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BackgroundThis study assessed longitudinal national data on mortality due to nontuberculous mycobacteriosis (NTMosis) and bronchiectasis and the association between the two diseases.MethodsWe analysed the national death statistics of Japan from 1970 to 2015. The International Classification of Disease (ICD) codes were used to extract the relevant data. Crude mortality, age-adjusted mortality and standardised mortality rates were calculated using vital statistics and the population in 2000. We also identified domestic publications related to NTMosis and bronchiectasis with an internet-based search system.ResultsThe total number of bronchiectasis-related deaths remained at the same level, which was approximately 1000, for 45 years, although the number of deaths has consistently decreased in males but increased in females since the mid-1990s. A substantial increasing trend in females was also observed for NTMosis in the same period. The age-adjusted mortality data showed an increase in mortality in women due to NTMosis and confirmed the trend in bronchiectasis in women. The patterns in the number of domestic reports showed a recent slight increase in bronchiectasis and a marked increase in NTMosis.ConclusionsThe trends in bronchiectasis-related mortality differed by sex. The epidemiological trends in the two diseases were associated, especially in elderly females since the mid-1990s. It is suggested that pulmonary NTMosis without pre-existing bronchiectasis might be a leading cause of postinfectious bronchiectasis in Japan.

The clinical importance of Mycobacterium abscessus species (MABS) infections has been increasing. However, the standard treatment regimens recommended in the current guidelines often result in unfavorable outcomes.

Background The effect of chronic sputum (CS) symptoms on health-related quality of life (HRQOL) in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) has not been studied. The aim of this study was to clarify the differences in the clinical characteristics of NTM-PD patients with and without CS and to investigate the effect of CS on HRQOL. Methods This cross-sectional study included patients with NTM-PD who were prescribed pulmonary rehabilitation at the Fukujuji Hospital from March 2016 to June 2019. HRQOL was evaluated using the MOS 36-Item Short-Form Health Survey (SF-36). Results Of the 99 subjects studied, 71 had CS (CS+) (71.7%), and 28 (28.3%) did not have CS (CS-). Patients in the CS + group had a lower body mass index, forced vital capacity percent predicted, and forced expiratory volume in 1 s percent predicted. Regarding the radiological evaluation, the proportion of patients with the fibrocavitary form and the radiological score were significantly higher in the CS + group. The mental component summary (MCS) score of the SF-36 were significantly lower in the CS + group. Multiple regression analysis showed that the presence of CS was independently associated with a lower MCS score of the SF-36. Conclusions NTM-PD patients with CS had more severe disease, with reduced pulmonary function and severe radiological findings. CS was shown to independently affect HRQOL, especially mental status.

Rationale: The clinical features and prognosis of nontuberculous mycobacterial (NTM) pleuritis and pleural effusion combined with NTM lung disease remain unclear. Objectives: To investigate the cli...

Clofazimine (CFZ) is used to treat pulmonary non-tuberculous mycobacterial (NTM) infection; however, its pharmacokinetics remain unexplored in patients with pulmonary NTM, and the relationship between CFZ serum concentration and adverse effects has not been investigated. The objectives of this study were to characterize the pharmacokinetics of CFZ in pulmonary NTM disease treatment and to investigate the relationship between the steady-state CFZ serum concentration and adverse effects. A prospective observational study was conducted on 45 patients with pulmonary NTM treated with CFZ (UMIN000041053). A maximum of five serum samples per patient were taken at the CFZ trough, and serum concentration was measured using high-performance liquid chromatography-mass spectrometry (HPLC-MS). The pharmacokinetics of CFZ were analyzed using a nonlinear mixed effect model. The relationships among steady-state CFZ serum concentration and adverse effects, pigmentation, and heart rate-corrected QT (QTc) interval were investigated. Twenty-six patients had M. avium or M. intracellulare infection and nineteen had M. abscessus infection. The primary CFZ dosage was 50 mg/day. The estimated apparent CFZ clearance, apparent volume of distribution, and half-life were 2.4 L/h, 2,960 L, and 36 days, respectively. The combined use of rifampicin and CFZ significantly reduced CFZ exposure by 22%. Although there was no relationship between CFZ serum concentration and pigmentation intensity, the QTc interval was significantly correlated with CFZ serum concentration. The estimation of accurate pharmacokinetics for CFZ required approximately 5 months of monitoring. The relationship between the serum concentration and specific adverse effects of CFZ confirmed that CFZ serum concentration was not associated with pigmentation but did affect the QTc interval.

