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Purpose: Both obstructive sleep apnea (OSA) and the common cold are disorders of the upper respiratory tract, and may be associated. However, studies on the association between OSA and upper respiratory tract infections (URTI) in children are scarce. The aim of this study was to investigate possible associations between snoring, the severity of OSA, and URTI in elementary school children. Methods: This was a cross-sectional study in a community cohort of elementary school children (first and second graders) in Japan. Information on sleep habits, history of URTI, and OSA risk was obtained from a parental questionnaire. Children underwent overnight tracheal sound recordings from which apnea–hypopnea index was estimated. Multivariable logistic analysis was employed to define the association between snoring, OSA, and URTI ≥ 3 episodes over six months. Results: Of the 922 potential enrollees, 653 children and their parents (71%) agreed to participate in the study. Multivariable-adjusted ORs for URTI were 1.73 (95%CI: 1.16 to 2.59) in children who snored 1 to 4 nights per week and 2.82 (95%CI: 1.26 to 6.28) in snoring ≥ 5 nights per week compared with never snoring (reference). Likewise, subjectively reported louder snoring, as well as objectively defined louder sound levels, were significantly associated with URTI. In addition, OR for URTI in children with an estimated apnea–hypopnea index ≥ 2.0 events/hour was 2.65 (95%CI: 1.32 to 5.31) compared to children with apnea–hypopnea index less than 1.0 events/hour (reference). Conclusions: Snoring and severity of OSA as measured by nocturnal tracheal sound recordings were associated with increased susceptibility to URTI in elementary school children. [ABSTRACT FROM AUTHOR]

Background: The culture of excessively long overtime work in Japan has not been recently addressed. New legislation on working hours, including a limitation on maximum overtime work for physicians, will be enforced in 2024. This study was performed to elucidate the working conditions of full-time hospital physicians and discuss various policy implications. Methods: A facility survey and a physician survey regarding physicians' working conditions were conducted in July 2022. The facility survey was sent to all hospitals in Japan, and the physician survey was sent to all physicians working at half of the hospitals. The physicians were asked to report their working hours from 11 to 17 July 2022. In addition to descriptive statistics, a multivariate logistic regression analysis on the factors that lead to long working hours was conducted. Results: In total, 11,466 full-time hospital physicians were included in the analysis. Full-time hospital physicians worked 50.1 h per week. They spent 45.6 h (90.9%) at the main hospital and 4.6 h (9.1%) performing side work. They spent 43.8 h (87.5%) on clinical work and 6.3 h (12.5%) on activities outside clinical work, such as research, teaching, and other activities. Neurosurgeons worked the longest hours, followed by surgeons and emergency medicine physicians. In total, 20.4% of physicians were estimated to exceed the annual overtime limit of 960 h, and 3.9% were estimated to exceed the limit of 1860 h. A total of 13.3% and 2.0% exceeded this level only at their primary hospital, after excluding hours performing side work. Logistic regression analysis showed that male, younger age, working at a university hospital, working in clinical areas of practice with long working hours, and undergoing specialty training were associated with long working hours after controlling for other factors. Conclusions: With the approaching application of overtime regulations to physicians, a certain reduction in working hours has been observed. However, many physicians still work longer hours than the designated upper limit of overtime. Work reform must be further promoted by streamlining work and task-shifting while securing the functions of university hospitals such as research, education, and supporting healthcare in communities. [ABSTRACT FROM AUTHOR]

Background: Autosomal dominant polycystic kidney disease (ADPKD) occurs in 1 in 500–4000 people worldwide. Genetic mutation is a biomarker for predicting renal dysfunction in patients with ADPKD. In this study, we performed a genetic analysis of Japanese patients with ADPKD to investigate the prognostic utility of genetic mutations in predicting renal function outcomes. Methods: Patients clinically diagnosed with ADPKD underwent a panel genetic test for germline mutations in PKD1 and PKD2. This study was conducted with the approval of the Ethics Committee of Juntendo University (no. 2019107). Results: Of 436 patients, 366 (83.9%) had genetic mutations. Notably, patients with PKD1 mutation had a significantly decreased ΔeGFR/year compared to patients with PKD2 mutation, indicating a progression of renal dysfunction (−3.50 vs. −2.04 mL/min/1.73 m2/year, p = 0.066). Furthermore, PKD1 truncated mutations had a significantly decreased ΔeGFR/year compared to PKD1 non-truncated mutations in the population aged over 65 years (−6.56 vs. −2.16 mL/min/1.73 m2/year, p = 0.049). Multivariate analysis showed that PKD1 mutation was a more significant risk factor than PKD2 mutation (odds ratio, 1.81; 95% confidence interval, 1.11–3.16; p = 0.020). Conclusions: The analysis of germline mutations can predict renal prognosis in Japanese patients with ADPKD, and PKD1 mutation is a biomarker of ADPKD. [ABSTRACT FROM AUTHOR]

Purpose: With a rapidly aging society, there is increasing interest in the health of female workers in the field of care services for older adults due to increasing demands to maintain 24-h care and to support older adults without errors or accidents. Therefore, the purpose of this cross-sectional study was to examine the association between sleep-disordered breathing (SDB) and sustained attention in women caring for older adults in Japan. Methods: The study was conducted in women aged 18–67 years old working in care service facilities for older adults in Japan. The sustained attention of participants was measured by the 10-min psychomotor vigilance task (PVT). SDB was assessed based on the respiratory disturbance index (RDI), which was measured using an ambulatory airflow monitor with a polyvinylidene fluoride (PVDF) film sensor to monitor the respiratory airflow of nasal and oral breathing. The participants wore the monitor to record the breathing status while asleep at home. The severity of SDB was categorized as follows: normal, RDI < 5 events/h; mild SDB, RDI 5–10 events/h; and moderate-to-severe SDB, RDI ≥ 10 events/h. Results: Of 688 women enrolled, medians of age, body mass index (BMI), sleep duration, and prevalence of hypertension tended to be higher with increasing RDI. No significant association was found between RDI and PVT parameters. However, when we limited the analysis to women with BMI ≥ 22 kg/m2, those with moderate-to-severe SDB had significantly higher odds of having the slowest 10% reaction times compared to those without SDB (OR = 2.03; 95% CI = 1.17–3.53). The association did not decrease after adjusting to account for sleep duration, alcohol drinking habits, and history of hypertension (OR = 1.97; 95% CI = 1.10–3.52). A significant increasing trend was also found between RDI and the slowest 10% of reaction times (p for trend = 0.03). Conclusions: Our findings suggest that SDB is associated with reduced sustained attention in participants with BMI ≥ 22 kg/m2, although the number of assessments of SDB and PVT was only once per participant due to the nature of the cross-sectional study. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) is a common cause of hypertension. Previous studies have demonstrated beneficial short-term effects of continuous positive airway pressure (CPAP) therapy on blood pressure. However, long-term antihypertensive effects of CPAP have not been properly verified. This study examined the longitudinal effect of CPAP therapy adherence on blood pressure among OSA patients. All patients diagnosed with OSA and undergoing subsequent CPAP therapy at a Kanagawa-area sleep clinic were clinically followed for 24 months to examine CPAP adherence, as well as longitudinal changes in blood pressure and body weight because it may become a confound factor for changes in blood pressure. The hours of CPAP usage were collected over the course of 30 nights prior to each follow-up visit (1st, 3rd, 6th, 12th, and 24th month). The relationship between CPAP adherence and blood pressure was analyzed using mixed-effect logistic regression models. A total of 918 OSA patients were enrolled in the study. We found a significant reduction in diastolic blood pressure among patients with good CPAP adherence during the 24-month follow-up period (β = − 0.13, p = 0.03), when compared to the group with poor CPAP adherence. No significant association was found between CPAP adherence and weight loss (β = − 0.02, p = 0.59). Long-term, good CPAP therapy adherence was associated with lower diastolic blood pressure without significant weight loss. [ABSTRACT FROM AUTHOR]

