

Materials: The four grades of breathing difficulty device were tested in 32 healthy participants.

Results: The 4-grade device linearly worsened the mBorg scale with increasing mouth pressure. The mean R5 (± standard deviation [SD]) with grade I, II, III, and IV devices were 5.6 ± 0.1, 10.3 ± 0.3, 21.5 ± 0.7, and 54.8 ± 2.0 kPa/L/s, respectively. The mean %FEV₁ predicted (± SD) were 83.6 ± 15.9% with grade I, 55.3 ± 11.8% with grade II, 32.0 ± 6.1% with grade III, and 15.3 ± 3.2% with the grade IV device. The mBorg scale was positively correlated with R5 (r = 0.79, p < 0.0001) and negatively with %FEV₁ predicted (r = −0.81, p < 0.0001). No severe adverse events were reported during the trial.

Conclusion: We demonstrated that the novel device could effectively reproduce the semi-quantitative artificial difficulty in breathing safely and easily in healthy individuals. These devices could be helpful to understand the mechanisms of difficulty in breathing.

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Background: Although the metabolic syndrome (MetS) is considered to be caused primarily by visceral fat accumulation, epidemiological evidence is lacking as to whether or not obesity is an essential element in the syndrome. Methods and Results: Between 1990 and 2005, the Japan Public Health Center-based Prospective (JPHC) Study conducted baseline measurements of metabolic risk factors in 12,412 men and 21,639 women, aged 40-69 years, with no history of cardiovascular disease (CVD) or cancer. To clarify the role of obesity, which the definition of MetS in Japan has adopted as an essential criterion, clustering of risk factors in data grouped according to overweight condition was examined. During a 12.3-year follow-up there were 2,040 deaths, including 947 from cancers and 304 from CVD. MetS significantly increased the hazard ratios for all-cause mortality in women and CVD mortality in . -overweight with ≥2 risk factors had a similar impact on all-cause and CVD mortality. Clustering of metabolic factors caused a linear increase in the hazard ratios for mortality. Conclusions: MetS caused moderate increases in all-cause and CVD mortality. However, the MetS definition requiring obesity may not necessarily identify non-overweight individuals who have a high mortality risk and are more prevalent than subjects with MetS. (Circ J 2009; 73: 878 - 884)

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Elevated triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels, hallmarks of the atherogenic lipid profile found in the metabolic syndrome and type 2 diabetes, are commonly seen in Japanese patients with coronary heart disease (CHD). In the setting of mildly to moderately elevated plasma TG (150−500 mg/dl), very-low-density lipoprotein (VLDL) accumulates and so do high levels of atherogenic TG-rich, cholesterol-enriched remnant particles. Indeed, in hypertriglyceridemia, abnormalities are seen in the quantity and quality of all lipoprotein B−containing lipoproteins. Non−HDL-C (total cholesterol minus HDL-C) provides a convenient measure of the cholesterol content of all atherogenic lipoproteins, and thus incorporates the potential risk conferred by elevated levels of atherogenic TG-rich remnants that is additional to the risk associated with low-density lipoprotein cholesterol (LDL-C). Non−HDL-C level has been found to be a strong predictor of future cardiovascular risk among patients whether or not they exhibit symptoms of vascular disease, and was recently recommended as a secondary treatment target (after LDL-C) in patients with elevated TG by the National Cholesterol Education Program Adult Treatment Panel III. Adoption of this readily available measure to assess risk and response to treatment in patients with elevated TG would improve treatment of dyslipidemia in a substantial number at risk for CHD.

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The human larynx is an essential organ not only for speech, but also for swallowing and respiration. Its tissues are affected by the presence of alcohol and cigarette smoke. In this report we present our findings on the effects of smoking and drinking on histological changes in laryngeal tissue.
The larynges studied were those of in autopsy patients: cases with damaged tissue were excluded. We studied the larynges of 84 (-smoker and non-drinker; 22 cases, smoker and drinker; 62 cases) and 48 women (non-smoker and non-drinker; 40 cases, smoker and drinker; 8 cases) between the ages of 12 and 88.
The squamous metaplasia of laryngeal epithelium was examined using the gross staining method Pyronine Y designed by Stell et al. The squamous epithelium is unstained, whereas the respiratory epithelium is stained with brilliant red.
Microscopic changes of the laryngeal epithelium were investigated using the hematoxylin eosin staining method. The thicknesses of the epithelium in the supraglottic region and vocal cord were measured by TV image processor.
Results: 1) The area of metaplasia in the supraglottic region increased with aging, tobacco and alcohol consumption.
2) The dysplasia were found in the squamous epithelium of the laryngeal surface of epiglottis in heavy drinker.
3) The thickness of epithelium of the supraglottic region and vocal cord increased with age.
4) There is a significant difference in the thickness of the epithelium of the supraglottic region and vocal cords of smoking and drinking patients, when compared with the same tissues of non-smokers and non-drinkers.
5) There is a significant difference in the thickness of the epithelium of the supraglottic region of heavy smokers, when compared with light smokers, but no significant difference when compared with drinkers. However, there is no significant difference in the thickness of vocal cord tissues between light smokers and drinkers, and heavy smokers and drinkers.