Multidrug chemotherapy is recommended for treating pulmonary Mycobacterium avium and Mycobacterium intracellulare disease. Although ethambutol has been demonstrated to inhibit macrolide resistance, the ethambutol dosage is sometimes decreased due to concerns about optic neuropathy. We aimed to assess whether lower ethambutol doses impact treatment outcomes.Patients treated over 12 months between 2016 and 2020 were collected retrospectively. Clinical outcomes, including negative culture conversion, microbiological cure, adverse events, resistance to macrolides, and recurrence, were compared according to daily ethambutol dosage.Among 146 patients, 42 were treated with ethambutol dosages over 12.5 mg/kg/day, and 104 were treated with lower dosages. Negative culture conversion was achieved for 125 patients, and 90 patients achieved microbiological cure. Recurrence was identified in 16 patients who achieved microbiological cure. No macrolide resistance was observed, and no significant difference was observed in the percentage of negative culture conversion (P = 1.00) or microbiological cure (P = 0.67) between the high- and low-dosage ethambutol groups. Sputum smear positivity was associated with a lower adjusted odds ratio (aOR) of negative culture conversion (aOR: 0.48, 95% CI: 0.29-0.80). A lower aOR of microbiological cure was independently associated with sputum smear positivity (aOR: 0.52, 95% CI: 0.37-0.74) and with the use of an intermittent regimen (aOR: 0.60, 95% CI: 0.41-0.87). Daily ethambutol dosage was not identified as a prognostic factor for any of the outcomes. Optic neuropathy was observed in 7.1% of the high-dose ethambutol group and 1.0% of the low-dosage ethambutol group (P = 0.07).An ethambutol dosage of 12.5 mg/kg/day or less in guideline-based chemotherapy may reduce optic neuropathy without worsening clinical outcomes.

Mycobacterium abscessus complex (MABC) is an emerging non-tuberculous mycobacterium (NTM). Specific MABC clones are reportedly spreading globally in cystic fibrosis (CF) patients, however, associated genomic epidemiology studies are lacking in East Asia. Analysis of whole-genome sequencing data for MABC isolates from 220 pre-treatment, non-CF patients in Japan and Taiwan revealed that 112/220, 105/220, and 3/220 were M. abscessus subsp. abscessus (ABS), M. abscessus subsp. massiliense (MAS), and M. abscessus subsp. bolletii (BOL), respectively. No significant differences in subspecies composition were noted based on location. Moreover, >50% of ABS and >70% of MAS were related to four predominant clones in the region. Known mutations conferring acquired macrolide resistance were rare (1.4%) and not enriched in the predominant clones. Conversely, the macrolide-susceptible erm(41) T28C mutation was significantly enriched in one predominant ABS clone. The most predominant ABS clone was genetically related to the dominant circulating clone (DCC). Hence, we have clarified the relationship between the predominant clones in Japan and Taiwan, and those reported in the international CF patient community. Our results provide insights regarding the genetic characteristics of globally dominant and area-specific strains isolated from patients with or without CF, as well as differences between globally spread and regionally-specific strains.

Gastric aspirate can be useful for the diagnosis of pulmonary tuberculosis (TB) in patients with smear-negative pulmonary TB or without sputum production. The gastric aspirate smear technique has low sensitivity, and a previous report demonstrated that no patient was diagnosed by only gastric aspirate analysis. However, some patients with TB have been negative on sputum examination but positive on gastric aspirate examination, and the incidence of such cases is uncertain. Therefore, this study investigated the usefulness of gastric aspirate in the diagnosis of pulmonary TB.To analyze the diagnostic accuracy of gastric aspirate examination, the data of 513 patients with negative sputum smears or a lack of sputum production, including 203 patients with pulmonary TB (39.6%) and 93 patients with nontuberculous mycobacteriosis who underwent gastric aspiration at Fukujuji Hospital from January 2016 to March 2021, were collected retrospectively.The accuracy rates of gastric aspirate examination for the diagnosis of pulmonary TB were as follows: 21.2% sensitivity and 91.9% specificity for smear positivity, 55.8% sensitivity and 99.6% specificity for nucleic acid amplification test positivity, and 71.4% sensitivity and 100% specificity for culture positivity. Twenty-three patients (11.2%) were diagnosed by gastric aspirate examination alone. Among the 356 patients who underwent three repeated sputum examinations in addition to gastric aspirate examination, the cumulative diagnostic rate for the 3 mycobacterial examinations plus gastric aspirate examination was higher than that for only three sputum examinations.Gastric aspirate is useful for the diagnosis of TB in patients with smear-negative pulmonary TB or without sputum production.