IL-17A and IL-17F are both involved in the pathogenesis of neutrophilic inflammation observed in COPD and severe asthma. To explore this, mice deficient in both Il17a and Il17f and wild type (WT) mice were exposed to cigarette smoke or environmental air for 5 to 28 days and changes in inflammatory cells in bronchoalveolar lavage (BAL) fluid were determined. We also measured the mRNA expression of keratinocyte derived chemokine (Kc), macrophage inflammatory protein-2 (Mip2), granulocyte–macrophage colony stimulating factor (Gmcsf) and matrix metalloproteinase-9 (Mmp9) in lung tissue after 8 days, and lung morphometric changes after 24 weeks of exposure to cigarette smoke compared to air-exposed control animals. Macrophage counts in BAL fluid initially peaked at day 8 and again on day 28, while neutrophil counts peaked between day 8 and 12 in WT mice. Mice dual deficient with Il17a and 1l17f showed similar kinetics with macrophages and neutrophils, but cell numbers at day 8 and mRNA expression of Kc, Gmcsf and Mmp9 were significantly reduced. Furthermore, airspaces in WT mice became larger after cigarette smoke exposure for 24 weeks, whereas this was not seen dual Il17a and 1l17f deficient mice. Combined Il17a and Il17f deficiency resulted in significant attenuation of neutrophilic inflammatory response and protection against structural lung changes after long term cigarette smoke exposure compared with WT mice. Dual IL-17A/F signalling plays an important role in pro-inflammatory responses associated with histological changes induced by cigarette smoke exposure. [ABSTRACT FROM AUTHOR]

Prior to the identification of proteins for proteomics analysis in human cells, separation of fluorogenic derivatized proteins with a fluorogenic reagent, 7‐chloro‐N‐[2‐(dimethylamino)ethyl]‐2,1,3‐benzoxadiazole‐4‐sulfonamide, has typically been performed by using a conventional reversed‐phase HPLC column. However, the number of proteins in human cells (HepaRG) that are separated by this conventional approach is limited to approximately 500. In this study, a nanoflow liquid chromatography system with an evaluated phenyl‐bonded monolithic silica capillary column (0.1 mm i.d., 700 mm length) was used to increase the number of separated fluorogenic derivatized proteins. This system was used to separate derivatized human cell proteins (K562) and yeast (Saccharomyces cerevisiae) proteins as model cell proteomes. More than 1,300 protein peaks were separated/detected from both cell proteomes. We present a straightforward comparison of multiple separation profiles using a novel chromatogram display approach, termed the "spiderweb" chromatogram. In addition, to validate that the detected peaks are derived from proteins, a mass spectrometer was connected to the capillary column and deconvolution of the obtained mass spectra was performed. Furthermore, different molecular weight distribution profiles of the expressed proteins were observed between the two cell proteomes. [ABSTRACT FROM AUTHOR]

Background and Aim: Longer diagnostic delay (DD) in Crohn's disease (CD) is associated with complications and related surgeries. However, the impact of DD on medical cost after CD diagnosis remains uncertain. Methods: This was a claims‐based cohort study. Our analysis used data from 2005 to 2018 from the Japanese Claims Database. We enrolled a total of 528 newly diagnosed CD patients (76.9% male) aged 31.5 ± 13.6 years. High medical cost was defined as the highest quartile of the average monthly medical cost. DD was defined as the interval between the first visit to a gastroenterologist and diagnosis with CD. In the multivariable logistic regression analysis, patients were stratified by the use of anti‐tumor necrosis factor alpha (anti‐TNFα) agents to exclude their influence on the observed effects. This study was approved by the ethics review board of the Juntendo University Faculty of Medicine (No. 2019178). Results: The multivariable‐adjusted odds ratios and 95% confidence intervals of high medical cost were 1.41 (0.81–2.43) and 0.91 (0.57–1.46), respectively, for a DD of >12 months and 1 to ≤12 months compared to <1 month. In patients receiving anti‐TNFα agents, the multivariable‐adjusted odds ratios for high medical cost were 2.63 (1.34–5.16) and 1.35 (0.79–2.28) for a DD of >12 months and 1 to ≤12 months, respectively, compared to <1 month. In patients without anti‐TNFα, multivariable logistic regression analyses were not presented because of a small number of patients categorized into the high medical cost group. Conclusion: A delayed diagnosis of CD may incur high medical cost in patients who develop aggressive disease that requires treatment with anti‐TNFα agents. [ABSTRACT FROM AUTHOR]