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In order to improve reproducibility of a quantitative hemagglutination inhibition for Human Chorionic Gonadotropin, effects of bovine serum albumin, normal rabbit serum and nonpregnant urine on the sensitivity of this test have been studied. As concentration of BSA in a diluent increases up to 1%, the sensitivity increases proportionally. Effect of 2% NRS is comparable to that of 0.1% BSA. Effect of nonpregnant urine on the sensitivity of the test is varied from one individual to another. mean effect of urine, however, nearly equals that of 0.1% BSA. From the comparison of a direct and a serial dilution method, and of dilution in cool and at temperature, it is suggested that the sensitivity increasing effect of protein could ascribed to its protective action to HCG molecules. The use of protein solution to dissolve standard HCG as well as urine samples is recommended for a quantitative or semi-quantitative assay of HCG in urine.

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A type of abnormal B cells was obtained from young NZB/n mice, a well-known experimental model for lupus type autoimmune disease, by immunization with sheep red blood cells (SRBC) . NZB mice of both sexes were immunized i.p with 4×10⁹of SRBC. Two weeks later, B cells were obtained by treatment of spleen cells with anti-Thy-1, 2 plus complement to remove T cells. Unlike B cells prepared from normal BALB/c mice by the same procedure, the B cells from NZB mice responded to SRBC with or without small numbers of T cells duringin vitroculture. The abnormal B cells were positive for Ly-1 (Lyt-1, CD5) as confirmed by depletion of the cells with anti-Ly-1 plus complement. Plaque-forming cell (PFC) response of the abnormal B cells was enhanced by β-estradiol but not by testosterone. The above results suggest that the Ly-1⁺B cells from NZB mice might be long-lived or memory B cells.

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A phosphorimetric assay of cystine aminopeptidase in biological samples is described. p-Nitroaniline, formed enzymatically from S-benzyl-L-cysteinyl-p-nitroanilide, is extracted with ether and determined phosphorimetrically in a mixture of ether and ethanol. The method is precise and very sensitive, requiring as little as 0.5μl of human serum or 0.5-1.0μg of protein of rat tissue.

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Background: We examined the associations of alcohol consumption and liver holidays with all-cause mortality and with mortality due to cancer, heart disease, cerebrovascular disease, respiratory disease, and injury using a large-scale prospective study in Japan.

Methods: We followed 102,849 Japanese who were aged between 40 and 69 years at baseline for 18.2 years on average, during which 15,203 deaths were reported. Associations between alcohol intake and mortality risk were assessed using a Cox proportional hazards model, with analysis by the number of liver holidays (in which a person abstains from drinking for several days a week).

Results: A J-shaped association was observed between alcohol intake and total mortality in men (nondrinkers: reference; occasional drinkers: hazard ratio [HR] 0.74; 95% confidence interval [CI], 0.68–0.80; 1–149 g/week: HR 0.76; 95% CI, 0.71–0.81; 150–299 g/week: HR 0.75; 95% CI, 0.70–0.80; 300–449 g/week: HR 0.84; 95% CI, 0.78–0.91; 450–599 g/week: HR 0.92; 95% CI, 0.83–1.01; and ≥600 g/week: HR 1.19; 95% CI, 1.07–1.32) and in women (nondrinkers: reference; occasional: HR 0.75; 95% CI, 0.70–0.82; 1–149 g/week: HR 0.80; 95% CI, 0.73–0.88; 150–299 g/week: HR 0.91; 95% CI, 0.74–1.13; 300–449 g/week: HR 1.04; 95% CI, 0.73–1.48; and ≥450 g/week: HR 1.59; 95% CI, 1.07–2.38). In current drinkers, alcohol consumption was associated with a linear, positive increase in mortality risk from all causes, cancer, and cerebrovascular disease in both men and women, but not heart disease in men. Taking of liver holidays was associated with a lower risk of cancer and cerebrovascular disease mortality in men.

Conclusions: Alcohol intake showed J-shaped associations with the risk of total mortality and three leading causes of death. However, heavy drinking increases the risk of mortality, which highlights the necessity of drinking in moderation coupled with liver holidays.