Mycobacterium europaeum (M. europaeum) was recently identified as a nontuberculous mycobacterium belonging to the Mycobacterium simiae complex. There have been only a few reported cases of M. europaeum lung disease, all of which occurred in patients with immunodeficiency or prior lung disease. We herein report a case of M. europaeum lung disease in an otherwise healthy Japanese individual. A 70-year-old woman who had no apparent immunodeficiency or medical history was diagnosed with M. europaeum lung disease by multiple positive sputum cultures. The patient was successfully treated with clarithromycin, rifampin, ethambutol, and amikacin. This report is the first case of M. europaeum lung disease occurring in an individual without predisposing risk factors.

A concave-shaped maximal expiratory flow-volume (MEFV) curve is a spirometric feature in chronic obstructive pulmonary disease (COPD). The MEFV curve is characterized by an increase in the Obstructive Index, which is defined as a ratio of forced vital capacity to the volume-difference between two points of half of the peak expiratory flow on the MEFV curve. We hypothesized that the Obstructive Index would reflect the severity of emphysema in patients with COPD and asthma-COPD overlap (ACO). Thus, the aim of this retrospective study was to evaluate whether the Obstructive Index on spirometry is associated with the extent of emphysema on computed tomography (CT) in patients with COPD, ACO, and asthma (N = 65, 15, and 53, respectively). The percentage of low-attenuation volume (LAV%) and wall area (WA%) were measured on CT. The Obstructive Index was higher in patients with COPD and ACO than in those with asthma. Spearman correlation showed that a greater Obstructive Index was associated with a higher LAV%, but not WA%. Multivariate analysis showed that Obstructive Index was associated with LAV% (standardized β = 0.43, P

The experience and causes of pain in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) have not been clarified. This study aimed to determine the prevalence and severity of bodily pain (BP) in patients with NTM-PD. We also investigated the clinical indicators that contribute to pain. We used a retrospective cross-sectional study design. The participants were 114 NTM-PD patients (109 women) with a mean age of 65 years. The prevalence and severity of pain were measured using 2 items from the 36-Item Short Form Survey version 2 (SF-36), and the BP score was calculated. Functional limitation due to dyspnea was quantified using the Modified Medical Research Council Dyspnea Scale (mMRC), depression was assessed using the Center for Epidemiological Studies Depression Scale (CES-D), sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI); health-related quality of life was assessed using the Leicester Cough Questionnaire (LCQ), and exercise tolerance was measured using the Incremental Shuttle Walk Test (ISWT). Pain was reported by 70.2% of the patients (n = 80), and of these, 35.7% (n = 25) reported moderate to very severe pain. NTM-PD patients with high levels of pain had significantly higher scores on the mMRC, CES-D, and PSQI scores, and significantly lower performance on the ISWT and LCQ. Multiple regression analysis identified ISWT, CES-D, and PSQI as independent factors that affected BP scores. Our findings suggest that pain significantly impacts daily life associated with reduced exercise tolerance, the presence of depressive symptoms, and poor sleep quality in patients with NTM-PD.

The clinical importance of Mycobacterium abscessus subsp. abscessus (M. abscessus) lung disease has been increasing, but few studies have assessed the clinical characteristics associated with the treatment outcome. We retrospectively analyzed 75 consecutive patients with M. abscessus lung disease diagnosed at a tertiary hospital from January 2004 to April 2018. Among 52 patients with sufficient clinical data, 19 patients (42.2%) achieved treatment success. Compared with 26 (57.8%) patients in the treatment failure group, body mass index (BMI) (19.8 vs 17.5 kg/m2, P = 0.022), previous nontuberculous mycobacterial (NTM) lung disease (26.3% vs 61.5%, P = 0.034), the presence of cavitary lesions (31.6% vs 69.2%, P = 0.017), and the bronchiectasis score (3.0 vs 5.0, P = 0.003) were significantly different in the treatment success group. Multivariate analysis showed that age (adjusted hazard ratio (aHR), 0.94; 95% confidence interval (CI), 0.90 to 0.99; P = 0.010), the presence of cavitary lesions (aHR, 0.34; 95% CI, 0.12 to 0.94; P = 0.039), and previous NTM lung disease (aHR, 0.28; 95% CI, 0.09 to 0.86; P = 0.026) were negatively associated with treatment success. This is the first study to show that previous NTM lung disease might be a clinically important factor related to unfavorable treatment outcomes in M. abscessus lung disease patients. To increase our understanding the characteristics of M. abscessus lung disease, this factor should be independently analyzed in future research.