To clarify how low BMI and weight loss were associated with risk of chronic obstructive pulmonary disease (COPD) mortality, in a large prospective cohort of the general population across Japan, the Japan Collaborative Cohort Study, conducted between 1988 and 2009. A total of 45,837 male residents were observed for a median period of 19.1 years. Self-administered questionnaires, collecting information on BMI, weight loss since the age of 20, lifestyles, history of diseases, as well as records of COPD mortality, were analysed at 2019. During follow-up, 268 participants died from COPD. The multivariate-adjusted hazard ratio (95% confidence interval) of COPD mortality associated with a 1-SD increment of body mass index (BMI) was 0.48 (0.41–0.57), while for weight change from age of 20 (+ 2.0 kg) it was 0.63 (0.59–0.68). These associations were persistently observed after stratifications with smoking status, excluding those having airway symptoms in the baseline survey, and excluding early COPD deaths within 5, 10 and 15 years. Our study suggests that BMI and weight change since the age of 20 could be markers for COPD prognosis, indicated by risk of COPD mortality. [ABSTRACT FROM AUTHOR]

Background: The proportion of non-regularly employed persons has increased in Japan, but few studies have examined the relationship between employment status and lung cancer screening (LCS) participation. Methods: Authors analyzed data from the 2010 Comprehensive Survey of Living Conditions in Japan. The anonymous responses of 28,951 people aged 40–69 years old were analyzed. Authors defined nine employment status categories: unemployed, regularly employed in a large-, middle-, and small-scale company, non-regularly employed in a large-, middle-, and small-scale company, self-employed, and other. LCS participation in the past year was surveyed through a self-reported questionnaire. Sex-specific prevalence ratios (PRs) and 95% confidence intervals (CIs) for LCS participation for all employment status categories, using the regularly employed in a middle-scale company category as the reference, were calculated using multivariable Poisson regression analysis, after adjusting for potentially confounding factors. Results: Multivariable-adjusted PRs (95% CI) for LCS participation for the regularly employed in a large-scale company were 1.33 (1.25–1.41) in men and 1.53 (1.38–1.71) in women. Multivariable-adjusted PRs (95% CI) for LCS participation for the non-regularly employed in a middle- and small-scale company compared with the regularly employed in a middle-scale company were 0.81 (0.72–0.92) and 0.62 (0.50–0.76) in men, and 0.89 (0.80–0.99) and 0.80 (0.71–0.91) in women, respectively. Conclusion: Regularly employed in a large-scale company had significantly higher LCS participation, and non-regularly employed in a middle- or small-scale company showed significantly lower LCS participation than those who were regularly employed in a middle-scale company. [ABSTRACT FROM AUTHOR]

Background Marital status is one of the socio-economic factors associated with health. Several studies have indicated a significant association between marital status and insomnia. The increases in the percentages of unmarried people in Japan are expected to produce a significant impact on insomnia. The purpose of this study was to examine the association between marital status and insomnia. Methods The participants were 35 288 people aged 30–59 years selected from the 2010 comprehensive survey of living conditions. We categorized marital status into five groups: single, married couples living with other family members, married couples living without other family members, widowed and divorced. Insomnia-related symptoms (IRS) were based on the participants who chose the answer, 'I couldn't sleep'. Sex-specific multivariable odds ratios (ORs) and 95% confidence intervals (CI) of IRS according to marital status were calculated using the logistic regression model, which was adjusted for potential confounding factors. Results The proportions of people with IRS were 2.5% in men and 2.8% in women. The multivariable ORs (95% CI) were 1.15 (0.89–1.49) for single, 1.69 (1.11–2.58) for divorced and 1.01 (0.73–1.39) for married couples living without other family members in men, and 1.56 (1.20–2.03) for single, 2.43 (1.83–3.22) for divorced and 1.31 (1.01–1.71) for married couples living without other family members in women. Conclusions We found divorced men and single, divorced and married women living without other family members had higher IRS than those who were married couples living with other family members in Japanese. This association was more evident in unemployed men. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate the association between hyperactivity/anxiety and obesity among elementary school students in Matsuyama City, Japan. Methods: We conducted a cross-sectional study of all 46 elementary school students (24, 296 students) in Matsuyama City. The questionnaire included question items from the Strengths and Difficulties Questionnaire (SDQ), as well as questions about height and weight. The students were classified into two groups according to Rohrer index. After separating the data by gender, we examined the association between (1) obesity and hyperactivity, (2) obesity and anxiety, and (3) obesity and combination of hyperactivity and anxiety, by estimating relative risk using Poisson regression model. We also conducted stratified analyses to examine the effect modification by age groups and unbalance of diet on those associations. Moreover, we calculated relative excess risk due to the interaction (RERI) to examine whether there was an additive interaction between hyperactivity and anxiety. Results: Sixteen thousand forty-eight students were included in the present analysis. The prevalence ratio (PR) of being obese in girls who had both hyperactivity and anxiety was higher compared to girls without those symptoms (PR = 1.80; 95% CI 1.04–3.13). There was no significant difference in the prevalence ratio for obesity in boys, whether they were hyperactive, anxious, or neither. RERI was 0.00 for boys and 0.18 for girls. Conclusion: We found a significant association between obesity and co-existence of hyperactivity and anxiety among elementary school girls. Our findings strengthen the need to further explore the association between childhood obesity, hyperactivity, and anxiety. [ABSTRACT FROM AUTHOR]

Background: Short sleep duration (SSD) is reported to be highly associated with socio-economic status. There are few studies on the relationship between employment status and SSD in Japan. Method: The authors used the 2006 Survey on Time Use and Leisure Activities conducted by the Ministry of Internal Affairs and Communications Japan, which provides representative samples of Japanese people. The anonymous data of 120,783 people aged 30–59 years were analyzed. Authors defined five categories of employment status: "unemployed," "regularly employed," "non-regularly employed," "self-employed," and "other." Authors also defined a sleep duration shorter than 5 h per night as SSD. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of SSD using regular employment as the reference group were calculated using the logistic regression model, adjusting for potential confounding factors, i.e., age, marital status, education level, communication device use, and the amount of time spent on various daily activities. Results: The prevalence of SSD was 2.8% (1639/58,308) in men and 3.2% (1976/62,475) in women. The multivariable-adjusted OR (95% CI) of SSD for the self-employed was 0.78 (0.65–0.92) in men and 1.78 (1.43–2.21) in women after adjustment for potential confounding factors, i.e., age, marital status, education level, and communication device use. Further adjustment for the time spent on daily activities revealed that the OR (95% CI) of SSD for the self-employed was 0.78 (0.65–0.92) in men and 1.89 (1.52–2.36) in women. Conclusion: Self-employed women had a higher prevalence of SSD. By contrast, self-employed men had a lower prevalence of SSD. [ABSTRACT FROM AUTHOR]