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Ethanol (ETOH) is added to unleaded gasoline to decrease environmental levels of carbon monoxide from automobiles emissions. Therefore, addition of ETOH in reformulated fuel will most likely increase and the involuntarily human exposure to this chemical will also increase. This preliminary study was undertaken to evaluate the possible neuromotor effects resulting from acute ETOH exposure by inhalation in humans. Five healthy non-smoking adult males, with no history of alcohol abuse, were exposed by inhalation, in a dynamic, controlled-environment exposure chamber, to various concentrations of ETOH (0, 250, 500 and 1,000 ppm in air) for six hours. Reaction time, body sway, hand tremor and rapid alternating movements were measured before and after each exposure session by using the CATSYS^TM 7.0 system and a diadochokinesimeter. The concentrations of ETOH in blood and in alveolar air were also measured. ETOH was not detected in blood nor in alveolar air when volunteers were exposed to 250 and 500 ppm, but at the end of exposure to 1,000 ppm, blood and alveolar air concentrations were 0.443 mg/100ml and 253.1 ppm, respectively. The neuromotor tests did not show conclusively significant differences between the exposed and non-exposed conditions. In conclusion, this study suggests that acute exposure to ethanol at 1,000 ppm or lower or to concentrations that could be encountered upon refueling is not likely to cause any significant neuromotor alterations in healthy males.

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九州大学医学部附属病院心療内科外来を1年間に受診した914名の新患全員を対象として,大うつ病における微熱の頻度と両者の関連を検討した.診断名と主訴に加えて,調査票で微熱の有無を調査し,Logistic回帰分析を行った.大うつ病を有する群の37%,有しない群の22%が調査票で微熱があると回答した.男性ないし女性における大うつ病の診断や女性におけるSDS (Self -rating Depression Scale)の高値は調査票での微熱の存在と統計学的に有意な関連を認めた.男女の大うつ病あるいは女性のSDS高値は微熱と関連すると結論された.微熱を訴える患者の診察においては,鑑別診断にうつ病を入れることが適切な診断治療と医療費削減につながると考えられる.

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Background: Annually, more than 1.2 million deaths due to road traffic accidents occur worldwide. Although previous studies have examined the association between cigarette smoking and injury death, the mortality outcome often included non-traffic accident-related deaths. This study aimed to examine the association between cigarette smoking and traffic accident death.

Methods: We conducted a prospective cohort study using data from the Ibaraki Prefectural Health Study conducted from 1993 through 2013. The cohort included 97,078 adults (33,138 men and 63,940 women) living in Ibaraki Prefecture who were aged 40–79 years at an annual health checkup in 1993. We divided participants into four smoking status groups: non-smokers, ex-smokers, and current smokers who smoked <20 and ≥20 cigarettes per day. Hazard ratios (HRs) of traffic accident death were calculated using a Cox proportional hazards model.

Results: During 20 years of follow-up, the average person-years of follow-up were 16.8 and 18.2 in men and women, respectively. Among men, after adjusting for age and alcohol intake, HRs for traffic accident death among current smokers of <20 cigarettes/day and ≥20 cigarettes/day compared to non-smokers were 1.32 (95% confidence interval [CI], 0.79–2.20) and 1.54 (95% CI, 0.99–2.39), respectively. In contrast, among women, we found no association between smoking status and traffic accident deaths.

Conclusion: In this prospective cohort study, we found a positive association, though marginally significant, between smoking and traffic accident death among men in Japan. Among women, because of the smaller number of deaths among smokers, adequate estimation could not be obtained.

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In order to determine whether or not resting ventilatory response to hypercapnia is changed by physical training, we studied the effect of long-term physical training on the slope of ventilatory response to CO₂ at rest. The subjects were 9 untrained freshmen ranging in age from 18 to 20 years. Five out of nine subjects belonged to the badminton team after entering university in April 1980, and participated in their team's training for about 3 hr per day, 3 times a week year round for about 4 years until March 1984. Maximum oxygen uptake (_??_O₂ max), maximum pulmonary ventilation (_??__E max) and maximum heart rate (HR max) were determined during maximal treadmill exercise before and after training. The slope (S) of ventilatory response to carbon dioxide at rest was measured by Read's rebreathing method. _??_O₂ max increased after training in the trained subjects and mean values of _??_O₂ max which were measured in 1982, 1983, and 1984, were statistically higher than that of 1980. Similar tendency was observed in _??__E max and _??_O₂ max/W. Average values and standard deviations of S before training were 1.91±0.52 liter/min/torr and were decreased gradually with increasing training period ; the differences in the S value before (1980) and after training, i.e., 1982, 1983, and 1984, were all significant. Such difference could still be seen after S was recalculated as S_N by using normalized ventilation for 70 kg body weight, while there were no significant differences in the S and S_N between baseline and repeated studies in the untrained group. In addition, CO₂ responsiveness was found to correlate negatively with maximum oxygen uptake in 4 out of the 5 trained subjects. These results suggest that in normal subjects, long-term physical training, as in the present study, decreases CO₂ responsiveness at rest.