Background Lymphopenia has been reported as a risk factor for poor prognosis in various infectious diseases, including Mycobacterium avium complex lung disease (MAC-LD), and recurrence in several infectious diseases. However, the association between lymphopenia and the risk of redeveloping nontuberculous lung disease (NTM-LD) after completed treatment for MAC-LD is unknown. Methods We performed a retrospective cohort study with 147 patients with MAC-LD who successfully completed guideline-based therapy. Lymphopenia was defined as an absolute lymphocyte count (ALC) Results During the median follow-up period of 41.9 months after treatment completion, 59 (40.1%) patients redeveloped NTM-LD. Patients with NTM-LD redevelopment had significantly lower posttreatment ALCs (median, 1260 vs 1420 cells/μL) than those without, and the univariate Cox proportional hazard analysis identified posttreatment ALC as a predictive factor for redevelopment (hazard ratio, .94 [95% confidence interval, .89–.99] for every increase of 100 cells/μL; P = .04). In the multivariate analysis, posttreatment ALC and the extent of bronchiectasis were independently associated with NTM-LD redevelopment. The cumulative rate of NTM-LD redevelopment was significantly higher in patients with posttreatment lymphopenia than in those without (P = .008). Conclusions Posttreatment lymphopenia could predict an increased risk of NTM-LD redevelopment after completed treatment for MAC-LD.

Chronic pulmonary aspergillosis (CPA) is associated with mortality in patients with Mycobacterium avium complex lung disease (MAC-LD). However, the clinical significance of the positivity of Aspergillus precipitating antibody (APAb), a serodiagnostic test for pulmonary aspergillosis (PA), at the time of MAC-LD diagnosis is unknown. The objective of this study was to investigate the effects of APAb test results on the clinical outcomes of patients with MAC-LD.We retrospectively analyzed patients who were newly diagnosed as having MAC-LD between 2007 and 2014 in our hospital and checked for APAb at the time of diagnosis.We enrolled 131 patients in this study. Of these patients, 20 (15.3%) tested positive for APAb at the diagnosis of MAC-LD. The APAb-positive patients were more frequently male (70.0% vs. 37.8%, P = 0.013) and more frequently had pulmonary emphysema (60.0% vs. 13.5%, P 0.001) and interstitial pneumonia (15.0% vs. 1.8%, P = 0.025) compared with the APAb-negative patients. During a median follow-up period of 4.0 years, PA developed in 12 of the APAb-positive patients (60.0%, CPA: 9 and allergic bronchopulmonary aspergillosis: 3) and 12 APAb-negative patients (10.8%, CPA: 12) (P 0.001). The APAb-positive patients had a significantly higher rate of mortality than did the APAb-negative patients (P = 0.004). A multivariate analysis indicated that older age, lower albumin, fibrocavitary or fibrocavitary and nodular/bronchiectatic radiographic features, and APAb positivity were negative prognostic factors.APAb-positive patients with MAC-LD more frequently develop PA and may have an unfavorable prognosis.

Background Although recent studies have identified anti-glycopeptidolipid (GPL)-core IgA antibodies as a serodiagnostic test for Mycobacterium avium complex lung disease (MAC-LD), this test shows insufficient sensitivity. This study aimed to determine the clinical utility of these antibodies in assessing disease progression and the clinical characteristics of MAC-LD patients with negative antibody results. Methods We retrospectively reviewed the medical records of consecutive newly diagnosed, untreated MAC-LD patients in two referral hospitals. We evaluated the association of anti-GPL-core IgA antibody results with disease progression requiring treatment and the factors associated with negative antibody results. Results In total, 229 patients (161 females; median age, 71 years; 185 with nodular/bronchiectatic disease phenotype; 69 with cavitary lesions) were enrolled; 146 patients (64%) were anti-GPL-core IgA antibody-positive. Radiological severity scores were associated with anti-GPL-core IgA antibody titers. During the median 364-day follow-up, 114 patients (49.8%) required treatment. Multivariate Cox proportional hazards analysis showed that positive anti-GPL-core IgA antibody results, a younger age, the absence of malignancy, and the presence of cavitary lesions were associated with disease progression requiring treatment. Multivariate logistic analysis revealed that significant factors related to the negative antibody results included underlying pulmonary disease, lower radiological scores, chronic sinusitis, and macrolide monotherapy. Conclusion In addition to cavitary lesions, anti-GPL-core IgA antibody positivity was associated with disease progression requiring treatment. Physicians should carefully use anti-GPL-core IgA antibody results for the diagnosis of patients with underlying pulmonary disease, chronic sinusitis, macrolide monotherapy, and lower radiological severity.