Background and objective: Coffee is a major caffeine-containing food source that can be used for treatment of apnea in prematurity. However, few studies have examined the association between coffee consumption and sleep-disordered breathing (SDB). We investigated whether coffee consumption is associated with the oxygen desaturation index (ODI) as a marker of SDB among middle-aged Japanese male workers. Methods: The subjects were 1126 male local government workers aged 22–59 who participated in SDB screening in 2011–2012. Daily coffee consumption was assessed by a self-administered questionnaire. We measured 3% oxygen desaturation (3%ODI) during a night's sleep using a pulse oximeter. A general linear model was used to calculate the multivariate-adjusted means of 3%ODI per quartile of coffee consumption. We further analyzed the data after stratifying by overweight and current smoking status. Results: A inverse association between coffee consumption and 3%ODI was found. The multivariate-adjusted mean of 3%ODI for the lowest and highest coffee consumption groups were 11.9 times/h and 10.6 times/h (p for trend = 0.06), respectively; 14.6 and 11.5 times/h (p for trend = 0.01) in overweight participants; and 12.7 and 11.0 times/h (p for trend = 0.06) in non-smokers. No associations were found in non-overweight and smoking workers. Conclusions: Our results suggest that higher coffee consumption was associated with lower 3% ODI as a marker of SDB in overweight and non-smoking workers. [ABSTRACT FROM AUTHOR]

Aim: The prevalence and clinical impact of snoring in the independent older adult population is unknown. To address this, we carried out this cross‐sectional epidemiological study of community‐dwelling independent older adults. Methods: The study data were collected by the Japan Gerontological Evaluation Study 2013, a postal survey distributed to a large cohort of independent community‐dwelling older adults (aged ≥65 years) in 2013, across 30 municipalities of 14 prefectures. We used data for 24 837 participants (13 135 women, mean age 73.5 years, and 11 702 men, mean age 73.3 years). The association of snoring with airway symptoms and history of hypertension, diabetes and heart disease were investigated using Poisson regression models. Results: The prevalence ratio (95% confidence intervals) for wheezing according to snoring frequency in men was 1.87 (1.45–2.43) among those who snored on 1–6 nights a week, and 2.95 (2.15–4.05) among those who snored every night. Similar relationships were observed for women. Expectoration, another airway symptom, was also associated with snoring frequency. Furthermore, snoring frequency was associated with a higher prevalence of hypertension, diabetes and heart disease. Both diabetes and heart disease were associated with snoring frequency in women independent of body mass index, but the association was only observed in men with a normal or lower body mass index. Conclusions: Snoring is a highly prevalent and pathogenic symptom in adults aged ≥65 years. Geriatr Gerontol Int 2019; 19: 1165–1171. [ABSTRACT FROM AUTHOR]

Background and purpose of the study:Pseudomonas aeruginosa commonly colonizes the airway of patients with chronic obstructive pulmonary disease (COPD) and exacerbates their symptoms. P. aeruginosa carries flagellin that stimulates toll-like receptor (TLR)-5; however, the role of flagellin in the pathogenesis of COPD remains unclear. The aim of the study was to evaluate the mechanisms of the flagellin-induced innate immune response in bronchial epithelial cells, and to assess the effects of anti-inflammatory agents for treatment. Materials and methods: We stimulated BEAS-2B cells with P. aeruginosa-derived flagellin, and assessed mRNA expression and protein secretion of interleukin (IL)-6 and IL-8. We also used mitogen-activated protein kinases (MAPK) inhibitors to assess the signaling pathways involved in flagellin stimulation, and investigated the effect of clinically available anti-inflammatory agents against flagellin-induced inflammation. Results: Flagellin promoted protein and mRNA expression of IL-6 and IL-8 in BEAS-2B cells and induced phosphorylation of p38, ERK, and JNK; p38 phosphorylation-induced IL-6 production, while IL-8 production resulted from p38 and ERK phosphorylation. Fluticasone propionate (FP) and dexamethasone (DEX) suppressed IL-6 and IL-8 production in BEAS-2B cells, but clarithromycin (CAM) failed to do so. Conclusions:P. aeruginosa-derived flagellin-induced IL-6 and IL-8 production in bronchial epithelial cells, which partially explains the mechanisms of progression and exacerbation of COPD. Corticosteroids are the most effective treatment for the suppression of flagellin-induced IL-6 and IL-8 production in the bronchial epithelial cells. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to examine the prevalence of sleep-disordered breathing (SDB) in women working in the field of aged care in Japan.Methods: A cross-sectional study was conducted for female employees aged 18-60 years in aged care facilities in Japan. The analyzed set consisted of 712 participants with complete data. SDB was determined by respiratory disturbance index (RDI), measured using an ambulatory airflow monitor with a polyvinylidene fluoride film sensor to detect nasal and oral airflow overnight at home. Based on the findings of previous studies, RDI 10 was considered equivalent to apnea-hypopnea index (AHI) 15.Results: The prevalence of moderate-to-severe SDB (RDI ≥ 10) was 22.8%. The mean age was 38.1 years, and mean sleeping time of participants was 6.1 h. The median body mass index (BMI) was 22.0. Women with moderate-to-severe SDB (RDI ≥ 10) had a higher age, neck circumference, neck-height ratio, BMI, systolic blood pressure, and increased prevalence of hypertension, short sleepers (amount of sleep on the SDB testing day < 6 h), and habitual snorers, compared to women with no or mild SDB (RDI < 10).Conclusions: Our study found that women working in the aged care services in Japan were heavily burdened by SDB even though they were relatively young and slim. To prevent CVD from developing in the future, programs through which workplaces can help their employees improve their lifestyle, and early diagnosis and treatment of SDB are highly recommended. [ABSTRACT FROM AUTHOR]