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Maternal adrenocortical function was studied by measuring plasma cortisol and urinary free cortisol during gestation. Changes in suppressibility of pituitary-adrenocortical function were determined by dexamethasone administration. Urinary free cortisol as well as plasma cortisol increased during the course of gestation. The suppressibility by dexamethasone became less effective as pregnancy advanced. These results suggest that pregnant women have pituitary-adrenocortical hyperfunction and tissue refractoriness to glucocorticoid which increases during the course of gestation.

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The aim of this paper is to shed new light upon relativisers in Shakespeare's drama frm a sociolinguistic perspective, paying particular attention to gender and social class of the characters. This paper focuses primarily on the ratio of wh-relativizers, which serves as a useful indicator of formality. We reveal that the sociolinguistic backgrounds of the characters exert influence on the distribution of relativizers in a way that seems to reflect the educational inequalities prevalent in Shakespeare's time: wh-relativizers occur most frequently in the speech of gentry, somewhat less frequently in the speech of gentry women, while non-gentry, men and women alike, make fairly limited use of them. We also demonstrate that our findings are useful as tools for interpreting the language of several characters. For example, examining the ratio of wh-relativizers and the use of a collocation consisting of a preposition plus a relativizer (e.g. on whom), it is suggested that Bottom (in A Midsummer Night's Dream) speaks in a way that fits the role he is given (i.e as a nobleman). The case of Prince Henry also illustrates a notable phenomenon in which discourse situations play a major role in the distribution of relativizers.

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Background: We investigated the association between cardiovascular disease (CVD) and the risk of major osteoporotic fracture in Taiwan.
Methods: Using the Taiwan National Health Insurance Database for the period 2000–2007, we classified 43 874 patients aged 50 years or older with newly diagnosed CVD (coronary artery disease, heart failure, cerebrovascular disease, or peripheral atherosclerosis) as the CVD group and 43 874 subjects without CVD (frequency-matched by sex, age, and date selected) as the non-CVD group. Incidence and hazard ratios (HRs) for major osteoporotic fracture of the spine, hip, humerus, and forearm/wrist were estimated for the period until the end of 2010.
Results: After adjustment for confounders, the overall HRs for major osteoporotic fracture were 1.24 (95% CI = 1.13, 1.36) in men with CVD and 1.18 (95% CI = 1.11, 1.25) in women with CVD, as compared with the non-CVD group. As compared with the non-CVD group, the adjusted HR for major osteoporotic fracture was highest among subjects with cerebrovascular disease (HR 1.31; 95% CI 1.23, 1.39), followed by those with heart failure (HR 1.18; 95% CI 1.11, 1.27), peripheral atherosclerosis (HR 1.12; 95% CI 1.04, 1.20), and coronary artery disease (HR 1.07; 95% CI 1.01, 1.12).
Conclusions: CVD is associated with risk of major osteoporotic fracture in men and women in Taiwan.

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The relationship between γ-glutamyltransferase (γ-GTP) and C-reactive protein (CRP) has not been established, particularly in the lean or non-overweight population. In the present study, we examined the associations between γ-GTP and CRP in non-overweight and overweight middle-aged Japanese men. We conducted a cross-sectional study of 4,271 apparently healthy men aged 40 to 64 y (mean±SD, 50.5±6.6 y) who participated in health checkups. Associations between serum CRP levels, other clinical parameters, and lifestyle factors were analyzed using Spearman's rank correlation coefficient analysis and multiple linear regression analysis in the non-overweight (body mass index [BMI]<25 kg/m²) and overweight (BMI≥25 kg/m²) men. Associations between serum γ-GTP activity and serum CRP levels were analyzed using analysis of covariance by comparisons of serum CRP levels of four subgroups according to γ-GTP status. In non-overweight men, BMI, high-density lipoprotein cholesterol, triacylglycerols, fasting blood glucose, aspartate aminotransferase, γ-GTP, and smoking habit were positively associated with serum CRP levels. In overweight men, BMI, diastolic blood pressure, triacylglycerols, and γ-GTP were positively associated with serum CRP levels. After adjustment for age, BMI, smoking status, and alcohol intake, dose-response relationships were observed between γ-GTP and CRP levels in both overweight and non-overweight men. The results of this study indicate that an increase in serum γ-GTP activity is closely associated with elevated CRP levels in both non-overweight and overweight middle-aged Japanese men.

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