Pleuritis caused by nontuberculous mycobacteria is uncommon and difficult to diagnose. We herein report a case of Mycobacterium avium complex (MAC) pleuritis with elevated anti-glycopeptidolipid (GPL)-core IgA antibody levels in the pleural effusion. A 73-year-old woman with MAC pulmonary disease presented with massive left pleural effusion. A pleural biopsy by video-assisted thoracoscopic surgery was performed, revealing many noncaseating epithelioid cell granulomas. MAC was not identified by culture of the pleural effusion or specimens, but the anti-GPL-core IgA antibody level was markedly elevated in the pleural effusion. Measurement of anti-GPL-core IgA levels in the pleural fluid may be useful for diagnosing MAC pleuritis.

Purpose: Waterproofing spray-associated pneumonitis (WAP) proceeds to acute respiratory failure and is characterized by diffuse bilateral ground-glass opacities on computed tomography. These features are similar to those of acute eosinophilic pneumonia (AEP) and hypersensitivity pneumonitis (HP). This study identified the characteristics of WAP and compared them with those of AEP and HP. Methods: We conducted a retrospective study of adult patients with WAP, AEP, and HP in Fukujuji Hospital from 1990 to 2018. Furthermore, data from patients with WAP were collected from publications in PubMed and the Japan Medical Abstracts Society and combined with data from our patients. Results: Twenty-nine patients with WAP, eleven patients with AEP, and thirty patients with HP were reviewed. There were no significant differences between the characteristics of WAP and AEP patients, such as age, sex, smoking habit, and laboratory findings. The features of WAP and HP were significantly different. The duration from symptom appearance to hospital visit was shorter in patients with WAP (median 1 day) than in patients with AEP (median 3 days, p =0.003) and HP (median 30 days, p

Introduction: Nontuberculous mycobacterial (NTM) pleuritis, pleural effusion combined with NTM lung disease (NTM-LD), has not been previously described as a common manifestation of NTM infections. Aims: This study aimed to investigate the clinical features and prognosis of NTM pleuritis. Methods: A retrospective observational study was performed including patients with NTM pleuritis fromJanuary 2001 to December 2017 at 8 hospitals. NTM pleuritis was defined as a positive culture of NTM from pleural effusion. Furthermore, we matched patients with NTM-LD but without pleuritis by sex and age (within a 10-year range) to obtain comparative data for individuals. We investigated the association between clinical parameters and prognosis. Results: We identified 58 patients with NTM pleuritis (median age, 72 years; 35 females; Mycobacterium avium complex [MAC], 48 patients). The median follow-up period was 16 months and 26 patients died. Patients with NTM pleuritis had significantly worse survival than sex- and age-matched patients presenting NTM-LD without pleuritis (P Conclusions: Our results suggest that prognosis of NTM pleuritis is worse than NTM-LD without pleuritis. Moreover, lower BMI, UPD, and no treatment history after pleuritis are associated with poor prognosis in patients with NTM pleuritis.

Pleuritis caused by nontuberculous mycobacteria is uncommon and difficult to diagnose. We herein report a case of Mycobacterium avium complex (MAC) pleuritis with elevated anti-glycopeptidolipid (GPL)-core IgA antibody levels in the pleural effusion. A 73-year-old woman with MAC pulmonary disease presented with massive left pleural effusion. A pleural biopsy by video-assisted thoracoscopic surgery was performed, revealing many noncaseating epithelioid cell granulomas. MAC was not identified by culture of the pleural effusion or specimens, but the anti-GPL-core IgA antibody level was markedly elevated in the pleural effusion. Measurement of anti-GPL-core IgA levels in the pleural fluid may be useful for diagnosing MAC pleuritis.

The incidence of nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing, while that of tuberculosis (TB) is decreasing in many industrialized countries, including Japan. However, the long-term evaluation of clinico-epidemiological features of NTM-PD in relation to TB are limited. We aimed to clarify the long-term changes in the epidemiology and clinical features of NTM-PD in relation to those of TB at a nationally-designated TB center in Japan.We reviewed all mycobacterial examination records at Fukujuji Hospital between 2006 and 2016. Cases of NTM-PD were defined according to the 2007 American Thoracic Society/Infectious Disease Society of America microbiologic criteria. The current characteristics of Mycobacterium avium complex pulmonary disease (MAC-PD) were compared with those in the 1980s and circa 2000.We identified a total of 3,546 pulmonary TB cases and 2,155 NTM-PD cases. While the annual number of incident pulmonary TB cases remained stable over the study period (P = 0.59), that of NTM-PD cases increased significantly from 165 to 278 (P 0.01). The mean age of pulmonary TB cases increased from 59.7 ± 16.3 to 66.2 ± 21.7 years, whereas that of NTM-PD cases remained unchanged. Regarding the age distribution, the greatest increases were observed in patients over 75 years for TB and in patients 50-74 years for NTM. The most common causative organism for NTM was Mycobacterium avium complex (87.3%), M. abscessus complex (5.5%) and M. kansasii (3.9%). Among patients with MAC-PD, the proportion of the nodular bronchiectatic (NB) form increased significantly from 60.0% to 84.4% between circa 2000 and 2016 (P 0.01). Significant increases in the NB form were observed in both males (33.3%-70.7%, P 0.01) and females (71.3%-89.2%, P 0.01).The annual number of incident NTM-PD cases increased markedly. In contrast to patients with TB, the mean age of new NTM-PD patients did not increase in the last 10 years. Among MAC-PD patients, the proportions accounted for by the NB form increased significantly in both sexes.