Background: Several retrospective studies have shown that bone disorders occur after gastric cancer surgery. This study was designed to prospectively evaluate the changes in bone metabolism after gastrectomy for gastric cancer.Methods: We prospectively enrolled 39 men with early gastric cancer who underwent gastrectomy. We excluded women to avoid the effects of menopause. We employed dual energy X-ray absorptiometry (DEXA) to measure bone mineral density (BMD) of the lumbar spine. DEXA was performed before and 1 and 2 years after surgery. The serum levels of alkaline phosphatase (ALP), 1,25-dihydroxy vitamin D [1,25(OH)2VD], 25-hydroxy vitamin D [25(OH)VD], and estradiol were measured before surgery and every 3 months until 2 years after surgery.Results: DEXA revealed that BMD significantly decreased by 0.036 ± 0.033 g/cm2 12 months after gastrectomy (P < 0.001) and by 0.046 ± 0.040 g/cm2 24 months after gastrectomy (P < 0.001). The serum ALP level significantly increased by 38.31 ± 103.8 IU/L 24 months after surgery (P = 0.013). The serum 25(OH)VD level significantly decreased by 4.88 ± 6.42 ng/ml 24 months after surgery (P < 0.001), whereas the serum 1,25(OH)2VD levels were consistently in the normal range. The serum estradiol level significantly increased by 2.94 ± 7.49 pg/ml 12 months after gastrectomy (P = 0.035). A lower preoperative body mass index (BMI) significantly correlated with the reduction in BMD 12 months after surgery; the correlation coefficient was 0.37 (P = 0.025).Conclusions: This study showed that a significant decrease in BMD was observed for up to 24 months after gastrectomy, not only 12 months. [ABSTRACT FROM AUTHOR]

Rationale: Neutrophilic airway inflammation plays a central role in chronic obstructive pulmonary disease (COPD). CXC chemokine ligand (CXCL)1 is a neutrophil chemokine involved in the pathogenesis of COPD. However, its clinical significance in COPD patients is poorly understood. Aim of the study: To assess the production of CXCL1 by bronchial epithelial cells in response to lipopolysaccharide (LPS) and tumor necrosis factor (TNF)α. Materials and Methods: We measured sputum CXCL1 and CXCL8 levels in patients with COPD, asthma, and asthma-COPD overlap (ACO), and compared them to those of patients with interstitial pneumonia (IP). Using primary human bronchial epithelial cells and BEAS-2B cells, CXCL1 protein release and mRNA expression were measured after LPS or TNFα stimulation. We evaluated signal transduction mechanisms for CXCL1 production using nuclear factor-κ B (NF-kB) and mitogen-activated protein kinase (MAPK) inhibitors, and examined the effects of anti-inflammatory agents on CXCL1 production in BEAS-2B cells. Results: Sputum CXCL1 levels in COPD and ACO patients were higher than in IP patients, whereas sputum CXCL8 levels were not. Sputum CXCL1 levels were not affected by inhaled corticosteroid usage, whereas sputum CXCL8 levels tended to be affected. LPS and TNFα stimulated CXCL1 production and mRNA expression in bronchial epithelial cells. NF-kB and MAPK p38 were involved in LPS-induced CXCL1 production. Therapeutic anti-inflammatory agents minimally attenuated CXCL1 production and considerably inhibited CXCL8 production in BEAS-2B cells. Conclusions: Sputum CXCL1 levels is a potentially better diagnostic marker for COPD than sputum CXCL8 levels, which is explained by that CXCL1 production in bronchial epithelial cells is less affected by therapeutic anti-inflammatory agents than CXCL8 production. [ABSTRACT FROM AUTHOR]

Abstract: The aim of the present review was to clarify the association between obstructive sleep apnea (OSA) and type 2 diabetes, and discuss the therapeutic role of continuous positive airway pressure (CPAP) in type 2 diabetes. OSA patients are more likely than non‐OSA populations to develop type 2 diabetes, while more than half of type 2 diabetes patients suffer from OSA. Similar to Western countries, in the East Asian population, the association between these two disorders has also been reported. CPAP is the primary treatment for OSA, but the effect of CPAP on comorbid diabetes has not been established. CPAP improved glucose metabolism determined by the oral glucose tolerance test in OSA patients, and several studies have shown that CPAP improves insulin resistance, particularly in obese populations undergoing long‐term CPAP. Diabetes is associated with other sleep‐related manifestations as well, such as snoring and excessive daytime sleepiness. Snoring is associated with the development of diabetes, and excessive daytime sleepiness appears to modify insulin resistance. Well‐designed studies are required to clarify the therapeutic effect of CPAP on diabetes. As both diabetes and OSA lead to cardiovascular disease, clinicians and healthcare professionals should be aware of the association between diabetes and OSA, and should take CPAP and health‐related behaviors into consideration when treating patients with diabetes and/or OSA. [ABSTRACT FROM AUTHOR]

Background and Purpose: Bronchial asthma (BA) is a chronic airway disease characterized by airway hyperresponsiveness and remodeling, which are intimately linked to chronic airway inflammation. Reactive oxygen species (ROS) such as hydrogen peroxide are generated by inflammatory cells that are involved in the pathogenesis of BA. However, the role of ROS in the management of BA patients is not yet clear. We attempted to determine the role of ROS as a biomarker in the clinical setting of BA. Subjects and Methods: We enrolled patients with BA from 2013 through 2015 and studied the degrees of asthma control, anti-asthma treatment, pulmonary function test results, fractional exhaled nitric oxide (FeNO), serum reactive oxygen metabolite (ROM) levels, and serum levels of interleukin (IL)-6 and IL-8. Results: We recruited 110 patients with BA. Serum ROM levels correlated with white blood cell (WBC) count (rs = 0.273, p = 0.004), neutrophil count (rs = 0.235, p = 0.014), CRP (rs = 0.403, p < 0.001), and IL-6 (rs = 0.339, p < 0.001). Serum ROM levels and IL-8 and CRP levels negatively correlated with %FEV1 (rs = -0.240, p = 0.012, rs = -0.362, p < 0.001, rs = -0.197, p = 0.039, respectively). Serum ROM levels were significantly higher in patients who experienced severe exacerbation within 3 months than in patients who did not (339 [302–381] vs. 376 [352–414] CARR U, p < 0.025). Receiver-operating characteristics analysis showed that ROM levels correlated significantly with the occurrence of severe exacerbation (area under the curve: 0.699, 95% CI: 0.597–0.801, p = 0.025). Conclusions: Serum levels of ROM were significantly associated with the degrees of airway obstruction, WBC counts, neutrophil counts, IL-6, and severe exacerbations. This biomarker may be useful in predicting severe exacerbations of BA. [ABSTRACT FROM AUTHOR]

Background:Recent reports have suggested an involvement of neutrophilic inflammation driven by interleukin (IL)-17 from Th17 cells, especially in severe, refractory asthma. It remains unknown about the possible interactions of this cytokine and other proinflammatory cytokines to direct neutrophilic airway inflammation.Materials and Methods:We evaluated the effects of IL-17A, IL-17E, and IL-17F in combination with other stimuli such as tumor necrosis factor (TNF) –α on the production and expression of IL-8 in human bronchial epithelial cells. We also studied their effects on other cytokine production. The possible role of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways was evaluated by specific inhibitors. We examined the effects of anti-asthma drugs, such as steroids or salmeterol.Results:IL-17A alone induced only a minimal effect on IL-8 expression. IL-17A, but not IL-17E or IL-17F, in combination with TNF-α showed a synergistic effect on IL-8 expression. Similar findings were found when combination with IL-1β and IL-17A were used, but such was not the case with lipopolysaccharide (LPS). In addition, we further found such synergy on GM-CSF production. The synergy with TNF-α and IL-17A was significantly inhibited by MAPKs inhibitors. Corticosteroids such as fluticasone propionate and dexamethasone, but not salmeterol, partially suppressed the IL-17A and TNF-α-induced IL-8 production.Conclusions:IL-17A in the combination with TNF-α or IL-1β showed a synergistic augmenting effect on IL-8 and GM-CSF production in human airway epithelial cells. [ABSTRACT FROM PUBLISHER]

Aim of the Study: Interleukin (IL)-10 is an anti-inflammatory cytokine, but its role in cigarette smoke (CS)-induced inflammation and chronic obstructive pulmonary disease (COPD) has not been fully elucidated. The purpose of this study was to investigate the effect of IL-10 deficiency on CS-induced pulmonary inflammation in mice in vivo and in vitro.Materials and Methods: IL-10-deficient and wild-type control mice with a C57BL6/J genetic background were exposed to CS, and inflammatory cells in bronchoalveolar lavage fluid (BALF) and mRNA of cytokines in lung were evaluated with enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR).Results: During 12 days of daily CS exposure to wild-type mice, neutrophil counts in BAL fluid and tumor necrosis factor (TNF)-α mRNA expression were increased, peaked at day 8, and then declined on day 12 when the level of IL-10 reached its peak. In IL-10-deficient mice, neutrophil recruitment and TNF-α mRNA levels induced by CS exposure were significantly greater than those in wild-type mice. Keratinocyte-derived chemokine (KC; murine ortholog of human CXCL8) and granulocyte macrophage colony-stimulating factor (GM-CSF) mRNA levels or matrix metalloproteinase(MMP)-9 protein levels were not correlated with neutrophil count.Conclusions: IL-10 had a modulatory effect on CS-induced pulmonary neutrophilic inflammation and TNF-α expression in mice in vivo and therefore appears to be an important endogenous suppressor of airway neutrophilic inflammation. [ABSTRACT FROM PUBLISHER]

Background: In this study we examined whether histopathological findings, specifically lymphatic vessel invasion identified by an anti-human podoplanin antibody, and several other factors are associated with lymph node metastasis in T1 colorectal cancer. Methods: We searched PubMed and Cochrane Library, and also handsearched relevant journals, for reports written in English and published between 1998 and 2012, utilizing combination headings, such as 'colorectal cancer,' 'lymph node metastasis,' and 'risk factors.' For the report to be included in our study, the following criteria had to be met: (1) data on the frequency of lymph node metastasis in T1 colorectal cancer in relation to histopathological factors were reported; (2) patients had undergone bowel resection and had histologically diagnosed T1 colorectal cancer; (3) lymphatic vessel invasion was identified by immunohistochemistry with an anti-human podoplanin antibody rather than by hematoxylin and eosin staining; (4) univariate and multivariate analyses were conducted. Studies investigating molecular markers were excluded. The independent predictive factors were confirmed in at least one study included in the meta-analysis in the present systematic review. Microsoft Excel 2013 for Windows was used for the statistical analysis. Results: Initially, 369 publications were identified in the database searches and handsearches, of which five ultimately met all of the inclusion criteria and selected for this systematic review. The meta-analysis revealed that only two factors were significantly associated with T1 colorectal cancer lymph node metastasis: (1) lymphatic vessel invasion identified by an anti-human podoplanin antibody [Mantel-Haenszel odds ratio (OR) 5.19; (95 % confidence interval (CI) 3.31-8.15; P = 0.01]; (2) tumor budding (OR 7.45; 95 % CI 4.27-13.02; P = 0.0077). Conclusion: Our meta-analysis revealed that lymphatic vessel invasion identified by an anti-human podoplanin antibody and tumor budding were significantly associated with T1 colorectal cancer lymph node metastasis. [ABSTRACT FROM AUTHOR]

Mycoplasma pneumoniae (Mp) is a leading cause of community acquired pneumonia. Knowledge regarding Mp pneumonia obtained from animal models or human subjects has been discussed in many different reports. Accumulated expertise concerning this critical issue has been hard to apply clinically, and potential problems may remain undiscovered. Therefore, our multidisciplinary team extensively reviewed the literature regarding Mp pneumonia, and compared findings from animal models with those from human subjects. In human beings, the characteristic pathological features of Mp pneumonia have been reported as alveolar infiltration with neutrophils and lymphocytes and lymphocyte/plasma cell infiltrates in the peri-bronchovascular area. Herein, we demonstrated the novel aspects of Mp pneumonia that the severity of the Mp pneumonia seemed to depend on the host innate immunity to the Mp, which might be accelerated by antecedent Mp exposure (re-exposure or latent respiratory infection) through up-regulation of Toll-like receptor 2 expression on bronchial epithelial cells and alveolar macrophages. The macrolides therapy might be beneficial for the patients with macrolide-resistant Mp pneumonia via not bacteriological but immunomodulative effects. This exhaustive review focuses on pathogenesis and extends to some therapeutic implications such as clarithromycin, and discusses the various diverse aspects of Mp pneumonia. It is our hope that this might lead to new insights into this common respiratory disease. [ABSTRACT FROM AUTHOR]