Although calcium antagonists elicit predominant dilation of afferent arterioles that might be associated with glomerular hypertension, there have been reported diverse observations demonstrating the effect of calcium antagonists on the progression of renal injury. The present study examined the effect of pranidipine (CAS 99522-79-9) on the renal microvascular tone in the isolated perfused hydronephrotic rat kidney, and the progression of renal insufficiency in subtotally nephrectomized spontaneously hypertensive rats. In the hydronephrotic kidney, angiotensin II caused marked constriction of both afferent and efferent arterioles. The subsequent addition of pranidipine (10 nmol/l, 100 nmol/l, 1 mumol/l) elicited dose-dependent afferent arteriolar dilation, with 97 +/- 3% reversal at 1 mumol/l. In contrast, efferent arterioles were resistant to pranidipine, with only 20 +/- 4% reversal at 1 mumol/l. In subtotally nephrectomized rats, 10-week treatment with pranidipine (3.0 mg/kg/day) markedly decreased blood pressure (from 270 +/- 6 to 158 +/- 8 mmHg) and improved renal histopathological changes, including glomerular and arteriolar sclerosis. Proteinuria was also less than than in the control rats (233 +/- 5 vs. 305 +/- 26 mg/day). Thus, although glomerular hypertension might develop as a consequence of preferential afferent arteriolar dilation, pranidipine actually improved the renal injury in subtotally nephrectomized SHR. These ostensibly discrepant observations could be attributed to the simultaneous reduction in blood pressure and the salutary actions of this agent mediated by non-hemodynamic mechanisms.

This paper aims to discuss necessary conditions for realizing independent living of users in social welfare facilities from the perspective of the subject theory. First, I show that users in the social welfare facilities cannot realize independent living, because their needs are not recognized and satisfied. It is clear if we compare livings in social welfare facilities and ones in communities. Second, through examining the development process of the subject theory in social welfare, I show that subjectivity can be realized when others' perspectives supplement subjective perspective. Third, I conclude that synthesizing perspectives of users and staffs in social welfare facilities and others in community is most important one of necessary conditions for realizing independent living of users in social welfare facilities.

Consideration of the ideal way of caring for social welfare facilities in Japan is added from the current of the community care and the institutional care. Care in social welfare institution has become a nucleus in the field of the elderly and the disable person, etc. in Japan. On the other hand, Community" is being asked to the ideal way of social welfare by the key word now. The ideal way of not the exception but the care in the future is asked in social welfare institution.

The reactive evaporation method of injected metal powders was investigated for preparing oxide nanoparticles. The method has advantages such as evaporation is enhancement of the injected powder owing to exothermic reaction heat of the metal powder oxidation in induction thermal plasmas. Tangential gas flow injection to the plasma tail flame controls the diameter and the yield of the oxide nanoparticles. The purpose of this research is to investigate the effect of the injection gas flow on the preparation mechanism of oxide nanoparticles in thermal plasmas by experimental work and numerical analysis. An increase in the flow rate of the injection gas leads to an increase in the diameter as well as the yield of the prepared nanoparticles. Numerical analysis for nucleation and growth provides the preparation mechanism of the oxide nanoparticles; however, a more sophisticated model should be developed.