Background: The management of T1 colorectal cancer after local resection is controversial. Regional lymph node metastasis often occurs, requiring subsequent colonic resection. The aim of this study was to reevaluate the risk factors of nodal metastasis of T1 colorectal cancer, especially to examine lymphatic vessel invasion in serially prepared hematoxylin and eosin sections and D2-40 immunostained sections to determine which is a better indicator of lymph node metastasis of T1 colorectal cancer. Methods: The study investigated 120 patients who underwent bowel resection and were histologically diagnosed to have T1 colorectal cancer in Kanagawa Cancer Center Hospital from 1995 to 2005. Serially prepared paraffin sections were stained with hematoxylin and eosin, or immunostained with D2-40 antibody or von Willebrand factor, and reevaluated for lymphatic vessel invasion and other risk factors, including venous invasion, histological grade, depth of submucosal invasion, and budding. Results: Lymphatic invasion diagnosed with either hematoxylin and eosin staining ( p = 0.022), or D2-40 immunostaining ( p = 0.001), and budding ( p = 0.013) were significant risk factors for lymph node metastasis in the univariate analysis. Venous involvement, histological grade, or depth of submucosal invasion was not significant. The multivariate logistic regression analysis for the three risk factors found lymphatic invasion diagnosed with D2-40 as an independent risk factor (odds ratio 6.048, p = 0.018, CI 1.360-26.89). The sensitivity, specificity, positive predictive value, and negative predictive value were 58 %, 88 %, 35 %, and 95 %, respectively. Conclusions: Lymphatic vessel invasion diagnosed with D2-40 was a better indicator to evaluate the risk for lymph node metastasis by T1 colorectal cancer. [ABSTRACT FROM AUTHOR]

Mycoplasma pneumoniae (Mp) may cause immune cell reactions as pivotal aspects of this clinically common respiratory pathogen. Our aim is to determine if Mp extract induces a cellular immune response associated with interleukin (IL)-17, leading to lung inflammation and lung injury. BALB/c mice were immunized with Mp extract intraperitoneally followed by its intratracheal administration, to mimic repeated Mp infection found in humans (repeated inoculation, RI group). Those with a single inoculation were compared as single inoculation group (SI group). Analysis of bronchoalveolar lavage fluid (BALF) demonstrated that keratinocyte-derived cytokine, tumor necrosis factor-α, and IL-6 were produced and peaked on days 0.5 or 1, followed by IL-17 on day 2. Levels of these mediators in BALF were higher in RI group than SI group ( P < 0.05). Further, significantly more neutrophils were recruited to the lungs of the RI group ( P < 0.05). These observations suggest that IL-17 is involved in the prolonged induction of neutrophils in mice treated with Mp extract. [ABSTRACT FROM AUTHOR]

Context and objective: Plasma arachidonate (20:4) levels in patients with chronic obstructive pulmonary disease (COPD) were investigated. Methods: Plasma was extracted and free fatty acids (FFAs) were separated using column chromatography and measured by fluorescence. Plasma 20:4 levels and its percentage relative to total FFA levels (%20:4) were measured in COPD ( n = 18) and control ( n = 20) subjects. Results and conclusions: FFA levels were lower in COPD compared with normals. However, there was a significant increase in %20:4 levels in COPD patients (GOLD stage I/II 0.9 ± 0.4%; GOLD stage III/IV 1.1 ± 0.1%) compared with control subjects (0.6 ± 0.1, p < 0.05). %20:4 is a potential biomarker for COPD. [ABSTRACT FROM AUTHOR]

Clinical results for linezolid (LZD) treatment of hospital-acquired pneumonia (HAP) caused by methicillin-resistant Staphylococcus aureus (MRSA), particularly microbiologically evaluable or severe cases, are limited in Japan. A prospective observational study was conducted in order to assess the usefulness of LZD in Japanese patients with MRSA pneumonia. The study tracked fifteen participants treated with LZD for pneumonia who met the criteria of the HAP guidelines and were confirmed to have pneumonia caused by MRSA. Of these, six were severe and 13 had received antibiotic treatment before treatment with LZD. Of the 13 participants assessed for their clinical responses, seven were rated as cures, three were rated as failures, and three were indeterminate. The overall cure rate (cure/cure + failure) was 70.0% (7/10), and the cure rate by severity was 33.3% (1/3) for severe cases and 85.5% (6/7) for moderate cases. The one severe case with a clinical response rating of cure had failed to respond to vancomycin. Among the seven participants with a clinical response rating of cure, the microbiological response was eradication in three, presumed eradication in three, and indeterminate in one. Three serious adverse events occurred in two of the 15 participants, but none were considered to be causally related to LZD. The results suggest that LZD has high potential for severe and multidrug-resistant cases. A higher cure rate was achieved in moderate cases. In cases of pneumonia that are most likely MRSA infections with poor prognosis, it was suggested to be important for patient outcome to implement the most effective therapy before the patient's condition becomes serious. [ABSTRACT FROM AUTHOR]

Context: In management of community-acquired pneumonia (CAP), excellent biomarkers for inflammation would be helpful in our practice. Objectives: Kinetics of c-reactive protein (CRP) and serum amyloid A (SAA) was characterized, using their biologic half-life times. Materials and methods: Time course of CRP and SAA levels in the successfully treated 36 CAP patients were investigated and their half-life times were determined and compared. Results & Discussions: SAA and CRP declined in an exponential mean and the biologic half-life times of SAA levels was 34.9 ± 28.7 h, significantly shorter than that of CRP, 46.4 ± 21.7 h ( p == 0.0014). Conclusion: The kinetic evidence, presented as biologic half-life times of CRP and SAA, helps us make a clinical assessment of CAP patients. [ABSTRACT FROM AUTHOR]

Recently, combination treatment with a macrolide and a steroid for Mycoplasma pneumoniae (Mp) pneumonia has been reported to be effective. Thus, the effect of this combination on a mouse model of lung inflammation associated with Mp extract (the LIMEX mouse) was studied. Interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were induced in Mp extract-treated RAW264.7 cells, and this induction was inhibited by dexamethasone, parthenolide, SB203580 or LY294002. This suggested that Mp extract activates nuclear factor κB-, p38- and PI-3K-linked pro-inflammatory signals. The LIMEX mice were then either treated with or without clarithromycin and/or dexamethasone. Clarithromycin administration enhanced the production of IL-6, TNF-α, macrophage inflammatory protein-1α, monocyte chemotactic protein-1 and RANTES, while their production was perfectly suppressed by the combination of clarithromycin and dexamethasone. IL-17, IL-23, keratinocyte-derived chemokine (KC) and interferon-γ levels were not affected by clarithromycin treatment, but they were significantly suppressed by the combination of dexamethasone and clarithromycin. Collectively, some components of Mp extract provoked an inflammatory reaction in the RAW 264.7 cell line and LIMEX mice. Whereas the lung reaction in LIMEX mice was further exacerbated by clarithromycin treatment, it was resolved by the combinational treatment with clarithromycin and dexamethasone. [ABSTRACT FROM AUTHOR]

Inappropriate elevation of matrix metalloproteinase-9 (MMP9) is reported to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The object of this study was to identify the molecular mechanism underlying this increase of MMP9 expression, and here we show that oxidative stress-dependent reduction of a protein deacetylase, SIRT1, known as a putative antiaging enzyme, causes elevation of MMP9 expression. A sirtuin inhibitor, splitomycin, and SIRT1 knockdown by RNA interference led an increase in MMP9 expression in human monocytic U937 cells and in primary sputum macrophages, which was detected by RT-PCR, Western blot, activity assay, and zymography. In fact, the SIRT1 level was significantly decreased in peripheral lungs of patients with COPD, and this increase was inversely correlated with MMP9 expression and MMP9 promoter activation detected by a chromatin immunoprecipitation assay. H2O2 reduced SIRT1 expression and activity in U937 cells; furthermore, cigarette smoke exposure also caused reduction of SIRT1 expression in lung tissue of A/J mice, with concomitant elevation of MMP9. Intranasal treatment of a selective and novel SIRT1 small molecule activator, SRT2172, blocked the increase of MMP9 expression in the lung as well as pulmonary neutrophilia and the reduction in exercise tolerance. Thus, SIRT1 is a negative regulator of MMP9 expression, and SIRT1 activation is implicated as a novel therapeutic approach to treating chronic inflammatory diseases, in which MMP9 is abundant. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma is a therapeutically challenging malignancy. This report describes a case where the patient received multimodal therapy, including surgery, adjuvant chemoradiation therapy, and combination chemotherapy and successfully achieved long-term survival. Specifically, the patient achieved an extended complete response after combination chemotherapy with TS-1 (an orally administered drug that is a combination of tegafur, 5-chloro-2, 4-dihydroxypyridine [CDHP], and oteracil potassium [Oxo]) and cisplatin for recurrence. This result suggests that chemoradiation or combination chemotherapy regimens using oral 5-fluorouracil (5-FU) analogues might therefore be helpful in patients with this malignancy. However, further clinical trials are required. [ABSTRACT FROM AUTHOR]

Abstract: Study objectives: The percentage of oxidized coenzyme Q10 in total coenzyme Q10 (%CoQ-10) has been shown to indicate the degree of systemic oxidative stress. Chronic obstructive pulmonary disease (COPD) is regarded as a systemic disease that is linked to oxidative stress in its pathogenesis. In this study, the plasma %CoQ-10 levels in COPD patients were determined and assessed. In addition, the effect of oxygen supplementation on plasma %CoQ-10 was also evaluated. Material and methods: Thirteen COPD patients who had not received oxygen supplementation (COPD-Pt), five COPD patients who had received oxygen supplementation (COPD+O2) and 20 age-matched control subjects (CONTROL) were enrolled. We have also enrolled 83 young healthy non/slight smokers (smoking index <20 pack-year) and 24 young healthy smokers (smoking index≥20 pack-year) in order to assess the effect of smoking history on %CoQ-10 level. Their plasma was collected and plasma %CoQ-10 levels were determined and compared. Results and conclusion: The plasma %CoQ-10 of COPD-Pt was 6.3±2.3, significantly higher than that of CONTROL, 4.7±1.6 (p <0.05), indicating an increased oxidative stress in the patients. In contrast, no significant difference in %CoQ-10 was observed between young healthy non/slight smokers (%CoQ-10=3.2±0.9) and young healthy smokers (%CoQ-10=3.7±1.3). Our observation of five COPD patients who received an oxygen supplementation revealed that their %CoQ-10 values (4.0±1.5) were significantly lower than those in COPD-Pt subjects (p <0.05), suggesting that oxygen supplementation ameliorates the oxidative stress. In contrast, our study showed that no significant difference was observed among the three groups in plasma levels of Vitamin C or E. In conclusion, plasma %CoQ-10 levels are increased in COPD patients and oxygen supplementation attenuates this increasing effect by COPD. This implies that %CoQ-10 might be used practically to assess the COPD patients systemically. [Copyright &y& Elsevier]

High-temperature gas chromatographic separation of several synthetic polymer mixtures with Dexsil-coated fiber-packed columns was studied. A bundle of heat-resistant filaments, Zylon, was longitudinally packed into a short metal capillary, followed by the conventional coating process with Dexsil 300 material. Prior to the packing process the metal capillary was deactivated by the formation of a silica layer. The typical size of the resulting column was 0.3-mm i.d., 0.5-mm o.d., 1-m length, and packed with about 170 filaments of the Dexsil-coated Zylon. The column temperature could be elevated up to 450°C owing to the good thermal stability of the fiber, Dexsil coating, and metal capillary; furthermore, this allowed the separation of low-volatile compounds to be studied. [ABSTRACT FROM AUTHOR]

Examines the effects of obstructive sleep apnea syndrome (OSAS) on circulating intercellular adhesion molecule-1 (ICAM-1), interleukin-8 (IL-8) and monocyte chemoattractant protein-1. Measurement of circulating ICAM-1 and IL-8 before and after nasal continuous positive airway pressure therapy in OSAS patients.

Abstract A water injection experiment was carried out by the scientific drilling program named the ‘Nojima Fault Zone Probe’ during the two periods 9–13 February and 16–25 March 1997. The pumping pressure at the surface was approximately 4 MPa. The total amount of injected water was 258 m3. The injection was made between depths of 1480 m and 1670 m in the Disaster Prevention Research Institute, Kyoto University (DPRI) 1800 m borehole drilled into the Nojima Fault zone. A seismic observation network was deployed to monitor seismic activity related to the water injections. Seismicity suddenly increased in the region not far from the injection hole 4 or 5 days after the beginning of each water injection. These earthquakes were likely to be induced by the water injections. Most of the earthquakes had magnitudes ranging from -2 to +1. Numerous earthquakes occurred during the first injection, but only one could be reliably located and it was approximately 2 km north of the injection site. Between the two injection periods, earthquakes concentrated in the region approximately 1 km northwest of the injection site. During and after the second injection experiment, earthquakes were located approximately 1.5 km west of the injection site. Those earthquakes were located approximately 3 km or 4 km from the injection point and between 2 km and 4 km in depth. Values of intrinsic permeability of 10-14–10-15 m2 were estimated from the time lapse of the induced seismic activity. The coefficient of friction in the area where the induced earthquakes occurred was estimated to be less than 0.3. [ABSTRACT FROM AUTHOR]