We examined the role of Rho/Rho-kinase in renal afferent and efferent arteriolar tone induced by angiotensin (Ang) II, KCl and elevated renal arterial pressure (from 80 to 180 mm Hg), using isolated perfused rat hydronephrotic kidney. In the condition with no vasoconstrictor stimuli, Y-27632, a Rho-kinase inhibitor, dilated only afferent (from 11.6 ± 0.4 to 14.1 ± 0.5 µm) but not efferent arterioles (from 11.6 ± 0.2 to 12.6 ± 0.7 µm) at 10–5 mol/l. During renal vasoconstriction by Ang II, Y-27632 restored the afferent arteriolar constriction (141 ± 10% reversal at 10–5 mol/l), whereas the ability of Y-27632 to inhibit the Ang II-induced efferent arteriolar constriction was diminished (73 ± 7% reversal). A similar action was observed with fasudil, another Rho-kinase inhibitor. Furthermore, Y-27632 impaired myogenic afferent arteriolar constriction, with 117 ± 17% inhibition at 10–5 mol/l. The inhibition by Y-27632 of the myogenic vasoconstriction was almost the same as that of the Ang II-induced tone of this vessel type. However, Y-27632 had a modest effect on KCl-induced vasoconstriction of afferent arterioles. In conclusion, the present study demonstrates a predominant role of Rho/Rho-kinase in mediating the basal and Ang II-induced tone of afferent, but not efferent, arterioles. Furthermore, the role of Rho/Rho-kinase in afferent arteriolar constriction differs, with a substantial contribution to Ang II-induced and myogenic constriction but a minimal role in depolarization-induced constriction. Since Ang II-induced, KCl-induced and myogenic constriction of afferent arterioles require calcium entry through voltage-dependent calcium channels, the interaction between Rho/Rho-kinase and the calcium entry pathway may determine the afferent arteriolar tone induced by these stimuli.

The present study was designed to test the hypothesis that growth from puberty to adulthood in the rat is associated with an increase in renal cortical nitric oxide synthase (NOS) activity that results in an augmented impact of nitric oxide (NO) on hemodynamic function. Two groups of male Sprague-Dawley rats were studied: juvenile rats (approximately 2 months old) and mature rats (approximately 5 months old). NOS activity, measured as -nitro-L-arginine (NNA)-sensitive (3)H-L-citrulline production from (3)H-L-arginine, was significantly higher in the renal cortex of mature rats (57+/-2 pmol/h per mg protein) than in juveniles (42+/-3 pmol/h per mg protein). Additional animals from each group were anesthetized to determine the acute impact of NOS inhibition on arterial pressure and renal cortical blood flow, measured by single-fiber Doppler flowmetry. Cortical blood flow was higher in mature rats than in juveniles, averaging 22+/-2 and 16+/-1 perfusion units, respectively. NOS inhibition (10 mg/kg NNA i.v.) decreased renal cortical blood flow in mature rats by 35+/-7%, but only by 9+/-4% in juvenile animals. These data support the hypothesis that maturational growth in the rat is associated with augmented NOS activity coupled with an increased tonic influence of NO on renal cortical blood flow.

1. The early stage of type 1 diabetes mellitus (DM) is characterized by renal hyperfiltration, which promotes the eventual development of diabetic nephropathy. The hyperfiltration state is associated with afferent arteriolar dilation and diminished responsiveness of this vascular segment to a variety of vasoconstrictor stimuli, whereas efferent arteriolar diameter and vasoconstrictor responsiveness are typically unaltered. 2. The contractile status of preglomerular vascular smooth muscle appears to be tightly coupled to membrane potential (E(m)) and its influence on Ca(2+) influx through voltage-gated channels. Efferent arteriolar tone is largely independent of electromechanical events. Hence, defective electromechanical mechanisms in vascular smooth muscle should engender selective changes in preglomerular microvascular function, such as those evident during the early stage of DM. 3. Afferent arteriolar contractile responses to K(+)-induced depolarization and BAYK8644 are diminished 2 weeks after onset of DM in the rat. Similarly, depolarization-induced Ca(2+) influx and the resulting increase in intracellular [Ca(2+)] are abated in the preglomerular microvasculature of diabetic rats. The intracellular [Ca(2+)] response to depolarization is rapidly restored by normalization of extracellular glucose levels. These observations suggest that hyperglycaemia in DM impairs regulation of afferent arteriolar voltage-gated Ca(2+) channels. 4. Dysregulation of E(m) may also contribute to afferent arteriolar dilation in DM. Vasodilator responses to pharmacological opening of ATP-sensitive K(+) channels are exaggerated in afferent arterioles from diabetic rats. Moreover, blockade of these channels normalizes afferent arteriolar diameter in kidneys from diabetic rats. These observations suggest that increased functional availability and basal activation of ATP-sensitive K(+) channels promote afferent arteriolar dilation in DM. 5. We propose that dysregulation of E(m) (involving ATP- sensitive K(+) channels) and a diminished Ca(2+) influx response to depolarization (involving voltage-gated Ca(2+) channels) may act synergistically to promote preglomerular vasodilation during the early stage of DM.

Background: Both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) are established as important factors determining the vascular tone. The relative contribution of these factors to the renal microvascular tone, however, has not been delineated. Methods: Isolated perfused hydronephrotic rat kidneys were used to characterize the relative role of NO and EDHF in mediating the tone of interlobular arteries (ILA) and afferent arterioles (AFF). Results: During the norepinephrine constriction, acetylcholine (ACH, 1 µmol/l) induced a sustained vasodilation of ILA (90 ± 9% reversal) and AFF (117 ± 13% reversal). In the presence of nitro-L-arginine methylester (LNAME), the ACH-induced vasodilation of ILA and AFF was converted to transient dilation, with only 53 ± 7 and 32 ± 7% reversal observed 10 min after 1 µmol/l ACH (i.e sustained phase). In contrast, LNAME had no effect on the initial phase of ACH-induced dilation. In the presence of apamin + charybdotoxin, the initial vasodilator response to ACH (1 µmol/l) was diminished (ILA, from 108 ± 8 to 46 ± 9%; AFF, from 108 ± 14 to 58 ± 8%), whereas no impairment was observed in sustained phases. Furthermore, the magnitude of the vasoconstriction caused by LNAME was greater at smaller vessel segments. Finally, the LNAME-induced inhibition of the sustained phase of ACH-induced vasodilation was greater as the vessel diameter decreased. Conclusions: That the relative contribution of NO and EDHF differs, with a greater role of NO in the basal tone and ACH-induced vasodilation at smaller vascular segments of ILA and AFF.

Experiments were performed to test the hypothesis that tyrosine kinase activity contributes to renal arteriolar contractile responses to angiotensin (Ang) II. Rats were subjected to short-term enalaprilat treatment to decrease endogenous Ang II formation before tissue was harvested for experiments with the in vitro blood-perfused juxtamedullary nephron technique. Acute surgical papillectomy was used to avoid the indirect afferent arteriolar effect of Ang II that arises through increased tubuloglomerular feedback sensitivity. Arteriolar lumen diameter responses to 1 and 10 nmol/L Ang II were monitored by videomicroscopic methods before and during treatment with various tyrphostin compounds: 100 μmol/L AG18 (broad-spectrum tyrosine kinase inhibitor), 100 nmol/L AG1478 (selective epidermal growth factor receptor tyrosine kinase inhibitor), or 100 μmol/L AG9 (inactive analog). Baseline afferent arteriolar lumen diameter averaged 23.5±1.2 μm and was not influenced by any tyrphostin. Ang II (10 nmol/L) decreased afferent diameter by 11.1±1.0 μm under untreated conditions, a response that was not altered by AG9 but significantly blunted by AG18 (34±9% inhibition) or AG1478 (52±8% inhibition). AG18 did not suppress afferent arteriolar contractile responses to membrane depolarization (20 to 55 mmol/L K + bath). Efferent arteriolar baseline diameter averaged 24.1±0.8 μm and was unaltered by AG18 or AG1478; however, efferent diameter responses to 10 nmol/L Ang II were diminished 52±10% by AG18 and 51±13% by AG1478. These observations indicate that Ang II signaling in renal afferent and efferent arteriolar vascular smooth muscle is either mediated or modulated by tyrosine kinase activity, including that of the epidermal growth factor receptor tyrosine kinase.

Aranidipine, a newly developed calcium antagonist, possesses unique pharmacologic characteristics in that its metabolite (M-1) still has antihypertensive action. We examined the effects of both agents on renal microcirculation using the isolated perfused hydronephrotic rat kidney. During norepinephrine-induced constriction, the addition of aranidipine dilated both afferent and efferent arterioles in a dose-dependent manner; at 10(-6) M, 83 +/- 6% and 90 +/- 6% reversal, respectively. In contrast, its active metabolite exerted dilator action predominantly on the afferent arteriole (79 +/- 4% vs. 44 +/- 17% at 10(-6) M for afferent and efferent arterioles, respectively). We further examined the long-term (8 weeks) effect of these agents on the development of renal injury in salt-loaded subtotally nephrectomized spontaneously hypertensive rats. Both aranidipine and M-1 reduced blood pressure by a similar magnitude. The decreases in proteinuria were observed in the aranidipine-treated group at weeks 6, 8, and 10, whereas in the M-1 group, significant reduction was attained only at week 6. Histopathologic examination revealed that both treatments improved glomerular and arteriolar sclerosis. Glomerular sclerosis, however, was less pronounced in the aranidipine-treated group than in the M-1 group. In conclusion, aranidipine has dilator action on both arterioles, whereas M-1 caused predominant dilation of afferent arterioles. Such metabolic changes may constitute a determinant of efferent arteriolar action of the calcium antagonist.